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Background: Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately provide new information to shape public policy response on cholera control and elimination. Methodology/Principal findings: Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions: WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers this provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic infectious disease neglected, caused by Mycobacterium leprae, considered a public health problem because may cause permanent physical disabilities and deformities, leading to severe limitations. This review presents an overview of the results of epidemiological studies on leprosy occurrence in childhood in Brazil, aiming to alert health planners and managers to the actual need to institute special control strategies. Methodology/Principal findings: Data collection consisted of an electronic search for publications in eight databases: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), PuBMed, Biblioteca Virtual em Saúde (BVS), SciVerse Scopus (Scopus), CAPES theses database, CAPES journals database and Web of Science of papers published up to 2016. After apply selection criteria, twenty-two papers of studies conducted in four different regions of Brazil and published between 2001 and 2016 were included in the review. The leprosy detection rate ranged from 10.9 to 78.4 per 100,000 inhabitants. Despite affecting both sexes, leprosy was more common in boys and in 10-14-year-olds. Although the authors reported a high cure proportion (82–90%), between 1.7% and 5.5% of the individuals developed a disability resulting from the disease. Conclusions/Significance: The findings of this review shows that leprosy situation in Brazilian children under 15 years is extremely adverse in that the leprosy detection rate remains high in the majority of studies. The proportion of cases involving disability is also high and reflects the difficulties and the poor effectiveness of actions aimed at controlling the disease. The authors suggest the development of studies in spatial clusters of leprosy, where beyond the routine actions established, are included news strategies of active search and campaigns and actions of educations inside the clusters of this disease. The new agenda needs to involve the precepts of ethical, humane and supportive care, in order to achieve a new level of leprosy control in Brazil. [ABSTRACT FROM AUTHOR]

Background: In 2005, there were outbreaks of febrile polyarthritis due to Chikungunya virus (CHIKV) in the Comoros Islands. CHIKV then spread to other islands in the Indian Ocean: La Réunion, Mauritius, Seychelles and Madagascar. These outbreaks revealed the lack of surveillance and preparedness of Madagascar and other countries. Thus, it was decided in 2007 to establish a syndrome-based surveillance network to monitor dengue-like illness. Objective: This study aims to evaluate the use of capillary blood samples blotted on filter papers for molecular diagnosis of CHIKV infection. Venous blood samples can be difficult to obtain and the shipment of serum in appropriate temperature conditions is too costly for most developing countries. Methodology and principal findings: Venous blood and dried-blood blotted on filter paper (DBFP) were collected during the last CHIKV outbreak in Madagascar (2010) and as part of our routine surveillance of dengue-like illness. All samples were tested by real-time RT-PCR and results with serum and DBFP samples were compared for each patient. The sensitivity and specificity of tests performed with DBFP, relative to those with venous samples (defined as 100%) were 93.1% (95% CI:[84.7–97.7]) and 94.4% (95% CI:[88.3–97.7]), respectively. The Kappa coefficient 0.87 (95% CI:[0.80–0.94]) was excellent. Conclusion: This study shows that DBFP specimens can be used as a cost-effective alternative sampling method for the surveillance and monitoring of CHIKV circulation and emergence in developing countries, and probably also for other arboviruses. The loss of sensitivity is insignificant and involved a very small number of patients, all with low viral loads. Whether viruses can be isolated from dried blood spots remains to be determined. Author Summary: Chikungunya is a mosquito-transmitted viral disease. No treatment is currently available. The only way to prevent infection is to avoid mosquito bites. Surveillance of circulation by early diagnosis is useful to prevent or limit outbreak. CHIKV, like all RNA viruses, is heat-labile. Consequently, confirmatory diagnosis classically requires blood samples that are transported in appropriate conditions (i.e. at 4°C within 48 hours, in liquid nitrogen, or frozen at −80°C and transported on dry ice) to prevent false negative results. This is not always possible in field conditions in low income countries. Dried blood spots are already used to diagnose parasitic, bacterial and viral infection. We compared venous sample to dried blood sample to make diagnosis of Chikungunya infection. We demonstrate the usefulness of this sampling method for the molecular diagnosis of Chikungunya infection. In particular, dried blood spots were very nearly as suitable as frozen serum specimens for the diagnosis of recent infection by CHIKV. [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]

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]

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: Despite elimination efforts, the number of Mycobacterium leprae (M. leprae) infected individuals who develop leprosy, is still substantial. Solid evidence exists that individuals living in close proximity to patients are at increased risk to develop leprosy. Early diagnosis of leprosy in endemic areas requires field-friendly tests that identify individuals at risk of developing the disease before clinical manifestation. Such assays will simultaneously contribute to reduction of current diagnostic delay as well as transmission. Antibody (Ab) levels directed against the M.leprae-specific phenolic glycolipid I (PGL-I) represents a surrogate marker for bacterial load. However, it is insufficiently defined whether anti-PGL-I antibodies can be utilized as prognostic biomarkers for disease in contacts. Particularly, in Bangladesh, where paucibacillary (PB) patients form the majority of leprosy cases, anti-PGL-I serology seems an inadequate method for leprosy screening in contacts as a directive for prophylactic treatment. Methods: Between 2002 and 2009, fingerstick blood from leprosy patients’ contacts without clinical signs of disease from a field-trial in Bangladesh was collected on filter paper at three time points covering six years of follow-up per person. Analysis of anti-PGL-I Ab levels for 25 contacts who developed leprosy during follow-up and 199 contacts who were not diagnosed with leprosy, was performed by ELISA after elution of bloodspots from filter paper. Results: Anti-PGL-I Ab levels at intake did not significantly differ between contacts who developed leprosy during the study and those who remained free of disease. Moreover, anti-PGL-I serology was not prognostic in this population as no significant correlation was identified between anti-PGL-I Ab levels at intake and the onset of leprosy. Conclusion: In this highly endemic population in Bangladesh, no association was observed between anti-PGL-I Ab levels and onset of disease, urging the need for an extended, more specific biomarker signature for early detection of leprosy in this area. Trial registration: ClinicalTrials.gov [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. [ABSTRACT FROM AUTHOR]

Background: There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. Methods: A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. Results: Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. Conclusions: Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Background: How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. Methods: 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990–1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. Results: In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3–5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990–1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Conclusions: Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). Methodology/Principal Findings: Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. Conclusions: It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes. [ABSTRACT FROM AUTHOR]

Background: Yaws is targeted for eradication by 2020 in the WHA66.12 resolution of the World Health Assembly. The objective of this study was to describe the occurrence of yaws in the Americas and to contribute to the compilation of evidence based on published data to undertake the certification of yaws eradication. Methodology: A systematic review of the epidemiological situation of yaws in the Americas was performed by searching in MEDLINE, Embase, LILACS, SCOPUS, Web of Science, DARE and Cochrane Database of Systematic Reviews. Experts on the topic were consulted, and institutional WHO/PAHO library databases were reviewed. Principal findings: Seventy-five full-text articles published between 1839 and 2012 met the inclusion criteria. Haiti and Jamaica were the two countries with the highest number of papers (14.7% and 12.0%, respectively). Three-quarters of the studies were conducted before 1970. Thirty-three countries reported yaws case count or prevalence data. The largest foci in the history were described in Brazil and Haiti. The most recent cases reported were recorded in eight countries: Suriname, Guyana, Colombia, Haiti, Martinique, Dominica, Trinidad and Tobago, and Brazil. Gaps in information and heterogeneity were detected in the methodologies used and outcome reporting, making cross-national and chronological comparisons difficult. Conclusions: The lack of recent yaws publications may reflect, in the best-case scenario, the interruption of yaws transmission. It should be possible to reach the eradication goal in the region of the Americas, but it is necessary to collect more information. We suggest updating the epidemiological status of yaws, especially in two countries that need to assess ongoing transmission. Twenty-four countries need to demonstrate the interruption of transmission and declare its status of yaws endemicity, and sixteen countries should declare if they are yaws-free. It is necessary to formally verify the achievement of this goal in Ecuador. [ABSTRACT FROM AUTHOR]

