RESUMO
BACKGROUND: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea. METHODS: In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group. RESULTS: A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed. CONCLUSIONS: The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
Assuntos
Transfusão de Componentes Sanguíneos , Doença pelo Vírus Ebola/terapia , Plasma , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Transfusão de Componentes Sanguíneos/efeitos adversos , Criança , Pré-Escolar , Convalescença , Ebolavirus/imunologia , Feminino , Guiné , Doença pelo Vírus Ebola/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Razão de Chances , Plasma/imunologia , Gravidez , Adulto JovemRESUMO
A neonate born to an Ebola virus-positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.
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Alanina/análogos & derivados , Anticorpos Monoclonais/administração & dosagem , Antivirais/administração & dosagem , Doença pelo Vírus Ebola/congênito , Doença pelo Vírus Ebola/terapia , Fatores Imunológicos/administração & dosagem , Ribonucleotídeos/administração & dosagem , Terapias em Estudo/métodos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Sangue/virologia , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado do Tratamento , Adulto JovemRESUMO
Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.
Assuntos
Ebolavirus/genética , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Tipagem Molecular/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Genes Virais , Guiné , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular/normas , RNA Viral , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Studies have shown high levels of distress and mental disorder among people living in refugee camps, yet none has confirmed diagnosis through clinical reappraisal. AIMS: To estimate the prevalence of mental disorders, related disability and treatment gap in adult refugees living in the Burj el-Barajneh camp. METHOD: Randomly selected participants were screened by household representative (n = 748) and individual (n = 315) interviews; clinical reappraisal was performed on a subset (n = 194) of 326 selected participants. Weighted prevalence estimates and 95% confidence intervals were calculated. RESULTS: The prevalence of current mental disorders was 19.4% (95% CI 12.6-26.2); depression was the most common diagnosis (8.3%, 95% CI 4.4-12.2) and multiple diagnoses were common (42%) among the 88 persons with mental disorder. Lifetime prevalence of psychosis was 3.3% (95% CI 1.0-5.5). Mental disorders were associated with moderate to severe dysfunction (odds ratio = 8.8, 95% CI 4.5-17.4). The treatment gap was 96% (95% CI 92-100). CONCLUSIONS: A range of mental disorders and associated disability are common in this long-term refugee setting. Combined with an important treatment gap, findings support the current consensus-based policy to prioritise availability of mental health treatment in refugee camps, especially for the most severe and disabling conditions.
Assuntos
Avaliação da Deficiência , Transtornos Mentais/epidemiologia , Refugiados/psicologia , Adulto , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Líbano/epidemiologia , Masculino , Prevalência , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to report the patient profile and treatment outcomes, including relapses, of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (AmBisome) in Gedaref, Sudan. METHODS: AmBisome was offered to two groups of patients: primary VL patients with specific criteria (age ≤2 or ≥45 years, advanced clinical disease, pregnancy, HIV co-infection and contraindications for antimonials) and VL relapses. AmBisome was given at a total dose of 30 mg/kg, over 10 days. Slow responders received up to 50 mg/kg. Treatment failure was confirmed parasitologically. Standardised treatment outcomes were assessed. RESULTS: Between March 2010 and June 2012, a total of 281 (74%) patients with primary VL and 98 (26%) patients with VL relapses received AmBisome (54% male, median age = 11 years, interquartile range 2-30). End-of-treatment outcomes for primary VL were 260 (92%) initial cure including three (1%) slow responders, three (1%) treatment failures, 14 (5%) deaths and four (1%) unknown outcomes. Outcomes for VL relapses were 92 (94%) initial cure with five (5%) slow responders, four (4%) treatment failures, one (1%) death and one (1%) unknown outcome. At 6 months, there were 19 (7%) relapses amongst primary VL and 10 (10%) VL relapses had a new relapse. Loss to follow-up in both groups was 38%. None of the deaths that occurred during the study period was attributed to AmBisome. CONCLUSION: AmBisome appears to be effective for initial cure of VL and the drug seems safe, but is expensive (400 USD/treatment). Sustained mechanisms to allow improved access of this expensive drug particularly in East Africa are urgently needed. Relapses and losses to follow-up require specific investigation.
