Peter M. Ndumbe

Bacterial vaginosis and HIV acquisition: A meta-analysis of published studies

Objectives:To assess and summarize the published literature on the extent to which bacterial vaginosis may increase the risk of HIV acquisition. Design:Meta-analysis of published studies. Methods:Medline and other electronic databases were systematically searched for eligible publications. The association between bacterial vaginosis and incident HIV was separately analyzed from that between bacterial vaginosis and prevalent HIV. The latter was further analyzed, stratified by bacterial vaginosis diagnostic method, HIV risk profile of the study population, and whether or not adjusted estimates were presented. Results:Twenty-three eligible publications were identified, including a total of 30 739 women. Bacterial vaginosis was associated with an increased risk of HIV acquisition in HIV-incidence studies (relative risk = 1.6, 95% confidence interval: 1.2, 2.1). All but one of 21 HIV-prevalence studies reported estimates above the null. The latter results were heterogeneous and showed some evidence of funnel plot asymmetry, precluding the estimation of a single summary measure. The association between bacterial vaginosis and HIV in prevalence studies appeared stronger for women without high-risk sexual behavior. Conclusion:Bacterial vaginosis was consistently associated with an increased risk of HIV infection. High bacterial vaginosis prevalence may result in a high number of HIV infections being attributable to bacterial vaginosis. More prospective studies are needed to accurately evaluate the role of bacterial vaginosis in HIV acquisition in low-risk versus high-risk women. Furthermore, randomized clinical trials may be worth considering to determine the effect of bacterial vaginosis control measures on HIV acquisition.

Individual and contextual factors associated with low childhood immunisation coverage in sub-Saharan Africa: a multilevel analysis

Background In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and Findings We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12–23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. Conclusion We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live.

Development and Application of a Broadly Sensitive Dried-Blood-Spot-Based Genotyping Assay for Global Surveillance of HIV-1 Drug Resistance

ABSTRACT As antiretroviral therapy (ART) is scaled up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first-line ART. We have developed and applied a broadly sensitive dried-blood-spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS samples were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (n = 58), Tanzania (n = 60), and China (n =53). In addition, 30 DBS and 40 plasma specimens collected from ART patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed at the protease and RT regions, 149 (87.1%) could be genotyped, including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART patient samples analyzed, 100% (30/30) of the Chinese DBS and 90% (36/40) of the Cameroonian plasma specimens were genotyped, including 8 samples with a viral load of <400 copies/ml. The results of phylogenetic analyses indicated that the subtype, circulating recombinant form (CRF), and unique recombinant form (URF) distribution was as follows: 73 strains were subtype C (34%), 37 were subtype B (17.2%), 24 each were CRF01_AE or CRF02_AG (11.2% each), 22 were subtype A1 (10.2%), and 9 were unclassifiable (UC) (4.2%). The remaining samples were minor strains comprised of 6 that were CRF07_BC (2.8%), 5 that were CRF10_CD (2.3%), 3 each that were URF_A1C and CRF08_BC (1.4%), 2 each that were G, URF_BC, and URF_D/UC (0.9%), and 1 each that were subtype F1, subtype F2, and URF_A1D (0.5%). Our results indicate that this broadly sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found.

Design and evaluation of an in-house HIV-1 (group M and O), SIVmnd and SIVcpz antigen capture assay.

An enzyme-linked immuno-sorbent assay (ELISA) for the detection of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIVcpz/SIVmnd) antigens was designed using immunoreagents from naturally infected individuals, and compared to the commercially available Vironostika HIV-1 Antigen Microelisa System (Organon Teknika). The in-house assay proved to be specific for HIV-1 isolates belonging to group M (A-H) and group O and for SIVcpz and SIVmnd isolates, but was less sensitive than the Vironostika HIV-1 Antigen Microelisa System, except for SIVmnd. For the strains belonging to HIV-2, SIVmac and SIVagm, the in-house assay could not detect antigen to an appreciable degree. This study shows that a considerably less expensive but sufficiently accurate HIV-1 antigen capture assay can be developed to monitor HIV-1 (group M and O), SIVcpv and SIVmnd antigen in the supernatants of virus cultures.

Increasing the value of health research in the WHO African Region beyond 2015—reflecting on the past, celebrating the present and building the future: a bibliometric analysis

Objective To assess the profile and determinants of health research productivity in Africa since the onset of the new millennium. Design Bibliometric analysis. Data collection and synthesis In November 2014, we searched PubMed for articles published between 2000 and 2014 from the WHO African Region, and obtained country-level indicators from World Bank data. We used Poisson regression to examine time trends in research publications and negative binomial regression to explore determinants of research publications. Results We identified 107 662 publications, with a median of 727 per country (range 25–31 757). Three countries (South Africa, Nigeria and Kenya) contributed 52% of the publications. The number of publications increased from 3623 in 2000 to 12 709 in 2014 (relative growth 251%). Similarly, the per cent share of worldwide research publications per year increased from 0.7% in 2000 to 1.3% in 2014. The trend analysis was also significant to confirm a continuous increase in health research publications from Africa, with productivity increasing by 10.3% per year (95% CIs +10.1% to +10.5%). The only independent predictor of publication outputs was national gross domestic product. For every one log US

Predominance of infection with HIV-1 circulating recombinant form CRF02_AG in major Cameroonian cities and towns.

billion increase in gross domestic product, research publications rose by 105%: incidence rate ratio (IRR=2.05, 95% CI 1.39 to 3.04). The association of private health expenditure with publications was only marginally significant (IRR=1.86, 95% CI 1.00 to 3.47). Conclusions There has been a significant improvement in health research in the WHO African Region since 2000, with some individual countries already having strong research profiles. Countries of the region should implement the WHO Strategy on Research for Health: reinforcing the research culture (organisation); focusing research on key health challenges (priorities); strengthening national health research systems (capacity); encouraging good research practice (standards); and consolidating linkages between health research and action (translation).

Prevalence of infections affecting the child among pregnant women in Yaounde, Cameroon

Our observations add to previous results on molecular epidemiology in different provinces in Cameroon demonstrating a high prevalence of CRF02_AG and subtype A accounting for 90% of circulating HIV-1 strains. The country-wide high prevalence of HIV-1 CRF02_AG in Cameroon compared with the relatively low prevalence of CRF02_AG in the Democratic Republic of Congo suggest an early founder effect of this AG recombinant in West Central Africa initiating major CRF02 epidemics. (excerpt)

Interpatient genetic variability of HIV-1 group O.

The prevalence of infections which have deleterious effects to either the mother or the fetus during pregnancy are unknown in Cameroon. To formulate appropriate antenatal screening policies for the Central Mother and Child Clinic in Yaounde, we tested random sera obtained from 1,014 stored samples previously obtained from pregnant women. One hundred and fifty sera were tested for the presence of the hepatitis B surface antigen (HBsAg), 544 for syphilis antibodies, 192 for antibodies to rubella and 192 for antibodies to Toxoplasma gondii. We found the HBsAg in 25.3% (38/150) of the subjects, antibodies against syphilis in 15.9% (87/544), antibodies to the rubella virus in 83.9% (161/192) and evidence of toxoplasma infection in 77.1 % (148/192). Of the 38 HBsAg-positive subjects, 5.2% and 55.3% were positive for the HBe antigen and HBe antibody, respectively. We found a high prevalence of these infections in the antenatal clinic attendants. The data will be used to develop an appropriate control strategy for them.

European and Developing Countries Clinical Trials Partnership (EDCTP): The Path Towards a True Partnership.

OBJECTIVE To analyse the genetic and phylogenetic characteristics of HIV-1 group O viruses. MATERIALS AND METHODS The env gene, encoding the gp160 glycoprotein, and a partial p24-encoding gag gene fragment of a Cameroonian (CA9) and a Gabonese (VI686) HIV-1 group O virus, isolated from cultured peripheral blood mononuclear cells of symptomatic patients, were sequenced, aligned with other representatives of group O for which the same region has been documented, and genetically and phylogenetically analysed. RESULTS Phylogenetic analysis of the env gene (gp160) revealed that CA9, VI686, ANT70, and four Ha strains formed a separate cluster, which was supported by 100% of all bootstrap trees. In addition, these seven isolates were part of the same clade in the p24 phylogeny. VAU and MVP5180 may represent two other subtypes. CONCLUSION We have characterized two group O viruses, originating from Cameroon and Gabon, which show a close evolutionary relationship to ANT70 and four Ha strains based on the entire env gene, suggestive of a first group O subgroup, tentatively named the HIV-1 group O env ANT70 clade or subtype.

Seroprevalence of hepatitis and HIV infection among rural pregnant women in Cameroon.

BackgroundEuropean and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases.MethodsEDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts.ResultsThe following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached € 150 m, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities.ConclusionWhile we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to lead to a sustainable programme. Current data shows that the number of projects supported by EDCTP is increasing. DCCC proposes that this success story of true partnership should be used as model by partners involved in the fight against other infectious diseases of public health importance in the region.