Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings.

BACKGROUND: Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. METHODS: We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. RESULTS: The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of - 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients' age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score. CONCLUSION: Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.

Assessment of genotyping array performance for genome-wide association studies and imputation in African cattle.

BACKGROUND: In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. RESULTS: We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. CONCLUSIONS: Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.

Evaluation of the first two Frontline cohorts of the field epidemiology training program in Guinea, West Africa.

BACKGROUND: The 2014-2016 Ebola virus disease outbreak in West Africa revealed weaknesses in the health systems of the three most heavily affected countries, including a shortage of public health professionals at the local level trained in surveillance and outbreak investigation. In response, the Frontline Field Epidemiology Training Program (FETP) was created by CDC in 2015 as a 3-month, accelerated training program in field epidemiology that specifically targets the district level. In Guinea, the first two FETP-Frontline cohorts were held from January to May, and from June to September 2017. Here, we report the results of a cross-sectional evaluation of these first two cohorts of FETP-Frontline in Guinea. METHODS: The evaluation was conducted in April 2018 and consisted of interviews with graduates, their supervisors, and directors of nearby health facilities, as well as direct observation of data reports and surveillance tools at health facilities. Interviews and site visits were conducted using standardized questionnaires and checklists. Qualitative data were coded under common themes and analyzed using descriptive statistics. RESULTS: The evaluation revealed a significant perception of improvement in all assessed skills by the graduates, as well as high levels of self-reported involvement in key activities related to data collection, analysis, and reporting. Supervisors highlighted improvements to systematic and quality case and summary reporting as key benefits of the FETP-Frontline program. At the health facility level, staff reported the training had resulted in improvements to information sharing and case notifications. Reported barriers included lack of transportation, available support personnel, and other resources. Graduates and supervisors both emphasized the importance of continued and additional training to solidify and retain skills. CONCLUSIONS: The evaluation demonstrated a strongly positive perceived benefit of the FETP-Frontline training on the professional activities of graduates as well as the overall surveillance system. However, efforts are needed to ensure greater gender equity and to recruit more junior trainee candidates for future cohorts. Moreover, although improvements to the surveillance system were observed concurrent with the completion of the two cohorts, the evaluation was not designed to directly measure impact on surveillance or response functions. Combined with the rapid implementation of FETP-Frontline around the world, this suggests an opportunity to develop standardized evaluation toolkits, which could incorporate metrics that would directly assess the impact of equitable field epidemiology workforce development on countries' abilities to prevent, detect, and respond to public health threats.

Surveillance system assessment in Guinea: Training needed to strengthen data quality and analysis, 2016.

The 2014-2016 Ebola virus disease outbreak revealed the fragility of the Guinean public health infrastructure. As a result, the Guinean Ministry of Health is collaborating with international partners to improve compliance with the International Health Regulations and work toward the Global Health Security Agenda goals, including enhanced case- and community-based disease surveillance. We assessed the case-based disease surveillance system during October 1, 2015-March 31, 2016, in the Boffa prefecture of Guinea. We conducted onsite interviews with public health staff at the peripheral (health center), middle (prefectural), and central (Ministry of Health) levels of the public health system to document leadership structure; methods for maintaining case registers and submitting weekly case reports; disease surveillance feedback; data analysis; and baseline surveillance information on four epidemic-prone diseases (cholera, meningococcal meningitis, measles, and yellow fever). The surveillance system was simple and paper-based at health centers and computer spreadsheet-based at the prefectural and central levels. Surveillance feedback to stakeholders at all levels was infrequent. Data analysis activities were minimal at the peripheral levels and progressively more robust at the prefectural and central levels. Reviewing the surveillance reports from Boffa during the study period, we observed zero reported cases of the four epidemic-prone diseases in the weekly reporting from the peripheral to the central level. Similarly, the national District Health Information System 2 had no reported cases of the four diseases in Boffa but did indicate reported cases among all four neighboring prefectures. Based on the assessment findings, which suggest low sensitivity of the case-based disease surveillance system in Boffa, we recommend additional training and support to improve surveillance data quality and enhance Guinean public health workforce capacity to use these data.

Recommendations for the COVID-19 Response at the National Level Based on Lessons Learned from the Ebola Virus Disease Outbreak in the Democratic Republic of the Congo.

The tenth outbreak of Ebola virus disease (EVD) in North Kivu, the Democratic Republic of the Congo (DRC), was declared 8 days after the end of the ninth EVD outbreak, in the Equateur Province on August 1, 2018. With a total of 3,461 confirmed and probable cases, the North Kivu outbreak was the second largest outbreak after that in West Africa in 2014-2016, and the largest observed in the DRC. This outbreak was difficult to control because of multiple challenges, including armed conflict, population displacement, movement of contacts, community mistrust, and high population density. It took more than 21 months to control the outbreak, with critical innovations and systems put into place. We describe systems that were put into place during the EVD response in the DRC that can be leveraged for the response to the current COVID-19 global pandemic.

The cost of insecurity: from flare-up to control of a major Ebola virus disease hotspot during the outbreak in the Democratic Republic of the Congo, 2019.

The ongoing Ebola outbreak in the eastern Democratic Republic of the Congo is facing unprecedented levels of insecurity and violence. We evaluate the likely impact in terms of added transmissibility and cases of major security incidents in the Butembo coordination hub. We also show that despite this additional burden, an adapted response strategy involving enlarged ring vaccination around clusters of cases and enhanced community engagement managed to bring this main hotspot under control.

Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.

BACKGROUND: The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. METHODS: From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. RESULTS: ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. CONCLUSION: HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.

How women are treated during facility-based childbirth in four countries: a cross-sectional study with labour observations and community-based surveys.

BACKGROUND: Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries. METHODS: We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment. FINDINGS: 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15-19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6-8·0) and younger women with some education (OR 1·6, 1·1-2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity. INTERPRETATION: More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context. FUNDING: United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO.

Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment.

BACKGROUND: The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. METHODS: We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. FINDINGS: The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. INTERPRETATION: The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. FUNDING: Defense Biological Product Assurance Office.

Methodological development of tools to measure how women are treated during facility-based childbirth in four countries: labor observation and community survey.

BACKGROUND: Efforts to improve maternal health are increasingly focused on improving the quality of care provided to women at health facilities, including the promotion of respectful care and eliminating mistreatment of women during childbirth. A WHO-led multi-country research project aims to develop and validate two tools (labor observation and community survey) to measure how women are treated during facility-based childbirth. This paper describes the development process for these measurement tools, and how they were implemented in a multi-country study (Ghana, Guinea, Myanmar and Nigeria). METHODS: An iterative mixed-methods approach was used to develop two measurement tools. Methodological development was conducted in four steps: (1) initial tool development; (2) validity testing, item adjustment and piloting of paper-based tools; (3) conversion to digital, tablet-based tools; and (4) data collection and analysis. These steps included systematic reviews, primary qualitative research, mapping of existing tools, item consolidation, peer review by key stakeholders and piloting. RESULTS: The development, structure, administration format, and implementation of the labor observation and community survey tools are described. For the labor observations, a total of 2016 women participated: 408 in Nigeria, 682 in Guinea, and 926 in Ghana. For the community survey, a total of 2672 women participated: 561 in Nigeria, 644 in Guinea, 836 in Ghana, and 631 in Myanmar. Of the 2016 women who participated in the labor observations, 1536 women (76.2%) also participated in the community survey and have linked data: 779 in Ghana, 425 in Guinea, and 332 in Nigeria. CONCLUSIONS: An important step to improve the quality of maternity care is to understand the magnitude and burden of mistreatment across contexts. Researchers and healthcare providers in maternal health are encouraged to use and implement these tools, to inform the development of more women-centered, respectful maternity healthcare services. By measuring the prevalence of mistreatment of women during childbirth, we will be able to design and implement programs and policies to transform maternity services.

Traumatic Brain Injury Related to Motor Vehicle Accidents in Guinea: Impact of Treatment Delay, Access to Healthcare, and Patient's Financial Capacity on Length of Hospital Stay and In-hospital Mortality.

BACKGROUND: Traumatic brain injury related to road traffic accidents poses a major challenge in resource-poor settings within Guinea. OBJECTIVE: To analyze the impact of treatment delay, access to healthcare, and patient's financial capacity on duration of hospital stay and in-hospital mortality. METHODOLOGY: Data from patients with traumatic brain injury secondary to motor vehicle accident admitted to a reference hospital (public or private) in Guinea during 2009 were analyzed. The association between various factors (treatment delay, access to healthcare, and patient's financial capacity) and prolonged hospital stay (>21 days) and in-hospital mortality were analyzed using two multivariate logistic regression models. RESULTS: The mean (±standard deviation) duration of hospital stay was 8.0 (±8.1) days. The risk of prolonged hospital stay increased by 60% when the time interval between accident and hospital arrival was greater than 12 hours compared with those in whom the time interval was less than 6 hours (adjusted odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.0-2.6, p = 0.03). Compared with patients with low-financial capacity, patients with medium-financial capacity (adjusted OR = 0.6, 95% CI = 0.4-0.8, p = 0.001) and those with high capacity (adjusted OR = 0.6, 95% CI = 0.4-0.9, p = 0.02) were less likely to have a prolonged hospital stay. The risk of in-hospital mortality was 2.6 times higher in patients with time interval between accident and hospital arrival greater than 12 hours compared with those in whom the time interval was less than 6 hours (adjusted OR = 2.6, 95% CI = 1.1-6.2 p = 0.03). In-hospital mortality was not related to patient's financial capacity. CONCLUSION: Prolonged hospital stay and higher in-hospital mortality was associated with longer time interval between accident and hospital arrival. This delay is attributed to inadequate condition of intercity roads and lack of emergency medical services.