During 2011 a large outbreak of typhoid fever affected an estimated 1430 people in Kikwit, Democratic Republic of Congo. The outbreak started in military camps in the city but then spread to the general population. This paper reports the results of an ecological analysis and a case-control study undertaken to examine water and other possible transmission pathways. Attack rates were determined for health areas and risk ratios were estimated with respect to spatial exposures. Approximately 15 months after the outbreak, demographic, environmental and exposure data were collected for 320 cases and 640 controls residing in the worst affected areas, using a structured interview questionnaire. Unadjusted and adjusted odds ratios were estimated. Complete data were available for 956 respondents. Residents of areas with water supplied via gravity on the mains network were at much greater risk of disease acquisition (risk ratio = 6.20, 95%CI 3.39–11.35) than residents of areas not supplied by this mains network. In the case control study, typhoid was found to be associated with ever using tap water from the municipal supply (OR = 4.29, 95% CI 2.20–8.38). Visible urine or faeces in the latrine was also associated with increased risk of typhoid and having chosen a water source because it is protected was negatively associated. Knowledge that washing hands can prevent typhoid fever, and stated habit of handwashing habits before cooking or after toileting was associated with increased risk of disease. However, observed associations between handwashing or plate-sharing with disease risk could very likely be due to recall bias. This outbreak of typhoid fever was strongly associated with drinking water from the municipal drinking water supply, based on the descriptive and analytic epidemiology and the finding of high levels of faecal contamination of drinking water. Future outbreaks of potentially waterborne disease need an integrated response that includes epidemiology and environmental microbiology during early stages of the outbreak. [ABSTRACT FROM AUTHOR]

Introduction: Assessment of attitude of health care professionals is important as negative attitude could constitute a major deterrent to care-seeking by persons affected by neglected tropical diseases (NTDs) such as leprosy. Leprosy continues to pose a major disease burden in India with an annual new case detection rate of 10.17 per 100,000 population. This paper reports on the development and validation of a culturally appropriate scale to measure attitude of health care providers (HCPs) towards persons affected by leprosy in Tamil Nadu, India. Methodology/Principal findings: The Affective, Behavioural and Cognitive (ABC) model of attitudes guided the development of the scale. Steps in scale development included qualitative interviews and focus group discussions with medical officers and paramedical staffs selected from high prevalence districts in Tamil Nadu, India which informed the development of the draft scale. Reviews of existing attitude questionnaires in related areas further contributed to scale development and together helped to generate a large pool of items which was then subjected to Thurston’s scaling method for selection of items from this pool. Face and content validity were obtained, following which internal consistency and test, re-test reliability were assessed. Scaling exercise resulted in 11 items being discarded from an initial pool of 38, owing to the poor agreement among experts regarding relevance. Face and content validity were good with experts endorsing relevance and applicability of items. The intra-class correlation coefficient (ICC) for test re-test reliability of the 27 item scale was 0.6 (95% CI: 0.20–0.78) indicating marginal intra-class correlation. The overall Cronbach’s alpha was 0.85 while the alphas for each of the affective and behavioural components was good at 0.78 and 0.69 respectively indicating a good degree of consistency and homogeneity between items but the alpha for the cognitive component was low at 0.53. Conclusions: The ABC model of attitudes guided the development of the scale, ensured a mix of 27 items tapping into the three domains of Affect, Behaviour and Cognition which best explained the attitude construct. With good validity and alphas for each of the affective, behavioural components and overall alpha estimates, this scale can be a valuable tool to provide accurate estimates of the true attitudes held by HCPs. This, in turn, would be useful to obtain insights for appropriate intervention programmes that would help change negative attitudes of HCPs towards persons affected by leprosy. With some adaptations, the scales can be validated for other NTDs as well. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings: We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance: This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a condition that has long been associated with stigma and discrimination, even when infected persons have been cured. This paper describes stigma and discrimination as viewed by caregivers who are associated with people affected by leprosy in Ghana. Methods: A qualitative interview with semi-structured interviews were conducted for twenty caregivers. Results: Findings indicated that caregivers were of the view that people affected by leprosy in Ghana are stigmatized and discriminated against by the larger society thus making their movements and interactions restricted to the Leprosarium. Besides, employments opportunities are unavailable to them thus making them exposed to financial challenges. The livelihood Empowerment Against poverty (LEAP) money given them is not sufficient for their daily upkeep. Conclusion: People affected by leprosy in Ghana are stigmatized and therefore find it difficult to interact freely with the public. The associated physical deformities with the disease also tend to impede their ability to relate to the general public. The LEAP cash given to people affected by leprosy is helpful however, it could be enhanced to keep pace with prevailing economic conditions in the country. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae causes over 2 million cases of cholera and 90,000 deaths each year. Serosurveillance can be a useful tool for estimating the intensity of cholera transmission and prioritizing populations for cholera control interventions. Current methods involving venous blood draws and downstream specimen storage and transport methods pose logistical challenges in most settings where cholera strikes. To overcome these challenges, we developed methods for determining cholera-specific immune responses from dried blood spots (DBS). Methodology/principal findings: As conventional vibriocidal assay methods were unsuitable for DBS eluates from filter paper, we adopted a drop-plate culture method. We show that DBS collected from volunteers in South Sudan, and stored for prolonged periods in field conditions, retained functional vibriocidal antibodies, the titers of which correlated with paired serum titers determined by conventional spectrophotometric methods (r = 0.94, p = 0.00012). We also showed that eluates from DBS Serum Separator cards could be used with conventional spectrophotometric vibriocidal methods, and that they correlated with paired serum at a wide range of titers (r = 0.96, p<0.0001). Similarly, we used ELISA methods to show that V. cholerae O-specific polysaccharide antibody responses from DBS eluates correlated with results from paired serum for IgG (r = 0.85, p = 0.00006), IgM (r = 0.79, p = 0.00049) and IgA (r = 0.73, p = 0.0019), highlighting its potential for use in determination of isotype-specific responses. Storage of DBS cards at a range of temperatures did not change antibody responses. Conclusion: In conclusion, we have developed and demonstrated a proof-of-concept for assays utilizing DBS for assessing cholera-specific immune responses. [ABSTRACT FROM AUTHOR]

Background: In the last two decades, several rapid lateral flow immunoassays (LFIs) for the diagnosis of human leptospirosis were developed and commercialized. However, the accuracy and reliability of these LFIs are not well understood. In this study, we aimed to evaluate the accuracy of leptospirosis LFIs as well as the factors affecting the test efficiency using systematic review and meta-analysis. Methods and results: Original articles reporting the accuracy of human leptospirosis LFIs against microagglutination tests (MAT) or immunofluorescent assays (IFA) were searched from PubMed, Embase, and Scopus, and selected as per pre-set inclusion and exclusion criteria. A total of 49 data entries extracted from 24 eligible records published between 2003 and 2023 were included for meta-analysis. A meta-analysis was performed using STATA. The quality of the included studies was assessed according to the revised QUADAS-2. Only nine studies (32.1%) were considered to have a low risk of bias and no concern for applicability. Pooled sensitivity and specificity were calculated to be 68% (95% confidence interval, CI: 57–78) and 93% (95% CI: 90–95), respectively. However, the ranges of sensitivity (3.6 – 100%) and specificity (53.5 – 100%) of individual entries are dramatically broad, possibly due to the heterogeneity found in both study designs and LFIs themselves. Subgroup analysis demonstrated that IgM detection has better sensitivity than detection of IgG alone. Moreover, the test performance seems to be unaffected by samples from different phases of infection. Conclusions: The pooled specificity of LFIs observed is somewhat acceptable, but the pooled sensitivity is low. These results, however, must be interpreted with caution because of substantial heterogeneity. Further evaluations of the LFIs with well-standardized design and referent test will be needed for a greater understanding of the test performance. Additionally, IgM detection type should be employed when leptospirosis LFIs are developed in the future. Author summary: Several rapid lateral flow immunoassays (LFIs) for the diagnosis of leptospirosis, the most common bacterial infection transmitted from animals to humans, have been developed during the last two decades. The test accuracy, however, seems inconsistent among studies, raising questions about their reliability and applicability. Systematic review and meta-analysis were exploited to answer these questions. A total of 28 studies evaluating the human leptospirosis LFIs were included in this review. Major findings from our analysis include: i) the overall specificity of the LFIs is likely acceptable (93%), but the sensitivity is significantly low (68%); ii) substantial variation among studies was observed, alerting the reliability of this meta-analysis results; iii) the accuracy of the LFIs seems to be unaffected by samples collected from different phases of infection (acute vs. convalescent); and iv) IgM detection LFIs exhibit higher sensitivity as compared to IgG detection type. From our findings, we suggest that IgM detection LFIs should be focused on for future development. Also, in order to understand the performance of the LFIs better, other evaluation studies are still needed. [ABSTRACT FROM AUTHOR]

This year PLOS Neglected Tropical Diseases (PLOS NTDs) celebrates its tenth anniversary following the publication of the first issue in 2007 []. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs) as an alternative to “other diseases” (as they were then referred to in the Millennium Development Goals) was just getting started—especially for Africa [, ]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD) Study 2015 (also launched with Gates Foundation support) that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015) [–], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 []. [ABSTRACT FROM AUTHOR]

