Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar : a cross-sectional study

Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts 64200/\u3bcl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-\u3b1A (3 isolates), VNII-\u3b1A (4 isolates) or hybrid VNI/VNII-\u3b1AA\u3b1 (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program

Taenia solium porcine cysticercosis in Madagascar: Comparison of immuno-diagnostic techniques and estimation of the prevalence in pork carcasses traded in Antananarivo city

Taenia solium cysticercosis was reported in official veterinary and medical statistics to be highly prevalent in pigs and humans in Madagascar, but few estimates are available for pigs. This study aimed to estimate the seroprevalence of porcine cysticercosis among pigs slaughtered in Antananarivo abattoirs. Firstly, the diagnostic performance of two antigen-ELISA techniques (B158B60 Ag-ELISA and HP10 Ag-ELISA) and an immunoblotting method were compared with meat inspection procedures on a sample of pigs suspected to be infected with (group 1; n = 250) or free of (group 2; n = 250) T. solium based on direct veterinary inspection in Madagascar. Sensitivity and specificity of the antigen ELISAs were then estimated using a Bayesian approach for detection of porcine cysticercosis in the absence of a gold standard. Then, a third set of pig sera (group 3, n = 250) was randomly collected in Antananarivo slaughterhouses and tested to estimate the overall prevalence of T. solium contamination in pork meat traded in Antananarivo. The antigen ELISAs showed a high sensitivity (>84%), but the B158B60 Ag-ELISA appeared to be more specific than the HP10 Ag-ELISA (model 1: 95% vs 74%; model 2: 87% vs 71%). The overall prevalence of porcine cysticercosis in Antananarivo slaughterhouses was estimated at 2.3% (95% credibility interval [95%CrI]: 0.09–9.1%) to 2.6% (95%CrI: 0.1–10.3%) depending on the model and priors used. Since the sample used in this study is not representative of the national pig population, village-based surveys and longitudinal monitoring at slaughter are needed to better estimate the overall prevalence, geographical patterns and main risk factors for T. solium contamination, in order to improve control policies. (Résumé d'auteur

Mass drug administration non-recipients

BACKGROUND: Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive chemotherapies received treatment. METHODS: Coverage of community-directed treatment with praziquantel (PZQ) and albendazole (ALB) was analyzed in 17 villages of Mayuge District, Uganda. National drug registers, household questionnaires, and parasitological surveys were collected to track 935 individuals before and after MDA. Multilevel logistic regressions, including household and village effects, were specified with a comprehensive set of socioeconomic and parasitological variables. The factors predicting who did not receive PZQ and ALB from community medicine distributors were identified. RESULTS: Drug receipt was correlated among members within a household, and nonrecipients of PZQ or ALB were profiled by household-level socioeconomic factors. Individuals were less likely to receive either PZQ or ALB if they had a Muslim household head or low home quality, belonged to the minority tribe, or had settled for more years in their village. Untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government. CONCLUSIONS: The findings demonstrate how to locate and target individuals who are not treated in MDA. Infection risk factors were not informative. In particular, age, gender, and occupation were unable to identify non-recipients, although World Health Organization guidelines rely on these factors. Individuals of low socioeconomic status, minority religions, and minority tribes can be targeted to expand MDA coverage.This work was supported by the Vice Chancellor’s Fund of the University of Cambridge, the Schistosomiasis Control Initiative, the Wellcome Trust (Programme grant 083931/Z/07/Z to D.W.D), and the Netherlands Organization for Scientific Research (N.W.O. grant 452-04-333 to E.B.).This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/cid/civ82

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.

BACKGROUND: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. METHODS: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. FINDINGS: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. INTERPRETATION: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. FUNDING: Bill & Melinda Gates Foundation

Caractérisation de la protection du sol contre l'érosion due à différents systèmes de culture en semis direct sur couverture végétale à l'aide de micro-lots dans le cadre d'un essai multidisciplinaire.

