ABSTRACT & COMMENTARY
Fever in African Children More than Malaria
By Philip R Fischer, MD
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
Dr. Fischer reports no financial relationships in this field of study.
SYNOPSIS: Most children presenting for care related to fever at two Tanzanian outpatient clinics had acute respiratory infections. Malaria accounted for "only" 11% of diagnoses and typhoid fever for 4%.
SOURCE:D'Acremont V, et al. Beyond malaria causes of fever in outpatient Tanzanian children. New Engl J Med 2014;370:809-17.
One thousand five children — age two months to ten years — presenting with fever at two outpatient clinics in Tanzania (one rural, one urban) were evaluated extensively for etiologic diagnoses. Acute respiratory infection was identified in 62% of the children; 5% of those children had radiographic evidence of pneumonia. Twelve percent had viral upper respiratory infection without respiratory signs. Other diagnoses included malaria (11%), gastroenteritis (10%), urinary tract infection (6%), typhoid fever (4%), and meningitis (0.2%). Multiple concurrent diagnoses were common (23% of children), and only 3% of study subjects had no identifiable cause of the fever. Overall, 71% of children had viral disease, 22% had bacterial disease, and 11% had parasitic disease.
Among the 71% of children with viral disease, influenza virus, adenovirus, and rhinovirus were commonly seen. In addition, respiratory syncytial virus, bocavirus, coronavirus, picornavirus, enterovirus, metapneumovirus, and parainfluenza virus were also identified in children with acute respiratory infection. Human herpesvirus 6, parvovirus B19, cytomegalovirus, and other viruses were identified in children with systemic infections. Salmonella or Shigella was found in 14% of children with febrile gastroenteritis. Bacteremia, Rickettsia, and Leptospira were found in some children. Of children with radiologically confirmed pneumonia and with severe acute respiratory infection, approximately 90% had PCR evidence of pneumococcal infection.
Thirty years ago, pediatric care providers in East and Central Africa were taught that "Fever = Chloroquine" meaning that the initial thought when facing a febrile child should be to give chloroquine. Obviously, the situation has changed. Chloroquine resistance emerged. And, even then — when half of febrile children in some areas were parasitemic with Plasmodium — those without malaria sometimes suffered poor outcomes because physicians and nurses did not consider other diagnoses.1 Further, laboratory infrastructures expanded so that causes of pediatric fever could be more accurately diagnosed. Now, a new study from Tanzania shows that malaria is far less common than before and points us to other likely causes of fever in children.
While the relative importance of malaria as a cause of fever is declining in some areas of Africa2 and childhood deaths due to malaria have dropped by 45% since 20003, malaria is still important. Eleven percent of febrile children presenting for care in Tanzania had malaria. Malaria still accounts for approximately 600,000 deaths of pre-school-aged children in Africa each year.3 According to World Health Organization guidelines, children presenting with fever in malaria-endemic areas should be tested for malaria.4
In parts of Tanzania, at least, most children presenting with fever do not have malaria. The vast majority had viral infections. Obviously, neither antibiotics nor anti-malarials were needed for these children. Protocols can be used whereby febrile outpatient children are tested for malaria and treated if positive, while those with fever and tachypnea can be treated with an antibiotic effective against pneumococcus. Children with fever and bloody diarrhea might be presumptively treated for bacterial dysentery (realizing that hydration and nutrition are likely most important while antibiotics can also play a positive role in management). At the same time, clinicians must also consider the possibilities of urinary tract infection, typhoid fever, and rickettsial disease. When a child is severely ill, hospitalization with presumptive treatment for malaria and bacteremia can still be reasonable.
Laboratory science has advanced dramatically, and only 3% of the children in the Tanzanian study had no etiologic diagnosis identified. Eventually, such detailed technology-dependent testing might become available throughout Africa, but we can already learn from studies like this that do extensive testing. We must remember that many children (23% in the Tanzanian study) are infected or colonized with multiple pathogens at the same time. Finding one pathogen (malaria, bacteria, or other) does not necessarily indicate that the identified pathogen is responsible for all or even part of the clinical illness. Clinicians must still interpret laboratory data in light of the clinical presentation. A recent Swedish study compared positive test results in children with acute respiratory illnesses and in healthy control children. Respiratory syncytial virus, metapneumovirus, and parainfluenza virus were associated with illness while some other potentially pathogenic respiratory viruses were identified equally in ill and well children.5 Similarly, a review of metagenomic analysis reminds us that highly sensitive tests are easily capable of identifying colonizing pathogens
unrelated to the symptoms.6
Thus disease frequencies are changing, and diagnostic strategies are expanding. While caring for children in Africa, we must continue to consider the possibilities of treatable life-threatening diseases such as malaria, pneumonia, typhoid fever, and bacteremia. We must remember to consider evaluation for urinary tract infection. We must consider covering with treatment for rickettsial infection in children with findings suggestive of this problem. But, at the same time, we must realize that the majority of febrile children in many areas — even in malaria-endemic developing countries — are sick with self-limited viral illnesses.
- Källander K et al. Delayed care seeking for fatal pneumonia in children aged under five years in Uganda: A case-series study. Bull World Health Organ 2008;86(5):332-8.
- D'Acremont V et al. Reduction in the proportion of fevers associated with Plasmodium falciparum parasitemia in Africa: a systematic review. Malaria J 2010;9:240.
- World Health Organization. Malaria. http://www.who.int/mediacentre/factsheets/fs094/en/
- World Health Organization. Guidelines for the treatment of malaria, 2nd edition. 2010. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/.
- Rhedin S et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics 2014;133:3538-45.
- Deresinski S. Febrile children in Nicaragua what can metagenomic analysis tell U.S.? Clin Infect Dis 2012;55(7):iii-iv.