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The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

ABSTRACT: The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.

SUBMITTER: van Griensven J

PROVIDER: S-EPMC4678103 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

van Griensven Johan J De Weiggheleire Anja A Delamou Alexandre A Smith Peter G PG Edwards Tansy T Vandekerckhove Philippe P Bah Elhadj Ibrahima EI Colebunders Robert R Herve Isola I Lazaygues Catherine C Haba Nyankoye N Lynen Lutgarde L

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20150810 1

The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD ...[more]

PMID: 26261205

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Project description:IntroductionSexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.MethodsWe prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.Results and discussionsThe diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.ConclusionsThe WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Project description:The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert.To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting.Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm").Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively.Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

Project description:AimTo determine whether intermediate hyperglycaemia, defined by fasting plasma glucose and HbA1c criteria, is associated with mortality in a 10-year cohort of people in a Latin American country.MethodsAnalysis of the PERU MIGRANT Study was conducted in three different population groups (rural, rural-to-urban migrant, and urban). The baseline assessment was conducted in 2007/2008, with follow-up assessment in 2018. The outcome was all-cause mortality, and the exposure was intermediate hyperglycaemia, using three definitions: (1) impaired fasting glucose, defined according to American Diabetes Association criteria [fasting plasma glucose 5.6-6.9 mmol/l (100-125 mg/dl)]; (2) intermediate hyperglycaemia defined according to American Diabetes Association criteria [HbA1c levels 39-46 mmol/mol (5.7-6.4%)]; and (3) intermediate hyperglycaemia defined according to the International Expert Committee criteria [HbA1c levels 42-46 mmol/mol (6.0-6.4%)]. Crude and adjusted hazard ratios and 95% CIs were estimated using Cox proportional hazard models.ResultsAt baseline, the mean (sd) age of the study population was 47.8 (11.9) years and 52.5% of the cohort were women. The study cohort was divided into population groups as follows: 207 people (20.0%) in the rural population group, 583 (59.7%) in the rural-to-urban migrant group and 198 (20.3%) in the urban population group. The prevalence of intermediate hyperglycaemia was: 6%, 12.9% and 38.5% according to the American Diabetes Association impaired fasting glucose definition, the International Expert Committee HbA1c -based definition and the American Diabetes Association HbA1c -based definition, respectively, and the mortality rate after 10 years was 63/976 (7%). Intermediate hyperglycaemia was associated with all-cause mortality using the HbA1c -based definitions in the crude models [hazard ratios 2.82 (95% CI 1.59-4.99) according to the American Diabetes Association and 2.92 (95% CI 1.62-5.28) according to the International Expert Committee], whereas American Diabetes Association-defined impaired fasting glucose was not [hazard ratio 0.84 (95% CI 0.26-2.68)]. In the adjusted model, however, only the American Diabetes Association HbA1c -based definition was associated with all-cause mortality [hazard ratio 1.91 (95% CI 1.03-3.53)], whereas the International Expert Committee HbA1c -based and American Diabetes Association impaired fasting glucose-based definitions were not [hazard ratios 1.42 (95% CI 0.75-2.68) and 1.09 (95% CI 0.33-3.63), respectively].ConclusionsIntermediate hyperglycaemia defined using the American Diabetes Association HbA1c criteria was associated with an elevated mortality rate after 10 years in a cohort from Peru. HbA1c appears to be a factor associated with mortality in this Peruvian population.

Dataset Information

The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

Publications

The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

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