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International audience; We analyzed monkeypox disease surveillance in Central African Republic (CAR) during 2001-2021. Surveillance data show 95 suspected outbreaks, 40 of which were confirmed as monkeypox, comprising 99 confirmed and 61 suspected monkeypox cases. After 2018, CAR's annual rate of confirmed outbreaks increased, and 65% of outbreaks occurred in 2 forested regions bordering the Democratic Republic of the Congo. The median patient age for confirmed cases was 15.5 years. The overall case-fatality ratio was 7.5% (12/160) for confirmed and suspected cases, 9.6% (8/83) for children

Objectives With a fourth of all under-five children affected, stunting remains one of the biggest health challenges worldwide. Even though the main underlying factors are known, the exact pathways to stunting varying in affected regions, and interventions thus need to be tailored to the local contexts. This study aimed assessing and comparing factors associated with stunting in two understudied sub-Saharan urban contexts with some of the highest stunting prevalence globally: Bangui, Central African Republic (~ 36%) and Antananarivo, Madagascar (42%). Methods We performed a case–control study on 175 + 194 stunted and 237 + 230 non-stunted control children aged 2–5 years and matched for age, gender and district of residency. Factors associated with stunting were identified using a standardized, paper questionnaire delivered by trained interviewers. Statistical analysis was done using logistic regression modelling. Results In both sites, formal maternal education lowered the risk of being stunted and restricted access to soap, suffering of anaemia and low birth weight were associated with higher risk of stunting. Short maternal stature, household head different from parents, diarrhoea and coughing were associated with an increased risk and continuing breastfeeding was associated with a lower risk of stunting in Antananarivo. Previous severe undernutrition and dermatitis/ fungal skin infections were associated with higher and changes in diet during pregnancy with lower risk of stunting in Bangui. Conclusions Our results suggest maternal education, antenatal care, iron supplementation and simple WASH interventions such as using soap and infection control as general and breastfeeding (Antananarivo) or better nutrition (Bangui) as area-specified interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s10995-021-03201-8.

Objectives The Central African Republic (CAR), a site of recurrent disease emergence, developed a noteworthy epidemiological surveillance system from the colonial period, but its health measures have remained among the world’s lowest. To understand this disparity between surveillance and public health, we examined selected moments in its history of surveillance and changing relations with public health structures. Methods We conducted archival research in CAR and French archives and 18 semi-structured interviews with key researchers working in CAR. Results We find long-term continuities in privileging surveillance over the health system and population health, making the CAR a ‘‘hotspot’’ for emerging diseases and a ‘‘blind spot’’ of primary health care. From the colonial period, the country attracted considerable support for surveillance, without concomitant investment in public health system. Political disputes and financial constraints have obscured real primary care needs on the ground. Conclusions As both a hotspot and a blind spot for global health, the CAR signals the need to reorient health interventions to address the long-term health of Central African people.

Background Limited epidemiological and antimicrobial resistance data are available on Salmonella enterica from sub-Saharan Africa. We determine the prevalence of resistance to antibiotics in isolates in the Central African Republic (CAR) between 2004 and 2013 and the genetic basis for resistance to third-generation cephalosporin (C3G). Methodology/Principal findings A total of 582 non-duplicate human clinical isolates were collected. The most common serotype was Typhimurium (n = 180, 31% of the isolates). A randomly selected subset of S. Typhimurium isolates were subtyped by clustered regularly interspaced short palindromic repeat polymorphism (CRISPOL) typing. All but one invasive isolate tested (66/68, 96%) were associated with sequence type 313. Overall, the rates of resistance were high to traditional first-line drugs (18–40%) but low to many other antimicrobials, including fluoroquinolones (one resistant isolate) and C3G (only one ESBL-producing isolate). The extended-spectrum beta-lactamase (ESBL)-producing isolate and three additional ESBL isolates from West Africa were studied by whole genome sequencing. The blaCTX-M-15 gene and the majority of antimicrobial resistance genes found in the ESBL isolate were present in a large conjugative IncHI2 plasmid highly similar (> 99% nucleotide identity) to ESBL-carrying plasmids found in Kenya (S. Typhimurium ST313) and also in West Africa (serotypes Grumpensis, Havana, Telelkebir and Typhimurium). Conclusions/Significance Although the prevalence of ESBL-producing Salmonella isolates was low in CAR, we found that a single IncHI2 plasmid-carrying blaCTX-M-15 was widespread among Salmonella serotypes from sub-Saharan Africa, which is of concern., Author summary Salmonella enterica infections are common causes of bloodstream infection in sub-Saharan Africa and associated with a high mortality rate. Levels of multidrug resistance have become alarmingly high. Then, third-generation cephalosporin (C3G) and fluoroquinolones have become standard for first-line empirical treatment. Recently, C3G-resistant Salmonella populations have emerged and spread over all continents. This resistance is mainly mediated by acquired extended-spectrum beta-lactamase (ESBL) genes carried by mobile genetic elements such as plasmids. We report here the prevalence of resistance to antibiotics in isolates in the Central African Republic (CAR) between 2004 and 2013 and the genetic basis for resistance to C3G. Overall, resistance rates to antimicrobials were low during the study period, for all classes other than conventional antimicrobials, confirming recommendations for first-line treatment based on C3G and fluoroquinolones. Only one ESBL-producing isolate was recovered. The ESBL gene and the majority of antimicrobial resistance genes found were present in a large plasmid highly similar to ESBL-carrying plasmids found in East and West Africa, highlighting its significant role in the spread of ESBL genes in Salmonella isolates in sub-Saharan Africa. These finding have implications for treatment of salmonellosis and support the growing necessity for increased microbiological surveillance based on networks of clinical laboratories in order to control dissemination of antibiotic resistance among Salmonella isolates.

