COVID-19 Genomic Surveillance in Bangui (Central African Republic) Reveals a Landscape of Circulating Variants Linked to Validated Antiviral Targets of SARS-CoV-2 Proteome.

Since its outbreak, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread rapidly, causing the Coronavirus Disease 19 (COVID-19) pandemic. Even with the vaccines' administration, the virus continued to circulate due to inequal access to prevention and therapeutic measures in African countries. Information about COVID-19 in Africa has been limited and contradictory, and thus regional studies are important. On this premise, we conducted a genomic surveillance study about COVID-19 lineages circulating in Bangui, Central African Republic (CAR). We collected 2687 nasopharyngeal samples at four checkpoints in Bangui from 2 to 22 July 2021. Fifty-three samples tested positive for SARS-CoV-2, and viral genomes were sequenced to look for the presence of different viral strains. We performed phylogenetic analysis and described the lineage landscape of SARS-CoV-2 circulating in the CAR along 15 months of pandemics and in Africa during the study period, finding the Delta variant as the predominant Variant of Concern (VoC). The deduced aminoacidic sequences of structural and non-structural genes were determined and compared to reference and reported isolates from Africa. Despite the limited number of positive samples obtained, this study provides valuable information about COVID-19 evolution at the regional level and allows for a better understanding of SARS-CoV-2 circulation in the CAR.

Five successive waves of SARS-CoV-2 infection in the Central African Republic: a prospective observational study from 2020-2022.

Introduction: the National Laboratory of Clinical Biology and Public Health (NLBPH) in Bangui in the Central African Republic (CAR) carries out the vast majority of molecular screening tests for SARS-CoV-2 infection nationwide. This study aimed to show the contribution of molecular diagnosis and genomic surveillance in monitoring the evolution of longitudinal variations of the SARS-CoV-2 infection epidemic in CAR between 2020 and the end of 2022. Methods: this is an observational study on the variations in the prevalence of detection of SARS-CoV-2 by RT-PCR at the NLCBPH from nasopharyngeal samples taken prospectively over a period of 3 years since the beginning of the COVID-19 epidemic. A subgroup of SARS-CoV-2 positive samples was selected for molecular sequencing performed by Illumina® and MinIon® at the National Institute for Biomedical Research in Kinshasa, Democratic Republic of the Congo. Results: from March 2020 to December 31th, 2022, 88,442 RT-PCR tests were carried out (4/5 of the country) and detected 9,156 cases of SARS-CoV-2 infection in 5 successive waves. The average age of the patients was 39.8 years (extremes ranging from to 92 years). Age(P=0.001), sex(P=0.001) and symptom presentation(P=0.001) were significantly associated with RT-PCR test positivity. Among the different variants identified during successive waves, the Omicron variant predominated during the last two waves. Conclusion: this prospective study over a period of 3 years, marked by 5 successive waves, made it possible to report that age, sex and the presence of clinical symptoms are associated with RT-PCR positivity. Among the different variants identified during successive waves, the Omicron variant predominated during the last two waves.

Circulation and seasonality of influenza viruses in different transmission zones in Africa.

BACKGROUND: Influenza is responsible for more than 5 million severe cases and 290,000 to 650,000 deaths every year worldwide. Developing countries account for 99% of influenza deaths in children under 5 years of age. This paper aimed to determine the dynamics of influenza viruses in African transmission areas to identify regional seasonality for appropriate decision-making and the development of regional preparedness and response strategies. METHODS: We used data from the WHO FluMart website collected by National Influenza Centers for seven transmission periods (2013-2019). We calculated weekly proportions of positive influenza cases and determined transmission trends in African countries to determine the seasonality. RESULTS: From 2013 to 2019, influenza A(H1N1)pdm2009, A(H3N2), and A(H5N1) viruses, as well as influenza B Victoria and Yamagata lineages, circulated in African regions. Influenza A(H1N1)pdm2009 and A(H3N2) highly circulated in northern and southern Africa regions. Influenza activity followed annual and regional variations. In the tropical zone, from eastern to western via the middle regions, influenza activities were marked by the predominance of influenza A subtypes despite the circulation of B lineages. One season was identified for both the southern and northern regions of Africa. In the eastern zone, four influenza seasons were differentiated, and three were differentiated in the western zone. CONCLUSION: Circulation dynamics determined five intense influenza activity zones in Africa. In the tropics, influenza virus circulation waves move from the east to the west, while alternative seasons have been identified in northern and southern temperate zones. Health authorities from countries with the same transmission zone, even in the absence of local data based on an established surveillance system, should implement concerted preparedness and control activities, such as vaccination.

Serotype Distribution and Antimicrobial Resistance of Shigella Species in Bangui, Central African Republic, from 2002 to 2013.

