Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from Africa, 1980-2015

Abstract

Background: The availability of reliable point-of-care tests for malaria has heralded a paradigm shift in the management of febrile illnesses away from presumptive antimalarial therapy. In the absence of a definitive diagnosis, health care providers are more likely to prescribe empirical antimicrobials to those who test negative for malaria. To improve management and guide further test development, better understanding is needed of the true causative agents and their geographic variability.

Methods: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in Africa (1980-2015). Literature searches were conducted in English and French languages in six databases: MEDLINE, EMBASE, Global Health (CABI), WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. A number of published articles (rather than incidence or prevalence) reporting a given pathogen were presented.

Results: A total of 16,523 records from 48 African countries were screened, of which 1065 (6.4%) met selection criteria. Bacterial infections were reported in 564 (53.0%) records, viral infections in 374 (35.1%), parasitic infections in 47 (4.4%), fungal infections in nine (0.8%), and 71 (6.7%) publications reported more than one pathogen group. Age range of the study population was not specified in 233 (21.9%) publications. Staphylococcus aureus (18.2%), non-typhoidal Salmonella (17.3%), and Escherichia coli (15.4%) were the commonly reported bacterial infections whereas Rift Valley fever virus (7.4%), yellow fever virus (7.0%), and Ebola virus (6.7%) were the most commonly reported viral infections. Dengue virus infection, previously not thought to be widespread in Africa, was reported in 54 (5.1%) of articles.

Conclusions: This review summarises the published reports of non-malaria pathogens that may cause febrile illness in Africa. As the threat of antimicrobial resistance looms, knowledge of the distribution of infectious agents causing fever should facilitate priority setting in the development of new diagnostic tools and improved antimicrobial stewardship.

Trial registration: PROSPERO, CRD42016049281.

Keywords: Aetiology; Africa; Diagnosis; Febrile illness; Fever; Malaria; Microbiology; Non-malarial febrile illness.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of publications screened in a systematic review of published aetiological studies and case reports from Africa, 1980–2015

Fig. 2

Location of study sites in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: Location of study sites reported on in this review (in blue) augmented with major cities (in red). Data on major cities were obtained from “maps” package in R software, and for the purpose of this review, only cities with population greater than 100,000 are shown. Case series included individual case reports or series of patients with the same condition. Studies were classed as fever series if the total population denominator tested was reported. Seroprevalence studies were those where serum samples were tested for one pathogen or a panel of pathogens simultaneously

Fig. 3

The number of publications by country, in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: The total number of studies reported from each of the country over the review period from 1980 to 2015. Case series included individual case reports or series of patients with the same condition. Studies were classed as fever series if the total population denominator tested was reported. Seroprevalence studies were defined if serum samples were tested for one pathogen or a panel of pathogens simultaneously

Fig. 4

The most commonly reported bacterial infections by mode of transmission, in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: The left-hand panel includes data from all study types (case series, fever series, and seroprevalence studies). The right-hand panel is restricted to fever series data. The graph presents the top 10 pathogens (based on the number of the published articles) by epidemiological mode of transmission. The numbers inside each dot represent the number of articles

Fig. 5

The most commonly reported viral infections by mode of transmission, in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: The left panel includes data from all the study types (case series, fever series, and seroprevalence studies). The right panel is restricted to the fever series data. The graph presents the top 10 pathogens (based on the number of the published articles) by epidemiological mode of transmission. The numbers inside each dot represent the number of articles

Fig. 6

Viral haemorrhagic fever, in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: CCHF Crimean-Congo haemorrhagic fever virus. The map shows the location of study sites reporting each pathogen. No distinction has been made between case series, fever series, and seroprevalence studies

Fig. 7

Reports of dengue, chikungunya, and Zika viral infections, a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: DENV dengue virus, ZIKV Zika virus. For DENV, serotypes were not reported in 35 publications. The map shows the location of study sites reporting each pathogen. No distinction has been made between case series, fever series, and seroprevalence studies

Fig. 8

Studies reporting vaccine-preventable infections which are part of the WHO routine Expanded Programme on Immunisation, in a systematic review of published aetiological studies and case reports from Africa, 1980–2015. Legend: The map shows the location of study sites reporting each pathogen. No distinction has been made between case series, fever series, and seroprevalence studies