A cross-sectional study to determine the prevalence of HCMV pneumonia, and viral loads predictive of mortality, in children admitted with severe pneumonia, at a large referral center in sub-Saharan Africa
- To determine HCMV prevalence and viral loads in HIV-infected, -exposed and uninfected-unexposed children admitted with severe pneumonia
- To compare blood, saliva, and urine specimens for the molecular diagnosis of HCMV pneumonia
- To establish HCMV viral load cut offs in this patient group that are highly predictive of severe morbidity and mortality
We will approach all children aged <15 admitted with severe pneumonia (in accordance with the WHO definition). We will include all children irrespective of HIV status to get a thorough measure of prevalence, and anticipate a 4:4:2 split between HIV-infected, HIV-exposed and HIV-uninfected -unexposed children. We will recruit roughly 36 patients/month (90% of all eligible patients) and anticipate an HCMV prevalence of roughly 68% based on a recent study from South Africa. Using the standard sample size calculation method for prevalence studies, we calculated a sample of 322 patients. This sample is sufficient to accurately assess prevalence of HCMV pneumonia. The primary outcome is death, and secondary outcome is time-to-discharge (as a general measure of morbidity), and we will compare HCMV viral loads, in different specimen types, between survivors and mortalities, and look for any correlation with time-to-discharge. We will attempt to define a viral load cut-off that is highly predictive of mortality.
Pneumonia is the leading cause of childhood mortalities globally, despite widespread use of broad-spectrum antibiotics. Viral causes of pneumonia have been severely neglected, due to the expense or lack of anti-viral drugs, but there are new drugs and formulations in the pipeline, and the HIV pandemic has shown that affordability increases where there are large markets. Our autopsy studies have demonstrated that HCMV is one of the leading viral causes of fatal severe pneumonia in HIV-infected children, and anti-HCMV drugs are already in use and saving lives in South Africa. This study will provide crucial evidence that will inform directly on the merits of future trials of anti-HCMV drugs in this patient group, and on appropriate study design. If the results indicate that trials are justified, we would be optimistic of securing funding for a phase 2b RCT.
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Classic 'owls eye' inclusions indicative of CMV disease