International audience; Burkholderia cepacia causes frequent infections in immunocompromised and hospitalized patients, with a significant mortality rate. This bacterial species has also been associated with epidemic outbreaks due to contamination of antiseptic solutions and parenteral and nebulized medications. In 2016, in the town of Bongonon in the north of the Central African Republic (CAR), a three-year-old boy with febrile meningeal syndrome (fever, neck stiffness and altered general condition) was admitted for a medical consultation provided by the nongovernmental organization MSF-Spain. On 20 March 2016, a sample of the boy's cerebrospinal fluid was sent to the Bacteriology Laboratory of the Pasteur Institute of Bangui for analysis. Conventional bacteriology showed that the isolate was a Gram-negative bacillus, which was identified as B. cepacia by using API 20 NE, with 99.9%confidence. In addition, the strain presented an acquired resistance to ticarcillin-clavulanate, ceftazidime and imipenem but remained susceptible to cotrimoxazole. As B. cepacia had never previously been isolated from cerebrospinal fluid in Africa, we chose to identify the strain by 16S rRNA gene sequencing. The molecular data showed that the isolate belonged to B. cepacia group. This is the first report of a case of meningitis caused by B. cepacia in CAR and developing countries.

International audience; Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication.

International audience; Chikungunya virus (CHIKV) is an alphavirus transmitted by the bite of mosquito vectors. Over the past 10 years, the virus has gained mutations that enhance its transmissibility by the Aedes albopictus vector, resulting in massive outbreaks in the Indian Ocean, Asia and Central Africa. Recent introduction of competent A. albopictus vectors into the Central African Republic (CAR) pose a threat of a Chikungunya fever (CHIKF) epidemic in this region. We undertook this study to assess the genetic diversity and background of CHIKV strains isolated in the CAR between 1975 and 1984 and also to estimate the ability of local strains to adapt to A. albopictus. Our results suggest that, local CHIKV strains have a genetic background compatible with quick adaptation to A. albopictus, as previously observed in other Central African countries. Intense surveillance of the human and vector populations is necessary to prevent or anticipate the emergence of a massive CHIKF epidemic in the CAR.

International audience; 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 cogni-tive 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, socioeconomic 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-forage z-score (HAZ) between-2 and-3 SD] while 49% (73/148) presented a severe delay (HAZ 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. PLOS ONE | https://doi.org/10.1371/journal.pone.

International audience; Rhabdoviridae is one of the most diversified families of RNA viruses whose members infect a wide range of plants, animals, and arthropods. The members of this family are classified into 13 genera and >150 unassigned viruses. Here, we sequenced the complete genome of a rhabdovirus belonging to the Hart Park serogroup, the Kamese virus (KAMV), isolated in 1977 from Culex pruina in the Central African Republic. The genomic sequence showed an organization typical of rhabdoviruses with additional genes in the P-M and G-L intergenic regions, as already reported for the Hart Park serogroup. Our Kamese strain (ArB9074) had 98% and 78.8% nucleotide sequence similarity with the prototypes of the KAMV and Mossuril virus isolated in Uganda and Mozambique in two different Culex species, respectively. Moreover, the protein sequences had 98-100% amino acid similarity with the prototype of the KAMV, except for an additional gene (U3) that showed a divergence of 6%. These molecular data show that our strain of the KAMV is genetically close to the Culex annuliorus strain that was circulating in Uganda in 1967. However, this study suggests the need to improve our knowledge of the KAMV to better understand its behavior, its life cycle, and its potential reservoirs.

International audience; Zika virus (ZIKV) is an emerging pathogen belonging to the Spondweni serocomplex within the genus Flavivirus. It has been isolated from several mosquito species. Two lineages of ZIKV have been defined by polyprotein homology. Using high-throughput sequencing, we obtained and characterized three complete genomes of ZIKV isolated between 1976 and 1980 in the Central African Republic. The three viruses were isolated from two species of mosquito, Aedes africanus and Ae. opok. Two sequences from Ae. africanus had 99.9% nucleotide sequence identity and 100% amino acid identity, whereas the complete genome obtained from Ae. opok had 98.3% nucleotide identity and 99.4% amino acid identity with the other two genomes. Phylogenetic analysis based on the amino acid sequence of the polyprotein showed that the three ZIKV strains clustered together but diverged from all other ZIKV strains. Our molecular data suggest that a different subtype of West African ZIKV strains circulated in Aedes species in Central Africa.

Background New sequencing technologies have opened the way to the discovery and the characterization of pathogenic viruses in clinical samples. However, the use of these new methods can require an amplification of viral RNA prior to the sequencing. Among all the available methods, the procedure based on the use of Phi29 polymerase produces a huge amount of amplified DNA. However, its major disadvantage is to generate a large number of chimeric sequences which can affect the assembly step. The pre-process method proposed in this study strongly limits the negative impact of chimeric reads in order to obtain the full-length of viral genomes. Findings Three different assembly softwares (ABySS, Ray and SPAdes) were tested for their ability to correctly assemble the full-length of viral genomes. Although in all cases, our pre-processed method improved genome assembly, only its combination with the use of SPAdes allowed us to obtain the full-length of the viral genomes tested in one contig. Conclusions The proposed pipeline is able to overcome drawbacks due to the generation of chimeric reads during the amplification of viral RNA which considerably improves the assembling of full-length viral genomes. Electronic supplementary material The online version of this article (doi:10.1186/s40659-016-0099-y) contains supplementary material, which is available to authorized users.

