Epidemiology of streptococcus pneumoniae post-pneumococcal conjugate vaccine introduction in South Africa

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 11 November 2016BACKGROUND Streptococcus pneumoniae is a leading cause of severe invasive bacterial infections globally; estimated to cause over 300,000 deaths in children <5 years in 2015. Pneumococcal conjugate vaccine (PCV) introduction in South Africa has been associated with changes in invasive pneumococcal disease (IPD) risk groups and emerging serotypes. Serotype 1 pneumococcal disease is highly invasive, fluctuates annually but tends to have lower mortality and antibiotic-resistance than other serotypes. Paediatric antiretroviral treatment (ART) and HIV prevention of mother-to-child transmission programme improvements in South Africa have resulted in a growing number of HIV-exposed-uninfected (HEU) children who have higher rates of infectious diseases than unexposed children. It is important to identify risk groups changes with new interventions and define IPD burden pre- and post- PCV introduction in developing countries. OBJECTIVES In South Africa we aimed to estimate severe pneumococcal disease burden in the pre- (2005- 2008) and post-PCV era (2013) amongst HIV-infected (HI) and HIV-uninfected (HU) children <5 years of age; describe the epidemiology of serotype 1 IPD in all age groups from 2003 to 2013; describe the epidemiology of IPD in HEU children <1 year of age from 2009 to 2013 and the risk factors related to IPD in HI and HU children post-PCV introduction (2010 to 2012). All analyses included PCV introduction impact. METHODS A model using national laboratory-based IPD surveillance data as the baseline was used to determine the total burden of severe hospitalised pneumococcal disease and related mortality in South Africa in children aged <5 years. Adjustments were made for specimen-taking practices and care seeking differences. Vaccine probe studies were used to calculate nonbacteraemic pneumococcal pneumonia case numbers. Observed case fatality ratios were applied to estimated case numbers to determine pneumococcal death numbers. All patients with laboratory-confirmed IPD were included in the serotype 1 analysis. We calculated incidence rates, determined factors associated with serotype 1 disease and conducted a space-time analysis using SaTScan with a Bernoulli model for comparison. Maps to visualise serotype 1 clusters were generated using ArcGIS. Surveillance data was used to compare IPD incidence and mortality in HEU, HIVunexposed- uninfected (HUU) and HI infants. Factors associated with HIV status were compared using a multinomial regression model and logistic regression for mortality factors. A matched case-control study nested within the surveillance programme was used to determine risk factors associated with IPD in HU and HI children aged <5 years. Data was analysed using conditional logistic regression. RESULTS In the pre-vaccine era (2005-2008) in South Africa, roughly 196,100 (148,000-251,000) cases of severe pneumococcal disease were estimated annually in children aged <5 years, an incidence of 3799/100,000; the rate was reduced by 67% in 2013, likely due to PCV and other interventions. In addition 8600 (7000-10220) pneumococcal-related annual deaths were estimated pre-vaccine and 3600 in 2013, a rate difference of 99/100,000 child-years. Over an 11-year period two clusters (2003-2004 and 2008-2012) of serotype 1 infection were detected in all age groups with reductions in incidence noted in 2013. Among children aged <5 years, those with serotype 1 IPD had shorter hospital stays, fewer penicillinnonsusceptible cases (adjusted odds ratio (aOR) 0.02, 95% confidence interval (CI) 0.01– 0.05), lower HIV prevalence (aOR 0.19, 95% CI 0.12–0.31) and lower in-hospital death rates (aOR 0.38, 95% CI 0.19–0.76) than children with non-serotype 1 IPD. The incidence of IPD was greatest in HI infants (272-654/100,000), then HEU infants (33- 88/100,000) and HUU infants (18-28/100,000). Young HEU infants (37% [59/175]) were more likely to die than HUU infants (32% [51/228]; adjusted relative risk ratio, 1.76, 95% CI 1.09–2.85]). On case-control analysis a number of factors were shown to be associated with an increased risk of IPD in the post-PCV period. In HU children these factors included underlying medical conditions (aOR = 1.99, 95% CI 1.22–3.22), attending day care (aOR = 1.58, 95% CI 1.01–2.47) or having been exposed to HIV perinatally (aOR = 1.62, 95% CI 1.10–2.37), while PCV vaccination reduced the odds of IPD (aOR = 0.67, 95% CI 0.46– 0.99). Predisposing factors in HI children included malnutrition (aOR = 2.68, 95% CI 1.40– 5.14) and recent tuberculosis (aOR = 5.12, 95% CI 1.69–15.50), while current ART reduced the odds of IPD (aOR = 0.13, 95% CI 0.05–0.38). CONCLUSION Pneumococcal disease represents a major public health burden in young children in South Africa. PCV and other HIV-associated interventions resulted in a significant reduction in both invasive disease and non-bacteraemic pneumonia. Serotype 1 IPD has distinctive clinical features with temporal decreases noted post-PCV13 introduction. With improvements in interventions to prevent and treat HIV, a resultant growing HEU infant population has been observed with an increased risk of IPD compared with HUU children. Risk factors related to socio-economic conditions and intense exposure to infection continues to be important causes of IPD in children. A full understanding of PCV impact on pneumococcal disease burden is needed to support ongoing national policy decisions on PCV use.MT201

Aetiology of childhood pneumonia in low- and middle-income countries in the era of vaccination: a systematic review.

