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Camille Maadjhou Mba,1 Wilfred Mbacham,1 Eugène Sobngwi,2,3 Jean Claude Mbanya2,3 1Department of Physiological Sciences/Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; 2Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; 3National Obesity Center and Endocrine and Metabolic Diseases Unit, Yaoundé Central Hospital, Yaoundé, CameroonCorrespondence: Camille Maadjhou MbaDepartment of Physiological Sciences/Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, PO Box 1364, Yaoundé, CameroonEmail camilya91@yahoo.frPurpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of circulating LDL cholesterol. There are inconsistent data in some populations concerning the association between PCSK9, LDL and CRP. The emerging importance of the inhibition of PCSK9 for the treatment of hypercholesterolemia warrants investigations in different populations. The aim of this study from a Sub-Saharan African population was to evaluate the association between PCSK9 and hs-CRP levels and plasma lipid levels in patients with type 2 diabetes (T2D) and obese and lean controls.Patients and methods: A cross-sectional analytical study was conducted in a major hospital in Yaoundé, Cameroon in a cohort of 162 participants (53% females). There were 54 non-obese T2D patients matched for age and sex to 54 obese nondiabetic and 54 nondiabetic lean subjects. PCSK9 level was assessed by sandwich ELISA method and hsCRP by nephelometry.Results: PCSK9 and hs-CRP levels were significantly higher in obese and T2D subjects when compared to lean controls (pr=0.56, p=0.02 and r=0.2 and p=0.1, respectively). Multilinear regression analysis identified BMI as an independent predictor for PCSK9 levels and this association was maintained after adjustment for confounders; adjusted β-coefficient; 36.1 (95% CI; 29.2–47.4). We did not find an association between PCSK9 and any plasma lipid levels in obese and T2D subjects, nor between PCSK9 and hs-CRP levels.Conclusion: Obese and type 2 diabetes subjects have higher PCSK9 levels when compared to lean controls, suggesting that these metabolic states potentially impact PCSK9 levels in Cameroonian patients.Keywords: PCSK9, LDL-cholesterol, type 2 diabetes, obesity

Carine Nguefeu Nkenfou,1,2 Barbara Atogho Tiedeu,1,2 Celine Nguefeu Nkenfou,3–5 Akindeh M Nji,1,2 Jean Paul Chedjou,1,2 Calvino Tah Fomboh,2,6 Charles Kouanfack,7,8 Wilfred F Mbacham1,2,91Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon; 2The Biotechnology Center, University of Yaoundé I, Yaoundé, Cameroon; 3Systems Biology, Chantal Biya’ International Reference Centre for Research on HIV and AIDS Prevention and Management (CBIRC), Yaoundé, Cameroon; 4Department of Biology, Higher Teachers’ Training College, University of Yaoundé I, Yaoundé, Cameroon; 5Molecular Biology Center Yaoundé, Yaoundé, Cameroon; 6Catholic University of Yaoundé (UCAC), Yaoundé, Cameroon; 7Day Care Unit, Central Hospital Yaoundé, Yaoundé, Cameroon; 8Department of Public Health, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon; 9Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CameroonCorrespondence: Wilfred F MbachamLaboratory for Public Health Research Biotechnologies, Biotechnology Center (BTC), P.O. Box 3851, Nkolbisson, Yaounde, CameroonTel +237-677579180Email wfmbacham@yahoo.comPurpose: The metabolism of antiretroviral drugs is subject to individual variations of the CYP 2B6 gene. The objective of this study was to evaluate the prevalence of CYP 2B6 516 G>T and 983 T>C polymorphisms and investigate their association with the development of adverse drug reactions (ADRs) in people living with HIV/AIDS in Cameroon.Patients and methods: A total number of 122 patients, attending the Yaoundé Central Hospital HIV Day Clinic, consented to take part in this study. Blood specimens were collected and DNA was extracted using the Chelex method. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed for the detection of CYP 2B6 Single-Nucleotide Polymorphisms (SNPs). Genotype frequencies were compared between groups with or without ADRs. Logistic regression analysis was performed to assess association between genotype and adverse effects of antiretroviral therapy (ART).Results: Three types of metabolizers were identified: extensive, intermediate and slow. For the 516G>T polymorphism, prevalences of 8.2% GG, 65.6% GT and 26.2% TT were obtained. For the 983T>C polymorphism, 89.3% TT, 4.1% CT and 6.6% CC prevalences were obtained. Those homozygous for the wild-type allele (516GG) were less likely to develop ADR with a statistically significant difference (OR=0.885, P=0.029). For the CYP2B6 T983C SNP, homozygous mutants (CC) may present a higher risk (threefold) of developing adverse reactions (OR=2.677, P=0.164).Conclusion: These findings demonstrate that ADRs among HIV/AIDS patients under ART may be associated with the genetic variability of the metabolizing enzyme CYP 2B6. Genotyping for this gene may guide the better administration of Efavirenz and Nevirapine to Cameroonian patients.Keywords: CYP 2B6 polymorphisms, association, adverse drug reactions, HIV/AIDS

