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1.
BMC Pregnancy Childbirth ; 23(1): 391, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37245008

RESUMO

INTRODUCTION: The composite coverage index (CCI) is the weighted average coverage of eight preventive and curative interventions received along the maternal and childcare continuum. This study aimed to analyse maternal and child health indicators using CCI. METHODS: We performed a secondary analysis of demographic and health surveys (DHS) focused on women aged 15 to 49 and their children aged 1 to 4. This study took place in Guinea. The CCI (meeting the need for planning, childbirth assisted by qualified healthcare workers, antenatal care assisted by qualified healthcare workers, vaccination against diphtheria, pertussis, tetanus, measles and Bacillus Calmette-Guérin, taking oral rehydration salts during diarrhoea and seeking care for pneumonia) is optimal if the weighted proportion of interventions is > 50%; otherwise, it is partial. We identified the factors associated with CCI using the descriptive association tests, the spatial autocorrelation statistic and multivariate logistic regression. RESULTS: The analyses involved two DHS surveys, with 3034 included in 2012 and 4212 in 2018. The optimal coverage of the CCI has increased from 43% in 2012 to 61% in 2018. In multivariate analysis, in 2012: the poor had a lower probability of having an optimal CCI than the richest; OR = 0.11 [95% CI; 0.07, 0.18]. Those who had done four antenatal care visits (ANC) were 2.78 times more likely to have an optimal CCI than those with less OR = 2.78 [95% CI;2.24, 3.45]. In 2018: the poor had a lower probability of having an optimal CCI than the richest OR = 0.27 [95% CI; 0.19, 0.38]. Women who planned their pregnancies were 28% more likely to have an optimal CCI than those who had not planned OR = 1.28 [95% CI;1.05, 1.56]. Finally, women with more than 4 ANC were 2.43 times more likely to have an optimal CCI than those with the least OR = 2.43 [95% CI; 2.03, 2.90]. The spatial analysis reveals significant disparities with an aggregation of high partial CCI in Labé between 2012 and 2018. CONCLUSION: This study showed an increase in CCI between 2012 and 2018. Policies should improve access to care and information for poor women. Besides, strengthening ANC visits and reducing regional inequalities increases optimal CCI.


Assuntos
Continuidade da Assistência ao Paciente , Cuidado Pré-Natal , Gravidez , Feminino , Humanos , Fatores Socioeconômicos , Guiné/epidemiologia , Demografia , Inquéritos Epidemiológicos
2.
S Afr J Infect Dis ; 38(1): 454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756241

RESUMO

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018-2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 - 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22-70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

3.
N Engl J Med ; 387(26): 2411-2424, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36516078

RESUMO

BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).


Assuntos
Vacinas contra Ebola , Ebolavirus , Doença pelo Vírus Ebola , Adulto , Criança , Humanos , Anticorpos Antivirais , República Democrática do Congo , Vacinas contra Ebola/uso terapêutico , Doença pelo Vírus Ebola/prevenção & controle
4.
Malar J ; 21(1): 309, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36316702

RESUMO

BACKGROUND: Despite its effectiveness, the optimal use of the combination of insecticide-treated nets (ITN) and intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) remains low in malaria-endemic areas. Therefore, this study analyzed its variations and predictors in Guinea. METHODS: This study was a secondary analysis of the 2012 and 2018 Guinea Demographic and Health Surveys (DHS). It included women who had given birth 3 years before each DHS, slept on ITN and took at least one dose of SP. Use was complete if a pregnant woman slept on ITNs and took SP (at least two doses in 2012; at least three doses in 2018). Moran indices were used to determine spatial autocorrelation and classification methods to identify malaria preventive measures (MPM) predictors. RESULTS: In 2012, 60.88% of pregnant women had incomplete use of MPMs compared with 79.11% in 2018. Associated factors with incomplete MPMs in 2012 were as follows: having an indirect link with the head of household (AOR = 2.23, 95% CI 1.08-4.61) and performing at least 4 ANC visits (AOR = 0.66, 95% CI 0.44-0.99). In 2018: Living in households of 2 to 5 people (AOR = 0.54, 95% CI 0.36-0.80), have a man as the head of the household (AOR = 0.56, 95% CI 0.35-0.89), perform the first ANC in the second trimester of pregnancy (AOR = 0.74, 95% CI 0.54-0.99), perform at least 4 ANC visits (AOR = 0.47, 95% CI 0.36-0.62), have a job (AOR = 0. 67, 95% CI 0.50-0.88), give birth in a public health facility (AOR = 0.53, 95% CI 0.39-0.72) and the middle wealth quintile (AOR = 1.56, 95% CI 1.07-2.26). Analyses revealed a global autocorrelation (Moran index = 0.0009, p = 0.2349) and high-high clusters in Mamou in 2012. In 2018, autocorrelation was found (I Moran = 0.0169, p ≤ 0.05), with spatial clusters in 4 regions. CONCLUSION: The link with the head of household and the number of ANC visits were the main factors in MPMs. It is essential to implement strategies at the household level and health system level and monitor them to reduce inequality across regions.


