Case Report: Three cases of suspected female genital schistosomiasis and precancerous lesions for cervical cancer in a highly endemic country—from clinical management to public health implications

Female genital schistosomiasis (FGS) is a chronic manifestation of schistosomiasis, usually caused by Schistosoma haematobium infection, which can be responsible for infertility, ectopic pregnancy, and abortion, and is associated with an increased prevalence of HIV infection. No screening programs are currently recommended for FGS. Colposcopy, the conventionally suggested diagnostic tool for FGS, is also considered a crucial screening tool for cervical cancer (CC). We performed an experimental screening via colposcopy for FGS at primary healthcare centers (PHCCs) in the Boeny region of Madagascar, allowing for the detection of patients with both FGS signs and HPV-related dysplasia (HPV-dy). All suspected FGS cases were treated with praziquantel on the day of colposcopy, and all images of suspected CC or HPV-dy were re-assessed by a gynecologist and, if needed, patients were then provided with additional colposcopy for histologic diagnosis and treatment. We describe three cases of FGS and HPV-related precancerous lesions detected during the project, discussing the state of art of the relationship between CC, FGS and HPV and the real-life challenges encountered in terms of both patient compliance and the diagnostic and treatment cascade. Despite the current diagnostic limitations, a screening for FGS via colposcopy may contribute to the early identification of CC or precancerous lesions. The addition of visual inspection with acetic acid (VIA) during colposcopy for FGS screening could improve its impact on CC screening. In addition, although there is limited evidence of the effectiveness of praziquantel in FGS, treatment should in any case be proposed for suspicious lesions, given its safety and ease of administration. The benefit of combined screening could be maximised by increasing the availability of good quality services and improve awareness of both diseases among wome

Are brucellosis, Q fever and melioidosis potential causes of febrile illness in Madagascar?

Brucellosis, Q fever and melioidosis are zoonoses, which can lead to pyrexia. These diseases are often under-ascertained and underreported because of their unspecific clinical signs and symptoms, insufficient awareness by physicians and public health officers and limited diagnostic capabilities, especially in low-resource countries. Therefore, the presence of Brucella spp., Coxiella burnetii and Burkholderia pseudomallei was investigated in Malagasy patients exhibiting febrile illness. In addition, we analyzed zebu cattle and their ticks as potential reservoirs for Brucella and C. burnetii, respectively. Specific quantitative real-time PCR assays (qPCRs) were performed on 1020 blood samples drawn from febrile patients. In total, 15 samples (1.5%) were Brucella-positive, mainly originating from patients without travel history, while DNA from C. burnetii and Bu. pseudomallei was not detected. Anti-C. burnetii antibodies were found in four out of 201 zebu serum samples (2%), whereas anti-Brucella antibodies could not be detected. Brucella DNA was detected in a single zebu sample. Three out of 330 ticks analyzed (1%) were positively tested for C. burnetii DNA but with high Ct values in the qPCR assay. Our data suggest that zebus as well as Amblyomma and Boophilus ticks have to be considered as a natural reservoir or vector for C. burnetii, but the risk of cattle-to-human transmission is low. Since bovine brucellosis does not seem to contribute to human infections in Madagascar, other transmission routes have to be assumed

Comparative genomics revealed adaptive admixture in Cryptosporidium hominis in Africa

Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 (gp60) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C. hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide diversity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses; (2) local anthroponotic transmission underpins the spread of this pathogen in Africa; (3) hybridization occurs between distinct geographical lineages; and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host–parasite coevolution

The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis

Background. Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. Methods. A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. Results. Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. Conclusions. SETA supports public health policy on typhoid immunization strategy in Africa

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

Peer reviewed: TrueBACKGROUND: 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)

Table_4_Madagascar's EPI vaccine programs: A systematic review uncovering the role of a child's sex and other barriers to vaccination.DOCX

BackgroundImmunizations 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.MethodsA 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.FindingsThe 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.InterpretationThe 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 registrationAH, 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).</p