Fathima Naby

Epidemiology of Respiratory Syncytial Virus- Associated Acute Lower Respiratory Tract Infection Hospitalizations Among HIV-Infected and HIV-Uninfected South African Children, 2010-2011

BACKGROUND There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. METHODS Children aged <5 years admitted to sentinel surveillance hospitals with physician-diagnosed neonatal sepsis or ALRTI were enrolled. Nasopharyngeal aspirates were tested by multiplex real-time polymerase chain reaction assays for RSV and other viruses. Associations between possible risk factors and severe outcomes for RSV infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. RESULTS Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. CONCLUSION HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

Epidemiology of Viral-associated Acute Lower Respiratory Tract Infection Among Children <5 Years of Age in a High HIV Prevalence Setting, South Africa, 2009–2012

Background: Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged <5 years. Methods: We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators. Results: We enrolled 8723 children aged <5 years with LRTI, including 64% <12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446–10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1–1.7)], be hospitalized >7 days (OR: 3.8, 95% CI: 2.8–5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6–6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2–6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1–5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7–17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2–55.9) were associated with death. Conclusions: HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.

Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants.

BACKGROUND: Increased morbidity and mortality from lower respiratory tract infection (LRTI) 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 HIV-unexposed 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.

Severity of respiratory syncytial virus lower respiratory tract infection with viral coinfection in HIV-uninfected children

Summary: It is not clear why some children have life-threatening RSV disease. We found RSV and any viral coinfection compared to RSV monoinfection is not associated with more severe disease. Increased life-threatening disease in RSV-ADV and RSV-Influenza coinfection warrants further study.

Profile of babies born before arrival at hospital in a peri-urban setting

Background . Babies born before arrival (BBAs) at hospital constitute a special group at risk of high morbidity and mortality. Objective. We conducted a 12-month retrospective review to describe maternal and neonatal characteristics of BBAs, and their outcomes compared with babies born in the state health sector. Methods. Using case-control sampling, all babies born outside a health facility and who presented to hospital within 24 hours of life were included and compared to the next in-hospital delivery occurring immediately after each BBA presented. Results. During the period reviewed, 135 BBAs (prevalence 1.8%) presented; 71% after hours with most deliveries occurring at home (73.8%). There was no birth attendant present at 70.5% of deliveries. Average birth weights were similar (2.86 kg in the BBA group, 95% confidence interval (CI) 2.73 - 2.95; 2.94 kg in the control group, 95% CI 2.78 - 3.02), but significantly more preterm babies were found in the BBA group (23% v. 9%, respectively; p <0.0001). Admitted BBAs had significantly lower average weights than those who were not admitted (2.19 kg v. 2.96 kg, respectively; p <0.0001). No significant differences were found when maternal age, parity, co-morbidities and distance from the hospital were compared. There were significantly more unbooked mothers in the BBA group (23.0% v. 6.7%, respectively; p <0.0001). Only 54.40% of the admitted BBAs’ mothers had booked antenatally, compared with 78.89% of mothers whose babies were discharged. Admission and complication rates were similar between the groups, but average length of stay was longer in admitted BBAs compared with controls. Conclusion. The prevalence of BBAs in this study is comparable to that in other developing countries, and is associated with poor antenatal attendance, prematurity, delay in presentation to hospital and lengthier hospital stays. These factors have implications for prehospital care of newborns and access to maternal and child healthcare in general

Performance of Surveillance Case Definitions in Detecting Respiratory Syncytial Virus Infection Among Young Children Hospitalized With Severe Respiratory Illness—South Africa, 2009–2014

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRTI) in young children, but data on surveillance case definition performance in estimating burdens have been limited. Methods We enrolled children aged <5 years hospitalized for ALRTI (or neonatal sepsis in young infants) through active prospective surveillance at 5 sentinel hospitals in South Africa and collected nasopharyngeal aspirates from them for RSV molecular diagnostic testing between 2009 and 2014. Clinical data were used to characterize RSV disease and retrospectively evaluate the performance of respiratory illness case definitions (including the World Health Organization definition for severe acute respiratory infection [SARI]) in identifying hospitalized children with laboratory-confirmed RSV according to age group (<3, 3-5, 6-11, 12-23, and 24-59 months). Results Of 9969 hospitalized children, 2723 (27%) tested positive for RSV. Signs and symptoms in RSV-positive children varied according to age; fever was less likely to occur in children aged <3 months (57%; odds ratio [OR], 0.8 [95% CI, 0.7-0.9]) but more likely in those aged ≥12 months (82%; OR, 1.7-1.9) than RSV-negative children. The sensitivity (range, 55%-81%) and specificity (range, 27%-54%) of the SARI case definition to identify hospitalized RSV-positive children varied according to age; the lowest sensitivity was for infants aged <6 months. Using SARI as the case definition would have missed 36% of RSV-positive children aged <5 years and 49% of those aged <3 months; removing the fever requirement from the definition recovered most missed cases. Conclusion Including fever in the SARI case definition lowers the sensitivity for RSV case detection among young children hospitalized with an ALRTI and likely underestimates its burden.

The Role of Human Immunodeficiency Virus in Influenza- and Respiratory Syncytial Virus–associated Hospitalizations in South African Children, 2011–2016

BACKGROUND Data describing influenza- or respiratory syncytial virus (RSV)-associated hospitalized illness in children aged <5 years in Africa are limited. METHODS During 2011-2016, we conducted surveillance for severe respiratory illness (SRI) in children aged <5 years in 3 South African hospitals. Nasopharyngeal aspirates were tested for influenza and RSV using real-time reverse transcription polymerase chain reaction. We estimated rates of influenza- and RSV-associated hospitalized SRI by human immunodeficiency virus (HIV) status and compared children who tested positive for influenza vs RSV using multivariable penalized logistic regression. RESULTS Among 3650 hospitalized children, 203 (5.6%) tested positive for influenza viruses, 874 (23.9%) for RSV, and 19 (0.5%) for both. The median age of children hospitalized with influenza was 13.9 months vs 4.4 months for RSV (P < .01). Annual influenza-associated hospitalization rates per 100000 were highest among infants aged 6-11 months (545; 95% confidence interval [CI], 409-703), while RSV-associated hospitalization rates were highest in infants aged 0-2 months (6593; 95% CI, 5947-7217). HIV exposure was associated with increased incidence of influenza- and RSV-associated hospitalization in infants aged 0-5 months, with relative risk (RR) 2.2 (95% CI, 1.4-3.4) and 1.4 (95% CI, 1.3-1.6), respectively. HIV infection was associated with increased incidence of influenza- and RSV-associated hospitalization in all age groups; RR 2.7 (95% CI, 2.0-3.5) and 3.8 (95% CI, 3.1-4.8), respectively. CONCLUSIONS Influenza- and RSV-associated hospitalizations are common among South African infants. HIV infection and HIV exposure in infants increase risk of influenza- and RSV-associated hospitalization.