Assuntos
Antimaláricos , Malária , Complicações Parasitárias na Gravidez , Feminino , Humanos , Masculino , Gravidez , Antimaláricos/uso terapêutico , Combinação de Medicamentos , Características da Família , Guiné/epidemiologia , Malária/prevenção & controle , Malária/tratamento farmacológico , Complicações Parasitárias na Gravidez/prevenção & controle , Complicações Parasitárias na Gravidez/tratamento farmacológico , Gestantes , Cuidado Pré-Natal , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico
5.
Am J Trop Med Hyg ; 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35213814

RESUMO

In this case report, we describe a clinical presentation and therapeutic history of a unique case diagnosed with Lassa fever and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 23-year-old man from Yomou prefecture in southeast Guinea identified with suspected Ebola Virus Disease (EVD) in the midst of an ongoing outbreak of that disease in the same region. On May 3, 2021, he was admitted to the Nzérékoré Epidemic disease treatment center where his clinical condition deteriorated significantly. Laboratory testing performed on the same day reveals a negative EVD polymerase chain reaction (PCR). Three days later, the patient was tested positive for SARS-CoV-2 and Lassa fever by reverse transcriptase PCR (RT-PCR) assays. Laboratory examination also indicated severe hematological and biochemical deteriorations in the patient. This case substantiates the need for systematic differential diagnosis during epidemic-prone disease outbreaks to better manage severely unwell patients.

6.
Infect Dis Obstet Gynecol ; 2021: 9914424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305392

RESUMO

Background: Malaria control interventions have been scaled up, particularly those in pregnant women in Guinea. Despite that, coverage of key malaria preventive measure (MPM) indicators remains low. Therefore, it is vital to understand the reasons behind that, especially for the low coverage of sulfadoxine-pyrimethamine (SP) and long-lasting insecticide-treated bed nets (LLIN). Methods: We conducted a cross-sectional survey in nine district hospitals in Guinea. Pregnant women received for delivery were interviewed to collect sociodemographic and obstetrical parameters. Associated factors with MPMs were investigated through univariate analysis and classification and regression tree (CART). Results: A total of 2248 parturients participated in this study. Among pregnant women using mosquito nets (63.5% (61.4%, 65.5%)), only 41.2% (39.1%, 43.3%) had used it regularly during the last two weeks preceding delivery. Similarly, most pregnant women (57.9% (55.8%, 59.9%)) had received less than three doses of SP, and only a few pregnant women (23.9% (22.1%, 25.7%)) have benefited from full MPMs. Parturient's age, marital status, time spent in residence, place of residence, level of education, distance from home to the health centre, health conditions, occupation, head of the household's occupation, the presence of garbage and stagnant water in the neighbourhood, source of running water, and the number of pregnancies were significantly statistically associated with MPMs in pregnant women. However, the number of antenatal care visits (ANC), means of transportation used by the pregnant woman to accomplish ANCs, and stagnant water in the neighbourhood were the three preponderant factors. Conclusion: The low coverage of SP and LLINs among pregnant women requires revitalising some strategies, especially improving ANC coverage and more efforts to reduce inequalities in access to those services due to sociodemographic status. Education on the benefits of these MPMs should also be emphasised.


