Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study.

BACKGROUND: Minimal data exist on pregnancy following recovery from Ebola in people of child-bearing potential (females aged roughly 18-45 years). The aim of this study was to assess viral persistence or reactivation in pregnancy, the frequency of placental transfer of anti-Ebola IgG antibodies, and pregnancy outcomes in this population. METHODS: In this observational cohort study, we studied self-reported pregnancies in two groups: seropositive people who had recovered from Ebola virus disease (seropositive group) and seronegative people who had close contact with people with Ebola (seronegative group). Participants had enrolled in the PREVAIL III longitudinal study and were exposed during the 2014-2016 Liberian Ebola outbreak. The primary outcome was pregnancy result. We assessed rates of livebirths and other pregnancy results in both study groups, and presence of Ebola RNA by PCR in samples of placenta, maternal and cord blood, breastmilk, and vaginal secretions from people who had recovered from Ebola who conceived a median of 14 months after acute Ebola virus disease. Mixed-model logistic regression evaluated associations between first-reported pregnancy outcome, age, and study group. Growth and neurodevelopment in the infants born to people in the seropositive group were assessed at 6-month intervals for 2 years. Data were accrued by PREVAIL III study staff. FINDINGS: 1566 participants were enrolled between June 17, 2015, and Dec 14, 2017, of whom 639 became pregnant (215 seropositive, 424 seronegative) and 589 reported pregnancy outcomes (206 seropositive, 383 seronegative). 105 infants born to 98 mothers in the seropositive group were enrolled in the birth cohort. Ebola RNA was not detected in 205 samples of placenta, cord blood, or maternal blood taken at birth from 54 mothers in the seropositive group, nor in 367 vaginal swabs. Viral RNA was found in two of 354 longitudinal breastmilk samples. All but one of 57 infants born during these 54 births were seropositive for anti-Ebola antibodies. Neonates showed high concentrations of anti-Ebola IgG, which declined after 6 months. Odds of adverse pregnancy outcome among the two groups were indistinguishable (OR 1·13, 95% CI 0·71-1·79). Compared with WHO standards, infants born to those in the seropositive group had lower median weight and length, and larger median head circumference over 2 years. Compared with a cohort from the USA accrual of gross motor developmental milestones was similar, whereas attainment of pincer grasp and early vocalisation were mildly delayed. INTERPRETATION: The risks of Ebola virus reactivation in the peripartum and postpartum period and of adverse birth outcomes are low in those who have recovered from Ebola virus disease and become pregnant approximately 1 year after acute Ebola virus disease. The implication for clinical practice is that care of people who are pregnant and who have recovered from Ebola can be offered without risks to health-care providers or stigmatisation of the mothers and their offspring. The implication for prospective mothers is that safe pregnancies are entirely possible after recovery from Ebola. FUNDING: National Institute of Allergy and Infectious Diseases and Liberia Ministry of Health.

Feasibility of digital contact tracing in low-income settings - pilot trial for a location-based DCT app.

BACKGROUND: Data about the effectiveness of digital contact tracing are based on studies conducted in countries with predominantly high- or middle-income settings. Up to now, little research is done to identify specific problems for the implementation of such technique in low-income countries. METHODS: A Bluetooth-assisted GPS location-based digital contact tracing (DCT) app was tested by 141 participants during 14 days in a hospital in Monrovia, Liberia in February 2020. The DCT app was compared to a paper-based reference system. Hits between participants and 10 designated infected participants were recorded simultaneously by both methods. Additional data about GPS and Bluetooth adherence were gathered and surveys to estimate battery consumption and app adherence were conducted. DCT apps accuracy was evaluated in different settings. RESULTS: GPS coordinates from 101/141 (71.6%) participants were received. The number of hours recorded by the participants during the study period, true Hours Recorded (tHR), was 496.3 h (1.1% of maximum Hours recordable) during the study period. With the paper-based method 1075 hits and with the DCT app five hits of designated infected participants with other participants have been listed. Differences between true and maximum recording times were due to failed permission settings (45%), data transmission issues (11.3%), of the participants 10.1% switched off GPS and 32.5% experienced other technical or compliance problems. In buildings, use of Bluetooth increased the accuracy of the DCT app (GPS + BT 22.9 m ± 21.6 SD vs. GPS 60.9 m ± 34.7 SD; p = 0.004). GPS accuracy in public transportation was 10.3 m ± 10.05 SD with a significant (p = 0.007) correlation between precision and phone brand. GPS resolution outdoors was 10.4 m ± 4.2 SD. CONCLUSION: In our study several limitations of the DCT together with the impairment of GPS accuracy in urban settings impede the solely use of a DCT app. It could be feasible as a supplement to traditional manual contact tracing. DKRS, DRKS00029327 . Registered 20 June 2020 - Retrospectively registered.

