If it’s not Malaria, What is Causing the Fever?

Manhiça District Hospital (Mozambique)

Malaria can be considered one of the most devastating diseases that has affected mankind. It has been present throughout history, with a terrible impact into population survival.  Indeed, the overwhelming public health burden imposed by this single disease to populations living in areas where this infection was heavily transmitted, has historically meant that in many of these settings, the term “fever” was traditionally considered a synonym of malaria, given that an elevated body temperature was its landmark symptom. Similarly, the term “quinine”, which should only refer to one of the most common therapeutic agents against malaria, was very loosely used as “drug for fever”, including any tablet or syrup administered when a person was perceived to be “hot”.

The term “fever” was traditionally considered a synonym of malaria, given that an elevated body temperature was its landmark symptom

Malaria diagnosis suffered a massive revolution with the advent and wide implementation of the rapid diagnostic tests (RDTs). These lateral flow immuno-chromatographic antigen-detection tests, which are extremely simple to use, can provide a robust diagnosis at the point of care, bypassing the need to perform more complex, and energy dependent diagnostic tests. Malaria RDTs have thus democratized malaria diagnosis, and as a result, it would now be considered inconceivable to diagnose malaria on the basis of its symptomatology alone.

Manhiça District Hospital (Mozambique)

In recent years, however, and particularly so in the last decade, malaria incidence has steadily decreased globally, and in some areas it represents no longer the primary cause of fever in the population, as it used to be. As an example, back in the year 2003, when I first went to Manhiça, a rural area in Southern Mozambique, to work as a pediatrician, malaria was by far the number one cause of health system consultation, causing over 60% of hospitalizations, and nearly half of all outpatient visits. After the abovementioned descending trends, malaria caused in the last 2 years (2017-28) less than 15-20% of all paediatric admission, and a mere 2.5% of all outpatient visits. It is therefore not difficult to understand that the proportion of febrile patients seen in settings like Manhiça, which have malaria as the cause of their fever, is swiftly decreasing. But then, if it’s not malaria, what is causing the fever?

This is a very important question that requires an adequate answer, as management algorithms for the febrile patients heavily depend on understanding the underlying cause of the fever, so as to trigger the most adequate treatment. Indeed, health professionals working in malaria endemic areas are increasingly faced with the diagnostic and therapeutic challenge of what to do with those febrile patients which have a negative malaria test.

Health professionals working in malaria endemic areas are increasingly faced with the diagnostic and therapeutic challenge of what to do with those febrile patients which have a negative malaria test

And this is a question the FIEBRE (Febrile Illness Evaluation in a Broad Range of Endemicities) study is trying to answer. FIEBRE is coordinated by the London School of Tropical Medicine and Hygiene (LSHTM), and simultaneously occurs in five countries of the world (Mozambique, Malawi, Zimbabwe in Sub-Saharan Africa, and Laos and Myanmar in South East Asia), whereby adult and children with fever are thoroughly studied to investigate the main pathogens associated with the increase of body temperature.

Beyond malaria and other typical viruses and bacteria well-established to cause fever, a panoply of other less common pathogens to be sought include blood parasites; bacterial, mycobacterial, and fungal bloodstream infections; typhus and spotted fever; and arboviruses including dengue, chikungunya, Zika, and Japanese encephalitis, among others. These pathogens will be systematically investigated, thus, allowing for the first time, the ascertainment of a robust and representative estimate of fever aetiology in the two continents.

 

 

 

 

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The first volunteer has enrolled this week in the #FIEBRE project! With this study, we aim to identify causes of fever in children and adults in sub-Saharan Africa and southeast Asia, and assess antimicrobial resistance. Have a good kick off, FIEBRE team! ������ ¡Esta semana se ha sumado el primer voluntario al proyecto FIEBRE! Con este estudio, queremos identificar las causas de la fiebre en la población infantil y adulta en el África Subhariana y el sudeste asiático, y evaluar la resistencia antimicrobiana. ¡Buen inicio de proyecto, equipo de FIEBRE! ������ #antimicrobialresistance #AMR #fiebre #fever #Mozambique #resistenciaantimicrobiana #antibióticos #antibiotics #ISGlobal

A post shared by ISGlobal (@isglobalorg) on Dec 11, 2018 at 10:47am PST

FIEBRE aims to recruit over 12,000 patients, and around 3,000 healthy community controls, and produce for the first time a detailed description of the causes of fever in such a large study population. FIEBRE will also provide a fantastic platform for monitoring antimicrobial susceptibility to the pathogens detected, allowing the generation of very useful data regarding one of the major global health crises in our current times, i.e antimicrobial resistance.

FIEBRE aims to recruit over 12,000 patients, and around 3,000 healthy community controls, and produce for the first time a detailed description of the causes of fever in such a large study population

At the Manhiça District Hospital, in Mozambique, investigators from the Centro de Investigação em Saúde de Manhiça (CISM), in close partnership with the Barcelona centre of Global Health (ISGlobal), have been recruiting study patients for the past four months, and over 300 children have already been included in the study, with adult recruitment having recently started. It is likely that the information generated through this project will be highly relevant both nationally, and also internationally; and may allow a more targeted management of fever, the most common symptom of disease, and a historical harbinger of bad outcomes among populations in poor countries.