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Etiology of Genital Ulcer Disease and Association With HIV Infection in Malawi

Phiri, Sam PhD, MSc, DCM*†; Zadrozny, Sabrina MS; Weiss, Helen A. MSc, DPhil; Martinson, Francis MD, PhD; Nyirenda, Naomi Cert Nursing; Chen, Cheng-Yen MD, PhD§; Miller, William C. MD, PhD; Cohen, Myron S. MD; Mayaud, Philippe MD, MSc, DTM&H; Hoffman, Irving F. PA, MPH

doi: 10.1097/OLQ.0000000000000051
Original Study

Background The World Health Organization recommends the use of syndromic management for patients presenting with genital ulcer disease (GUD) in developing countries. However, effective treatment guidelines depend on a current country-specific GUD etiological profile, which may change over time.

Methods From 2004 to 2006, we conducted a cross-sectional analysis of baseline data from patients presenting with GUD at a reference STI clinic in Lilongwe, Malawi. Participants were enrolled in a randomized clinical trial of acyclovir added to syndromic management and followed up for up to 28 days. Serologies for HIV (using parallel rapid tests), herpes simplex virus type 2 (HSV-2; using Focus HerpeSelect IgG2 ELISA [Focus Technologies, Cypress Hill, CA]), and syphilis (rapid plasma reagin confirmed by Treponema pallidum hemagglutination) were determined, with plasma HIV-1 RNA and CD4 count in HIV-positive patients. Genital ulcer disease etiology was determined by real-time multiplex polymerase chain reaction from lesional swabs.

Results A total of 422 patients with GUD (313 men; 74%) were enrolled. Overall seroprevalence of HIV-1, HSV-2, and syphilis were 61%, 72%, and 5%, respectively. Ulcer etiology was available for 398 patients and showed the following: HSV-2, 67%; Haemophilus ducreyi, 15%; T. pallidum, 6%; lymphogranuloma venereum, 6%; mixed infections, 14%, and no etiology, 20%. Most HSV-2 ulcers were recurrent (75%). Among all patients with HSV-2, HIV prevalence was high (67%) and HIV seroprevalence was higher among patients with recurrent HSV-2 compared with patients with first-episode HSV-2 (78% vs. 39%, P < 0.001).

Conclusions Herpes simplex virus type 2 ulcers are highly prevalent in this symptomatic population and strongly associated with HIV. Unlike most locations in sub-Saharan Africa, H. ducreyi remains prevalent in this population and requires periodic monitoring and an appropriate treatment regimen.

Herpes simplex virus type 2 ulcers are highly prevalent and strongly associated with HIV in this symptomatic population. Unlike most locations in sub-Saharan Africa, Haemophilus ducreyi remains prevalent and requires monitoring and appropriate treatment.

From the *Lighthouse Centre, Lilongwe, Malawi; †University of North Carolina, Chapel Hill, NC; ‡Infectious Disease Epidemiology Unit, London School of Hygiene & Tropical Medicine, London, UK; §University of North Carolina Project, Lilongwe, Malawi; §Centres for Disease Control and Prevention, Atlanta, GA; and ¶Clinical Research Unit, London School of Hygiene & Tropical Medicine, London, UK

Acknowledgments: The authors thank all men and women who participated in this study, the clinical staff at Kamuzu Central Hospital STI clinic, and all staff involved in the study from University of North Carolina (UNC) Project teams, both at the Tidziwe Centre in Lilongwe and at Chapel Hill, NC. They also thank Debbie Kamwendo who supervised the laboratory analysis in Lilongwe; Kai-Hua Chi, who performed all genital ulcer disease testing at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA; and the members of the Data Safety and Monitoring Committee (Chair: Professor Simon Cousens from the London School of Hygiene and Tropical Medicine; Dr Peter Leone from UNC, Chapel Hill; and the late Dr George Joaki from the UNC Project, Lilongwe). The authors like to express their gratitude to the Malawi National STI Task Force chaired by the Reproductive Health Unit of the Ministry of Health who commissioned and supported this study.

Conflict of interest: The authors declare that they have no commercial or other association that might pose a conflict of interest (eg, pharmaceutical stock ownership, consultancy, advisory board membership, patents, or research funding)

Financial support: The study was funded by the UK Department for International Development through the Malawi National AIDS Commission and by grants from the UNC at Chapel Hill, NC. The views expressed are those of the authors and cannot be taken to reflect the official opinions of the Department for International Development or of the US CDC.

Presentation: This work was presented as an oral presentation at the XVII International AIDS Conference, Mexico City, Mexico, 3rd–8th August 2008: Phiri S. Hoffman I, Weiss HA, et al. Impact of acyclovir on ulcer healing and HIV-1 lesional and genital shedding among patients with genital ulcer disease in Malawi: A randomized controlled trial. [Oral THAC0303].

Trial registration: The trial was registered with International Standard Randomised Controlled Trial Register No. ISRCTN32121857.

Contributions: Sam Phiri, Irving Hoffman, Helen Weiss, William C. Miller, and Philippe Mayaud designed the study. Myron Cohen contributed to the study concept. Sam Phiri coordinated and supervised the field implementation of the study with assistance of Francis Martinson and Naomi Nyirenda. Cheng-Yen Chen supervised the laboratory analysis at CDC in Atlanta, GA. Sam Phiri, Helen Weiss, Sabrina Zadrozny, and William C. Miller undertook all statistical analyses. Sam Phiri, Irving Hoffman, Sabrina Zadrozny, Myron Cohen, Helen Weiss, William C. Miller, and Philippe Mayaud produced the first draft of the manuscript. All authors contributed to the interpretation of results and writing of the manuscript.

Correspondence: Sam Phiri, PhD, Lighthouse Centre, Kamuzu Central Hospital, PO Box 106, Lilongwe, Malawi. E-mail:

Received for publication June 4, 2013, and accepted September 23, 2013.

© Copyright 2013 American Sexually Transmitted Diseases Association