Epidemics In sub-Saharan Africa Research Articles

Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher community viral load?

The HIV epidemic has carved contrasting trajectories around the world with sub-Saharan Africa (SSA) being most affected. We hypothesized that mean HIV-1 plasma RNA viral loads are higher in SSA than other areas, and that these elevated levels may contribute to the scale of epidemics in this region.To evaluate this hypothesis, we constructed a database of means of 71,668 viral load measurements from 44 cohorts in seven regions of the world. We used linear regression statistical models to estimate differences in viral load between regions. We also constructed and analyzed a mathematical model to describe the impact of the regional viral load differences on HIV epidemic trajectory.We found substantial regional viral load heterogeneity. The mean viral load in SSA was 0.58 log(10) copies/ml higher than in North America (95% confidence interval 0.45-0.71); this represents about a four-fold increase. The highest mean viral loads were found in Southern and East Africa, whereas in Asia, Europe, North America, and South America, mean viral loads were comparable. Mathematical modeling indicated that conservatively 14% of HIV infections in a representative population in Kenya could be attributed to the enhanced infectiousness of patients with heightened viral load.We conclude that community viral load appears to be higher in SSA than in other regions and this may be a central driver of the massive HIV epidemics in this region. The elevated viral loads in SSA may reflect, among other factors, the high burden of co-infections or the preponderance of HIV-1 subtype C infection.

Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher community viral load?

The HIV epidemic has carved contrasting trajectories around the world with sub-Saharan Africa (SSA) being most affected. We hypothesized that mean HIV-1 plasma RNA viral loads are higher in SSA than other areas, and that these elevated levels may contribute to the scale of epidemics in this region. To evaluate this hypothesis, we constructed a database of means of 71,668 viral load measurements from 44 cohorts in seven regions of the world. We used linear regression statistical models to estimate differences in viral load between regions. We also constructed and analyzed a mathematical model to describe the impact of the regional viral load differences on HIV epidemic trajectory. We found substantial regional viral load heterogeneity. The mean viral load in SSA was 0.58 log(10) copies/ml higher than in North America (95% confidence interval 0.45-0.71); this represents about a four-fold increase. The highest mean viral loads were found in Southern and East Africa, whereas in Asia, Europe, North America, and South America, mean viral loads were comparable. Mathematical modeling indicated that conservatively 14% of HIV infections in a representative population in Kenya could be attributed to the enhanced infectiousness of patients with heightened viral load. We conclude that community viral load appears to be higher in SSA than in other regions and this may be a central driver of the massive HIV epidemics in this region. The elevated viral loads in SSA may reflect, among other factors, the high burden of co-infections or the preponderance of HIV-1 subtype C infection.

High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria, Uganda.

IntroductionHIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour.MethodsBetween September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011–January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 18–49 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models.ResultsOverall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, p<0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR =1.50, 95%; 1.20, 1.87) and participants aged 30–39 years (adj.PPR=1.40, 95%; 1.10, 1.79) and 40–49 years (adj.PPR=1.41, 95%; 1.04, 1.92) compared to those aged 18–24 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p=0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p=0.004).ConclusionsThe HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the “high-risk” fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials.

Meningococcal meningitis epidemics in sub-Saharan Africa and the meningococcal A conjugate vaccine

Group A meningococci are primarily responsible for the epidemic meningococcal diseases in the countries of the meningitis belt of sub-Saharan Africa. In 1995-1996 major epidemics (>200000 cases) impeded effective management and ultimately resulted in many improvements. Since 2003, the Multi-Disease Center (MDSC) in Ouagadougou (Burkina Faso) and the WHO in Geneva have collected epidemiologic and laboratory data; new alert and epidemic thresholds are applied; and management has improved, with a single dose of ceftriaxone or of oily chloramphenicol now recommended. Trivalent ACW vaccine has been introduced against serogroup W135 epidemics. In 2010, preventive vaccination campaigns using the meningococcal conjugate vaccine MenAfriVac(®) began. Their use in all countries of the meningitis belt could eliminate serogroup A outbreaks in the region.