Assuntos
Antimaláricos , Mosquiteiros Tratados com Inseticida , Malária , Complicações Parasitárias na Gravidez , Antimaláricos/uso terapêutico , Estudos Transversais , Feminino , Guiné/epidemiologia , Humanos , Malária/epidemiologia , Malária/prevenção & controle , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/prevenção & controle , Gestantes
7.
PLoS One ; 16(2): e0245751, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529216

RESUMO

Guinea, like many other African countries, has been facing an unprecedented COVID-19 outbreak, since March 2020. In April 2020, Guinean National agency for health security recorded 1351 confirmed cases of COVID-19, including 313 recoveries and 07 deaths. To address this health crisis, some drastic measures were implemented to prevent the spread of COVID-19. Those measures might potentially cause some psychological problems among Guineans. Thus, we conducted this study to assess the psychosocial impacts of COVID-19 in the Guinean population. We carried out an online cross-sectional survey among internet users in Guinea. A free e-survey platform was used, and questionnaires were sent to internet users. The study ran from May 1 through May 10 2020. Participation in the study was voluntary. Data collection was based on sociodemographic information and self-reported questionnaires: Impact of Event Scale-Revised (IES-R) for stress evaluation, Penn state worry questionnaire (PSWQ), and an adapted Social Psychological Measurements of COVID-19. A total of 280 participants took part in the study; responses from 5 participants were deleted because of incompleteness. The average age of participants was 28.9 [95% CI: 28.1;29.6]. Most of participants were male 65.5% [95% CI: 59.5%;71.1%]. Unemployed participants stood for 48.7% [95% CI: 42.7%;54.8%]. IES-R scale for stress evaluation yielded the following findings: 19.6% (mild), 5.23% (moderate) and 9.15% (severe); 82.8% and 17.2% of participants had respectively reported low and moderate worry. No significant statistical association was found between sociodemographic variables and traumatic events (IES-R and PSWQ). However, 82% of our participants had to cope with the negative impacts of COVID-19. Although there were few cases of traumatic events, negative impacts of COVID-19 on study participants deserve to be underlined. So, further investigations are necessary to identify and disentangle specific psychosocial problems in different Guinean socio-cultural contexts.


Assuntos
COVID-19/psicologia , Adulto , Ansiedade/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Estudos Transversais , Surtos de Doenças , Feminino , Guiné/epidemiologia , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
8.
Pan Afr Med J ; 36: 360, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33224426

RESUMO

The purpose of this study was to perform correlation of 5 cases and literature review. The study involved both children and adults. The major cause of retropharyngeal abscess was fish bone foreign body. Dysphagia associated with pain, fever and torticollis were the most common symptoms. Retropharyngeal abscess mainly occurred in the oropharyngeal and hypopharyngeal regions. Imaging tests, in particular CT scan, allowed for accurate information in 3 cases. Aerodigestive tract obstruction was found in most of our patients. Only 4 patients underwent incision and drainage. All patients received medical treatment. A 2-year-old died 5 days after surgery due to septic shock. This study highlights the rarity of this condition in our context as well as the importance of early diagnosis and treatment to prevent life-threatening complications.


Assuntos
Transtornos de Deglutição/etiologia , Corpos Estranhos/complicações , Abscesso Retrofaríngeo/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Drenagem/métodos , Feminino , Humanos , Masculino , Abscesso Retrofaríngeo/etiologia , Abscesso Retrofaríngeo/terapia , Choque Séptico/etiologia , Tomografia Computadorizada por Raios X , Torcicolo/etiologia
9.
Pan Afr Med J ; 36: 176, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32952820

