Risk Factors and Human coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana.

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2014.
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Abstract
Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. In spite of its importance, information on the viral aetiology and risk factors associated with ARI are limited in Ghana. Even though human coronaviruses (HCoVs) are known to be associated with respiratory disease outbreaks and severe infections in some developed countries, their epidemiological role is understudied in many African countries including Ghana. It is therefore not known whether HCoVs are pathogenic viruses associated with ARI or only exist as normal commensals of the upper respiratory tract. The aim of this study was to find the association between HCoVs and ARIs, describe the sero-molecular epidemiology of HCoVs and identify the risk factors associated with upper respiratory tract infection. An unmatched case control study was conducted in Buoyem, Forikrom and Kwamang communities of Ghana. Subjects were interviewed on various socio-demographic factors and hygienic practices using structured questionnaires. Nasal/Nasopharyngeal swabs were taken from older children and adults, and tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. A total of 1272 subjects were recruited comprising of 662 (52%) controls and 610 (48%) cases. Risk factors associated with upper respiratory tract infections were school attendance to the level of Senior High and tertiary education, and being a health worker. Out of 322 subset of cases interviewed, 212 (66%) covered their nose with handkerchiefs when they sneezed, 52 (16%) covered with their hands upon xix sneezing and 79 (25%) sneezed in the open. Self-administered drugs such as herbs (2%), analgesics (25%) and antibiotics (16%) were used to manage upper respiratory tract infections. Out of the 1,272 subjects recruited, nasal swabs were taken from 1,213. Of the 1,213, 150 (12.4%) subjects were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95% CI = 2.24 – 11.78), HCoV-OC43 (OR = 6.16, 95% CI = 1.77 – 21.65) and combine HCoVs (OR = 2.36, 95% CI = 1.5 = 3.72) were associated with upper respiratory tract infections. Significant median virus concentration difference was observed for only HCoV- NL63 (cases: 2.41 x 106 copies per PCR reaction; IQR = 1.96 x 104 - 2.3 x 106 vrs controls: 1876.5 copies per PCR reaction; IQR =387.2 – 8.6 x 104, P=0.003) and the clinically relevant cut-off viral concentration was determined to be 7,510 copies per PCR reaction. HCoVs were found to be seasonally dependent with high proportions identified in the harmattan season (54/215, 25.1%) compared to the wet (80/516, 15.5%) seasons. The most frequent viruses detected in the harmattan and wet seasons were HCoV-229E and HCoV-NL63 respectively. HCoV-OC43 and HCoV-HKU1 were almost distributed equally throughout the year. Sequencing of the partial spike region was successful for 53 out of 146 samples (36.3%). Of the 53, 12 (22.6%) were HCoV-OC43, 14 (26.4%) were HCoV-NL63, 24 (45.3%) were HCoV-229E and 3 (5.7%) were HCoV-HKU1. A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. xx This study has identified risk factors of URTI and also demonstrated that HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural arrears of Ghana. This information could be useful to policy makers, public health practitioners and other stakeholders in Ghana.
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A Thesis submitted to the Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology in partial fulfilment of the requirement for the degree of Doctor of Philosophy , School of Medical Sciences , College of Health Sciences,
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