Marie Nicole Ngoufack,1,2 Céline Nguefeu Nkenfou,2,3 Barbara Atogho Tiedeu,1 Linda Chapdeleine Mekue Mouafo,2,4 Beatrice Dambaya,2,5 Elvis Ndukong Ndzi,2,4 Charles Kouanfack,6 Georges Nguefack-Tsague,7 Wilfred Fon Mbacham,1 Alexis Ndjolo2 1Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon; 2Systems Biology, Chantal Biya’ International Reference Centre for Research on HIV and AIDS Prevention and Management (CBIRC), Yaoundé, Cameroon; 3Department of Biology, Higher Teachers’ Training College, University of Yaoundé I, Yaoundé, Cameroon; 4Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon; 5Department of Animal Sciences, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon; 6Department of Public Health, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon; 7Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CameroonCorrespondence: Céline Nguefeu NkenfouLaboratory of Systems Biology “Chantal Biya” International Reference Centre for Research on HIV and AIDS Prevention and Management (CBIRC), P.O. Box 3077, Messa, Yaoundé, CameroonTel +237 675 57 35 19Fax +237 222 3154 56Email nkenfou@yahoo.comBackground and objectives: The association of chemokine receptor-2 (CCR2) polymorphism with HIV transmission or disease progression remains highly controversial. The role of CCR2-64I allele in HIV infection may differ from one population to another because of their genetic background. The objectives of this study were to characterize the CCR2 genetic polymorphism and to determine its potential effect in HIV acquisition in children living in the Northern Region of Cameroon.Materials and methods: A cross-sectional study was carried out in five health facilities in the Northern region of Cameroon. DNA was extracted from the Buffy coat of each participant using the QIAamp®DNA mini kit. The DNA extract was then subjected to polymorphic analyses. CCR2 genotypes were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The Chi-Squared test was used for the assessment of the Hardy-Weinberg equilibrium.Results: A total of 134 children under 15 years comprised of 38 HIV-exposed infected (28.36%) and 96 HIV-exposed un-infected (71.64%) participants were recruited. Prevalences of 44.78% wild type homozygous, 48.52% heterozygous and 6.7% mutant homozygous alleles were found in the overall population. An allelic frequency of 29.69% for the mutant allele CCR2-64I was found in HIV-exposed un-infected individuals as compared to 34.21% in HIV-infected children (p=0.47).Conclusion: The CCR2-64I allele is relatively common in the Northern Region of Cameroon, with a similar distribution among HIV-exposed un-infected and infected children. As this allele alone does not seem to confer protection against HIV-1 infection, further studies using genotype-combination of CCR2 polymorphism and other single nucleotide polymorphisms would be of great relevance in both HIV prevention and novel therapeutic strategies.Keywords: HIV acquisition, CCR2 gene, pediatric population

Abstract Background Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. Methods Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. Results The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 μM and 13.0 μM) and falcipain-2 (IC50s 35.4 and 6.1 μM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 μg/ml and compounds (1) and (2) values of 6.3 and 36.1 μM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight. Conclusions Fractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate.

Abstract Background Governments and donors all over Africa are searching for sustainable, affordable and cost-effective ways to improve the quality of malaria case management. Widespread deficiencies have been reported in the prescribing and counselling practices of health care providers treating febrile patients in both public and private health facilities. Cameroon is no exception with low levels of adherence to national guidelines, the frequent selection of non-recommended antimalarials and the use of incorrect dosages. This study evaluates the effectiveness and cost-effectiveness of introducing two different provider training packages, alongside rapid diagnostic tests (RDTs), designed to equip providers with the knowledge and practical skills needed to effectively diagnose and treat febrile patients. The overall aim is to target antimalarial treatment better and to facilitate optimal use of malaria treatment guidelines. Methods/Design A 3-arm stratified, cluster randomized trial will be conducted to assess whether introducing RDTs with provider training (basic or enhanced) is more cost-effective than current practice without RDTs, and whether there is a difference in the cost effectiveness of the provider training interventions. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit public and mission health facilities. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider knowledge. Costs will be estimated from a societal and provider perspective using standard economic evaluation methodologies. Trial Registration ClinicalTrials.gov: NCT00981877

Abstract Background Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches. Methods 3721 samples from five African countries, which were known to contain genotypically drug resistant parasites, were analysed. These parasites were collected from patients who subsequently failed to clear their infection following drug treatment, as expected, but also from patients who successfully cleared their infections with drug-resistant parasites. 67 human polymorphisms (SNPs) on 17 chromosomes were analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify regions of the human genome, which contribute to enhanced clearance of drug resistant parasites. Results An analysis of all data from the five countries revealed significant associations between the phenotype of ability to clear drug-resistant Plasmodium falciparum infection and human immune response loci common to all populations. Overall, three SNPs showed a significant association with clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384 (95% CI 0.71-0.92, P = 0.005), 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P = 0.03), and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05), after adjustment for possible confounding factors. The first two SNPs (rs2706384 and rs1805015) are within loci involved in pro-inflammatory (interferon-gamma) and anti-inflammatory (IL-4) cytokine responses. The third locus encodes a protein involved in the degradation of misfolded proteins within the endoplasmic reticulum, and its role, if any, in the clearance phenotype is unclear. Conclusions The study showed significant association of three loci in the human genome with the ability of parasite to clear drug-resistant P. falciparum in samples taken from five countries distributed across sub-Saharan Africa. Both SNP rs2706384 and SNP1805015 have previously been reported to be associated with risk of malaria infection in African populations. The loci are involved in the Th1/Th2 balance, and the association of SNPs within these genes suggests a key role for antibody in the clearance of drug-resistant parasites. It is possible that patients able to clear drug-resistant infections have an enhanced ability to control parasite growth.

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.

Abstract Background The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Methods Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. Results The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group. Conclusion AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. Trial registration NCT00484900 http://www.clinicaltrials.gov.

