BackgroundThe use of drug combinations, including non-artemisinin-based and artemisinin-based combination therapy (ACT), is a novel strategy that enhances therapeutic efficacy and delays the emergence of multidrug-resistant Plasmodium falciparum. Its use is strongly recommended in most sub-Saharan African countries, namely Cameroon, where resistance to chloroquine is widespread and antifolate resistance is emerging.MethodsStudies were conducted in Cameroonian children with acute uncomplicated P. falciparum malaria according to the standard World Health Organization protocol at four sentinel sites between 2003 and 2007. A total of 1,401 children were enrolled, of whom 1,337 were assigned to randomized studies and 64 were included in a single non-randomized study. The proportions of adequate clinical and parasitological response (PCR-uncorrected on day 14 and PCR-corrected on day 28) were the primary endpoints to evaluate treatment efficacy on day 14 and day 28. The relative effectiveness of drug combinations was compared by a multi-treatment Bayesian random-effect meta-analysis.FindingsThe results based on the meta-analysis suggested that artesunate-amodiaquine (AS-AQ) is as effective as other drugs (artesunate-sulphadoxine-pyrimethamine [AS-SP], artesunate-chlorproguanil-dapsone [AS-CD], artesunate-mefloquine [AS-MQ], dihydroartemisinin-piperaquine [DH-PP], artemether-lumefantrine [AM-LM], amodiaquine, and amodiaquine-sulphadoxine-pyrimethamine [AQ-SP]). AM-LM appeared to be the most effective with no treatment failure due to recrudescence, closely followed by DH-PP.ConclusionAlthough AM-LM requires six doses, rather than three doses for other artemisinin-based combinations, it has potential advantages over other forms of ACT. Further studies are needed to evaluate the clinical efficacy and tolerance of these combinations in different epidemiological context.

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BackgroundCoinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon.MethodsA retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine.ResultsOf 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm3 (interquartile range [IQR] 67-218), 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 × 107 IU/mL for HBV (IQR 3680-1.59 × 108) and 928 000 IU/mL for HCV (IQR 178 400-2.06 × 106). Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p < 0.01). The response to antiretroviral therapy was however comparable between monoinfected and coinfected patients in terms of CD4 cell count increase (p = 0.8), HIV-1 viral load below 400 copies/mL (p = 0.9), death (p = 0.3) and death or new AIDS-defining event (p = 0.1). Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity.ConclusionThis study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be a decisive argument for testing when hepatitis status is unknown.

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BackgroundDespite the progress in the Prevention of the Mother-to-Child Transmission of HIV (PMTCT), the paediatric HIV epidemic remains worrying in Cameroon. HIV prevalence rate for the population of pregnant women was 7.6 % in 2010 in Cameroon. The extent of the paediatric HIV epidemic is needed to inform policymakers. We developed a stochastic simulation model to estimate the number of new paediatric HIV infections through MTCT based on the observed uptake of services during the different steps of the PMTCT cascade in Cameroon in 2011. Different levels of PMTCT uptake was also assessed.MethodsA discrete events computer simulation-based approach with stochastic structure was proposed to generate a cohort of pregnant women followed-up until 6 weeks post-partum, and optionally until complete breastfeeding cessation in both prevalent and incident lactating HIV-infected women. The different parameters of the simulation model were fixed using data sources available from the 2011 national registry surveys, and from external cohorts in Cameroon. Different PMTCT coverages were simulated to assess their impact on MTCT. Available data show a low coverage of PMTCT services in Cameroon in 2011.ResultsBased on a simulation approach on a population of 995, 533 pregnant women, the overall residual MTCT rate in 2011 was estimated to be 22.1 % (95 % CI: 18.6 %–25.2 %), the 6-week perinatal MTCT rate among prevalent HIV-infected mothers at delivery is estimated at 12.1 % (95 % CI: 8.1 %–15.1 %), with an additional postnatal MTCT rate estimated at 13.3 % (95 % CI: 9.3 %–17.8 %). The MTCT rate among children whose mothers seroconverted during breastfeeding was estimated at 20.8 % (95 % CI: 14.1 %–26.9 %). Overall, we estimated the number of new HIV infections in children in Cameroon to be 10, 403 (95 % CI: 9, 054–13, 345) in 2011. When PMTCT uptake have been fixed at 100 %, 90 % and 80 %, global MTCT rate failed to 0.9 % (95 % CI: 0.5 %–1.7 %), 2.0 % (95 % CI: 0.9 %–3.2 %) and 4.3 % (95 % CI: 2.4 %–6.7 %) respectively.ConclusionsThis model is helpful to provide MTCT estimates to guide the national HIV policy in Cameroon. Increasing supply and uptake of PMTCT services among prevalent HIV infected pregnant women, as well as HIV-prevention interventions including the offer and acceptance of HIV testing and counselling in lactating women could reduce significantly the residual HIV MTCT in Cameroon. A public health effort should be made to encourage health care workers and pregnant women to use PMTCT services until complete breastfeeding cessation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1336-2) contains supplementary material, which is available to authorized users.

BackgroundMalaria remains a burden in Sub-Saharan Countries. The strategy proposed by the World Health Organization (WHO) is to systematically compare the therapeutic efficacy of antimalarial drugs using as primary outcome for efficacy, a four-category ordered criterion. The objective of the present work was to analyze the treatment effects on this primary outcome taking into account both a center-effect and individual covariates. A three-arm, three-centre trial of Amodiaquine (AQ), sulfadoxine-pyrimethamine (SP) and their combination (AQ + SP), conducted by OCEAC-IRD in 2003, in 538 children with uncomplicated Plasmodium falciparum malaria, is used as an illustration.MethodsAnalyses were based on ordinal regression methods, assuming an underlying continuous latent variable, using either the proportional odds (PO) or the proportional hazards (PH) models. Different algorithms, corresponding to both frequentist- and bayesian-approaches, were implemented using the freely available softwares R and Winbugs, respectively. The performances of the different methods were evaluated on a simulated data set, and then they were applied on the trial data set.ResultsGood coverage probability and type-1 error for the treatment effect were achieved. When the methods were applied on the trial data set, results highlighted a significance decrease of SP efficacy when compared to AQ (PO, odds ratio [OR] 0.14, 95% confidence interval [CI] 0.04-0.57; hazard ratio [HR] 0.605, 95% CI 0.42-0.82), and an equal effectiveness between AQ + SP and AQ (PO, odds ratio [OR] 1.70, 95% confidence interval [CI] 0.25-11.44; hazard ratio [HR] 1.40, 95% CI 0.88-2.18). The body temperature was significantly related to the responses. The patient weights were marginally associated to the clinical response.ConclusionThe proposed analyses, based on usual statistical packages, appeared adapted to take into account the full information contained in the four categorical outcome in malaria trials, as defined by WHO, with the possibility of adjusting on individual and global covariates.

We establish, by means of a large class of continuous t-representable intuitionistic fuzzy t-conorms, a factorization of an intuitionistic fuzzy relation IFR into a unique indifference component and a family of regular strict components. This result generalizes a previous factorization obtained by Dimitrov 2002 with the max, min intuitionistic fuzzy t-conorm. We provide, for a continuous t-representable intuitionistic fuzzy t-norm T, a characterization of the T-transitivity of an IFR. This enables us to determine necessary and sufficient conditions on a T-transitive IFR R under which a strict component of R satisfies pos-transitivity and negative transitivity.

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