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RefWorks
Reference Manager
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Zotero
EndNote
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Siddiqi OK, Ghebremichael M, Dang X, Atadzhanov M, Kaonga P, Khoury MN, Koralnik IJ, 2014. Molecular diagnosis of central nervous system opportunistic infections in HIV-infected Zambian adults. Clin Infect Dis 58: 1771–1777.
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Wall EC, Everett DB, Mukaka M, Bar-Zeev N, Feasey N, Jahn A, Moore M, van Oosterhout JJ, Pensalo P, Baguimira K, Gordon SB, Molyneux EM, Carrol ED, French N, Molyneux ME, Heyderman RS, 2014. Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000–2012. Clin Infect Dis 58: e137–e145.
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Beyene T, Woldeamanuel Y, Asrat D, Ayana G, Boulware DR, 2013. Comparison of cryptococcal antigenemia between antiretroviral naïve and antiretroviral experienced HIV positive patients at two hospitals in Ethiopia. PLoS ONE 8: e75585.
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O'Grady J, Bates M, Chilukutu L, Mzyece J, Cheelo B, Chilufya M, Mukonda L, Mumba M, Tembo J, Chomba M, Kapata N, Maeurer M, Rachow A, Clowes P, Hoelscher M, Mwaba P, Zumla A, 2012. Evaluation of the Xpert MTB/RIF assay at a tertiary care referral hospital in a setting where tuberculosis and HIV infection are highly endemic. Clin Infect Dis 55: 1171–1178.
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Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort
Radha Rajasingham
Radha Rajasingham
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Joshua Rhein
Joshua Rhein
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Kate Klammer
Kate Klammer
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Abdu Musubire
Abdu Musubire
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Henry Nabeta
Henry Nabeta
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Andrew Akampurira
Andrew Akampurira
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Eric C. Mossel
Eric C. Mossel
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Darlisha A. Williams
Darlisha A. Williams
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Dave J. Boxrud
Dave J. Boxrud
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Mary B. Crabtree
Mary B. Crabtree
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Barry R. Miller
Barry R. Miller
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Melissa A. Rolfes
Melissa A. Rolfes
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Supatida Tengsupakul
Supatida Tengsupakul
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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Alfred O. Andama
Alfred O. Andama
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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David B. Meya
David B. Meya
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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David R. Boulware
David R. Boulware
University of Minnesota, Minneapolis, Minnesota; Infectious Disease Institute, Makerere University, Kampala, Uganda; Minnesota Department of Health, St. Paul, Minnesota; Centers for Disease Control and Prevention, Fort Collins, Colorado; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
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There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical.
Author Notes
Financial support: Research support for aspects of this project was received from the National Institutes of Health and Fogarty International Center (R21NS065713, K23AI073192, U01AI089244, T32AI055433, R25TW009345, T32HD068229). Partially funded by an Interagency Agreement between CDC and the Defense Threat Reduction Agency.
Authors' addresses: Radha Rajasingham, University of Minnesota, Infectious Diseases and International Medicine, Minneapolis, MN, and Infectious Diseases Institute, Makarere University, Kampala, Uganda, E-mail: radha.rajasingham@gmail.com. Joshua Rhein and Darlisha A. Williams, University of Minnesota, Medicine, Minneapolis, MN, and Infectious Diseases Institute, Makarere University, Kampala, Uganda, E-mails: joshua.rhein@gmail.com and coat.trial@gmail.com. Kate Klammer, Minnesota Department of Health, N/A, St. Paul, MN, E-mail: kate.klammer@mn.state.us. Abdu Musubire, Henry Nabeta, and Andrew Akampurira, Infectious Diseases Institute, Makarere University, Kampala, Uganda, E-mails: amusubire@yahoo.com, hwnabeta@gmail.com, and scandrie@yahoo.com. Eric C. Mossel and Barry R. Miller, Centers for Disease Control and Prevention, N/A, Fort Collins, CO, and Centers for Disease Control and Prevention/Fort Collins, Division of Vector-Borne Infectious Diseases, Fort Collins, CO, E-mails: ilv8@cdc.gov and brm4@cdc.gov. Dave J. Boxrud, Minnesota Department of Health, N/A, St Paul, MN, E-mail: dave.boxrud@state.mn.us. Melissa A. Rolfes and Supatida Tengsupakul, University of Minnesota, Medicine, Minneapolis, MN, E-mails: melissa.rolfes@gmail.com and tengs001@umn.edu. Alfred O. Andama, Makerere University College of Health Sciences, Department of Medicine, Kampala, Uganda, E-mail: andama.alf@gmail.com. David B. Meya, Makerere University, Faculty of Medicine, Kampala, Uganda, E-mail: david.meya@gmail.com. David R. Boulware, University of Minnesota, Medicine, Minneapolis, MN, E-mail: boulw001@umn.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
WHO, 2013. Health Topics: Meningitis. Available at: http://www.who.int/topics/meningitis/en/. Accessed January 20, 2013.
-
2.
WHO, 2007. Standardized Treatment of Bacterial Meningitis in Africa in Epidemic and Non-Epidemic Situations. WHO/CDS/EPR/2007.3. Geneva: WHO Press.
-
3.
Jarvis JN, Meintjes G, Williams A, Brown Y, Crede T, Harrison TS, 2010. Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis 10: 67.
-
4.
Hakim JG, Gangaidzo IT, Heyderman RS, Mielke J, Mushangi E, Taziwa A, Robertson VJ, Musvaire P, Mason PR, 2000. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS 14: 1401–1407.
-
5.
Amuron B, Levin J, Birunghi J, Namara G, Coutinho A, Grosskurth H, Jaffar S, 2011. Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study. AIDS Res Ther 8: 39.
-
6.
Bhagwan S, Naidoo K, 2011. Aetiology, clinical presentation, and outcome of meningitis in patients coinfected with human immunodeficiency virus and tuberculosis. Aids Res Treat 2011: 180352.
-
7.
Cohen DB, Zijlstra EE, Mukaka M, Reiss M, Kamphambale S, Scholing M, Waitt PI, Neuhann F, 2010. Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Trop Med Int Health 15: 910–917.
-
8.
Siddiqi OK, Ghebremichael M, Dang X, Atadzhanov M, Kaonga P, Khoury MN, Koralnik IJ, 2014. Molecular diagnosis of central nervous system opportunistic infections in HIV-infected Zambian adults. Clin Infect Dis 58: 1771–1777.
-
9.
Wall EC, Everett DB, Mukaka M, Bar-Zeev N, Feasey N, Jahn A, Moore M, van Oosterhout JJ, Pensalo P, Baguimira K, Gordon SB, Molyneux EM, Carrol ED, French N, Molyneux ME, Heyderman RS, 2014. Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000–2012. Clin Infect Dis 58: e137–e145.
-
10.
National Institute for Communicable Diseases, 2012. GERMS-SA Annual Report 2012. Meiring S, Quan V, Govender N, Crowther-Gibson P, eds. Available at: http://www.nicd.ac.za/?page=publications&id=155. Accessed October 28, 2014.
-
11.
Berhe T, Melkamu Y, Amare A, 2012. The pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestation in Ethiopia: a retrospective study. AIDS Res Ther 9: 11.
-
12.
Alemu AS, Kempker RR, Tenna A, Smitson C, Berhe N, Fekade D, Blumberg HM, Aseffa A, 2013. High prevalence of cryptococcal antigenemia among HIV-infected patients receiving antiretroviral therapy in Ethiopia. PLoS ONE 8: e58377.
-
13.
Beyene T, Woldeamanuel Y, Asrat D, Ayana G, Boulware DR, 2013. Comparison of cryptococcal antigenemia between antiretroviral naïve and antiretroviral experienced HIV positive patients at two hospitals in Ethiopia. PLoS ONE 8: e75585.
-
14.
Afifi S, Karsany MS, Wasfy M, Pimentel G, Marfin A, Hajjeh R, 2009. Laboratory-based surveillance for patients with acute meningitis in Sudan, 2004–2005. Eur J Clin Microbiol Infect Dis 28: 429–435.
-
15.
Trachtenberg JD, Kambugu AD, McKellar M, Semitala F, Mayanja-Kizza H, Samore MH, Ronald A, Sande MA, 2007. The medical management of central nervous system infections in Uganda and the potential impact of an algorithm-based approach to improve outcomes. Int J Infect Dis 11: 524–530.
-
16.
Torok ME, Chau TT, Mai PP, Phong ND, Dung NT, Chuong LV, Lee SJ, Caws M, de Jong MD, Hien TT, Farrar JJ, 2008. Clinical and microbiological features of HIV-associated tuberculous meningitis in Vietnamese adults. PLoS One 3: e1772.
-
17.
Kennedy DH, Fallon RJ, 1979. Tuberculous meningitis. JAMA 241: 264–268.
-
18.
Caws M, Thwaites GE, Duy PM, Tho DQ, Lan NT, Hoa DV, Chau TT, Huyen MN, Anh PT, Chau NV, Chinh TN, Stepniewska K, Farrar J, 2007. Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis. Int J Tuberc Lung Dis 11: 202–208.
-
19.
Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, White NJ, Parry CM, Farrar JJ, 2002. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet 360: 1287–1292.
-
20.
Juan RS, Sanchez-Suarez C, Rebollo MJ, Folgueira D, Palenque E, Ortuno B, Lumbreras C, Aguado JM, 2006. Interferon gamma quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis. J Neurol 253: 1323–1330.
-
21.
Patel VB, Singh R, Connolly C, Kasprowicz V, Ndung'u T, Dheda K, 2011. Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis. J Clin Microbiol 49: 3971–3976.
-
22.
O'Grady J, Bates M, Chilukutu L, Mzyece J, Cheelo B, Chilufya M, Mukonda L, Mumba M, Tembo J, Chomba M, Kapata N, Maeurer M, Rachow A, Clowes P, Hoelscher M, Mwaba P, Zumla A, 2012. Evaluation of the Xpert MTB/RIF assay at a tertiary care referral hospital in a setting where tuberculosis and HIV infection are highly endemic. Clin Infect Dis 55: 1171–1178.
-
23.
Patel VB, Theron G, Lenders L, Matinyena B, Connolly C, Singh R, Coovadia Y, Ndung'u T, Dheda K, 2013. Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. PLoS Med 10: e1001536.
-
24.
Nhu NT, Heemskerk D, Thu do DA, Chau TT, Mai NT, Nghia HD, Loc PP, Merson L, Thinh TT, Day J, Chau N, Wolbers M, Farrar J, Caws M, 2014. Evaluation of GeneXpert MTB/RIF for diagnosis of tuberculous meningitis. J Clin Microbiol 52: 226–233.
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