Effect of Ebola virus disease on maternal and child health services in Guinea: a retrospective observational cohort study

Background The 2014 west African epidemic of Ebola virus disease posed a major threat to the health systems of the countries affected. We sought to quantify the consequences of Ebola virus disease on maternal and child health services in the highly-affected Forest region of Guinea. Methods We did a retrospective, observational cohort study of women and children attending public health facilities for antenatal care, institutional delivery, and immunisation services in six of seven health districts in the Forest region (Beyla, Guéckédou, Kissidougou, Lola, Macenta, and N’Zérékoré). We examined monthly service use data for eight maternal and child health services indicators: antenatal care (≥1 antenatal care visit and ≥3 antenatal care visits), institutional delivery, and receipt of five infant vaccines: polio, pentavalent (diphtheria, tetanus, pertussis, hepatitis B virus, and Haemophilus influenzae type b), yellow fever, measles, and tuberculosis. We used interrupted time series models to estimate trends in each indicator across three time periods: pre-Ebola virus disease epidemic (January, 2013, to February, 2014), during-epidemic (March, 2014, to February, 2015) and postepidemic (March, 2015, to Feb, 2016). We used segmented ordinary least-squares (OLS) regression using Newey- West standard errors to accommodate for serial autocorrelation, and adjusted for any potential effect of birth seasonality on our outcomes. Findings In the months before the Ebola virus disease outbreak, all three maternal indicators showed a significantly positive change in trend, ranging from a monthly average increase of 61 (95% CI 38–84) institutional deliveries to 119 (95% CI 79–158) women achieving at least three antenatal care visits. These increasing trends were reversed during the epidemic: fewer institutional deliveries occurred (–240, 95% CI –293 to –187), and fewer women achieved at least one antenatal care visit (–418, 95% CI –535 to –300) or at least three antenatal care visits (–363, 95% CI –485 to –242) per month (p<0·0001 for all). Compared with the negative trend during the outbreak, the change in trend during the post-outbreak period showed that 173 more women per month (95% CI 51–294; p=0·0074) had at least one antenatal care visit, 257 more (95% CI 117–398; p=0·0010) had at least three antenatal care visits and 149 more (95% CI 91–206; p<0·0001) had institutional deliveries. However, although the numbers for these indicators increased in the post-epidemic period, the trends for all stagnated. Similarly, the increasing trend in child vaccination completion during the pre-epidemic period was followed by significant immediate and trend reductions across most vaccine types. Before the outbreak, the number of children younger than 12 months who had completed each vaccination ranged from 5752 (95% CI 2821–8682) for tuberculosis to 8043 (95% CI 7621–8464) for yellow fever. Immediately after the outbreak, significant reductions occurred in the level of all vaccinations except for yellow fever for which the reduction was marginal. The greatest reductions were noted for polio and tuberculosis at –3594 (95% CI –4811 to –2377; p<0·0001) and –3048 (95% CI –5879 to –216; p=0·0362) fewer vaccines administered, respectively. Compared with pre-Ebola virus disease outbreak trends, significant decreases occurred for all vaccines except polio, with the trend of monthly decreases in the number of children vaccinated ranging from –419 (95% CI –683 to –155; p=0·0034) fewer for BCG to –313 (95% CI–446 to –179; p<0·0001) fewer for pentavalent during the outbreak. In the post-Ebola virus disease outbreak period, vaccination coverage for polio, measles, and yellow fever continued to decrease, whereas the trend in coverage for tuberculosis and pentavalent did not significantly differ from zero. Interpretation Most maternal and child health indicators significantly declined during the Ebola virus disease outbreak in 2014. Despite a reduction in this negative trend in the post-outbreak period, the use of essential maternal and child health services have not recovered to their pre-outbreak levels, nor are they all on a course that suggests that they will recover without targeted interventions

Structural controls of gold mineralisation in Seguelen pit of Siguiri gold mine, Guinea

The present study provides the results of detailed mapping and analysis of structures encountered in Seguelen pit of Siguiri gold mine, Guinea, where the Siguiri mine is geo-tectonically located in the Baoulé-Mossi domain of Man Shield in West African craton. The gold deposit is hosted in low-grade metamorphic sediments of turbidites sequences which form part of the Lower Proterozoic of Birimian Super group. Three rock formations of Balato, Fatoya and Kintinian underlay the overall pits. The Siguiri gold mine is characterized by the deep weathering profile, developed over the rocks reaching 200 m below the surface in some areas and often capped by the lateritic gravel or duricrust. The rock formations at Seguelen area are characterised by strong bedding monotonously dipping towards SW and trending NW-SE. The lithology of the host rocks has strong control on the disseminated mineralisation throughout the deposit. Two domains of rock formations are clearly distinguished at Seguelen: Fatoya Formation(Ffm) domain ; and Kintinian Formation (Kfm) domain. The two domains are separated by a contact zone of 1.7 m wide parallel to bedding and characterised by the presence of quartz fragments as well as thinly sheeted shale and black shale. This contact zone is identified as disconformity. The major tectonic deformation which has affected the region is known as D2 corresponding to the Eburnean orogeny. The major D2 related structures is the regional thrust striking N-S over an area of 12 km long and 3 km wide and within which corridors all Siguiri gold Mine open pits are located. In the N-S trending structures, there is east-northeast shortening and north-northwest extension. There is pervasive hydrothermal alteration (carbonatization and sideritization) and supergene alteration in the all pits. The hydrothermal alteration attests the intensity of hydrothermal fluid-flow over the host rocks. The hydrothermal fluids flowed along the fractures and within the wall rocks through bedding plans to form numerous auriferous quartz veins bearing disseminated sulphides through chemical reaction between fluids and wall rocks, which are remarkable at Seguelen pit. Three quartz vein sets are distinguished at Seguelen: NNE-SSW quartz vein set NE-SW quartz vein set NW-SE quartz vein set The NE-SW and NNE-SSW quartz veins are often lenticular and associated with the bulk mineralisation

Fistula recurrence, pregnancy, and childbirth following successful closure of female genital fistula in Guinea : a longitudinal study

Background: Female genital fistula is a devastating maternal complication of delivery in developing countries. We sought to analyse the incidence and proportion of fistula recurrence, residual urinary incontinence, and pregnancy after successful fistula closure in Guinea, and describe the delivery-associated maternal and child health outcomes. Methods: We did a longitudinal study in women discharged with a closed fistula from three repair hospitals supported by Engender Health in Guinea. We recruited women retrospectively (via medical record review) and prospectively at hospital discharge. We used Kaplan-Meier methods to analyse the cumulative incidence, incidence proportion, and incidence ratio of fistula recurrence, associated outcomes, and pregnancy after successful fistula closure. The primary outcome was recurrence of fistula following discharge from repair hospital in all eligible women who consented to inclusion and could provide follow-up data. Findings: 481 women eligible for analysis were identified retrospectively (from Jan 1, 2012, to Dec 31, 2014; 348 women) or prospectively (Jan 1 to June 20, 2015; 133 women), and followed up until June 30, 2016. Median follow-up was 28.0 months (IQR 14.6-36.6). 73 recurrent fistulas occurred, corresponding to a cumulative incidence of 71 per 1000 person-years (95% CI 56.5-89.3) and an incidence proportion of 18.4% (14.8-22.8). In 447 women who were continent at hospital discharge, we recorded 24 cases of post-repair residual urinary incontinence, equivalent to a cumulative incidence of 23.1 per 1000 person-years (14.0-36.2), and corresponding to 10.3% (5.2-19.6). In 305 women at risk of pregnancy, the cumulative incidence of pregnancy was 106.0 per 1000 person-years, corresponding to 28.4% (22.8-35.0) of these women. Of 50 women who had delivered by the time of follow-up, only nine delivered by elective caesarean section. There were 12 stillbirths, seven delivery-related fistula recurrences, and one maternal death. Interpretation: Recurrence of female genital fistula and adverse pregnancy-related maternal and child health outcomes were frequent in women after fistula repair in Guinea. Interventions are needed to safeguard the health of women after fistula repair

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study

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 fl uid, 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 fl uid 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 immunodefi cient mice to test for infectivity. We used a linear mixed-eff ect model to analyse the dynamics of virus persistence in seminal fl uid over time. Findings We enrolled 26 participants and tested 130 seminal fl uid 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 fl uid 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 fl uid 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 aff ected 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 fl uid 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

Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable protease to promote cell death.

Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death

Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.Howard Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002]info:eu-repo/semantics/publishedVersio

The analysis of operation of the three phase-two phase Kubler's converter on the modified scheme

In this work, it is analysed the operation of the three phase-two phase Kublera’s converter on the modified scheme. The received results of the coefficient of the asymmetry do not satisfy requirements of state standard specification.В работе проанализирована работа трехфазно-двухфазного преобразователя Кюблера по модифицированной схеме. Полученные результаты коэффициента несимметрии не удовлетворяют требованиям ГОСТа

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study.

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

COMPARISON OF WEIGHT AND DIMENSIONAL INDICA TORS OF THE THREE-PHASE AND TWO-PHASE CONVERTERS OF KYUBLER

Проведено сопоставление весо-габаритных показателей трансформаторных трехфазно-двухфазных преобразователей, построенных на основе схемы Кюблера – исходной и модифицированной. Показано, что модифицированная схема уступает исходной.Comparison of weight and dimensional indicators of the three-phase and twophase converters of transformer constructed on the basis of Kyubler's scheme initial and modified is carried out. It is shown that the modified scheme is inferior to the initial