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Owing to the increased reports in Aedes-borne diseases in the Caribbean and Latin America, the United States Agency for International Development assisted the Jamaican Ministry of Health and Wellness in conducting insecticide susceptibility tests on Aedes aegypti populations. Sentinel sites were established in seven parishes of Jamaica (St. Catherine, Kingston and St. Andrew, St. Thomas, Portland, St. Mary and St. Ann) and Aedes aegypti eggs were collected, reared to adults per collected population and their susceptibility to varying pyrethroids and organophosphates were tested using the World Health Organization paper bioassays for these insecticides. The Centers for Disease Control and Prevention bottle bioassay was used to assess susceptibility to the carbamate, bendiocarb. The voltage gated sodium channel gene mutations V1016I and I1011V, normally associated with pyrethroid resistance, were also analysed. The results showed that Aedes aegypti collected from all parishes exhibited resistance to pyrethroids at the following concentrations, permethrin 0.25–2.5%; deltamethrin 0.03–0.15%; lambda-cyhalothrin 0.03–0.3%; and etofenprox 0.5–2.5%. The insecticide deltamethrin at concentration 0.3% was the only pyrethroid tested that resulted in high mortality, 94.9 ± 0.34% knockdown within 1 hour of exposure and 98.95 ± 0.01% mortality (p <0.01) at 24 hours post exposure. The frequency of the voltage gated sodium channel gene mutation V1016I was high in the tested population, possibly accounting for the reduced sensitivity to pyrethroids. Organophosphate resistance was also observed in all populations tested. Mortality rates for 0.8% Malathion was 0.8 ± 0.02–60.68 ± 0.01% after 24 hour and 0.00–47.10 ± 0.09%, for pirimiphos-methyl 0.21%. Bendiocarb applied as 12.5 μg/ bottle resulted in mortality rates of 76.25 ± 4.30–100 ± 0.00% after 30 minutes of exposure. The results showed that Ae. aegypti from the seven parishes analysed demonstrated resistance to the insecticides tested. Deltamethrin and bendiocarb at concentrations 0.3% and 12.5μg respectively, were considered most effective, causing high mortality in the local populations. Routine monitoring and evaluations of Ae. aegypti populations from the included parishes are recommended. Additionally, the study results represent the most comprehensive testing to date with local Aedes aegypti populations distributed across different parishes of Jamaica and should be useful to guide national and sub national strategies for vector control and surveillance. Author summary: The recent outbreaks of chikungunya, Zika and dengue viruses in the Caribbean and Latin America during 2013–2018, have motivated local health authorities in individual countries to seek international assistance from multiple agencies and adjust their vector management strategies in order to contain the transmission of Aedes-borne diseases. Countries within the region rely mainly on the use of commercially available insecticides to manage the mosquito populations and by extension, reduce the transmission of vector-borne diseases. However, this practice is stymied by the ability of these insects to develop resistance mechanisms to insecticides of frequent use. Many countries in the Caribbean and Latin America regions lack the facilities and supplies to conduct routine insecticide susceptibility testing. In an effort to ascertain knowledge on the presence of insecticide resistance in Aedes aegypti populations, and to determine which insecticide is more effective to reduce vector populations of Jamaica, we conducted an array of bioassays with three different types of insecticides (pyrethroid, organophosphate, carbamate) to use local evidence and inform public health authorities on vector control status and alternatives. [ABSTRACT FROM AUTHOR]

Approximately 300,000 persons in the United States (US) are infected with Trypanosoma cruzi, the protozoan that causes Chagas disease, but less than 1% are estimated to have received antiparasitic treatment. Benznidazole was approved by the US Food and Drug Administration (FDA) for treatment of T. cruzi infection in 2017 and commercialized in May 2018. This paper analyzes factors that affect access to benznidazole following commercialization and suggests directions for future actions to expand access. We applied an access framework to identify barriers, facilitators, and key actors that influence the ability of people with Chagas disease to receive appropriate treatment with benznidazole. Data were collected from the published literature, key informants, and commercial databases. We found that the mean number of persons who obtained benznidazole increased from just under 5 when distributed by the CDC to 13 per month after the commercial launch (from May 2018 to February 2019). Nine key barriers to access were identified: lack of multi-sector coordination, failure of health care providers to use a specific order form, lack of an emergency delivery system, high medical costs for uninsured patients, narrow indications for use of benznidazole, lack of treatment guidelines, limited number of qualified treaters, difficulties for patients to make medical appointments, and inadequate evaluation by providers to determine eligibility for treatment. Our analysis shows that access to benznidazole is still limited after FDA approval. We suggest six areas for strategic action for the pharmaceutical company that markets benznidazole and its allied private foundation to expand access to benznidazole in the US. In addition, we recommend expanding the existing researcher-clinician network by including government agencies, companies and others. This paper's approach could be applied to access programs for benznidazole in other countries or for other health products that target neglected populations throughout the world. Author summary: Less than 1% of persons in the United States with Trypanosoma cruzi infection, the cause of Chagas disease, have received antiparasitic treatment. In this paper, we examine the status of access to benznidazole in the United States following its approval by the FDA for treatment of Chagas disease treatment in 2017 and its commercialization in 2018. We found that the average number of patients who received benznidazole from the manufacturer increased after commercialization from just under 5 (when distributed by the CDC) to 13 patients (when sold in commercial channels) per month. We identified various barriers to access to treatment such as problems in the drug ordering process, low demand from health care providers, inadequate clinical assessment of patient eligibility for treatment, obstacles for patients to make medical appointments or to pay medical costs, and weak coordination among key actors in the health system. To overcome these access barriers, we propose strategic actions that can be taken by the pharmaceutical producer in collaboration with other key actors. Our work contributes to expanding access to Chagas disease treatment in the United States, and our approach could be applied to efforts to expand access to health products for other neglected diseases. [ABSTRACT FROM AUTHOR]

Due to the success of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) many countries have either eliminated the disease as a public health problem or are scheduled to achieve this elimination status in the coming years. The World Health Organization (WHO) recommend that the Transmission Assessment Survey (TAS) is used routinely for post-mass drug administration (MDA) surveillance but it is considered to lack sensitivity in low prevalence settings and not be suitable for post-validation surveillance. Currently there is limited evidence to support programme managers on the design of appropriate alternative strategies to TAS that can be used for post-validation surveillance, as recommended by the WHO. We searched for human and mosquito LF surveillance studies conducted between January 2000 and December 2018 in countries which had either completed MDA or had been validated as having eliminated LF. Article screening and selection were independently conducted. 44 papers met the eligibility criteria, summarising evidence from 22 countries and comprising 83 methodologically distinct surveillance studies. No standardised approach was reported. The most common study type was community-based human testing (n = 42, 47.2%), followed by mosquito xenomonitoring (n = 23, 25.8%) and alternative (non-TAS) forms of school-based human testing (n = 19, 21.3%). Most studies were cross-sectional (n = 61, 73.5%) and used non-random sampling methods. 11 different human diagnostic tests were described. Results suggest that sensitivity of LF surveillance can be increased by incorporating newer human diagnostic tests (including antibody tests) and the use of mosquito xenomonitoring may be able to help identify and target areas of active transmission. Alternative sampling methods including the addition of adults to routine surveillance methods and consideration of community-based sampling could also increase sensitivity. The evidence base to support post-validation surveillance remains limited. Further research is needed on the diagnostic performance and cost-effectiveness of new diagnostic tests and methodologies to guide policy decisions and must be conducted in a range of countries. Evidence on how to integrate surveillance within other routine healthcare processes is also important to support the ongoing sustainability of LF surveillance. Author summary: Lymphatic filariasis (LF) is a mosquito-borne disease, which can result in complications including swelling affecting the limbs (lymphoedema) or scrotum (hydrocele). LF can be eliminated by mass drug administration (MDA) which involves whole communities taking drug treatment at regular intervals. After MDA programmes, country programmes conduct the Transmission Assessment Survey (TAS), which tests school children for LF. It is important to continue testing for LF after elimination because there can be a 10-year period between becoming infected and developing symptoms, but it is thought that the use of TAS in such settings is likely to be too expensive and also not sensitive enough to detect low-level infections. Our study assesses the results from 44 studies in areas of low LF prevalence that have investigated methods of surveillance for LF which differ from the standardised TAS approach. These include both human and mosquito studies. Results show that there is currently no standardised approach to testing, but that surveillance can be made more sensitive through the use of new diagnostic tests, such as antibody testing, and also by targeting higher risk populations. However, further research is needed to understand whether these approaches work in a range of settings and whether they are affordable on the ground. [ABSTRACT FROM AUTHOR]

