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

Molecular surveillance and genetic divergence of rotavirus A antigenic epitopes in Gabonese children with acute gastroenteritis

Background Rotavirus A (RVA) causes acute gastroenteritis in children <5 years of age in sub-Saharan Africa. In this study, we described the epidemiology and genetic diversity of RVA infecting Gabonese children and examined the antigenic variability of circulating strains in relation to available vaccine strains to maximize the public health benefits of introducing rotavirus vaccine through the Expanded Programme on Immunization (EPI) in Gabon. Methods Stool samples were collected consecutively between April 2018 and November 2019 from all hospitalized children <5 years with gastroenteritis and community controls without gastroenteritis. Children were tested for rotavirus A by quantitative RT-PCR and subsequently sequenced to identify circulating rotavirus A genotypes in the most vulnerable population. The VP7 and VP4 (VP8*) antigenic epitopes were mapped to homologs of vaccine strains to assess structural variability and potential impact on antigenicity. Findings Infections were mostly acquired during the dry season. Rotavirus A was detected in 98/177 (55%) hospitalized children with gastroenteritis and 14/67 (21%) of the control children. The most common RVA genotypes were G1 (18%), G3 (12%), G8 (18%), G9 (2%), G12 (25%), with G8 and G9 reported for the first time in Gabon. All were associated either with P[6] (31%) or P[8] (38%) genotypes. Several non-synonymous substitutions were observed in the antigenic epitopes of VP7 (positions 94 and 147) and VP8* (positions 89, 116, 146 and 150), which may modulate the elicited immune responses. Interpretation This study contributes to the epidemiological surveillance of rotavirus A required before the introduction of rotavirus vaccination in the EPI for Gabonese children.Peer Reviewe

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century