Assuntos
Anfotericina B/uso terapêutico , Leishmania donovani , Leishmaniose Visceral/tratamento farmacológico , Doenças Negligenciadas , Tripanossomicidas/uso terapêutico , Adolescente , Adulto , Anfotericina B/administração & dosagem , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Leishmaniose Visceral/complicações , Leishmaniose Visceral/mortalidade , Leishmaniose Visceral/parasitologia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Recidiva , Sudão/epidemiologia , Falha de Tratamento , Resultado do Tratamento , Tripanossomicidas/administração & dosagem , Adulto JovemRESUMO
Médecins sans Frontières (MSF) conducted a study to identify health needs and access barriers of Venezuelan migrants and refugees at La Guajira and Norte de Santander Colombian border states. The Migration History tool was used to gather information that included various health-related issues such as referred morbidity, exposure to violence, mental health, and access to health care services. A group migration profile with long-term permanence plans was identified. Was evidenced an important share of young population (50% under 20), indigenous people (20%), and returnees (11%). The respondents referred to a mixed pattern of chronic and acute diseases, for which the main difficulty was accessing diagnosis and continuous treatment. Health-seeking behavior was identified as the main barrier to access health care services. The article compiles main findings on the Venezuelan migrants and refugees' health conditions, contributing important evidence for the humanitarian responses in migration contexts.
Assuntos
Refugiados , Migrantes , Colômbia , Humanos , Saúde Mental , VenezuelaRESUMO
Emerging infectious diseases such as Ebola Virus Disease (EVD), Nipah Virus Encephalitis and Lassa fever pose significant epidemic threats. Responses to emerging infectious disease outbreaks frequently occur in resource-constrained regions and under high pressure to quickly contain the outbreak prior to potential spread. As seen in the 2020 EVD outbreaks in the Democratic Republic of Congo and the current COVID-19 pandemic, there is a continued need to evaluate and address the ethical challenges that arise in the high stakes environment of an emerging infectious disease outbreak response. The research presented here provides analysis of the ethical challenges with regard to allocation of limited resources, particularly experimental therapeutics, using the 2013-2016 EVD outbreak in West Africa as a case study. In-depth semi-structured interviews were conducted with senior healthcare personnel (n = 16) from international humanitarian aid organizations intimately engaged in the 2013-2016 EVD outbreak response in West Africa. Interviews were recorded in private setting, transcribed, and iteratively coded using grounded theory methodology. A majority of respondents indicated a clear propensity to adopt an ethical framework of guiding principles for international responses to emerging infectious disease outbreaks. Respondents agreed that prioritization of frontline workers' access to experimental therapeutics was warranted based on a principle of reciprocity. There was widespread acceptance of adaptive trial designs and greater trial transparency in providing access to experimental therapeutics. Many respondents also emphasized the importance of community engagement in limited resource allocation scheme design and culturally appropriate informed consent procedures. The study results inform a potential ethical framework of guiding principles based on the interview participants' insights to be adopted by international response organizations and their healthcare workers in the face of allocating limited resources such as experimental therapeutics in future emerging infectious disease outbreaks to ease the moral burden of individual healthcare providers.
Assuntos
Doenças Transmissíveis Emergentes/terapia , Surtos de Doenças/ética , Alocação de Recursos para a Atenção à Saúde/ética , Doença pelo Vírus Ebola/terapia , Ensaios Clínicos Adaptados como Assunto/ética , Adulto , África Ocidental/epidemiologia , Feminino , Pessoal de Saúde/ética , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Terapias em Estudo/éticaRESUMO
The capacity to rapidly distinguish Ebola virus disease from other infectious diseases and to monitor biochemistry and viremia levels is crucial to the clinical management of suspected Ebola virus disease cases. This article describes the design and practical considerations of a laboratory straddling the high- and low-risk zones of an Ebola treatment center to produce timely diagnostic and clinical results for informed case management of Ebola virus disease in real-life conditions. This innovation may be of relevance for actors requiring flexible laboratory implementation in contexts of high-communicability, high-lethality disease outbreaks.