Background: This paper assesses the impact of a counselling intervention on reducing leprosy-related stigma in Cirebon District, Indonesia. The unique features of this intervention are its rights-based approach, the underlying Cognitive Behavioural Therapy (CBT) model, the three types of counselling and the lay and peer counsellors who were involved. Methodology/principal findings: Mixed methods (e.g. three scales, interviews, focus group discussions and reflection notes) were used to assess the impact of the intervention, which ran over a two-year period. There was a control area with no interventions. The study participants were people affected by leprosy and other key persons (e.g. family members). The sample size differs per method, for example, data regarding 67 counselling clients and 57 controls from a cohort, and notes from 207 counselling clients were examined. The notes showed that most clients faced stigma on a daily basis, whether internalized, anticipated and/or enacted. A significant reduction was found between the before and after total scores of the SARI Stigma Scale (p-value < 0.001), Participation Scale Short (p-value < 0.001) and WHO Quality of Life score (p-value < 0.001) among the counselling clients. While there is also an effect in the control group, it is much larger in the intervention group. Qualitative data indicates that knowledge and rights trigger change. Clients took steps to improve their life such as re-connecting with neighbours, helping in household activities and applying for jobs. Challenges include the wish to conceal their condition. Conclusion/significance: The findings show that the counselling intervention was effective in reducing stigma, promoting the rights of people with leprosy and facilitating their social participation. More research is needed on how to create a more sustainable intervention, preferably structurally embedded in the health or social services. [ABSTRACT FROM AUTHOR]

Background: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods: A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results: Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion: This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is the second-most widespread tropical parasitic disease after malaria. Various research strategies and treatment programs for achieving the objective of eradicating schistosomiasis within a decade have been recommended and supported by the World Health Organization. One of these approaches is based on the control of snail vectors in endemic areas. Previous field studies have shown that competitor or predator introduction can reduce snail numbers, but no systematic investigation has ever been conducted to identify snail microbial pathogens and evaluate their molluscicidal effects. Methodology/Principal findings: In populations of Biomphalaria glabrata snails experiencing high mortalities, white nodules were visible on snail bodies. Infectious agents were isolated from such nodules. Only one type of bacteria, identified as a new species of Paenibacillus named Candidatus Paenibacillus glabratella, was found, and was shown to be closely related to P. alvei through 16S and Rpob DNA analysis. Histopathological examination showed extensive bacterial infiltration leading to overall tissue disorganization. Exposure of healthy snails to Paenibacillus-infected snails caused massive mortality. Moreover, eggs laid by infected snails were also infected, decreasing hatching but without apparent effects on spawning. Embryonic lethality was correlated with the presence of pathogenic bacteria in eggs. Conclusions/Significance: This is the first account of a novel Paenibacillus strain, Ca. Paenibacillus glabratella, as a snail microbial pathogen. Since this strain affects both adult and embryonic stages and causes significant mortality, it may hold promise as a biocontrol agent to limit schistosomiasis transmission in the field. Author Summary: The present paper reports the isolation and the characterization of a new microbial pathogen of the freshwater snail, Biomphalaria glabrata. Genetic analyses revealed that the species has not been previously described and could be classified into the Paenibacillus genus. These bacteria invade most snail tissues and proliferate, causing massive lethality. Moreover, the bacterial infection can be transmitted both vertically and horizontally to other snails, causing their death in 30 days. This discovery is potentially important because B. glabrata, as an intermediate host, plays an important role in transmitting schistosomiasis, the second-most widespread human parasitic disease. The World Health Organization's objective of schistosomiasis eradication in a decade encourages the development of multiple approaches for countering the disease, one of which is vector population control. This new bacterial strain clearly could be a potential agent for such a strategy. [ABSTRACT FROM AUTHOR]

Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum, where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply, but is also responsible for several of the pathological processes seen in this disease. Effective canine vaccines are therefore a highly desirable prevention tool. In this randomised, double-blinded, controlled trial, the efficacy of the LiESP/QA-21 vaccine (CaniLeish, Virbac, France) was assessed by exposing 90 naïve dogs to natural L. infantum infection during 2 consecutive transmission seasons, in two highly endemic areas of the Mediterranean basin. Regular PCR, culture, serological and clinical examinations were performed, and the infection/disease status of the dogs was classified at each examination. The vaccine was well-tolerated, and provided a significant reduction in the risk of progressing to uncontrolled active infection (p = 0.025) or symptomatic disease (p = 0.046), with an efficacy of 68.4% and a protection rate of 92.7%. The probability of becoming PCR positive was similar between groups, but the probability of returning to a PCR negative condition was higher in the vaccinated group (p = 0.04). In conclusion, we confirmed the interest of using this vaccine as part of a comprehensive control program for canine leishmaniasis, and validated the use of a protocol based on regular in-depth assessments over time to assess the efficacy of a canine leishmaniasis vaccine. Author Summary: Canine leishmaniasis is caused by uncontrolled infection with Leishmania infantum. The dog is also the principle reservoir of this parasite which can infect humans. The key determinant of the outcome of infection is the ability of the dog's immune system to respond appropriately. This should be mainly cell-mediated immunity; the antibody responses often desired for viral or bacterial infections are not protective. Therefore, vaccines capable of inducing this cell-mediated immune profile are a desirable prevention tool. Previous studies with CaniLeish (consisting of the parasite's excreted-secreted proteins with an adjuvant) have demonstrated the ability of this vaccine to induce an appropriate immune profile and to protect against an intravenous challenge, as well as to reduce the risk of transmission of the parasite to the sandfly vector. This paper reports a study where vaccinated dogs were exposed to natural parasite transmission over two full seasons in two Mediterranean locations (one in Italy and one in Spain). Data from the unvaccinated control group confirmed that the levels of exposure were high. We demonstrated that the vaccine significantly reduces the risk of progressive infections and disease confirming the interest of using vaccination as part of a comprehensive control program for this disease. [ABSTRACT FROM AUTHOR]

Background: Although trachoma causes more cases of preventable blindness than any other infectious disease, a combination of strategies is reducing its global prevalence. As a district moves toward eliminating trachoma as a public health problem, national programs conduct trachoma impact surveys (TIS) to assess whether to stop preventative interventions and trachoma surveillance surveys (TSS) to determine whether the prevalence of active trachoma has rebounded after interventions have halted. In some contexts, programs also conduct trachomatous trichiasis (TT)-only surveys. A few costing studies of trachoma prevalence surveys exist, but none examine TIS, TSS, or TT-only surveys. Methodology/Principal findings: We assessed the incremental financial cost to the national program of TIS, TSS, and TT-only surveys, which are standardized cluster-sampled prevalence surveys. We conducted a retrospective review of expenditures and grant disbursements for TIS and TSS in 322 evaluation units in 11 countries between 2011 and 2018. We also assessed the costs of three pilot and five standard TT-only surveys in four countries between 2017 and 2018. The median cost of TIS and TSS was $8,298 per evaluation unit [interquartile range (IQR): $6,532–$10,111, 2017 USD]. Based on a linear regression with bootstrapped confidence intervals, after controlling for country, costs per survey did not change significantly over time but did decline by $83 per survey implemented in a single round (95% CI: -$108 –-$63). Of total costs, 80% went to survey fieldwork; of that, 58% went towards per diems and 38% towards travel. TT-only surveys cost a median of $9,707 (IQR: $8,537–$11,635); within a given country, they cost slightly more (106% [IQR: 94%–136%]) than TIS and TSS. Conclusions/Significance: The World Health Organization requires trachoma prevalence estimates for validating the elimination of trachoma as a public health problem. This study will help programs improve their planning as they assemble resources for that effort. [ABSTRACT FROM AUTHOR]

Background: Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. Methods: From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. Results: Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. Conclusions: Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics. Author summary: Typhoid and paratyphoid fever, caused by Salmonella Typhi and Paratyphi A respectively, are common in areas lacking safe water and optimum infrastructure. With increasing multidrug resistance in Salmonella Typhi, newer antimicrobials like ceftriaxone and azithromycin are frequently prescribed for the empirical treatment of both typhoid and paratyphoid fever. This is because Salmonella Paratyphi A is less prevalent in most endemic countries, and typhoid and paratyphoid fever are often symptomatically indistinguishable. In this study, we conducted comprehensive surveillance of Salmonella Paratyphi A in Bangladesh over a period of 23 years and identified 2,725 blood culture-confirmed paratyphoid cases. Our findings indicate that Salmonella Paratyphi A remained susceptible to most of the older generation of antibiotics as over 97% of the isolates continue to be susceptible to ampicillin, chloramphenicol and cotrimoxazole, and no isolate detected was resistant to all three drugs. Although 99% of the isolates exhibited reduced fluoroquinolone susceptibility, 99% and 100% were sensitive to azithromycin and ceftriaxone. These findings are important and can guide evidence-based policy decisions for the empirical treatment of paratyphoid fever. While newer antimicrobials such as azithromycin and ceftriaxone remain effective, successful implementation of typhoid conjugate vaccines and rapid diagnostics may re-enable the use of older generation antibiotics for empirical treatment of enteric fever without compromising the treatment efficacy. This approach can contribute to the antimicrobial stewardship efforts by preserving critically important antimicrobials such as ceftriaxone and azithromycin for the treatment of numerous other multidrug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

