Estimating pneumococcal carriage dynamics in adults living with HIV in a mature infant pneumococcal conjugate vaccine programme in Malawi, a modelling study

Abstract

Background: Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation.

Methods: We collected longitudinal nasopharyngeal swabs from individuals aged 18-45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality.

Results: We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25-37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant.

Conclusions: The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV.

Keywords: Human immunodeficiency virus; Malawi; Modelling; Pneumococcal acquisition; Pneumococcal duration; Serotype.

Fig. 1

Participant demographic and epidemiologic characteristics of follow-up samples stratified by vaccine-serotype (VT) and non-VT (NVT) carriage and potential risk factors. a The prevalence of pneumococcal carriage in all samples at each sampling visit stratified by serotype group and human immunodeficiency virus (HIV) status, with an insert showing pneumococcal carriage prevalence of samples aggregated across all visits. b Distribution of pneumococcal carriage density in HIV- adults, adults living with HIV (ALWHIV) on antiretroviral therapy (ART) at most 3 months and at least 1 year. The share of all pneumococcal carriage stratified by serotype group and HIV/ART status among c adults living with 1 child or at least 2 children < 5y, d males or females, e 18–33 years or 34–44 years, f low or high social economic status, and g antibiotic use. h The map shows Blantyre district with circular points on the map indicating the residential location of the adults from whom the nasopharyngeal samples were collected during the study. The size of the circular point is proportion to the number of samples collected in adults from that location. Overall, the map indicates that samples were mostly collected within the high-density informal settlements of urban Blantyre

Fig. 2

Pneumococcal carriage acquisition probability and duration by serotype group and human immunodeficiency virus (HIV) infection status among potential risk groups. Daily pneumococcal carriage acquisition probability for a overall carriage, and carriage stratified by vaccine-serotype group and HIV status among b all participants, c females or males, d adults aged 18–33 or 34–44 years old (y), e adults living with 1 child or at least 2 children in the house, and f adults in low or high social economic status (SES). Pneumococcal carriage duration in days for g overall carriage, and carriage stratified by vaccine-serotype group and HIV status among h all participants, i females or males, and j adults aged 18–33 or 34–44 years old (y)

Fig. 3

Pneumococcal serotype-specific carriage dynamics in considered serotypes with relative high sampling frequency. a Prevalence of each serotype in all samples, with ‘uNVT’ representing unknown non-PCV13 serotypes because they were not included in the serotyping assay which could only identify up to 23 serotypes including all VT. Insert in a is the carriage prevalence of each serotype or serogroup with a relatively high sample frequency, where ‘kVT’ represents known PCV13 serotypes with very low sample frequency (1, 4, 9 V, 14, 18C, and 23F), and ‘kNVT’ represents non-PCV13 serotypes with known serotypes with very low sample frequency (22A/F, serogroup 33 and 18, 12A/B/F, 19B/C, 8, and 6D). b Network diagram showing the acquisition of a serotype replacing a specific serotype in a colonisation chain. The size of the edges reflects the pairs of serotype transition events in the colonisation chain that occur more likely than expected, and the node represents the serotype or serotype group or vaccine-serotype group. c Daily pneumococcal carriage acquisition probability under a log scale and d daily average pneumococcal serotype carriage duration