Typhoid Fever and the Challenge of Nonmalaria Febrile Illness in Sub-Saharan Africa

In this issue of Clinical Infectious Diseases, 2 papers shed important light on the problem of typhoid fever in Sub-Saharan Africa and stimulate reflection on the challenges raised by the syndrome of fever in low-resource settings. Neil et al [1] report the investigation of an increase in intestinal perforations from rural western Uganda. By improving the clinical microbiology services available in the outbreak area and by implementing active surveillance at healthcare facilities in the district, the research team was able to confirm Salmonella enterica serovar Typhi as the etiologic agent and estimate the typhoid fever annual incidence in the study area at 8092 cases per 100 000 persons. This very high typhoid fever incidence rate was associated not only with hundreds of hospitalizations and intestinal perforations but also with 47 deaths. Lutterloh and colleagues [2] investigated an outbreak of unexplained febrile illnesses with neurologic findings along the Malawi–Mozambique border. Again, making diagnostic services available in the rural and remote outbreak area allowed Salmonella Typhi to be established as the cause. A careful clinical and epidemiologic investigation, including enhanced surveillance of suspected, probable, and confirmed cases of typhoid fever, characterized 40 patients with debilitating focal neurologic manifestations, including upper motor neuron signs, ataxia, and Parkinsonism, and 11 deaths. Fever is among the most common syndromes prompting persons to seek healthcare in Sub-Saharan Africa, and the numerous causes of febrile illness are often difficult to distinguish clinically. Although malaria may be ruled out by blood film examination or a malaria rapid diagnostic test, clinicians in resource-limited areas often have few diagnostic tools to determine the etiology and inform treatment decisions for those patients without malaria [3]. With encouraging gains in malaria control in some parts of Sub-Saharan Africa [4], the proportion of febrile patients without malaria grows. Invasive bacterial diseases represent a major cause of severe illness on the continent [5]. The ability to detect invasive bacterial disease by blood culture is invaluable not only to rationalize initial broad antimicrobial therapy but also to inform empiric treatment policies and to detect outbreaks when systematically collected bloodstream infection data are aggregated for a geographic area [5]. However, in resource-limited areas, the laboratory capacity to detect invasive bacterial disease is often restricted to major referral centers and research sites. Even when available, blood culture services may not be accessible to all patients with a clinical indication, and there may be concerns about the quality of the service [6]. In both of the outbreaks described here, the complications of intestinal perforation and neurologic manifestations provided the initial clue of typhoid fever as the possible cause, in turn leading to the identification of a much larger group of patients with typhoid fever presenting with undifferentiated fever. A typhoid rapid antibody test that has poor performance characteristics when assessed for individual patient diagnosis [7, 8] was applied during the initial stages of each investigation to help to support or rule out typhoid fever as the cause while conventional bacteriology services were being established. The application of a simple, rapid antibody test with performance characteristics that would normally preclude use for routine, individual patient management to groups of patients during the initial investigation of an outbreak of uncertain etiology in a remote area is notable and warrants further study. The epidemiology of the invasive salmonelloses, including typhoid fever, in Sub-Saharan Africa is incompletely Received 18 December 2011; accepted 22 December 2011; electronically published 22 February 2012. Correspondence: John A. Crump, MB, ChB, DTM&H, Centre for International Health, Dept of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin 9054, New Zealand (john.crump@otago.ac.nz). Clinical Infectious Diseases 2012;54(8):1107–9 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cis024