Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study

Abstract

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for 10 months for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (>=18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9-80.5%) than older children (5-17 years-old) (31.7-50.0%) or adults (11.5-23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7-15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91-1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2-12.8 vs 6.0 days, 95%CI: 5.6 - 6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507-714 vs 389, 95%CI: 311.1-435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.

Social mixing patterns relevant to infectious diseases spread by close contact in urban Blantyre, Malawi

“…In this high HIV prevalence population with good access to ART, we found no evidence that HIV status per se influences contact rates or age-assortativeness. Given that immunosuppressed individuals may be at increased risk of prolonged COVID-19 infectiousness and generation of new variants as well as increased pneumococcal carriage ( Heinsbroek et al, 2015 , Corey et al, 2021 ), this suggests that HIV-positive individuals may have equivalent or increased potential for contributing to respiratory disease transmission in this setting ( Thindwa et al, 2021 ). We have not, however, assessed the other drivers of pathogen transmissibility, such as carriage density and duration of infection, and so cannot confirm a likely disproportionate role in transmission.…”

Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi

“…We used a robust dataset with adequate samples to compute estimates for the overall, VT and risk factor-dependent carriage prevalence. Nonetheless, there were some limitations to our work, including limited data on risk factors such as viral load, use of tobacco, presence of other chronic comorbidities, adherence to ART and history of antibiotics, which may independently influence pneumococcal carriage dynamics [59]. However, population-level viral suppression has increased from 68% in 2015 to 87% in 2020 suggesting improved ART adherence [43].…”

Social mixing patterns relevant to infectious diseases spread by close contact in urban Blantyre, Malawi

“…In this high HIV prevalence population with good access to ART, we found no evidence that HIV status per se influences contact rates or age-assortativeness. Given that immunosuppressed individuals may be at increased risk of prolonged COVID-19 infectiousness and generation of new variants as well as increased pneumococcal carriage 43, 44 , this suggests that HIV-positive individuals may have equivalent or increased potential for contributing to respiratory disease transmission in this setting 45 . We have not, however, assessed the other drivers of pathogen transmissibility, such as carriage density and duration of infection, and so cannot confirm a likely disproportionate role in transmission.…”