Brucellosis is a neglected zoonotic disease of remarkable importance worldwide. The focus of this systematic review was to investigate occupational brucellosis and to identify the main infection risks for each group exposed to the pathogen. Seven databases were used to identify papers related to occupational brucellosis: CABI, Cochrane, Pubmed, Scielo, Science Direct, Scopus and Web of Science. The search resulted in 6123 studies, of which 63 were selected using the quality assessment tools guided from National Institutes of Health (NIH) and Case Report Guidelines (CARE). Five different job-related groups were considered greatly exposed to the disease: rural workers, abattoir workers, veterinarians and veterinary assistants, laboratory workers and hunters. The main risk factors and exposure sources involved in the occupational infection observed from the analysis of the articles were direct contact with animal fluids, failure to comply with the use of personal protective equipment, accidental exposure to live attenuated anti-brucellosis vaccines and non-compliance with biosafety standards. Brucella species frequently isolated from job-related infection were Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis. In addition, a meta-analysis was performed using the case-control studies and demonstrated that animal breeders, laboratory workers and abattoir workers have 3.47 [95% confidence interval (CI); 1.47–8.19] times more chance to become infected with Brucella spp. than others individuals that have no contact with the possible sources of infection. This systematic review improved the understanding of the epidemiology of brucellosis as an occupational disease. Rural workers, abattoir workers, veterinarians, laboratory workers and hunters were the groups more exposed to occupational Brucella spp. infection. Moreover, it was observed that the lack of knowledge about brucellosis among frequently exposed professionals, in addition to some behaviors, such as negligence in the use of individual and collective protective measures, increases the probability of infection. Author summary: Brucellosis is a zoonotic bacterial infection of major importance worldwide, affecting not only domestic animals but different wildlife species. Due to its ways of transmission, direct or indirect contact with infected animals or their contaminated biological products, the disease exhibits a strong occupational character. This systematic review addressed the main occupations affected by Brucella spp. infection, due to the regular exposure to aerosol and contact of non-intact skin (e.g. wounds and abrasion) with infected materials, such as carcasses, viscera and live attenuated anti-brucellosis vaccines. The main risk factors for the disease were identified, as well as the most common forms of exposure to the pathogen. In addition, the most frequently Brucella species isolated from farmers, abattoir workers, veterinarians and veterinary technicians, laboratory workers and hunters were also described. The constant contact with the pathogen, the lack of information and instructions to occupational groups exposed, as well as the low adhesion to personal protective equipment in the work environment are determining factors for the occurrence of brucellosis among these individuals. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidiosis is an emerging infectious disease of public health significance worldwide. The burden of disease caused by Cryptosporidium varies between and within countries/areas. To have a comprehensive understanding of epidemiological status and characteristics of human Cryptosporidium infection in China since the first report in 1987, a retrospective epidemiological analysis was conducted by presenting differences in the prevalence of Cryptosporidium by province, year, population, living environment and season and possible transmission routes and risk factors as well as genetic characteristics of Cryptosporidium in humans. Methodology/Principal findings: A systematic search was conducted to obtain epidemiological papers of human Cryptosporidium infection/cryptosporidiosis from PubMed and Chinese databases. Finally, 164 papers were included in our analysis. At least 200,054 people from 27 provinces were involved in investigational studies of Cryptosporidium, with an average prevalence of 2.97%. The prevalence changed slightly over time. Variable prevalences were observed: 0.65–11.15% by province, 1.89–47.79% by population, 1.77–12.87% and 0–3.70% in rural and urban areas, respectively. The prevalence peak occurred in summer or autumn. Indirect person-to-person transmission was documented in one outbreak of cryptosporidiosis in a pediatric hospital. 263 Cryptosporidium isolates were obtained, and seven Cryptosporidium species were identified: C. hominis (48.3%), C. andersoni (22.43%), C. parvum (16.7%), C. meleagridis (8.36%), C. felis (3.04%), C. canis (0.76%) and C. suis (0.38%). Conclusions/Significances: This systematic review reflects current epidemiological status and characteristics of Cryptosporidium in humans in China. These data will be helpful to develop efficient control strategies to intervene with and prevent occurrence of human Cryptosporidium infection/cryptosporidiosis in China as well as have a reference effect to other countries. Further studies should focus on addressing a high frequency of C. andersoni in humans and a new challenge with respect to cryptosporidiosis with an increasing population of elderly people and patients with immunosuppressive diseases. Author summary: Cryptosporidium is a major cause of diarrheal disease in humans globally. Due to the lack of effective drug treatment and vaccine prevention against cryptosporidiosis, it is particularly important to develop efficient control strategies to intervene with and prevent Cryptosporidium infection in humans. The present review presented and analyzed epidemiological status and characteristics of Cryptosporidium infection in humans in China since the first report in 1987. To date, epidemiological investigations of Cryptosporidium infecion have been carried out in different populations in 27 provinces, autonomous regions, and municipalities. Average prevalence of Cryptosporidium was 2.97% (5,933/200,054). Like other infectious disease, due to poor sanitation conditions in rural areas, people living in rural areas had a significantly higher prevalence of Cryptosporidium (1.77–12.87%) than those living in urban areas (0–3.70%). Seven Cryptosporidium species were identified, including C. hominis, C. andersoni, C. parvum, C. meleagridis, C. felis, C. canis and C. suis. This retrospective epidemiological analysis indicates wide geographical distribution of human Cryptosporidium infection/cryptosporidiosis in China. [ABSTRACT FROM AUTHOR]

Background: Animal trypanosomosis caused by Trypanosoma evansi is known as "surra" and is a widespread neglected tropical disease affecting wild and domestic animals mainly in South America, the Middle East, North Africa and Asia. An essential necessity for T. evansi infection control is the availability of reliable and sensitive diagnostic tools. While DNA-based PCR detection techniques meet these criteria, most of them require well-trained and experienced users as well as a laboratory environment allowing correct protocol execution. As an alternative, we developed a recombinase polymerase amplification (RPA) test for Type A T. evansi. The technology uses an isothermal nucleic acid amplification approach that is simple, fast, cost-effective and is suitable for use in minimally equipped laboratories and even field settings. Methodology/Principle findings: An RPA assay targeting the T. evansi RoTat1.2 VSG gene was designed for the DNA-based detection of T. evansi. Comparing post-amplification visualization by agarose gel electrophoresis and a lateral flow (LF) format reveals that the latter displays a higher sensitivity. The RPA-LF assay is specific for RoTat1.2-expressing strains of T. evansi as it does not detect the genomic DNA of other trypanosomatids. Finally, experimental mouse infection trials demonstrate that the T. evansi specific RPA-LF can be employed as a test-of-cure tool. Conclusions/Significance: Compared to other DNA-based parasite detection methods (such as PCR and LAMP), the T. evansi RPA-LF (TevRPA-LF) described in this paper is an interesting alternative because of its simple read-out (user-friendly), short execution time (15 minutes), experimental sensitivity of 100 fg purified genomic T. evansi DNA, and ability to be carried out at a moderate, constant temperature (39°C). Therefore, the TevRPA-LF is an interesting tool for the detection of active T. evansi infections. Author summary: Neglected tropical diseases (NTDs) affecting humans and/or domestic animals severely impair the socio-economic development of endemic areas. One of these diseases, animal trypanosomosis, affects livestock and is caused by the parasites of the Trypanosoma genus. The most widespread causative agent of animal trypanosomosis is T. evansi, which is found in large parts of the world (Africa, Asia, South America, Middle East, and the Mediterranean). Proper control and treatment of the disease requires the availability of reliable and sensitive diagnostic tools. DNA-based detection techniques are powerful and versatile in the sense that they can be tailored to achieve a high specificity and usually allow the reliable detection of low amounts of parasite genetic material. However, many DNA-based methodologies (such as PCR) require trained staff and well-equipped laboratories, which is why the research community has actively investigated in developing amplification strategies that are simple, fast, cost-effective and are suitable for use in minimally equipped laboratories and field settings. In this paper, we describe the development of a diagnostic test under a dipstick format for the specific detection of T. evansi, based on a DNA amplification principle (Recombinase Polymerase Amplification aka RPA) that meets the above-mentioned criteria. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. Methods/Principle findings: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. Conclusion: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed. Author summary: Onchocerciasis is a vector-borne tropical disease caused by the parasitc worm, Onchocerca volvulus. The vector is Simulium flies that breed in fast flowing rivers and streams. The infection can cause skin disease and loss of vision, giving risk to the common name of 'river blindness' for the condition. Ivermectin (Mectizan) mass drug administration (MDA) given at high coverage for many years can interrupt transmission such that MDA can eventually be stopped. The present paper provides highlights of onchocerciasis transmission interruption in the first known coordinated international cross border focus with ivermectin MDA program in Africa, where 99% of the global onchocerciasis burden exists. This focus known as Galabat-Metema is shared between Ethiopia and Sudan, both of which have established a nationwide policy for elimination of onchocerciasis. The paper provides the history of MDA in the border area and the results leading a coordinated end to MDA in the focus in 2017. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) currently classifies 20 diseases and conditions as neglected tropical diseases (NTDs). However, since its inception in 2007, PLOS Neglected Tropical Diseases has considered an expanded list that includes additional diseases with the chronic and/or debilitating, and poverty-promoting features of NTDs. Described here is an update of our current scope, which attempts to embrace all of the NTDs, and a discussion of the status of some of the more debated medical conditions in terms of whether or not they constitute an NTD. [ABSTRACT FROM AUTHOR]

Trachoma is the world's most frequent cause of blindness from an infectious agent. The disease caused by infection is associated with lack of access to sanitation and low hygiene standards. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list and is administered as preventative chemotherapy against two neglected tropical diseases (NTDs)—onchocerciasis, as an annual or bi-annual treatment, and lymphatic filariasis, as an annual treatment in combination with albendazole. Ivermectin has a known inhibitive effect on insects that reproduce in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration was associated with greater likelihood of trachoma control. Results show an association suggesting that EUs that received both IVM and AZM MDA benefit from improved control of trachoma in persistent or recrudescent areas, when compared to EUs that received AZM MDA. This initial investigation supports the potential for ivermectin's use to support SAFE. Findings warrant further work to validate ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies. Author summary: Trachoma is the world's most frequent cause of blindness from an infectious agent. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list, administered against two neglected tropical diseases (NTDs)–onchocerciasis and lymphatic filariasis. Ivermectin has an inhibitive effect on insects reproducing in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration could have controlled the putative vector, unintentionally enhancing trachoma control. Results suggest that EUs receiving both IVM and AZM MDA had improved control of trachoma, when compared to EUs that have only received AZM MDA. This initial investigation supports conducting further work into ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies. [ABSTRACT FROM AUTHOR]

Background: Dengue (DENV), Ross River (RRV) and Barmah Forest viruses (BFV) are the most common human arboviral infections in Australia and the Pacific Island Countries and Territories (PICTs) and are associated with debilitating symptoms. All are nationally notifiable in Australia, but routine surveillance is limited to a few locations in the PICTs. Understanding the level of human exposure to these viruses can inform disease management and mitigation strategies. To assess the historic and current seroprevalence of DENV, RRV and BFV in Australia and the PICTs we conducted a systematic literature review of all published quantitative serosurveys. Methodology and principal findings: The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses procedures were adopted to produce a protocol to systematically search for published studies reporting the seroprevalence of DENV, RRV and BFV in Australia and the PICTs. Data for author, research year, location, study population, serosurvey methods and positive tests were extracted. A total of 41 papers, reporting 78 serosurveys of DENV, RRV and BFV including 62,327 samples met the inclusion criteria for this review. Seroprevalence varied depending on the assay used, strategy of sample collection and location of the study population. Significant differences were observed in reported seropositivity depending on the sample collection strategy with clinically targeted sampling reporting the highest seroprevalence across all three viruses. Non-stratified seroprevalence showed wide ranges in reported positivity with DENV 0.0% -95.6%, RRV 0.0%-100.0%, and BFV 0.3% to 12.5%. We discuss some of the causes of variation including serological methods used, selection bias in sample collection including clinical or environmental associations, and location of study site. We consider the extent to which serosurveys reflect the epidemiology of the viruses and provide broad recommendations regarding the conduct and reporting of arbovirus serosurveys. Conclusions and significance: Human serosurveys provide important information on the extent of human exposure to arboviruses across: (1) time, (2) place, and (3) person (e.g., age, gender, clinical presentation etc). Interpreting results obtained at these scales has the potential to inform us about transmission cycles, improve diagnostic surveillance, and mitigate future outbreaks. Future research should streamline methods and reduce bias to allow a better understanding of the burden of these diseases and the factors associated with seroprevalence. Greater consideration should be given to the interpretation of seroprevalence in studies, and increased rigour applied in linking seroprevalence to transmission dynamics. Author summary: Mosquito-borne viruses contribute significantly to the global burden of diseases. Understanding infection rates in human populations is important for informing management of disease burden and public health policy. Serosurveys measure population exposure and immunity after arbovirus infections. We systematically reviewed serosurveys conducted for dengue virus (DENV), Ross River virus (RRV), and Barmah Forest virus (BFV) in Australia and the PICTs. We identified 41 studies reporting 78 serosurveys published between 1966 and 2020. For DENV we found the highest seroprevalence, greater than 95.0%, was reported in American Samoa. For RRV we found early evidence (1960–1969) of circulation outside Australia. There were three studies of BFV reporting 16 serosurveys within Australia and reporting low seroprevalence (<13%). Researchers used different serological methods so study comparisons must be nuanced. [ABSTRACT FROM AUTHOR]

