Etiology and management of hospitalized and outpatient diarrhea among children less than 5 years of age in Lambaréné, Gabon

Objectives: Diarrhea remains a significant cause of global under-5 mortality, particularly in SubSaharan Africa (SSA). To reduce morbidity and mortality, the World Health Organization (WHO) recommends oral rehydration salts (ORS), zinc supplementation, and continued feeding or breastfeeding for all children with diarrhea to prevent dehydration and malnutrition; antibiotics only for bloody diarrhea (i.e. probable shigellosis), suspected cholera, or severe non-intestinal infections (e.g. pneumonia or sepsis); and avoidance of antidiarrheals and antiemetics owing to lack of benefit and potential for harm in young children. Gabon is an upper-middle income country in SSA for which there is a lack of recent, high quality data on the etiology and management of childhood diarrhea. This prospective study aimed to describe the etiology and management of hospitalized and outpatient cases of diarrhea in Gabonese children under five years of age. Methods: Children ≤ 59 months presenting to the Albert Schweitzer or George Rawiri Regional hospitals (February-July 2017) in Lambaréné, Gabon were included if they had ≥ 3 liquid stools per day within the past 3 days. Data was obtained via medical records and standardized questionnaires with caregivers. Diarrheaogenic Escherichia coli, Salmonella enterica, and Shigella spp. were detected using conventional culture techniques. Rotavirus, adenovirus, and Cryptosporidium spp. antigens were detected with commercial rapid immunoassays. Multiplex PCR was used for Cryptosporidium spp., Giardia intestinalis, and Cyclospora cayetanensis detection. Results: Forty-five children were included, 34 of whom were hospitalized. Mean age was 12.2 months; 58% were female. 49% were infected with one or more sought-for pathogens, most commonly with Giardia intestinalis (28.9%) or Cryptosporidium spp. (24.4%). 33% and 36% of hospitalized and outpatient children, respectively, received ORS. Zinc was given to one (3%) hospitalized patient and zero outpatients. Antidiarrheals were frequently given to hospitalized (48%) and outpatient (73%) children. Antibiotics were prescribed in 85% and 36% of hospitalized and outpatient cases, respectively, while only 8 children (18%) presented with bloody stools. 79% of children presented with severe acute malnutrition; 21% had never been breastfed. Conclusions: Ongoing education of healthcare workers and communities regarding WHO-recommended management of childhood diarrhea is needed. The overuse of antibiotics observed in this study is consistent with previous reports and is concerning given high levels of antimicrobial resistance in SSA. Strategies to increase provider awareness of indicated uses of antimicrobials in the setting of childhood diarrhea may help limit the spread of resistance

Genetic Diversity of Enteric Viruses in Children under Five Years Old in Gabon

Enteric viruses are the leading cause of diarrhea in children globally. Identifying viral agents and understanding their genetic diversity could help to develop effective preventive measures. This study aimed to determine the detection rate and genetic diversity of four enteric viruses in Gabonese children aged below five years. Stool samples from children <5 years with (n = 177) and without (n = 67) diarrhea were collected from April 2018 to November 2019. Norovirus, astrovirus, sapovirus, and aichivirus A were identified using PCR techniques followed by sequencing and phylogenetic analyses. At least one viral agent was identified in 23.2% and 14.9% of the symptomatic and asymptomatic participants, respectively. Norovirus (14.7%) and astrovirus (7.3%) were the most prevalent in children with diarrhea, whereas in the healthy group norovirus (9%) followed by the first reported aichivirus A in Gabon (6%) were predominant. The predominant norovirus genogroup was GII, consisting mostly of genotype GII.P31-GII.4 Sydney. Phylogenetic analysis of the 3CD region of the aichivirus A genome revealed the presence of two genotypes (A and C) in the study cohort. Astrovirus and sapovirus showed a high diversity, with five different astrovirus genotypes and four sapovirus genotypes, respectively. Our findings give new insights into the circulation and genetic diversity of enteric viruses in Gabonese children.Peer Reviewe

High-throughput analysis of human cytomegalovirus genome diversity highlights the widespread occurrence of gene-disrupting mutations and pervasive recombination

Human cytomegalovirus is a widespread pathogen of major medical importance. It causes significant morbidity and mortality in the immunocompromised and congenital infections can result in severe disabilities or stillbirth. Development of a vaccine is prioritized, but no candidate is close to release. Although correlations of viral genetic variability with pathogenicity are suspected, knowledge about strain diversity of the 235kb genome is still limited. In this study, 96 full-length human cytomegalovirus genomes from clinical isolates were characterized, quadrupling the available information for full-genome analysis. These data provide the first high-resolution map of human cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus is significantly more divergent than all other human herpesviruses and highlight hotspots of diversity in the genome. Importantly, 75% of strains are not genetically intact, but contain disruptive mutations in a diverse set of 26 genes, including immunomodulative genes UL40 and UL111A. These mutants are independent from culture passaging artifacts and circulate in natural populations. Pervasive recombination, which is linked to the widespread occurrence of multiple infections, was found throughout the genome. Recombination density was significantly higher than in other human herpesviruses and correlated with strain diversity. While the overall effects of strong purifying selection on virus evolution are apparent, evidence of diversifying selection was found in several genes encoding proteins that interact with the host immune system, including UL18, UL40, UL142 and UL147. These residues may present phylogenetic signatures of past and ongoing virus-host interactions.status: publishe

