The prevalence, distribution and risk of viral haemorrhagic fevers in Tanzania

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Date

2023

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SOKOINE UNIVERSITY OF AGRICULTURE,

Abstract

Viral haemorrhagic fevers (VHFs) are a group of infectious diseases caused by viruses belonging to the Flaviviridae, Phenuiviridae, Arenaviridae, and Filoviridae families. They are characterized by fever, a constellation of initially nonspecific signs and symptoms, and a propensity for bleeding and shock. The VHFs reported in Sub-Saharan Africa include Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Lassa fever (LF), Lujo haemorrhagic fever (LUHF), Marburg virus disease (MVD), Rift Valley fever (RVF), and yellow fever (YF). Knowledge surrounding the distribution and risk of VHFs in Tanzania is limited. Accurate epidemiological information of VHFs is critical to implementing appropriate control and prevention strategies. This study aimed to determine the prevalence, risk of introduction, and factors associated with VHF in Tanzania. The findings provided in this thesis consolidate our knowledge of the diseases in Tanzania and the need for improved surveillance, early detection, and prompt response. The thesis is divided into two major approaches, namely systematic review and research studies. A systematic review was undertaken to analyse EVD outbreak reports, identify challenges and opportunities in detection and response in sub-Saharan Africa and propose effective control approaches. A research study was conducted to estimate the probability of introducing EVD from DRC to Tanzania. This study involved collection of national data for flights, boats, and car transport schedules from DRC to Tanzania covering a period between May 2018 to June 2019. A population study was carried out in all ecological zones of Tanzania to determine the seroprevalence and associated risk of selected five VHFs. In this epidemiological study, blood samples were collected from households and healthcare facilities in Buhigwe, Kalambo, Kilindi, Kinondoni, Kondoa, Kyela, Mvomero, and Ukerewe districts of Tanzania. The samples were screened for immunoglobulin G (IgG) and M (IgM) antibodies against CCHF, EVD, MVD, RVF, and YF. The prevalence of VHF and malaria co-infections was also determined among participants seeking care from health care facilities. Malaria infections were investigated using rapid diagnostics tests (RDT). In addition, Community knowledge, awareness and practices regarding VHF was assessed in eight districts of Tanzania. Archived sera that tested positive for immunoglobulin IgG antibodies to EBOV and RVFV using a commercially available ELISA were reanalysed using the in-house EBOV whole antigen (WAg) and RVFV inhibition enzyme-linked immunosorbent assay. The findings of the systematic review indicate that between 1979 and 2020 a total of 34 EVD outbreaks affecting 34,356 cases and causing 14,823 deaths were reported in 11 countries in Sub-Saharan Africa. The overall case fatality rate (95% CI) was 66% (62 to 71) and this did not change substantially over time (OR in 2019 versus 1976=1.6 (95% CI 1.5 to 1.8), p<0.001). The challenges to control EVD outbreaks are related to epidemiological, sociocultural and health system factors. As regards to the risk of introduction of EVD from DRC to Tanzania, the findings indicate that the most likely pathways were the entry of infected humans through air, land, and water travels. The land border crossings were considered the most frequently used means of travel (highest), while water and air travel were deemed less often (high). High probabilities of introducing EVD from DRC to Tanzania were associated with the viability of the pathogen and low detection capacity at the ports of entry. The epidemiological survey indicated that the overall, CCHF, EVD, MVD, RVF, and YF seroprevalence were 2.0%, 3.4%, 1.2%, 4.8%, and 1.4, respectively. The highest VHF antibody seroprevalence was recorded in western Tanzania (6.0%), characterized by unimodal rainfall pattern and altitude below 2,300m. The lowest seroprevalence (0.4%) was observed in the semi-arid central Tanzania, characterized by moderate precipitation and a unimodal rainfall pattern. The association between seroprevalence of VHFs and geographical location was found to be significant (P= 0.001). Contact with wild animals (OR = 1.2, CI = 1.3–1.6) and keeping goats (OR = 1.3, CI = 1.5–1.9) were significantly associated with RVF while contact with bats (OR = 1.2, CI = 1.1–1.5) was associated with MVD. The prevalence of VHF and malaria co-infections was 1.9%. The age group 46-60 years had the highest malaria co-infection p < 0.05. Over half (57%) of malaria and VHF- infected individuals reported headaches, while over one-third (37%) reported muscle, bone, back, and joint pains (p= 0.001). All EBOV positive sera turned out to be negative by In-House WAg EBOV ELISA. Two of the nine positive IgG RVF commercial ELISA samples were reactive to the RVF Inhouse ELISA, with inhibitory rates ranging from 66% to 99.6%. A slight agreement was observed between the RVF in-house and the commercial ELISA (kappa value, 0.08; 28%, 11/40 in disagreement). As regards to community, knowledge, attitudes and practice, slightly over a quarter (29.4%) of the respondents was knowledgeable, 25% had a positive attitude, and 17.9% had unfavourable practice habits. There were increased odds of having poor practice among participants aged 36–45 years (AOR: 3.566, 95% CI: 1.593– 7.821) and those living in Buhigwe, Kilindi and Ukerewe areas (AOR: 2.529, 95% CI: 1.071–6.657; AOR: 2.639, 95% CI: 1.130–7.580 AOR: 2.248, 95% CI: 1.073–3.844) than their peers. In conclusion, Sub-Saharan Africa faces considerable challenges in EVD control, whereby there are no significant changes in case fatality rates observed during the past four decades. Socioeconomic and cultural factors need to be critically considered to shape the community behaviours that lead to EVD outbreaks. The risk of introducing EVD from DRC to Tanzania is high. Infected humans arriving via land are the most likely pathway of EVD entry, and therefore, mitigation strategies should be directed towards this pathway. Although, CCHF, EVD, MVD, and YF outbreaks have not been reported in Tanzania, the viruses are prevalent and vary from one ecological zone to another, with the western part of the country at the highest risk. Co-infections of malaria and viral haemorrhagic fevers are frequent in Tanzania. The rate was higher in the age group 46-60 years. Both malaria and VHF presented with similar symptoms. There were increased odds of having poor practice among participants aged 36–45 years (AOR: 3.566, 95% CI: 1.593– 7.821) and those who reside in Buhigwe, Kilindi and Ukerewe areas (AOR: 2.529, 95% CI: 1.071– 6.657; AOR: 2.639, 95% CI: 1.130–7.580 AOR: 2.248, 95% CI: 1.073–3.844) than their peers. According to the study, 29.4% of respondents were knowledgeable, 25% had a positive mindset, and 17.9% had unfavourable practice habits. We found poor agreement between in-house and commercial ELISA tests for EBOV and fair agreement between in-house and commercial ELISA tests for RVFV, with the commercial ELISA detecting more cases than the validated in-house ELISA. The current study emphasizes the difficulties in diagnosing viral hemorrhagic fever in Tanzania. Frequent EVD outbreaks in DRC urge the need to intensify the surveillance system, including laboratory screening of suspects, thermal screening of all arrivals from endemic areas, and registering travellers within all the border entry points to prevent disease importation. Equally important, there is a need for strengthening the sensitization and awareness campaigns focusing on cross-border communities. The border healthcare facilities need to be well equipped to ensure a high disease containment capacity. The findings that VHFs are prevalent in Tanzania call for the need to strengthen the surveillance system and management of febrile illnesses in Tanzania. The discrepancy was observed between validated in-house and commercial ELISA tests. Hence, the serological results should be interpreted with caution and this emphasizes the challenges related to the diagnosis of VHFs. Overall, broad-based, one-health approach, effective communication, social mobilisation, and strengthening of the health systems need to be addressed to prevent future outbreaks.

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Ph.D Dissertations

Keywords

haemorrhagic, fevers, infectious diseases, viruses, Ebola

Citation