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

Abstract

BackgroundDespite 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.MethodsWe 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.FindingsNPH-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.ConclusionsThis 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.

Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings

“…[51][52][53] Not all bacterial causes of fever lead to bacteraemia, but, for example, in young children with uncomplicated febrile illness in Zanzibar, just 22% had an infection retrospectively considered to require antibiotics. 54 At a population level it is likely that relatively few patients in our studies had bacterial infections requiring antibiotic treatment, and the incidence is unlikely to be anywhere near the 69% suggested by antibiotic prescription to those with negative results of malaria tests.…”

Global Emergency Medicine: A Review of the Literature From 2016

“…The 2016 global EM articles selected for full review are listed in Table 4. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Nineteen articles were selected for inclusion, of which 15 (79%) were categorized as emergency care, three (16%) were categorized as development, and one (5%) was categorized as disaster response articles. Eighteen (95%) articles were original research manuscripts and one (5%) was a review article.…”

“…A study from Baudin et al 16 reports on the association of Rift Valley fever on miscarriages among women in Sudan. Traditional infectious diseases emergencies, such as undifferentiated fever in children, also remain prominent in the literature, as exemplified by Elfving et al 20 who evaluated the etiology and management of febrile children in Zanzibar using modern nucleic acid-based diagnostic testing in an area that has benefited from a marked decrease in malaria. The continued challenge of managing febrile infants took a significant step forward with the article by Mir et al, 23 who demonstrated that simplified antibiotic regimens, with an emphasis on oral therapy as outpatients, was equivalent to traditional inpatient management with parenteral antibiotics.…”

Epidemiology and molecular characterization of influenza viruses in Burkina Faso, sub‐Saharan Africa

“…The vast majority of ILI patients enrolled in this study were treated with antibiotics, despite that viruses are usually the main cause of uncomplicated ILI . This high proportion, which is not uncommon and not solely an issue of low‐income countries, highlights the need for revision of clinical best practice to identify cases of bacterial (co)infections . Education and awareness of the healthcare personnel as well as the patients’ parents toward the risks linked to antibiotic resistance will also be necessary to efficiently control over‐prescriptions …”