Estimates of the impact of HIV infection on fertility in a rural Ugandan population cohort

Fertility rates in a population-based cohort of over 3500 women aged 15-49 years living in rural southwest Uganda are described and examined in relation to infection with HIV. Over a six-year follow-up period (1989/90 to 1995/6) the average general fertility rate was estimated as 199 births per thousand woman-years of observation (95 % confidence interval 191 to 207) with a total fertility rate of 6.2 births per woman. The overall prevalence of infection with HIV was 12 per cent and remained relatively stable during follow-up. With the exception of women aged 15-19 years, women who were not infected with HIV had higher fertility than HIV-infected women. The overall age-adjusted fertility rate in HIV-infected women was 0.74 of that of uninfected women (95% confidence interval 0.63 to 0.87, P<0.001) and this result was unaffected by additional adjustment for marital status. When combined with an overall HIV prevalence rate of 12 per cent, this corresponds to a three per cent reduction in fertility rates in the whole population. The lower fertility in HIV-positive women is unlikely to be explained by increased use of contraception, as use of modern contraceptive methods in rural Uganda is low and fewer than ten per cent of women are aware of their HIV-serostatus. More likely explanations are reduced sexual activity due to clinical symptoms associated with HIV infection or lower fertility associated with coexisting infections with other sexually transmitted diseases, such as syphilis. A reduction in fertility caused by HIV infection itself cannot be excluded. The implications of these findings for the use of antenatal clinic data to provide population estimates of HIV prevalence are discussed

Biomass fuel use and indoor air pollution in homes in Malawi

Background: Air pollution from biomass fuels in Africa is a significant cause of mortality and morbidity both in adults and children. The work describes the nature and quantity of smoke exposure from biomass fuel in Malawian homes. Methods: Markers of indoor air quality were measured in 62 homes (31 rural and 31 urban) over a typical 24 h period. Four different devices were used (one gravimetric device, two photometric devices and a carbon monoxide (HOBO) monitor. Gravimetric samples were analysed for transition metal content. Data on cooking and lighting fuel type together with information on indicators of socioeconomic status were collected by questionnaire. Results: Respirable dust levels in both the urban and rural environment were high with the mean (SD) 24 h average levels being 226 μg/m3 (206 μg/m3). Data from real-time instruments indicated respirable dust concentrations were >250 μg/m3 for >1 h per day in 52% of rural homes and 17% of urban homes. Average carbon monoxide levels were significantly higher in urban compared with rural homes (6.14 ppm vs 1.87 ppm; p<0.001). The transition metal content of the smoke was low, with no significant difference found between urban and rural homes. Conclusions: Indoor air pollution levels in Malawian homes are high. Further investigation is justified because the levels that we have demonstrated are hazardous and are likely to be damaging to health. Interventions should be sought to reduce exposure to concentrations less harmful to health

MaiMwana women’s groups: a community mobilisation intervention to improve mother and child health and reduce mortality in rural Malawi

This article presents a detailed description of a community mobilization intervention involving women’s groups in Mchinji District, Malawi. The intervention was implemented between 2005 and 2010.The intervention aims to build the capacities of communities to take control of the mother and child health issues that affect them. To achieve this it comprises trained local female facilitators establishing groups and using a manual, participatory rural appraisal tools and picture cards to guide them through a community action cycle to identify and implement solutions to mother and child health problems. Significant resource inputs include salaries for facilitators and supervisors, and training, equipment and materials to support their work with groups.It is hypothesized that the groups will catalyse community collective action to address mother and child health issues and improve the health and reduce the mortality of mothers and children. Their impact, implementation and cost-effectiveness have been rigorously evaluated through a randomizedcontrolled trial design. The results of these evaluations will be reported in 2011

Brief report: active HIV case finding in the city of Kigali, Rwanda: assessment of voluntary assisted partner notification modalities to detect undiagnosed HIV infections

