Tiered laboratory analyses for common infections to characterize febrile morbidity not related to malaria in Sierra Leone

Abstract

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 (