What Impact Will Reducing Concurrency Have on Decreasing the Incidence of HIV in Heterosexual Populations?

What Impact Will Reducing Concurrency Have on Decreasing the Incidence of HIV in Heterosexual Populations?

Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision

BackgroundA key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou...

Modelling the impact of antiretroviral therapy on the epidemic of HIV.

Thirty years after HIV first appeared it has killed close to 30 million people but transmission continues unchecked. In 2009, an estimated 1.8 million lives were lost and 2.6 million more people were infected with HIV [1]. To cut transmission, many social, behavioural and biomedical interventions have been developed, tested and tried but have had little impact on the epidemic in most countries. One substantial success has been the development of combination antiretroviral therapy (ART) that reduces viral load and restores immune function. This raises the possibility of using ART not only to treat people but also to prevent new HIV infections. Here we consider the impact of ART on the transmission of HIV and show how it could help to control the epidemic.Much needs to be known and understood concerning the impact of early treatment with ART on the prognosis for individual patients and on transmission. We review the current literature on factors associated with modelling treatment for prevention and illustrate the potential impact using existing models. We focus on generalized epidemics in sub-Saharan Africa, with an emphasis on South Africa, where transmission is mainly heterosexual and which account for an estimated 17% of all people living with HIV. We also make reference to epidemics among men who have sex with men and injection drug users where appropriate. We discuss ways in which using treatment as prevention can be taken forward knowing that this can only be the beginning of what must become an inclusive dialogue among all of those concerned to stop acquired immune deficiency syndrome (AIDS).

HIV, HSV-2 and syphilis among married couples in India: patterns of discordance and concordance

ObjectivesDifferences in sexual networks probably explain the disparity in the scale of HIV epidemics in sub-Saharan Africa and India. HIV and sexually transmitted infection (STI) discordant couple studies provide insights...

P1-81 HIV, HSV-2 and syphilis among married couples in India: patterns of discordance and concordance

IntroductionDifferences in sexual networks likely explain the disparity in the scale of HIV epidemics in sub-Saharan Africa and India. HIV and sexually transmitted infection (STI) discordant couple studies provide insights...

Incorporating household structure into a discrete-event simulation model of tuberculosis and HIV

Human immunodeficiency virus (HIV) increases the risks of developing tuberculosis (TB) disease following infection, and speeds up disease progression. This has had a devastating effect on TB epidemics in sub-Saharan Africa, where incidence rates have more than trebled in the past twenty years. Current control methods for TB disease have failed to keep pace with this growth, and there is an urgent need to find TB control strategies that are effective in high-HIV prevalent settings. This article describes a discrete-event simulation model of endemic TB that includes the effects of HIV and of household structure on the transmission dynamics of TB. Incorporating a social structure allows us to compare the effectiveness of contact-tracing interventions with case-finding targeted at high risk groups. We describe the modeling of the household structure in some detail, as this has applications to the modeling of other infectious diseases.

Socio-Demographic Characteristics and Behavioral Risk Factors of Female Sex Workers in Sub-Saharan Africa: A Systematic Review

Sex work remains an important contributor to HIV transmission within early, advanced and regressing epidemics in sub-Saharan Africa, but its social and behavioral underpinnings remain poorly understood, limiting the impact of HIV prevention initiatives. This article systematically reviews the socio-demographics of female sex workers (FSW) in this region, their occupational contexts and key behavioral risk factors for HIV. In total 128 relevant articles were reviewed following a search of Medline, Web of Science and Anthropological Index. FSW commonly have limited economic options, many dependents, marital disruption, and low education. Their vulnerability to HIV, heightened among young women, is inextricably linked to the occupational contexts of their work, characterized most commonly by poverty, endemic violence, criminalization, high mobility and hazardous alcohol use. These, in turn, predict behaviors such as low condom use, anal sex and co-infection with other sexually transmitted infections. Sex work in Africa cannot be viewed in isolation from other HIV-risk behaviors such as multiple concurrent partnerships-there is often much overlap between sexual networks. High turn-over of FSW, with sex work duration typically around 3 years, further heightens risk of HIV acquisition and transmission. Targeted services at sufficiently high coverage, taking into account the behavioral and social vulnerabilities described here, are urgently required to address the disproportionate burden of HIV carried by FSW on the continent.