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Assistência ao Convalescente/métodos , Técnicas de Laboratório Clínico/métodos , Doença pelo Vírus Ebola/terapia , Monitorização Fisiológica/métodos , Assistência ao Convalescente/tendências , Fortalecimento Institucional/métodos , Fortalecimento Institucional/tendências , Técnicas de Laboratório Clínico/tendências , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Ebolavirus , Humanos , Monitorização Fisiológica/tendências , Desenvolvimento de Programas/métodosRESUMO
During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted.
Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto/organização & administração , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/epidemiologia , Pirazinas/uso terapêutico , Ensaios Clínicos como Assunto/normas , Confidencialidade , Surtos de Doenças , Guiné/epidemiologia , Humanos , Consentimento Livre e Esclarecido , Prontuários Médicos/normas , Projetos de PesquisaRESUMO
BACKGROUND: The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic. METHODS AND FINDINGS: In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD. CONCLUSIONS: Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000939962.
Assuntos
Antivirais/uso terapêutico , Citosina/análogos & derivados , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adulto , Antivirais/farmacologia , Citosina/farmacologia , Citosina/uso terapêutico , Ebolavirus/efeitos dos fármacos , Feminino , Doença pelo Vírus Ebola/virologia , Humanos , Libéria , Masculino , Pessoa de Meia-Idade , Organofosfonatos/farmacologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Maternal infection with cholera may negatively affect pregnancy outcomes. The objective of this research is to systematically review the literature and determine the risk of fetal, neonatal and maternal death associated with cholera during pregnancy. MATERIALS AND METHODS: Medline, Global Health Library, and Cochrane Library databases were searched using the key terms cholera and pregnancy for articles published in any language and at any time before August 2013 to quantitatively summarize estimates of fetal, maternal, and neonatal mortality. 95% confidence intervals (CIs) were calculated for each selected study. Random-effect non-linear logistic regression was used to calculate pooled rates and 95% CIs by time period. Studies from the recent period (1991-2013) were compared with studies from 1969-1990. Relative risk (RR) estimates and 95% CIs were obtained by comparing mortality of selected recent studies with published national normative data from the closest year. RESULTS: The meta-analysis included seven studies that together involved 737 pregnant women with cholera from six countries. The pooled fetal death rate for 4 studies during 1991-2013 was 7.9% (95% CIs 5.3-10.4), significantly lower than that of 3 studies from 1969-1990 (31.0%, 95% CIs 25.2-36.8). There was no difference in fetal death rate by trimester. The pooled neonatal death rate for 1991-2013 studies was 0.8% (95% CIs 0.0-1.6), and 6.4% (95% CIs 0.0-20.8) for 1969-1990. The pooled maternal death rate for 1991-2013 studies was 0.2% (95% CIs 0.0-0.7), and 5.0% (95% CIs 0.0-16.0) for 1969-1990. Compared with published national mortality estimates, the RR for fetal death of 5.8 (95% CIs 2.9-11.3) was calculated for Haiti (2013), 1.8 (95% CIs 0.3-10.4) for Senegal (2007), and 2.6 (95% CIs 0.5-14.9) for Peru (1991); there were no significant differences in the RR for neonatal or maternal death. CONCLUSION: Results are limited by the inconsistencies found across included studies but suggest that maternal cholera is associated with adverse pregnancy outcomes, particularly fetal death. These findings can inform a research agenda on cholera in pregnancy and guidance for the timely management of pregnant women with cholera.
Assuntos
Cólera/mortalidade , Mortalidade Fetal , Mortalidade Infantil , Complicações Infecciosas na Gravidez/mortalidade , Feminino , Haiti/epidemiologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Mortalidade Materna , Paquistão/epidemiologia , Peru/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Senegal/epidemiologiaRESUMO
OBJECTIVE: To describe long-term treatment outcomes of a pediatric HIV cohort in Mozambique. DESIGN: Retrospective analysis of routine monitoring data. SETTING: Secondary health care facilities in the Chamanculo Health District of Maputo. SUBJECTS: A total of 1,335 antiretroviral treatment (ART) naïve children <15 years of age enrolled in HIV care between 2002 and 2010. INTERVENTION: HIV care, ART (since 2003), task shifting to lower cadre nurses, counseling by lay counselors, active patient tracing, nutritional support, support by a psychologist, targeted viral load testing, and switch to second-line treatment. MAIN OUTCOME MEASURES: Kaplan-Meier estimates for retention in care (RIC), CD4 cell percentage, body mass index for age z-score, and adjusted incidence rate ratios for attrition (death or loss to follow-up) as calculated by Poisson regression. RESULTS: The RIC at 6 years in the pre-ART cohort was 44% (95% confidence interval: 38-49), and the one at 8 years in the ART cohort was 70% (64-75). Risk factors for attrition included young age, low CD4 percentage, underweight, active tuberculosis, and enrollment/treatment initiation after 2006. The mean CD4 percentage increased strongly at 1 year on treatment and remained high thereafter. The body mass index for age z-score sharply increased at 1 year after treatment initiation before stabilizing at pre-ART levels thereafter. CONCLUSIONS: Good clinical and immunological treatment outcomes up to 8 years of follow-up on ART can be achieved in a context of shortage of health workers and a high level of task-shifting approach.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/mortalidade , Infecções por HIV/terapia , Educação de Pacientes como Assunto/organização & administração , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Fatores Etários , Índice de Massa Corporal , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Aconselhamento , Dieta , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Lactente , Estimativa de Kaplan-Meier , Perda de Seguimento , Masculino , Moçambique/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tuberculose/epidemiologia , Carga ViralRESUMO
INTRODUCTION: This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART) in Swaziland. METHODS: This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving) enhanced adherence counselling. RESULTS: From 12,063 patients undergoing routine viral load monitoring, 1941 (16%) had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5-4.5), as were adolescents (AOR 3.2, 95%CI 2.2-4.8), patients with last CD4<350 cells/µl (AOR 2.2, 95%CI 1.7-2.9) or WHO Stage 3/4 disease (AOR 1.3, 95%CI 1.1-1.6), and patients on ART for longer (AOR 1.1, 95%CI 1.1-1.2). At retesting, 450 (54% of those tested) showed viral re-suppression. Children were less likely to re-suppress (AOR 0.2, 95%CI 0.1-0.7), as were adolescents (AOR 0.3, 95%CI 0.2-0.8), those with initial viral load> 1000 copies/ml (AOR 0.3, 95%CI 0.1-0.7), and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2-0.7). Receiving (or not receiving) enhanced adherence counselling was not associated with likelihood of re-suppression. CONCLUSIONS: Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the elements of optimal enhanced adherence support for patients of all ages with detectable viral loads.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Aconselhamento , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Criança , Essuatíni , Feminino , Humanos , Modelos Logísticos , Masculino , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction. METHODS: We used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50 ml/min/1.73 m2. We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors. RESULTS: There were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30-50 ml/min/1.73 m2 and were maintained on TDF-based ART, but 5 were changed to another regimen: 4 because of CrCl <30 ml/min/1.73 m2. Risk factors for renal dysfunction included age ≥45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200 cells/mm3. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30-49 ml/min/1.73 m2 in five patients while the remainder regained normal renal function. CONCLUSIONS: In a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/patologia , Tenofovir/administração & dosagem , Adolescente , Adulto , Contagem de Linfócito CD4 , Creatinina/metabolismo , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mianmar , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/complicações , Fatores de Risco , Suíça , Tenofovir/efeitos adversosRESUMO
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.
Assuntos
Mycobacterium tuberculosis/classificação , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Evolução Biológica , Evolução Molecular , Genoma Bacteriano , Genótipo , Saúde Global , Humanos , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
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.
Assuntos
Úlcera de Buruli/diagnóstico , Mycobacterium ulcerans/isolamento & purificação , Doenças Negligenciadas , África , Úlcera de Buruli/tratamento farmacológico , Diagnóstico Precoce , Humanos , Pesquisa OperacionalRESUMO
BACKGROUND: Buruli ulcer is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear. METHODS: This was a retrospective study of data collected at the Akonolinga District Hospital, Cameroon, from January 1, 2002 to March 27, 2013. Human immunodeficiency virus prevalence among BU patients was compared with regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients and according to CD4 cell count strata in the latter group. Buruli ulcer time-to-healing was assessed in different CD4 count strata, and factors associated with BU main lesion size at baseline were identified. RESULTS: Human immunodeficiency virus prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). Individuals who were HIV positive had a more severe form of BU, with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (ß-coefficient, -0.50; P = .015; 95% confidence interval [CI], -0.91-0.10). Buruli ulcer time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm(3) (hazard ratio, 2.39; P = .001; 95% CI, 1.44-3.98). CONCLUSION: Patients who are HIV positive are at higher risk for BU. Human immunodeficiency virus-induced immunosuppression seems to have an impact on BU clinical presentation and disease evolution.
RESUMO
OBJECTIVE: To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. DESIGN: Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). RESULTS: Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization-defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The "fully loaded" cost of VL monitoring was $35 per patient-year. CONCLUSIONS: Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization-defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Adolescente , Adulto , Contagem de Linfócito CD4 , Criança , Estudos de Coortes , Análise Custo-Benefício , Aconselhamento , Essuatíni , Feminino , Infecções por HIV/economia , Humanos , Masculino , Adesão à Medicação , Estudos Retrospectivos , Estatísticas não Paramétricas , Carga Viral , Adulto JovemRESUMO
BACKGROUND: There is little evidence on the effectiveness of services for the care of people with mental disorders among refugee populations. Médecins sans Frontières (MSF) has established a mental health centre in a mixed urban-refugee population in Beirut to respond to the significant burden of mental health problems. Patients received comprehensive care through a multidisciplinary team. A cohort of people with common and severe mental disorders has been analysed between December 2008 and June 2011 to evaluate individual outcomes of treatment in terms of functionality. METHODS: All patients diagnosed with mental disorders were included in the study. The Global Assessment of Functioning (GAF) and the Self Reporting Questionnaire-20 items (SRQ 20) were used as tools for baseline assessment, monitoring and evaluation of patients. Predictors of evolution of SRQ20 and GAF over visits were explored using a linear mixed model. RESULTS: Up to June 2011, 1144 patients were followed, 63.7% of them Lebanese, 31.8% Palestinians and 1.2% Iraqis. Females represented 64.2% of the patient population. Mean age was 39.2 years (28.5-46.5). The most frequent primary diagnoses were depressive disorders (28.8%), anxiety disorders (15.6%) and psychosis (11.5%). A lower baseline SRQ20 score/higher baseline GAF score (indicators of severity), being diagnosed with anxiety (compared to being diagnosed with depression or psychosis) and a higher level of education were associated with better outcomes. DISCUSSION: In this MSF program, we observed a significant decrease of SRQ20 individual scores and a significant increase of individual GAF scores. This corresponded to an improvement in the functionality of our patients. Analysis of the predictors of this positive evolution indicates that we need to adapt our model for the more severe and less educated patients. It also makes us reflect on the length of the individual follow-up. Further research could include a qualitative evaluation of the intervention. Results of this study have been presented at the World Congress of the World Federation for Mental Health in Cape Town, October 2011.
Assuntos
Transtornos Mentais/diagnóstico , Saúde Mental/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Inquéritos e Questionários , Adolescente , Adulto , Ansiedade/diagnóstico , Ansiedade/psicologia , Ansiedade/terapia , Árabes/etnologia , Estudos de Coortes , Depressão/diagnóstico , Depressão/psicologia , Depressão/terapia , Feminino , Humanos , Iraque/etnologia , Líbano , Masculino , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Saúde Mental/etnologia , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Refugiados/psicologia , Adulto JovemRESUMO
Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts.