Dog ecology and rabies control including canine vaccination coverage: Impacts from a survey in Madagascar.

BACKGROUND: Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans. Despite the existence of safe and effective vaccines to prevent the disease, an estimated 99% of human rabies deaths worldwide are caused by dog-mediated rabies with children at the highest risk of infection. Rabies has been endemic in Madagascar for over a century, yet there has been little research evaluating local knowledge and practices impacting on the rabies control and prevention. Thus, this study was undertaken to better understand the dog ecology including canine vaccine coverage and to assess knowledge and practices of dog owners and veterinarians. METHODOLOGY: A cross-sectional study was conducted among 123 dog-owning households in thirteen fokontanys in Mahajanga from July 4 to September 13, 2016. Single and multi-member dog-owning households in the study area on the day of the interview were eligible for inclusion and purposively selected with the support of a local guide. The survey included a household questionnaire capturing information on the dog's demographics, husbandry practices, knowledge and practices towards rabies and its control measures; the dog ecology questionnaire collected dog characteristics, vaccination status and husbandry practices. All households that reported a dog bite incident, were invited to participate in a dog bite questionnaire. In addition, direct observations of roaming dogs were conducted to assess dog population demographics and to document behavioural characteristics. Two veterinarians were purposively selected and took part in an interview during the survey period, providing information on rabies control activities, including dog-care practices in the area. Descriptive and inferential data analyses were performed using Epi Info version 7.1.5.0 (CDC Atlanta, USA). RESULTS: We recorded a total of 400 dogs, of which 338 (84.5%) were owned amongst 123 households. More than half (67.8%) of owned dogs were between 1 to 5 years old and 95.6% were kept for guarding purposes. 45% of the surveyed dogs had free access to roam outside the premises. The majority (85.4%) of dog owners were knowledgeable that a dog bite could potentially transmit RABV to humans. 19 dog bites were reported and of these 73.6% were caused by the owner's or a neighbour's dog. In 6 of the 19 cases, children between 7 and 15 years of age were the victims. Dog vaccination coverage against rabies was 34% among owned dogs. Of the participants aware of a veterinarian, the majority (55/82) indicated that they accessed veterinarian services at irregular intervals. The main obstacles to vaccinations cited by dog owners were limited financial resources and difficulty accessing veterinary care. CONCLUSION: This study contributes to enhanced understanding of the dog ecology including canine vaccine coverage as well as knowledge and practices of dog owners in Madagascar. Most dogs in the study area were accessible for preventive vaccination through their owners, however only one third of the investigated canine population was vaccinated against rabies. Concerted national efforts towards rabies prevention and control should aim to address financial challenges and access to veterinary services.

Schistosome infection among pregnant women in the rural highlands of Madagascar: A cross-sectional study calling for public health interventions in vulnerable populations.

INTRODUCTION: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. METHODS: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. RESULTS: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3-58.5). A statistically significant association was found with age group (increased prevalence in 31-47 years old, compared to 16-20 years old (aPR = 1.15, CI 95%: 1.02-1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77-0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. DISCUSSION AND CONCLUSION: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis.

ESBL-Type and AmpC-Type Beta-Lactamases in Third Generation Cephalosporin-Resistant Enterobacterales Isolated from Animal Feces in Madagascar.

Third generation cephalosporin-resistant (3GCR) Enterobacterales are known to be prevalent in Madagascar, with high colonization or infection rates in particular in Madagascan patients. Extended spectrum beta-lactamases (ESBLs) have been reported to be the predominant underlying resistance mechanism in human isolates. So far, little is known on antimicrobial resistance and its molecular determinants in Enterobacterales and other bacteria causing enteric colonization of Madagascan wild animals. To address this topic, swabs from 49 animal stool droppings were collected in the Madagascan Tsimanapesotsa National Park and assessed by cultural growth of bacterial microorganisms on elective media. In addition to 7 Acinetobacter spp., a total of 31 Enterobacterales growing on elective agar for Enterobacterales could be isolated and subjected to whole genome sequencing. Enterobacter spp. was the most frequently isolated genus, and AmpC-type beta-lactamases were the quantitatively dominating molecular resistance mechanism. In contrast, the blaCTX-M-15 gene, which has repeatedly been associated with 3GC-resistance in Madagascan Enterobacterales from humans, was detected in a single Escherichia coli isolate only. The identification of the fosfomycin-resistance gene fosA in a high proportion of isolates is concerning, as fosfomycin is increasingly used to treat infections caused by multidrug-resistant bacteria. In conclusion, the proof-of-principle assessment indicated a high colonization rate of resistant bacteria in stool droppings of Madagascan wild animals with a particular focus on 3GCR Enterobacterales. Future studies should confirm these preliminary results in a more systematic way and assess the molecular relationship of animal and human isolates to identify potential routes of transmission.

