CNS and HIV Infections

Central nervous system infections are thought to result in six million disability adjusted life years annually, and the vast majority of disease is in developing countries. In the CNS-HIV research group we focus on infectious diseases of the central nervous system affecting HIV infected and uninfected patients, opportunistic infections complicating HIV, and HIV drug resistance. Research areas are chosen because of their direct relevance to the population of patients we serve. Diseases of particular interest are tuberculous meningitis, cryptococcal meningitis, penicilliosis, bacterial meningitis and encephalitis. In addition we are interested in the rates of accumulation of HIV drug resistance in patients receiving treatment within the national treatment programme, how this impacts treatment response and can be mitigated.

Research activities are based around large clinical trials, powered to pragmatic and easily understood endpoints such as mortality and disability, to ensure that the results of research are able to inform policy. Multidisciplinary research activities are associated with the clinical trials and include epidemiology, ecology, pathogenicity, population dynamics, host responses, modelling and drug resistance. The results of research have influenced national and international guidelines in the treatment of TB meningitis and cryptococcal meningitis.

The group enjoys collaborating with researchers across Viet Nam, Asia and Africa, with multi-site clinical trials running in Viet Nam, Thailand, Indonesia, Laos, Uganda and Malawi.

 

CNS-HIV Group – research leaders

  • Dr Ho Dang Trung Nghia – main interests: the epidemiology and aetiology of CNS infections of humans, and the interaction with animal health through the VIZIONS collaboration.
  • Dr Tran Thi Hong Chau – main interests: are cryptococcal and tuberculous meningitis
  • Dr Nguyen Thi Hoang Mai – main interests: bacterial meningitis and tuberuclous meningitis
  • Dr Thuy Le – main interests: penicilliosis and HIV drug resistance
  • Dr Justin Beardsley – main interests: cryptococcal meningitis
  • Dr Jeremy Day – main interests: cryptococcal disease, CNS opportunistic infections and TB meningitis.

 

Current Randomized Controlled Trials

  • A Randomized, Open-Label, Comparative Study of the Effectiveness of Itraconazole versus Amphotericin B in the Induction Treatment of Penicilliosis in HIV-Infected Adults
  • CryptoDex: A Randomized, Double Blind, Placebo-Controlled Phase III Trial of Adjunctive Dexamethasone in HIV infected Adults with Cryptococcal Meningitis
  • Intensified Treatment for Tuberculous Meningitis in Adult Patients with Enhanced Rifampicin and Levofloxacin.

 

Key Outcomes

The group has been successful in generating evidence that has improved the treatment of CNS infections, and resulted in changes in national and international guidelines. Highlights include demonstrating that dexamethasone reduces mortality in adult patients with tuberculous meningitis and bacterial meningitis, and that the antifungal drug flucytosine is key in reducing the mortality from cryptococcal meningitis in HIV infected patients:

Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004 Oct 21;351(17):1741-51 PMID: 15496623

Nguyen TH, Tran TH, Thwaites G, Ly VC, Dinh XS, Ho Dang TN, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007 Dec 13; 357(24):2431-40 PMID: 18077808

Day JN, Chau TT, Wolbers M, Mai PP, Dung NT, Mai NH, et al. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med. 2013 Apr 4; 368(14):1291-302 PMID: 23550668

 

Our research locations

We are located in the Clinical Sciences Building at the Hospital for Tropical Diseases, Ho Chi Minh City. We have enjoyed a long and successful collaboration with the Hospital for Tropical Diseases, and with Pham Ngoc Thach Hospital, Ho Chi Minh City, which has enabled us to run large trials in tuberculosis. Current active study sites are located in these hospitals: Cho Ray Hospital, HCMC; Bach Mai Hospital and the National Hospital for Tropical Diseases, Hanoi; and in Laos, Uganda, Thailand, Indonesia and Malawi.

 

Our CNS-HIV research collaborations/partnerships

We have research collaborations with the MRC Uganda, MORU Thailand, the Faculty of Medicine, University of Indonesia, Hasan Sidikin Hospital Indonesia, Wellcome Trust-Mahosot-Oxford University Tropical Medicine Research Collaboration in Vientiane, Lao PDR, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Sydney, Duke University, Albert Einstein College of Medicine, the University of Hawaii, the Genome Institute Singapore, and the Sanger Institute UK.

 

Key milestones in our research

Recent milestones include successful funding applications to the MRC-DfID-Wellcome Trust Joint Global Health Trials Scheme.

 

Selected Other Publications

Day JN, Hoang TN, Duong AV, Hong CT, Diep PT, Campbell JI, et al. Most cases of cryptococcal meningitis in HIV-uninfected patients in Vietnam are due to a distinct amplified fragment length polymorphism-defined cluster of Cryptococcus neoformans var. grubii VN1. J Clin Microbiol. 2011 Feb;49(2):658-64. PMID: 21159929

Chau TT, Mai NH, Phu NH, Nghia HD, Chuong LV, Sinh DX, et al. A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam – high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease. BMC Infect Dis. 2010 Jul 9;10:199. PMID: 20618932

Nghia HD, Tu le TP, Wolbers M, Thai CQ, Hoang NV, Nga TV, et al. Risk factors of Streptococcus suis infection in Vietnam. A case-control study. PLoS One. 2011 Mar 8;6(3):e17604. doi: 10.1371/journal.pone.0017604. Erratum in: PLoS One. 2011;6(4). PMID: 21408132

Ho Dang Trung N, Le Thi Phuong T, Wolbers M, Nguyen Van Minh H, Nguyen Thanh V, Van MP, et al. Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study. PLoS One. 2012;7(5):e37825. PMID: 22662232

T??r??k ME, Nguyen DB, Tran TH, Nguyen TB, Thwaites GE, Hoang TQ, et al. Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents. PLoS One. 2011;6(12):e27821. PMID: 22174748

Thao VP, Le T, T??r??k EM, Yen NT, Chau TT, Jurriaans S, et al. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam. Antivir Ther. 2012;17(5):905-13. PMID: 22473024

T??r??k ME, Yen NT, Chau TT, Mai NT, Phu NH, Mai PP, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis. Clin Infect Dis. 2011 Jun;52(11):1374-83. PMID: 21596680

Pouplin T, Pouplin JN, Van Toi P, Lindegardh N, Rogier van Doorn H, Hien TT, Farrar J, T??r??k ME, Chau TT. Valacyclovir for herpes simplex encephalitis. Antimicrob Agents Chemother. 2011 Jul;55(7):3624-6.

Le T, Wolbers M, Chi NH, Quang VM, Chinh NT, Lan NP, et al. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis. 2011 Apr 1;52(7):945-52. PMID: 21427403

Le T, Huu Chi N, Kim Cuc NT, Manh Sieu TP, Shikuma CM, Farrar J, Day JN. AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis. 2010 Dec 15;51(12):1458-62. PMID: 21054180

Henk DA, Shahar-Golan R, Devi KR, Boyce KJ, Zhan N, Fedorova ND, et al. Clonality despite sex: the evolution of host-associated sexual neighborhoods in the pathogenic fungus Penicillium marneffei. PLoS Pathog. 2012;8(10). PMID: 23055919

Le T, Hong Chau TT, Kim Cuc NT, Si Lam P, Manh Sieu TP, Shikuma CM, Day JN. AIDS?associated Cryptococcus neoformans and Penicillium marneffei coinfection: a therapeutic dilemma in resource?limited settings. Clin Infect Dis. 2010 Nov 1;51(9):e65-8. PMID: 20887205