Abstract Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason for the failure of molecular resistance markers to live up to their potential is that data on the their prevalence is scattered in disparate databases with no linkage to the clinical, in vitro and pharmacokinetic data that are needed to relate the genetic data to relevant phenotypes. The ongoing replacement of older monotherapies for malaria by new, more effective combination therapies presents an opportunity to create an open access database that brings together standardized data on molecular markers of drug resistant malaria from around the world. This paper presents a rationale for creating a global database of molecular markers for drug resistant malaria and for linking it to similar databases containing results from clinical trials of drug efficacy, in vitro studies of drug susceptibility, and pharmacokinetic studies of antimalarial drugs, in a World Antimalarial Resistance Network (WARN). This database will be a global resource, guiding the selection of first line drugs for treating uncomplicated malaria, for preventing malaria in travelers and for intermittent preventive treatment of malaria in pregnant women, infants and other vulnerable groups. Perhaps most important, a global database for molecular markers of drug resistant malaria will accelerate the identification and validation of markers for resistance to artemisinin-based combination therapies and, thereby, potentially prolong the useful therapeutic lives of these important new drugs.

Competing Interests: The authors declare no conflict of interest related to this Opinion paper. OA has served as a paid consultant to the World Health Organization, including its Global Malaria Program, and was founding director of the Affordable Medicines Facility for Malaria. PY is a globally recognized expert in supply chain management. RP has served as Director of the United States President’s Malaria Initiative. WM is Executive Director of the Multilateral Initiative on Malaria.

Introduction: in areas with intense perennial malaria transmission, limited data is available on the impact of environmental conditions especially rainfall on naturally acquired immunity against promising malaria vaccine candidates. For this reason, we have compared IgG antibody responses specific to Plasmodium spp. derived MSP3 and UB05 vaccine candidates, in plasma of children living in two areas of Cameroon differing in rainfall conditions., Methods: data about children less than 5 years old was collected during the years 2017 and 2018. Next malaria asymptomatic P. falciparum (Pf) infected children were selected following malaria test confirmation. MSP3 and UB05 specific IgG antibody responses were measured in participant´s plasma using enzyme-linked immunosorbent assay (ELISA)., Results: interestingly, IgG antibody responses specific to UB05 were significantly higher (p<0.0001) in Pf-negative children when compared to their asymptomatic Pf-infected counterparts living in monomodal rainfall areas. In contrast, a significantly higher (p<0.0001) IgG response to MSP3 was observed instead in asymptomatic Pf-infected children in the same population. In addition, IgG responses specific to UB05 remained significantly higher in bimodal when compared to monomodal rainfall areas irrespective of children´s Pf infection status (p<0.0055 for Pf-positive and p<0.0001 for negative children). On the contrary, IgG antibody responses specific to MSP3 were significantly higher in bimodal relative to monomodal rainfall areas (P<0.0001) just for Pf-negative children., Conclusion: thus IgG antibody responses specific to UBO5 are a better correlate of naturally acquired immunity against malaria in Pf-negative Cameroonian children especially in monomodal rainfall areas., Competing Interests: The authors declare no competing interests., (Copyright: Loveline Ngu et al.)

Background: Accurate, cost-effective, and noninvasive alternative molecular methods are needed for detecting low malaria parasitemia. The currently-used nested polymerase chain reaction (nPCR) requires blood as well as skilled personnel in order to minimise the risk of bloodborne disease transmission. Therefore, this study is aimed at assessing the accuracy of a noninvasive and more affordable malaria diagnosis with saliva using the loop-mediated isothermal amplification (LAMP) technique., Methods: A cross-sectional study was conducted in the Centre and Southwest regions of Cameroon. Matched blood and saliva samples collected from symptomatic and asymptomatic participants were tested for malaria using rapid diagnostic tests, microscopy, PCR, and LAMP. Statistics were performed using R studio software at 95% confidence interval., Results: A total of 100 participants (65% symptomatic and 35% asymptomatic) aged between 1 and 74 years with a balanced gender distribution ratio of 1.08 were included in our study. The prevalence of malaria was 61%, 57%, 59%, 42%, 35%, 17%, and 16% for blood-RDT, blood-PCR, blood-LAMP, blood-RT-LAMP, saliva-PCR, saliva-RT-LAMP, and saliva-LAMP, respectively. Both saliva and blood showed a sensitivity of 43.90% and respective specificities of 68.75% and 57.62%. When using RT-LAMP, sensitivities of 49.38% and 48.21% and specificities of 94.11% and 66.67% were recorded for saliva and blood, respectively. Sensitivities of 70.23% and 73.49% and specificities of 62.5% and 76.47% were recorded, respectively, for saliva-LAMP and saliva-RT-LAMP when compared to saliva-PCR as the gold standard. Saliva-LAMP and saliva-RT-LAMP had a fair agreement ( к = 0.221 and 0.352, respectively) with saliva-PCR. Homemade LAMP and RT-LAMP technologies match the WHO recommendations and after proper validation in a larger sample size, could serve for malaria diagnosis in developing countries., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Palmer Masumbe Netongo et al.)

Background: Despite the introduction of efficacious interventions for malaria control, sub-Saharan Africa continues to bear the highest burden of malaria and its associated effects on vulnerable populations, such as pregnant women and children. This meta-ethnographic review contributes to literature on malaria in pregnancy interventions in sub-Saharan Africa by offering insights into the multiple factors that motivate or demotivate women from accessing MiP interventions., Methods: A meta-ethnographic approach was used for the synthesis. Original qualitative research articles published from 2010 to November 2021 in English in sub-Saharan Africa were searched for. Articles focusing on WHO's recommended interventions such as intermittent preventive treatment with sulfadoxine-pyrimethamine, long-lasting insecticidal nets and testing and treatment of Malaria in Pregnancy (MiP) were included. Selected articles were uploaded into Nvivo 11 for thematic coding and synthesis., Results: Twenty-seven original qualitative research articles were included in the analysis. Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women's knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather condition and nearness to a health facility. Factors that demotivated women from using MiP services were: (1) stock-outs, ANC charges and health providers failure to provide women with ample education on the need for MiP care; (2) perception of not being at risk and the culture of self-medication; (3) fear of being bewitched if pregnancy was noticed early, women's lack of decision-making power and dependence on traditional remedies and (4) warm weather, long distances to health facilities and the style of construction of houses making it difficult to hang LLINs., Conclusions: Health system gaps need to be strengthened in order to ensure that MiP interventions become accessible to women. Additionally, health managers need to involve communities in planning, designing and implementing malaria interventions for pregnant women. It is important that the health system engage extensively with communities to facilitate pregnant women and communities understanding of MiP interventions and the need to support pregnant women to access them., (© 2022. The Author(s).)

