Streptococcus pneumoniae carriage diversity, evolution and transmission among adults living with or without HIV in Malawi

Abstract

Background: Despite the successful rollout of the pneumococcal conjugate vaccines, vaccine serotype carriage remains high among People Living with Human Immunodeficiency Virus (PLHIV) on antiretroviral therapy (ART). However, the carriage dynamics in adults are poorly understood compared to children. I therefore investigated pneumococcal carriage prevalence, density, shedding (as a surrogate for transmission), antimicrobial resistance (AMR) and associated pneumococcal genomic changes among adults living with or without HIV.

Methods: In a prospective cohort study, I recruited 90 asymptomatic PLHIV on ARTfor more than one year (PLHIV>1yr) and 54 HIV-uninfected adults aged 18-45 years and followed them up weekly for the first month and then monthly to 12 months. Standard microbiological techniques were used to determine pneumococcal nasopharyngeal carriage and shedding (from cough on an agar plate, nose poke and modified facemask) and then inferred phenotypic serotype and AMR. I also analysed genomic data from single-colony derived and whole plate-sweep culture.

Results: PLHIV>1yr had a higher pneumococcal carriage density and were more likely to shed pneumococcus than HIV-uninfected adults. A generalised linear mixed model demonstrated that PLHIV>1yr or having higher carriage density were independently associated with an increased propensity for pneumococcal shedding.Aerosol-shed pneumococci from PLHIV>1yr were more often multidrug-resistant and associated with multiple pneumococcal carriage than nasopharyngeal isolates. Furthermore, pneumococci from PLHIV>1yr were associated with high intra-host single nucleotide variants compared to those from HIV-uninfected adults. Moreover, a persistent carriage episode in an adult was associated with high intra-host single nucleotide variants related to antimicrobial resistance and host-bacterial adaptation.

Conclusion: This thesis has demonstrated that PLHIV>1yr not only have a higher prevalence of pneumococcal carriage but also have significant pneumococcal genomic changes and a higher propensity for shedding of AMR pneumococci than HIV-uninfected adults. Furthermore, I have generated evidence showing that adults in high transmission and disease-burdened settings can carry pneumococci for prolonged periods. These findings suggest that adults could be an essentialreservoir of pneumococcal transmission, including AMR pneumococci, and this is exacerbated in PLHIV>1yr.