Sur les hautes terres de Madagascar (1200-1800 m), à la pluviométrie importante (1000-1800 mm/an), une forte érosion affecte les cultures pluviales avec labour, entraînant une dégradation de la fertilité, des faibles productions et l'abandon rapide des parcelles (Rollin, 1994). Pour palier à ces difficultés les systèmes de culture en semis direct sur couverture végétale (SCV) ont été introduits au début des années 90. Avec ces systèmes le sol n'est plus perturbé, les couvertures le protègent de l'érosion, le bilan hydrique est modifié (Scopel et al., 1998; Alberts et Neibling, 1994) et on observe divers effets positifs sur le sol (Gobat et al., 1998; Razafimbelo et al., 2005; Lai, 1997). Des systèmes à une culture par an ont d'abord été testés et montré qu'ils maintenaient, voire augmentaient, les productions (cf. rapports TAFA). Récemment des systèmes à base de successions ou associations de riz pluvial, vivriers, et fourrages, ont été conçus pour mieux répondre aux attentes des paysans (Séguy, 2002). Un dispositif multidisciplinaire a été installé en 2002 à Andranomanelatra (1640 m) près d'Antsirabe pour étudier leurs fonctionnements et impacts sur le milieu (porosité, séquestration du carbone, érosion, bilan d'azote, activités biologiques) sur le long terme, et y évaluer des écotypes de riz pluvial (Séguy, 2002). Les systèmes ont été choisis par rapport à leurs effets potentiels sur le milieu (en fonction des biomasses). Des témoins labourés sont présents et différentes fumures sont comparées. Cet essai est original par ses objectifs et sa complexité (40 traitements; 120 parcelles; 3,2 Ha). Le sol est ferrallitique argileux développé sur substrat fluvio-lacustre (ferralsol), représentatif de la zone. La topographie est plane. Notre étude est menée sur ce dispositif et vise à évaluer les capacités de certains systèmes à limiter l'érosion. Vue la topographie et pour ne pas perturber les parcelles seuls des micro-lots pouvaient y être utilisés. S'ils ne peuvent donner des valeurs vraies des ruissellements et érosions (Hudson, 1993; Roose, 1994), des travaux ont montré leur intérêt pour hiérarchiser des facteurs et établir des indicateurs (Le Bissonnais et al., 1998; Dunjo et al., 2004; Uson et Ramos, 2001). On suivra sur plusieurs années l'évolution des effets protecteurs des systèmes. (Résumé d'auteur

Taenia solium porcine cysticercosis in Madagascar: Comparison of immuno-diagnostic techniques and estimation of the prevalence in pork carcasses traded in Antananarivo city.

Taenia solium cysticercosis was reported in official veterinary and medical statistics to be highly prevalent in pigs and humans in Madagascar, but few estimates are available for pigs. This study aimed to estimate the seroprevalence of porcine cysticercosis among pigs slaughtered in Antananarivo abattoirs. Firstly, the diagnostic performance of two antigen-ELISA techniques (B158B60 Ag-ELISA and HP10 Ag-ELISA) and an immunoblotting method were compared with meat inspection procedures on a sample of pigs suspected to be infected with (group 1; n=250) or free of (group 2; n=250) T. solium based on direct veterinary inspection in Madagascar. Sensitivity and specificity of the antigen ELISAs were then estimated using a Bayesian approach for detection of porcine cysticercosis in the absence of a gold standard. Then, a third set of pig sera (group 3, n=250) was randomly collected in Antananarivo slaughterhouses and tested to estimate the overall prevalence of T. solium contamination in pork meat traded in Antananarivo. The antigen ELISAs showed a high sensitivity (>84%), but the B158B60 Ag-ELISA appeared to be more specific than the HP10 Ag-ELISA (model 1: 95% vs 74%; model 2: 87% vs 71%). The overall prevalence of porcine cysticercosis in Antananarivo slaughterhouses was estimated at 2.3% (95% credibility interval [95%CrI]: 0.09-9.1%) to 2.6% (95%CrI: 0.1-10.3%) depending on the model and priors used. Since the sample used in this study is not representative of the national pig population, village-based surveys and longitudinal monitoring at slaughter are needed to better estimate the overall prevalence, geographical patterns and main risk factors for T. solium contamination, in order to improve control policies

Sickle-cell disease in febrile children living in a rural village of Madagascar and association with malaria and respiratory infections

International audienceBACKGROUND: In Madagascar, the last study on sickle cell disease (SCD) was done in the early 1980s. The country is known as endemic for malaria and respiratory infections. The main objective of this study was to estimate the prevalence of SCD; the secondary objective was to evaluate its association with malaria and respiratory infections. METHODS: This is a cross-sectional study which was carried out in a rural village in the south east coast of Madagascar between May 2011 and November 2013. Participants were children aged between 2-59 months presenting with fever measured by axillary temperature >=37.5~°C at inclusion. Genotyping of haemoglobin S was done by PCR and malaria was diagnosed by Rapid Diagnostic Test. Research for viral and atypical bacterial respiratory pathogens was performed on nasopharyngeal swabs. Uni-and multivariate polytomous logistic regression was done to assess associations between microbiological results and SCD status, with HbAA phenotype as reference. RESULTS: A total of 807 children were analysed. Prevalence of SCD among febrile children was 2.4% (95% CI, 1.5-3.7%) and that of SCT was 23.8% (95% CI, 20.9-26.9%). There was no difference in the prevalence of malaria infection according to haemoglobin status (p = 0.3). Rhinovirus (22.5%), adenovirus (14.1%), and bocavirus (11.6%) were the most common respiratory pathogens detected. After univariate analysis, patients with SCD were more frequently infected by parechovirus (p = 0.01), while patients with SCT were more prone to RSV A or B infection (p = 0.01). After multivariate analysis, HbAS phenotype was associated with higher risk of RSV A and B infection compared to HbAA (adjusted OR = 1.9; 95% CI: 1.2-3.1, p = 0.009), while HbSS phenotype was associated with higher risk of parechovirus infection (adjusted OR = 6.0; 95% CI: 1.1-31.3, p = 0.03) compared to HbAA, independently of age, gender, period per quarter, and the other viruses. CONCLUSION: The prevalence of SCD among under-five children presenting with fever was high in the study population. No association was found between SCT and malaria but few viruses, especially parechovirus, seem to play an important role in the occurrence of pneumoniae among SCD patients

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study

BACKGROUND: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. METHODS: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. FINDINGS: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. INTERPRETATION: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. FUNDING: Bill & Melinda Gates Foundation

Validation and Identification of Invasive Salmonella Serotypes in Sub-Saharan Africa by Multiplex Polymerase Chain Reaction

Salmonella enterica serovar Typhi and nontyphoidal Salmonella (NTS) cause the majority of bloodstream infections in sub-Saharan Africa; however, serotyping is rarely performed. We validated a multiplex polymerase chain reaction (PCR) assay with the White-Kauffmann-Le Minor (WKLM) scheme of serotyping using 110 Salmonella isolates from blood cultures of febrile children in Ghana and applied the method in other Typhoid Fever Surveillance in Africa Program study sites. In Ghana, 47 (43%) S. Typhi, 36 (33%) Salmonella enterica serovar Typhimurium, 14 (13%) Salmonella enterica serovar Dublin, and 13 (12%) Salmonella enterica serovar Enteritidis were identified by both multiplex PCR and the WKLM scheme separately. Using the validated multiplex PCR assay, we identified 42 (66%) S. Typhi, 14 (22%) S. Typhimurium, 2 (3%) S. Dublin, 2 (3%) S. Enteritidis, and 4 (6%) other Salmonella species from the febrile patients in Burkina Faso, Guinea-Bissau, Madagascar, Senegal, and Tanzania. Application of this multiplex PCR assay in sub-Saharan Africa could advance the knowledge of serotype distribution of Salmonella