Shigella is a major cause of severe diarrhea in children less than the age of 5 years in sub-Saharan Africa. The aim of this study was to describe the (sub-)serotype distribution and antimicrobial susceptibility of Shigella serogroups from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443 Shigella isolates in total. The most common serogroups were Shigella flexneri (N = 243, 54.9%), followed by Shigella sonnei (N = 90, 20.3%) and Shigella dysenteriae (N = 72, 16.3%). The high diversity of (sub-)serotypes of S. flexneri and S. dysenteriae may impede the development of an efficient vaccine. Rates of resistance were high for ampicillin, chloramphenicol, tetracycline, and cotrimoxazole but low for many other antimicrobials, confirming recommendations for the use of third-generation cephalosporins (only one organism resistant) and fluoroquinolones (no resistance). However, the detection of one extended-spectrum beta-lactamase-producing Shigella organism highlights the need for continued monitoring of antimicrobial drug susceptibility.

Factors associated with stunting in healthy children aged 5 years and less living in Bangui (RCA).

Stunting remains a major public health concern worldwide. Although its global prevalence is slowly decreasing, the actual number of affected children is still rising in Sub-Saharan Africa. In the Central African Republic (CAR), about one third of all children below the age of five are stunted. Stunting is correlated with many long-term consequences, including poor cognitive development and a higher rate of morbidity and mortality, making stunting a major contributor to poverty. In CAR, little is known about the factors that contribute to stunting. This study aimed at analysing, in a cross-sectional study, the main factors associated with stunting in a group of 414 children recruited between December 2011 and November 2013, aged five years or less and living in Bangui. For all children, demographic, socio-economic and anthropometric data were recorded and asymptomatic enteropathogen carriage was assessed in stool samples using classical microbiological assays. The study group had a mean age of 14.2±10 months. Fifty-eight percent (292/414) were boys, and 36 percent (148/414) exhibited stunted growth. Of the stunted children, 51% (75/148) showed a moderate delay in linear growth for their age group [height-for-age z-score (HAZ) between -2 and -3 SD] while 49% (73/148) presented a severe delay (HAZ < -3). Factors significantly associated with stunting included gender (aOR: 1.67; 95% CI: 1.07; 2.62 for boys compared to girls) and age (aOR of 3.98 (95% CI: 2.45; 6.46) for toddlers and aOR 4.42 (95% CI: 2.36; 8.28) for children compared to infants). Most importantly, we identified being overweight [weight-for-height z-score (WHZ) > 2 SD; aOR: 3.21; 95% CI: 1.50; 6.90 of overweight compared to normal weight] as also being significantly associated with stunting. This is the first study showing that even in the poorest countries of the world there is an association of stunting with being overweight.

Etiology and Epidemiology of Diarrhea in Hospitalized Children from Low Income Country: A Matched Case-Control Study in Central African Republic.

BACKGROUND: In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic. METHODS: All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent's written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases. RESULTS: A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%. CONCLUSIONS: Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR's Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries.

Dissemination of IncF-type plasmids in multiresistant CTX-M-15-producing Enterobacteriaceae isolates from surgical-site infections in Bangui, Central African Republic.

BACKGROUND: Surgical-site infection is the most frequent health care-associated infection in the developing world, with a strikingly higher prevalence than in developed countries We studied the prevalence of resistance to antibiotics in Enterobacteriaceae isolates from surgical-site infections collected in three major tertiary care centres in Bangui, Central African Republic. We also studied the genetic basis for antibiotic resistance and the genetic background of third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae. RESULTS: Between April 2011 and April 2012, 195 patients with nosocomial surgical-site infections were consecutively recruited into the study at five surgical departments in three major tertiary care centres. Of the 165 bacterial isolates collected, most were Enterobacteriaceae (102/165, 61.8%). Of these, 65/102 (63.7%) were 3GC-R, which were characterized for resistance gene determinants and genetic background. The bla CTX-M-15 and aac(6')-Ib-cr genes were detected in all strains, usually associated with qnr genes (98.5%). Escherichia coli, the most commonly recovered species (33/65, 50.8%), occurred in six different sequence types, including the pandemic B2-O25b-ST131 group (12/33, 36.4%). Resistance transfer was studied in one representative strain of the resistance gene content in each repetitive extragenic palindromic and enterobacterial repetitive intergenic consensus sequence-PCR banding pattern. Plasmids were characterized by PCR-based replicon typing and sub-typing schemes. In most isolates (18/27, 66.7%), bla CTX-M-15 genes were found in incompatibility groups F/F31:A4:B1 and F/F36:A4:B1 conjugative plasmids. Horizontal transfer of both plasmids is probably an important mechanism for the spread of bla CTX-M-15 among Enterobacteriaceae species and hospitals. The presence of sets of antibiotic resistance genes in these two plasmids indicates their capacity for gene rearrangement and their evolution into new variants. CONCLUSIONS: Diverse modes are involved in transmission of resistance, plasmid dissemination probably playing a major role.