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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]

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]

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: 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: 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]