RESUMO

During the ongoing pandemic, anosmia, whether or not associated with aguesia, has been a common symptom in patients with SARS-CoV-2 infection causing COVID-19. We here report two cases of anosemia without aguesia in adults with COVID-19. The onset was brutal and symptomsa persisted for a few weeks after healing. The patients presented to the ENT Department where they received no therapy and underwent outpatient surveillance. After 5 weeks, patients reported they had recovered the sense of smell. This study highlights that anosmia can occur without aguesia and persist after healing in COVID-19 patients. Recovery of the smell is possible after a few weeks without medical treatment. That is why, patients follow-up is essential in subjects recovered from COVID-19 to better understand the course of persistent symptoms.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Transtornos do Olfato/virologia , Pneumonia Viral/complicações , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/diagnóstico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , Fatores de Tempo
10.
J Infect Dis ; 220(2): 195-202, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-30788508

RESUMO

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. RESULTS: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Ebolavirus/efeitos dos fármacos , Doença pelo Vírus Ebola/tratamento farmacológico , Pirazinas/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Ensaios de Uso Compassivo/métodos , Feminino , Guiné , Doença pelo Vírus Ebola/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos , Adulto Jovem
11.
Med Sci (Paris) ; 33(10): 891-897, 2017 Oct.
Artigo em Francês | MEDLINE | ID: mdl-28994386

RESUMO

During the 2013-2016 west African Ebola outbreak that affected West Africa, accelerated clinical trials, testing unproven but promising and potentially lifesaving experimental interventions emerged as a key component of the global outbreak. In 2017, no Ebola medical countermeasures had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried a list of potential drug candidates developed or repurposed with demonstrated antiviral efficacy in vitro or in animal models. Numerous therapeutics were considered or explored during the outbreak, including nucleoside and nucleotide analogues, nucleic acid-based drugs and immunotherapeutics. Drugs in clinical trials were tested within the framework of optimized supportive care with fluids and electrolytes and management of severe compromise of multiple organs resulting from viral cytopathology and immune-mediated cell damage. Assessment of those therapeutics with encouraging preliminary efficacy or safety profile, like the repurposed direct antiviral agent favipiravir or the combination of antibodies ZMapp requires further investigation to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations. During the lull before the next epidemic, major challenges for managing future Ebola epidemics include scientific, clinical and public health preparedness with establishment of innovative patient care and clinical research support in remote poor areas where Ebola and other deadly infectious diseases typically reemerge.


Assuntos
Pesquisa Biomédica/organização & administração , Epidemias/prevenção & controle , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Saúde Pública/métodos , Integração de Sistemas , África Ocidental/epidemiologia , Animais , Surtos de Doenças/prevenção & controle , Humanos , Organização Mundial da Saúde
12.
PLoS Negl Trop Dis ; 11(6): e0005545, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28640812

RESUMO

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 Pesquisa
13.
Lancet Glob Health ; 5(1): e80-e88, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27955791

RESUMO

BACKGROUND: By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. METHODS: In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. FINDINGS: We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. INTERPRETATION: Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. FUNDING: This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking.


Assuntos
Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/transmissão , RNA , Sêmen , Sobreviventes , Adulto , Ebolavirus/genética , Guiné , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Fatores de Tempo
15.
PLoS Med ; 13(3): e1001967, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26930627

RESUMO

BACKGROUND: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. METHODS AND FINDINGS: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 µmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 µmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 µmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 µmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. CONCLUSIONS: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Pirazinas/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Ebolavirus/genética , Estudos de Viabilidade , Feminino , Guiné , Doença pelo Vírus Ebola/diagnóstico , Estudo Historicamente Controlado , Humanos , Lactente , Masculino , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Terapias em Estudo , Resultado do Tratamento , Carga Viral , Adulto Jovem
16.
Clin Infect Dis ; 62(7): 903-905, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26679622

RESUMO

We report 2 cases of Ebola viral disease (EVD) in pregnant women who survived, initially with intact pregnancies. Respectively 31-32 days after negativation of the maternal blood EVD-polymerase chain reaction (PCR) both patients delivered a stillborn fetus with persistent EVD-PCR amniotic fluid positivity.


Assuntos
Doença pelo Vírus Ebola , Complicações Infecciosas na Gravidez , Adulto , Líquido Amniótico/virologia , Feminino , Sangue Fetal/virologia , Humanos , Placenta/virologia , Gravidez , Natimorto , Adulto Jovem
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