Alain Le Faou

The prevalence of hepatitis B virus markers in a cohort of students in Bangui, Central African Republic.

BackgroundHepatitis B virus (HBV) is the major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The global epidemiological scenario of HBV infection has been changing rapidly over the last two decades due to an effective immunization programme initiated by the World Health Organization. The objective of this study is to estimate the prevalence of HBV in apparently healthy young people and to identify the risk factors of transmission of the HBV among this population in Bangui.MethodsDried blood Spots from 801 adolescent high school and young adult university students were prepared by spotting a drop of whole blood (4 spots) from the same fingerprick onto Whatman filter paper. A blood sample aliquot eluted from DBS was then processed with commercial ELISA tests (Abbott Murex, Dartfort, UK) to detect HBsAg antigen, Anti-HBc and Anti-HBs antibodies).ResultsThe overall prevalence was 42.3% for antibody to hepatitis B core antigen, 15.5% for HBsAg of which 1.3% of HBsAg alone. HBV familial antecedents, sexual activity and socioeconomic conditions were the main risk factors of HBV infection encountered in the adolescents and young adults.ConclusionThese results show for the first time the high prevalence of HBV in apparently healthy young people in Bangui. This high prevalence is age- and sex-independent. Transmission risk factors were a familial antecedent of HBV, no utilisation of condoms and public scholarship. To lower HBV prevalence, an adequate program of active screening and vaccination for adolescents and young adults should be implemented, along with a universal immunization program.

Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial.

BackgroundThe efficacy of artemisinin-based combination therapy (ACT) has been established. The objective of the present study was to compare the efficacy and safety in the Central African Republic (CAR) of three commercially available artemisinin-based combinations, artemether + lumefantrine (AL), artesunate + sulphamethoxypyrazine–pyrimethamine (AS-SMP) and artesunate + amodiaquine (AS-AQ), with those of sulphadoxine–pyrimethamine + amodiaquine (SP-AQ), which was the first-line reference treatment in the country from 2004, until it was replaced by ACT in 2006 in accordance with changes in international recommendations based on resistance identified in other regions.MethodsChildren aged six to 59 months with uncomplicated Plasmodium falciparum malaria were recruited in Bangui, the capital of the CAR. The 251 patients selected were randomly assigned to receive AL (n = 60), AS-SMP (n = 58), AS-AQ (n = 68) or SP-AQ (n = 65) and were followed up for 28 days. Clinical outcome was classified according to the standard 2003 World Health Organization protocol.ResultsAt day 28, the cure rates in a per-protocol analysis were 92% (48/52) with AL, 93% (50/54) with AS-SMP, 93% (55/59) with AS-AQ and 100% (57/57) with SP-AQ, with no statistically significant difference between the four treatments. Defervescence was significantly faster with AS-AQ than with AL (p <0.035). Fatigue was reported significantly more frequently by patients receiving AQ than by those treated with AS-SMP or AL (p = 0.006). All the other adverse events reported were mild, and no significant difference was noted by treatment.ConclusionThe three artemisinin-bsed combinations show similar, satisfactory results, comparable to that with SP-AQ. This evaluation is the first conducted in CAR since the official introduction of ACT. It should guide the National Malaria Control Programme in choosing the appropriate ACT for treatment of uncomplicated P. falciparum malaria in the future.

Cross-sectional study of hepatitis B virus infection in rural communities, Central African Republic.

BackgroundAs most data on hepatitis in resource-poor countries relate to urban communities, surveys in the rural environment are necessary to determine the ‘true’ prevalence of these viral infections. We undertook a survey to determine the prevalence of hepatitis B virus (HBV) infection in an apparently healthy rural population in the Central African Republic (CAR).MethodsThe cross-sectional study was based on dried blood spots (DBS) from 273 people recruited in four prefectures (Lobaye, Nana-Mambéré, Ouham and Ouaka). Eluates from DBS were tested with commercial ELISA kits to detect markers of HBV infection. DBS were directly used for DNA extraction, followed by PCR and genotyping based on preS/S gene sequences.ResultsThe overall prevalence of HBc antibodies was 27.1% (Lobaye 29%, Nana-Mambéré 28%, Ouaka 29% and Ouham 23%) and that of HBsAg was 10.6% (Lobaye 9%, Nana-Mambéré 9%, Ouaka 19% and Ouham 8%), with no statistically significant difference among the surveyed communities. Nineteen sequences obtained from 74 anti-HBc-positive patients all belonged to genotype E. Risk factor analysis of HBV infection pointed to sexual transmission of the virus.ConclusionThe prevalence of HBV is high in rural communities in the CAR and comparable to that observed in urban areas. In addition, genotype E is prevalent in these areas. These findings underline the importance of instituting a programme of active HBV surveillance and vaccination of the population.