Avidity of Serogroup A Meningococcal IgG Antibodies after Immunization with Different Doses of a Tetravalent A/C/Y/W135 Polysaccharide Vaccine

In the absence of an affordable conjugate meningococcal vaccine, mass vaccination campaigns with polysaccharide vaccines are the means to control meningitis epidemics in sub-Saharan Africa. Facing global vaccine shortage, the use of reduced doses, which have been shown to be protective by serum bactericidal activity, can save many lives. In this study, we investigated the antibody responses and avidity of IgG antibodies evoked against the serogroup A capsule of Neisseria meningitidis by different doses of an A/C/Y/W135 polysaccharide vaccine. Volunteers in Uganda were vaccinated with 1/10, 1/5 or a full dose (50 μg) and revaccinated with a full dose after 1 year. Specific IgG geometric mean concentrations and geometric mean avidity indices (GMAI) were determined by a modified enzyme-linked immunosorbent assay (ELISA) using thiocyanate as a chaotropic agent. After vaccination with 1/10 or 1/5 doses, the GMAI increased from 1 month to 1 year. One year following the initial dose, the GMAI levels were higher in the arm receiving reduced doses than for the arm receiving a full dose. Following the second full dose, avidity indices equalized at approximately the same level in the three arms. Although there are practical challenges to the use of reduced doses in the field, our findings suggest that reduced doses of polysaccharide vaccine are able to elicit antibodies of as good avidity against serogroup A polysaccharide as a full dose.

HIV and Concurrent Sexual Partnerships: Modeling the Role of Coital Dilution

Background: The concurrency hypothesis asserts that high prevalence of long-term, overlapping sexual partnerships explains extraordinarily high HIV levels in sub-Saharan Africa. Earlier simulation models show that the network effect of concurrency can increase HIV incidence, but these models do not account for the coital dilution effect (non-primary partnerships have lower coital frequency than primary partnerships). Methods: We modify the model of Eaton et al. (AIDS and Behavior September 2010) to incorporate coital dilution by assigning lower coital frequencies to non-primary partnerships. We parameterize coital dilution based on the empirical work of Morris et al. (PLoS ONE December 2010) and others. Following Eaton et al., we simulate the daily transmission of HIV over 250 years for 10 levels of concurrency. Results: At every level of concurrency, our focal coital-dilution simulation produces epidemic extinction. Our sensitivity analysis shows that this result is quite robust; even modestly lower coital frequencies in non-primary partnerships lead to epidemic extinction.Conclusion: In order to contribute usefully to the investigation of HIV prevalence, simulation models of concurrent partnering and HIV epidemics must incorporate realistic degrees of coital dilution. Doing so dramatically reduces the role that concurrency can play in accelerating the spread of HIV and suggests that concurrency cannot be an important driver of HIV epidemics in sub-Saharan Africa. Alternative explanations for HIV epidemics in sub-Saharan Africa are needed.

Exploring the condom gap: is supply or demand the limiting factor – condom access and use in an urban and a rural setting in Kilifi district, Kenya

