• Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

      Blanc, F-X; Sok, T; Laureillard, D; Borand, L; Rekacewicz, C; Nerrienet, E; Madec, Y; Marcy, O; Chan, S; Prak, N; et al. (2011-10-20)
      Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
    • Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort.

      Ford, Nathan; Darder, Marta; Spelman, Tim; Maclean, Emi; Mills, Edward; Boulle, Andrew; Médecins Sans Frontières, Cape Town, South Africa. nathan.ford@joburg.msf.org (2010-05)
      OBJECTIVE: Previous studies have demonstrated a cross-sectional relationship between antiretroviral adherence and HIV virological suppression. We assessed the predictive value of baseline adherence in determining long-term virological failure. DESIGN: We assessed baseline adherence via an adherence questionnaire between administered to all consenting patients attending antiretroviral clinics in Khayelitsha township, South Africa, between May 2002 and March 2004. Virological status was ascertained after five years of follow up and multivariate analysis used to model associations of baseline variables and medication adherence with time to viral suppression or failure. RESULTS: Our adherence cohort comprised 207 patients, among whom 72% were female. Median age was 30 years and median CD4 count at initiation was 55 cells/mm(3). We found no statistically significant differences between baseline characteristics and early adherence groups. Multivariate analysis adjusting for baseline CD4 and age found that patients with suboptimal baseline adherence had a hazard ratio of 2.82 (95% CI 1.19-6.66, p = 0.018) for progression to virological failure compared to those whose baseline adherence was considered optimal. CONCLUSIONS: Our longitudinal study provides further confirmation of adherence as a primary determinant of subsequent confirmed virological failure, and serves as a reminder of the importance of initial early investments in adherence counseling and support as an effective way to maximize long-term treatment success.
    • Early Antiretroviral Therapy initiation: Access and Equity of Viral Load Testing for HIV Treatment Monitoring

      Peter, T; Ellenberger, D; Kim, AA; Boeras, D; Messele, T; Roberts, T; Stevens, W; Jani, I; Abimiku, A; Ford, N; et al. (Elsevier, 2016-10-20)
      Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.
    • Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda

      Ojuka, Patrick; Boum, Yap; Denoeud-Ndam, Lise; Nabasumba, Carolyn; Muller, Yolanda; Okia, Michael; Mwanga-Amumpaire, Juliet; Debeaudrap, Pierre; Protopopoff, Natacha; Etard, Jean-François (BioMed Central, 2015-04-09)
      Southwestern Uganda has high malaria heterogeneity despite moderate vector control and other interventions. Moreover, the early biting transmission and increased resistance to insecticides might compromise strategies relying on vector control. Consequently, monitoring of vector behaviour and insecticide efficacy is needed to assess the effectiveness of strategies aiming at malaria control. This eventually led to an entomological survey in two villages with high malaria prevalence in this region.
    • Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.

      Ford, Nathan; Kranzer, Katharina; Hilderbrand, Katherine; Jouquet, Guillaume; Goemaere, Eric; Vlahakis, Nathalie; Triviño, Laura; Makakole, Lipontso; Bygrave, Helen; Médecins Sans Frontières, University of Cape Town, South Africa. Nathan.ford@msf.org (2010-11-13)
      INTRODUCTION: The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/μl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/μl) and late (CD4 cell counts ≤200 cells/μl) initiation. METHODS: We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/μl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori. RESULTS: Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/μl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/μl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/μl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/μl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73). CONCLUSION: Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations.
    • Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

      Fenner, Lukas; Brinkhof, Martin W G; Keiser, Olivia; Weigel, Ralf; Cornell, Morna; Moultrie, Harry; Prozesky, Hans; Technau, Karl; Eley, Brian; Vaz, Paula; et al. (2010-08-15)
      BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.
    • Early Outcomes of Decentralized Care for Rifampicin-Resistant Tuberculosis in Johannesburg, South Africa: An Observational Cohort Study

      Berhanu, R; Schnippel, K; Mohr, E; Hirasen, K; Evans, D; Rosen, S; Sanne, I (PloS One, 2016-11-03)
      OBJECTIVE: We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB). METHODS: Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months), transfer out, or a final outcome (loss from treatment (LFT) or death). RESULTS: 214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186), followed by direct PCR on AFB positive specimen in 14 (7%) and indirect PCR on cultured isolate in 5 (2%). Median time between sputum testing and treatment initiation was 10 days (IQR 6-21). Interim outcomes were available in 148 patients of whom 78% (n = 115) were still on treatment, 9% (n = 13) had died, and 14% (n = 20) were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9%) were culture negative at 6 months, 12 were still sputum culture positive (9.2%) and 34 had no culture documented or contaminated culture (26%). Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98). HIV co-infection occurred in 178 patients (83%) with a median CD4 count 88 cells/ml3 (IQR 27-218). CONCLUSIONS: Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.
    • Early Physical and Functional Rehabilitation of Trauma Patients in the Médecins Sans Frontières Trauma Centre in Kunduz, Afghanistan: Luxury or Necessity?

