Molecular epidemiology of non-falciparum Plasmodium infections in three different areas of the Ivory Coast.

BACKGROUND: Malaria is a major public health problem, particularly in the tropical regions of America, Africa and Asia. Plasmodium falciparum is not only the most widespread but also the most deadly species. The share of Plasmodium infections caused by the other species (Plasmodium ovale and Plasmodium malariae) is clearly underestimated. The objective of the study was to determine the molecular epidemiology of plasmodial infection due to P. malariae and P. ovale in Côte d'Ivoire. METHODS: The study was cross-sectional. The study participants were recruited from Abengourou, San Pedro and Grand-Bassam. Sample collection took place from May 2015 to April 2016. Questionnaires were administered and filter paper blood samples were collected for parasite DNA extraction. The molecular analysis was carried out from February to March 2021. A nested PCR was used for species diagnosis. The data was presented in frequencies and proportions. RESULTS: A total of 360 patients were recruited, including 179 men (49,7%) for 181 women (50,3%). The overall Plasmodium positive rate was 72.5% (261/360). The specific index was 77.4% and 1.5% for P. falciparum and P. malariae in mono-infection, respectively. There was also 15% P. falciparum and P. malariae co-infection, 3.4% P. falciparum and P. ovale co-infection and 2.3% P. falciparum, P. malariae and P. ovale triple-infection. Typing of P. ovale subspecies showed a significant predominance of P. ovale curtisi (81.2% of cases). CONCLUSION: Plasmodium falciparum remains the most prevalent malaria species in Côte d'Ivoire, but P. malariae and P. ovale are also endemic mostly in co-infection. Malaria elimination requires a better understanding of the specific epidemiological characteristics of P. malariae and P. ovale with a particular emphasis on the identification of asymptomatic carriers.

Knowledge and practices of private pharmacy auxiliaries on malaria in Abidjan, Côte d'Ivoire.

BACKGROUND: The emergence of resistance to artemisinin derivatives in Southeast Asia constitutes a serious threat for other malaria endemic areas, particularly in Côte d'Ivoire. To delay this resistance, the application of the control measures recommended by the National Malaria Control Programme (NMCP) for a correct management, in the private pharmacies, is a necessity. The purpose of this study was, therefore, to assess the level of knowledge and practices of private pharmacy auxiliary in Abidjan about the management of malaria. METHODS: A descriptive cross-sectional study was conducted from April to November 2015. It included auxiliaries of private pharmacies in Abidjan. Data collection material was a structured an open pretested questionnaire. Data analysis was carried out using Package for Social Science (SPSS) software version 21.1. Chi square test was used to compare proportions for a significance threshold of 0.05 for the p value. RESULTS: A total, 447 auxiliaries from 163 private pharmacies were interviewed. It was noted that the auxiliaries had a good knowledge of clinical signs of uncomplicated malaria (99.1%), biological examinations (54.6% for the thick film and 40.7% for rapid diagnostic tests (RDTs) and anti-malarial drugs (99.3% for artemether + lumefantrine, AL). The strategies of vector control (long-lasting insecticide-treated mosquito nets (LLITNs, Repellent ointments, cleaning gutters, elimination of larvae breeding site and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) in pregnant women were also known by the auxiliaries, respectively 99.8% and 77.4%. However, the malaria pathogen (25.1%) and the NMCP recommendations (e.g. use of AL or AS + AQ as first-line treatment for uncomplicated malaria and IPTp-SP in pregnant women) were not well known by the auxiliaries (28.2% and 26.9% for uncomplicated and severe malaria). Concerning the practices of the auxiliaries, 91.1% offered anti-malarial drugs to patients without a prescription and 47.3% mentioned incorrect dosages. The combination artemether + lumefantrine was the most recommended (91.3%). The delivery of anti-malarial drugs was rarely accompanied by advice on malaria prevention, neither was it carried out on the result of an RDT. CONCLUSION: The epidemiology and the NMCP recommendations for the diagnostic and therapeutic management of malaria, are not well known to auxiliaries, which may have implications for their practices. These results show the need to sensitize and train private pharmacy auxiliaries, and also to involve them in NMCP activities.

Virological failure and drug resistance in West African HIV-infected adults who started ART immediately or deferred ART initiation.

BACKGROUND: Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance. METHODS: In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation. RESULTS: Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04). CONCLUSIONS: Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited.

Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy.