Background Rift Valley fever virus (RVFV) causes a viral zoonosis, with discontinuous epizootics and sporadic epidemics, essentially in East Africa. Infection with this virus causes severe illness and abortion in sheep, goats, and cattle as well as other domestic animals. Humans can also be exposed through close contact with infectious tissues or by bites from infected mosquitoes, primarily of the Aedes and Culex genuses. Although the cycle of RVFV infection in savannah regions is well documented, its distribution in forest areas in central Africa has been poorly investigated. Methodology/Principal Findings To evaluate current circulation of RVFV among livestock and humans living in the Central African Republic (CAR), blood samples were collected from sheep, cattle, and goats and from people at risk, such as stock breeders and workers in slaughterhouses and livestock markets. The samples were tested for anti-RVFV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. We also sequenced the complete genomes of two local strains, one isolated in 1969 from mosquitoes and one isolated in 1985 from humans living in forested areas. The 1271 animals sampled comprised 727 cattle, 325 sheep, and 219 goats at three sites. The overall seroprevalence of anti-RVFV IgM antibodies was 1.9% and that of IgG antibodies was 8.6%. IgM antibodies were found only during the rainy season, but the frequency of IgG antibodies did not differ significantly by season. No evidence of recent RVFV infection was found in 335 people considered at risk; however, 16.7% had evidence of past infection. Comparison of the nucleotide sequences of the strains isolated in the CAR with those isolated in other African countries showed that they belonged to the East/Central African cluster. Conclusion and significance This study confirms current circulation of RVFV in CAR. Further studies are needed to determine the potential vectors involved and the virus reservoirs., Author Summary Rift valley fever virus (RVFV) is an arthropod-borne virus that causes serious illness in both animals and humans. RVFV is transmitted by direct contact with infectious tissues or by the bites of infected mosquito species of the Aedes and Culex genuses. Its distribution in tropical forests in central Africa is poorly documented. We assessed the current circulation of RVFV among livestock and humans in the Central African Republic (CAR) by detecting anti-RVFV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in sheep, cattle and goats and in people living in Bangui who were considered at risk. We also sequenced the complete genomes of two local strains, one isolated in 1969 from mosquitoes and one isolated in 1985 from humans living in forested areas. Sheep were the most frequently infected ruminants. IgM antibodies were found only during the rainy season; the frequency of IgG antibodies did not differ according to season. No evidence of recent RVFV infection was found in humans at risk; however, 16.7% had evidence of past infection. Phylogenetic analysis showed a perfect match of CAR strains with the East/Central African cluster. Our results confirm current circulation of RVFV in CAR. Further studies should be conducted to determine the vectors involved and the virus reservoirs.

Background In many African countries malaria has declined sharply due to a synergy of actions marked by the introduction of vector control strategies, but the disease remains a leading cause of morbidity and mortality in Central African Republic (CAR). An entomological study was initiated with the aim to characterize the malaria vectors in Bangui, the capital of CAR, and determine their vector competence. Methods A cross-sectional entomological study was conducted in 15 sites of the district of Bangui, the capital of CAR, in September–October 2013 and a second collection was done in four of those sites between November and December 2013. Mosquitoes were collected by human landing catch (HLC) indoors and outdoors and by pyrethrum spray catch of indoor-resting mosquitoes. Mosquitoes were analysed for species and multiple other attributes, including the presence of Plasmodium falciparum circumsporozoite protein or DNA, blood meal source, 2La inversion karyotype, and the L1014F kdr insecticide resistance mutation. Results Overall, 1292 anophelines were analysed, revealing a predominance of Anopheles gambiae and Anopheles funestus, with a small fraction of Anopheles coluzzii. Molecular typing of the An. gambiae complex species showed that An. gambiae was predominant (95.7 %) as compared to An. coluzzii (2.1 %), and Anopheles arabiensis was not present. In some areas the involvement of secondary vectors, such as Anopheles coustani, expands the risk of infection. By HLC sampling, An. funestus displayed a stronger endophilic preference than mosquitoes from the An. gambiae sister taxa, with a mean indoor-capture rate of 54.3 % and 67.58 % for An. gambiae sister taxa and An. funestus, respectively. Human biting rates were measured overall for each of the species with 28 or 29 bites/person/night, respectively. Both vectors displayed a strong human feeding preference as determined by blood meal source, which was not different between the different sampling sites. An. coustani appears to be highly exophilic, with 92 % of HLC samples captured outdoors. The mean CSP rate in head-thorax sections of all Anopheles was 5.09 %, and was higher in An. gambiaes.l. (7.4 %) than in An. funestus (3.3 %). CSP-positive An. coustani were also detected in outdoor HLC samples. In the mosquitoes of the An. gambiae sister taxa the kdr-w mutant allele was nearly fixed, with 92.3 % resistant homozygotes, and no susceptible homozygotes detected. Conclusions This study collected data on anopheline populations in CAR, behaviour of vectors and transmission levels. Further studies should investigate the biting behaviour and susceptibility status of the anophelines to different insecticides to allow the establishment of appropriate vector control based on practical entomological knowledge. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1431-2) contains supplementary material, which is available to authorized users.

International audience; The aim of this study was to estimate the prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) in faeces of healthy children aged 0-59 months in Bangui (Central African Republic). Stool samples of 134 children, recruited for a matched case-control study, were cultured on a commercial ESBL-selective chromogenic medium (CHROMagar ESBL, France). The phenotypic resistance patterns of isolated strains were investigated, as well as the genetic basis for antibiotic resistance. The factors associated with increased risk for ESBL-E carriage were also studied. The prevalence of ESBL-E carriage was 59% (79/134), one of the highest reported worldwide. The only factor found to be associated with carriage was living in a highest-income family (p=0.03). In all, 83 ESBL-E were recovered as simultaneous carriage of two strains was detected in four children. blaCTX-M-15 was found in all strains except two, frequently associated with qnr (54/81, 66%) and aac(6')-Ib-cr (35/81, 43%) genes. Escherichia coli, the most commonly recovered species (51/83, 61%), was assigned mainly to the pandemic B2-O25b-ST131 group (39/51, 76%). Resistance transfer, which was studied in 20 randomly selected ESBL-E strains, was successful in 13 (13/20, 65%) isolates. In eight of these isolates (8/13, 62%), blaCTX-M-15 genes were found in incompatibility group FIb conjugative plasmids. We found one of the highest prevalence rates of faecal carriage of ESBL-E reported worldwide, highlighting the need to improve control of the distribution of antibiotics in limited-resource countries.

