Epidemiology and pulmonary sequelae in children with human metapneumovirus associated lower respiratory tract infection

Ramocha, Lesego Matlhogonolo
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Background: Human Metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI). Aims: 1) Conduct a systematic review on epidemiology of hMPV-associated LRTI in African children; 2) Determine the incidence and clinical course of hMPV-associated hospitalisation during the first five years of life in South African children; 3) Investigate the effect of maternal HIV-1 status on transplacental transfer of anti-hMPV neutralisation antibodies from mother to babies; 4) Describe the pulmonary sequelae of children hospitalised with hMPV associated LRTI during the first two years of life. Methods: We conducted a systematic review and meta-analysis to evaluate the epidemiology of hMPV associated LRTI in African children under five years of age. We used the search terms “(“Human metapneumovirus” AND “Africa”) OR (“hMPV” AND “Africa”)” up to September 17, 2020. Incidence estimation and clinical course of hMPV-associated hospitalisation in Soweto, South Africa, 2015-2017, was nested within a larger study in which children under five years of age hospitalised at a large public hospital in Soweto, South Africa, with symptoms consistent with LRTI, were tested for presence of a panel of common respiratory pathogens, including hMPV. The hMPV neutralizing antibodies study was a case-control study of the level of transplacental transfer of hMPV neutralising antibody in 53 mother-infant dyads in which the mother was living with HIV-1 matched to 53 mother-infant dyads in which the mother was HIV-1 negative. To describe the hMPV pulmonary sequelae we conducted a case-control study that drew data from infant pulmonary function tests in 98 cases and 496 controls. Results: The prevalence of hMPV-associated LRTI among hospitalised cases was 4.7% [95% confidence interval (CI): 3.9–5.6, I2=95.0]. In the hMPV-associated LRTI hospitalisation study, hospitalisation was higher in children less than six months compared with other age groups. In the third study, transplacental transfer of hMPV neutralizing antibodies was significantly lower in women living with HIV-1 compared with women without HIV-1; with cord blood to mother ratio being 0.71 median (interquartile range [IQR], 0.50- 1.0) vs 1.4 [IQR 0.71- 2.0] (genotype A) and 0.71 median [IQR 0.50-1.4] vs 1.4 [IQR 0.71- 2.0] (genotype B). hMPV LRTI lead to abnormal lung function in the first two years of life. In the first year of life hMPV-associated LRTI was associated with higher respiratory rate (27.91 [IQR 25.88-31.78] than controls (27.17 [IQR 24.44-30.72], p=0.05). Furthermore, the inspiratory time (Ti) and lung clearance index (LCI) were higher in controls (1.00 seconds [IQR 0.89-1.10] than in cases (0.93 seconds [IQR 0.86-1.04], p=0.03) and 7.27 [IQR 6.79- 8.03] than in cases 6.81 [IQR 6.43-7.59] p=0.0001) respectively. Lung function at two years also showed higher respiratory rate in cases (25.19 [IQR 24.41-28.01] than controls (24.35 [IQR 22.21-26.89], p=0.05). Conclusion: Infants are at increased risk of hMPV-associated LRTI hospitalisation and subsequent pulmonary sequelae. Transplacental transfer of the maternal hMPV neutralizing antibody was lower in women living with HIV, however, it was not associated with any difference in risk of the infants being hospitalised for hMPV- associated lower respiratory tract infections.
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, 2022