Mapping the incidence rate of typhoid fever in sub-Saharan Africa.

BACKGROUND: With more than 1.2 million illnesses and 29,000 deaths in sub-Saharan Africa in 2017, typhoid fever continues to be a major public health problem. Effective control of the disease would benefit from an understanding of the subnational geospatial distribution of the disease incidence. METHOD: We collated records of the incidence rate of typhoid fever confirmed by culture of blood in Africa from 2000 to 2022. We estimated the typhoid incidence rate for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates representing access to improved water and sanitation, health conditions of the population, and environmental conditions. RESULTS: We identified six published articles and one pre-print representing incidence rate estimates in 22 sites in 2000-2022. Estimated incidence rates showed geospatial variation at sub-national, national, and regional levels. The incidence rate was high in Western and Eastern African subregions followed by Southern and Middle African subregions. By age, the incidence rate was highest among 5-14 yo followed by 2-4 yo, > 14 yo, and 0-1 yo. When aggregated across all age classes and grids that comprise each country, predicted incidence rates ranged from 43.7 (95% confidence interval: 0.6 to 591.2) in Zimbabwe to 2,957.8 (95% CI: 20.8 to 4,245.2) in South Sudan per 100,000 person-years. Sub-national heterogeneity was evident with the coefficient of variation at the 20 km × 20 km grid-level ranging from 0.7 to 3.3 and was generally lower in high-incidence countries and widely varying in low-incidence countries. CONCLUSION: Our study provides estimates of 20 km × 20 km incidence rate of typhoid fever across sub-Saharan Africa based on data collected from 2000 through 2020. Increased understanding of the subnational geospatial variation of typhoid fever in Africa may inform more effective intervention programs by better targeting resources to heterogeneously disturbed disease risk.

Awareness and knowledge of female genital schistosomiasis in a population with high endemicity: a cross-sectional study in Madagascar.

Introduction: Female genital schistosomiasis (FGS) is a neglected disease with long-term physical and psychosocial consequences, affecting approximately 50 million women worldwide and generally representing an unmet medical need on a global scale. FGS is the chronic manifestation of a persistent infection with Schistosoma haematobium. FGS services are not routinely offered in endemic settings with a small percentage of women at risk receiving adequate care. Madagascar has over 60% prevalence of FGS and no guidelines for the management of the disease. This study aimed to determine FGS knowledge among women and health care workers (HCWs) in a highly endemic area of Madagascar. Methods: A convenience sampling strategy was used for this cross-sectional study. Descriptive statistics including proportions and 95% confidence intervals (CI) were calculated, reporting socio-demographic characteristics of the population. Knowledge sources were evaluated descriptively. Binary Poisson regression with robust standard errors was performed; crude (CPR) and adjusted prevalence ratio (APR) with 95% CIs were calculated. Results: A total of 783 participants were included in the study. Among women, 11.3% (n = 78) were aware of FGS while among the HCWs 53.8% (n = 50) were aware of FGS. The highest level of knowledge was observed among women in an urban setting [24%, (n = 31)] and among those with a university education/vocational training [23% (n = 13)]. A lower APR of FGS knowledge was observed in peri-urban [APR 0.25 (95% CI: 0.15; 0.45)] and rural [APR 0.37 (95% CI 0.22; 0.63)] settings in comparison to the urban setting. Most HCWs reported other HCWs [40% (n = 20)] while women mainly reported their family [32% (n = 25)] as being their main source of information in the 6 months prior to the survey. Discussion and conclusions: Our study shows limited awareness and knowledge of FGS among population groups in the highly endemic Boeny region of Madagascar. With this study we contribute to identifying an important health gap in Madagascar, which relates to a disease that can silently affect millions of women worldwide. In alignment with the targets of the NTD roadmap, addressing schistosomiasis requires a paradigm shift for its control and management including a greater focus on chronic forms of the disease.

