A Prospective Three-Year Cohort Study of the Epidemiology and Virology of Acute Respiratory Infections of Children in Rural India

Abstract

BackgroundAcute respiratory infection (ARI) is a major killer of children in developing countries. Although the frequency of ARI is similar in both developed and developing countries, mortality due to ARI is 10–50 times higher in developing countries. Viruses are common causes of ARI among such children, yet the disease burden of these infections in rural communities is unknown.Methodology/Principal FindingsA prospective longitudinal study was carried out in children enrolled from two rural Indian villages at birth and followed weekly for the development of ARI, classified as upper respiratory infection, acute lower respiratory infection (ALRI), or severe ALRI. Respiratory syncytial virus (RSV), influenza, parainfluenza viruses and adenoviruses in nasopharyngeal aspirates were detected by direct fluorescent antibody testing (DFA) and, in addition, centrifugation enhanced culture for RSV was done. 281 infants enrolled in 39 months and followed until 42 months. During 440 child years of follow-up there were 1307 ARIs, including 236 ALRIs and 19 severe ALRIs. Virus specific incidence rates per 1000 child years for RSV were total ARI 234, ALRI 39, and severe ALRI 9; for influenza A total ARI 141, ALRI 39; for INF B total ARI 37; for PIV1 total ARI 23, for PIV2 total ARI 28, ALRI 5; for parainfluenza virus 3 total ARI 229, ALRI 48, and severe ALRI 5 and for adenovirus total ARI 18, ALRI 5. Repeat infections with RSV were seen in 18 children.Conclusions/SignificanceRSV, influenza A and parainfluenza virus 3 were important causes of ARI among children in rural communities in India. These data will be useful for vaccine design, development and implementation purposes.

Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors

“…A dual split-protein cell content mixing assay was used to quantify the extent of cell-to-cell fusion mediated by RSV F. For transfection, 293T cells received plasmid DNA encoding eGFP-renilla luciferase dual-split fusion proteins DSP 1-7 or DSP [8][9][10][11] (37), respectively. One cell population also received plasmid DNA encoding RSV L19F or, for control, MeV F and H proteins (35).…”

“…To determine infection kinetics, 293T cells transfected with the plasmids encoding the DSP 1-7 or DSP [8][9][10][11] (37), respectively, were mixed at equal ratios, preloaded with EnduRen life cell substrate as described (60), and spin-inoculated with recRSV A2-L19F (1,000 × g; 30 min; 4°C; MOI = 6 pfu per cell) in the presence of GPAR-3710 or DMSO. Activity of reconstituted luciferase was recorded at the specified time points.…”

“…Although ribavirin was approved for RSV treatment, clinical use is minimal because of efficacy and toxicity issues (8,9). The humanized neutralizing antibody palivizumab is used for immunoprophylaxis of high-risk pediatric patients, but high costs prohibit broad-scale implementation (5,(10)(11)(12)(13).…”

Design and initiation of a study to assess the direct and indirect effects of influenza vaccine given to children in rural India

“…The study site in Ballabgarh builds on the commitment to research from the AIIMS faculty members who provide primary care in the CRHSP and their rapport among the study population. The investigators at AIIMS, UAB, and the CDC were familiar with the study population and had established relationships that facilitated implementation of the study [8].…”

“…In the area in which the current study is ongoing, 11% of acute lower respiratory infections in young children are due to influenza [8].…”