BACKGROUND: Voluntary assisted partner notification (VAPN) services that use contract, provider, or dual referral modalities may be efficient to identify individuals with undiagnosed HIV infection. We aimed to assess the relative effectiveness of VAPN modalities in identifying undiagnosed HIV infections. SETTING: VAPN was piloted in 23 health facilities in Kigali, Rwanda. METHODS: We identified individuals with a new HIV diagnosis before antiretroviral therapy initiation or individuals on antiretroviral therapy (index cases), who reported having had sexual partners with unknown HIV status, to assess the association between referral modalities and the odds of identifying HIV-positive partners using a Bayesian hierarchical logistic regression model. We adjusted our model for important factors identified through a Bayesian variable selection. RESULTS: Between October 2018 and December 2019, 6336 index cases were recruited, leading to the testing of 7690 partners. HIV positivity rate was 7.1% (546/7690). We found no association between the different referral modalities and the odds of identifying HIV-positive partners. Notified partners of male individuals (adjusted odds ratio 1.84; 95% credible interval: 1.50 to 2.28) and index cases with a new HIV diagnosis (adjusted odds ratio 1.82; 95% credible interval: 1.45 to 2.30) were more likely to be infected with HIV. CONCLUSION: All 3 VAPN modalities were comparable in identifying partners with HIV. Male individuals and newly diagnosed index cases were more likely to have partners with HIV. HIV-positive yield from index testing was higher than the national average and should be scaled up to reach the first UNAIDS-95 target by 2030

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: a cross-sectional nationally representative survey

BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results >/=1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm(3) (IQR, 197-484 cells/mm(3)). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs

HIV genotypic resistance among pregnant women initiating ART in Uganda: a baseline evaluation of participants in the Option B+ clinical trial

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda.Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda’s National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL&gt;1000 copies/mL as one sample failed to amplify.Results: 159/540 (29.4%) had a VL &lt; 1000 copies/ml and 381/540 (70.6%) had a VL &gt;1,000 copies/ml. Of the women with VL&gt;1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4).Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens

Update on pathology laboratory development and research in advancing regional cancer care in Malawi

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs

Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

BACKGROUND: Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. METHODS: A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. RESULTS: Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. CONCLUSIONS: HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study

Intracellular survival of Streptococcus pneumoniae in human alveolar macrophages is augmented with HIV infection

People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against Streptococcus pneumoniae of primary human AM obtained from PLHIV and HIV-uninfected adults. We found that pneumococcus survived intracellularly in AMs at least 24 hours post ex vivo infection, and this was more frequent in PLHIV than HIV-uninfected adults. Corroborating these findings, in vivo evidence showed that PLHIV had a higher propensity for harboring S. pneumoniae within their AMs than HIV-uninfected adults. Moreover, bacterial intracellular survival in AMs was associated with extracellular propagation of pneumococcal infection. Our data suggest that failure of AMs to eliminate S. pneumoniae intracellularly could contribute to the increased risk of pneumococcal pneumonia in PLHIV

Reaching the poor with health interventions: Programme-incidence analysis of seven randomised trials of women's groups to reduce newborn mortality in Asia and Africa

Background Efforts to end preventable newborn deaths will fail if the poor are not reached with effective interventions. To understand what works to reach vulnerable groups, we describe and explain the uptake of a highly effective community-based newborn health intervention across social strata in Asia and Africa. Methods We conducted a secondary analysis of seven randomised trials of participatory women's groups to reduce newborn mortality in India, Bangladesh, Nepal and Malawi. We analysed data on 70 574 pregnancies. Socioeconomic and sociodemographic differences in group attendance were tested using logistic regression. Qualitative data were collected at each trial site (225 focus groups, 20 interviews) to understand our results. Results Socioeconomic differences in women's group attendance were small, except for occasional lower attendance by elites. Sociodemographic differences were large, with lower attendance by young primigravid women in African as well as in South Asian sites. The intervention was considered relevant and interesting to all socioeconomic groups. Local facilitators ensured inclusion of poorer women. Embarrassment and family constraints on movement outside the home restricted attendance among primigravid women. Reproductive health discussions were perceived as inappropriate for them. Conclusions Community-based women's groups can help to reach every newborn with effective interventions. Equitable intervention uptake is enhanced when facilitators actively encourage all women to attend, organise meetings at the participants' convenience and use approaches that are easily understandable for the less educated. Focused efforts to include primigravid women are necessary, working with families and communities to decrease social taboos