Availability of Antimalarial Drugs and Evaluation of the Attitude and Practices for the Treatment of Uncomplicated Malaria in Bangui, Central African Republic

National malaria management policy is based upon the availability of effective and affordable antimalarial drugs. This study was undertaken to evaluate the quality of the treatment of uncomplicated malaria cases in Bangui, an area with multidrug-resistant parasites, at a time preceding implementation of a new therapeutic policy relying on the artemisinin derivative combined treatment artemether-lumefantrine. A cross-sectional study was carried out in Bangui city to assess availability of antimalarial drugs and the performances of health workers in the management of uncomplicated malaria. Availability of drugs was recorded in all drugs wholesalers (n = 3), all pharmacies in health facilities (n = 14), private drugstores (n = 15), and in 60 non-official drug shops randomly chosen in the city. Despite a limited efficacy at the time of the survey, chloroquine remained widely available in the official and nonofficial markets. Artemisinin derivatives used in monotherapy or in combination were commonly sold. In health care facilities, 93% of the uncomplicated malaria cases were treated in the absence of any laboratory confirmation and the officially recommended treatment, amodiaquine-sulfadoxine/pyrimethamine, was seldom prescribed. Thus, the national guidelines for the treatment of uncomplicated malaria are not followed by health professionals in Bangui. Its use should be implemented while a control of importation of drug has to be reinforced.

Pattern of the Antimalarials Prescription during Pregnancy in Bangui, Central African Republic

Introduction. The aim of this study was to identify the antimalarials prescribed during the pregnancy and to document their timing. Method. From June to September 2009, a survey was conducted on 565 women who gave birth in the Castors maternity in Bangui. The antenatal clinics cards were checked in order to record the types of antimalarials prescribed during pregnancy according to gestational age. Results. A proportion of 28.8% ANC cards contained at least one antimalarial prescription. The commonest categories of antimalarials prescribed were: quinine (56.7%), artemisinin-based combinations (26.8%) and artemisinin monotherapy (14.4%). Among the prescriptions that occurred in the first trimester of pregnancy, artemisinin-based combinations and artemisinin monotherapies represented the proportions of (10.9%) and (13.3%). respectively. Conclusion. This study showed a relatively high rate (>80%) of the recommended antimalarials prescription regarding categories of indicated antimalarials from national guidelines. But, there is a concern about the prescription of the artemisinin derivatives in the first trimester of pregnancy, and the prescription of artemisinin monotherapy. Thus, the reinforcement of awareness activities of health care providers on the national malaria treatment during pregnancy is suggested.

Relatively Low Prevalence of Peripheral and Placental Plasmodium Infection at Delivery in Bangui, Central African Republic

Introduction. The aim of this study was to estimate the prevalence of malaria among women giving birth in Bangui. Association between sociodemographic characteristics of those women and malaria, as well as prevention compliance (use of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTsp) and insecticide-treated bed nets (ITNs)), was analyzed. Methods. During September 2009, a survey was conducted on 328 women who gave birth at two main maternities of Bangui. Information was obtained by standardized questionnaire about sociodemographic criteria, IPTsp, other antimalarial treatment, and use of bet nets. Smears prepared from peripheral and placental blood were analysed for malaria parasites. Findings and Discussion. Positive results were found in 2.8% of thick peripheral blood smears and in 4.0% of placental slides. A proportion of 30.5% of the women had received at least two doses of IPTsp during the current pregnancy. Only a proportion of 42.4% of this study population had ITNs. Multigravid women were less likely to use IPTsp and ITNs. However, use of IPTsp was associated with personal income and secondary or university educational status. Hence, although this relatively prevalence was observed, more efforts are needed to implement IPTsp and ITNs, taking into account sociodemographic criteria.

Buruli Ulcer, Central African Republic

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.

Rational case management of malaria with a rapid diagnostic test, Paracheck Pf®, in antenatal health care in Bangui, Central African Republic.