There has been little evidence of a decline in the global burden of cholera in recent years as the number of cholera cases reported to WHO continues to rise. Cholera remains a global threat to public health and a key indicator of lack of socioeconomic development. Overall socioeconomic development is the ultimate solution for control of cholera as evidenced in developed countries. However, most research has focused on cross-county comparisons so that the role of individual- or small area-level socioeconomic status (SES) in cholera dynamics has not been carefully studied. Reported cases of cholera in Matlab, Bangladesh have fluctuated greatly over time and epidemic outbreaks of cholera continue, most recently with the introduction of a new serotype into the region. The wealth of longitudinal data on the population of Matlab provides a unique opportunity to explore the impact of socioeconomic status and other demographic characteristics on the long-term temporal dynamics of cholera in the region. In this population-based study we examine which factors impact the initial number of cholera cases in a bari at the beginning of the 0139 epidemic and the factors impacting the number of cases over time. Cholera data were derived from the ICDDR,B health records and linked to socioeconomic and geographic data collected as part of the Matlab Health and Demographic Surveillance System. Longitudinal zero-inflated Poisson (ZIP) multilevel regression models are used to examine the impact of environmental and socio-demographic factors on cholera counts across baris. Results indicate that baris with a high socioeconomic status had lower initial rates of cholera at the beginning of the 0139 epidemic (γ01 = −0.147, p = 0.041) and a higher probability of reporting no cholera cases (α01 = 0.156, p = 0.061). Populations in baris characterized by low SES are more likely to experience higher cholera morbidity at the beginning of an epidemic than populations in high SES baris. Author Summary: Cholera is a bacterial disease usually spread through contaminated water that causes severe diarrhea and dehydration. Modern sewage and water treatment have virtually eliminated cholera in industrialized countries but cholera is still present throughout much of SE Asia, Latin America and sub-Saharan Africa. One of the reasons cholera is still problematic is that genetically distinct forms of the bacteria (often called biotypes) have developed and spread rapidly because the population has no natural immunity to the new biotype. In Bangladesh, the 0139 biotype developed in 1993 and caused a large epidemic. Although it is widely accepted that poor conditions place people at risk for cholera, very few studies have examine what role low socioeconomic status plays in cholera risk, especially during a new epidemic of the disease. In this paper, we explore how local-level socioeconomic status, measured using assets, education and sanitation, affect the severity of the cholera outbreak experienced during the O139 epidemic in Matlab, Bangladesh. We believe our study highlights the importance of improving overall socioeconomic status, not just sanitation and water treatment, in controlling the spread of cholera. [ABSTRACT FROM AUTHOR]

Objectives: A national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were launched in the regions of Kayes and Koulikoro in 2003. MDA was discontinued after three annual rounds in 2006, and an impact survey conducted. We resurveyed all districts in Kayes and Koulikoro in 2009 to reassess trachoma prevalence and determine intervention objectives for the future. In this paper we present findings from both the 2006 and 2009 surveys. Methods: Population-based cluster surveys were conducted in each of the nine districts in Koulikoro in 2006 and 2009, whilst in Kayes, four of seven districts in 2006 and all seven districts in 2009 were surveyed. Household members present were examined for clinical signs of trachoma. Results: Overall, 29,179 persons from 2,528 compounds, in 260 clusters were examined in 2006 and 32,918 from 7,533 households in 320 clusters in 2009. The prevalence of TF in children aged 1–9 years in Kayes and Koulikoro was 3.9% (95%CI 2.9–5.0%, range by district 1.2–5.4%) and 2.7% (95%CI 2.3–3.1%, range by district 0.1–5.0%) respectively in 2006. In 2009 TF prevalence was 7.26% (95%CI 6.2–8.2%, range by district 2.5–15.4%) in Kayes and 8.19% (95%CI 7.3–9.1%, range by district 1.7–17.2%) in Koulikoro among children of the same age group. TT in adults 15 years of age and older was 2.37% (95%CI 1.66–3.07%, range by district 0.30–3.54%) in 2006 and 1.37% (95%CI 1.02–1.72%, range by district 0.37–1.87%) in 2009 in Kayes and 1.75% (95%CI 1.31–2.23%, range by district 1.06–2.49%) in 2006 and 1.08% (95%CI 0.86–1.30%, range by district 0.34–1.78%) in 2009 in Koulikoro. Conclusions: Using WHO guidelines for decision making, four districts, Bafoulabe in Kayes Region; and Banamba, Kolokani and Koulikoro in Koulikoro Region, still meet criteria for district-wide implementation of the full SAFE strategy as TF in children exceeds 10%. A community-by-community approach to trachoma control may now be required in the other twelve districts. Trichiasis surgery provision remains a need in all districts and should be enhanced in six districts in Kayes and five in Koulikoro where the prevalence exceeded 1.0% in adults. Since 1997 great progress has been observed in the fight against blinding trachoma; however, greater effort is required to meet the elimination target of 2015. Author Summary: Trachoma, a blinding bacterial disease, is targeted for elimination by 2020. To achieve the elimination target, the World Health Organization (WHO) recommends member states implement the SAFE strategy; surgery, mass administration of antibiotics, promotion of hygiene and facial cleanliness and water and sanitation as environmental improvements. We present results from evaluation surveys conducted in 2006 and 2009 from the regions of Kayes and Koulikoro, Mali. Prevalence of active trachoma in 2006 was below baseline intervention thresholds in all surveyed districts and the national program stopped antibiotic distribution. The prevalence of trachoma in 2009 remained well below levels in 1998. However, in 8 of 13 districts compared, the prevalence of active trachoma was higher in 2009 than 2006. Three years of antibiotic intervention did not equate in all districts to a sustained reduction of active trachoma. No surveillance activities were implemented after stopping interventions. Surgical interventions may have reduced the burden of blinding trachoma but there is an ongoing need for surgeries specifically targeting affected women. Four districts meet the WHO criteria for resuming district-wide mass antibiotic distribution. A community-by-community approach to elimination may be needed in other districts. The promotion of facial cleanliness and good hygiene behavior should be reintroduced. [ABSTRACT FROM AUTHOR]