      Gohy, B; Ali, E; Van den Bergh, R; Schillberg, E; Nasim, M; Naimi, MM; Cheréstal, S; Falipou, P; Weerts, E; Skelton, P; et al. (Oxford University Press, 2016-10-13)
      In Afghanistan, Médecins Sans Frontières provided specialised trauma care in Kunduz Trauma Centre (KTC), including physiotherapy. In this study, we describe the development of an adapted functional score for patient outcome monitoring, and document the rehabilitation care provided and patient outcomes in relation to this functional score.
    • Early prediction of treatment efficacy in Second-Stage Gambiense Human African Trypanosomiasis

      Priotto, G; Chappuis, F; Bastard, M; Flevaud, L; Etard, J-F; Epicentre, Paris, France. gpriotto@neuf.fr (2012-06-05)
      Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators.
    • Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study

      Ferlazzo, G; Mohr, E; Laxmeshwar, C; Hewison, C; Hughes, J; Jonckheere, S; Khachatryan, N; De Avezedo, V; Egazaryan, L; Shroufi, A; et al. (Elsevier, 2018-02-13)
      Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa.
    • Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

      Marconi, Vincent C; Wu, Baohua; Hampton, Jane; Ordóñez, Claudia E; Johnson, Brent A; Singh, Dinesh; John, Sally; Gordon, Michelle; Hare, Anna; Murphy, Richard; et al. (2013-12)
      Abstract We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after≥5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL≤1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures.
    • The Ebola Clinical Trials: a Precedent for Research Ethics in Disasters

      Calain, P (BMJ Publishing Group, 2016-08-29)
      The West African Ebola epidemic has set in motion a collective endeavour to conduct accelerated clinical trials, testing unproven but potentially lifesaving interventions in the course of a major public health crisis. This unprecedented effort was supported by the recommendations of an ad hoc ethics panel convened in August 2014 by the WHO. By considering why and on what conditions the exceptional circumstances of the Ebola epidemic justified the use of unproven interventions, the panel's recommendations have challenged conventional thinking about therapeutic development and clinical research ethics. At the same time, unanswered ethical questions have emerged, in particular: (i) the specification of exceptional circumstances, (ii) the specification of unproven interventions, (iii) the goals of interventional research in terms of individual versus collective interests, (iv) the place of adaptive trial designs and (v) the exact meaning of compassionate use with unapproved interventions. Examination of these questions, in parallel with empirical data from research sites, will help build pragmatic foundations for disaster research ethics. Furthermore, the Ebola clinical trials signal an evolution in the current paradigms of therapeutic research, beyond the case of epidemic emergencies.
    • Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned

      Borchert, Matthias; Mutyaba, Imaam; Van Kerkhove, Maria D; Lutwama, Julius; Luwaga, Henry; Bisoborwa, Geoffrey; Turyagaruka, John; Pirard, Patricia; Ndayimirije, Nestor; Roddy, Paul; et al. (BioMed Central, 2011-12-28)
    • Ebola in Africa: beyond epidemics, reproductive health in crisis

      Delamou, A; Hammonds, R M; Caluwaerts, S; Utz, B; Delvaux, T (Elsevier, 2014-12-13)
    • Ebola Management Centre Proximity Associated With Reduced Delays of Healthcare of Ebola Virus Disease (EVD) Patients, Tonkolili, Sierra Leone, 2014-15

