Efficacy of amodiaquine, sulphadoxine-pyrimethamine and their combination for the treatment of uncomplicated Plasmodium falciparum malaria in children in Cameroon at the time of policy change to artemisinin-based combination therapy

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The efficacy of amodiaquine (AQ), sulphadoxine-pyrimethamine (SP) and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time. Methods Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest), Yaoundé (forest-savannah mosaic) and Garoua (guinea-savannah). Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) or adequate clinical and parasitological response (ACPR). The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures. Results After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11%) and Pfmdr1 86Y mutations (73.83%) were associated with quinoline resistance in the south compared to the north, 31.67% (76T) and 22.08% (86Y). There was a significant variation (p < 0.001) of the prevalence of the SGK haplotype between Garoua in the north (8.33%), Yaoundé (36.29%) in the savannah-forest mosaic and Mutengene (66.41%) in the South of Cameroon and a weak relation between SGK haplotype and SP failure. The 540E mutation on the dhps gene was extremely rare (0.3%) and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites. Conclusion In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that suggested alternative treatments were needed in Cameroon since 2005.Published versio

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Cameroon (2011): Etude TRaC sur l'utilisation des methodes de longue duree au Cameroun. Premier Passage

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An evaluation of human immunodeficiency virus oral screening test awareness and preferences in the West region of Cameroon

Summary: HIV serological diagnosis has evolved during the last decade to give rise to rapid testing using biological materials, such as blood or oral mucosal transudate (OMT). However, blood collection is not always welcomed, justifying the evaluation of OMT-based devices. In a cross sectional study carried out in May 2011 aimed at evaluating the level of awareness about OMT based HIV tests, questionnaires were administered to participants who consented to take part in the study. Eighty-five percent (n = 1520) of participants reported a lack of awareness of HIV oral screening before the study, and surprisingly, no association was found between the awareness of participants and their educational level (p = 0.768). There was also no association (p = 0.743) found between having had previous screening tests and awareness of oral testing. The percentage of participants who accepted the oral test before being informed about it was 31.3% (n = 1520). After sensitization, 76.3% (n = 1520) preferred oral screening for future tests (p = 0). These results reveal that if the OMT based test is affordable, its implementation as a screening tool in the general population could greatly increase participation in screening campaigns and is welcomed by those who want to self-test in a non-invasive way. This will create a better estimation of the national HIV prevalence. Its use could then have a significant public health impact on HIV prevention and clinical management. Keywords: Awareness, Control programs, HIV, Oral test, Preferenc

Rates of HBV, HCV, HDV and HIV type 1 among pregnant women and HIV type 1 drug resistance-associated mutations in breastfeeding women on antiretroviral therapy

Abstract Background HBV, HCV, HDV and HIV are blood borne and can be transmitted from mother-to-child. Reports of HBV infection rates show up to 11.9% in Cameroon while for HCV, the rate is less than 2%. More so, as pregnant women get enrolled in the HIV PMTCT Programme and stay in the care continuum, selection of HIV-1 drug resistant strains is evident. We sought to determine the seroprevalence of HBV, HCV, HDV and HIV among pregnant women, assess their knowledge, attitudes and practices on transmission and prevention of HBV infection, and determine HIV drug resistance profile of breastfeeding women. Methods A serosurvey of HBV, HCV, HDV and HIV was carried out among 1005 pregnant women in Yaounde, Cameroon. In 40 HIV-infected breastfeeding women enrolled in the PMTCT Programme, HIV-1 genotypes and HIV-1 resistance to NRTIs, NNRTIs and PIs, were determined by phylogeny and the Stanford University HIV Drug Resistance interpretation tool, respectively. Results Among the pregnant women, the rates of HIV-1, HBV, HCV and HDV infections were 8.5, 6.4, 0.8 and 4.0%, respectively. About 5.9% of the women knew their HBV status before pregnancy unlike 63.7% who knew their HIV status. Although 83.3% reported that vaccination against HBV infection is a method of prevention, and 47.1% knew that HBV could be transmitted from mother-to-child, only 2.5% had received the Hepatitis B vaccine. Of the 40 women on antiretroviral therapy (ART), 9 had at least one major resistance-associated mutation (RAM, 22.5%) to NRTI, NNRTI or PI. Of these M184 V (12.5%), K70R (10.0%), K103 N (12.5%), Y181C (10.0%), M46 L (2.5%) and L90 M (2.5%) were most frequently identified, suggesting resistance to lamivudine, nevirapine, efavirenz and zidovudine. Eighty four percent were infected with HIV-1 recombinant strains with CRF02_AG predominating (50%). Conclusions The rates of HBV and HIV-1 infections point to the need for early diagnosis of these viruses during pregnancy and referral to care services in order to minimize the risk of MTCT. Furthermore, our results would be useful for evaluating the HIV PMTCT Programme and Treatment Guidelines for Cameroon

Host candidate gene polymorphisms and associated clearance ofP. falciparumamodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon

Background: In this post-hoc analysis, we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon.<p></p> Methods: Human DNA from 760 patients from a previous clinical trial was subjected to mass spectrometry-based single nucleotide polymorphism (SNP) genotyping. Allele frequencies of candidate immune genes were calculated for 62 SNPs on 17 human chromosomes for their possible involvement in clearance of drug-resistant parasites with the triple mutations of pfcrt76T, pfmdr86Y, and pfmdr1246Y (TY) and pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps437G (IRNG) which were determined by dotblot or PCR-restriction analysis. Differences in SNP frequencies and association analysis were carried out by comparing Chi-square odds ratios (ORs) and stratified by Mantel–Haenzel statistics. An adjusted P value (OR) <0·0008 was considered significant.<p></p> Results: Post-treatment drug failure rates were amodiaquine (36·4%); sulpadoxine/pyrimethamine-amodiaquine combination (15·4%); and sulphadoxine/pyrimethamine (18·1%). SNPs in IL22, IL-4R1, and CD36 appeared to have been associated with clearance of resistant parasites [p  =  0·017, OR (C allele):1·44, 95% CI (OR): 1·06–1·95]; [P  =  0·014, OR  =  1·31, 95% CI (OR): 1·07–1·83]; [P  =  5·78×10−5, OR  =  0·27, 95%CI (OR): 0·13–0·54], respectively, with high fever (>39°C for 48 hours) [IL-22, P  =  0·01, OR  =  1·5, 95% CI (OR): 1·8–2·1] and also in high frequency among the Fulani participants [P  =  0·006, OR  =  1·83, 95% CI (OR): 1·11–3·08)]. The CD36-1264 null allele was completely absent in the northern population.<p></p> Conclusion: Independent association of SNPs in IL22 and IL-4 with clearance of amodiaquine- and sulphadoxine/pyrimethamine-resistant parasites did not reach statistical significance, but may suggest that not all drug-resistant mutants are adversely affected by the same immune-mediated mechanisms of clearance