Background: Melioidosis is a tropical infectious disease associated with significant mortality due to early onset of sepsis. Objective: We sought to review case reports of melioidosis from Malaysia. Methods: We conducted a computerized search of literature resources including PubMed, OVID, Scopus, MEDLINE and the COCHRANE database to identify published case reports from 1975 to 2015. We abstracted information on clinical characteristics, exposure history, comorbid conditions, management and outcome. Results: Overall, 67 cases were reported with 29 (43%) deaths; the median age was 44 years, and a male preponderance (84%) was noted. Forty-one cases (61%) were bacteremic, and fatal septic shock occurred in 13 (19%) within 24–48 hours of admission; nine of the 13 cases were not specifically treated for melioidosis as confirmatory evidence was available only after death. Diabetes mellitus (n = 36, 54%) was the most common risk factor. Twenty-six cases (39%) had a history of exposure to contaminated soil/water or employment in high-risk occupations. Pneumonia (n = 24, 36%) was the most common primary clinical presentation followed by soft tissue abscess (n = 22, 33%). Other types of clinical presentations were less common—genitourinary (n = 5), neurological (n = 5), osteomyelitis/septic arthritis (n = 4) and skin (n = 2); five cases had no evidence of a focus of infection. With regard to internal foci of infection, abscesses of the subcutaneous tissue (n = 14, 21%) was the most common followed by liver (18%); abscesses of the spleen and lung were the third most common (12% each). Seven of 56 males were reported to have prostatic abscesses. Mycotic pseudoaneurysm occurred in five cases. Only one case of parotid abscess was reported in an adult. Of the 67 cases, 13 were children (≤ 18 years of age) with seven deaths; five of the 13 were neonates presenting primarily with bronchopneumonia, four of whom died. Older children had a similar presentation as adults; no case of parotid abscess was reported among children. Conclusions: The clinical patterns of cases reported from Malaysia are consistent for the most part from previous case reports from South and Southeast Asia with regard to common primary presentations of pneumonia and soft tissue abscesses, and diabetes as a major risk factor. Bacteremic melioidosis carried a poor prognosis and septic shock was strong predictor of mortality. Differences included the occurrence of: primary neurological infection was higher in Malaysia compared to reports outside Malaysia; internal foci of infection such as abscesses of the liver, spleen, prostate, and mycotic pseudoaneurysms were higher than previously reported in the region. No parotid abscess was reported among children. Early recognition of the disease is the cornerstone of management. In clinical situations of community-acquired sepsis and/or pneumonia, where laboratory bacteriological confirmation is not possible, empirical treatment with antimicrobials for B. pseudomallei is recommended. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is an occupational, neglected febrile disease of bacterial origin transmitted between humans and animals. In this manuscript we summarize available data on Leptospira infection in HIV uninfected and in people living with HIV from the Southern African Development Community (SADC) countries, identifying gaps in knowledge and recommend future research priorities. Methodology: Articles published between 1990 and 2021 were accessed by an online search of Google Scholar and Medline/PubMed performed between February 2020 and July 2022. The STATA program was used for the Meta-analysis. Pooled prevalence values with 95% confidence intervals and heterogeneity were determined. Results: Thirty studies from eight SADC countries, reporting the prevalence on Leptospira were reviewed. A pooled prevalence of 19% (CI: 13–25%), a heterogeneity level of 96% and index score ranging from 2 to 9 was determined. Only four (4) studies reported HIV co-infection status. Three species of Leptospira (Leptospira interrogans (4), L. kirschneri (3), Leptospira borgpetersenii (1) and 23 serogroups were identified. The most frequently reported serogroups were Icterohaemorrhagiae (13), Grippotyphosa and Australis (10) followed by Sejroe (8). Conclusion: Studies on human leptospirosis in the SADC region are scarce, especially in people living with HIV. Additional studies aimed at determining the prevalence and the role of the pathogen in people living with HIV, including detailed clinical, molecular and demographic data are recommended. Author summary: The SADC region is severely affected by infections such as HIV, tuberculosis and malaria, which divert attention from several other diseases with major public health impacts. These critically neglected tropical diseases, include leptospirosis, cysticercosis, onchocerciasis, lymphatic filariasis, intestinal parasites and schistosomiasis among others. Leptospirosis is often misdiagnosed as one of several other febrile diseases including malaria, brucellosis and rickettsiosis because of similarities in symptoms. It is also likely underdiagnosed because of the complexity of laboratory diagnostic methodologies. Our review found that there is a scarcity of studies on leptospirosis, and lack of standardization tools for data collection, especially in the framework of leptospirosis in people living with HIV. In this review we summarize the pooled prevalence of leptospirosis in the SADC countries and the reported circulating serovars and species of Leptospira and uncover gaps in knowledge about the epidemiology of the pathogen. Misconceptions about the prevalence of leptospirosis among the scientific community, health care providers and policy makers coupled with complexity of clinical and laboratory diagnosis have resulted in a systematic underestimation of the public health impact of this important neglected pathogen. [ABSTRACT FROM AUTHOR]

Background: Foodborne and zoonotic diseases such as brucellosis present many challenges to public health and economic welfare. Increasingly, researchers and public health institutes use disability-adjusted life years (DALYs) to generate a comprehensive comparison of the population health impact of these conditions. DALYs calculations, however, entail a number of methodological choices and assumptions, with data gaps and uncertainties to accommodate. Thisreview identifies existing brucellosis burden of disease studies and analyzes their methodological choices, assumptions, and uncertainties. It supports the Global Burden of Animal Diseases programme in the development of a systematic methodology to describe the impact of animal diseases on society, including human health. Methods/Principal findings: A systematic search for brucellosis burden of disease calculations was conducted in pre-selected international and grey literature databases. Using a standardized reporting framework, we evaluated each estimate on a variety of key methodological assumptions necessary to compute a DALY. Fourteen studies satisfied the inclusion criteria (human brucellosis and quantification of DALYs). One study reported estimates at the global level, the rest were national or subnational assessments. Data regarding different methodological choices were extracted, including detailed assessments of the adopted disease models. Most studies retrieved brucellosis epidemiological data from administrative registries. Incidence data were often estimated on the basis of laboratory-confirmed tests. Not all studies included mortality estimates (Years of Life Lost) in their assessments due to lack of data or the assumption that brucellosis is not a fatal disease. Only two studies used a model with variable health states and corresponding disability weights. The rest used a simplified singular health state approach. Wide variation was seen in the duration chosen for brucellosis, ranging from 2 weeks to 4.5 years, irrespective of the whether a chronic state was included. Conclusion: Available brucellosis burden of disease assessments vary widely in their methodology and assumptions. Further research is needed to better characterize the clinical course of brucellosis and to estimate case-fatality rates. Additionally, reporting of methodological choices should be improved to enhance transparency and comparability of estimates. These steps will increase the value of these estimates for policy makers. Author summary: Brucellosis is a bacterial disease transmitted to humans by consumption of contaminated, unpasteurized milk or through direct contact with infected animals and their excretions. This disease causes production losses and has major economic impacts on individuals and communities. The disability-adjusted life year (DALY) is a metric for measuring the burden. It summarizes mortality (years of life lost) and morbidity (years lived with disability) into a single metric. This review aimed to identify existing brucellosis burden of disease studies and analyse their methodological choices, assumptions, and uncertainties. The results suggested that some parameters carry considerable uncertainty, particularly mortality and disease duration. This highlights the importance of strengthening routine reporting systems, collecting better mortality data and conducting further research on the course of brucellosis. Additionally, estimates of DALYs will benefit from a deeper understanding of the symptoms and the different sources of attribution. Finally, current reporting of methodological choices should be improved to enhance transparency, comparability, and consistency of brucellosis burden. [ABSTRACT FROM AUTHOR]

Background: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. Methods: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. Results: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. Conclusions: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. Trial registration: Registration at ClinicalTrials.gov NCT03957447. Author summary: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified were invited to participate in the wound management study simultaneously carried out in the survey area. We surveyed approximately 4000 HDSS-registered persons and found a high overall wound prevalence (13.0%), predominately in children. Mechanical trauma was the leading cause, followed by furuncles, burns and Buruli ulcer. Most wounds were acute and had a size of less than 5 cm2, but a substantial proportion was large, complicated, or chronic, some of the latter persisting neglected for years. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. [ABSTRACT FROM AUTHOR]

Background: The lack of an effective diagnostic tool for Carrion’s disease leads to misdiagnosis, wrong treatments and perpetuation of asymptomatic carriers living in endemic areas. Conventional PCR approaches have been reported as a diagnostic technique. However, the detection limit of these techniques is not clear as well as if its usefulness in low bacteriemia cases. The aim of this study was to evaluate the detection limit of 3 PCR approaches. Methodology/Principal Findings: We determined the detection limit of 3 different PCR approaches: Bartonella-specific 16S rRNA, fla and its genes. We also evaluated the viability of dry blood spots to be used as a sample transport system. Our results show that 16S rRNA PCR is the approach with a lowest detection limit, 5 CFU/μL, and thus, the best diagnostic PCR tool studied. Dry blood spots diminish the sensitivity of the assay. Conclusions/Significance: From the tested PCRs, the 16S rRNA PCR-approach is the best to be used in the direct blood detection of acute cases of Carrion’s disease. However its use in samples from dry blood spots results in easier management of transport samples in rural areas, a slight decrease in the sensitivity was observed. The usefulness to detect by PCR the presence of low-bacteriemic or asymptomatic carriers is doubtful, showing the need to search for new more sensible techniques. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a zoonotic disease prevalent throughout the world, but with particularly high burden in Oceania (including the Pacific Island Countries and Territories). Leptospirosis is endemic in Fiji, with outbreaks often occurring following heavy rainfall and flooding. As a result of non-specific clinical manifestation and diagnostic challenges, cases are often misdiagnosed or under-ascertained. Furthermore, little is known about the duration of persistence of antibodies to leptospirosis, which has important clinical and epidemiological implications. Methodology and principal findings: Using the results from a serosurvey conducted in Fiji in 2013, we fitted serocatalytic models to estimate the duration of antibody positivity and the force of infection (FOI, the rate at which susceptible individuals acquire infection or seroconversion), whilst accounting for seroreversion. Additionally, we estimated the most likely timing of infection. Using the reverse catalytic model, we estimated the duration of antibody persistence to be 8.33 years (4.76–12.50; assuming constant FOI) and 7.25 years (3.36–11.36; assuming time-varying FOI), which is longer than previous estimates. Using population age-structured seroprevalence data alone, we were not able to distinguish between these two models. However, by bringing in additional longitudinal data on antibody kinetics we were able to estimate the most likely time of infection, lending support to the time-varying FOI model. We found that most individuals who were antibody-positive in the 2013 serosurvey were likely to have been infected within the previous two years, and this finding is consistent with surveillance data showing high numbers of cases reported in 2012 and 2013. Conclusions: This is the first study to use serocatalytic models to estimate the FOI and seroreversion rate for Leptospira infection. As well as providing an estimate for the duration of antibody positivity, we also present a novel method to estimate the most likely time of infection from seroprevalence data. These approaches can allow for richer, longitudinal information to be inferred from cross-sectional studies, and could be applied to other endemic diseases where antibody waning occurs. Author summary: Leptospirosis is a bacterial zoonotic disease that occurs in almost all regions of the world, with a particularly high burden of disease in Oceania. It is widely considered to be a Neglected Zoonotic Disease, and it is often mis-diagnosed and under-ascertained. Very little information exists about the persistence of antibodies to leptospirosis, which is important for understanding how long individuals may have partial protection against reinfection. In this study, we show how data collected from a large population survey of leptospirosis antibodies can be used to estimate the duration of antibody persistence. Knowledge of the duration of antibody persistence enables an estimation of the duration of immunity to re-infection, which is most likely antibody-mediated. We also estimate the rate at which susceptible individuals acquire infection (force of infection), whilst accounting for antibody waning. This provides more accurate estimates of population-wide disease burden. Finally, we show how the results from a cross-sectional population survey can be used to estimate when infections may have occurred. This is particularly useful in areas with limited surveillance. This approach could be applied to other neglected diseases for which data are limited and where antibody waning occurs. [ABSTRACT FROM AUTHOR]

