Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

Abstract

Introduction

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods and Findings

We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions

Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.

Author Summary

The syndrome of fever is caused by a large number of infectious diseases. Malaria is thought to have been declining in the tropics since 2004. Increasing use of malaria diagnostic tests reveal a growing proportion of patients with fever who do not have malaria. While malaria diagnostic tests may be available, healthcare workers have few tools to diagnose causes of fever other than malaria. In order to identify major causes of fever other than malaria in northern Tanzania, we studied 870 patients with fever who were sufficiently ill to require admission to hospital. Malaria was uncommon and over-diagnosed, whereas invasive infections, including bloodstream infections, were underappreciated. Infections associated with animals such as brucellosis, leptospirosis, Q fever, and spotted fever group rickettsioses as well as viral infections transmitted by mosquitoes were common yet overlooked. We recommend that research on the syndrome of fever in resource-limited areas should focus on a wide range of potential causes. Animal-associated infections should be prioritized in patient management and disease control.