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA ≥ 2,000 IU/ml; HBsAg-positive with HBV DNA < 2,000 IU/ml; isolated HBcAb-positive; resolved infection (HBsAb-positive/HBcAb-positive); and HBV non-immune/vaccinated (HBcAb-negative). We compared square-root CD4-cell count increases using mixed-effect, non-linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all-cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti-HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non-immune/vaccinated. We found no significant difference in CD4 cell increases between HBV-infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all-cause mortality (1.9/100 person-years, 95% Credibile Interval [CrI] = 1.0-3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = -79%, -13%), 60% (95%CrI = -82%, -12%) and 66% (95%CrI = -84%, -23%) in those who had isolated anti-HBcAb-positive, resolved HBV infection and HBV non-immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti-HBcAb-positive serology, much like HBV non-immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV-related management would not be necessary for these individuals.

High prevalence of Schistosoma haematobium × Schistosoma bovis hybrids in schoolchildren in Côte d'Ivoire.

Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman® FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Côte d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.

[A plea for introduction of hepatitis B vaccination at birth in Côte d'Ivoire]. / Plaidoyer pour l?introduction du vaccin contre l?hépatite virale B à la naissance en Côte d?Ivoire.

The Côte d'Ivoire National Immunization Technical Advisory Group 2015 work plan included elaboration of an opinion on inclusion of hepatitis B vaccination at birth in the Expanded Program on Immunization (EPI) in Côte d'Ivoire. A task force was set up to conduct this assessment according to a systematized method. The task force analysed scientific articles on the burden of hepatitis B in Côte d'Ivoire, the burden of mother-child transmission, the impact of hepatitis B vaccination at birth in countries which have adopted this strategy, the efficacy and safety of hepatitis B vaccine in newborns, the cost-effectiveness of hepatitis B vaccination at birth, and the best strategy to introduce hepatitis B vaccination at birth in the EPI. The National Immunization Technical Advisory Group of Côte d'Ivoire finally recommended introduction of a dose of hepatitis B vaccine at birth in the context of the Expanded Program on Immunization with maintenance of three doses of pentavalent vaccine (DPT-HepB-Hib) at 6, 10, and 14 weeks of age.

Molecular epidemiology reveals genetic diversity among 363 isolates of the Cryptococcus neoformans and Cryptococcus gattii species complex in 61 Ivorian HIV-positive patients.

Cryptococcal meningitis is a severe opportunistic infection in HIV-infected patients. In Ivory Coast, despite the availability of antiretroviral treatment (ART), this infection is still prevalent. The study investigates the genetic diversity of 363 clinical isolates of Cryptococcus from 61 Ivorian HIV-positive patients, the occurrence of mixed infections and the in vitro antifungal susceptibility of the isolates. Serotyping was performed via LAC1 and CAP64 gene amplification. Genotyping was performed using the phage M13 core (GACA)4 and (GTG)5 primers and restriction fragment length polymorphism analysis of the URA5 gene. By PCR fingerprinting, the presence of the three serotypes were demonstrated among the 363 isolates in the population studied: A (n=318; 87.6%), AD (n=40; 11%) and B (n=4; 1.1%). Using PCR fingerprinting with primers M13 (GACA)4 and (GTG)5 , we grouped the isolates into 56 molecular subtypes. We observed a high frequency (39.3%) of mixed infections, with up to two different genotypes per sample. None of the isolates were resistant to amphotericin B. Only 0.3% and 1.1% of the isolates were resistant to fluconazole and flucytosine respectively. This study revealed the high genetic diversity among Cryptococcus isolates, the occurrence of mixed infections and a high antifungal susceptibility for the majority of Ivorian cryptococcal isolates.

Assessment of the performance of five malaria rapid diagnostic tests in health facilities in Abidjan (Côte d'Ivoire).

Regular monitoring of malaria rapid diagnostic tests (RDTs) for the management of uncomplicated malaria in healthcare facilities is a key factor in improving diagnostic quality and ensuring better case management. This study aimed to assess the performance of five RDTs (Standard Q Malaria P.f Ag and Standard Q Malaria P.f/Pan (SD Biosensor, Korea), One Step Malaria HRP2/pLDH (P.f/Pan) (Guangzhou Wondfo Biotech Co., Ltd., China), Malaria Pf/Pan (B&O Pharm, France), and Malaria test P.f/pan (Das Labor, Germany)) in two healthcare facilities in Abidjan. This cross-sectional study was conducted between September and October 2022. Overall, 250 patients suffering from uncomplicated malaria were included with a predominance of female patients (56.6%). The mean age was 22.3 years (SD = 20.6; range, 0.17-73). Of the patients tested, forty-six (46) tested positive for thick smears, reflecting a prevalence of 18.5%. Plasmodium falciparum was the most commonly detected species (93.5%). The geometric mean parasitemia was 6,111.80 parasites/µl (SD = 80,026.93) (range: 116-412461). The sensitivity ranged from 95.24% to 95.65%, whereas the specificity ranged from 93.07 to 94.09% for all five tests evaluated. The false positive rate of the tests was less than 10%. No invalid test results were reported. Two-thirds of P. malariae cases detected by microscopy showed also positive results with all the RDTs. All five RDTs showed 100% sensitivity at low parasitemia levels (< 1,000 parasites/µl blood) including three cases of parasites < 200 parasites/µl blood. This study demonstrated the importance of monitoring the performance of RDTs in clinical samples.

