• Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries.

      Greig, Jane; Casas, Esther C; O'Brien, Daniel P; Mills, Edward J; Ford, Nathan; Médecins Sans Frontières, London, UK. jane.greig@london.msf.org (2012-07-31)
      Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa.
    • Burden of HIV-Related Cytomegalovirus Retinitis in Resource-Limited Settings: A Systematic Review

      Ford, Nathan; Shubber, Zara; Saranchuk, Peter; Pathai, Sophia; Durier, Nicolas; O'Brien, Daniel P; Mills, Edward J; Pascual, Fernando; Hoen, Ellen 't; Holland, Gary N; et al. (Oxford University Press, 2013-09-02)
      Background. Cytomegalovirus (CMV) is a late-stage opportunistic infection in people living with human immunodeficiency virus (HIV)/AIDS. Lack of ophthalmological diagnostic skills, lack of convenient CMV treatment, and increasing access to antiretroviral therapy have all contributed to an assumption that CMV retinitis is no longer a concern in low- and middle-income settings. Methods. We conducted a systematic review and meta-analysis of published and unpublished studies reporting prevalence of CMV retinitis in low- and middle-income countries. Eligible studies assessed the occurrence of CMV retinitis by funduscopic examination within a cohort of at least 10 HIV-positive adult patients. Results. We identified 65 studies from 24 countries, mainly in Asia (39 studies, 12 931 patients) and Africa (18 studies, 4325 patients). By region, the highest prevalence was observed in Asia with a pooled prevalence of 14.0% (11.8%-16.2%). Almost a third (31.6%, 95% confidence interval [CI], 27.6%-35.8%) had vision loss in 1 or both eyes. Few studies reported immune status, but where reported CD4 count at diagnosis of CMV retinitis was <50 cells/µL in 73.4% of cases. There was no clear pattern of prevalence over time, which was similar for the period 1993-2002 (11.8%; 95% CI, 8%-15.7%) and 2009-2013 (17.6%; 95% CI, 12.6%-22.7%). Conclusions. Prevalence of CMV retinitis in resource low- and middle-income countries, notably Asian countries, remains high, and routine retinal screening of late presenting HIV-positive patients should be considered. HIV programs must ensure capacity to manage the needs of patients who present late for care.
    • Causes of false-positive HIV rapid diagnostic test results

      Klarkowski, Derryck; O'Brien, Daniel P; Shanks, Leslie; Singh, Kasha P (Informa Healthcare, 2014-01)
      HIV rapid diagnostic tests have enabled widespread implementation of HIV programs in resource-limited settings. If the tests used in the diagnostic algorithm are susceptible to the same cause for false positivity, a false-positive diagnosis may result in devastating consequences. In resource-limited settings, the lack of routine confirmatory testing, compounded by incorrect interpretation of weak positive test lines and use of tie-breaker algorithms, can leave a false-positive diagnosis undetected. We propose that heightened CD5+ and early B-lymphocyte response polyclonal cross-reactivity are a major cause of HIV false positivity in certain settings; thus, test performance may vary significantly in different geographical areas and populations. There is an urgent need for policy makers to recognize that HIV rapid diagnostic tests are screening tests and mandate confirmatory testing before reporting an HIV-positive result. In addition, weak positive results should not be recognized as valid except in the screening of blood donors.
    • Clinical Features and Risk Factors of Oedematous Mycobacterium ulcerans Lesions in an Australian Population: Beware Cellulitis in an Endemic Area

      O'Brien, Daniel P; Friedman, N Deborah; McDonald, Anthony; Callan, Peter; Hughes, Andrew; Athan, Eugene (Public Library of Science, 2014)
      Oedematous lesions are a less common but more severe form of Mycobacterium ulcerans disease. Misdiagnosis as bacterial cellulitis can lead to delays in treatment. We report the first comprehensive descriptions of the clinical features and risk factors of patients with oedematous disease from the Bellarine Peninsula of south-eastern Victoria, Australia.
    • False positive HIV diagnoses in resource limited settings: operational lessons learned for HIV programmes

      Shanks, Leslie; Klarkowski, Derryck; O'Brien, Daniel P; Médecins Sans Frontières, Amsterdam, The Netherlands. (Public Library of Science, 2013-03-20)
      Access to HIV diagnosis is life-saving; however the use of rapid diagnostic tests in combination is vulnerable to wrongly diagnosing HIV infection when both screening tests give a false positive result. Misclassification of HIV patients can also occur due to poor quality control, administrative errors and lack of supervision and training of staff. Médecins Sans Frontières discovered in 2004 that HIV negative individuals were enrolled in some HIV programmes. This paper describes the result of an audit of three sites to review testing practices, implement improved testing algorithms and offer re-testing to clients enrolled in the HIV clinic.
    • Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

      Marshall, Catherine S; Curtis, Andrea J; Spelman, Tim; O'Brien, Daniel P; Greig, Jane; Shanks, Leslie; du Cros, Philipp; Casas, Esther C; da Fonseca, Marcio Silveira; Athan, Eugene; et al. (PLoS, 2013-07)
      To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.
    • Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

      Curtis, Andrea J; Marshall, Catherine S; Spelman, Tim; Greig, Jane; Elliot, Julian H; Shanks, Leslie; Du Cros, Philipp; Casas, Esther C; Da Fonseca, Marcio Silveria; O'Brien, Daniel P; et al. (2012-12-20)
      To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS).
    • Moxifloxacin for Buruli ulcer/HIV coinfected patients: kill two birds with one stone?