to explore the extent of the condom gap, investigating the relative roles of supply-side and demand-side factors in determining condom use. GPS mapping of condom outlets, and population-based survey. an urban and a rural site were selected within the Epidemiological and Demographic Surveillance Site in Kilifi district, Kenya. Potential condom outlets (n = 281) were mapped and surveyed, and questionnaires on condom access and use (n = 630) were administered to a random sample of men and women aged 15-49. Multivariate logistic regression was performed to assess the relative roles of supply-side and demand-side barriers on condom use. the median straight-line distance to free condoms was 18-fold higher in the rural versus urban site. Among sexually active respondents, 42% had ever used a condom, and 23% had used a condom over the past 12 months, with lower levels among rural versus urban respondents (P < 0.05). The mean number of condoms used was 2.2/person per year among all sexually active individuals (condom users and nonusers), amounting to 8.2% protected sex acts/person per year. The adjusted odds of condom use (past 12 months) were 8.1 times greater among individuals experiencing no supply-side or demand-side barriers, compared with individuals experiencing both types of barriers. Despite low levels of usage and the presence of supply-side and demand-side barriers, reported unmet need for condoms was low. there is an urgent need for renewed condom promotion efforts aimed at building demand, in addition to improving physical access, in resource-limited settings with generalized HIV epidemics in sub-Saharan Africa.

HIV and concurrent sexual partnerships: modelling the role of coital dilution.

BackgroundThe concurrency hypothesis asserts that high prevalence of overlapping sexual partnerships explains extraordinarily high HIV levels in sub-Saharan Africa. Earlier simulation models show that the network effect of concurrency can increase HIV incidence, but those models do not account for the coital dilution effect (non-primary partnerships have lower coital frequency than primary partnerships).MethodsWe modify the model of Eaton et al (AIDS and Behavior, September 2010) to incorporate coital dilution by assigning lower coital frequencies to non-primary partnerships. We parameterize coital dilution based on the empirical work of Morris et al (PLoS ONE, December 2010) and others. Following Eaton et al, we simulate the daily transmission of HIV over 250 years for 10 levels of concurrency.ResultsAt every level of concurrency, our focal coital-dilution simulation produces epidemic extinction. Our sensitivity analysis shows that this result is quite robust; even modestly lower coital frequencies in non-primary partnerships lead to epidemic extinction.ConclusionsIn order to contribute usefully to the investigation of HIV prevalence, simulation models of concurrent partnering and HIV epidemics must incorporate realistic degrees of coital dilution. Doing so dramatically reduces the role that concurrency can play in accelerating the spread of HIV and suggests that concurrency cannot be an important driver of HIV epidemics in sub-Saharan Africa. Alternative explanations for HIV epidemics in sub-Saharan Africa are needed.

Vaccination strategies to combat an infectious globe: Oral cholera vaccines

Cholera is a substantial health burden in many countries in Africa and Asia, where it is endemic. It is as well responsible for ongoing epidemics in sub-Saharan Africa which are becoming greater in terms of frequency, extension, and duration. Given the availability of two oral cholera vaccines and the new data on their efficacy, field effectiveness, feasibility, and acceptance in cholera-affected populations and in travelers, these vaccines should be used in endemic areas, in travelers for these areas and should be considered in areas at risk for outbreaks. The two vaccines currently available in worldwide are: (1) The killed oral vaccine (Dukoral, licensed by SBL–Sweden to Crucell–Holland) is recommended since 1999 by WHO and consists of a mixture of four preparations of heat or formalin killed whole cell Vibrio cholera O1 (Inaba and Ogaba serotypes, and classical and El Tor biotypes) that are then added with purified recombinant cholera toxin (CT) B subunit. Because CT cross-reacts with Escherichia coli LT the vaccine also provides short-term protection against ETEC (enterotoxigenic E. coli) which is of added benefit for travelers. It is available in more than 60 countries. (2) A bivalent O1 and O139 whole cell oral vaccine without CT B subunit (Shanchol) has been lately developed in Vietnam (licensed by VaBiotech–Viet Nam to Shantha Biotechnics–India. It is available in India and Indonesia. A structured search of papers in PubMed and reports on cholera vaccines by WHO and CDC, as well as critical reading and synthesis of the information was accomplished. Inclusion criteria were defined according to reports quality and relevance.

