CMV viral load as a predictor of the clinical course of CMV-associated pneumonia in hiv infected and uninfected infants

Thesis (MMed)--Stellenbosch University, 2017.Background Lower respiratory tract infections is one of the leading causes of death in children under 5 years of age. In the advent of HIV, much of these lower respiratory tract infections are attributed to opportunistic infections such as Pneumocystis jiroveci pneumonia (PJP) and Cytomegalovirus (CMV). Short of a lung biopsy, diagnosing CMV pneumonia has proven difficult. Some studies suggest that blood CMV viral load might be of benefit in making the diagnosis of CMV-associated pneumonia. There is currently a scarcity of literature with regards to classifying severity of CMV-associated pneumonia and whether the CMV viral load can be used as a predictive indicator of severity and outcome of CMV-associated pneumonia. Objectives To determine whether CMV viral load is a positive predictor of severity and outcome of CMV-associated hypoxic pneumonia. Methods This was a retrospective descriptive study done in the Paediatric Intensive Care Unit (PICU) in Tygerberg Children’s Hospital, Western Cape, South Africa. Study participants were identified from the National Health Laboratory Service (NHLS) database as those patients in PICU less than 1 year of age with a positive cytomegalovirus viral load between 1 January 2014 to 31 December 2015. Patient clinical, radiological, and biochemical data was collected and analyzed. Results A total of 87 patients were included in the study. Twenty-seven of these patients were HIV-positive, 3 of which were on antiretroviral therapy. Comparisons were made between two groups (CMV VL ≤ 4 and > 4) based on the median blood CMV viral load in our study of 4.0 (IQR 3.3-4.79). There was no difference in severity of disease based on Pa02/Fi02 ratio and x-ray findings between the two groups. The mortality in the two groups was similar with a 90% survival rate. (p=0.37). Patients with higher CMV VL required a longer duration of high frequency oscillation ventilation (HFOV) (p=0.005), yet the mean length of PICU stay between the two groups was not statistically different. (p=0.43). Patients who had CMV viral load > 4, had an increased incidence of PJP co-infection (p=0.018), lower CD4 counts (p=0.0001) and higher HIV viral loads (p=0.049). All the patients with PJP-CMV co-infection were successfully treated and discharged. Conclusion CMV viral load alone cannot diagnose pneumonia and showed limited utility in predicting the course and outcome of CMV-associated pneumonia in young infants. The association between CMV VL, PJP co-infection, lower blood CD4 count and HIV viral load suggests that CMV-associated pneumonia occurs in more immune suppressed young infants but the lack of disease severity being associated with the CMV VL limits the usefulness of the test in diagnosing CMV-associated pneumonia and the need for antiviral therapy.Agtergrond Lae lugweginfeksies is een van die hoofoorsake van dood in kinders onder 5 jaar. Met die aanslae van MIV, kan baie van hierdie infeksies toegeskryf word aan opportunistiese infeksies, soos Pneumocystis Jirovecii Longontsteking (PJL) en sitomegalovirus (SMV). Buiten‘n longbiopsie, is dit moeilik om SMV-longontsteking te diagnoseer. Sommige studies stel voor dat bloed met ‘n SMV viruslade mag bydrae tot ‘n suksesvolle diagnose van SMV-geassosieerde longontsteking. Huidiglik is daar‘n tekort aan navorsing aangaande die klassifisering van SMV-geassosieerde longonsteking se ernstigheid, sowel as antwoorde rondom maniere hoe die SMV viruslade mag bydrae tot ‘n voorspelling van ernstigheidsgraad en uitkoms van SMV-geassosieerde longonsteking. Mikpunte Om vas te stel of SMV-viruslade ‘n positiewe voorspeller is vir die graad van ernstigheid en uikoms van SMV-geassosieerde longontsteking. Metodes Hierdie was ‘n retrospektiewe beskrywende studie, afgelê in die Pedriatiese Intensiewe Sorgeenheid (PISE) by Tygerberg Kinderhospitaal in die Wes Kaap, Suid Afrika. Deelname aan die studie was vasgestel deur pasiënte te identifiseer (op die Nasionale Gesondheidslabrotorium Diens databasis) wat in die PISE opgeneem is, minder as een jaar oud is, en gediagnoseer is met ‘n positiewe SMV-viruslade tussen 1 Januarie 2014 en 31 Desember 2015. Kliniese, radiologiese, en biochemiese data is ingesamel en analiseer. Uitslae 87 Pasiënte is in die studie ingesluit. Van hierdie, is 27 getoets as MIV-positief, waarvan 3 op antiretrovirale-terapie was. Twee groepe was onderskei (SMV VL ≤ 4 en > 4) gebaseer op die mediaan bloed SMV-virale lade in ons studie van 4.0 (IQR 3.3-4.79). Daar was geen verskil in ernstigheid van die siekte gebaseer op Pa02/Fi02 verhouding en X-strale nie. Die sterftekoers in die twee groepe was soortgelyk, met ‘n 90% oorlewingssyfer. (p=0.37). Pasiënte met ‘n hoër SMV VL het langer behandelings van hoëfrekewensie ventilasie (HFV) benodig (p=0.005), tog het die gemiddelde lengte van PISE-opname tussen die twee groepe nie statisties verskil nie (p=0.43). Pasiënte met ‘n SMV VL van > 4 het ‘n groter kans gestaan van ‘n PJP mede-infeksie (p=0.018), laer CD4-tellings (p=0.0001), en hoër MIV-tellings (p=0.049). Al die pasiënte met PJP-SMV infeksie was suksesvol behandel en ontslaan. Gevolgtrekking SMV-VL alleen kan nie longontsteking diagnoseer nie. Dít dui op ‘n beperkte bruikbaarheid in die voorspelling van die verloop en uitkoms van SMV-geassosieerde longontsteking in jong kinders. Die assosiëring tussen SMV VL, PJP mede-infeksie, laer bloed CD4 telling, en MIV VL stel voor dat SMV-geassosieerde longontsteking meer gereeld voorkom in jong kinders met verswygde-immuunstelsels. Die tekort aan siekte-ernstigheid assosiasie met die SMV VL beperk egter die bruikbaarheid van die toets in die diagnose van SMV-geassosieerde longontsteking en die noodsaaklikheid vir ‘n antivirale terapie