Date of Award

January 2014

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Jamie Childs

Second Advisor

Sibel Ascioglu

Abstract

Objective: Crimean Congo Hemorrhagic Fever (CCHF) is caused by a Nairovirus of the Bunyaviridae family. It was first reported in Turkey in 2002. Infections commonly result from bites from ticks of Hyalomma marginatum marginatum or Rhipicephalus bursa species. Nosocomial infections also occur. CCHF infection occurs in over 30 countries in Europe, Asia and Africa. No vaccine exists and the effectiveness of ribavirin treatment remains controversial. This study's objective was to identify significant epidemiological, environmental, and clinical risk factors associated with disease and death caused by CCHF in Turkey. This study also evaluated the effectiveness of ribavirin as treatment for patients infected by CCHF.

Methods: Chi-square, t-tests and univariate statistical comparisons were used to determine associations between risk factors and death by CCHF. Multivariate logistic regression was used to determine variables associated with death. ArcGIS was used to map the yearly and cumulative incidence of CCHF per province. Propensity scores were used to evaluate the effectiveness of ribavirin treatment. Data were obtained from a surveillance database maintained by the Turkish Ministry of Health, Section of Zoonosis.

Results: A total of 6,070 laboratory confirmed cases of CCHF was reported from Turkey between 2007 and 2012. The six-year case fatality was 5%. A greater percentage of cases were male (54.7%), persons residing in villages (82.5%), those visiting rural areas (52.9%), farmers (34.5%), persons exposed to animals (75.6%) and those reporting a tick bite (75.9%). However, except for age and tick bite history, none of these risk factors were significant in fatal cases. Significant risk factors for death included exposure to infected persons (OR: 2.16, 95%CI: 1.10-4.24) and days of symptoms before hospital admission (OR: 0.92, protective, 95%CI: 0.86-0.98). Clinical risk factors for death included leukopenia (OR: 0.20, 95%CI: 0.14-0.30), thrombocytopenia (OR: 8.75, 95%CI: 3.46-22.17), hypotension (OR: 3.54, 95%CI: 2.43-5.15), bleeding (OR: 3.88, 95%CI: 2.75-5.48), anemia (OR: 2.72, 95%CI: 1.92-3.84) and combined elevated plasma aspartate aminotransferase/ alanine aminotransferase (AST/ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) levels (OR: 1.74, 95%CI 1.01-2.98). Ribavirin treatment was not found to significantly affect mortality (OR: 0.85, 95%CI: 0.57-1.26). Stratified propensity score analysis verified the ineffectiveness of ribavirin as treatment for CCHF as no statistically significant benefits of treatment were identified.

Conclusion: Despite environmental control and public health education measures to prevent the spread of CCHF in Turkey, the case fatality remains stagnant and incidence has increased. While gender, village residence, and exposure to animals are not significant risk factors of death caused by CCHF, exposure to infected individuals, average days of symptoms before hospital admission, and clinical factors including hypotension, leukopenia, thrombocytopenia, bleeding, anemia and elevated AST/ALT, LDH, CK levels are significantly associated with death and increase the odds of death by CCHF. While history of tick bite is significantly associated with death, it does not significantly increase the odds of death in an infected individual when all other variables are considered. Significant risk factors should be studied further to understand prevention of disease and death.

Comments

This is an Open Access Thesis.

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