Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar

Abstract

BackgroundThe increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases.MethodologyConsenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status.Principal findingsA total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections.ConclusionsThese results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar.

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

“…In the absence of reliable data, health care providers often resort to prescription of empiric antimicrobial therapies [5][6][7], potentially promoting the emergence and spread of antimicrobial resistance (AMR). This has catapulted the improvement of fever case management into the limelight as a global health priority, with a recent proliferation of articles describing aetiologies of non-malarial febrile illnesses (NMFI) in low-and middleincome countries [4,6,[8][9][10][11][12].…”

Leukocytosis in Negative Malaria Rapid Diagnostic Test Febrile Illness Among Children Under Five Years in a District Hospital

“…Some studies have gone ahead to attempt confirmatory tests without very convincing results. In one of these works after administering specialized tests, the vast majority (59.5%) of febrile childhood illnesses did not demonstrate an identifiable causative agent (3). From this particular study, it may be inferred that the quest for an exhaustive panel of specialized diagnostic tests for tropical infections among children would, perhaps, not be cost-effective after all.…”

“…It is not unusual in endemic communities for malaria to be present in the same patient alongside other leukocytosis-eliciting microbial infections but this situation could not be accounted for in the study because of the stated objectives. Occasionally, febrile presentation among children under five years have nothing to do with any pathogen (3,9) and this could be one reason, perhaps, for which more than half of RDT-negative febrile children were observed to have normal WBC counts. This significance of this category of patients should be appreciated and examined in any future studies.…”

“…Coinfections, sometimes, could prove challenging in the determination of the primary pathology causing a fever. D'Acremont et al, in their two-centre nonramdomized study in Tanzania discovered 22.6% of their 1005 study participants had coinfections (9) while this was the case in 6% of the 682 participants evaluated by Guillebaud et al (3). However, be it viral, bacterial or polymicrobial in etiology, febrile leukocytosis once confirmed, would still support the likely association with some form of infection in most tropical settings among children under five years of age.…”

“…This was a drop from the 48% RDT-positive prevalence rate observed in the 2011 Ghana -Multiple Indicator Cluster Survey (MICS) (2). These findings suggest that a sizeable population of febrile children under-5 may not have malaria (3) and require, perhaps, further investigations to ascertain their diagnosis and, subsequently, the appropriate treatment. The actual proportion of malaria-related U-5 febrile illness presenting to district hospitals in Ghana has been suspected in some studies to be much higher than reported in the national surveys (4).…”