Intestinal helminth parasites (worms) have afflicted humans throughout history and their eggs are readily detected in archaeological deposits including at locations where intestinal parasites are no longer considered endemic (e.g. the UK). Parasites provide valuable archaeological insights into historical health, sanitation, hygiene, dietary and culinary practices, as well as other factors. Differences in the prevalence of helminths over time may help us understand factors that affected the rate of infection of these parasites in past populations. While communal deposits often contain relatively high numbers of parasite eggs, these cannot be used to calculate prevalence rates, which are a key epidemiological measure of infection. The prevalence of intestinal helminths was investigated through time in England, based on analysis of 464 human burials from 17 sites, dating from the Prehistoric to Industrial periods. Eggs from two faecal-oral transmitted nematodes (Ascaris sp. and Trichuris sp.) and the food-derived cestodes (Taenia spp. and Diphyllobothrium latum syn Dibothriocephalus latus) were identified, although only Ascaris was detected at a high frequency. The changing prevalence of nematode infections can be attributed to changes in effective sanitation or other factors that affect these faecal-oral transmitted parasites and the presence of cestode infections reflect dietary and culinary preferences. These results indicate that the impact of helminth infections on past populations varied over time, and that some locations witnessed a dramatic reduction in parasite prevalence during the industrial era (18th-19th century), whereas other locations continued to experience high prevalence levels. The factors underlying these reductions and the variation in prevalence provide a key historical context for modern anthelmintic programs. Author summary: Parasitic worms (helminths) cause many health problems in poorer countries, particularly those in tropical and sub-tropical regions. In modern Europe these infections are very rare and mostly found in those travelling from endemic areas but this wasn't always the case. Archaeological studies have detected eggs of parasitic helminths in numerous European sites. Key questions include how prevalent these infections were in past communities and whether (or when) these patterns changed over time? This paper addresses both of these questions using a large number of single grave samples from archaeological sites in England dating between Prehistoric and Industrial periods. Helminth infections were detected across all periods but the overall prevalence rates changed over time, being highest in the Roman and Late-Medieval periods. The Industrial period was interesting in that two of the three sites contained very few (or no) parasites whereas the third, London, contained high levels of infection. We discuss factors that may have contributed to the changing parasite landscape and how understanding these factors may influence efforts to control helminth infections in modern endemic areas. [ABSTRACT FROM AUTHOR]

Background: The focus on laboratory-based diagnosis of coronavirus disease 2019 (COVID-19) warrants alternative public health tools such as rapid antigen tests. While there are a number of commercially available antigen tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), all cross-react with the genetically similar SARS-CoV-1 or require an instrument for results interpretation. Methodology/Principal findings: We developed and validated rapid antigen tests that use pairs of murine-derived monoclonal antibodies (mAbs), along with gold nanoparticles, to detect SARS-CoV-2 with or without cross-reaction to SARS-CoV-1 and other coronaviruses. In this development, we demonstrate a robust antibody screening methodology for the selection of mAb pairs that can recognize SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. Linear epitope mapping of the mAbs helped elucidate SARS-CoV-2 S and N interactions in lateral flow chromatography. A candidate rapid antigen test for SARS-CoV-2 N was validated using nasal swab specimens that were confirmed positive or negative by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Test results were image-captured using a mobile phone and normalized signal pixel intensities were calculated; signal intensities were inversely correlated to RT-PCR cycle threshold (Ct) value. Conclusion/Significance: Overall, our results suggest that the rapid antigen test is optimized to detect SARS-CoV-2 N during the acute phase of COVID-19. The rapid antigen tests developed in this study are alternative tools for wide scale public health surveillance of COVID-19. Author summary: The delays in diagnostic testing and lack of proper surveillance during the COVID-19 pandemic have contributed, in part, to the unprecedented death toll and impediment to wellbeing. As asymptomatic individuals have contributed to a large portion of disease spread, improved public health tools for widespread screening are necessary to maintain low transmission levels. We developed new rapid antigen tests that can be administered in less than 15 minutes without instrumentation, offering potential for frequent asymptomatic screening at-home and for point-of-care use in high-traffic areas such as schools, hospitals, and airports. The SARS-CoV-2 monoclonal antibody screening methodology resulted in pairs with or without cross-reaction to SARS-CoV-1, offering new opportunities for public health tools such as wide scale surveillance. This paper provides important insights for nanoparticle-based immunochromatographic assays. [ABSTRACT FROM AUTHOR]

Background: American Samoa completed seven rounds of mass drug administration from 2000–2006 as part of the Global Programme to Eliminate Lymphatic Filariasis (LF). However, resurgence was confirmed in 2016 through WHO-recommended school-based transmission assessment survey and a community-based survey. This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF. Method: Non-spatial clustering of infection markers (antigen [Ag], microfilaraemia [Mf], and antibodies (Ab [Wb123, Bm14, Bm33]) was assessed using intra-cluster correlation coefficients (ICC) at household and village levels. Spatial dependence, clustering and hotspots were examined using semivariograms, Kulldorf's scan statistic and Getis-Ord Gi* statistics based on locations of surveyed households. Results: The survey included 2671 persons (750 households, 730 unique locations in 30 villages). ICCs were higher at household (0.20–0.69) than village levels (0.10–0.30) for all infection markers. Semivariograms identified significant spatial dependency for all markers (range 207–562 metres). Using Kuldorff's scan statistic, significant spatial clustering was observed in two previously known locations of ongoing transmission: for all markers in Fagali'i and all Abs in Vaitogi. Getis-Ord Gi* statistic identified hotspots of all markers in Fagali'i, Vaitogi, and Pago Pago-Anua areas. A hotspot of Ag and Wb123 Ab was identified around the villages of Nua-Seetaga-Afao. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili'ili-Tafuna. Conclusion: Our study demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, the benefits of using multiple infection markers, and the value of triangulating results between methods. Author summary: Lymphatic filariasis is a parasitic infection caused by thread-like filarial nematodes and transmitted by mosquitoes. Lymphatic filariasis was endemic in American Samoa and seven rounds of mass drug administration were distributed between 2000 and 2006. Routine blood surveys in 2011 and 2015 did not identify any evidence of ongoing transmission. However, research studies conducted at around the same time showed evidence of residual hotspots and ongoing transmission, which was confirmed by both school-based and community-based surveys in 2016. This study analysed data from the 2016 community survey to identify clusters and hotspots using both non-spatial and spatial analytical methods. The findings confirmed previously known locations of ongoing lymphatic filariasis transmission in American Samoa and identified other potential hotspots that warrant further investigation. We demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, and different information provided by each method. Noting the added value of these methods, they could potentially be considered as additional tools for improving lymphatic filariasis surveillance and optimising operational activities for elimination programmes, particularly for identifying areas of ongoing transmission or resurgence that may not be identified through current surveillance strategies. [ABSTRACT FROM AUTHOR]

Leprosy, or Hansen's disease, is one of the oldest infectious diseases in the world. It has long been associated with stigma and discrimination, but only in recent years has this aspect been formally recognized by the international community as a human rights issue. The UN Human Rights Council first adopted a resolution on leprosy in 2008, and this was later followed by a UN General Assembly resolution in 2010. Nonbinding principle and guidelines on elimination of discrimination against persons affected by leprosy and their family members accompanied the 2010 resolution, but these have yet to be fully implemented. In 2017, the Human Rights Council appointed a Special Rapporteur on leprosy to investigate the extent to which the principles and guidelines have been implemented, and her term was extended for a further 3 years in 2020. Considering the proper implementation of the principles and guidelines to be key to eliminating the discrimination that persons affected by leprosy and their families face in various parts of the world, this paper looks at the contribution the Special Rapporteur can make. Based on an assessment of her activities to date, it concludes that the Special Rapporteur has actively worked to build networks with persons affected by leprosy and related organizations and gain their trust, but has faced challenges in organizing official country visits. It goes on to analyze what sort of legacy the Special Rapporteur should aim to leave behind after completing her second term and how she can go about doing so in the time remaining. To this end, it makes 5 suggestions: (1) gather information systematically on the actual situation of discrimination; (2) compile a collection of success stories; (3) ensure that there is consistency between legally binding international covenants and treaties and the principles and guidelines; (4) present proposals for concrete actions that can be taken after the Special Rapporteur's second term ends; and (5) initiate a feasibility study on creating an "index" and "indicators" to measure the current status of stigma and discrimination and the extent to which the principles and guidelines have been implemented. [ABSTRACT FROM AUTHOR]