Background: Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana., Methods: This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcribed and imported into NVivo for analysis. Using the World Health Organization (WHO) Health Systems Framework as the theoretical basis, thematic analysis was conducted under broad themes of the building blocks. Findings are presented in narrative quotes, with a mindmap used to summarize the various health system factors and their interrelated relationship influencing the delivery of IPTp-SP and ITN., Results: Health system factors identified included health staff untrained on malaria delivery directives due to an ineffective trainer of trainer (ToT) system. Additionally, health worker confusion on when to commence SP (at quickening or ≥ 16 weeks) was found to result in delayed start of SP. Stock-outs in facilities due to procurement delays at the national level resulted in missed opportunities to deliver SP to eligible pregnant women at the ANC. Similarly, ITN stock outs led to eligible pregnant women not receiving one at ANC clinics., Conclusion: Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC., (© 2022. The Author(s).)

Background: Procalcitonin is an inflammatory marker strongly associated with the presence of bacterial infection. It has been considered raised in severe malaria infection as opposed to uncomplicated malaria. There are suggestions that it may be raised only when there is concomitant unnoticeable bacterial infection during a malaria crisis. We aimed to assess the difference in plasma procalcitonin levels between children affected by severe and uncomplicated malaria., Methods: We assessed plasma procalcitonin levels in 83 children diagnosed with malaria with no clinical and biological evidence of concomitant bacterial infection. Severity of malaria was established using WHO guidelines. Procalcitonin was determined using the ELISA method. Non-parametric Mann-Whitney U test was used to compare medians across the 2 groups. Statistical significance was set for all p values < 0.05., Results: Of the 83 participants, 28 had uncomplicated malaria, and 55 had severe malaria. PCT levels were obtained in 24 and 40 subjects of each group, respectively, and were similar in both groups; [2.76 (2.52-2.93) vs 2.74 (2.52-2.98) ng/ml, p = 0.916]. The parasite density was lower in the uncomplicated malaria group than in the severe malaria group, but not statistically significant; [22,192 (9110-44 654) vs 31 684 (13 960-73 500) parasites/μl, p = 0.178]. There was no correlation between the parasite density in the general study population and PCT levels (r = 0.072, p = 0.572)., Conclusion: In the absence of overt bacterial infection, procalcitonin levels are not different between children affected with uncomplicated malaria and those with severe malaria. Therefore, bacterial infection should be thoroughly checked for in children with raised serum procalcitonin diagnosed with severe malaria., (© 2022. The Author(s).)

Haptoglobin is a protein involved in protecting the body from the harmful effects of free hemoglobin. The haptoglobin gene exhibits a polymorphism, and the different genotypes do not have the same capacity to combat the free hemoglobin effects. The present study aimed at determining the polymorphic distribution of haptoglobin in sickle cell patients (SCPs) from West Cameroon and their impact on the hematological parameters, as well as clinical manifestations of the disease severity. Haptoglobin genotype of 102 SCPs (SS) and 115 healthy individuals (60 AA and 55 AS) was determined by allele-specific polymerase chain reaction, and the complete blood count was determined using the AutoAnalyser. Results showed that the genotype Hp2-2 was significantly ( p  < 0.05) represented in SS patients (54%) than in controls AA and AS (27% and 29%, respectively), while Hp2-1 was mostly found ( p  < 0.05) in AS (42%) and AA (38%), against 15% in SS. The allelic distribution in SS patients was Hp 2 : 0.613, Hp 1S : 0.304, and Hp 1F : 0.084. In AA and AS controls, the proportions of the Hp 1 and Hp 2 alleles were similar (around 0.5 each), with 0.282 for Hp 1S and 0.218 for Hp 1F in AS and 0.283 for Hp 1S and 0.258 for Hp 1F in AA. The distribution of the haptoglobin genotypes did not reveal any significant difference across hematological parameters and clinical manifestations of disease severity in SCP and controls. SCP with Hp1S-1F genotype presented the highest level of hemoglobin. Although Hp2-2 was more frequent in SS patients, it appeared not to be related to the hematological parameters and to the disease's severity. Further investigations are necessary to explore the impact of Hp polymorphism such as antioxidant, lipid profile, and functionality of some tissues in SCP in Cameroon., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Christian Bernard Kengne Fotsing et al.)

Introduction: Malaria interventions including use of Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment (IPTp-SP) and distribution of Insecticide Treated Nets (ITNs) have been implemented through ante-natal clinic (ANC) services in Ghana. Yet, the high ANC attendance is not commensurate with the uptake of these interventions, with missed opportunities to deliver the interventions. This study sought to assess the health system factors affecting access and delivery of IPTp-SP and ITN as defined by the Ghana Malaria Policy Guideline to eligible pregnant women attending ANC clinic sessions., Methods: A quantitative cross-sectional study was conducted in the Volta Region of Ghana, with data collected across three levels of health care delivery facilities, including hospitals, health centres and Community-Based Health Planning Service (CHPS) compounds. Data collection included structured observation checklists to document the communication and interaction between the ANC health staff and pregnant women. Additionally, structured questionnaires were used to elicit information on cadre, trainings attended, knowledge and delivery practices of health workers on IPTp-SP and ITN. Stata 16 was used for data analysis, and a defined delivery algorithm was used to compute appropriate and inappropriate delivery practices, using the Ghana policy directive as a guide. Predictors of appropriate delivery were determined using logistic regression analysis., Results: Approximately 97% of the 680 ANC observations had complete information for analysis. Of these, 78% (511/657) were eligible for IPTp-SP after excluding women who have less than 16 weeks of gestation, G6PD deficient, malaria positive and have taken 5 doses of IPTp-SP prior to day of observation. Appropriate delivery of IPTp-SP was 76% (390/511). Despite the availability of SP, 15% (75/511) of all eligible women were not offered the medication and 37% (44/119) of inappropriate delivery was recorded during periods of stock out. ITNs were appropriately delivered to 59% (139) out of 237 eligible women. Thirty-two percent (77/237) of eligible women, mostly continuing ANC clients, were not given ITN despite stock availability., Conclusions: IPTp-SP was appropriately delivered to most of the eligible pregnant women compared to ITN. While stock out of both intervention could account for inappropriate delivery, despite stock availability, IPTp-SP and ITN were not delivered to some eligible women., (© 2021. The Author(s).)

Objective Inflammatory markers such as C-reactive protein and procalcitonin have been shown to be independent markers of cardiovascular diseases. We aimed to assess the correlation between serum levels of procalcitonin, C-reactive protein and cardiovascular risk in type 2 diabetes. Methods We carried out a cross-sectional study at a tertiary level reference hospital in Yaounde, Cameroon. We assessed the cardiovascular risk using the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) cardiovascular risk prediction model in 80 adults with type 2 diabetes. Serum procalcitonin and C-reactive protein were measured in 80 and 76 subjects respectively, using a highly sensitive quantitative enzyme-linked immunosorbent assay (ELISA) method. Correlations were examined using Spearman's rank correlation test and the correlation coefficients were compared using the Z-test statistic. Results Females represented the majority of the study population (62.5%). The median duration of diabetes was 5 (3-10) years and 62.5% of participants had a high cardiovascular risk score. Median serum procalcitonin levels was significantly higher in females compared to male participants: 2.48 (1.76-3.01 ng/mL) vs 1.42 (0.86-1.87 ng/mL); p<0.001. There was no difference in the serum C-reactive protein levels between females and males: 1.20 (0.33-3.33) mg/L vs 0.85 (0.36-2.77) mg/L; p=0.669. Procalcitonin was moderately correlated with cardiovascular risk (r=0.58, p<0.001). The correlation was slightly higher in females (R=0.56, p<0.001) versus males (R=0.49, p=0.005) although not significantly different (Z-statistic=0.734, p=0.463). Serum C-reactive protein did not show a meaningful correlation with cardiovascular risk (R=0.23, p=0.050). At a threshold of 2 ng/ml, serum procalcitonin identified participants with a high cardiovascular risk score, with a sensitivity and specificity of 64% and 80% respectively. Conclusion Compared to C-reactive protein, procalcitonin may be a better surrogate marker for cardiovascular risk prediction in this population with type 2 diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Katte et al.)

Background: The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal., Methods: Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens' collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software., Results: Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months; P  = .46, Mann-Whitney U -test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site ( P  < .001) and CD4 < 350 cells/mm 3 ( P  < .006). Strong correlates of DR also included Saint-Louis ( P  < .009), CD4 < 350 cells/mm 3 ( P  <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies; P  < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75], P  = .038), self-reported missing doses (OR = 3.30 [1.13-10.24], P  = .029), and medical appointments (OR = 2.91 [1.05-8.47], P  = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35], P  = .035)., Conclusion: At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Co-infection with malaria and intestinal parasites is common in children in Africa and may affect their immune response to a malaria parasite infection. Prior studies suggest that co-infections may lead to increased susceptibility to malaria infection and disease severity; however, other studies have shown the reverse. Knowledge on how co-morbidities specifically affect the immune response to malaria antigens is limited. Therefore, this study sought to determine the prevalence of co-infection of malaria and intestinal parasites and its association with antibody levels to malaria merozoite antigens., Methods: A cross sectional study was carried out in two villages with high transmission of malaria in Cameroon (Ngali II and Mfou) where mass drug administration (MDA) had been administered at ~6-month intervals (generally with albendazole or mebendazole). Children aged 1-15 years were enrolled after obtaining parental consent. A malaria rapid diagnostic test was used on site. Four (4) ml of peripheral blood was collected from each participant to determine Plasmodium falciparum infections by microscopy, haemoglobin levels and serology. Fresh stool samples were collected and examined by wet mount, Kato-Katz method and modified Ritchie concentration techniques. A Multiplex Analyte Platform assay was used to measure antibody levels., Results: A total of 320 children were enrolled. The prevalence of malaria by blood smear was 76.3% (244/320) and prevalence of malaria and intestinal parasites was 16.9% (54/320). Malaria prevalence was highest in young children; whereas, intestinal parasites (IP+) were not present until after 3 years of age. All children positive for malaria had antibodies to MSP142, MSP2, MSP3 and EBA175. No difference in antibody levels in children with malaria-co infections compared to malaria alone were found, except for antibody levels to EBA-175 were higher in children co-infected with intestinal protozoa (p = 0.018), especially those with Entamoeba histolytica infections (p = 0.0026)., Conclusion: Antibody levels to EBA175 were significantly higher in children co-infected with malaria and E. histolytica compared to children infected with malaria alone. It is important to further investigate why and how the presence of these protozoans might modulate the immune response to malaria antigens., Competing Interests: The authors have declared that no competing interests exist.

Background: There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given., Methods: Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007-2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones., Results: Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of < 5-year-olds not prescribed ACT ranged up to 41.8% across sites. The odds of not being prescribed an ACT were 2-32 times higher for patients in settings with lower-transmission intensity (using test positivity as a proxy) compared to areas of higher transmission. mRDT-positive children in low-transmission settings were especially likely not to be prescribed ACT, with proportions untreated up to 70%. Of the 7426 mRDT-positive patients not prescribed an ACT, 4121 (55.5%) were prescribed other, non-recommended non-ACT antimalarial medications, and the remainder (44.5%) were prescribed no antimalarial., Conclusions: In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children < 5 years and those in low-transmission settings, were most likely to not be prescribed antimalarials, and young children in low-transmission settings were least likely to be treated for malaria. This major public health risk must be addressed in training and practice., Trial Registration: Reported in individual primary studies.

Background: Several studies have demonstrated the role of meteorological parameters in the seasonality of influenza viruses in tropical and subtropical regions, most importantly temperature, humidity, and rainfall., Objectives: This study aimed to describe the influence of meteorological parameters in the seasonality of influenza viruses in Northern Cameroon, a region characterized by high temperatures., Methods: This was a retrospective study performed in Garoua Cameroon from January 2014 to December 2016. Monthly proportions of confirmed influenza cases from six sentinel sites were considered as dependent variables, whereas monthly values of mean temperature, average relative humidity, and accumulated rainfall were considered as independent variables. A vector error correction model was used to determine the relationship between influenza activity and the meteorological variables., Results and Conclusion: Analysis showed that there was a statistically significant association between overall influenza activity and influenza A activity with respect to average relative humidity. A unit increase in humidity within a given month leads to more than 85% rise in the overall influenza and influenza A activity 2 months later. Meanwhile, none of the three meteorological variables could explain influenza B activity. This observation is essential in filling the gap of knowledge and could help in the prevention and control strategies to strengthen influenza surveillance program in Cameroon., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

In 2009, Influenza A(H1N1)pdm09 caused the first influenza pandemic of the 21st century with high mortality rates of about 284 500 deaths. This virus, however, continues to circulate as a seasonal influenza virus and to cause illness and deaths worldwide. In this study, we describe the genetic diversity of A(H1N1)pdm09 viruses collected between 2014 and 2016 in Cameroon. Three gene segments (HA, NA and M) of Cameroon strains were studied. The phylogenetic tree of the coding nucleotide sequences was generated by MEGA version 6.0 using a Maximum Likelihood method. The NA and M protein coding sequences were analyzed for the reported genetic markers of resistance against neuraminidase inhibitors and adamantanes, while predicted vaccine efficacy was estimated using the Pepitope method. Overall 39 strains were obtained. Phylogenetic analysis of the HA gene of influenza A(H1N1)pdm09 showed that Cameroon strains belonged to two major clades. The 2014 Cameroon sequences belonged to clade 6C while all sequences collected between 2015 and 2016 belonged to clade 6B. Majority of the samples had some mutations in the NA gene notably: I117M, N248D, and N369K while the amantadine-resistant M mutant, S31N, was found to be absent only in the two sequences collected in 2014. Overall, A/California/07/2009 vaccine strain showed a predicted vaccine efficacy of 24.55% to 35.77% against Cameroon A(H1N1)pdm09 strains circulating between 2014 and 2016. Our findings confirms the fast evolution of A(H1N1)pdm09 since its first introduction and highlights on the importance of influenza vaccine in reducing the burden caused by influenza in the community., Competing Interests: The authors have declared that no competing interests exist.

In May 2016, highly pathogenic avian influenza virus of the subtype A/H5N1 was detected in Cameroon in an industrial poultry farm at Mvog-Betsi, Yaoundé (Centre region), with a recorded sudden increase of deaths among chickens, and an overall mortality rate of 75%. The virus spread further and caused new outbreaks in some parts of the country. In total, 21 outbreaks were confirmed from May 2016 to March 2017 (six in the Centre, six in the West, eight in the South and one in the Adamaoua regions). This resulted in an estimated total loss of 138,252 birds (44,451 deaths due to infection and 93,801 stamped out). Only domestic birds (chickens, ducks and geese) were affected in farms as well as in poultry markets. The outbreaks occurred in three waves, the first from May to June 2016, the second in September 2016 and the last wave in March 2017. The topology of the phylogeny based on the haemagglutinin gene segment indicated that the causative H5N1 viruses fall within the genetic clade 2.3.2.1c, within the same group as the A/H5N1 viruses collected in Niger in 2015 and 2016. More importantly, the gene constellation of four representative viruses showed evidence of H5N1/H9N2 intra-clade reassortment. Additional epidemiological and genetic data from affected countries in West Africa are needed to better trace the origin, spread and evolution of A/H5N1 in Cameroon. RESEARCH HIGHLIGHTS HPAI A/H5N1 was detected in May 2016 in domestic chickens in Yaoundé-Cameroon. Twenty-one outbreaks in total were confirmed from May 2016 to March 2017. The causative H5N1 viruses fall within the genetic clade 2.3.2.1c. The viral gene constellation showed evidence of H5N1/H9N2 intra-clade reassortment.