BACKGROUND: This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries. METHODS: We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830]. RESULTS: We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis. CONCLUSIONS: Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination

Eff ectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine eff ectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the eff ectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identifi ed through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine eff ectiveness as a percentage, with the equation 1 – [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine eff ectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The eff ectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (–35 to 100) among three case-control sets of children with HIV infection. PCV13 eff ectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI –12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine eff ectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is eff ective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine eff ectiveness in children infected with HIV was high, it did not reach signifi cance, possibly because of the small sample size. These fi ndings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa

INTRODUCTION : Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. METHODS : We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005±2008) and post-PCV introduction (2012± 2013) in children aged 0±59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. RESULTS : In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000±140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000±50,000) severe pneumococcal disease cases were estimated in 2012±2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000±6000) pneumococcal-related annual deaths were estimated in the prevaccine period and 1,900 (95% CI 1000±2500) in 2012±2013, a mortality rate difference of 61 per 100,000 child-years. CONCLUSIONS : While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0±59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.S1 Text. Supplementary material: Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa.S1 Table. Population denominators from the Thembisa model for children <5 years of age in South Africa, 2005-2008 and 2012-2013.S2 Table. Sensitivity analysis for case numbers showing key variables altered in analysis, 2005-2008 and 2012-2013.S3 Table. Sensitivity analysis for numbers of deaths showing key variables altered in analysis, 2005-2008 and 2012-2013.S1 Fig. Initial step in estimating the burden of invasive and non-invasive pneumococcal cases in children aged <5 years in South Africa, 2005-2008 and 2012-2013.S2 Fig. Second step in estimating the burden of invasive and non-invasive pneumococcal cases in children <5 years in South Africa, 2005-2008 and 2012-2013.S3 Fig. Tornado sensitivity diagram representing change in pneumococcal case estimates in children <5 years of age in the pre-vaccine era, when values of key variables are modified.S4 Fig. Tornado sensitivity diagram representing change in pneumococcal death estimates in children <5 years of age in the pre-vaccine era, when values of key variables are modified.The National Institute for Communicable Diseases/National Health Laboratory Service (NICD/NHLS), South Africa and the Centers for Disease Control and Prevention (CDC) Global AIDS Program (GAP) Cooperative Agreement (U62/PSO022901).http://www.plosone.orgam2017Paediatrics and Child Healt

Assessing the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease using polymerase chain reaction-based surveillance : an experience from South Africa

BACKGROUND : The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods. METHODS : We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009–2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012). RESULTS : During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/ serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased −63.8 % (95 % CI: −79.3 % to −39.1 %) among lytA-positive cases and −91.7 % (95 % CI: −98.8 % to −73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (−71.7 %; 95 % CI: −81.1 % to −58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: −96.7 % to 58.4 %). CONCLUSIONS : Significant downward trends in IPD PCV-7 serotype-associated rates were observed among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ctvalues. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.Additional file 1: Assessing the Impact of Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease Using Polymerase Chain Reaction-Based Surveillance: An Experience from South AfricaThis work was supported by Pfizer South Africa (investigator-initiated research agreement number: WS1167521) and the US Centers for Disease Control and Prevention (co-operative agreement number: 5U51IP000155).http://www.biomedcentral.com/bmcinfectdis/am2016Medical Virolog

Epidemiology of acute lower respiratory tract infection in HIV exposed uninfected infants

BACKGROUND : Increased morbidity and mortality from lower respiratory tract infection (LRTI) abstract has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIVunexposed uninfected (HUU) and HEU infants aged <6 months in South Africa. METHODS : We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010–2011 was estimated at 1 site with population denominators. RESULTS : We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3–1.5) and HIV infected (IRR 3.8; 95% CI 3.3–4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3–1.6) and human metapneumovirus–associated (IRR 1.4; 95% CI 1.1–2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8–1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1–3.8, and 12.2, 95% CI 1.7–infinity, respectively) of death than HUU. CONCLUSIONS : HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.http://pediatrics.aappublications.orgam2017Medical Virolog

Epidemiology of pneumonia in the pre-pneumococcal conjugate vaccine era in children 2-59 months of age, in Ulaanbaatar, Mongolia, 2015-2016.

BACKGROUND: Respiratory diseases, including pneumonia, are the second largest cause of under-five mortality in Mongolia and the most common cause of childhood hospitalization. However information regarding the contribution of Streptococcus pneumoniae to pneumonia causation in Mongolia is limited. We aimed to describe the epidemiology of hospitalized children aged 2-59 months with pneumonia, enrolled into a surveillance program in the period prior to pneumococcal conjugate vaccine (PCV) introduction, in Mongolia. METHODS: An expanded pneumonia surveillance program enrolled children, who met the surveillance case definition, at participating hospitals, between April 2015 and May 2016. Cumulative incidence rates were calculated by district for all pneumonia endpoints using district specific denominators from the Mongolian Health Department census for 2016. Socio-economic and disease-associated factors were compared between districts using chi-squared tests. RESULTS: A total of 4318 eligible children with pneumonia were enrolled over the 14 month period. Overall the incidence for all-cause pneumonia in children aged 12-59 months was 31.8 per 1000 population; children aged 2-11 months had an almost four-fold higher incidence than children aged 12-59 months. Differences were found between districts with regards to housing type, fuel used for cooking, hospital admission practices and the proportions of severe and primary endpoint pneumonia. DISCUSSION: This study shows a high burden of pneumonia in children aged 2-59 months in Mongolia prior to PCV introduction. Rates differed somewhat by district and age group and were influenced by a number of socio-economic factors. It will be important to consider these differences and risk factors when assessing the impact of PCV introduction

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008

BACKGROUND: An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa. METHODS: IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent. RESULTS: Among 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5) and 19F (OR 2.9, 95%CI 1.4-6.1) vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years); meningitis (OR 4.1, 95%CI 3.0-5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases. CONCLUSION: Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization

The impact of influenza and tuberculosis interaction on mortality among individuals aged >= 15 years hospitalized with severe respiratory illness in South Africa, 2010-2016

BACKGROUND: Data on the prevalence and impact of influenza–tuberculosis coinfection on clinical outcomes from high–HIV and –tuberculosis burden settings are limited. We explored the impact of influenza and tuberculosis coinfection on mortality among hospitalized adults with lower respiratory tract infection (LRTI). METHODS: We enrolled patients aged ≥15 years admitted with physician-diagnosed LRTI or suspected tuberculosis at 2 hospitals in South Africa from 2010 to 2016. Combined nasopharyngeal and oropharyngeal swabs were tested for influenza and 8 other respiratory viruses. Tuberculosis testing of sputum included smear microscopy, culture, and/or Xpert MTB/Rif. RESULTS: Among 6228 enrolled individuals, 4253 (68%) were tested for both influenza and tuberculosis. Of these, the detection rate was 6% (239/4253) for influenza, 26% (1092/4253) for tuberculosis, and 77% (3113/4053) for HIV. One percent (42/4253) tested positive for both influenza and tuberculosis. On multivariable analysis, among tuberculosis-positive patients, factors independently associated with death were age group ≥65 years compared with 15–24 years (adjusted odds ratio [aOR], 3.6; 95% confidence interval [CI], 1.2–11.0) and influenza coinfection (aOR, 2.3; 95% CI, 1.02–5.2). Among influenza-positive patients, laboratory-confirmed tuberculosis was associated with an increased risk of death (aOR, 4.5; 95% CI, 1.5–13.3). Coinfection with other respiratory viruses was not associated with increased mortality in patients positive for tuberculosis (OR, 0.7; 95% CI, 0.4–1.1) or influenza (OR, 1.6; 95% CI, 0.4–5.6). CONCLUSIONS: Tuberculosis coinfection is associated with increased mortality in individuals with influenza, and influenza coinfection is associated with increased mortality in individuals with tuberculosis. These data may inform prioritization of influenza vaccines or antivirals for tuberculosis patients and inform tuberculosis testing guidelines for patients with influenza.National Institute for Communicable Diseases, of the National Health Laboratory Service and US Centers for Disease Control and Prevention.https://academic.oup.com/ofidpm2020Medical Virolog

Household transmission of seasonal influenza from HIV-infected and HIV-uninfected individuals in South Africa, 2013-2014

BACKGROUND : We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. METHODS : Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. RESULTS : We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio [OR] 0.2; 95% confidence interval [CI], 0.1–0.6; SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1–4 years (OR 3.6; 95% CI, 1.2–11.3) and 25–44 years (OR 8.0; 95% CI, 1.8–36.7), and contact age group 1–4 years (OR 3.5; 95% CI, 1.2–10.3) compared to 5–14 years, and sleeping with index case (OR 2.7; 95% CI, 1.3–5.5). HIV infection of index case was not associated with SI. CONCLUSIONS : HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.The National Institute for Communicable Diseases of the National Health Laboratory Service and the US Centers for Disease Control and Prevention [co-operative agreement number: 5U51IP000155.https://academic.oup.com/jid2020-05-15hj2019Medical Virolog