Background: Stigma plays in an important role in the lives of persons affected by neglected tropical diseases, and assessment of stigma is important to document this. The aim of this study is to test the cross-cultural validity of the Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the field of leprosy in Cirebon District, Indonesia. Methodology/principle findings: Cultural equivalence was tested by assessing the conceptual, item, semantic, operational and measurement equivalence of these instruments. A qualitative exploratory study was conducted to increase our understanding of the concept of stigma in Cirebon District. A process of translation, discussions, trainings and a pilot study followed. A sample of 259 community members was selected through convenience sampling and 67 repeated measures were obtained to assess the psychometric measurement properties. The aspects and items in the SDS and EMIC-CSS seem equally relevant and important in the target culture. The response scales were adapted to ensure that meaning is transferred accurately and no changes to the scale format (e.g. lay out, statements or questions) of both scales were made. A positive correlation was found between the EMIC-CSS and the SDS total scores (r = 0.41). Cronbach's alphas of 0.83 and 0.87 were found for the EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an adequate fit as unidimensional scale. A standard error of measurement of 2.38 was found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were found. Conclusions/significance: According to current international standards, our findings indicate that the EMIC-CSS and the SDS have adequate cultural validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking population of Cirebon District. We believe the scales can be further improved, for instance, by adding, changing and rephrasing certain items. Finally, we provide suggestions for use with other neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is highly endemic in Vietnam, but scrub typhus—although recognized as an endemic disease—remains underappreciated. These diseases together are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. Scrub typhus (ST) is a bacterial disease requiring antimicrobial treatment, while dengue fever (DF) is of viral etiology and does not. The access to adequate diagnostics and the current understanding of empirical treatment strategies for both illnesses remain limited. In this study we aimed to contribute to the clinical decision process in the management of these two important etiologies of febrile illness in Vietnam. Methods: Using retrospective data from 221 PCR-confirmed scrub typhus cases and 387 NS1 protein positive dengue fever patients admitted to five hospitals in Khanh Hoa province (central Vietnam), we defined predictive characteristics for both diseases that support simple clinical decision making with potential to inform decision algorithms in future. We developed models to discriminate scrub typhus from dengue fever using multivariable logistic regression (M-LR) and classification and regression trees (CART). Regression trees were developed for the entire data set initially and pruned, based on cross-validation. Regression models were developed in a training data set involving 60% of the total sample and validated in the complementary subsample. Probability cut points for the distinction between scrub typhus and dengue fever were chosen to maximise the sum of sensitivity and specificity. Results: Using M-LR, following seven predictors were identified, that reliably differentiate ST from DF; eschar, regional lymphadenopathy, an occupation in nature, increased days of fever on admission, increased neutrophil count, decreased ratio of neutrophils/lymphocytes, and age over 40. Sensitivity and specificity of predictions based on these seven factors reached 93.7% and 99.5%, respectively. When excluding the "eschar" variable, the values dropped to 76.3% and 92.3%, respectively. The CART model generated one further variable; increased days of fever on admission, when eschar was included, the sensitivity and specificity was 95% and 96.9%, respectively. The model without eschar involved the following six variables; regional lymphadenopathy, increased days of fever on admission, increased neutrophil count, increased lymphocyte count, platelet count ≥ 47 G/L and age over 28 years as predictors of ST and provided a sensitivity of 77.4% and a specificity of 90.7%. Conclusions: The generated algorithms contribute to differentiating scrub typhus from dengue fever using basic clinical and laboratory parameters, supporting clinical decision making in areas where dengue and scrub typhus are co-endemic in Vietnam. Author summary: Dengue fever is highly endemic in Vietnam, while scrub typhus is recognized as a re-emerging neglected disease. Both diseases are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. However, scrub typhus is a bacterial disease requiring antimicrobial treatment, while dengue fever—of viral etiology—does not. Misdiagnosis and treatment delays cause potentially severe or fatal complications among scrub typhus patients, even though it is easily treatable. In this study, we used simple clinical and laboratory markers, which were identified upon admission of 221 PCR-confirmed scrub typhus cases and 387 NS1-positive dengue fever patients from Khanh Hoa province to identify the differences between scrub typhus and dengue. We found seven predictors that served to construct a simple clinical decision tree, holding great potential to distinguish scrub typhus from dengue using readily available clinical or laboratory findings. These predictors can strongly support medical staff in identifying scrub typhus cases from dengue, without using sophisticated diagnostic tests, and could improve the quality of diagnoses and appropriate treatment strategies at the primary health care level–especially in areas where scrub typhus and dengue fever are co-endemic in Vietnam and many parts of Asia and where diagnostic tests are not readily available. [ABSTRACT FROM AUTHOR]

Background: Anthrax is a disease that affects humans and animals. In Ethiopia, anthrax is a reportable disease and assumed to be endemic, although laboratory confirmation has not been routinely performed until recently. We describe the findings from the investigation of two outbreaks in Amhara region. Methods: Following reports of suspected outbreaks in Wag Hamra zone (Outbreak 1) and South Gondar zone (Outbreak 2), multi-sectoral teams involving both animal and public health officials were deployed to investigate and establish control programs. A suspect case was defined as: sudden death with rapid bloating or bleeding from orifice(s) with unclotted blood (animals); and signs compatible with cutaneous, ingestion, or inhalation anthrax ≤7 days after exposure to a suspect animal (humans). Suspect human cases were interviewed using a standard questionnaire. Samples were collected from humans with suspected anthrax (Outbreak 1 and Outbreak 2) as well as dried meat of suspect animal cases (Outbreak 2). A case was confirmed if a positive test was returned using real-time polymerase chain reaction (qPCR). Results: In Outbreak 1, a total of 49 cows died due to suspected anthrax and 22 humans developed symptoms consistent with cutaneous anthrax (40% attack rate), two of whom died due to suspected ingestion anthrax. Three people were confirmed to have anthrax by qPCR. In Outbreak 2, anthrax was suspected to have caused the deaths of two livestock animals and one human. Subsequent investigation revealed 18 suspected cases of cutaneous anthrax in humans (27% attack rate). None of the 12 human samples collected tested positive, however, a swab taken from the dried meat of one animal case (goat) was positive by qPCR. Conclusion: We report the first qPCR-confirmed outbreaks of anthrax in Ethiopia. Both outbreaks were controlled through active case finding, carcass management, ring vaccination of livestock, training of health professionals and outreach with livestock owners. Human and animal health authorities should work together using a One Health approach to improve case reporting and vaccine coverage. Author summary: Anthrax is a bacterial disease that causes rapid death in livestock, particularly cattle. Humans can be infected when they touch or eat animal carcasses or animal products, or when they inhale bacterial spores that have been aerosolized from the environment. Depending on how the bacterium enters the body, it causes cutaneous, gastrointestinal/oropharyngeal or respiratory disease in humans; death is rare for cutaneous anthrax but is more common with ingestion and inhalation forms of the disease. Anthrax has a global distribution but some areas of the world–such as Ethiopia–experience annual outbreaks in animals and humans. In this report, we present the findings from the first PCR-confirmed outbreaks in Ethiopia. In both outbreaks, the lack of farmer awareness and inherent economic value of livestock led farmers to salvage carcasses of animals that died, for meat and hides. Community members who participated in skinning and butchering of carcasses, eating or handling the meat, or processing hides/skins of suspect animal cases developed clinical signs consistent with anthrax (22 humans in Outbreak 1 including two suspected deaths; and 18 in Outbreak 2 including one suspected death). Further, animal parts from index cases (one cow in Outbreak 1; and one cow and one goat from Outbreak 2) were improperly discarded around the environment, leading a further 48 cows to become infected and die in Outbreak 1. Three humans in Outbreak 1 tested positive for anthrax on PCR. In addition, a swab taken from the dried meat of an animal that died in Outbreak 2 was positive by PCR. In both outbreaks, control was enacted through recalling and disposing remaining animal products, vaccination of livestock in surrounding areas and community education. [ABSTRACT FROM AUTHOR]

