The Role of Acute and Early HIV Infection in the Spread of HIV-1 in Lilongwe, Malawi: Implications for “Test and Treat” and Other Transmission Prevention Strategies

HIV transmission risk during acute and early HIV infection (EHI) is sharply elevated, but the contribution of EHI to ongoing HIV transmission is controversial. However, in settings where EHI contributes substantially to secondary transmissions, early diagnosis and intervention may be critical for HIV prevention. We estimated the contribution of EHI to HIV incidence in Lilongwe, Malawi and predicted the future impact of hypothetical prevention interventions affecting EHI only, chronic HIV infection (CHI) only, or both stages

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Effects of community-level bed net coverage on malaria morbidity in Lilongwe, Malawi

Abstract Background The protective effect of insecticide-treated bed nets against individual-level malaria transmission is well known, however community-level effects are less understood. Protective effects from community-level bed net use against malaria transmission have been observed in clinical trials, however, the relationship is less clear outside of a controlled research setting. The objective of this research was to investigate the effect of community-level bed net use against malaria transmission outside of a bed net clinical trial setting in Lilongwe, Malawi following national efforts to scale-up ownership of long-lasting, insecticide-treated bed nets. Methods An annual, cross-sectional, household-randomized, malaria transmission intensity survey was conducted in Lilongwe, Malawi (2011–2013). Health, demographic, and geographic-location data were collected. Participant blood samples were tested for Plasmodium falciparum presence. The percentage of people sleeping under a bed net within 400-m and 1-km radii of all participants was measured. Mixed effects logistic regression models were used to measure the relationship between malaria prevalence and surrounding bed net coverage. Each year, 800 people were enrolled (400 <5 years; 200 5–19 years; 200 ≥20 years; total n = 2400). Results From 2011 to 2013, malaria prevalence declined from 12.9 to 5.6%, while bed net use increased from 53.8 to 78.6%. For every 1% increase in community bed net coverage, malaria prevalence decreased among children under 5 years old [adjusted odds ratio: 0.98 (0.96, 1.00)]. Similar effects were observed in participants 5–19 years [unadjusted odds ratio: 0.98 (0.97, 1.00)]; the effect was attenuated after adjusting for individual-level bed net use. Community coverage was not associated with malaria prevalence among adults ≥20 years. Supplemental analyses identified more pronounced indirect protective effects from community-level bed net use against malaria transmission among children under 5 years who were sleeping under a bed net [adjusted odds ratio: 0.97 (0.94, 0.99)], compared to children who were not sleeping under a bed net [adjusted odds ratio: 0.99 (0.97, 1.01)]. Conclusions Malawi’s efforts to scale up ownership of long-lasting, insecticide-treated bed nets are effective in increasing reported use. Increased community-level bed net coverage appears to provide additional protection against malaria transmission beyond individual use in a real-world context