The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui., Author Summary Rabies is an endemic and zoonotic disease circulating in most African and Asian countries and is mainly transmitted by dogs. Despite its importance for public health, little is known about the spatiotemporal dynamics of rabies in dogs in an urban setting. Using spatial, temporal and virus genetic information, we reconstructed the fine-scale evolutionary and epidemiological dynamics of RABV among the dog population in a major African city—Bangui in the Central African Republic. Notably, we document that rabies is not self-sustaining in the city, and that numerous reintroductions of the virus occur in the city, generating a succession of epidemic waves. The data obtained here will inform the development of tailored control measures and avoid wasting resources, revealing that control measures are probably best targeted towards neighbouring geographic areas rather than to the city itself.

International audience; OBJECTIVES: Peripheral artery disease (PAD) is a common condition in Western countries, mostly in the elderly. Little is known about the epidemiology of PAD in Africa. We sought to determine the prevalence of this condition in the elderly in two community-dwelling cohorts in Central Africa. DESIGN: Prospective cross-sectional survey in general population over the age of 65 years in Bangui (Central African Republic) and Brazzaville (Congo). METHODS: We conducted a systematic door-to-door survey in two representative districts of each city. Demographic, clinical and biological data were collected. The ankle-brachial index (ABI) was used to detect PAD (ABI ≤ 0.90). RESULTS: Among the 976 participants, the prevalence of PAD was 15.0% in Bangui and 32.4% in Brazzaville, increasing with age. Adjusted to age, regular alcohol consumption was protective for women in Bangui (OR = 0.50, CI95%:0.25-0.98) and men in Brazzaville (OR = 0.43, CI95%:0.21-0.88). Hypertension was associated with PAD in women (OR = 4.14, CI95%:1.65-10.42 in Bangui and OR = 2.17, CI95%:1.16-4.06 in Brazzaville). Diabetes and smoking showed different associations according to gender and city. CONCLUSIONS: This first population study in Central Africa highlights the high prevalence of PAD in the older population, and emphasizes specificities regarding the risk factors, being different from data published in Western countries.

International audience; Rabies is endemic in the Central African Republic (CAR) and a neglected enzootic disease which represents a serious public health problem. Before April 2009, rabies was not a notifiable disease in CAR. Vaccination of animals is expensive and not commonly done. In 2005, none rabies case was recorded in Bangui. To understand how rabies was introduced and propagated in the city of Bangui from 2006 to 2008, we analyzed samplings of dog brain as well as reviewed the records of dog owners. A total of 86 out of 101 samples (84.8%) tested positive for rabies virus during this period. Previous phylogenetic analysis of some strains circulating in Bangui between 2006 and 2008 indicated that virus of cosmopolitan and Africa 2 clade are found. Given the time frame and location of these samples, one possible explanation for this alarming result may be that two different strains of rabies virus were introduced at different times in Bangui. Stray dogs are solely responsible for the spread of the epidemic.

International audience; The Bunyaviridae family is currently composed of five genera, including Phlebovirus, in which several phleboviruses are associated with human diseases. Using high-throughput sequencing, we obtained and characterized one complete genome of the Arumowot virus (AMTV) isolated in 1978 from Turdus libonyanus, the Kurrichane Thrush, in the Central African Republic (CAR). The genomic segment of the new strain of AMTV isolated in the CAR had 75.4-83.5% sequence similarity and 82-98.4% amino acid similarity to the prototype sequence of AMTV. The different conserved proteins of the small (S) and large (L) segments (Nc, NSP, and RNA polymerase) showed close similarity at the amino acid level, whereas the polyprotein of the medium (M) segment was highly divergent, with 18% and 37.7%, respectively, for the prototype sequence of AMTV and the Odrenisrou virus (ODRV) isolated from Culex (Cx.) albiventris mosquitoes in the Tai forest, Ivory Coast. Phylogenetic analysis confirmed the sequence homology analysis and indicated that AMTV-CAR clustered into the Salehabad virus antigenic complex. The two closest viruses were the prototype sequences of AMTV originally isolated from Cx. antennatus mosquitoes and ODRV. These molecular data suggest the need for a deep genetic characterization of the diversity of this viral species to enhance its detection in the Central African region and to understand better its behavior and life cycle so that its potential spread to the human population can be prevented.

BackgroundPseudomonas aeruginosa (PA) has a non-clonal, epidemic population with a few widely distributed and frequently encountered sequence types (STs) called 'high-risk clusters'. Clinical P. aeruginosa (clinPA) has been studied in all inhabited continents excepted in Africa, where a very few isolates have been analyzed. Here, we characterized a collection of clinPA isolates from four countries of West and Central Africa.Methodology184 non-redundant isolates of clinPA from hospitals of Senegal, Ivory Coast, Nigeria, and Central African Republic were genotyped by MLST. We assessed their resistance level to antibiotics by agar diffusion and identified the extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) by sequencing. The population structure of the species was determined by a nucleotide-based analysis of the entire PA MLST database and further localized on the phylogenetic tree (i) the sequence types (STs) of the present collection, (ii) the STs by continents, (iii) ESBL- and MBL-producing STs from the MLST database.Principal findingsWe found 80 distinct STs, of which 24 had no relationship with any known STs. 'High-risk' international clonal complexes (CC155, CC244, CC235) were frequently found in West and Central Africa. The five VIM-2-producing isolates belonged to CC233 and CC244. GES-1 and GES-9 enzymes were produced by one CC235 and one ST1469 isolate, respectively. We showed the spread of 'high-risk' international clonal complexes, often described as multidrug-resistant on other continents, with a fully susceptible phenotype. The MBL- and ESBL-producing STs were scattered throughout the phylogenetic tree and our data suggest a poor association between a continent and a specific phylogroup.ConclusionsESBL- and MBL-encoding genes are borne by both successful international clonal complexes and distinct local STs in clinPA of West and Central Africa. Furthermore, our data suggest that the spread of a ST could be either due to its antibiotic resistance or to features independent from the resistance to antibiotics.

Objectives To investigate the association between peripheral arterial disease (PAD) and dementia in native elderly African populations. Design Two successive door-to-door cross-sectional surveys in the general population. Settings Representative districts of Bangui (Central African Republic) and Brazzaville (Republic of Congo). Participants Population aged 65 and older. Measurements Peripheral arterial disease was defined as an ankle–brachial index (ABI) of 0.90 or less. Cognitive screening was performed using the Community Screening Interview for Dementia and the Five-Word Test. Diagnosis of dementia was confirmed after further neuropsychological tests and neurological examination according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Multivariate logistic regression models were used to quantify the association between PAD and dementia in those populations, with adjustments for cardiovascular disease (CVD) and other variables. Results A significant association was observed between PAD and prevalent dementia (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.44–4.13, P = .001), even after adjustment for age, city, sex, CVD risk factors, education, and depressive disorders (OR = 2.37, 95% CI = 1.31–4.26, P = .004). This association was stronger with lower ABI. Conclusion These findings support the hypothesis of a link between atherosclerosis (represented by a low ABI) and cognitive disorders in native Africans and are similar to previous reports in African Americans and other ethnic groups.

We determined the genomic features and the taxonomic classification of Sebokele virus 1 (SEBV1), a previously unclassified arbovirus isolated in 1972 from rodents collected in Botambi, Central African Republic. The complete genome sequence was obtained using a deep sequencing approach (Illumina technology) and dedicated bioinformatics workflows for data analysis. Molecular analysis identified SEBV1 as a picornavirus, most closely related to Ljungan viruses of the genusParechovirus. The genome has a typical Ljungan virus-like organization, including the presence of two unrelated 2A protein motifs. Phylogenetic analysis confirmed that SEBV1 belongs to the parechovirus phylogroup and was most closely related to theLjungan virusspecies. However, it appeared clearly distinct from all members of this phylogroup, suggesting that it represents a novel species of the genusParechovirus.

International audience; Given the gradual improvement of living conditions and aging, dementia and related syndromes are becoming serious problems in the developing countries. A cross-sectional door to door type study in neighbourhood, was conducted from October 2008 to January 2009, in the general population in Bangui, order to help get a better understanding of the prevalence and risk factors of dementia among people over 65 living in the Central African capital. Of the 496 elderly respondents, 188 had cognitive disorders. After a neuropsychological examination, 40 of these subjects were diagnosed with dementia. The prevalence of dementia was 8.1% (IC 95% = [5.7-10.5]). The average age of subjects with dementia, ranging from 65 to 90 years, was 76.0 ± 7.1 years. There was a significant risk of developing dementia for an increase of ten years old (OR = 2.6, 95% CI [1.5 to 4.5]). The sex-ratio was 6/34. 82.5% of the demented had never attended school. 70.0% showed a state of malnutrition (BMI ≤ 18,5 kg/m(2)), significantly associated with dementia (OR = 3.3; IC 95% = [1.5-7.3]). The blood pressure was high in 67.5% of demented which is significantly associated with dementia (OR = 2.4; IC 95% = [1.1-5.4]). A recent change in financial status was a factor significantly associated with dementia (OR = 6.4; IC 95% = [1.8-22.5]). These results support the existence of dementia in urban Africa. The observed prevalence is close to those found in high-income countries. Further studies should be conducted which includes both the rural and urban Africa, to better understand the problem and solutions consider to comprehensive care and prevention axes adapted to our context.

International audience; Risk factors for dementia in American and European countries have been well investigated. However, little research has been carried out in sub-Saharan Africa, where life events as well as environmental, socio-economic, and modifiable risk factors (i.e., cardiovascular risk factors) may differ. Two cross-sectional surveys were conducted in representative samples of the older general population living in Bangui (Central African Republic) and Brazzaville (Congo). Dementia was defined according to the DSM-IV criteria. Multivariate regression analyses were performed in order to identify independent factors associated with dementia. Among the 977 elderly Africans included in this analysis, 75 (7.6%) were diagnosed as having dementia. Increasing age, female gender, hypertension, a body mass index

International audience; Sleeping sickness is more prevalent in three historical regions of Central African Republic. Control measures were organized by the colonial authorities through health services to fight against this disease and other major diseases. Multivariate analysis and the government helped in controlling the disease in the focus of Nola-Bilolo, which was formerly hyperendemic. The authors report the results of the control measures that resulted in the extinction of the disease in this outbreak. This is a retrospective study from 1991 to 2008, and the data were collected from the National Program to fight against human African trypanosomiasis in Bangui and in the diagnostic and treatment center of Nola. It was highly endemic, with more than 300 cases recorded in the year 1991. The average number of cases was 200.8 per year between 1992 and 1998. Less than 50 cases per year were recorded from 2000 to 2006, and no cases have been detected since 2007. 69.35% of the patients were actively screened. 5,000 conical deltamethrin-impregnated traps (Gouteux and Lancien) had been used in 15 districts in the city of Nola and 46 surrounding villages by 20 trappers fully supported by the program. This is an example of regular active mass screening. Systematic treatment of detected cases and well-conducted vector control measures give hope to the affected populations to live peacefully in order to contribute to the development of their country.

In June, 2010, two boys aged 14 years and 15 years were found to have di! use maculopapular lesions associated with pustules and crusts (fi gure). They had been living in a settlement in the deep forest area of the southern Central African Republic (CAR). The cases were reported to the Institut Pasteur at Bangui. The lesions developed after the boys had hunted and eaten a wild rodent (

International audience; BACKGROUND: The simultaneous emergence of human immunodeficiency virus (HIV)-1 group M and HIV-2 into human populations, circa 1921-1940, is attributed to urbanization and changes in sexual behavior. We hypothesized that the initial dissemination of HIV-1, before sexual transmission predominated, was facilitated by the administration, via reusable syringes and needles, of parenteral drugs against tropical diseases. As proxies for highly lethal HIV-1, we investigated risk factors for hepatitis C virus (HCV) and human T cell lymphotropic virus 1 (HTLV-1) infections, blood-borne viruses compatible with prolonged survival, in an area known in 1936-1950 as the most virulent focus of African trypanosomiasis. METHODS: Cross-sectional survey of individuals 55 years and older in Mbimou land and Nola, Central African Republic. Dried blood spots were used for HCV and HTLV-1 serologic testing and nucleic acid detection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were measured by logistic regression. RESULTS: The only risk factor for HCV genotype 4 infection was treatment of trypanosomiasis before 1951 (OR, 3.13; 95% CI, 1.38-7.09). HTLV-1 infection was associated with having received 2 injections of pentamidine for trypanosomiasis chemoprophylaxis (adjusted OR, 2.03; 95% CI, 1.01-4.06) and with transfusions (adjusted OR, 2.82; 95% CI, 1.04-7.67). From historical data, we predicted that 59% of Mbimous 65 years and older would report treatment for trypanosomiasis before 1951; only 11% did so. CONCLUSIONS: Treatment of trypanosomiasis before 1951 may have caused iatrogenic HCV transmission. Population-wide half-yearly intramuscular pentamidine for trypanosomiasis chemoprophylaxis in 1947-1953 may have caused iatrogenic HTLV-1 transmission. These and other interventions against tropical diseases could have iatrogenically transmitted SIV(cpz), jump-starting the HIV-1 epidemic. The excess mortality among patients with trypanosomiasis treated before 1951 supports this hypothesis.

International audience; SUMMARY METHODS: Mosquito aquatic stages were collected in domestic and peri-domestic areas, and epidemic risk indexes (Breteau, Container) were calculated for each prospected location. Adult female mosquitoes were captured by human landing catches, while larvae were sampled by inspecting artificial and natural breeding sites in randomly selected premises. RESULTS: Seventy-eight adults Aedes albopictus were collected in Bangui and Bayanga. Mosquito biting rate and abundance were, respectively, 0.33-1.70 bites/human/hour and 14.6% in Bangui and 0.04-0.16 and 0.4% in Bayanga. Larval sampling revealed a large diversity of water container harbouring the species in Bangui, Bayanga, Nola and Salo including unused containers, old tires, vehicle carcasses, buckets, barrels and stem of bamboo. The epidemic risk indices were erratic according to the location, ranging between 1.5-27.6 for Breteau and 1.3-47.1 for Container. CONCLUSION: This is the first record of Ae. albopictus in two bioclimatic zones of CAR This observation emphasizes the need to further investigate its potential impact on dengue and chikungunya viruses transmission regarding their recent emergencies in Africa (Côte d'Ivoire, Senegal, Mali, Somalia, Gabon, Cape Verde Islands).

Background: Data on dementia from low- and middle-income countries are still necessary to quantify the burden of this condition. This multicenter cross-sectional study aimed at estimating the prevalence of dementia in 2 large cities of Central Africa. Methods: General population door-to-door surveys were conducted in the districts of Bangui (Republic of Central Africa) and Brazzaville (Congo) in elderly aged ≧65 years. The subjects were screened with the Community Screening Interview for Dementia and the Five-Words Test. Diagnosis of dementia was made according to the DSM-IV criteria and to the clinical criteria proposed by the NINCDS-ADRDA for Alzheimer’s disease. Results: We enrolled 496 subjects in Bangui and 520 in Brazzaville. The prevalence of dementia was estimated at 8.1% (95% CI = 5.8–10.8) in Bangui and 6.7% (95% CI = 4.7–9.2) in Brazzaville. Conclusion: The prevalence of dementia in urban areas of Central Africa is close to those observed in high-income countries.

International audience; Multidrug-resistant (MDR) strains were identified in 40% of 54 strains from patients presenting with tuberculosis (TB) treatment failure or relapse in Bangui, Central African Republic. Results obtained with the MTBDRplus line-probe assay or rpoB sequencing were 86% concordant with rifampicin (RMP) resistant phenotypes, while the amplification refractory mutation system test was 71% concordant. No mutation was found in RMP-susceptible strains. MTBDRplus and sequencing were concordant with the detection of the S315T mutation in katG in 95% of MDR strains. Sequencing of pncA suggested pyrazinamide resistance in 50% of MDR strains. Knowledge of these resistances should help to implement treatment in low-income countries.

To the Editor: Buruli ulcer, the third most common mycobacterial disease of humans after tuberculosis and leprosy, is an important disfiguring and disabling cutaneous infection disease caused by Mycobacterium ulcerans. Buruli ulcer was declared an emerging skin disease of public health concern by the World Health Organization (WHO) in 1998. Although the disease is known to be associated with swampy areas and environmental changes, the mode of transmission is not yet clearly understood. A possible role for water bugs in the transmission has been postulated in the last 10 years. In this direction, several researchers have proposed that biting water bugs could be vectors for M. ulcerans (1). M. ulcerans produces a potent toxin known as mycolactone (2), which lyses dermal cells, leading to the development of continuously expanding ulcers with undermined edges. Surgery is the only treatment for late lesions, which involves excision of necrotic tissues, followed by skin grafting. After such treatment, patients suffer from functional limitations, social stigmatization, and the loss of livelihood (3). Antimicrobial drug treatment is available (a combination of rifampin and streptomycin), but it is effective only for early lesions (4). The disease is endemic in rural wetlands of tropical countries of Africa, the Americas, and Asia. Over the past decade, the prevalence of Buruli ulcer was highest in western Africa (3,5), with an alarming increase in detected cases. In central Africa, foci of Buruli ulcer have been reported in Gabon, Equatorial Guinea, Cameroon, Congo, the Democratic Republic of Congo, and Sudan (6), which are all neighboring countries of the Central African Republic (CAR). Surprisingly, in CAR, no cases of Buruli ulcer have been reported so far, even though its presence in this country was suspected in 2006, although not confirmed. This situation motivated us to begin a passive survey in the hospitals of Bangui, the capital of CAR. We report here 2 confirmed cases of Buruli ulcer that were found through this survey. The 2 patients were admitted in April 2007 to Hopital de l’Amitie, Bangui, CAR, with extensive skin ulcers, which might correspond to Buruli ulcer according to WHO guidelines (7). Both patients were farmers from the Ombella M’poko region. They lived on the border of the M’poko River and carried out daily activities in an aquatic environment. The first patient was a 62-year-old man who had a large ulceration of the right limb (Figure, panel A). Differential diagnosis eliminated other ulcerative diseases such as drepanocytosis, and the patient was HIV negative. For bacteriologic diagnosis, 4 samples were taken with sterile cotton swabs from beneath the undermined edges of the ulcer. Proteus mirabilis was isolated from the lesion, and a few acid-fast bacilli were shown by Ziehl-Neelsen (ZN) staining. Unfortunately, 1 week later, the patient died of an unknown cause. Figure Patient 1: extensive ulcer of the right limb (A). Patient 2: ulcer of the left ankle before treatment (B) and 8 weeks after specific antimicrobial drug therapy (C). Scale bars = 12 cm (A), 5 cm (B), and 2 cm (C). The second patient was a man of the same age who had an ulceration 6.5 cm in diameter on the left ankle (Figure, panel B). His condition had been treated with various antimicrobial agents without any result. Blood testing showed minor anemia (hemoglobin 12.4 g/dL) and that the patient was HIV negative. Bacteriologic analysis found no gram-positive and gram-negative bacteria, and ZN staining showed the presence of acid-fast bacilli. He received the specific recommended treatment for M. ulcerans infection (antimicrobial drug regimen: rifampin, 10 mg/kg, and streptomycin, 15 mg/kg), and the lesions had receded 2 months later (Figure, panel C). The identification of M. ulcerans was confirmed by PCR on the basis of the IS2404 repeated insertion sequences of M. ulcerans as described by Stinear et al. (8). The positive results were confirmed by quantitative real-time PCR, in the Laboratory of Bacteriology at Central Hospitalier Universistaire, Angers, France, on 2 specific sequences: IS2404 sequence and ketoreductase B domain of the mycolactone polyketide synthase gene from the plasmid pMUM001 (9). According to WHO criteria, 2 confirmative test results should be obtained of 4 laboratory tests (ZN staining, positive culture of M.ulcerans, specific gene amplification, pathognomonic histopathologic features) to establish a definitive diagnosis (7). Concerning the 2 patients in this study, results of ZN staining and PCR were positive, thus confirming the diagnosis of Buruli ulcer. Samples were inoculated on Lowenstein-Jensen (LJ) media and incubated at 30°C for 2 months, but the culture did not grow the organism. This result could be accounted for by the paucity of bacilli in the samples. In conclusion, our study confirms that, although infrequently diagnosed, Buruli ulcer is an endemic disease in CAR. Identification and control of Buruli ulcer remain difficult in CAR, where this disease is often not considered. Even with evocative clinical signs, confirmation of diagnosis by biological analysis is still not easy. It is therefore of high importance that the public health authorities are fully informed and properly trained to identify this neglected disease in the early stages so patients can be cured before the onset of functional impairment and the appearance of extensive lesions. Further investigation to isolate strains present in CAR is also essential.

The molecular epidemiology of hepatitis C virus (HCV) in the Central African Republic (CAR) is poorly documented. Thus, we conducted phylogenetic analyses of NS5B gene sequences from 58 HCV-infected inhabitants of a remote area of south-west CAR, which indicated that 48 (82.8 %) were infected with genotype 4 (HCV-4), five (8.6 %) with genotype 2 and five (8.6 %) with genotype 1. HCV-4 strains were highly heterogeneous, containing previously described subtypes 4k (48 %), 4c (27 %), 4r (4 %), 4f (4 %) and unclassified subtypes (17 %). To estimate the epidemic history of these HCV-4 strains, an evolutionary analysis using the coalescent approach was used. The estimated date of the most recent common ancestor of the CAR HCV-4 strains was 1539 (95 % confidence intervals, 1317–1697). They exhibited a rapid, exponential spread from 1935 to 1965, simultaneously with what was recently reported in neighbouring Cameroon and Gabon. The hypothesis of a massive iatrogenic transmission during interventions for the control of endemic tropical diseases is discussed.