Background: Breast-feeding holds considerable potential to reduce infant mortality. Feeding choices, already complex, take on additional complexity against a backdrop of the risk of transmissible Ebola Virus. This review describes the factors that influence infant feeding and attitudes of pregnant women, mothers, family members and health practitioners, policy makers and providers (midwives) concerning infant feeding when there is a risk of Mother-to-Child (MTC) transmission of Ebola Virus Disease (EVD). Methodology: A systematic review of qualitative studies identified through rigorous searches of thirteen online databases and additional citation searches of included studies was undertaken. Search terms included breast-feeding, breast-feeding, infant feeding; Ebola; and qualitative, interview(s) and findings. Independent extraction of data by two reviewers using predefined extraction forms. Studies were assessed using the CASP Qualitative checklist. Principal findings: 5219 references were screened. 38 references related specifically to Ebola, and five papers met the inclusion criteria with data gathered from two settings: Guinea and Sierra Leone. The EVD outbreak had a significant impact on beliefs, attitudes, and resources to support infant feeding practices negatively affecting the nutritional status of children. The evidence from these studies highlight the need for guidance and appropriate psychosocial support need to be available to mothers who display symptoms and become infected and to front-line staff who are giving advice. Communities need to be engaged because stigma and fear may hinder uptake of appropriate interventions. The EVD outbreak caused multi-level system disruption akin to that seen following a natural disaster, meaning that logistics and coordination are critical and need adequate resourcing. Food production and distribution, and malnutrition screening are also disrupted and thereby compounding compromised nutritional status. The limited number of relevant studies highlights the need for further primary research, particularly in translation of messages to local settings. Conclusions: An EVD outbreak causes multi-level disruption that negatively impacts infant feeding and child care practices. Negative impacts have multiple causes and successful planning for Ebola outbreaks requires that nutrition of infants and young children is a priority. Lessons from the Ebola pandemic have wider applicability to other pandemic contexts including Covid-19. Author summary: An Ebola outbreak has been likened to a natural disaster in its devastating impact on child health and nutritional status. The ease of transmission of a disease with a 50% mortality rate for those once infected raises particular challenges for breast-feeding women. This systematic review explored the attitudes and preferences of pregnant women, mothers, family members, health practitioners and policy makers concerning infant feeding during an Ebola epidemic as documented in qualitative studies. Participants reported confusion and inconsistent guidance regarding breast-feeding practice, together with difficulties in conveying recommendations to separate mothers infected with Ebola from their breast-feeding infants. Disruption impacted on access to supplementary and complementary feeds, health systems monitoring child growth and support to child health. Widespread distrust and suspicion of health professionals hindered health care provision. Wider family assumed roles in feeding and caring for young children, within the context of reduced access to nutritious foods and supplementary feeds. The work of humanitarian agencies, while valuable, lacked coordination. Planning for an Ebola outbreak requires advance preparation of health messaging for mothers and caregivers, coordinated provision of complementary feeds and support for families who assume caring responsibilities. Strategies to ensure linked up working between government and humanitarian agencies are essential. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004–2018 period, as well as the safety and efficacy of CD treatment on this population. Methodology/Principal findings: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. Conclusions/Significances: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern. Author summary: Chagas disease, caused by the protozoan Trypanosoma cruzi, has traditionally been confined to endemic locations in South America (with vectorial transmission), but is nowadays emerging in Europe, mainly in Spain, due to immigration. A series of characteristics of this disease condition its management. It is usually asymptomatic (especially in early stages), it can be transmitted from mothers to child (vertical transmission) and treatment is more effective at a younger age or during the early stages of infection. For these reasons early diagnosis and treatment of infected children is a priority. To date, there are few publications on pediatric CD series in non-endemic regions. In this paper we describe the epidemiological and clinical characteristics of 51 children diagnosed with pediatric CD in a non-endemic area, as well as the the safety and efficacy of treatment in this patient population. We found that most patients were asymptomatic at diagnosis. The cure percentage was clearly higher when they were treated before one year-old (80% vs 4.3% in children older than one).Adverse events to treatment have occurred especially in older children, being frequent in this age group (median age 11 years). The high proportion of patients lost to follow-up that occurs in this vulnerable population is also noteworthy (35.3% in our case). We highlight, as a conclusion of our study, the need of carrying out systematic screening for this disease (women of childbearing age, children of mothers with positive serology) to reduce the rate of vertical transmission and to achieve higher cure rates and better tolerance to treatment. [ABSTRACT FROM AUTHOR]

Diagnosing the causative agent of febrile illness in resource-limited countries is a challenge in part due to lack of adequate diagnostic infrastructure to confirm cause of infection. Most febrile illnesses (>60%) are non-malarial, with a significant proportion being zoonotic and likely from animal origins. To better characterize the pathways for zoonotic disease transmission and control in vulnerable communities, adequate information on the communities' experiences and lexicon describing fever, and their understanding and perceptions of risk pathways is required. We undertook an ethnographic study to understand behaviors, exposures, and attitudes toward fever at the community level. Our hope is to better elucidate areas of priority surveillance and diagnostic investment. A focused ethnography consisting of participant observation, informal conversations, 4 barazas (community meetings), and formal ethnographic interviews (13 Focus group discussions and 17 Key informant interviews) was conducted between April and November 2015 in Kasese and Hoima Districts in Uganda. Perception of illness and associated risk factors was heavily influenced by the predominant livelihood activity of the community. The term "fever" referred to multiple temperature elevating disease processes, recognized as distinct pathological occurrences. However, malaria was the illness often cited, treated, or diagnosed both at the health facilities and through self-diagnosis and treatment. As expected, fever is as an important health challenge affecting all ages. Recognition of malarial fever was consistent with a biomedical model of disease while non-malarial fevers were interpreted mainly through ethno etiological models of explanation. These models are currently being used to inform education and prevention strategies and treatment regimens toward the goal of improving patients' outcomes and confidence in the health system. Development of treatment algorithms that consider social, cultural, and economic contexts, especially where human-animal interaction is prevalent, should factor animal exposure and zoonotic illnesses as important differentials. Author summary: Across the tropics malaria prevalence has been steadily declining over the last 15 years. This has revealed the importance of non-malarial febrile illnesses and their link to livestock production. Unlike malaria, managing NMFI in resource limited settings is challenging due to the limited number of diagnostic tools available and communities' health seeking behavior. To develop effective NMFI prevention and management strategies, a comprehensive exploration of the socio-cultural drivers of NMFIs among rural livestock keeping communities is required. Towards this end we conducted a focused ethnographic study in Western Uganda among communities with high human livestock interaction to describe communities' a) perception of the syndrome of fever b), important biosocial pathways associated with febrile illness and c) their management of these febrile illnesses. This paper describes important biosocial drivers of NMFI, highlights important aspects of the cultural epidemiology of NMFIs, and illustrates the unintended consequences of global health policies on the management of NMFIs at the community level. It concludes by proposing important additions to NMFI clinical algorithms that could improve the sensitivity of such tools in areas of limited diagnostic capacities. [ABSTRACT FROM AUTHOR]

Background: In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities. Methods: Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day's community coverage informed the following day's vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated. Results: During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff. Conclusion: The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives. Author Summary: The World Health Organization (WHO) recently endorsed the creation of a global oral cholera vaccine (OCV) stockpile as part of an integrated, strategic framework to address the re-emerging threat that cholera causes worldwide. In conjunction, the WHO also called for continued monitoring and evaluation around the use of OCV in different settings. In response to the cholera epidemic in Haiti that began in October 2010, Partners In Health, an implementing partner of Haiti's Ministry of Health, vaccinated 50,000 Haitians in two rural communities in the Artibonite Valley in 2012. In this paper, the authors describe the use of mobile health (mHealth) technology for data collection and geospatial mapping to document this rural OCV campaign, focusing on the utility, benefits, and challenges of mHealth in a reactive campaign in the midst of the ongoing epidemic. [ABSTRACT FROM AUTHOR]

Background: Scientific literature on cystic echinococcosis (CE) reporting data on risk factors is limited and to the best of our knowledge, no global evaluation of human CE risk factors has to date been performed. This systematic review (SR) summarizes available data on statistically relevant potential risk factors (PRFs) associated with human CE. Methodology/Principal Findings: Database searches identified 1,367 papers, of which thirty-seven were eligible for inclusion. Of these, eight and twenty-nine were case-control and cross-sectional studies, respectively. Among the eligible papers, twenty-one were included in the meta-analyses. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for the two study designs. PRFs derived from case-control studies that were significantly associated with higher odds of outcome were “dog free to roam” (OR 5.23; 95% CI 2.45–11.14), “feeding dogs with viscera” (OR 4.69; 95% CI 3.02–7.29), “slaughter at home” (OR 4.67; 95% CI 2.02–10.78) or at “slaughterhouses” (OR 2.7; 95% CI 1.15–6.3), “dog ownership” (OR 3.54; 95% CI 1.27–9.85), “living in rural areas” (OR 1.83; 95% CI 1.16–2.9) and “low income” (OR 1.68; 95% CI 1.02–2.76). Statistically significant PRFs from cross-sectional studies with higher odds of outcome were “age >16 years” (OR 6.08; 95% CI 4.05–9.13), “living in rural areas” (OR 2.26; 95% CI 1.41–3.61), “being female” (OR 1.38; 95% CI 1.06–1.8) and “dog ownership” (OR 1.37; 95% CI 1.01–1.86). Conclusions/Significance: Living in endemic rural areas, in which free roaming dogs have access to offal and being a dog-owner, seem to be among the most significant PRFs for acquiring this parasitic infection. Results of data analysed here may contribute to our understanding of the PRFs for CE and may potentially be useful in planning community interventions aimed at controlling CE in endemic areas. [ABSTRACT FROM AUTHOR]

Background: In the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal. Methodology/principal findings: With 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km2 for the five-year period 2016–2020. This reduction of 83% from the 2000–2004 baseline (i.e. 709,000 km2) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d'Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO). Conclusions/significance: The steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021–2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts). Author summary: Human African trypanosomiasis (HAT) is a lethal neglected tropical disease (NTD) transmitted by the bite of infected tsetse flies. The disease is also known as "sleeping sickness". During the 20th century it caused enormous suffering in the endemic areas in sub-Saharan Africa. HAT transmission last soared in the late 1990s, triggering a renewed, coordinated and very successful control effort. In this paper, we present achievements towards HAT elimination, with a focus on the WHO road map targets for 2020. In particular, reported cases continue to decline, from over 30,000 cases per year at the turn of the century to 663 cases in 2020. Despite the impact of the COVID-19 pandemic, HAT surveillance was largely sustained, and the network of health facilities able to diagnose and treat the disease further expanded. Looking to the future, the World Health Organization (WHO) set bold new targets for HAT in its 2021–2030 road map for NTDs, namely: the elimination of transmission of gambiense HAT, which occurs in western and central Africa, and the elimination as a public health problem of rhodesiense HAT, which is found in eastern and southern Africa. The strong commitment of national health authorities and the international community will be essential if these goals are to be achieved. [ABSTRACT FROM AUTHOR]

Background: As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods: We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results: A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (convention PCR, qPCR, Digital droplet PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions: Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals. Author summary: Schistosoma japonicum is a parasite that can cause serious intestinal schistosomiasis. The infection is mainly diagnosed by parasitological and immunological methods, such as Kato-Katz test and indirect hemagglutination assay. However, both of these are not sensitive enough to accurately assess schistosomiasis elimination/eradication. PCR assays, detecting parasite DNA, are theoretically a highly suitable, sensitive and specific, alternative. However, reported performance varies greatly among studies. Therefore, we performed this meta-analysis (PROSPERO, registered No. CRD42021233165) to analyze and summarize the data from relevant studies of variable-temperature PCR for the diagnosis of S. japonicum infections, using stool or blood samples from humans in endemic areas. We retrieved a total of 13 articles including data from 4268 participants across 16 studies. There was high heterogeneity among studies, but no publication bias was found. Analyses revealed that PCR techniques had a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas, with both high sensitivity and specificity. Further research on S. japonicum diagnostic techniques, especially in low endemicity areas and for detection of dual-sex and single-sex infections are required. These may be best using highly sensitive gene targets in nested PCR reactions. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease characterized by a wide geographical distribution in the Mediterranean basin and is endemic in several of its countries. In addition, the vector Phlebotomus sergenti is abundantly present all around the basin. Its transmission cycle is still subject to debate. In some countries, the presence of an animal reservoir has been confirmed. In Morocco, CL due to L. tropica has risen since the 1980s and has spread widely to become the most abundant form of leishmaniasis in the territory. However, the anthroponotic transmission is so far the only recognized mode, despite recordings of L. tropica infection in animal hosts. In this review article, we assess the situation of CL due to L. tropica in the Mediterranean basin with a focus on Morocco and gather knowledge about any potential zoonotic transmission in the country. A concomitant zoonotic transmission could explain the persistence of the disease in areas where human protective measures combined with vector management did not help reduce the disease burden. Author summary: Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease still considered to be anthroponotic in Morocco despite evidence of zoonotic transmission in other endemic countries of the Mediterranean basin. Its high incidence in the country makes it necessary to investigate whether or not a potential concomitant zoonotic transmission exists alongside the anthroponotic one. Moreover, several reports of natural animal infection have been noted in the country. In this paper, we review how CL due to L. tropica is present around the Mediterranean basin, with a particular focus on the Moroccan foci, and try to unveil the existence of a zoonotic transmission in the area. A deep understanding of the transmission patterns of L. tropica in the region is necessary for the implementation of effective control measures and a better assessment of the disease burden. In addition, the complexity of this neglected disease requires more fundamental and applied research to unveil potential factors involved in its spread. [ABSTRACT FROM AUTHOR]