Background: In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence. Methods: We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower risk of disease than those who had blood drawn. We assessed clinical and demographic predictors of having blood taken for culture, and predictors of culture-positive results. Missing blood culture data were imputed using multiple imputations. Results: During the first year of surveillance, 2392 fever presentations were recorded and 1615 (68%) of these had blood cultures. Children were more likely to have blood taken for culture if they were older, had fever for longer, a current temperature ≥38 degrees, or if typhoid or a urinary tract infection were suspected. Based on imputation models, those with blood cultures were 1.87 times more likely to have blood culture-positive fever than those with missing data. Conclusion: Clinical opinion on the cause of the fever may play a large part in the decision to offer blood culture, regardless of study protocol. Crude typhoid incidence estimates should be adjusted for the proportion of cases that go undetected due to missing blood cultures while adjusting for the lower likelihood of culture-positivity in the group with missing data. Author summary: Typhoid fever is a serious illness caused by a bacterial infection in the blood. Typhoid spreads through contaminated water sources, poor sanitation or poor hygiene, and occurs most often in low-resource environments, with children being most at risk. It is hard to determine how common typhoid infections are in low-resource setting as there are many pathogens that can cause diseases with similar characteristics, and not all patients present to health-care facilities. The culture test to detect the presence of bacteria in the blood is poorly sensitive, costly to perform, and not available in all facilities. Therefore, true disease cases often go undetected, resulting in an underestimation of the true burden of disease. We examined factors associated with blood culture collection in fever patients attending typhoid surveillance clinics in Kathmandu, Nepal. We aimed to determine whether those who did not have a blood culture were different in terms of clinical and demographic characteristics to those who did have blood taken for culture and, additionally, whether they were more or less likely to test blood culture positive for typhoid fever. We provide estimates of inflation factors that can be used to adjust the crude incidence rate to account for the under-detection of typhoid cases. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. Methodology/Principal findings: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). Conclusions/Significance: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential. Author summary: Acute fever without localized signs is a common presentation of communicable neglected tropical diseases (NTDs). Scrub typhus, a potentially severe chigger-borne intracellular bacterial infection, is also an important differential diagnosis of acute febrile NTDs, which is endemic particularly in Asia. In Vietnam, the proportion of scrub typhus cases among patients with acute fever is currently unknown even in a tertiary hospital, because both clinical and laboratory diagnoses of scrub typhus are challenging. In this study, we enrolled acute fever patients hospitalized in the department of infectious diseases at a national tertiary hospital in Hanoi through a year. Scrub typhus was diagnosed using serological and PCR assays in 2.9% of enrolled patients. We found that the characteristics of scrub typhus patients were generally non-specific and most cases were missed based on clinical diagnosis alone. We also found that currently available serological assays were sub-optimal in Vietnam by comparing multiple diagnostic assays. Since the diagnostic antigens were not originally from Vietnam, the serological findings may underrepresent the actual number of cases. The presented data underlines the importance of a preemptive treatment strategy for scrub typhus among acute fever patients and adaptation of diagnostic assays to cover endemic strains. [ABSTRACT FROM AUTHOR]

Background: Trachoma is the leading infectious cause of blindness. However, little is known about the behavioural and environmental determinants of transmission of the causative organism, Chlamydia trachomatis. We conducted formative research in a trachoma hyper-endemic area of Ethiopia to explore the behaviours which are likely to contribute to trachoma transmission and map their determinants. Methodology/Principal findings: Data on water use, hygiene, defecation, and sleeping arrangements were collected from five communities during the dry and rainy seasons in 2016. Data collection involved direct observation in households (n = 20), interviews with caregivers (n = 20) and focus group discussions (n = 11). Although several behaviours that likely contribute to trachoma transmission were identified, no single behaviour stood out as the dominant contributor. Hygiene practices reflected high levels of poverty and water scarcity. Face washing and soap use varied within and between households, and were associated with other factors such as school attendance. Children’s faces were rarely wiped to remove nasal or ocular discharge, which was not perceived to be socially undesirable. Bathing and laundry were performed infrequently due to the amount of time and water required. Open defecation was a normative practice, particularly for young children. Latrines, when present, were poorly constructed, maintained and used. Young children and parents slept closely together and shared bedding that was infrequently washed. Conclusions/Significance: Existing norms and enabling factors in this context favour the development of interventions to improve facial cleanliness as more feasible than those that reduce unsafe faeces disposal. Interventions to increase the frequency of bathing and laundry may also be infeasible unless water availability within the home is improved. [ABSTRACT FROM AUTHOR]

Introduction: In Tunisia, almost 77% of clinically and bacteriologically diagnosed cases of extrapulmonary tuberculosis (EPTB) are zoonotic TB, caused by M. bovis. Although several studies have analyzed bovine TB in cattle in Tunisia, no study has evaluated the risk of transmission to humans in such an endemic country. We aimed to study the genetic diversity of M. bovis human isolates, to ascertain the causes of human EPTB infection by M. bovis and to investigate the distribution and population structure of this species in Tunisia. Materials and methods: A total of 110 M. bovis isolates taken from patients with confirmed EPTB were characterized by spoligotyping and MIRU-VNTR typing methods. Results: Among the 15 spoligotypes detected in our study, 6 (SB0120, SB0121, SB2025, SB1200, SB1003 and SB0134) were the most prevalent (83.5%) of which SB0120, SB0121 and SB2025 were the most prevailing. MIRU-VNTR typing method showed a high genotypic and genetic diversity. The genetic differentiation based on MIRU-VNTR was significant between populations from South East (Tataouine, Medenine) and Central West (Gafsa, Sidi Bouzid, Kasserine) regions. Of note, 13/15 (86.7%) spoligotypes detected in our study were previously identified in cattle in Tunisia with different frequencies suggesting a peculiar ability of some genotypes to infect humans. Using combined spoligotyping and MIRU-VNTR method, a high clustering rate of 43.9% was obtained. Our results underlined that human EPTB due to M. bovis was more commonly found in female gender and in young patients. Most of our patients, 66.4% (73/110) were raw milk or derivatives consumers, whereas 30.9% (34/110) patients would have contracted EPTB through contact with livestock. The findings suggest that the transmission of Zoonotic TB caused by M. bovis to humans mainly occurred by oral route through raw milk or derivatives. Conclusion: Our study showed the urgent need of a better veterinary control with the implementation of effective and comprehensive strategies in order to reach a good protection of animals as well as human health. [ABSTRACT FROM AUTHOR]

Background: Integrated disease management, disability and inclusion (DMDI) for NTDs is increasingly prioritised. There is limited evidence on the effectiveness of integrated DMDI from the perspective of affected individuals and how this varies by differing axes of inequality such as age, gender, and disability. We used narrative methods to consider how individuals’ unique positions of power and privilege shaped their illness experience, to elucidate what practical and feasible steps could support integrated DMDI in Liberia and beyond. Methods: We purposively selected 27 participants affected by the clinical manifestations of lymphatic filariasis, leprosy, Buruli Ulcer, and onchocerciasis from three counties in Liberia to take part in illness narrative interviews. Participants were selected to ensure maximum variation in age, gender and clinical manifestation. Narrative analysis was grounded within feminist intersectional theory. Findings: For all participants, chronic illness, morbidity and disability associated with NTDs represented a key moment of ‘biographical disruption’ triggering the commencement of a restitution narrative. Complex health seeking pathways, aetiologies and medical syncretism meant that adoption of the ‘sick role’ was initially acceptable, but when the reality of permanency of condition was identified, a transition to periods of chaos and significant psycho-social difficulty occurred. An intersectional lens emphasises how biographical disruption is mediated by intersecting social processes. Gender, generation, and disability were all dominant axes of social inequity shaping experience. Significance: This is one of the first studies to use narrative approaches to interrogate experience of chronic disabling conditions within LMICs and is the only study to apply such an analysis to NTDs. The emotive power of narrative should be utilised to influence the value base of policy makers to ensure that DMDI strategies respond holistically to the needs of the most marginalised, thus contributing to more equitable people-centred care. [ABSTRACT FROM AUTHOR]

