Acute Febrile Illness in Africa

1. Up-close and Candid with Acute Febrile Illness in Africa
Map of Africa(Wainaina et al., 2022)
Written by:
Stephen Olubulyera
Senior Public Health Specialist|Epidemiologist|Health Systems Strengthening
Specialist|Researcher|IT Enthusiast|FELTP Resident
Ministry of Health-Kenya
August 2022

2. Acute Febrile Illness (AFI)
Acute Febrile Illness(AFI), synonymous with acute undifferentiated febrile illness (AUFI), is
defined as fevers resolving in 3 weeks, lacking any localisable organ-specific signs or
symptoms(Bhaskaran et al., 2019). Febrile illness; defined as temperature >38˚C (fever)
without localising features (Nyaoke et al., 2019).
Globally, the burden of febrile illness and the contribution of many fever-inducing pathogens
have been challenging to quantify and characterise. Furthermore, it is clear that fever is a
common symptom, and febrile illness is a significant cause of illness and death in Sub-
Saharan Africa (Maze et al., 2018). In addition, AFI is a common cause of morbidity and
mortality in children and adults in low and middle-income countries (Bhaskaran et al., 2019).
The most common symptom among people living in Africa is fever, and its similar clinical
features in a broad spectrum of potential aetiologies challenge clinicians(Maze et al., 2018).
Clinical diagnosis is complex for patients with fever without localising features (Nyaoke et
al., 2019). In Sub-Saharan Africa, acute febrile illness is a frequent malaria diagnosis (Iroh
Tam et al., 2016).
Cases of febrile illnesses are empirically managed due to limited access to clinical laboratory
diagnostics(Hercik et al., 2017). Empirical management of cases for patients presenting with
acute febrile illness can result in disease treatment with unnecessary drugs or untreated
completely (Shimelis et al., 2020). Implementing comprehensive febrile surveillance through
robust epidemiological investigation enhanced with clinical microbiology and advanced
diagnostics could enable differential diagnosis for syndromic fevers for healthcare
providers, facilitating appropriate treatment and care(Hercik et al., 2017).
Despite being not recognised as a disease state by the World Health Organization, AFI
commonly causes hospital admission. Its association with infections contributes to
significant morbidity and mortality cases among children worldwide. Studies show that
hospitalisation cases have documented between 5% to 24% case fatality ratios in adults with
febrile illness (Iroh Tam et al., 2016). Pediatric studies investigating febrile illnesses with
fever for more than seven days reported that the most common cause of fever was infections;
autoimmune and oncologic diseases followed, respectively (Yoshizato & Koga, 2020).
While previous studies have globally adopted the syndromic approach in estimating the
burden of diseases (e.g. pneumonia and diarrhoea), none of the approaches considered cases
of syndromic fevers in evaluating the burden of disease in the absence of other
characterising features such as gastroenteritis, etc. Approaches have, however, been used to
evaluate febrile illness caused by specific pathogens, e.g. malaria, typhoid fever, and dengue
virus. As a result, the global burden estimates of fever associated with organisms are
uncertain (Hercik et al., 2017).
In places where the presence of fever used to be equated with malaria, malaria rapid
diagnostic tests (RDTs) have identified the often-large proportion of patients who do not

3. have malaria. However, diagnosing patients with febrile illness is challenging due to the non-
specific presentation of various conditions and the lack of available diagnostic tests.
Therefore, understanding the epidemiology of causes of fever has important implications for
managing febrile patients (Maze et al., 2018). Furthermore, the receding of malaria in Africa
leaves more cases of unexplained fevers: a justification for developing programs to detect
non-malarial febrile diseases (Mediannikov & Raoult, 2012). Public health data on AFI
etiological investigation are valuable sources. In addition, improved access to malaria
diagnostics has generated much research interest in fevers originating from non-malaria
causes, especially in countries with declining malaria incidence(Rhee et al., 2019).
Sentinel surveillance sites play a critical role in providing real-time information on the
epidemiology of febrile illness (Maze et al., 2018). World Health Organization has recognised
the significance of studying fever aetiologies in different settings while considering
population dynamics and level of care (Shimelis et al., 2020). Studies for multiple potential
causes of fever are scarce, and for many participants, the infecting organism remains
unidentified, or numerous co-infecting microorganisms are identified and establishing
causation is challenging (Hercik et al., 2017). Specific infections causing fever include
malaria, bacterial sepsis, a range of zones, and viral infections that are consequently
unaccounted for. Early diagnosis and management remain challenging issues to date.
(Shankar et al., 2014). Among ambulatory patients, self-limiting arboviral and viral upper
respiratory infections are common, occurring in up to 60% of children attending health
centres. The prevalence of potentially fatal infections that require special treatment is high
among hospitalised patients. Bacterial bloodstream infection and bacterial zoonoses are
significant causes of fever. Lack of multiple pathogen diagnostic approaches, temporal
coverage and geographical limitations in accounting for global disease variations are some
of the significant gaps identified by recent studies evaluating global surveillance status
(Hercik et al., 2017). Infections caused by zoonotic bacteria are commonly resistant to
standard antibiotics. Rickettsia or Coxiella burnetii were detected in 13% of cases of acute
febrile illness in Tanzania(Robinson & Manabe, 2017).
Most studies focus on a narrow range of suspected pathogens due to economic constraints
and practicability (Marks et al., 2021).
Studies in African countries found that acute respiratory or gastrointestinal infections
affected most children presenting with fever, mainly attributed to viral pathogens; therefore,
antimicrobial treatment was not amenable. Moreover, the studies also documented urinary
tract infections and blood infections resulting from treatable pathogens (Shimelis et al.,
2020). A regime for case management of different febrile illnesses is required, given that
various pathogens can cause the diseases. Pathogens include parasites (Plasmodium),
bacteria (Salmonella, Rickettsia or Leptospira) and viruses (Dengue, Chikungunya or Zika
virus). Thus, the misinterpretation of non-specific fever and the practice of solely empirical
diagnoses can lead to inadequate treatment, resulting in high mortality risk, continued
disease transmission and increased antimicrobial resistance(Hin et al., 2021).

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