Seroprevalence of Leptospira spp. infection in Cattle from Central and Northern Madagascar

Leptospirosis is a zoonotic disease of global importance, especially in tropical countries. The current Leptospira spp. seroprevalence in cattle from central and northern Madagascar is unknown. Thus, the aim of this study was to determine the seroprevalence resulting from infections with pathogenic Leptospira spp. in zebu cattle from these areas. Serum samples from 194 animals were tested by microscopic agglutination test (MAT) using a panel of 12 serovars as antigens. Samples with a titer of ≥1:100 were considered positive. The overall seroprevalence was 59.3% (95% CI; 52.0-66.2%) with titers ranging from 1:100 to 1:1600. Among the seropositive animals, the most frequent antibody reactions were against serovar L. Tarassovi (serogroup L. Tarassovi) with 40.2% (33.3-47.5%), followed by L. Hardjo (L. Sejroe) with 13.9% (9.5-19.8%), L. Grippotyphosa (L. Grippotyphosa) with 9.8% (6.2-15.1%), L. Pomona (L. Pomona) with 7.7% (4.5-12.7%) and L. Autumnalis (L. Autumnalis) with 5.2% (2.6-9.5%). Less than 5% of the samples reacted positively against the remaining serovars. These results indicate a very high exposure of Malagasy cattle to Leptospira spp. which, consequently, poses a definite risk for people working with cattle acquiring this zoonotic infection

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

Pathogens that cause acute febrile illness among children and adolescents in Burkina Faso, Madagascar and Sudan

BACKGROUND: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. METHODS: Blood samples taken from study participants with acute fever (>/=37.5 degrees C) or a history of fever and recruited into the previous Typhoid-Fever-Surveillance-in-Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral and parasitic pathogens. Clinical metadata were also assessed. RESULTS: A total of 615 blood samples available for analysis originated from Burkina Faso (n=53), Madagascar (n=364) and Sudan (n=198) and were taken from participants ranging from 0-19 years of age. Most individuals [86.4% (531/615)] presenting at healthcare facilities were outpatient adolescents (11-19 years-old). Leading clinical diagnoses were respiratory tract infections [45.9% (282/615)], malaria [27.3% (168/615)], and gastrointestinal tract infections [10.7% (66/615)]. Through the TaqMan-Array Card, at least one pathogen was detected in 62% (33/53), 24% (86/364), and 60% (118/198) of specimens, from Burkina Faso, Madagascar and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25/53), 2.2% (8/364) and 45% (90/198) of AFI at respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357/516) of patients with clinical diagnoses of malaria, respiratory, or gastrointestinal infections were prescribed a WHO-guideline-recommended empiric antibiotic,whereas only 45% (106/237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. CONCLUSIONS: A PCR-approach for identifying multiple bacterial, viral and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome

Determining the Best Immunization Strategy for Protecting African Children Against Invasive Salmonella Disease.

BACKGROUND: The World Health Organization recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons ≥6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations. METHODS: The Typhoid Fever Surveillance in Africa Program (TSAP) was a blood culture-based surveillance of febrile patients from defined populations presenting at healthcare facilities in 10 African countries. TF and invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-olds in one-year age increments. RESULTS: Salmonella Typhi and iNTS were the most frequently isolated pathogens; 135 and 94 cases were identified, respectively. Analysis from three countries was excluded (incomplete person-years of observation (PYO) data). Thirty-seven of 123 TF cases (30.1%) and 71/90 iNTS disease cases (78.9%) occurred in children aged <5 years. No TF and 8/90 iNTS infections (8.9%) were observed in infants aged <9 months. The TF incidences (/100 000 PYO) for children aged <1 year and 1 to <2 years were 5 and 39, respectively; the highest incidence was 304 per 100 000 PYO in 4 to <5 year-olds. The iNTS disease incidence in the defined age groups ranged between 81 and 233 per 100 000 PYO, highest in 1 to <2 year-olds. TF and iNTS disease incidences were higher in West Africa. CONCLUSIONS: High burden of TF detected in young children strengthens the need for TCV introduction. Given the concurrent iNTS disease burden, development of a trivalent vaccine against S. Typhi, S. Typhimurium, and S. Enteritidis may be timely in this region

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

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

The global burden and epidemiology of invasive non-typhoidal Salmonella infections

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas