Multidrug-Resistant Typhoid Fever With Neurologic Findings on the Malawi-Mozambique Border


Emily Lutterloh, Andrew Likaka, James Sejvar, Robert Manda, Jeremias Naiene, Stephan S. Monroe, Tadala Khaila, Benson Chilima, Macpherson Mallewa, Sam D. Kampondeni, Sara A. Lowther, Linda Capewell, Kashmira Date, David Townes, Yanique Redwood, Joshua G. Schier, Benjamin Nygren, Beth Tippett Barr, Austin Demby, Abel Phiri, Rudia Lungu, James Kaphiyo, Michael Humphrys, Deborah Talkington, Kevin Joyce, Lauren J. Stockman, Gregory L. Armstrong, and Eric Mintz


Background: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi–Mozambique border.

Methods: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE).

Results: We identified 303 cases from 18 villages with onset during March–November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE.

Conclusions: The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.


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