Non-malarial Febrile Illness in Children in Areas of Perennial Malaria Transmission

2014-08-27 03:16:52 | BioPortfolio


To evaluate the causes of non-malarial febrile illness in children living in an area of perennial malaria transmission and to determine if these children who test negative for malaria by rapid diagnostic test receive any benefit from antimalarial therapy.


Until recently, national and global malaria control authorities recommended clinical diagnosis—based solely on the presence or history of fever—for most malaria treatment settings in sub-Saharan Africa where malaria transmission is sustained and intense. To some extent this recommendation was based on the fact that conventional antimalarial treatments like chloroquine or sulfadoxine-pyrimethamine (SP) were relatively affordable and safe and that microscopic diagnosis was complex and difficult to maintain in remote rural settings. It was economically advantageous and logistically more feasible to treat all potential cases as malaria than to extend microscopic diagnosis to every level of the health system. This approach has resulted in extensive over-treatment, particularly among older children and adults, and may have contributed to the rapid development of antimalarial drug resistance.

Although much has been written recently on the cost-effectiveness of expanding malaria diagnosis, available information is scarce on a number of other important reasons why clinical diagnosis has been recommended for so long, especially among children living in high transmission settings. First, uncomplicated malaria can progress to severe or fatal illness within 24 to 48 hours of onset. Numerous care-seeking studies have demonstrated that caretakers seldom arrive at formal health facilities within 24 or 48 hours after the onset of uncomplicated febrile illness. If a diagnostic test imposes additional barriers—such as cost, time delay, or referral—requiring a positive parasitological diagnosis could put children whose cause of fever is malaria infection at greater risk of progressing to severe or fatal illness. Second, although the current approach based on clinical diagnosis appears to result in substantial over-treatment, it is still possible to demonstrate that children living in malaria transmission areas benefit from additional scheduled doses of antimalarial treatment, even when they are not ill. For example, a meta-analysis of six trials of sulfadoxine-pyrimethamine (SP) given to children at routine immunization visits demonstrated an average decrease of 30% in episodes of clinical malaria, 15% in anemia, and 24% in all-cause hospital admissions among children receiving SP compared to children who did not receive the drug at these visits. Finally, providers and clients may be inclined to disregard a negative blood slide or RDT, especially in situations where they have not identified an additional treatable cause of illness. Withholding antimalarial treatments from such children might adversely affect provider and client satisfaction and poor client satisfaction may reduce subsequent health facility utilization. It might also encourage disappointed clients to seek treatment in the private sector where a broad range of antimalarial drugs—most of them single drug treatments that contribute to the development of resistance and which are not recommended in the national treatment policy—can be obtained without diagnostic confirmation.

We propose a longitudinal cohort study to evaluate the identifiable causes of treatable fever among 1000 malaria-negative children presenting to outpatient health clinics in Miono, Bagamoyo District, Tanzania using a variety of clinical, microbiological and serologic methods. In addition we intend to follow these 1000 malaria-negative children for up to 91 days or until their next malaria infection to assess their clinical progress and need for further malaria treatment. To compare the relative benefit of providing antimalarial treatment even to malaria-negative children, half of the participants will be randomized to receive first-line treatment for malaria as currently recommended; the other half will receive treatment only for other identified illnesses.

Alternative Hypothesis: Febrile, parasite-negative children treated for malaria have better clinical and longitudinal outcomes (as measured by prevalence of anemia at the end of the follow up period, reticulocyte count repeat visits to the health facility, hospitalization, and time to next infection with malaria parasites) than febrile, parasite-negative children not treated for malaria in areas of high transmission.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment






Miono Health Center
Bagamoyo District


Not yet recruiting


Centers for Disease Control and Prevention

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:16:52-0400

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Medical and Biotech [MESH] Definitions

Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.

Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.

A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.

Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.

A protozoan parasite that occurs naturally in the macaque. It is similar to PLASMODIUM VIVAX and produces a type of malaria similar to vivax malaria (MALARIA, VIVAX). This species has been found to give rise to both natural and experimental human infections.

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