Our Acute Febrile Syndrome strategy

The need for better tests and diagnostic strategies for non-malaria febrile illness

If a febrile patient consulting a clinician/ health-worker in a malaria endemic area is tested and not just treated presumptively for malaria, they are most likely tested for malaria via microscopy or RDT. The test results are often negative, since non-malarial causes of fever are generally more common.

This creates a problem: the patient is still sick and needs care, while the health worker has limited capacity to distinguish between the many possible remaining causes of fever to decide on the best management. The patient, untreated, will usually recover, but alternatively the illness may progress to severe sickness and death. In fact, more people die of such illnesses in malaria-endemic areas than die of malaria,1 although most fatal cases of non-malarial febrile illness (NMFI) would have been cured if treated early with the right drugs. While the cause may become obvious later (e.g. a productive cough indicates pneumonia), the disease may have progressed to a point where prolonged illness or death ensues. If the patient could just access accurate diagnosis, either to identify the cause of illness or to identify whether the illness is likely to be severe or mild, outcomes of fever across much of the world could be vastly different.

To improve management of non-malarial fever, it’s not always necessary to identify the exact cause of the illness. Many causes of fever, in any country and any population, are mild and self-limiting, and are best managed by just controlling temperature or simply by observing. The illness resolves after a few days. Many mild viral throat infections are examples of this.

Other causes may respond to common antibiotics, and it is not necessary to identify the exact cause, but just the class of organisms that a particular antibiotic is effective against. On a basic level, careful questioning, observation and examination (clinical diagnosis) may be sufficient to guide management. The WHO's Integrated Management of Childhood Illnesses (IMCI) and Integrated Management of Adolescent and Adult Illnesses (IMAI) protocols used in many countries are based on this principle.

However, good clinical diagnosis is difficult to ensure, and in the best hands is poorly specific, unable to distinguish many potentially severe infections in their early stages. We need better information on infectious diseases to improve this. The role of a diagnostic test is to provide such information. This can tell us which are the most common causes encountered in a specific area, thus guiding clinical diagnosis, and can tell us whether a particular patient has an organism that is likely to result in severe illness avoidable by early, appropriate treatment.

1. Black, R. E., S. Cousens, et al. (2010). "Global, regional, and national causes of child mortality in 2008: a systematic analysis." Lancet: 11.

The ultimate aim is to have accurate point of care (POC) tests for all diseases
. In the meantime, much can be gained by investing in less specific tests which are achievable with current technology and which will take us a long way toward achieving this goal.


Our approach

To address acute fever as a syndrome (AFS - acute febrile syndrome), we:

  • consider that a sick person with acute fever may have:
  • malaria (treatable, must be detected quickly)
  • one of a number of other potentially severe infections (mostly treatable, must be detected quickly; NMFI)
  • other mild and self-limiting infection(s), such as viral respiratory tract infection (NMFI);
  • recognize that resources, both financial and human, are limited in our target countries and concentrate on diagnostic interventions that provide the highest return;
  • allow more effective use of existing drugs;
  • ensure tests/strategies are appropriate for the skills and workplace of clinicians/health workers;
  • minimize the need for additional logistical and other resource requirements for health services;
  • concentrate on platforms and tests that are compatible with existing tools (e.g. malaria tests);
  • concentrate on tests/strategies that are sustainable within a national health programme, minimizing need for long-term external support.

Specifically, we:

  1. improve knowledge of aetiology to improve current clinical algorithms;
  2. develop Markers of Severity and Responsiveness to treatment (MSR) to guide treatment with common antimicrobials and decisions on referral/safe return home;
  3. develop pathogen-specific tests, ideally in a multiplex format (e.g. with malaria tests).


AFS strategy

Animated presentation on FIND's AFS strategy


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