Schistosoma haematobium infection morbidity, praziquantel effectiveness and reinfection rate among children and young adults in Gabon

Background: Sub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon. Methods: Eligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR). Results: A total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%. Conclusions: The prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT 02769103. Registered 11 May 2016, retrospectively registered

Association of low birth weight and polyparasitic infection during pregnancy in Lambaréné, Gabon

OBJECTIVE: To report the prevalence of polyparasitism during pregnancy in the Lambaréné region of Gabon and its association with newborn birth weight. METHOD: Pregnant women in their third trimester were recruited in a prospective study between November 2011 and March 2015. Parasite infection status was assessed microscopically in stool, urine and blood samples. Maternal demographic and obstetrical characteristics and newborns anthropometric data were collected. Multivariable logistic regression was used to assess the association between low birth weight and polyparasitism. RESULTS: 678 of 927 pregnant women were included for analysis with mean age (SD) of 25 (6.8) years. The analysis showed that 69% (468/678) were infected with at least one parasite (Plasmodium spp., Schistosoma spp., soil-transmitted helminths, filarial infections). This comprised of 38% with monoparasitism and 31% polyparasitism. The proportion of newborn babies with a weight below 2500 g (LBW) in our study was 21% (142/678). Compared to pregnant women without infection, women with monoparasitic infection had adjusted Odds Ratio confidence interval 95% CI (aOR [95%CI]) of 1.6 [0.95-2.73], those with two parasites had aOR 95%CI of 2.63 [1.51-4.62], and those with more than two parasites had aOR of 5.08 [2.5-10.38] for delivering a newborn with low birth weight. CONCLUSION: In Lambaréné, an endemic area for multiple parasite infections, there is a high prevalence of polyparasitism in pregnant women. Polyparasitism is associated with low birth weight. Therefore, there is an urgent need for active screening and treatment of parasite infections in pregnant women to assess the potential public health benefit of such interventions

Codiversification of gut microbiota with humans

International audienceThe gut microbiomes of human populations worldwide have many core microbial species in common. However, within a species, some strains can show remarkable population specificity. The question is whether such specificity arises from a shared evolutionary history (codiversification) between humans and their microbes. To test for codiversification of host and microbiota, we analyzed paired gut metagenomes and human genomes for 1225 individuals in Europe, Asia, and Africa, including mothers and their children. Between and within countries, a parallel evolutionary history was evident for humans and their gut microbes. Moreover, species displaying the strongest codiversification independently evolved traits characteristic of host dependency, including reduced genomes and oxygen and temperature sensitivity. These findings all point to the importance of understanding the potential role of population-specific microbial strains in microbiome-mediated disease phenotypes

Performance of a rapid diagnostic test for the detection of Cryptosporidium spp. in African children admitted to hospital with diarrhea.

BackgroundCryptosporidium is a protozoan parasite that causes mild to severe diarrhoeal disease in humans. To date, several commercial companies have developed rapid immunoassays for the detection of Cryptosporidium infection. However, the challenge is to identify an accurate, simple and rapid diagnostic tool for the estimation of cryptosporidiosis burden. This study aims at evaluating the accuracy of CerTest Crypto, a commercialized rapid diagnostic test (RDT) for the detection of Cryptosporidium antigens in the stool of children presenting with diarrhoea.MethodsA cross-sectional study was conducted in four study sites in Sub-Saharan Africa (Gabon, Ghana, Madagascar, and Tanzania), from May 2017 to April 2018. Stool samples were collected from children under 5 years with diarrhoea or a history of diarrhoea within the last 24 hours. All specimens were processed and analyzed using CerTest Crypto RDT against a composite diagnostic panel involving two polymerase chain reaction (PCR) tests (qPCR and RFLP-PCR,) as the gold standard.ResultsA total of 596 stool samples were collected. Evaluation of the RDT yielded a very low overall sensitivity of 49.6% (confidence interval (CI) 40.1-59.0), a specificity of 92.5% (CI 89.8-94.7), positive predictive value of 61.3% (CI 50.6-71.2), and negative predictive value of 88.5% (85.3-91.1) when compared to the composite reference standard of qPCR and RFLP-PCR for the detection of Cryptosporidium species. Moreover, the performance of this test varied across different sites.ConclusionThe weak performance of the studied RDT suggests the need to carefully evaluate available commercial RDTs before their use as standard tools in clinical trials and community survey of Cryptosporidium infections in pediatric cohorts