Respiratory Virus-Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

Abstract

Background: We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering.

Methods: From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection.

Results: Hospital-attended influenza virus-positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)-infected children aged 5-9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4-3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3-3.0) and rainy season (aRR, 2.4; 95% CI, 1.6-3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs.

Conclusions: Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.

Keywords: Africa; SARI; children; influenza; viral coinfection.

Figure 1.

Seasonal plots of severe acute respiratory infection (SARI) with warning signs, influenza virus infection, and respiratory syncytial virus (RSV) infection in pediatric SARI cases, Blantyre, Malawi, 2011–2014. A, The red line denotes influenza virus–positive SARI, the dotted black line denotes SARI with warning signs, and the dotted gray line denotes SARI cases tested. B, The red bars denote 2009 pandemic influenza A(H1N1) virus, the green bars denotes influenza A(H2N3) virus, the yellow bars denote influenza B virus, and the purple bars denote other influenza virus types. C, The red line denotes RSV-positive SARI, the dotted black line denotes SARI with warning signs, and the dotted gray line denotes SARI cases tested.

Figure 2.

Dendrogram of coviral clusters. Six coviral clusters (A–F) were identified in 362 pediatric SARI cases, in whom >2 viral pathogens were detected in the nasopharynx. Each severe acute respiratory infection (SARI) case is a member of only one cluster; clusters membership is based on similarity of viral pathogens detected. As shown here, characteristics such as SARI severity, number of viruses detected per child, and particular season and year of recruitment are more common in some clusters than others. Green bars denote SARI without warning signs, red bars denote SARI with warning signs, bluish-gray bars denote detection of <3 viruses detected, orange bars denote detection of ≥3 viruses, lavender bars denote recruitment in the rainy season, yellow bars denote recruited outside of the rainy season, gray bars denote recruitment in 2011, blue bars denote recruitment in 2012, pink bars denote recruitment in 2013, and light green bars denote recruitment in 2014.