Confirmation by necropsy of a high prevalence of porcine cysticercosis in a rural district of Madagascar.

Neurocysticercosis is recognized as an important health issue in the Malagasy population. To date, investigations into prevalence of infection with the causative agent, Taenia solium, in the parasite's natural animal intermediate hosts, have relied on serological methods which have been found to be non-specific. We determined the prevalence of porcine cysticercosis among pigs from a contiguous area of the Betafo and Mandoto administrative districts, Vakinankaratra Region, Madagascar. One hundred and four slaughter-weight pigs were examined by detailed necropsy examination including slicing of the heart, tongue, masseter muscles, diaphragm and carcase musculature. Thirty-seven animals (35.6%) were found infected with T. solium, representing one of the highest rates of infection ever reported, worldwide. These findings highlight the importance of T. solium in Madagascar and support the need for increased efforts to prevent the parasite's transmission to reduce its burden on the health of the Malagasy population.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

Madagascar's EPI vaccine programs: A systematic review uncovering the role of a child's sex and other barriers to vaccination.

Background: Immunizations are one of the most effective tools a community can use to increase overall health and decrease the burden of vaccine-preventable diseases. Nevertheless, socioeconomic status, geographical location, education, and a child's sex have been identified as contributing to inequities in vaccine uptake in low- and middle-income countries (LMICs). Madagascar follows the World Health Organization's Extended Programme on Immunization (EPI) schedule, yet vaccine distribution remains highly inequitable throughout the country. This systematic review sought to understand the differences in EPI vaccine uptake between boys and girls in Madagascar. Methods: A systematic literature search was conducted in August 2021 through MEDLINE, the Cochrane Library, Global Index Medicus, and Google Scholar to identify articles reporting sex-disaggregated vaccination rates in Malagasy children. Gray literature was also searched for relevant data. All peer-reviewed articles reporting sex-disaggregated data on childhood immunizations in Madagascar were eligible for inclusion. Risk of bias was assessed using a tool designed for use in systematic reviews. Data extraction was conducted with a pre-defined data extraction tool. Sex-disaggregated data were synthesized to understand the impact of a child's sex on vaccination status. Findings: The systematic search identified 585 articles of which a total of three studies were included in the final data synthesis. One additional publication was included from the gray literature search. Data from included articles were heterogeneous and, overall, indicated similar vaccination rates in boys and girls. Three of the four articles reported slightly higher vaccination rates in girls than in boys. A meta-analysis was not conducted due to the heterogeneity of included data. Six additional barriers to immunization were identified: socioeconomic status, mother's education, geographic location, supply chain issues, father's education, number of children in the household, and media access. Interpretation: The systematic review revealed the scarcity of available sex-stratified immunization data for Malagasy children. The evidence available was limited and heterogeneous, preventing researchers from conclusively confirming or denying differences in vaccine uptake based on sex. The low vaccination rates and additional barriers identified here indicate a need for increased focus on addressing the specific obstacles to vaccination in Madagascar. A more comprehensive assessment of sex-disaggregated vaccination status of Malagasy children and its relationship with such additional obstacles is recommended. Further investigation of potential differences in vaccination status will allow for the effective implementation of strategies to expand vaccine coverage in Madagascar equitably. Funding and registration: AH, BT, FM, GN, and RR are supported by a grant from the Bill and Melinda Gates Foundation (grant number: OPP1205877). The review protocol is registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021265000).

Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia.

BACKGROUND: We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. METHODS: We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. RESULTS: Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana. CONCLUSIONS: Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

High seroprevalence of SARS-CoV-2 in Burkina-Faso, Ghana and Madagascar in 2021: a population-based study.

BACKGROUND: The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. METHODS: A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. RESULTS: Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. CONCLUSIONS: High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk.

Clustering of Cryptosporidium species infections among sheep and cattle but not children in remote highland communities of Madagascar.