Incidence of serious morbidity in HIV-infected adults on antiretroviral therapy in a West African care centre, 2003-2008.

BACKGROUND: In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. METHODS: We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Côte d'Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3-4 event, ANRS grade 3-4 adverse event, or any event leading to death or to hospitalization. RESULTS: 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. CONCLUSION: Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa.

AIDS and non-AIDS morbidity and mortality across the spectrum of CD4 cell counts in HIV-infected adults before starting antiretroviral therapy in Cote d'Ivoire.

BACKGROUND: In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count-specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)-infected adults with high CD4 cell counts. In sub-Saharan Africa, these CD4 cell count-specific estimates are scarce. METHODS: From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d'Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/µL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count-specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. RESULTS: Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500-649, 350-499, 200-349, 100-199, 50-99, and 0-49 cells/µL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/µL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200-349 and ≥650 cells/µL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). CONCLUSIONS: Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/µL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.

Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon, Ivory Coast and Senegal.

BACKGROUND: This multicentre study was carried out in Cameroon, Ivory Coast and Senegal to evaluate the non-inferiority of the new paediatric formulation of artesunate/amodiaquine (AS+AQ)(Camoquin-Plus Paediatric®) in suspension form versus artemether/lumefantrine (AL)(Coartem®) in the management of African children with uncomplicated falciparum malaria. METHODS: It was an open randomized trial including children aged between 7 months and 7 years. The endpoints were Adequate Clinical and Parasitological Response (ACPR) at day 28, the clinical and biological tolerability. Statistical analyses were done in Intention To Treat (ITT) and in Per protocol (PP). RESULTS: At the end of the study 481 patients were enrolled in the three countries (249 in the AS+AQ arm and 232 in the AL arm). ACRP in ITT after PCR correction did not show any statistical difference between the two groups with 97.6% for AS+AQ versus 94.8% for AL. In the PP analysis, the corrected ACRP were respectively 98.7% and 96.9% for the two regimens. The clinical tolerance was good without significant difference. Anaemia was significantly higher at D7 in the two groups compared to D0. CONCLUSION: This study demonstrates the non-inferiority of AS+AQ versus AL, its efficacy and tolerance in the management of uncomplicated Plasmodium falciparum malaria in African children.

Genotyping Canadian Cyclospora cayetanensis Isolates to Supplement Cyclosporiasis Outbreak Investigations.

Cyclospora cayetanensis is an emerging foodborne parasite that causes cyclosporiasis, an enteric disease of humans. Domestically acquired outbreaks have been reported in Canada every spring or summer since 2013. To date, investigations into the potential sources of infection have relied solely on epidemiological data. To supplement the epidemiological data with genetic information, we genotyped 169 Canadian cyclosporiasis cases from stool specimens collected from 2010 to 2021 using an existing eight-marker targeted amplicon deep (TADS) scheme specific to C. cayetanensis as previously described by the US Centers for Disease Control and Prevention (CDC). This is the first study to genotype Canadian Cyclospora cayetanensis isolates, and it focuses on evaluating the genotyping performance and genetic clustering. Genotyping information was successfully collected with at least part of one of the markers in the TADS assay for 97.9% of specimens, and 81.1% of cyclosporiasis cases met the minimum requirements to genetically cluster into 20 groups. The performance of the scheme suggests that examining cyclosporiasis cases genetically will be a valuable tool for supplementing epidemiological outbreak investigations and to minimize further infections. Further research is required to expand the number of discriminatory markers to improve genetic clustering.

Population genetic structure of Schistosoma haematobium and Schistosoma haematobium × Schistosoma bovis hybrids among school-aged children in Côte d'Ivoire.