      O'Brien, Daniel P; Comte, Eric; Ford, Nathan; Christinet, Vanessa; du Cros, Philipp; aManson Unit, Médecins Sans Frontières, London, UK bDepartment of Infectious Diseases, Geelong Hospital, Geelong cDepartment of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia dMedical Unit, Médecins Sans Frontières, Geneva, Switzerland eCenter for Infectious Diseases Epidemiology Research, University of Cape Town, Cape Town, South Africa fDepartment of HIV, University Hospitals of Geneva, Geneva, Switzerland. (2013-09-10)
    • Mycobacterium ulcerans treatment - can antibiotic duration be reduced in selected patients?

      Cowan, Raquel; Athan, Eugene; Friedman, N Deborah; Hughes, Andrew J; McDonald, Anthony; Callan, Peter; Fyfe, Janet; O'Brien, Daniel P (Public Library of Science, 2015-02-06)
      Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks.
    • Pre-emptive steroids for a severe oedematous Buruli ulcer lesion: a case report

      O'Brien, Daniel P; Huffam, Sarah (BioMed Central, 2015-05-01)
      Severe oedematous forms of Buruli ulcer (BU) often result in extensive tissue destruction, even with the institution of appropriate antibiotic treatment, leading to reconstructive surgery and long-term disability. We report a case of a patient with severe oedematous BU, which describes for the first time the pre-emptive use of prednisolone therapy commenced at the time of antibiotic initiation aimed at limiting the ongoing tissue destruction and its secondary sequelae.
    • Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

      O'Brien, Daniel P; Venis, Sarah; Greig, Jane; Shanks, Leslie; Ellman, Tom; Sabapathy, Kalpana; Frigati, Lisa; Mills, Clair; Public Health Department, Médecins Sans Frontières, Amsterdam, Netherlands; 2Department of Infectious Diseases, Geelong Hospital, Geelong, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia; Médecins Sans Frontières, London, UK; School of Child and Adolescent Health, Red Cross Childrens' Hospital, Capetown, South Africa; Te Kupenga Hauora Maori, Faculty of Medical and Health Sciences,University of Auckland, Auckland, New Zealand (2010-06-17)
      ABSTRACT: INTRODUCTION: Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. METHODS: From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. RESULTS: In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145). At analysis, 2645 (64%) remained on ART, 422 (10%) had died, 466 (11%) lost to follow-up, 417 (10%) transferred to another programme, and 195 (5%) had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3.Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. CONCLUSIONS: With commitment, simplified treatment and monitoring, and adaptations for potential instability, HIV treatment can be feasibly and effectively provided in conflict or post-conflict settings.
    • Similar mortality and reduced loss to follow-up in integrated compared with vertical programs providing antiretroviral treatment in sub-saharan Africa.

      Greig, Jane; O'Brien, Daniel P; Ford, Nathan; Spelman, Tim; Sabapathy, Kalpana; Shanks, Leslie; Manson Unit, Médecins sans Frontières, Saffron Hill, London, UK. jane.greig@london.msf.org (2012-04-15)
      Vertical HIV programs have achieved good results but may not be feasible or appropriate in many resource-limited settings. Médecins sans Frontières has treated HIV in vertical programs since 2000 and over time integrated HIV treatment into general health care services using simplified protocols. We analyzed the survival probability among patients receiving antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical programs in 9 countries in sub-Saharan Africa.
    • Treating HIV in Africa: Case Report From Rural Congo.

      Pottie, Kevin; Bamoueni, Sam; Alas, Ahmed; Tu, David; O'Brien, Daniel P; Elisabeth Bruyère Research Institute and Department of Family Medicine, University of Ottawa, Ontario; Medecins Sans Frontieres, Brazzaville; Division of International Health in the Department of Family Practice, University of British Columbia, Vancouver; Medecins Sans Frontieres, Amsterdam (2010-05-01)
    • The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa

      O'Brien, Daniel P; Comte, Eric; Serafini, Micaela; Ehounou, Geneviève; Antierens, Annick; Vuagnat, Hubert; Christinet, Vanessa; Hamani, Mitima D; du Cros, Philipp; Manson Unit, Médecins Sans Frontières, London, UK; Department of Infectious Diseases, Geelong Hospital, Geelong, VIC, Australia; Department of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. Electronic address: daniel.obrien@amsterdam.msf.org. (Elsevier, 2013-12-02)
      Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality.
    • Viral load testing in a resource-limited setting: quality control is critical.

      Greig, Jane; du Cros, Philipp; Klarkowski, Derryck; Mills, Clair; Jørgensen, Steffen; Harrigan, P Richard; O'Brien, Daniel P; Manson Unit, Médecins Sans Frontières, London, UK. jane.greig@london.msf.org. (2011-05)
      ABSTRACT: