Abstract
Background
Africa bears a disproportionately high burden of globally significant disease but has lagged in knowledge production to address its health challenges. In this contribution, we ...discuss the challenges and approaches to health research capacity strengthening in sub-Saharan Africa and propose that the recent shift to an African-led approach is the most optimal.
Methods and findings
We introduce several capacity building approaches and recent achievements, explore why African-led research on the continent is a potentially paradigm-shifting and innovative approach, and discuss the advantages and challenges thereof. We reflect on the approaches used by the African Academy of Sciences (AAS)-funded Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) consortium as an example of an effective African-led science and capacity building programme. We recommend the following as crucial components of future efforts: 1. Directly empowering African-based researchers, 2. Offering quality training and career development opportunities to large numbers of junior African scientists and support staff, and 3. Effective information exchange and collaboration. Furthermore, we argue that long-term investment from international donors and increasing funding commitments from African governments and philanthropies will be needed to realise a critical mass of local capacity and to create and sustain world-class research hubs that will be conducive to address Africa’s intractable health challenges.
Conclusions
Our experiences so far suggest that African-led research has the potential to overcome the vicious cycle of brain-drain and may ultimately lead to improvement of health and science-led economic transformation of Africa into a prosperous continent.
One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for ...manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 μl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.
Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to ...date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.
Summary Background Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV ...transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. Methods We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001–02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. Findings We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55·1% to 92·7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60·3% to 94·2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35·7% to 60·3% of heterosexually transmitted HIV infections that would otherwise occur. Interpretation Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples. Funding US National Institute of Mental Health, National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, Fogarty AIDS International Training and Research Program, Emory Center for AIDS Research, and the International AIDS Vaccine Initiative.
Rwanda 20 years on: investing in life Binagwaho, Agnes, Dr; Farmer, Paul E, MD; Nsanzimana, Sabin, MD ...
Lancet,
07/2014, Letnik:
384, Številka:
9940
Journal Article
Recenzirano
Odprti dostop
Summary Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a ...devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwanda's health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.
Rwanda has high unmet need for family planning (FP), especially in the postpartum period when women are advised to space pregnancies at least two years for improved maternal-child health. Despite ...interest in the copper intrauterine device (IUD), a highly cost-effective method, access and uptake remain low. This study aimed to determine factors associated with postpartum IUD (PPIUD) uptake after postpartum family planning (PPFP) counseling as well as provider perceptions of facilitators and barriers to clients' PPIUD uptake. Postpartum women who received PPFP counseling and were less than 6 weeks postpartum were recruited for a case-control study in Kigali, Rwanda in 2018. We recruited n = 74 women who had accepted and n = 91 women who had declined the PPIUD. Multivariate logistic regression analyses evaluated associations between women's socio-demographics, FP knowledge and decision-making, and the outcome of PPIUD uptake. Six focus groups (FGs) were conducted with FP providers (n = 24) and community health workers (n = 17) trained to deliver PPFP counseling to assess perceptions of PPFP counseling and facilitators and barriers to PPIUD uptake. FG discussions were recorded, translated, and analyzed for themes. Factors associated (P<0.1) with PPIUD uptake included citing its non-hormonal nature, effectiveness, and duration of protection against pregnancy as advantages. Exclusive male partner control over FP decisions (relative to women's control or joint decision-making) was associated with non-use. Overall, limited knowledge about some aspects of the PPIUD persisted among clients even after counseling. Provider FGs highlighted client concerns, inconsistent FP messaging, and lack of male partner involvement as factors influencing non-use. Knowledge of the IUD and its benefits was associated with PPIUD uptake. There is need to refine PPFP counseling messages to address remaining knowledge gaps and concerns. Additionally, male partner involvement in FP counseling and decisions with their partners could be a key strategy to increase both PPIUD and FP uptake in Rwanda.
The longstanding inadequacies of syndromic management for genital ulceration and inflammation are well-described. The Rwanda National Guidelines for sexually transmitted infection (STI) syndromic ...management are not yet informed by the local prevalence and correlates of STI etiologies, a component World Health Organization guidelines stress as critical to optimize locally relevant algorithms.
Radio announcements and pharmacists recruited symptomatic patients to seek free STI services in Kigali. Clients who sought services were asked to refer sexual partners and symptomatic friends. Demographic, behavioral risk factor, medical history, and symptom data were collected. Genital exams were performed by trained research nurses and physicians. We conducted phlebotomy for rapid HIV and rapid plasma reagin (RPR) serologies and vaginal pool swab for microscopy of wet preparation to diagnose Trichomonas vaginalis (TV), bacterial vaginosis (BV), and vaginal Candida albicans (VCA). GeneXpert testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were conducted. Here we assess factors associated with diagnosis of NG and CT in men and women. We also explore factors associated with TV, BV and VCA in women. Finally, we describe genital ulcer and RPR results by HIV status, gender, and circumcision in men.
Among 974 men (with 1013 visits), 20% were positive for CT and 74% were positive for NG. Among 569 women (with 579 visits), 17% were positive for CT and 27% were positive for NG. In multivariate analyses, factors associated with CT in men included younger age, responding to radio advertisements, <17 days since suspected exposure, and not having dysuria. Factors associated with NG in men included not having higher education or full-time employment, <17 days since suspected exposure, not reporting a genital ulcer, and having urethral discharge on physical exam. Factors associated with CT in women included younger age and < = 10 days with symptoms. Factors associated with NG in women included younger age, lower education and lack of full-time employment, sometimes using condoms vs. never, using hormonal vs. non-hormonal contraception, not having genital ulcer or itching, having symptoms < = 10 days, HIV+ status, having BV, endocervical discharge noted on speculum exam, and negative vaginal wet mount for VCA. In multivariate analyses, only reporting >1 partner was associated with BV; being single and RPR+ was associated with TV; and having < = 1 partner in the last month, being pregnant, genital itching, discharge, and being HIV and RPR negative were associated with VCA. Genital ulcers and positive RPR were associated with being HIV+ and lack of circumcision among men. HIV+ women were more likely to be RPR+. In HIV+ men and women, ulcers were more likely to be herpetic rather than syphilitic compared with their HIV- counterparts.
Syndromic management guidelines in Rwanda can be improved with consideration of the prevalence of confirmed infections from this study of symptomatic men and women representative of those who would seek care at government health centers. Inclusion of demographic and risk factor measures shown to be predictive of STI and non-STI dysbioses may also increase diagnostic accuracy.
Antiretroviral therapy (ART) efficacy for HIV prevention among discordant couples has been demonstrated in clinical trials. Effectiveness outside of research settings is less well understood.
...HIV-discordant couples were enrolled in couples' testing and follow-up at 20 government clinics in Kigali from 2010 to 2014. We performed viral linkage analysis on seroconverting couples to determine infection sources (intracouple vs. extracouple). Antiretroviral therapy use in index partners was collected at baseline and during follow-up by self-report with verification of government medical records.
A total of 3777 HIV-discordant couples were identified and followed up at government health clinics. Fifty-four incident HIV infections were identified, of which 36 were confirmed linked to the index partner, 4 were unlinked, and 14 were unknown. Among the 50 linked or unknown transmission pairs, 38% occurred among couples in which the index partner was on ART (HIV incidence rate of 0.63/100 person-years), whereas 62% occurred among couples in which the index partner was not on ART (HIV incidence rate of 5.51/100 person-years; adjusted rate ratio, 6.9). HIV acquisition was higher in women than in men with non-ART using index partners (P < 0.001).
Couples in a government clinic couples' HIV testing and follow-up program in Rwanda had an 89% reduction in HIV incidence when index partners were using ART, slightly lower than efficacy estimates from randomized trials. Antiretroviral therapy for prevention should be prioritized for key populations including discordant couples identified via couples' voluntary counseling and testing, with increased efforts to improve uptake, adherence, and viral load monitoring.
A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust ...antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages.
PDF