Objective: Mycobacterium tuberculosis isolates that fail to hybridize to at least one rpoB wild-type or any mutation probe on the Genotype MTBDRplus strip are assumed to be rifampicin-resistant. However, the precise mutation(s) are unknown. We sought to identify the mutations in isolates with such hybridization patterns and determine if the mutations are associated with resistance to rifampicin., Methods: In this study, 275 M. tuberculosis isolates were screened with the Genotype MTBDRplus assay to identify isolates with the hybridization pattern. These isolates were sequenced and their minimum inhibitory concentrations (MIC) determined using the Bactec MGIT 960 system., Results: Among the 275 isolates tested, 15 (6%) isolates with the hybridization pattern were identified. Sequencing showed that failure to hybridize to rpoB wild-type probes resulted from the presence of 'disputed' rifampicin mutations, which are mutations not always associated with a rifampicin-resistant phenotype. All, except 3/15, isolates had a rifampicin-resistant phenotype (MIC > 1 μg/mL). One of the three isolates with a rifampicin-susceptible phenotype had the same mutation at position 526 (His526Leu) as another isolate that had a rifampicin-resistant phenotype., Conclusion: The recommendation of the Genotype MTBDRplus assay to assume rifampicin resistance based solely on failure to hybridize to rpoB wild-type probe allows the identification of important RIF-resistant isolates. About 20% (3/15) of such isolates could be missed by relying only on the standard MGIT 960 DST assay for drug susceptibility testing., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Hypertension holds a unique place in population health and health care because it is the leading cause of cardiovascular disease and the most common noncommunicable condition seen in primary care worldwide. Without effective prevention and control, raised blood pressure significantly increases the risk of stroke, myocardial infarction, chronic kidney disease, heart failure, dementia, renal failure, and blindness. There is an urgent need for stakeholders-including individuals and families-across the health system, researchers, and decision makers to work collaboratively for improving prevention, screening and detection, diagnosis and evaluation, awareness, treatment and medication adherence, management, and control for people with or at high risk for hypertension. Meeting this need will help reduce the burden of hypertension-related disease, prevent complications, and reduce the need for hospitalization, costly interventions, and premature deaths., Objective: This review aims to synthesize evidence on the epidemiological landscape and control of hypertension in Cameroon, and to identify elements that could potentially inform interventions to combat hypertension in this setting and elsewhere in sub-Saharan Africa., Methods: The full search process will involve several steps, including selecting relevant databases, keywords, and Medical Subject Headings (MeSH); searching for relevant studies from the selected databases; searching OpenGrey and the Grey Literature Report for gray literature; hand searching in Google Scholar; and soliciting missed publications (if any) from relevant authors. We will select qualitative, quantitative, or mixed-methods studies with data on the epidemiology and control of hypertension in Cameroon. We will include published literature in French or English from electronic databases up to December 31, 2016, and involving adults aged 18 years or older. Both facility and population-based studies on hypertension will be included. Two reviewers of the team will independently search, screen, extract data, and assess the quality of selected studies using suitable tools. Selected studies will be analyzed by narrative synthesis, meta-analysis, or both, depending on the nature of the data retrieved in line with the review objectives., Results: This review is part of an ongoing research program on disease prevention and control in the context of the dual burden of communicable and noncommunicable diseases in Africa. The first results are expected in 2017., Conclusions: This review will provide a comprehensive assessment of the burden of hypertension and control measures that have been designed and implemented in Cameroon. Findings will form the knowledge base relevant to stakeholders across the health system and researchers who are involved in hypertension prevention and control in the community and clinic settings in Cameroon, as a yardstick for similar African countries., Trial Registration: PROSPERO registration number: CRD42017054950; http://www.crd.york.ac.uk/PROSPERO/ display&#95;record.asp?ID=CRD42017054950 (Archived by WebCite at http://www.webcitation.org/6qYSjt9Jc)., (©Barthelemy Kuate Defo, Jean Claude Mbanya, Jean-Claude Tardif, Olugbemiga Ekundayo, Sylvie Perreault, Louise Potvin, Robert Cote, Andre Pascal Kengne, Simeon Pierre Choukem, Felix Assah, Samuel Kingue, Lucie Richard, Roland Pongou, Katherine Frohlich, Jude Saji, Pierre Fournier, Eugene Sobngwi, Valery Ridde, Marie-Pierre Dubé, Simon De Denus, Wilfred Mbacham, Jean-Philippe Lafrance, Dickson Shey Nsagha, Warner Mampuya, Anastase Dzudie, Lyne Cloutier, Christina Zarowsky, Agatha Tanya, Paul Ndom, Marie Hatem, Evelyne Rey, Louise Roy, Roxane Borgès Da Silva, Christian Dagenais, David Todem, Robert Weladji, Dora Mbanya, Elham Emami, Zakariaou Njoumemi, Laurence Monnais, Carl-Ardy Dubois. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 29.05.2017.)

Background: In sub-Saharan Africa, intense perennial Plasmodium species transmission coincides with areas of high prevalence of the human immunodeficiency virus type 1 (HIV) infection. This implies that antiretroviral naïve HIV-infected people living within these regions are repeatedly exposed to Plasmodium species infection and consequently malaria. Natural killer (NK) cells are known to contribute to malaria immunity through the production of IFN-γ after exposure to Plasmodium falciparum -infected erythrocytes (infected red blood cells [iRBC]). However, in antiretroviral naïve HIV-1 infection, these functions could be impaired. In this study we assess the ability of NK cells from antiretroviral naïve HIV-1-infected people to respond to iRBC., Method: Magnetically sorted NK cells from antiretroviral naïve HIV-1-infected people were tested for their ability to respond to iRBC following in vitro coculture. NK cell IFN-γ production after coculture was measured through multiparametric flow cytometry analysis., Results: Our data show a significant reduction ( p = 0.03) in IFN-γ production by NK cells from antiretroviral naïve HIV-1-infected people after coculture with iRBCs. This was in contrast to the NK cell response from healthy controls, which demonstrated elevated IFN-γ production. NK cell IFN-γ production from untreated HIV-1-infected participants correlated inversely with the viral load ( r = -0.5, p = 0.02) and positively with total helper CD4 + T-cell count ( r = 0.4, p = 0.04). Thus, antiretroviral naïve HIV-1 infection can dampen NK cell-mediated immunity to P. falciparum infection in malaria-intense regions. This could in effect escalate morbidity and mortality in people chronically infected with HIV-1., (Copyright © 2017 by S. Karger AG, Basel.)