While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Côte d'Ivoire. The purpose of this study was to analyze both genetic variability and genetic structure among S. haematobium populations and to quantify the frequency of S. haematobium × S. bovis hybrids in school-aged children in different parts of Côte d'Ivoire. Urine samples were subjected to a filtration method and examined microscopically for Schistosoma eggs in four sites in the western and southern parts of Côte d'Ivoire. A total of 2692 miracidia were collected individually and stored on Whatman® FTA cards. Of these, 2561 miracidia were successfully genotyped for species and hybrid identification using rapid diagnostic multiplex mitochondrial cox1 PCR and PCR Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the nuclear ITS2 region. From 2164 miracidia, 1966 (90.9%) were successfully genotyped using at least 10 nuclear microsatellite loci to investigate genetic diversity and population structure. Significant differences were found between sites in all genetic diversity indices and genotypic differentiation was observed between the site in the West and the three sites in the East. Analysis at the infrapopulation level revealed clustering of parasite genotypes within individual children, particularly in Duekoué (West) and Sikensi (East). Of the six possible cox1-ITS2 genetic profiles obtained from miracidia, S. bovis cox1 × S. haematobium ITS2 (42.0%) was the most commonly observed in the populations. We identified only 15 miracidia (0.7%) with an S. bovis cox1 × S. bovis ITS2 genotype. Our study provides new insights into the population genetics of S. haematobium and S. haematobium × S. bovis hybrids in humans in Côte d'Ivoire and we advocate for researching hybrid schistosomes in animals such as rodents and cattle in Côte d'Ivoire.

Title: Structuration génétique des populations de Schistosoma haematobium et des hybrides Schistosoma haematobium × Schistosoma bovis chez les enfants d'âge scolaire en Côte d'Ivoire. Abstract: Alors que la génétique des populations de Schistosoma haematobium a été étudiée en Afrique de l'Ouest, seules quelques données sont disponibles pour la Côte d'Ivoire. Le but de cette étude était d'analyser à la fois la variabilité génétique et la structure génétique des populations de S. haematobium et de quantifier la fréquence des hybrides S. haematobium × S. bovis chez les enfants d'âge scolaire dans différentes régions de la Côte d'Ivoire. Des échantillons d'urine ont été soumis à une méthode de filtration et examinés au microscope pour les œufs de Schistosoma dans quatre sites de l'ouest et du sud de la Côte d'Ivoire. Au total, 2 692 miracidia ont été collectés individuellement et stockés sur des cartes Whatman® FTA. Parmi ceux-ci, 2 561 miracidia ont été génotypés avec succès pour l'identification des espèces et des hybrides à l'aide de la PCR multiplex de diagnostic rapide du cox1 mitochondrial et d'une analyse du polymorphisme de longueur des fragments de restriction de PCR (PCR-RFLP) de la région ITS2 de l'ADN nucléaire. Sur 2 164 miracidia, 1 966 (90,9 %) ont été génotypés avec succès en utilisant au moins 10 loci microsatellites nucléaires pour étudier la diversité génétique et la structure de la population. Des différences significatives ont été trouvées entre les sites dans tous les indices de diversité génétique et une différenciation génotypique a été observée entre le site de l'Ouest et les trois sites de l'Est. L'analyse au niveau de l'infrapopulation a révélé un regroupement des génotypes de parasites au sein de chaque enfant, en particulier à Duekoué (Ouest) et Sikensi (Est). Parmi les six profils génétiques cox1-ITS2 possibles obtenus à partir de miracidia, S. bovis cox1 × S. haematobium ITS2 (42,0 %) était le plus fréquemment observé dans les populations. Nous avons identifié seulement 15 miracidia (0,7 %) avec un génotype S. bovis cox1 × S. bovis ITS2. Notre étude apporte de nouvelles connaissances sur la génétique des populations de S. haematobium et des hybrides S. haematobium × S. bovis chez l'homme en Côte d'Ivoire et nous plaidons pour la recherche de schistosomes hybrides chez les animaux (rongeurs et bovins) en Côte d'Ivoire.

Elite and viremic HIV-1 controllers in West Africa.

BACKGROUND: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. METHODS: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral <2000 copies/ml and still off ART at month 30 were defined as HIV-1 controllers. Controllers with all viral loads <50 copies/ml were defined as elite controllers, the rest as viremic controllers. RESULTS: Of the 1023 HIV-1-infected adults randomized in the Temprano deferred-ART group, 18 (1.8%) met the criteria for classification as HIV controllers, of whom seven (0.7%) were elite controllers and 11 (1.1%) viremic controllers. The HIV-1 controllers had low peripheral blood mononuclear cell HIV-1 DNA and low inflammatory marker levels. They maintained high CD4+ cell count and percentages and had a low morbidity rate. DISCUSSION: HIV controllers exist in Africa at a proportion close to that reported elsewhere. They represent a small fraction of all HIV-1-infected patients but raise important questions. Further studies should assess whether starting ART might represent more risk than benefit for some controllers, and where it does, how to identify these patients before they start ART.