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi'an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi'an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was also found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics. Author summary: Hemorrhagic fever with renal syndrome (HFRS) is an infectious disease transmitted by the infected reservoir hosts, which chiefly include rodents, shrews, and moles. The mechanism of HFRS infection is determined by a complex interplay of various natural and socioeconomic factors. Previous studies have identified a close relationship between urbanization processes and HFRS transmission dynamics. However, the relationship involves a dual response and has not yet been quantitatively identified. This research aimed to spatiotemporally characterize how rapid urbanization affects the dynamics of HFRS. In addition, the role of water bodies, vegetation, rainfall, and occupation types in epidemic transmissions has also not been adequately investigated at the interurban scale over a long time period. Therefore, we analyzed the spatiotemporal association between the distributions of water bodies and HFRS infections and also investigated the interactions between urbanization, water body, vegetation, rainfall, and different occupation types by using multi-source data through both traditional statistical and geospatial techniques. Our work revealed biphasic associations among HFRS infection with both rapid urbanization and distribution of water bodies. Hence, it can provide useful information to formulate effective strategies for the prevention and control of HFRS. [ABSTRACT FROM AUTHOR]

Background: West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. Methodology and principal findings: References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts' opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. Conclusions: This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa. Author summary: Since its discovery in the African continent in 1937, West Nile virus expansion and invasion into new regions represent a serious concern today for an increasing number of countries worldwide. Although about 80% of infected individuals are asymptomatic, this zoonotic virus is pathogenic for humans other than for some animal species, displaying a range of clinical manifestation spanning from influenza-like symptoms to severe neurological complication and death. This study provides an updated overview on the current knowledge of WNV epidemiology in each African country, summarizing available data on incidence of the infection in humans and animals, the circulating lineages and clades, other than an updated list of the principal arthropod vectors found naturally infected and the availability of vector competence studies. However, this review highlights also the lack of knowledge regarding the occurrence and intensity of circulation of WNV in many African countries. Therefore, considering the sensitivity of WNV transmission system to climate and other environmental changes, along with the increasing level of interconnections among continents due to globalization, the intensification of the research activities on WNV and a promotion of a coordinated surveillance actions across African and European countries would provide the information of utility for a better evaluation of the actual risk of WNV and disease burden at trans-continental scale. [ABSTRACT FROM AUTHOR]

Introduction: In Colombia, organochloride, organophosphate, carbamate, and pyrethroid insecticides are broadly used to control Aedes aegypti populations. However, Colombian mosquito populations have shown variability in their susceptibility profiles to these insecticides, with some expressing high resistance levels. Materials and methods: In this study, we analyzed the susceptibility status of ten Colombian field populations of Ae. aegypti to two pyrethroids; permethrin (type-I pyrethroid) and lambda-cyhalothrin (type-II pyrethroid). In addition, we evaluated if mosquitoes pressured with increasing lambda-cyhalothrin concentrations during some filial generations exhibited altered allelic frequency of these kdr mutations and the activity levels of some metabolic enzymes. Results: Mosquitoes from all field populations showed resistance to lambda-cyhalothrin and permethrin. We found that resistance profiles could only be partially explained by kdr mutations and altered enzymatic activities such as esterases and mixed-function oxidases, indicating that other yet unknown mechanisms could be involved. The molecular and biochemical analyses of the most pyrethroid-resistant mosquito population (Acacías) indicated that kdr mutations and altered metabolic enzyme activity are involved in the resistance phenotype expression. Conclusions: In this context, we propose genetic surveillance of the mosquito populations to monitor the emergence of resistance as an excellent initiative to improve mosquito-borne disease control measures. Author summary: The main method of preventing Aedes-borne diseases such as dengue, Zika, and chikungunya is by targeting the primary mosquito vector, Aedes aegypti, with insecticides. However, the success of these vector control strategies is jeopardized by the widespread development of insecticide resistance in mosquito populations. Furthermore, the molecular mechanisms of insecticide resistance in Ae. aegypti are still not well understood, resulting in limited resistance mitigation and management strategies. In this paper, we found that resistance to some pyrethroid insecticides in different Colombian cities is associated with three allelic substitutions V419L, V1016I, and F1534C, on the voltage-gated sodium channel gene, known as kdr ('knock-down resistance') mutations, with all three mutations present in mosquitoes resistant to pyrethroids. The data also showed that kdr mutations are important in conferring low resistance levels, but after around 10-fold intensity, the allele frequencies don't change, indicating that other mechanisms contribute to the resistance. Thus, we found that mosquitoes under selective pressure with insecticides present also altered enzymatic activities such as esterases and mixed-function oxidases, indicating that kdr mutations and metabolic enzymes are involved in the resistance expression. The findings on the extent of insecticide resistance and the molecular mechanisms underpinning the problem will impact the surveillance, selection, and rational use of insecticides by local health authorities. [ABSTRACT FROM AUTHOR]

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5–14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes. Author summary: The question of 'ecology or immunology' as determinants of the shape of age intensity profiles of infection is still not resolved, but a degree of immunity is believed to slowly build up over long periods of exposure. In this study we show that acquired immunity dependent on the integral of past exposure to infection has a strong effect on the potential impact of MDA programmes to control morbidity induced by schistosome infection. We employ an individual based stochastic model of parasite transmission and control to demonstrate the effects of acquired immunity. In particular, we show that MDA programmes are less effective if human hosts acquire some level of immunity in proportion to the sum of an individual's past exposure to infection. If acquired immunity is acting with strength, in some moderate to high transmission settings, we show that the current treatment guidelines are unlikely to achieve morbidity control and elimination as a public health problem. This suggests that programme adaptations to increase the frequency of treatment where at all possible are required. This study aims to provide health workers with quantitative tools to assess what treatment strategies are best applied in given epidemiological settings. [ABSTRACT FROM AUTHOR]

Background: The Bangladesh Lymphatic Filariasis (LF) Elimination Programme has made significant progress in interrupting transmission through mass drug administration (MDA) and has now focussed its efforts on scaling up managing morbidity and preventing disability (MMDP) activities to deliver the minimum package of care to people affected by LF clinical conditions. This paper highlights the Bangladesh LF Programme's success in conducting a large-scale cross-sectional survey to determine the number of people affected by lymphoedema and hydrocoele, which enabled clinical risk maps to be developed for targeted interventions across the 34 endemic districts (19 high endemic; 15 low endemic). Methodology/Principal findings: In the 19 high endemic districts, 8,145 community clinic staff were trained to identify and report patients in their catchment area. In the 15 low endemic districts, a team of 10 trained field assistants conducted active case finding with cases reported via a SMS mHealth tool. Disease burden and prevalence maps were developed, with morbidity hotspots identified at sub-district level based on a combination of the highest prevalence rates per 100,000 and case-density rates per square kilometre (km2). The relationship between morbidity and baseline microfilaria (mf) prevalence was also examined. In total 43,678 cases were identified in the 19 high endemic districts; 30,616 limb lymphoedema (70.1%; female 55.3%), 12,824 hydrocoele (29.4%), and 238 breast/female genital swelling (0.5%). Rangpur Division reported the highest cases numbers and prevalence of lymphoedema (26,781 cases, 195 per 100,000) and hydrocoele (11661 cases, 169.6 per 100,000), with lymphoedema predominately affecting females (n = 21,652). Rangpur and Lalmonirhat Districts reported the highest case numbers (n = 11,199), and prevalence (569 per 100,000) respectively, with five overlapping lymphoedema and hydrocoele sub-district hotspots. In the 15 low endemic districts, 732 cases were identified; 661 lymphoedema (90.2%; female 39.6%), 56 hydrocoele (7.8%), and 15 both conditions (2.0%). Spearman's correlation analysis found morbidity and mf prevalence significantly positively correlated (r = 0.904; p<0.01). Conclusions/Significance: The Bangladesh LF Programme has developed one of the largest, most comprehensive country databases on LF clinical conditions in the world. It provides an essential database for health workers to identify local morbidity hotspots, deliver the minimum package of care, and address the dossier elimination requirements. Author summary: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) requires lymphatic filariasis (LF) endemic countries, such as Bangladesh, to estimate the number of lymphoedema and hydrocoele cases in order to deliver the minimum package of care required to control morbidity and reduce patient suffering. This paper highlights the Bangladesh LF Elimination Programme's progress in training more than 8000 community health workers to identify more than 44,000 cases across 34 endemic districts where approximately 70 million people are at risk. The morbidity data collected enabled the creation of a national database and a series of risk maps of lymphoedema and hydrocoele to be developed, which highlighted the significant burden in northern Rangpur Division, especially of lymphoedema among female patients. The Bangladesh LF Elimination Programme's efforts to identify LF cases across all endemic districts represents one of the most comprehensive national databases on LF clinical cases in the world. It provides an informative database for health workers to use in the delivery of the minimum package of care and a template for other countries to adopt and develop national strategies to manage morbidity and prevent disability as recommended by GPELF. [ABSTRACT FROM AUTHOR]

Background: Scabies is a common dermatological condition, affecting more than 130 million people at any time. To evaluate and/or predict the effectiveness and cost-effectiveness of scabies interventions, disease transmission modelling can be used. Objective: To review published scabies models and data to inform the design of a comprehensive scabies transmission modelling framework to evaluate the cost-effectiveness of scabies interventions. Methods: Systematic literature search in PubMed, Medline, Embase, CINAHL, and the Cochrane Library identified scabies studies published since the year 2000. Selected papers included modelling studies and studies on the life cycle of scabies mites, patient quality of life and resource use. Reference lists of reviews were used to identify any papers missed through the search strategy. Strengths and limitations of identified scabies models were evaluated and used to design a modelling framework. Potential model inputs were identified and discussed. Findings: Four scabies models were published: a Markov decision tree, two compartmental models, and an agent-based, network-dependent Monte Carlo model. None of the models specifically addressed crusted scabies, which is associated with high morbidity, mortality, and increased transmission. There is a lack of reliable, comprehensive information about scabies biology and the impact this disease has on patients and society. Discussion: Clinicians and health economists working in the field of scabies are encouraged to use the current review to inform disease transmission modelling and economic evaluations on interventions against scabies. [ABSTRACT FROM AUTHOR]