BACKGROUND: The aim of this study was to identify local transmission patterns of Cryptosporidium spp. infections among livestock and humans in four extremely rural and remote highland communities in Madagascar. METHODS: In this cross-sectional study, households were randomly sampled throughout a 1-year study period, with one feces sample collected from each child (≤ 5 years old), sheep and cattle. Cryptosporidium spp. were identified using a nested PCR assay targeting the 18S ribosomal RNA gene. All samples positive for Cryptosporidium hominis were further subtyped by sequencing the 60-kDa glycoprotein gene (gp60). Spatial clustering methods were applied to analyze potential transmission patterns. RESULTS: In total, 252 households participated in the study, and samples from 197 children, 862 cattle and 334 sheep were collected and included in the study. Of the samples collected, 11 (5.6%) from children, 30 (3.5%) from cattle and 42 (12.6%) from sheep tested positive for Cryptosporidium spp. Very little overlap in the species distribution between human and animal infections was found. Global (overall) and local (spatially defined) clustering was observed for Cryptosporidium spp. infections in sheep and for Cryptosporidium xiaoi/bovis infections among sheep and cattle. DISCUSSION: The results of this analysis do not support the occurrence of defined disease outbreaks, rather they point to a continuous series of transmission events that are spatially aggregated. Despite the close coexistence between humans, sheep and cattle in the study area, mutual transmission was not observed. Hence, the study underlines the importance of sustained sanitation and hygiene measures to prevent cryptosporidiosis transmission among infants, since asymptomatic children serve as an infection reservoir. Similarly, the study highlights the importance of improving hygiene to reduce the transmission of Cryptosporidium spp. in livestock, an infection with serious consequences, especially in newborn calves.

Fcγ-Receptor-Based Enzyme-Linked Immunosorbent Assays for Sensitive, Specific, and Persistent Detection of Anti-SARS-CoV-2 Nucleocapsid Protein IgG Antibodies in Human Sera.

Sensitive and specific serological tests are mandatory for epidemiological studies evaluating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence as well as coronavirus disease 2019 (COVID-19) morbidity and mortality rates. The accuracy of results is challenged by antibody waning after convalescence and by cross-reactivity induced by previous infections with other pathogens. By employing a patented platform technology based on capturing antigen-antibody complexes with a solid-phase-bound Fcγ receptor (FcγR) and truncated nucleocapsid protein as the antigen, two SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISAs), featuring different serum and antigen dilutions, were developed. Validation was performed using a serum panel comprising 213 longitudinal samples from 35 COVID-19 patients and a negative-control panel consisting of 790 pre-COVID-19 samples from different regions of the world. While both assays show similar diagnostic sensitivities in the early convalescent phase, ELISA 2 (featuring a higher serum concentration) enables SARS-CoV-2 IgG antibody detection for a significantly longer time postinfection (≥15 months). Correspondingly, analytical sensitivity referenced to indirect immunofluorescence testing (IIFT) is significantly higher for ELISA 2 in samples with a titer of ≤1:640; for high-titer samples, a prozone effect is observed for ELISA 2. The specificities of both ELISAs were excellent not only for pre-COVID-19 serum samples from Europe, Asia, and South America but also for several challenging African sample panels. The SARS-CoV-2 IgG FcγR ELISAs, methodically combining antigen-antibody binding in solution and isotype-specific detection of immune complexes, are valuable tools for seroprevalence studies requiring the (long-term) detection of anti-SARS-CoV-2 IgG antibodies in populations with a challenging immunological background and/or in which spike-protein-based vaccine programs have been rolled out.

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective.

While typhoid fever has largely been eliminated in high-income regions which have developed modern water, sanitation, and hygiene facilities, it remains a significant public health burden resulting in morbidity and mortality among millions of individuals in resource-constrained settings. Prevention and control efforts are needed that integrate several high-impact interventions targeting facilities and infrastructure, including those addressing improvements in sanitation, access to safe water, and planned urbanization, together with parallel efforts directed at effective strategies for use of typhoid conjugate vaccines (TCV). The use of TCVs is a critical tool with the potential of having a rapid impact on typhoid fever disease burden; their introduction will also serve as an important strategy to combat evolving antimicrobial resistance to currently available typhoid fever treatments. Well-designed epidemiological surveillance studies play a critical role in establishing the need for, and monitoring the impact of, typhoid fever control and prevention strategies implemented by public health authorities. Here, we present a perspective based on a narrative review of the impact of typhoid fever on morbidity and mortality in sub-Saharan Africa and discuss ongoing surveillance activities and the role of vaccination in prevention and control efforts.