      Theocharopoulos, G; Danis, K; Greig, J; Hoffmann, A; De Valk, H; Jimissa, A; Tejan, S; Sankoh, M; Kleijer, K; Turner, W; et al. (Public Library of Science, 2017-05-01)
      Between August-December 2014, Ebola Virus Disease (EVD) patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF) Ebola Management Centres (EMCs) outside the district (distant EMCs). In December 2014, MSF opened an EMC in Tonkolili District (district EMC). We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA), and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR) using Binomial regression. Of 249 confirmed Ebola cases, 206 (83%) were admitted to the distant EMCs and 43 (17%) to the district EMC. Of them 110 (45%) have died. Confirmed cases dead on arrival (n = 10) were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8) in distant EMCs and 3 days (IQR 2,7) in the district EMC (p<0.001). Cases were 2.0 (95%CI 1.4-2.9) times more likely to have delayed admission (>3 days after symptom onset) in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6-1.0) to have a high viral load (cycle threshold ≤22). A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8-3.6) and vomiting at first presentation (aRR 1.4; 95%CI 1.0-2.0). The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks.
    • The Ebola Outbreak and Staffing in Public Health Facilities in Rural Sierra Leone: Who is Left to do the Job?

      Sylvester Squire, J; Hann, K; Denisiuk, O; Kamara, M; Tamang, D; Zachariah, R (International Union Against Tuberculosis and Lung Disease, 2017-06-21)
      Setting: The 82 public health facilities of rural Kailahun District, Sierra Leone. Objective: The 2014-2015 Ebola virus disease outbreak in Sierra Leone led the Ministry of Health and Sanitation and stakeholders to set minimum standards of staffing (medical/non-medical) for a basic package of essential health services (BPEHS). No district-level information exists on staffing levels in relation to the Ebola outbreak. We examined the staffing levels before the Ebola outbreak, during the last month of the outbreak and 4 months after the outbreak, as well as Ebola-related deaths among health care workers (HCWs). Design: This was a retrospective cross-sectional study. Results: Of 805 recommended medical staff (the minimum requirement for 82 health facilities), there were deficits of 539 (67%) pre-Ebola, 528 (65%) during the Ebola outbreak and 501 (62%) post-Ebola, hovering at staff shortages of >50% at all levels of health facilities. Of the 569 requisite non-medical staff, the gap remained consistent, at 92%, in the three time periods. Of the 1374 overall HCWs recommended by the BPEHS, the current staff shortage is 1026 (75%). Of 321 facility-based HCWs present during Ebola, there were 15 (14 medical and one non-medical staff) Ebola-related and three non-Ebola related deaths among HCWs. Conclusion: The post-Ebola health-related human resource deficit is alarmingly high, with very few staff available to work. We call for urgent political will, resources and international collaboration to address this situation.
    • Ebola outbreak in Conakry, Guinea: Epidemiological, clinical, and outcome features

      Barry, M; Traoré, F A; Sako, F B; Kpamy, D O; Bah, E I; Poncin, M; Keita, S; Cisse, M; Touré, A (Elsevier, 2014-10-22)
      The authors studied the epidemiological, clinical, and outcome features of the Ebola virus disease in patients hospitalized at the Ebola treatment center (ETC) in Conakry to identify clinical factors associated with death.
    • Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes

      Dallatomasinas, Silvia; Crestani, Rosa; Squire, James Sylvester; Declerk, Hilde; Caleo, Grazia Marta; Wolz, Anja; Stinson, Kathyrn; Patten, Gabriela; Brechard, Raphael; Gbabai, Osman Bamba-Moi; et al. (Wiley-Blackwell, 2015-01-07)
      To describe Ebola cases in the district Ebola Management Centre of in Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin, patient and hospitalization characteristics, treatment outcomes and time from symptom onset to admission.
    • Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone.

      Tiffany, Amanda; Vetter, Pauline; Mattia, John; Dayer, Julie-Anne; Bartsch, Maria; Kasztura, Miriam; Sterk, Esther; Tijerino, Ana Maria; Kaiser, Laurent; Ciglenecki, Iza (2016-03-21)
       Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone.
    • Ebola Virus Disease in Pregnancy: Clinical, Histopathologic and Immunohistochemical Findings

      Muehlenbachs, A; de la Rosa Vázquez, O; Bausch, DG; Schafer, IJ; Paddock, CD; Nyakio, JP; Lame, P; Bergeron, E; McCollum, AM; Goldsmith, CS; et al. (Oxford University Press We regret that this article is behind a paywall., 2016-05-25)
      Here we describe clinicopathologic features of EVD in pregnancy. One woman infected with Sudan virus in Gulu, Uganda in 2000 had a stillbirth and survived, and another woman with Bundibugyo virus had a livebirth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemistry, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malaria pigment-laden macrophages. These data suggest trophoblast infection may be a mechanism of transplacental ebolavirus transmission.