Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis

Shi, Ting; McLean, Kenneth; Campbell, Harry; Nair, Harish

Another essential criterion required for the determination of causality is establishment of the temporal sequence of exposure and outcome [57] . As exposure is investigated after the outcome in case-control studies, these cannot provide this evidence. Therefore, there is a rationale for the conduct of birth cohort studies with routine surveillance of children to track the circulation and course of respiratory viral infections. "Vaccine-probe studies" could be used to gain experimental evidence of each virus as a causal pathogen [66] , although this is limited by vaccine availability of effective vaccines. These would allow conclusive assessment of the burden of ALRI attributable to each virus. Considerations of the causal role of these viruses are further complicated by the fact that a recent respiratory virus infection may have caused temporary immune-suppression leading to a subsequent viral or bacterial infection even though the initial infection can no longer be detected. Influenza viral infections leading to subsequent pneumococcal or staphylococcal respiratory infections have been well described [67] . This may result in an under-estimation of the burden of disease associated with respiratory viral infection.