Long-Term Decrease in Intraocular Pressure in Survivors of Ebola Virus Disease in the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Study.

Objective: Survivors of Ebola virus disease (EVD) experience decreased intraocular pressure (IOP) relative to unaffected close contacts during the first year of convalescence. Whether this effect persists over time and its relationship to intraocular pathology are unclear. We sought to determine whether IOP remained lower in survivors of EVD over 4 years of follow-up and to identify associated risk factors. Design: Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III is a 5-year, longitudinal cohort study of survivors of EVD and their close contacts and is a collaboration between the Liberian Ministry of Health and the United States National Institutes of Health. Participants: Participants who enrolled in PREVAIL III at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 who underwent comprehensive ophthalmic evaluation annually for 5 consecutive visits. Methods: Intraocular pressure was measured at each visit by a handheld rebound tonometer using sterile tips. Comparisons are made between antibody-positive survivors and antibody-negative close contacts. Main Outcome Measures: Intraocular pressure, measured in mmHg, at each study visit. Results: Of 565 antibody-positive survivors and 644 antibody-negative close contacts enrolled in the study at baseline, the majority of participants returned annually, with 383 (67.8%) and 407 (63.2%) participants, respectively, presenting for the final study visit at a median of 60 months after symptom onset. A sustained, relative decrease in IOP was observed in survivors relative to close contacts, with mean difference of -0.72 mmHg (95% confidence interval [CI] -1.18 to -0.27) at the final study visit. This difference remained constant throughout the study period (P = 0.4 for interaction over time). Among survivors, physical examination findings of vitreous cell and OCT findings of vitreous opacities both demonstrated a significant association with decreased IOP at baseline (P < 0.05 for both). After adjusting for such factors, the difference throughout the follow-up (-0.93 mmHg, 95% CI, -1.23 to -0.63) remained significant. Conclusions: Survivors of EVD experienced a sustained decrease in IOP relative to close contacts over a 5-year period after EVD. The results highlight the importance of considering long-term sequelae of emerging infectious diseases within a population. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Identifying Paucisymptomatic or Asymptomatic and Unrecognized Ebola Virus Disease Among Close Contacts Based on Exposure Risk Assessments and Screening Algorithms.

BACKGROUND: There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). METHODS: We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. RESULTS: This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4-4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%-99%), 87% with high-risk exposure (82%-92%), and 97% with intermediate- to high-risk exposures (93%-99%). The proportion of false-positives was 2% with RDT and 53%-93% with intermediate- and/or high-risk exposures. CONCLUSION: We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD.

Clinical sequelae among individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease in Liberia: a longitudinal cohort study.