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens. Author summary: Distribution of poor quality medicines are an increasing global concern, especially in low- and middle-income countries (LMICs) where the effectiveness of antimicrobials can be a matter of life-or-death for patients with malaria and other potentially fatal infectious diseases. Substandard and falsified antimalarial drugs, including artemisinin-based combination therapies are widely distributed across LMICs. This endangers patients and in the longer term threatens malaria control and elimination campaigns by promoting the development of drug resistance. New field detection devices are increasingly available and could enhance the inspection process with prompt and actionable, real-time results. We conducted a cost-effectiveness analysis of the implementation of six portable devices for medicine quality screening during pharmacy post-market surveillances in Laos. This analysis conservatively focused only on the benefits of these devices in detecting substandard and falsified artemisinin-based combination therapies (ACTs), measured in terms of health outcomes for malaria patients obtaining treatment from pharmacies. Our findings suggest that using these portable devices for routine surveillance of ACT quality is likely to be cost-effective. Policy-makers and regulators might therefore consider investment in these field detection devices to minimise undesired health and economic burdens associated with substandard and falsified medicines. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis, also known as bilharzia, is a chronic parasitic blood fluke infection acquired through contact with contaminated surface water. The illness may be mild or can cause significant morbidity with potentially serious complications. Children and those living in rural areas with limited access to piped water and services for healthcare are the most commonly infected. To address the prevalence of the disease in parts of South Africa (SA) effective national control measures are planned, but have not yet been implemented. This study aimed to estimate the prevalence and trends of public sector laboratory-confirmed schistosomiasis cases in SA over an eight-year (2011–2018) period, to inform future control measures. Methodology & principal findings: This is a descriptive analysis of secondary data from the National Health Laboratory Service (NHLS). The study included all records of patients for whom microscopic examination detected Schistosoma species eggs in urine or stool specimens from January 2011 to December 2018. Crude estimates of the prevalence were calculated using national census mid-year provincial population estimates as denominators, and simple linear regression was used to analyse prevalence trends. A test rate ratio was developed to describe variations in testing volumes among different groups and to adjust prevalence estimates for testing variations. A total number of 135 627 schistosomiasis cases was analysed with the highest prevalence observed among males and individuals aged 5–19 years. We describe ongoing endemicity in the Eastern Cape Province, and indicate important differences in the testing between population groups. Conclusion: While there was no overall change in the prevalence of schistosomiasis during the analysis period, an average of 36 people per 100 000 was infected annually. As such, this represents an opportunity to control the disease and improve quality of life of affected people. Laboratory-based surveillance is a useful method for reporting occurrence and evaluating future intervention programs where resources to implement active surveillance are limited. Author summary: This is the first paper to describe the prevalence of human schistosomiasis in South Africa using nationally representative data. The prevalence remained consistent during the eight-year period, independent of increasing annual testing volumes. Groups with the highest burden included males and individuals aged 5–19 years. The schistosomiasis-endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal emerged as the highest-burdened areas, and ongoing endemicity in Eastern Cape Province was demonstrated. Western Cape Province likely reported cases imported from endemic provinces rather than being acquired by local transmission. In summary, schistosomiasis remains an important public health problem in South Africa that needs long-term sustainable, effective standardised interventions to reduce the burden. Passive laboratory-based surveillance is a practical tool for reporting prevalence, and could be used to monitor and evaluate future intervention programs. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m–km, days–weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input. [ABSTRACT FROM AUTHOR]

Background: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. Methods and findings: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. Conclusions: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination. Author summary: Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), targets the skin and nerves and often results in irreversible disabilities as well as social exclusion. Though the disease can be efficiently treated, leprosy elimination is hampered by ongoing transmission of M. leprae. Currently, elimination is monitored by the number of new cases. Since only a small percentage of individuals infected with M. leprae develops disease, this does not accommodate monitoring of transmission. Previous studies have shown that antibody levels against M. leprae in blood correspond to the bacterial load in an individual and can be used as a proxy for infection, although antibodies cannot distinguish between past and present infection. In young children, infection is recent by definition, which allows assessment of more current state of transmission in an area. Thus, this literature review investigated studies on leprosy serology in children without leprosy. Our findings underscore that young children are a fitting group for up-to-date monitoring of M. leprae transmission in an area as seropositivity is inversely related with age. Importantly, a standardized, field-friendly test quantitatively measuring anti-M. leprae antibodies should be applied for population screening to monitor the status of transmission and thereby elimination in an area. [ABSTRACT FROM AUTHOR]

Background: Anthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May–June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidence-based control measures. Methods: A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015–August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths. Results: There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30–39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3–11), butchering (ORM-H = 22, 95%CI: 5.5–89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95%CI: 3.0–16) were associated with illness. Conclusions: Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015–2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly. Author summary: We are honored to submit an original research article entitled "Cutaneous anthrax associated with handling carcasses of animals that died suddenly of unknown cause: Arua District, Uganda, January 2015–August 2017". Anthrax is a vaccine-preventable disease that can be transmitted to humans from infected animals. Our paper is based on 68 cutaneous anthrax case-patients and cases occurred throughout the three-year period, peaking during dry seasons in Arua District of Uganda. All cases occurred following sudden livestock deaths in the villages. Our findings are based on outbreak investigation which gives a better representation of the actual situation. Our article looks at the scope of the anthrax outbreak, exposures associated with illness, and evidence-based control measures. In this manuscript, we show that exposure to carcasses of animals that died suddenly was a risk factor for cutaneous anthrax in Arua District during 2015–2017. We believe the content and objectives of our work provide knowledge on epidemiology of cutaneous anthrax. [ABSTRACT FROM AUTHOR]

Background: Sustainability within neglected tropical disease (NTD) programs is a complex and challenging issue. The need for a shared understanding about what sustainability means for NTD programs is more important than ever as stakeholders are currently realigning for the next decade of NTD programming with the launch of WHO's new NTD roadmap for 2012–2030. The aim of this paper is to assess different perspectives to generate a working definition of sustainability for NTD programs. Methodology/Principal findings: This study surveyed affiliates of the NTD NGO Network (NNN) about their definitions of sustainability and then analyzed the data using an inductive and deductive process. The research team drafted a sustainability statement based on the survey findings and then solicited and incorporated feedback on the statement from a diverse group of expert reviewers. The final statement includes a working definition of sustainability for NTD programs that highlights three key essential components to sustainability: domestic commitment, responsive resource mobilization, and accountability. Conclusions/Significance: This research resulted in a sustainability statement, based on a survey and extensive consultation with stakeholders, that represents a starting point for shared understanding around the concept of sustainability for NTD programs. Future collaborative work should build off this definition and seek to incorporate indicators for sustainability into programmatic decision-making. Author summary: The question of whether a global public health program can be sustainable is as important as whether that program is effective. While neglected tropical disease (NTD) programs have achieved tangible success in reducing the burden of NTDs over the past decade through a massive collaboration between global and local stakeholders, the achievement of global NTD control and elimination goals will depend in large part on whether these efforts are sustained. This study seeks to encourage more and better dialogue around NTD program sustainability by incorporating a wide variety of expert perspectives to create and propose a shared definition of sustainability upon which future NTD programming decisions can be made. The sustainability statement based on the findings from this study suggests that three essential components to NTD program sustainability are commitment from decision-makers within NTD-endemic countries, resource mobilization that is responsive to local needs, and enhanced mechanisms for accountability. [ABSTRACT FROM AUTHOR]

Background: The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection. Methods: This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library. Results: We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor. Conclusions: Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay. Author summary: Leprosy remains an important public health problem with many new leprosy patients diagnosed with visible physical deformities, indicating a long delay in the detection of cases. For effective prevention programs, it is important to know the factors at the level of the individual and the community that contribute to the delay. We reviewed all published studies that reported individual and community factors related to delayed case detection in leprosy and included 27 studies in our analysis, published between January 1, 2000, and January 31, 2021. Health-service-seeking behavior was the most common factor associated with delay in case detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge about leprosy. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor associated with detection delay. The presence of physical disability in newly diagnosed leprosy patients is clearly related to the delay in detecting these patients. Leprosy control interventions should take factors related to detection delay into account more comprehensively. Also, there is a need to study health service-related factors that contribute to detection delay of leprosy patients. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or elimination: lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (STH), trachoma, Chagas’ disease, human African trypanosomiasis (HAT), leprosy, and visceral leishmaniasis (VL). Methodology: We conducted a systematic literature review, including publications between 2004–2013 found in Embase, Medline (OvidSP), Cochrane Central, Web of Science, Popline, Lilacs, and Scielo. We included publications in international peer-reviewed journals on studies concerning the top 20 countries in terms of the burden of the NTD under study. Principal findings: We identified 5,516 publications, of which 93 met the inclusion criteria. Of these, 59 papers reported substantial and statistically significant socioeconomic inequalities in NTD distribution, with higher odds of infection or disease among poor and less-educated people compared with better-off groups. The findings were mixed in 23 studies, and 11 studies showed no substantial or statistically significant inequality. Most information was available for STH, VL, schistosomiasis, and, to a lesser extent, for trachoma. For the other NTDs, evidence on their socioeconomic distribution was scarce. The magnitude of inequality varied, but often, the odds of infection or disease were twice as high among socioeconomically disadvantaged groups compared with better-off strata. Inequalities often took the form of a gradient, with higher odds of infection or disease each step down the socioeconomic hierarchy. Notwithstanding these inequalities, the prevalence of some NTDs was sometimes also high among better-off groups in some highly endemic areas. Conclusions: While recent evidence on socioeconomic inequalities is scarce for most individual NTDs, for some, there is considerable evidence of substantially higher odds of infection or disease among socioeconomically disadvantaged groups. NTD control activities as proposed in the London Declaration, when set up in a way that they reach the most in need, will benefit the poorest populations in poor countries. [ABSTRACT FROM AUTHOR]

Correction: Long-term Chikungunya sequelae and quality of life 2.5 years post-acute disease in a prospective cohort in Curaçao Reference 1 Doran C, Elsinga J, Fokkema A, Berenschot K, Gerstenbluth I, et al. (2022) Long-term Chikungunya sequelae and quality of life 2.5 years post-acute disease in a prospective cohort in Curaçao. There is an error in the Author Summary section that affects the understanding of the results and conclusion of the paper. [Extracted from the article]