Seroprevalence of SARS-CoV-2 in urban settings in three sub-Saharan African countries (SeroCoV): a study protocol for a household-based cross-sectional prevalence study using two-stage cluster sampling.

INTRODUCTION: The current COVID-19 pandemic has impacted the entire world with increasing morbidity and mortality and has resulted in serious economic and social consequences. Assessing the burden of COVID-19 is essential for developing efficient pandemic preparedness and response strategies and for determining the impact of implemented control measures. Population-based seroprevalence surveys are critical to estimate infection rates, monitor the progression of the epidemic and to allow for the identification of persons exposed to the infection who may either have been asymptomatic or were never tested. This is especially important for countries where effective testing and tracking systems could not be established and where non-severe cases or under-reported deaths might have blurred the true burden of COVID-19. Most seroprevalence surveys performed in sub-Saharan Africa have targeted specific high risk or more easily accessible populations such as healthcare workers or blood donors, and household-based estimates are rarely available. Here, we present the study protocol for a SARS-CoV-2 seroprevalence estimation in the general population of Burkina Faso, Ghana and Madagascar in 2021. METHODS AND ANALYSIS: The SeroCoV study is a household-based cross-sectional prevalence investigation in persons aged 10 years and older living in urban areas in six cities using a two-stage geographical cluster sampling method stratified by age and sex. The presence of anti-SARS-CoV-2 IgG antibodies will be determined using a sensitive and specific SARS-CoV-2 IgG ELISA. In addition, questionnaires will cover sociodemographic information, episodes of diseases and history of testing and treatment for COVID-like symptoms, travel history and safety measures. We will estimate the seroprevalence of SARS-CoV-2, taking into account test performance and adjusting for the age and sex of the respective populations. ETHICS AND DISSEMINATION: Ethical approval was received for all participating countries. Results will be disseminated through reports and presentations at the country level as well as peer-reviewed publications and international scientific conferences presentations.

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic.

Molecular Evidence for Flea-Borne Rickettsiosis in Febrile Patients from Madagascar.

Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia > 38.5 °C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment.

A cluster randomized controlled trial for assessing POC-CCA test based praziquantel treatment for schistosomiasis control in pregnant women and their young children: study protocol of the freeBILy clinical trial in Madagascar.

BACKGROUND: Mass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high-endemic regions in MDA campaigns, they are usually not treated without a diagnosis. Diagnostic tools identifying infections at the primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a test-based schistosomiasis treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years. METHODS: A two-armed, cluster-randomized, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni. The participants are being tested with the point of care-circulating cathodic antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar's highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers. DISCUSSION: This trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research. TRIAL REGISTRATION: Pan-African Clinical Trial Register PACTR201905784271304. Retrospectively registered on 15 May 2019.

Detection of Pathogens of Acute Febrile Illness Using Polymerase Chain Reaction from Dried Blood Spots.

Quantitative polymerase chain reaction (qPCR) of dried blood spots (DBS) for pathogen detection is a potentially convenient method for infectious disease diagnosis. This study tested 115 DBS samples paired with whole blood specimens of children and adolescent from Burkina Faso, Sudan, and Madagascar by qPCR for a wide range of pathogens, including protozoans, helminths, fungi, bacteria, and viruses. Plasmodium spp. was consistently detected from DBS but yielded a mean cycle threshold (Ct) 5.7 ± 1.6 higher than that from whole blood samples. A DBS qPCR Ct cutoff of 27 yielded 94.1% sensitivity and 95.1% specificity against the whole blood qPCR cutoff of 21 that has been previously suggested for malaria diagnosis. For other pathogens investigated, DBS testing yielded a sensitivity of only 8.5% but a specificity of 98.6% compared with whole blood qPCR. In sum, direct PCR of DBS had reasonable performance for Plasmodium but requires further investigation for the other pathogens assessed in this study.

The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries.

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. METHODS: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. RESULTS: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries. CONCLUSIONS: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.