BACKGROUND: Whether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts. METHODS: Between June 17, 2015, and June 30, 2017, we studied a cohort of Ebola virus disease survivors and their contacts in Liberia. Surveys, current symptoms and physical examination findings, and serology were used to characterise disease status of reported Ebola virus disease, unrecognised Ebola virus disease, pauci-symptomatic or asymptomatic Ebola virus infection, or no infection. We pre-specified findings known to be differentially prevalent among Ebola virus disease survivors versus their contacts (urinary frequency, headache, fatigue, muscle pain, memory loss, joint pain, neurological findings, chest findings, muscle findings, joint findings, abdominal findings, and uveitis). We estimated the prevalence and incidence of selected clinical findings by disease status. FINDINGS: Our analytical cohort included 991 reported Ebola virus disease survivors and 2688 close contacts. The median time from acute Ebola virus disease onset to baseline was 317 days (IQR 271-366). Of 222 seropositive contacts, 115 had pauci-symptomatic or asymptomatic Ebola virus infection and 107 had unrecognised Ebola virus disease. At baseline, prevalent findings of joint pain, memory loss, muscle pain, and fatigue were lowest among those with pauci-symptomatic or asymptomatic infection or no infection, higher among contacts with unrecognised Ebola virus disease, and highest in reported survivors of Ebola virus disease. Joint pain was the most prevalent finding, and was reported in 434 (18%) of 2466 individuals with no infection, 14 (12%) of 115 with pauci-symptomatic or asymptomatic infection, 31 (29%) of 107 with unrecognised Ebola virus disease, and 476 (48%) of 991 with reported Ebola virus disease. In adjusted analyses, this pattern remained for joint pain and memory loss. Survivors had an increased odds of joint pain compared with unrecognised Ebola virus disease contacts (adjusted odds ratio [OR] 2·13, 95% CI 1·34-3·39); unrecognised Ebola virus disease contacts had an increased odds of joint pain compared with those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 1·89, 95% CI 1·21-2·97). The adjusted odds of memory loss was more than four-times higher among survivors than among unrecognised Ebola virus disease contacts (adjusted OR 4·47, 95% CI 2·41-8·30) and two-times higher among unrecognised Ebola virus disease contacts than in those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 2·05, 95% CI 1·10-3·84). By 12 months, prevalent findings had decreased in the three infected groups. INTERPRETATION: Our findings provide evidence of post-Ebola virus disease clinical sequelae among contacts with unrecognised Ebola virus disease but not in people with pauci-symptomatic or asymptomatic Ebola virus infection. FUNDING: National Cancer Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Coordinated support for local action: Modeling strategies to facilitate behavior adoption in urban-poor communities of Liberia for sustained COVID-19 suppression.

BACKGROUND: Long-term suppression of SARS-CoV-2 transmission will involve strategies that recognize the heterogeneous capacity of communities to undertake public health recommendations. We highlight the epidemiological impact of barriers to adoption and the potential role of community-led coordination of support for cases and high-risk contacts in urban slums. METHODS: A compartmental model representing transmission of SARS-CoV-2 in urban poor versus less socioeconomically vulnerable subpopulations was developed for Montserrado County, Liberia. Adoption of home-isolation behavior was assumed to be related to the proportion of each subpopulation residing in housing units with multiple rooms and with access to sanitation, water, and food. We evaluated the potential impact of increasing the maximum attainable proportion of adoption among urban poor following the scheduled lifting of the state of emergency. RESULTS: Without intervention, the model estimated higher overall infection burden but fewer severe cases among urban poor versus the less socioeconomically vulnerable population. With self-isolation by mildly symptomatic individuals, median reductions in cumulative infections, severe cases, and maximum daily incidence were 7.6% (IQR: 2.2%-20.9%), 7.0% (2.0%-18.5%), and 9.9% (2.5%-31.4%), respectively, in the urban poor subpopulation and 16.8% (5.5%-29.3%), 15.0% (5.0%-26.4%), and 28.1% (9.3%-47.8%) in the less socioeconomically vulnerable population. An increase in the maximum attainable percentage of behavior adoption by the urban slum subpopulation was associated with median reductions of 19.2% (10.1%-34.0%), 21.1% (13.3%-34.2%), and 26.0% (11.5%-48.9%) relative to the status quo scenario. CONCLUSIONS: Post-lockdown recommendations that prioritize home-isolation by confirmed cases are limited by resource constraints. Investing in community-based initiatives that coordinate support for self-identified cases and their contacts could more effectively suppress COVID-19 in settings with socioeconomic vulnerabilities.

Triangulating Evidence to Infer Pathways that Influence Ebola Virus Disease-Related Stigma and Clinical Findings among Survivors: An Observational Cohort Study.

Visible signs of disease can evoke stigma while stigma contributes to depression and mental illness, sometimes manifesting as somatic symptoms. We assessed these hypotheses among Ebola virus disease (EVD) survivors, some of whom experienced clinical sequelae. Ebola virus disease survivors in Liberia were enrolled in an observational cohort study starting in June 2015 with visits every 6 months. At baseline and 18 months later, a seven-item index of EVD-related stigma was administered. Clinical findings (self-reported symptoms and abnormal findings) were obtained at each visit. We applied the generalized estimating equation method to assess the bidirectional concurrent and lagged associations between clinical findings and stigma, adjusting for age, gender, educational level, referral to medical care, and HIV serostatus as confounders. When assessing the contribution of stigma to later clinical findings, we restricted clinical findings to five that were also considered somatic symptoms. Data were obtained from 859 EVD survivors. In concurrent longitudinal analyses, each additional clinical finding increased the adjusted odds of stigma by 18% (95% CI: 1.11, 1.25), particularly palpitations, muscle pain, joint pain, urinary frequency, and memory loss. In lagged associations, memory loss (adjusted odds ratio [AOR]: 4.6; 95% CI: 1.73, 12.36) and anorexia (AOR: 4.17; 95% CI: 1.82, 9.53) were associated with later stigma, but stigma was not significantly associated with later clinical findings. Stigma was associated with select symptoms, not abnormal objective findings. Lagged associations between symptoms and later stigma substantiate the possibility of a pathway related to visible symptoms identified by community members and leading to fear of contagion.

Equitable and Feasible Distribution of SARS-CoV-2 Vaccines for All in Africa.

As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative's campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization's Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations' populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

Characterization of Ebola Virus-Associated Eye Disease.

Importance: Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease. Objective: To assess features of ophthalmic disease specific to EVD. Design, Setting, and Participants: This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020. Exposures: All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein. Main Outcomes and Measures: Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts. Results: A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 µm; mean difference, 14.4 µm; 95% CI, 1.9-26.9 µm). Conclusions and Relevance: In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.

Towards a better understanding of attitudes and beliefs held by traditional healers and recipients of traditional medicine concerning mental health conditions in post-conflict Liberia: a qualitative investigation.

BACKGROUND: A better understanding of attitudes and beliefs held by traditional healers and utilizers of traditional medicine concerning mental health conditions in Liberia is important as Liberia seeks to improve its delivery of mental healthcare in the context of scarce resources and recovery from civil war. METHODS: A qualitative research design was used to collect data from 24 Liberian traditional healers, and 11 utilizers of Liberian traditional medicine. Participants were queried about mental health problems in Liberia, treatments, and attitudes towards modern healthcare. Qualitative data were probed and aggregated using content analysis. RESULTS: Mental health problems described by study participants included: Open Mole, African Science, Epilepsy, Depression and Mental Illness (trauma/substance use). Mental health problems were often associated with socioeconomic distress, and participants described their attitudes and beliefs concerning mental healthcare, traditional medicine, and modern healthcare. CONCLUSION: Traditional medicine is an important part of mental healthcare in Africa. Mental illness, social factors, and healthcare access were important problems in Liberia. Mental health problems blended local cultural beliefs with Westernized nosology and social factors. Traditional healer's attitudes towards Western medicine reflected ambivalence. There is a desire for collaboration with 'modern' health care providers, but this will require reciprocal trust-building.

Literacy is power: structural drivers of child malnutrition in rural Liberia.

BACKGROUND: In Liberia, an estimated 32% of children under 5 are stunted. Malnutrition and hunger worsened during the country's civil war and were further exacerbated by the 2014-2016 outbreak of Ebola virus disease. Studies examining adherence to recommended infant and young child feeding practices frequently do so with an emphasis on the knowledge, attitudes and beliefs of mothers and caregivers. Often overlooked are the structural factors that enable or constrain their agency to practise evidence-based recommendations. METHODS: Between July and December 2017, we surveyed 100 Liberian mothers to assess the sociodemographic factors associated with the risk of severe acute malnutrition in children in Maryland County, Liberia. We also conducted 50 in-depth interviews at two government health facilities to qualitatively explore mothers' experiences, as well as health workers' understandings of the determinants of malnutrition in the region. We applied logistic regression to analyse quantitative data and inductive content analysis to thematically interpret qualitative data. RESULTS: Mothers were less likely to have a child with severe acute malnutrition if they had an income greater than US$50 per month (adjusted OR (aOR)=0.14, p<0.001), were literate (aOR=0.21, p=0.009) or exclusively breast fed during the first 6 months of life (aOR=0.18, p=0.049); they were more likely to have a child with severe acute malnutrition if they were married or in domestic partnerships (aOR=8.41, p<0.001). In-depth interviews elucidated several social, economic and programmatic factors that shaped suboptimal feeding practices, as well as decisions for and against seeking formal care for malnutrition. DISCUSSION: The lived experiences of Liberian mothers and health workers illustrate that child malnutrition is a direct consequence of abject poverty, food insecurity, illiteracy, the precarious nature of formal and informal work, and the lack of robust social protection. Behaviour change and health education interventions that do not seek to alleviate structural barriers to compliance are unlikely to be effective.