BackgroundBoth treatment and prevention strategies are recommended by the World Health Organization for the control of malaria during pregnancy in tropical areas. The aim of this study was to assess use of a rapid diagnostic test for prompt management of malaria in pregnancy in Bangui, Central African Republic.MethodsA cohort of 76 pregnant women was screened systematically for malaria with ParacheckPf® at each antenatal visit. The usefulness of the method was analysed by comparing the number of malaria episodes requiring treatment in the cohort with the number of prescriptions received by another group of pregnant women followed-up in routine antenatal care.ResultsIn the cohort group, the proportion of positive ParacheckPf® episodes during antenatal clinics visits was 13.8%, while episodes of antimalarial prescriptions in the group which was followed-up routinely by antenatal personnel was estimated at 26.3%. Hence, the relative risk of the cohort for being prescribed an antimalarial drug was 0.53. Therefore, the attributable fraction of presumptive treatment avoided by systematic screening with ParacheckPf® was 47%.ConclusionsUse of a rapid diagnostic test is useful, affordable and easy for adequate treatment of malaria in pregnant women. More powerful studies of the usefulness of introducing the test into antenatal care are needed in all heath centres in the country and in other tropical areas.

Adaptive HIV-Specific B Cell-Derived Humoral Immune Defenses of the Intestinal Mucosa in Children Exposed to HIV via Breast-Feeding

Background We evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding. Methods Couples of HIV-1-infected mothers (n = 14) and their breastfed non HIV-infected (n = 8) and HIV-infected (n = 6) babies, and healthy HIV-negative mothers and breastfed babies (n = 10) as controls, were prospectively included at the Complexe Pédiatrique of Bangui, Central African Republic. Immunoglobulins (IgA, IgG and IgM) and anti-gp160 antibodies from mother’s milk and stools of breastfed children were quantified by ELISA. Immunoaffinity purified anti-gp160 antibodies were characterized functionally regarding their capacity to reduce attachment and/or infection of R5- and X4- tropic HIV-1 strains on human colorectal epithelial HT29 cells line or monocyte-derived-macrophages (MDM). Results The levels of total IgA and IgG were increased in milk of HIV-infected mothers and stools of HIV-exposed children, indicating the activation of B cell-derived mucosal immunity. Breast milk samples as well as stool samples from HIV-negative and HIV-infected babies exposed to HIV by breast-feeding, contained high levels of HIV-specific antibodies, mainly IgG antibodies, less frequently IgA antibodies, and rarely IgM antibodies. Relative ratios of excretion by reference to lactoferrin calculated for HIV-specific IgA, IgG and IgM in stools of HIV-exposed children were largely superior to 1, indicating active production of HIV-specific antibodies by the intestinal mucosa. Antibodies to gp160 purified from pooled stools of HIV-exposed breastfed children inhibited the attachment of HIV-1NDK on HT29 cells by 63% and on MDM by 77%, and the attachment of HIV-1JRCSF on MDM by 40%; and the infection of MDM by HIV-1JRCSF by 93%. Conclusions The intestinal mucosa of children exposed to HIV by breast-feeding produces HIV-specific antibodies harbouring in vitro major functional properties against HIV. These observations lay the conceptual basis for the design of a prophylactic vaccine against HIV in exposed children.

Antimicrobial Resistance of Enteric Salmonella in Bangui, Central African Republic.

Introduction. The number of Salmonella isolated from clinical samples that are resistant to multiple antibiotics has increased worldwide. The aim of this study was to determine the prevalence of resistant Salmonella enterica isolated in Bangui. Methods. All enteric Salmonella strains isolated from patients in 2008 were identified and serotyped, and the phenotypes of resistance were determined by using the disk diffusion method. Nine resistance-associated genes, bla TEM, bla OXA, bla SHV, tetA, aadA1, catA1, dhfrA1, sul I, and sul II, were sought by genic amplification in seven S.e. Typhimurium strains. Results. The 94 strains isolated consisted of 47 S.e. Typhimurium (50%), 21 S.e. Stanleyville (22%), 18 S.e. Enteritidis (19%), 4 S.e. Dublin (4%), 4 S.e. Hadar (4%), and 1 S.e. Papuana (1%). Twenty-five (28%) were multiresistant, including 20 of the Typhimurium serovar (80%). Two main phenotypes of resistance were found: four antibiotics (56%) and to five antibiotics (40%). One S.e. Typhimurium isolate produced an extended-spectrum β-lactamase (ESBL). Only seven strains of S.e. Typhimurium could be amplified genically. Only phenotypic resistance to tetracycline and aminosides was found. Conclusion. S. Typhimurium is the predominant serovar of enteric S. enterica and is the most widely resistant. The search for resistance genes showed heterogeneity of the circulating strains.