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Title: Tiered laboratory analyses for common infections to characterize febrile morbidity not related to malaria in Sierra Leone
Author: Ansumana, Rashid
ISNI:       0000 0004 5372 3413
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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In tropical Africa, fever is commonly associated with malaria. However, there are many other illnesses presenting with fever. Non-malaria febrile illnesses (NMFIs) may be attributable to multiple etiologic agents including viral, bacterial and parasitic infections in malaria-endemic resource-poor countries. NMFIs pose challenges to peripheral health systems such that they are clinically under-diagnosed while malaria remains over-diagnosed. Misdiagnoses of a febrile condition may lead to wrong prescription that delays treatment and increases expenditure on health-care and also leads to increased morbidity and mortality. In Sierra Leone, dealing with infections other than malaria remain a serious problem, starting from diagnosis to providing care. Several factors make it difficult to test and treat for NMFIs. Fewer febrile people report their fevers to healthcare centers and there are fewer resources generally which include: fewer laboratories, insufficiently trained laboratory technicians, inadequate standardized infrastructure and unsuitable equipment, epileptic power supplies as well as poor cold-chain storage conditions for reagents among others. The primary goal of this Ph.D. study was to investigate the prevalence/incidence of NMFIs in Bo, Sierra Leone, using a tiered laboratory analyzes method. The specific objectives were to: investigate the types and etiology of non-malarial febrile illnesses in Bo, Sierra Leone; determine the prevalence/incidence of non-malarial pathogens causing febrile illnesses, and investigate the distribution of NMFIs. The study started with a baseline and syndromic survey of all households in the study community (n=882 households with 5410 persons). A total cohort of 1403 persons was recruited and followed for a period of one year. After obtaining informed-consent, bio-samples were obtained from febrile subjects and used for laboratory analyses involving three tiers. The first tier (T1) included the use of rapid, lateral flow assays (RLFAs). T1 tests were: chikungunya, malaria, typhoid fever, syphilis, HIV, hepatitis A, B and C, dengue fever, leptospirosis, influenza A and B, RSV and Streptococcus aureus. Subsequent tests at Tier 2 included singleplex and multiplex PCR and bacterial culture; with resequencing pathogen microarray at Tier 3. From the initial survey 882 households with 5410 individuals and 76.6% reported having malaria in a month prior to the study. About 1402 (25.9%) of persons in participating households were reported to have had a fever within the past six months. The rate of fever reported differed by age group and sex, with young children having the highest rate (p<0.001) and females reporting more fevers than males (p<0.001). Viral infections detected included; 46% chikungunya (95%CI 43.5-48.7), 24.2 human rhino virus/enterovirus (95%CI: 17.4-32.6), 19.2% corona virus (95%CI: 13.1-27.1), 9.7% HIV (95%CI: 8.2-11.4), 8.5% hepatitis B(HbSAg) (95%CI: 7.1-10.1), 8.7%HAV(IgG)(95%CI:7.3-10.3), 8.3% influenza B (95%CI:4.6-14.7 ), 5% adenovirus(95%CI: 2.1-11.0), 4.7% hepatitis C(95%CI: 3.7-5.9), 2.8% dengue fever (95%CI: 2.0-3.8), 1.7% parainfluenza virus and 1.7% influenza A(H1N1) (95%CI: 0.5-5.9), 0.8% cytomegalovirus (95%CI: 0.04-5.2) and 0.2 % human coxsackie virus A24 and A22(95%CI: 0.07-0.6). Bacterial infections detected included: 16.9% of Escherichia. coli (95%CI: 11.6-23.9); 12.6% of Klebsiella pneumonia (95%CI: 8.2-19.2); 12% of Citrobacter freundii (95%CI: 7.6-18.3); 8.5% of Enterobacter cloacae (95%CI: 4.9-14.2), 7.5% Haemophilus influenzae (95%CI: 3.7-14.2), 5%Chlamydophila pneumonia (95%CI: 2.9-11.6), 4.7% Burkholderia pseudomallei (95%CI: 3.7-5.9), 3.3% Moraxella catharrhalis (95%CI: 1.3-8.3), 2.8% Kluyvera spp. and 2.8% Serratia plymuthica /marcescens (95%CI: 1.1-7.0), 2.5% Mycoplasma pneumonia (95%CI: 0.9-7.1), 1.6% Treponema pallidum (95%CI: 1.1-2.5) and 0.7% Enterobacter intermedium, 0.7 Enterobacter aerogenes and 0.7% Escherichia hermannii (95%CI: 0.1-3.9) ), 1.1% Yersinia pestis(95%CI 0.7-1.8). Helminths detected included: 19.3% Ascaris lumbricoides (95% CI: 14.2-25.8); 10.8% hookworms (95% CI: 7.0-16.3); 6.3% Schistosoma mansoni (95% CI: 3.5-10.8); 1.1% had Schistosoma haematobium; 1.2% Strongyloides stercoralis (95% CI: 0.3-4.1); and 2.8% had Trichuris trichiura (95% CI: 1.2-6.5). It is worthy to note that these helminthes are collectively neglected tropical diseases and also known as diseases of poverty. Though malaria remains endemic, the results provide evidence of several other pathogens in circulation in Bo, Sierra Leone, one of which, Chikungunya, has a higher prevalence (46%) than malaria (23%). Among the bacteria, Salmonella enterica serotype Typhi is of importance as the population antibody levels has risen such that three-fifth of the study population had up to 1:120 titers of both Anti-O and Anti-H antibodies. A new cut-off point for the Widal test at about 1:160 or above is recommended to prevent over prescription of antibiotics for cases not related to typhoid. This study demonstrates the need to prioritize diagnosis and treatment of NMFIs in Sierra Leone.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral