Etiology of Pediatric Fever in Western Kenya: A Case–Control Study of Falciparum Malaria, Respiratory Viruses, and Streptococcal Pharyngitis

Abstract

Abstract. In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed.

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda

“…For 20% of NP swabs and 33.3% of serum samples, no microbial species met our thresholds for detection. These proportions are consistent with previous reports [32,34,35,39].…”

“…Additionally, in the above study, 9% of the children had malaria and 4.2% had bacteremia. In febrile children in Kenya, reported pathogens were spotted fever group Rickettsiae (22.4%), influenza (22.4%), adenovirus (10.5%), parainfluenza virus 1-3 (10.1%), Q fever (8.9%), RSV (5.3%), malaria (5.2%), scrub typhus (3.6%), human metapneumovirus (3.2%), group A Streptococcus (2.3%) and typhus group Rickettsiae (1.0%) [35,36]. Another study reported bacteremia in 19.1% of children admitted to a referral hospital in Uganda [37].…”

Serologic evidence for hepatitis E virus infection among patients with undifferentiated acute febrile illness in Kibera, Kenya

“…Previous studies in the East African region demonstrate that respiratory viruses account for the majority of febrile illness [18–19], malaria was an infrequent cause of fever in Kenya (≤5%) [19–20], and viral hepatitis was rare [18]. Unfortunately, data on these concomitant infections were not available for our analysis.…”

Challenges in the Etiology and Diagnosis of Acute Febrile Illness in Children in Low- and Middle-Income Countries

“…One patient who had neither a clinical nor a biologic malaria diagnosis was also treated with an antimalarial agent [97]. In a Kenyan study, 80% of all children who presented with acute febrile illness, including 72% of children with a negative malaria smear result, were prescribed antimalarial agents [13]. In a study performed in India, 33.8% of >1600 febrile patients received antimalarial drugs, 75% of whom had 1 negative malaria test result [98].…”

“…However, since the introduction of rapid diagnostics for malaria and implementation of malaria-control strategies in several countries, the number of diagnosed malaria cases has declined substantially [4][5][6][7][8][9]. As a consequence, the overdiagnosis of malaria and overtreatment in febrile illness has been increasingly recognized [10][11][12][13] and necessitates an improved understanding of nonmalarial causes of acute febrile illness [14].…”