Journal Article

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome

Omar, Rahila S., Ali, Abdullah S., Petzold, Max, Mårtensson, Andreas, Bachelard, Marc, Msellem, Mwinyi I., Parola, Philippe, Falk, Kerstin I., Elfving, Kristina, Lindh, Magnus, Trollfors, Birger, Xu, Weiping, Shakely, Deler, Björkman, Anders, Baltzell, Kimberly, Ljung, Annika, Andersson, Maria

2016

Overview

Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute Disease / Anti-Bacterial Agents - therapeutic use / Antibiotics / Bacteria / Bacterial infections / Biology / Biology and Life Sciences / Blood / C-reactive protein / Care and treatment / Case-Control Studies / Child, Preschool / Children / Coccidioidomycosis / Complications and side effects / Dengue / Dengue fever / Diagnosis / Diarrhea / Disease transmission / Dosage and administration / Etiology / Febrile seizures / Female / Fever / Fever - drug therapy / Fever - virology / Genetic aspects / Health care / Human health and pathology / Humans / Illnesses / Independent variables / Infant / Infections / Infectious diseases / Influenza / Influenza A / Influenza, Human - drug therapy / Laboratories / Life Sciences / Malaria / Male / Maternal & child health / Medical diagnosis / Medicine and Health Sciences / Pathogens / Patients / Pediatrics / Pediatrik / People and Places / Plasmodium falciparum / Pneumonia / Polymerase chain reaction / Primary care / Prospective Studies / Rectum / Regression analysis / Respiratory syncytial virus / Respiratory Syncytial Virus Infections - drug therapy / Respiratory Syncytial Virus Infections - epidemiology / Respiratory tract / Respiratory tract diseases / Rhinovirus / Rift Valley fever / Studies / Tanzania - epidemiology / Treatment Outcome / Urine / Vector-borne diseases / Viral diseases / Viruses