Coverage of intermittent prevention treatment with sulphadoxine-pyrimethamine among pregnant women and congenital malaria in Côte d'Ivoire.

BACKGROUND: The World Health Organization (WHO) recommends using insecticide-treated mosquito nets (ITNs) and intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP) to prevent malaria in sub-Saharan Africa. Data on IPT-SP coverage and factors associated with placental malaria parasitaemia and low birth weight (LBW) are scarce in Côte d'Ivoire. METHODS: A multicentre, cross-sectional survey was conducted in Côte d'Ivoire from March to September 2008 at six urban and semi-urban antenatal clinics. Standardized forms were used to collect the demographic information and medical histories of women and their offspring. IPT-SP coverage (≥2 doses) as well as placental and congenital malaria prevalence parasitaemia were estimated. Regression logistics were used to study factors associated with placental malaria and LBW (birth weight of alive babies < 2,500 grams). RESULTS: Overall, 2,044 women with a median age of 24 years were included in this study. Among them 1017 (49.8%) received ≥2 doses of IPT-SP and 694 (34.0%) received one dose. A total of 99 mothers (4.8%) had placental malaria, and of them, four cases of congenital malaria were diagnosed. Factors that protected from maternal placental malaria parasitaemia were the use of one dose (adjusted odds ratio (aOR), 0.32; 95%CI: 0.19-0.55) or ≥2 doses IPT-SP (aOR: 0.18; 95%CI: 0.10-0.32); the use of ITNs (aOR: 0.47; 95%CI: 0.27-0.82). LBW was associated with primigravidity and placental malaria parasitaemia. CONCLUSION: IPT-SP decreases the rate of placental malaria parasitaemia and has a strong dose effect. Despite relatively successful IPT-SP coverage in Côte d'Ivoire, substantial commitments from national authorities are urgently required for such public health campaigns. Strategies, such as providing IPT-SP free of charge and directly observing treatment, should be implemented to increase the use of IPT-SP as well as other prophylactic methods.

Comparative study of the efficacy and tolerability of dihydroartemisinin-piperaquine-trimethoprim versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal.

BACKGROUND: The ACT recommended by WHO is very effective and well-tolerated. However, these combinations need to be administered for three days, which may limit adherence to treatment.The combination of dihydroartemisinin-piperaquine phosphate-trimethoprim (Artecom®, Odypharm Ltd), which involves treatment over two days, appears to be a good alternative, particularly in malaria-endemic areas. This study intends to compare the efficacy and tolerability of the combination dihydroartemisinin-piperaquine phosphate-trimethoprim (DPT) versus artemether-lumefantrine (AL) in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal. METHODS: This was a randomized, controlled, open-label clinical trial with a 28-day follow-up period comparing DPT to AL as the reference drug. The study involved patients of at least two years of age, suffering from acute, uncomplicated Plasmodium falciparum malaria with fever. The WHO 2003 protocol was used. RESULTS: A total of 418 patients were included in the study and divided into two treatment groups: 212 in the DPT group and 206 in the AL group. The data analysis involved the 403 subjects who correctly followed the protocol (per protocol analysis), i.e. 206 (51.1%) in the DPT group and 197 (48.9%) in the AL group. The recovery rate at D14 was 100% in both treatment groups. The recovery rate at D28 was 99% in the DPT and AL groups before and after PCR results with one-sided 97.5% Confidence Interval of the rates difference > -1.90%. More than 96% of patients who received DPT were apyrexial 48 hours after treatment compared to 83.5% in the AL group (p < 0.001). More than 95% of the people in the DPT group had a parasite clearance time of 48 hours or less compared to approximately 90% in the AL group (p = 0.023). Both drugs were well tolerated. No serious adverse events were reported during the follow-up period. All of the adverse events observed were minor and did not result in the treatment being stopped in either treatment group. The main minor adverse events reported were vomiting, abdominal pain and pruritus. CONCLUSION: The overall efficacy and tolerability of DPT are similar to those of AL. The ease of taking DPT and its short treatment course (two days) may help to improve adherence to treatment. Taken together, these findings make this medicinal product a treatment of choice for the effective management of malaria in Africa.

Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts.

BACKGROUND: Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4+ cell counts in this association is poorly defined. We aimed to determine whether HIV-HBV co-infection influences changes in CD4+ cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4+. METHODS: 2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4+ cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4+ counts ≤350, 351-500, >500/mm3 and were compared between HBV-status groups as incidence rate ratios (IRR). RESULTS: At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40-69). Between co-infection groups, there were no differences in CD4+ decline before ART initiation and no differences in CD4+ increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4+ levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm3 (adjusted-IRR = 3.82, 95% CI = 1.11-9.70) and 351-500/mm3 (adjusted-IRR = 4.37, 95% CI = 0.98-13.02), but not >500/mm3 (adjusted-IRR = 1.07, 95% CI = 0.01-4.91). CONCLUSION: Despite no effect of HBV-infection on CD4+ levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4+ is <500/mm3.

Efficacy and safety of artesuante-amodiaquine and artemether lumefantrine, the first line malaria treatment in six sentinel's sites of Côte d'Ivoire, West Africa.

The purpose of this study was to update efficacy data of Artesunate-Amodiaquine (AS+AQ) and Artemether-Lumefantrine (AL) used as first-line malaria treatment in Côte d'Ivoire since 2005. This was an open-label, randomized trial conducted in patients older than 6 months with uncomplicated P. falciparum malaria at six sentinel sites. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used with primary outcomes as ACPR corrected by PCR at day 42. Secondary endpoints were parasite and fever clearance times and safety. From January to July 2016, 712 patients were included in the trial. 353 and 359 patients were randomly assigned respectively to the AS+AQ and AL arm. Day 42 PCR-adjusted ACPR in the per-protocol analysis was 99.4% and 98.8% in AS+AQ and AL arm respectively. Delayed parasite clearance was observed in six patients at Abidjan and Yamousssoukro sites. Both ACTs were well tolerated. Both ACTs remain efficacious for uncomplicated P. falciparum malaria treatment in Côte d'Ivoire. But regarding delayed parasite clearance observed in this study, a close monitoring and supervision for ACT resistance are essential for future malaria treatment and control strategies in Côte d'Ivoire.

Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts.

BACKGROUND: High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa. METHODS: In the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality. FINDINGS: 2019 patients were followed for 9253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm3 [IQR 368-571], the median plasma HIV-1 RNA 4.7 log10 copies/ml [IQR 4.0-5.2], and the median HIV-1 DNA 2.9 log10 copies/million PBMC [IQR 2.5-3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68-4.22) for patients with HIV-1 DNA ≥3 log10 copies/million PBMC vs. others, and 2.10 (95% CI, 1.38-3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log10 copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24-3.52, p= 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant. INTERPRETATION: In these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era. FUNDING: This trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253).

Dynamics of Plasmodium falciparum genetic diversity among asymptomatic and symptomatic children in three epidemiological areas in Cote d'Ivoire.

Asymptomatic carriers of Plasmodium are considered a reservoir of the parasite in humans. Therefore, in order to be effective, new malaria elimination strategies must take these targets into account. The aim of this study was to analyse genetic diversity of Plasmodium falciparum among schoolchildren in three epidemiological areas in Côte d'Ivoire. This was a cross-sectional study carried out from May 2015 to April 2016 in a primary school in rural and urban areas of San Pedro, Grand-Bassam and Abengourou, during the rainy season and the dry season. A total of 282 Plasmodium falciparum isolates were genotyped using Nested PCR of Pfmsp1 and Pfmsp2 genes. The overall frequency of K1, Mad20 and RO33 alleles was 81.6%, 53.4% and 57% for Pfmsp1 respectively. For Pfmsp2, this frequency was 84.3% and 72.2% for 3D7 and FC27. K1, Mad20 and FC27 Frequencies were significantly higher in Abengourou compared to other sites. Overall, the frequency of MIs was significantly higher in Abengourou for Pfmsp1 and Pfmsp2. However, Mad20 and RO33 alleles were significantly higher in the rainy season. No significant difference was observed between Pfmsp2 alleles in both seasons. Frequency of the 3D7 allele was significantly higher in symptomatic patients. MIs and COI increased with parasitemia for Pfmsp1and Pfmsp2. The data can be added to that available for monitoring and control of P. falciparum malaria. Further studies combining the entomological inoculation rate and the genetic diversity of P. falciparum will allow us to shed light on our understanding of the epidemiology of this parasite.