Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia

Hopkins, Heidi; Bassat, Quique; Chandler, Clare I R; Crump, John A.; Feasey, Nicholas; Ferrand, Rashida A; Kranzer, Katharina; Lalloo, David G.; Mayxay, Mayfong; Newton, Paul N.; Mabey, David

doi:10.1136/bmjopen-2019-035632

Cited by 29 publications

(22 citation statements)

References 43 publications

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“…For instance, acute respiratory infections have been demonstrated as leading causes of febrile illness in children under five years [ 36 , 49 ]. However, there exists a rising number of standardised protocols from large multi-centre studies investigating non-malarial fevers which offer an opportunity to harmonise this important source of study heterogeneity in Africa [ 101 , 105 , 153 – 155 ]. Only a few studies included both cases and controls in the study design.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Host biomarkers will be selected on the basis of biological plausibility 39 , systematic review of the literature 29,33 , and the results of ongoing prospective studies 40,41 . The aim is to identify and test biomarkers that discriminate bacterial from viral infections, and those that are implicated in final common pathways to sepsis and severe febrile illness independent of microbial aetiology.…”

Section: Development Of Prognostic Clinical Prediction Models For Feb...mentioning

confidence: 99%

Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project

et al. 2022

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In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.

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“…were found to cause febrile disease in children less than 5 years in nearly half of the investigated cases in Burkina Faso, while in 24% of the cases, no causative agent was detected [ 18 ]. Recently, the Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study was established to investigate causes of febrile illness in three SSA countries as well as two Asian countries [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…While large-scale surveillance programs have investigated each syndrome on its own (e.g. the PERCH study among those with severe pneumonia [ 13 ], the GEMS study among those with GI [ 20 ] and the FIEBRE study among those with febrile illness but excluding ARI and GI cases [ 19 ]), simultaneous surveillance of all three highly related disease syndromes, across ecosystems and demographic settings, is still lacking to date. These syndromes are often treated empirically due to limited access to broad high-quality laboratory diagnostics, which hinders informed treatment decisions and targeted health interventions.…”

Section: Introductionmentioning

confidence: 99%

The African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents

et al. 2021

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Background In sub-Saharan Africa, acute respiratory infections (ARI), acute gastrointestinal infections (GI) and acute febrile disease of unknown cause (AFDUC) have a large disease burden, especially among children, while respective aetiologies often remain unresolved. The need for robust infectious disease surveillance to detect emerging pathogens along with common human pathogens has been highlighted by the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA) is a sentinel surveillance study on the aetiology and clinical characteristics of ARI, GI and AFDUC in sub-Saharan Africa. Methods ANDEMIA includes 12 urban and rural health care facilities in four African countries (Côte d’Ivoire, Burkina Faso, Democratic Republic of the Congo and Republic of South Africa). It was piloted in 2018 in Côte d’Ivoire and the initial phase will run from 2019 to 2021. Case definitions for ARI, GI and AFDUC were established, as well as syndrome-specific sampling algorithms including the collection of blood, naso- and oropharyngeal swabs and stool. Samples are tested using comprehensive diagnostic protocols, ranging from classic bacteriology and antimicrobial resistance screening to multiplex real-time polymerase chain reaction (PCR) systems and High Throughput Sequencing. In March 2020, PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and analysis of full genomic information was included in the study. Standardised questionnaires collect relevant clinical, demographic, socio-economic and behavioural data for epidemiologic analyses. Controls are enrolled over a 12-month period for a nested case-control study. Data will be assessed descriptively and aetiologies will be evaluated using a latent class analysis among cases. Among cases and controls, an integrated analytic approach using logistic regression and Bayesian estimation will be employed to improve the assessment of aetiology and associated risk factors. Discussion ANDEMIA aims to expand our understanding of ARI, GI and AFDUC aetiologies in sub-Saharan Africa using a comprehensive laboratory diagnostics strategy. It will foster early detection of emerging threats and continued monitoring of important common pathogens. The network collaboration will be strengthened and site diagnostic capacities will be reinforced to improve quality management and patient care.

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Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia

Cited by 29 publications

References 43 publications

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

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

Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project

The African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents

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