Objectives: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts., Design: A comparative case study approach, analysing variation in outcomes across different settings., Setting: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case., Participants: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria., Interventions: The interventions included different mRDT training packages, supervision, supplies and community sensitisation., Outcome Measures: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial)., Results: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs., Conclusions: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Severe malaria is a leading cause of morbidity and mortality in under-fives in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. Artesunate has been shown to be cost-effective in African children, but whether these findings are transferable to Cameroonian children remains to be explored., Objectives: To conduct a cost-analysis of four different regimens used in the treatment from the perspective of the healthcare payer., Methods: An economic evaluation alongside a randomized comparative study was conducted in children aged 3 months to 15 years, admitted at the Ebolowa Regional Hospital with severe malaria due to Plasmodium falciparum. Patients were randomized to receive one of the four treatment alternatives. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H 0 , H 12 , H 24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 h later by an 8-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 h, and Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. The main outcome measure for effectiveness of treatment was the parasite reduction rate. Based on a healthcare perspective, an evaluation of direct medical costs was done, including costs of anti-malarials, nursing care materials, adjuvant treatment, laboratory investigations, hospitalisation and professional fees. Guided by a cost minimalization approach, the relative costs of these treatment alternatives was compared and reported., Results: Overall cost was higher for ARTES group at $65.14 (95% CI $57.68-72.60) than for quinine groups ($52.49-$62.40), but the difference was not statistically significant. Cost of the anti-malarial drug was significantly higher for artesunate-treated patients than for quinine-treated patients, whereas cost of hospitalization was significantly lower for artesunate-treated patients than for quinine-treated patients. Incremental analysis of ARTES against QLD as a baseline resulted in an ICER of $46.8/PRR 24 and suggests ARTES as the most cost effective of all four treatment options., Conclusion: Artesunate is a cost effective malaria treatment option relative to quinine alternatives with the lowest incremental cost per unit of effectiveness. Trial registration clinicaltrials.gov identifier: NCT02563704. Registered 19 September 2015, retrospectively registered.

The World Health Organization (WHO) classifies snake bites as neglected public health problem affecting mostly tropical and subtropical countries. In Africa there are an estimated 1 million snake bites annually with about half needing a specific treatment. Women, children and farmers in poor rural communities in developing countries are the most affected. Case management of snake bites are not adequate in many health facilities in developing countries where personnel are not always abreast with the new developments in snake bite management and in addition, quite often the anti-venom serum is lacking. We report the case of a medical doctor bitten by a cobra in the rural area of Poli, Cameroon while asleep in his bedroom. Lack of facilities coupled with poor case management resulted in a fatal outcome., Competing Interests: The authors declare no competing interests.

Background: Artemisinin combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Cameroon since 2004 and Nigeria since 2005, though many febrile patients receive less effective antimalarials. Patients often rely on providers to select treatment, and interventions are needed to improve providers' practice and encourage them to adhere to clinical guidelines., Methods: Providers' adherence to malaria treatment guidelines was examined using data collected in Cameroon and Nigeria at public and mission facilities, pharmacies and drug stores. Providers' choice of antimalarial was investigated separately for each country. Multilevel logistic regression was used to determine whether providers were more likely to choose ACT if they knew it was the first-line antimalarial. Multiple imputation was used to impute missing data that arose when linking exit survey responses to details of the provider responsible for selecting treatment., Results: There was a gap between providers' knowledge and their practice in both countries, as providers' decision to supply ACT was not significantly associated with knowledge of the first-line antimalarial. Providers were, however, more likely to supply ACT if it was the type of antimalarial they prefer. Other factors were country-specific, and indicated providers can be influenced by what they perceived their patients prefer or could afford, as well as information about their symptoms, previous treatment, the type of outlet and availability of ACT., Conclusions: Public health interventions to improve the treatment of uncomplicated malaria should strive to change what providers prefer, rather than focus on what they know. Interventions to improve adherence to malaria treatment guidelines should emphasize that ACT is the recommended antimalarial, and it should be used for all patients with uncomplicated malaria. Interventions should also be tailored to the local setting, as there were differences between the two countries in providers' choice of antimalarial, and who or what influenced their practice., (Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014.)

Background: Severe malaria is a medical emergency with high mortality in children below 5 years of age especially in sub-Saharan Africa. Recently, quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. No local data are yet available on the efficacy of artesunate with respect to the different quinine regimens used in this setting. This study was undertaken at the Ebolowa Regional Hospital (ERH), which is located in a region of perennial transmission of malaria., Methods: This was a randomized, open-label trial in children aged 3 months to 15 years, admitted in the hospital with severe malaria due to Plasmodium falciparum confirmed on microscopy after informed parental consent. Patients were randomized into four groups. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H0, H12, H24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 hours later by an eight-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 hours; and, Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. All patients invariably received a minimum of 24 h parenteral treatment, then, oral drugs were prescribed. The endpoints were fever clearance time, time to sit unsupported, time to eat, parasite clearance time, and parasitaemia reduction rate at H24. Survival analysis was used to compare the outcomes., Results: One-hundred and sixteen patients completed the study: 29 in ARTES arm, 28 in QLD arm, 30 in QNLD3 arm, and 29 in QNLD2 arm. There was no major differences in baseline characteristics in the treatment groups. On analysis of endpoints, fever clearance time and parasite clearance time were significantly shorter for artesunate-treated patients than for quinine-treated patients. Parasitaemia reduction rate at H24 was also significantly higher for artesunate. Time to sit unsupported and time to eat were shorter with artesunate, but the difference was not statistically significant., Conclusion: Artesunate is more effective than quinine in the treatment of severe malaria in Cameroonian children.