Background: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil. Methodology/Principal findings: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25–1.97) and Northeast (OR = 1.44; 95%CI 1.17–1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01–1.69), no income (OR = 1.41; 95%CI 1.07–1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13–1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28–1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10–1.66). Conclusions: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control. [ABSTRACT FROM AUTHOR]

Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period. Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae. [ABSTRACT FROM AUTHOR]

Background: The role of rodents in Leptospira epidemiology and transmission is well known worldwide. Rats are known to carry different pathogenic serovars of Leptospira spp. capable of causing disease in humans and animals. Wild rats (Rattus spp.), especially the Norway/brown rat (Rattus norvegicus) and the black rat (R. rattus), are the most important sources of Leptospira infection, as they are abundant in urban and peridomestic environments. In this study, we compiled and summarized available data in the literature on global prevalence of Leptospira exposure and infection in rats, as well as compared the global distribution of Leptospira spp. in rats with respect to prevalence, geographic location, method of detection, diversity of serogroups/serovars, and species of rat. Methods: We conducted a thorough literature search using PubMed without restrictions on publication date as well as Google Scholar to manually search for other relevant articles. Abstracts were included if they described data pertaining to Leptospira spp. in rats (Rattus spp.) from any geographic region around the world, including reviews. The data extracted from the articles selected included the author(s), year of publication, geographic location, method(s) of detection used, species of rat(s), sample size, prevalence of Leptospira spp. (overall and within each rat species), and information on species, serogroups, and/or serovars of Leptospira spp. detected. Findings: A thorough search on PubMed retrieved 303 titles. After screening the articles for duplicates and inclusion/exclusion criteria, as well as manual inclusion of relevant articles, 145 articles were included in this review. Leptospira prevalence in rats varied considerably based on geographic location, with some reporting zero prevalence in countries such as Madagascar, Tanzania, and the Faroe Islands, and others reporting as high as >80% prevalence in studies done in Brazil, India, and the Philippines. The top five countries that were reported based on number of articles include India (n = 13), Malaysia (n = 9), Brazil (n = 8), Thailand (n = 7), and France (n = 6). Methods of detecting or isolating Leptospira spp. also varied among studies. Studies among different Rattus species reported a higher Leptospira prevalence in R. norvegicus. The serovar Icterohaemorrhagiae was the most prevalent serovar reported in Rattus spp. worldwide. Additionally, this literature review provided evidence for Leptospira infection in laboratory rodent colonies within controlled environments, implicating the zoonotic potential to laboratory animal caretakers. Conclusions: Reports on global distribution of Leptospira infection in rats varies widely, with considerably high prevalence reported in many countries. This literature review emphasizes the need for enhanced surveillance programs using standardized methods for assessing Leptospira exposure or infection in rats. This review also demonstrated several weaknesses to the current methods of reporting the prevalence of Leptospira spp. in rats worldwide. As such, this necessitates a call for standardized protocols for the testing and reporting of such studies, especially pertaining to the diagnostic methods used. A deeper understanding of the ecology and epidemiology of Leptospira spp. in rats in urban environments is warranted. It is also pertinent for rat control programs to be proposed in conjunction with increased efforts for public awareness and education regarding leptospirosis transmission and prevention. [ABSTRACT FROM AUTHOR]

Bubonic is the most prevalent plague form in Madagascar. Indoor ground application of insecticide dust is the conventional method used to control potentially infected rodent fleas that transmit the plague bacterium from rodents to humans. The use of bait stations is an alternative approach for vector control during plague epidemics, as well as a preventive control method during non-epidemic seasons. Bait stations have many advantages, principally by reducing the amount of insecticide used, lowering the cost of the treatment and minimizing insecticide exposure in the environment. A previous study reported promising results on controlling simultaneously the reservoir and vectors, when slow-acting rodenticide was incorporated in bait stations called “Boîtes de Kartman”. However, little evidence of an effective control of the fleas prior to the elimination of rodents was found. In this study, we evaluated bait stations containing insecticide powder and non-toxic attractive rodent bait for their potential to control rat fleas. Its efficacy was compared to the standard method. The impact of both methods on indoor and outdoor rodent fleas, as well as the human household flea Pulex irritans were analyzed at different time points after treatments. Bait stations did not cause any significant immediate or delayed reduction of rat fleas and increasing the number of operational bait stations per household did not significantly improve their efficacy. Insecticide ground dusting appeared to be the most efficient method to control indoor rat fleas. Both methods appeared to have little impact on the density of outdoor rat fleas and human fleas. These results demonstrate limited effectiveness for bait stations and encourage the maintenance of insecticide dusting as a first-line control strategy in case of epidemic emergence of plague, when immediate effect on rodent fleas is needed. Recommendations are given to improve the efficacy of the bait station method. [ABSTRACT FROM AUTHOR]

Over recent decades, Salmonella infection research has predominantly relied on murine infection models. However, in many cases the infection phenotypes of Salmonella pathovars in mice do not recapitulate human disease. For example, Salmonella Typhimurium ST313 is associated with enhanced invasive infection of immunocompromised people in Africa, but infection of mice and other animal models with ST313 have not consistently reproduced this invasive phenotype. The introduction of alternative infection models could help to improve the quality and reproducibility of pathogenesis research by facilitating larger-scale experiments. To investigate the virulence of S. Typhimurium ST313 in comparison with ST19, a combination of avian and insect disease models were used. We performed experimental infections in five lines of inbred and one line of outbred chickens, as well as in the alternative chick embryo and Galleria mellonella wax moth larvae models. This extensive set of experiments identified broadly similar patterns of disease caused by the African and global pathovariants of Salmonella Typhimurium in the chicken, the chicken embryo and insect models. A comprehensive analysis of all the chicken infection experiments revealed that the African ST313 isolate D23580 had a subtle phenotype of reduced levels of organ colonisation in inbred chickens, relative to ST19 strain 4/74. ST313 isolate D23580 also caused reduced mortality in chicken embryos and insect larvae, when compared with ST19 4/74. We conclude that these three infection models do not reproduce the characteristics of the systemic disease caused by S. Typhimurium ST313 in humans. [ABSTRACT FROM AUTHOR]

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. [ABSTRACT FROM AUTHOR]

Background: Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology: A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings: The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion: Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure. [ABSTRACT FROM AUTHOR]

Background: The Alliance for the Global Elimination of Trachoma has set the target for eliminating trachoma as a public health problem by 2020. However, challenges remain, including socio-cultural issues. Districts in Northern Tanzania, predominantly inhabited by the Maasai ethnic group, remain endemic for trachoma. We explored socio-cultural factors that may impact the elimination of trachoma. Methods/Findings: This study was nested within a larger ethnographic study of trachoma among Maasai in Northern Tanzania. We used stratified random sampling and semi-structured interviews to examine knowledge and understanding. Interviews were conducted and recorded in Maa, by a native Maa speaking trained interviewer. Transcripts were translated into English. A framework method for a content analysis was used. There was awareness of trachoma and basic symptoms. Yet understanding of etiology and prevention was poor. Trachoma was attributed to pollen, dust, and smoke. Water was recognized as beneficial, but seen as treatment and not prevention. Traditional medicines were most often used for treating conjunctival inflammation, with the most common being a rough leaf used to scratch the inside of the eyelid until it bleeds. Knowledge of mass drug administration (MDA) was inconsistent, although many thought it helped the community, but it was perceived as only for children and the sick. Many participants reported not taking azithromycin and some had no recollection of MDA six months earlier. There was little connection between childhood infection, trichiasis and related blindness. Trichiasis was often seen as a problem of old women, and treated locally by epilation. Conclusion/Significance: Understanding indigenous knowledge may help guide control programs, tailor them to local contexts, address local beliefs and dispel misunderstandings. There is an essential need to understand the social, cultural and political context of the target community to deliver effective programs. Despite limited knowledge, the community recognized trachoma as a public health problem. Results have implications for disease control programs in other marginalized communities. [ABSTRACT FROM AUTHOR]

The article offers information on the prevention of Cholera and control in refugee settings. Topics discussed Cholera is considered as a serious threat for refugee populations; mentions the humanitarian community developed the sphere standards for the living conditions and availability of health services in refugee camps; and highlights several historic outbreaks in refugee camps.