With increasing geographic spread, frequency, and magnitude of outbreaks, dengue continues to pose a major public health threat worldwide. Dengvaxia, a dengue live-attenuated tetravalent vaccine, was licensed in 2015, but post hoc analyses of long-term data showed serostatus-dependent vaccine performance with an excess risk of hospitalized and severe dengue in seronegative vaccine recipients. The World Health Organization (WHO) recommended that only persons with evidence of past dengue infection should receive the vaccine. A test for pre-vaccination screening for dengue serostatus is needed. To develop the target product profile (TPP) for a dengue pre-vaccination screening test, face-to-face consultative meetings were organized with follow-up regional consultations. A technical working group was formed to develop consensus on a reference test against which candidate pre-vaccination screening tests could be compared. The group also reviewed current diagnostic landscape and the need to accelerate the evaluation, regulatory approval, and policy development of tests that can identify seropositive individuals and maximize public health impact of vaccination while avoiding the risk of hospitalization in dengue-naive individuals. Pre-vaccination screening strategies will benefit from rapid diagnostic tests (RDTs) that are affordable, sensitive, and specific and can be used at the point of care (POC). The TPP described the minimum and ideal characteristics of a dengue pre-vaccination screening RDT with an emphasis on high specificity. The group also made suggestions for accelerating access to these RDTs through streamlining regulatory approval and policy development. Risk and benefit based on what can be achieved with RDTs meeting minimal and optimal characteristics in the TPP across a range of seroprevalences were defined. The final choice of RDTs in each country will depend on the performance of the RDT, dengue seroprevalence in the target population, tolerance of risk, and cost-effectiveness. Author summary: This paper describes the consensus on the minimum and ideal performance and operational characteristics of rapid tests that would be used for dengue pre-vaccination screening. This profile will incentivize industry to develop better pre-vaccination screening tests. The choice of which test to use depends on the seroprevalence of the population targeted for vaccination and the optimal balance between benefit and risks. The group also made suggestions for accelerating access to these pre-vaccination screening tests through streamlining regulatory approval and policy development. [ABSTRACT FROM AUTHOR]

Background: In Peru, the information regarding sand fly vectors of leishmaniasis and bartonellosis in the Amazon region is limited. In this study, we carried out sand fly collections in Peruvian lowland and highland jungle areas using different trap type configurations and screened them for Leishmania and Bartonella DNA. Methodology/Principal findings: Phlebotomine sand flies were collected in Peruvian Amazon jungle and inter Andean regions using CDC light trap, UV and color LED traps, Mosquito Magnet trap, BG Sentinel trap, and a Shannon trap placed outside the houses. Leishmania spp. screening was performed by kDNA PCR and confirmed by a nested cytochrome B gene (cytB) PCR. Bartonella spp. screening was performed by ITS PCR and confirmed by citrate synthase gene (gltA). The PCR amplicons were sequenced to identify Leishmania and Bartonella species. UV and Blue LED traps collected the highest average number of sand flies per hour in low jungle; UV, Mosquito Magnet and Shannon traps in high jungle; and Mosquito Magnet in inter Andean region. Leishmania guyanensis in Lutzomyia carrerai carrerai and L. naiffi in Lu. hirsuta hirsuta were identified based on cytB sequencing. Bartonella spp. related to Bartonella bacilliformis in Lu. whitmani, Lu. nevesi, Lu. hirsuta hirsuta and Lu. sherlocki, and a Bartonella sp. related to Candidatus B. rondoniensis in Lu. nevesi and Lu. maranonensis were identified based on gltA gene sequencing. Conclusions/Significance: UV, Blue LED, Mosquito Magnet and Shannon traps were more efficient than the BG-Sentinel, Green, and Red LED traps. This is the first report of L. naiffi and of two genotypes of Bartonella spp. related to B. bacilliformis and Candidatus B. rondoniensis infecting sand fly species from the Amazon region in Peru. Author summary: Leishmaniasis and human bartonellosis, two neglected tropical diseases, are endemic in Peruvian Andean regions. However, no human bartonellosis cases has been reported in the Amazon jungle where leishmaniasis has high prevalence. The improvement of sand fly trapping methods and identification of putative Leishmania and Bartonella vectors across Andean and Amazonian regions are important steps towards the design of better control strategies and reducing the risk of transmission in endemic areas. In this paper the authors explored the effectiveness of different trap types, based in LED colors and odor attractants, for sand fly collections in endemic areas of leishmaniasis and bartonellosis. Also, we reported for the first time the detection of Bartonella DNA in sand fly species from the Peruvian Amazon jungle, and the first record in Peru of L. (V.) naiffi infecting Lu. hirsuta hirsuta. The information provided by this manuscript will serve as a baseline for future surveillance and intervention studies about sand fly species as potential vectors of Leishmania and Bartonella in highly endemic areas. [ABSTRACT FROM AUTHOR]

Leprosy, podoconiosis, and lymphatic filariasis (LF) are among the priority neglected tropical diseases (NTDs) in Ethiopia. The disability, psychosocial, and mental health status of people affected by these NTDs are still overlooked in global NTD discourse. The objective of this systematic review was to synthesize the existing evidence describing the disability, psychosocial, and mental health status of people affected by leprosy, podoconiosis, and LF prior to developing a holistic physical and psychosocial care package for these individuals. We searched papers reporting on disability, psychosocial, and mental health status linked to these 3 NTDs. The protocol was registered in PROSPERO with registration number CRD42019128400. Peer-reviewed articles were searched and extracted from Medline, PsycINFO, Global Health, and Embase. Articles published in English, irrespective of the year of publication, using a quantitative study methodology, were included. Abstracts and full texts were reviewed by 2 reviewers. Data were extracted and narratively summarized, as the studies were heterogeneous and used different outcome measures. Out of 1,318 titles/abstracts screened and 59 full text studies reviewed, 24 fulfilled the inclusion criteria. Fourteen studies provided evidence of the disability associated with leprosy, podoconiosis, or LF. Ten studies provided evidence on the association between the 3 NTDs and mental health or psychosocial outcomes. The prevalence of grade 2 disability varied from 3.9% to 86%. The most commonly reported mental health impacts were depression and mental distress. A high burden of mental illness was reported, varying from 12.6% to 71.7%; the suicidal ideation was also high (18.5%). In conclusion, disability and poor psychosocial and mental health status are associated with leprosy, podoconiosis, and LF. For optimum management of these NTDs, holistic care including both physical and psychosocial interventions is vital. Author summary: Podoconiosis, lymphatic filariasis (LF), and leprosy are neglected tropical diseases (NTDs) that are commonly found among disadvantaged rural and some poor urban communities. These diseases lead to disabilities of the leg, which may result in reduced productivity. The longer the duration of the disease, the more severe the disability. People affected by these diseases also commonly experience stigma and discrimination, which, in turn, affect health-seeking behavior. Due to this disability, stigma, and discrimination, people affected by these 3 NTDs have a poor quality of life. We also found a range of mental health problems related to these 3 NTDs. Among these, the most common were mental distress and depression. As all 3 NTDs are associated with poor physical, psychosocial, and mental health outcomes, management should be holistic, incorporating physical, psychosocial, and mental health interventions. Following this review, we are working on the development of a holistic integrated care package for people affected by leprosy, podoconiosis, and LF in northwestern Ethiopia. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer disease (BUD) results in disabilities and deformities in the absence of early medical intervention. The extensive role of caregiving in BUD is widely acknowledged, however, associated caregiver burden is poorly understood. In this paper we assessed the burden which caregivers experience when supporting patients with BUD in Ghana. Method/ principal findings: This qualitative study was conducted in 3 districts in Ghana between August and October 2019. 13 semi-structured interviews were conducted on caregivers of BUD patients in the local language of Twi. Data was translated into English, coded into broad themes, and direct content analysis approach was used to analyse results. The results show the caregivers face financial, psychological and health issues as a consequence of their caregiving role. Conclusion/ significance: This study found significant caregiver burden on family members. It also highlighted the psychological burden caregivers experience and the limited knowledge of the disease within endemic communities. Further research is needed to quantify the caregiver burden of BUD at different economic levels in order to better understand the impact of possible caregiver interventions on patient outcomes. Author summary: Buruli ulcer disease (BUD) is a stigmatizing skin condition caused by the bacteria, Mycobacterium ulcerans. The disease results in permanent functional limitations in the absence of early medical intervention. The disabling BUD conditions, financial constraints and frequent hospital visits support the role of caregiving for affected individuals. Caregiver burden is poorly understood although the role and need for caregiving is widely recognised in BUD. This study identified a previously unrecognized burden on the caregivers of BUD patients in 3 endemic districts in Ghana. Specifically, we identified significant financial and psychological pressure on affected families in meeting healthcare related costs and physical care while also providing for their own and other family members' needs. We also highlight the emotional burden experienced by caregivers, their reduced work productivity, the barriers caregivers face in accessing healthcare with BUD patients and the limited support available for caregivers. Our study highlights the serious social consequences of BUD in Ghana. Further quantitative research within different economic regions affected by BUD is warranted to better understand the caregiver burden of BUD. [ABSTRACT FROM AUTHOR]

Rapid diagnosis by using small, simple, and portable devices could represent one of the best strategies to limit the damage and contain the spread of viral, bacterial or protozoa diseases, principally when they can be transmitted by air and are highly contagious, as some respiratory viruses are. The presence of antibodies in blood or serum samples is not the best option for deciding when a person must be quarantined to stop transmission of disease, given that cured patients have antibodies, so the best diagnosis methods rely on the use of nucleic acid amplification procedures. Here we present a very simple device and detection principle, based a paper discs coupled to contactless conductivity (C4D) sensors, can provide fast and easy diagnostics that are needed when an epidemic outbreak develops. The paper device presented here solves one of the main drawbacks that nucleic acid amplification tests have when they are performed outside of central laboratories. As the device is sealed before amplification and integrally disposed in this way, amplimers release cannot occur, allowing repetitive testing in the physician's practice, ambulances, or other places that are not prepared to avoid cross-contamination of new samples. The use of very low volume samples allows efficient reagent use and the development of low cost, simple, and disposable point-of-care diagnostic systems. Author summary: In 2005, the World Health Organization (WHO) recognized Chagas Disease as a neglected tropical disease. Meanwhile the serological tests, recommended by WHO, can be performed for chronic disease diagnosis, the nucleic acid amplification tests must be performed for the detection of the acute phase of the disease. Although the existing laboratory diagnosis tests for Chagas Disease are sensitive and highly reproducible, they cannot be performed in rural, low infrastructure environments, where this disease prevails. In this sense, the use of simple and portable analytical devices may be able to offer an affordable solution to this problem, allowing fast sampling, diagnosis and treatment prescription in one simple and fast intervention, as the performed by short term medical missions. In this study we show for the first time a diagnosis test comprising low cost materials and employing a contactless and label-free conductivity detection system that is used to read the result of a nucleic acid amplification reaction. The test showed high sensitivity for Chagas Disease diagnosis showing the potential to be used in rural and low income places. [ABSTRACT FROM AUTHOR]

BackgroundWe were tasked by the World Health Organization (WHO) to address the following question: What techniques should be used to diagnose Schistosoma infections in snails and in the water in potential transmission sites? Our goal was to review and evaluate the available literature and provide recommendations and insights for the development of WHO's Guidelines Development Group for schistosomiasis control and elimination.MethodologyWe searched several databases using strings of search terms, searched bibliographies of pertinent papers, and contacted investigators who have made contributions to this field. Our search covered from 1970 to Sept 2020. All papers were considered in a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, and retained papers were grouped by technique and subjected to our GRADE (Grading of Recommendations, Assessment, Development and Evaluations) evidence assessment profile determined in consultation with WHO. We also considered issues of sensitivity, specificity, coverage, cost, robustness, support needs, schistosome species discrimination, and relevant detection limits.Principal findingsOur PRISMA process began with the perusal of 949 articles, of which 158 were retained for data extraction and evaluation. We identified 25 different techniques and for each applied a GRADE assessment considering limitations, inconsistency, imprecision, indirectness, and publication bias. We also provide advantages and disadvantages for each category of techniques.ConclusionsOur GRADE analysis returned an assessment of moderate quality of evidence for environmental DNA (eDNA), qPCR and LAMP (Loop-mediated isothermal amplification). No single ideal diagnostic approach has yet been developed, but considerable recent progress has been made. We note a growing trend to use eDNA techniques to permit more efficient and replicable sampling. qPCR-based protocols for follow-up detection offer a versatile, mature, sensitive, and specific platform for diagnosis though centralized facilities will be required to favor standardization. Droplet digital PCR (ddPCR) can play a complementary role if inhibitors are a concern, or more sensitivity or quantification is needed. Snail collection, followed by shedding, is encouraged to provide specimens for sequence verifications of snails or schistosomes. LAMP or other isothermal detection techniques offer the prospect of less expensive and more distributed network of analysis but may face standardization and verification challenges related to actual sequences amplified. Ability to detect schistosome infections in snails or in the water is needed if control and elimination programs hope to succeed. Any diagnostic techniques used need to be regularly verified by the acquisition of DNA sequences to confirm that the detected targets are of the expected species. Further improvements may be necessary to identify the ideal schistosome or snail sequences to target for amplification. More field testing and standardization will be essential for long-term success.

Background: Over the last few years, momentum has gathered around the feasibility and opportunity of eliminating gambiense human African trypanosomiasis (g-HAT). Under the leadership of the World Health Organization (WHO), a large coalition of stakeholders is now committed to achieving this goal. A roadmap has been laid out, and indicators and milestones have been defined to monitor the progress of the elimination of g-HAT as a public health problem by 2020. Subsequently, a more ambitious objective was set for 2030: to stop disease transmission. This paper provides a situational update to 2012 for a number of indicators of elimination: number of cases annually reported, geographic distribution of the disease and areas and populations at different levels of risk. Results: Comparing the 5-year periods 2003-2007 and 2008-2012, the area at high or very high risk of g-HAT shrank by 60%, while the area at moderate risk decreased by 22%. These are the areas where g-HAT is still to be considered a public health problem (i.e. > 1 HAT reported case per 10,000 people per annum). This contraction of at-risk areas corresponds to a reduction of 57% for the population at high or very high risk (from 4.1 to 1.8 million), and 20% for moderate risk (from 14.0 to 11.3 million). Discussion: Improved data completeness and accuracy of the Atlas of HAT enhanced our capacity to monitor the progress towards the elimination of g-HAT. The trends in the selected indicators suggest that, in recent years, progress has been steady and in line with the elimination goal laid out in the WHO roadmap on neglected tropical diseases. Author Summary: Control activities conducted over the last 15 years against gambiense human African trypanosomiasis (g-HAT) have had a tremendous impact on disease transmission, and the elimination of g-HAT now appears achievable. In this context, accurate monitoring is crucial. This paper analyzes g-HAT epidemiological trends by comparing two periods: 2003–2007 and 2008–2012. The number of reported cases decreased from 19,963 in 2003 to 7,106 in 2012. The areas at high or very high risk shrank by 60% between the two study periods. For 2008–2012, 43.4 million people out of a total of 56.4 million at risk lived in areas at low or very low risk of infection, and they have therefore met the criterion of elimination as a public health problem (i.e. < 1 case per 10,000 inhabitants per year). The challenge for the future is twofold. First, to prevent these 43.4 million people from sliding back into a situation of higher risk through effective surveillance. Second, to develop sustainable and adapted strategies to curb transmission in the areas where people are still living at moderate to very high risk. The WHO network for g-HAT elimination provides an opportunity to synergize efforts and to overcome the hurdles in this challenging endeavour. [ABSTRACT FROM AUTHOR]

The article reflects on impact of vector biology research on old and emerging neglected tropical diseases such as vector-borne diseases (VBDs). Topics include observation of trypanosomes in the human blood in 1901 by surgeon Robert Michael Forde; threat imposed by increase in insecticide resistance on the sustainability of vector control programs in several tropical regions; and research on triatomine-transmitted Chagas disease.

Background: In the Cameroon, previous efforts to identify Buruli ulcer (BU) through the mobilization of community health workers (CHWs) yielded poor results. In this paper, we describe the successful creation of a BU community of practice (BUCOP) in Bankim, Cameroon composed of hospital staff, former patients, CHWs, and traditional healers. Methods and principle findings: All seven stages of a well-defined formative research process were conducted during three phases of research carried out by a team of social scientists working closely with Bankim hospital staff. Phase one ethnographic research generated interventions tested in a phase two proof of concept study followed by a three- year pilot project. In phase three the pilot project was evaluated. An outcome evaluation documented a significant rise in BU detection, especially category I cases, and a shift in case referral. Trained CHW and traditional healers initially referred most suspected cases of BU to Bankim hospital. Over time, household members exposed to an innovative and culturally sensitive outreach education program referred the greatest number of suspected cases. Laboratory confirmation of suspected BU cases referred by community stakeholders was above 30%. An impact and process evaluation found that sustained collaboration between health staff, CHWs, and traditional healers had been achieved. CHWs came to play a more active role in organizing BU outreach activities, which increased their social status. Traditional healers found they gained more from collaboration than they lost from referral. Conclusion/ Significance: Setting up lines of communication, and promoting collaboration and trust between community stakeholders and health staff is essential to the control of neglected tropical diseases. It is also essential to health system strengthening and emerging disease preparedness. The BUCOP model described in this paper holds great promise for bringing communities together to solve pressing health problems in a culturally sensitive manner. [ABSTRACT FROM AUTHOR]

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium bovis (M. bovis) is the main causative agent of bovine zoonotic tuberculosis. The aim of this systematic review is to highlight the occupational exposure to bovine tuberculosis due to M. bovis. Methodology/principal findings: A computer based literature search was carried out to identify papers published between January 2006 and March 2017. “PubMed, Cochrane Library and Science Direct” databases were searched systematically. Articles presenting the following properties were included: (i) focusing on M. bovis; (ii) concerning occupational exposure to bovine tuberculosis. A quality assessment was performed after selection of studies. Our search strategy identified a total of 3,264 papers of which 29 studies met the inclusion criteria. Of the 29 articles, 17 were cross-sectional studies (6 were of high quality and scored in the range of 6–7, 11 were of moderate quality and scored in the range 3–5), 10 were case reports, and 2 were reviews. Different occupational fields exposing to the disease were described: livestock sector, particularly in contact with dairy cattle (farmers, veterinaries and assistants, abattoir workers) and working in contact with wildlife (hunters, taxidermists). Conclusions: A specific guideline for occupational practitioners taking care of employees exposed to bovine tuberculosis is warranted and should be tailored to level of exposure. This review was intended to be the first step of such a project. Articles were identified from various continents and countries with different socio-economic situations, broadening our understanding of the worldwide situation. Published data on occupational exposure in developed countries are scarce. We had to extrapolate findings from countries with higher prevalence of the disease. [ABSTRACT FROM AUTHOR]

Background: Control of cutaneous leishmaniasis by public health systems in the Americas relies on case identification and treatment. Point-of-care diagnostics that can be performed by health workers within or near affected communities could effectively bring the health system to the resource-limited sites providing early diagnosis and treatment, reducing morbidity and the burden of disease. Methodology/principal findings: A cross-sectional study was undertaken to evaluate the diagnostic test performance of Isothermal Recombinase Polymerase Amplification (RPA) targeting Leishmania kinetoplast DNA, coupled with a lateral flow (LF) immunochromatographic strip, in a field setting and a laboratory reference center. Minimally invasive swab and FTA filter paper samples were obtained by community health workers and highly trained technicians from ulcerated lesions of > 2 weeks' evolution from 118 patients' ≥ 2 years of age in the municipality of Tumaco, Nariño. Extracted DNA was processed by RPA-LF at a reference center or in a primary health facility in the field. Evaluation was based on a composite "gold standard" that included microscopy, culture, biopsy and real-time polymerase chain reaction detection of Leishmania 18S rDNA. Standard of care routine diagnostic tests were explored as comparators. Sensitivity and specificity of RPA-LF in the reference lab scenario were 87% (95%CI 74–94) and 86% (95%CI 74–97), respectively. In the field scenario, the sensitivity was 75% (95%CI 65–84) and specificity 89% (95%CI 78–99). Positive likelihood ratios in both scenarios were higher than 6 while negative likelihood ratios ranged to 0.2–0.3 supporting the usefulness of RPA-LF to rule-in and potentially to rule-out infection. Conclusions/significance: The low complexity requirements of RPA-LF combined with non-invasive sampling support the feasibility of its utilization by community health workers with the goal of strengthening the diagnostic capacity for cutaneous leishmaniasis in Colombia. Trial registration: ClinicalTrials.gov NCT04500873. Author summary: Limited access to diagnosis is a critical determinant of the "neglect" that defines the so-called Neglected Tropical Diseases (NTDs) including cutaneous leishmaniasis. Diagnostic tests that can be performed close to and involve the participation of the affected communities would improve access to treatment as well as diagnosis. Using non-invasive swab and filter paper samples obtained by Community Health Workers, we evaluated the diagnostic performance of an innovative and technically simple molecular test: Isothermal Recombinase Polymerase Amplification (RPA) to detect Leishmania DNA, coupled with a lateral flow (LF) strip to read the results with the naked eye. The RPA-LF test demonstrated high sensitivity and specificity and capacity to rule in or rule out a diagnosis of cutaneous leishmaniasis in both an endemic field setting and reference laboratory. The findings encourage the further optimization of the test format for Point-of-Care diagnosis by health personnel and rural health workers in endemic settings. [ABSTRACT FROM AUTHOR]