Chronology and evolution of the HIV-1 subtype C epidemic in Ethiopia

To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world. HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003. Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models. Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for the origin of the clade. In addition, we reveal that the HIV-1C epidemic in Ethiopia has grown at a faster rate than the epidemic of subtype C in sub-Saharan Africa. Reconstruction of the epidemic history in Ethiopia revealed that subtype C likely originated from either a single lineage or multiple descendents in the late 1960s or early 1970s where it grew exponentially throughout the mid-1970s and early 1980s, corresponding to a wave of urbanization and migration. In light of these findings, we suggest that subtype C strains were circulating at least a decade before previous estimates and the first recognition of symptomatic patients in Ethiopia. The timing of the Ethiopian epidemic is also in agreement with similar HIV-1 epidemics in sub-Saharan Africa.

HIV-1 subtypes and differences in heterosexual HIV transmission among HIV-discordant couples in Rakai, Uganda

To determine whether heterosexual transmission of HIV differs according to HIV-1 subtype. A retrospective observational cohort. HIV-1 subtype effects on heterosexual HIV-1 transmission were determined among 268 HIV-discordant couples retrospectively identified from a population cohort in Rakai, Uganda. HIV-1 subtype (gag and gp41 sequencing and multiregion hybridization assay) and viral loads (reverse transcriptase PCR) were determined. Adjusted incidence rate ratios (adj IRR) of HIV transmission by subtype were estimated by multivariable Poisson regression adjusting for characteristics of index HIV-positive and HIV-negative partners. Adjusting for index HIV-positive partners' age, viral load, stage of disease, genital ulcer disease, and HIV-negative partners' genital ulcer disease and nonuse of condoms, subtype A viruses were associated with a higher rate of transmission than subtype D [adj.IRR 1.98, 95% confidence interval (CI) 1.17-3.34], but no differences in transmission were observed between recombinant viruses and subtype D (aIRR 1.53, P = 0.25). Index-positive partners' age less than 30 years (adj.IRR 3.44, 95% CI 1.75-6.78) and viral load (adj.IRR 2.37, 95% CI 1.75-3.21), and index-negative partners' genital ulcer disease (adj.IRR 1.71, 95% CI 1.08-2.70) and nonuse of condoms (adj.IRR 1.94, 95% CI 1.15-3.28) were significant determinants of HIV transmission. In Rakai, Uganda, subtype A viruses have a significantly higher rate of heterosexual transmission than subtype D viruses. Differential subtype transmission efficiency may be important for HIV vaccine evaluation and could contribute to subtype-specific HIV epidemics in sub-Saharan Africa.

Concurrent Partnerships as a Driver of the HIV Epidemic in Sub-Saharan Africa? The Evidence is Limited

Little evidence supports the hypothesis that sexual behavior differs dramatically in Africa compared to the rest of the world nor that sexual behavior in Africa is different in countries with high versus low HIV prevalence. And it bears repeating that the most rigorous field studies on this topic did not find evidence for an association between concurrency and HIV prevalence in five diverse African cities or in 22 countries. Theoretical plausibility-provided by the mathematical models-does not provide sufficient evidence to conclude that what could happen is actually what has happened. Without strong data showing that people have more concurrent partnerships in Africa than elsewhere and that places with high levels of concurrency also have high levels of HIV we can only conclude that under certain conditions concurrency may be a significant driver of the HIV epidemics in sub-Saharan Africa. To definitively answer this question additional studies are needed. First improved methods for measuring sexual behavior and particularly partnership duration and overlap are needed. Without a common definition of concurrency it is futile to make valid comparisons across populations and between studies. Second better study designs must be used. Current data comes from cross-sectional and ecological studies only. Longitudinal studies that prospectively measure concurrency and incidence of HIV infection are needed to validly assess whether concurrency causes increased transmission of HIV. Once there is evidence that concurrency is a causal factor that increases the risk of HIV infection it will make sense to measure the effect of population-level concurrency on HIV epidemics. Whether concurrency is a significant driver of the HIV epidemic in sub-Saharan Africa is a question that has yet to be answered. Finally designing prevention interventions around concurrency without a better understanding of the intricacies of the relationship between concurrency and HIV transmission may well not produce the intended result of preventing new HIV infections. (excerpt)

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing GRFT. Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, we also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes.