A systematic review and meta-analysis of the aetiological agents of non-malarial febrile illnesses in Africa

Abstract

Background The awareness of non-malarial febrile illnesses (NMFIs) has been on the rise over the last decades. Therefore, we undertook a systematic literature review and meta-analysis of causative agents of non-malarial fevers on the African continent. Methodology We searched for literature in African Journals Online, EMBASE, PubMed, Scopus, and Web of Science databases to identify aetiologic agents that had been reported and to determine summary estimates of the proportional morbidity rates (PMr) associated with these pathogens among fever patients. Findings A total of 133 studies comprising 391,835 patients from 25 of the 54 African countries were eligible. A wide array of aetiologic agents were described with considerable regional differences among the leading agents. Overall, bacterial pathogens tested from blood samples accounted for the largest proportion. The summary estimates from the meta-analysis were low for most of the agents. This may have resulted from a true low prevalence of the agents, the failure to test for many agents or the low sensitivity of the diagnostic methods applied. Our meta-regression analysis of study and population variables showed that diagnostic methods determined the PMr estimates of typhoidal Salmonella and Dengue virus. An increase in the PMr of Klebsiella spp. infections was observed over time. Furthermore, the status of patients as either inpatient or outpatient predicted the PMr of Haemophilus spp. infections. Conclusion The small number of epidemiological studies and the variety of NMFI agents on the African continent emphasizes the need for harmonized studies with larger sample sizes. In particular, diagnostic procedures for NMFIs should be standardized to facilitate comparability of study results and to improve future meta-analyses. Reliable NMFI burden estimates will inform regional public health strategies.

Epidemiology, biology, pathogenesis, clinical manifestations, and diagnosis of dengue virus infection, and its trend in Ethiopia: a comprehensive literature review

“…In regions where DF case is found as endemic and/or epidemic, particularly in tropical and subtropical countries including in Ethiopia, patients with febrile illness compliance are main public disease, commonly sought medical attention [10]. In Ethiopia and in Africa as a whole, these febrile illnesses would likely caused by various infectious pathogens, complicating control and response programs to epidemic and pandemic diseases, such as malaria, Ebola and COVID-19 [11]. The manifestations of the febrile illnesses are the manifestations of DF and other arboviruses illness [12][13][14].…”

Metagenomic next-generation sequencing to characterize potential etiologies of non-malarial fever in a cohort living in a high malaria burden area of Uganda

“…In addition, the ability to generate whole viral genomes through mNGS could be leveraged to fill in existing gaps in pathogen genomic data from resource-limited settings for important pathogens. Continuing to refine our understanding of the pathogen landscape of non-malarial febrile illness [ 4 , 63 ] in different settings and age groups could open the way to inform control interventions and case management guidelines, allow for the implementation and design of new rapid, low-cost diagnostics to inform clinical decision-making, and improve public health surveillance systems.…”

“…falciparum is unlikely to be the cause of febrile illness. Taken together, the limited availability of diagnostics for pathogens beyond malaria results in many undiagnosed illnesses [ 4 ], missed opportunities for targeted treatments [ 5 ], unnecessary empiric use of antibiotics [ 6 ], and public health surveillance systems that provide an incomplete picture of the pathogen landscape [ 7 ].…”

Metagenomic next-generation sequencing to characterize etiologies of non-malarial fever in a cohort living in a high malaria burden area of Uganda

“…In addition, the ability to generate whole viral genomes through mNGS could be leveraged to fill in existing gaps in pathogen genomic data from resourcelimited settings for important pathogens. Continuing to refine our understanding of the pathogen landscape of non-malarial febrile illness [4,59] in different settings and age groups could open the way to inform control interventions and case management guidelines, allow for the implementation and design of new rapid, low-cost diagnostics to inform clinical decision-making, and improve public health surveillance systems. Table 1: Demographic and clinical characteristics of the study participants.…”

“…In individuals with parasitemia who have acquired high levels of clinical immunity, P. falciparum is unlikely to be the cause of febrile illness. Taken together, the limited availability of diagnostics for pathogens beyond malaria results in many undiagnosed illnesses [4], missed opportunities for targeted treatments [5], unnecessary empiric use of antibiotics [6], and public health surveillance systems that provide an incomplete picture of the pathogen landscape [7].…”