The WHO recommendations for the immunization of children infected with human immunodeficiency virus (HIV) differ slightly from the guidelines for uninfected children. The introduction of antiretroviral therapy for HIV-infected infants should considerably prolong their life expectancy. The question of the response to the whole-cell pertussis (wP) vaccine should now be addressed, particularly in countries in which pertussis remains endemic. To evaluate the persistence of antibodies to the wP vaccine in HIV-infected and uninfected children who had previously received this vaccine in routine clinical practice, we conducted a cross-sectional study of children aged 18 to 36 months, born to HIV-infected mothers and living in Cameroon or the Central African Republic. We tested blood samples for antibodies to the wP vaccine and for antibodies to diphtheria and tetanus toxoids (D and T, respectively) in the context of the use of a combined DTwP vaccine. We enrolled 50 HIV-infected children and 78 uninfected, HIV-exposed children in the study. A lower proportion of HIV-infected children than uninfected children had antibodies against the antigens tested for all valences of the DTwP vaccine. Agglutinin levels were substantially lower in HIV-infected than in HIV-exposed but uninfected children (30.0% versus 55.1%, respectively; P = 0.005). We also observed a high risk of low antibody levels in response to the DTwP vaccine in HIV-infected children with severe immunodeficiency (CD4 T-cell level

One hundred twenty CTX-M-15-producing Escherichia coli strains isolated in 10 different hospitals from Paris (France), in the Hospital Charles Nicolle in Tunis (Tunisia), and in the Pasteur Institute in Bangui, Central African Republic (CAR), between 2000 and 2004 were studied. Eighty isolates, recovered from the three countries, were clonally related by repetitive extragenic palindromic PCR and pulsed-field gel electrophoresis. Various resistance profiles were identified among these clonal strains. After conjugation or electroporation of plasmids from E. coli strains representative of each profile and each geographic region, we observed seven resistance profiles in the recipient strains. Incompatibility typing showed that all the plasmids transferred from the clonal strains studied, except one, belonged to the incompatibility group FII. They all shared a multidrug resistance region (MDR) resembling the MDR region located in pC15-1a, a plasmid associated with an outbreak of a CTX-M-15-producing E. coli strain in Canada. They also shared the common backbone of an apparent mosaic plasmid, including several features present in pC15-1a and in pRSB107, a plasmid isolated from a sewage treatment plant. This study suggests that although the plasmid-borne bla CTX-M-15 gene could be transferred horizontally, its dissemination between France, Tunisia, and CAR was due primarily to its residence in an E. coli clone with a strong propensity for dissemination.

International audience; A sentinel serosurveillance study was conducted in Central African Republic to estimate the prevalence of HIV seropositivity in the general adult population in each province so that the public health authorities can target HIV prevention programmes to the priority areas. Blood samples were collected from women attending 48 antenatal clinics in urban and rural areas of the Central African Republic. These samples were tested for HIV antibodies in an anonymous and unlinked manner using strategy II recommended by WHO. The data were extrapolated to all women of reproductive age in Central African Republic by use of a parity-based adjustment involving the application of correction factors to the observed prevalence rates. A total of 9,305 pregnant women were recruited from November 2001 to October 2002. HIV seroprevalence was high in all age groups (12% in the less than 20 year age group to 17% in the 25-29 year age group). The median prevalence of HIV in antenatal clinics was similar for rural areas, for Bangui and for other urban areas (16.5, 15.0, and 12.5% respectively). Adjustment for parity and fertility pattern increased the prevalence of HIV in all antenatal clinics except in Bangui. This first national study of HIV prevalence in Central African Republic revealed that the HIV epidemic is continuing to spread in both urban and rural areas. Thus, efforts to reduce transmission should be made in every part of the country.

The threefold purpose of this report is to describe the epidemiology of acute flaccid paralysis (AFP), to determine the impact of the National Immunization Days (NID), and evaluate the quality of active surveillance in the Central African Republic (CAR) and Chad. The data in this study was obtained from the Enterovirus Division of the Pastear Institute in Bangui (National WHO Inter-country Reference Laboratory for the CAR and Chad and Regional Poliovirus Reference Laboratory in Africa). An increase in the number of AFP cases was observed in the CAR between 1995 and 2000 and in Chad between 1997 and 2000, mainly as a result of enhancement of the surveillance system. The goals set by the WHO in terms of the proportion of AFP cases with 2 specimens collected within 14 days of onset of paralysis and the number of cases with 60-day follow-up have not been reached in either country. The presence of 2 strains of wild poliovirus (types 1 and 3) and several genotypes (West African 13 and West African 7 for type 1 and Central African and Nigeria-P3 for type 3) not only show that Central Africa is still a significant reservoir for poliovirus transmission but also raise serious doubts about the quality of the NID organized over the last 3 years. The priority of the next NID round must be to reach unimmunized children who have been missed by routine immunization coverage., A partir des données du Laboratoire des Entérovirus de l’Institut Pasteur de Bangui (Laboratoire National OMS Inter pays de Référence pour la poliomyélite pour la République Centrafricaine (RCA) et le Tchad et Centre Régional OMS de référence pour la poliomyélite pour l’Afrique ), nous décrivons l’épidémiologie des paralysies flasques aiguës (PFA) dans ces deux pays entre 1995 et 2000, nous estimons l’impact des Journées Nationales de Vaccination (JNV) et nous évaluons la qualité de la surveillance active dans les deux pays. Une augmentation du nombre de cas PFA a été observée en RCA entre 1995 et 2000 et au Tchad entre 1997 et 2000, essentiellement en raison de l’amélioration du système de surveillance. La proportion des cas de PFA pour lesquels 2 échantillons de selles sont recueillis dans les 14 jours suivant l’apparition de la paralysie et le nombre de cas de PFA bénéficiant d’un suivi après 60 jours, n’ont jamais atteint les objectifs fixés par l’OMS dans les 2 pays. La présence de 2 types de poliovirus sauvages (types 1 et 3) et de plusieurs génotypes (West African 13 et West African 7 pour le type 1 , Central African et Nigeria - P3 pour le type 3) témoigne de l’intense circulation du poliovirus en Afrique Centrale, mettant en cause la qualité des JNV organisées au cours de ces 3 dernières années. De ce fait, l’objectif des prochaines JNV doit être avant tout d’atteindre les enfants non immunisés contre la poliomyélite ayant échappé à la vaccination de routine.