Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

Pregnancy and breastfeeding in the context of Ebola: a systematic review.

The outbreaks of Ebola virus between 2014 and 2020 have drawn attention to knowledge gaps related to Ebola virus disease in pregnant women. The aim of this study was to systematically evaluate available data on pregnant and lactating women with acute Ebola virus disease or following recovery. We searched MEDLINE, Embase, Cochrane Library (CENTRAL), Web of Science Core Collection, CINAHL, POPLINE, Global Health, and WHO Global Index Medicus, in addition to grey literature, for relevant articles. Studies of all types and published between database inception and Aug 19, 2019, were eligible (PROSPERO 129335). We identified 1060 records, of which 52 studies met our inclusion criteria. Overall, mortality in 274 pregnant women with Ebola virus disease was 72% (197 women died); mortality for pregnant women with Ebola virus disease were not higher than those in the general population of patients with Ebola virus disease. Nearly all women with Ebola virus disease had adverse pregnancy outcomes. Among survivors, Ebola virus RNA was detected by RT-PCR in amniotic fluid up to 32 days after maternal clearance of Ebola virus from the blood and in breastmilk 26 days after symptom onset. A risk of transmission of Ebola virus from pregnancy-related fluids and breastmilk probably exists, and precautions should be taken.

Clustering of chronic hepatitis B screening intentions in social networks of Moroccan immigrants in the Netherlands.

BACKGROUND: Early detection, identification, and treatment of chronic hepatitis B through screening is vital for those at increased risk, e.g. born in hepatitis B endemic countries. In the Netherlands, Moroccan immigrants show low participation rates in health-related screening programmes. Since social networks influence health behaviour, we investigated whether similar screening intentions for chronic hepatitis B cluster within social networks of Moroccan immigrants. METHODS: We used respondent-driven sampling (RDS) where each participant ("recruiter") was asked to complete a questionnaire and to recruit three Moroccans ("recruitees") from their social network. Logistic regression analyses were used to analyse whether the recruiters' intention to request a screening test was similar to the intention of their recruitees. RESULTS: We sampled 354 recruiter-recruitee pairs: for 154 pairs both participants had a positive screening intention, for 68 pairs both had a negative screening intention, and the remaining 132 pairs had a discordant intention to request a screening test. A tie between a recruiter and recruitee was associated with having the same screening intention, after correction for sociodemographic variables (OR 1.70 [1.15-2.51]). CONCLUSIONS: The findings of our pilot study show clustering of screening intention among individuals in the same network. This provides opportunities for social network interventions to encourage participation in hepatitis B screening initiatives.

Implementation of a study to examine the persistence of Ebola virus in the body fluids of Ebola virus disease survivors in Sierra Leone: Methodology and lessons learned.

BACKGROUND: The 2013-2016 West African Ebola virus disease epidemic was unprecedented in terms of the number of cases and survivors. Prior to this epidemic there was limited data available on the persistence of Ebola virus in survivors' body fluids and the potential risk of transmission, including sexual transmission. METHODOLOGY/PRINCIPAL FINDINGS: Given the urgent need to determine the persistence of Ebola virus in survivors' body fluids, an observational cohort study was designed and implemented during the epidemic response operation in Sierra Leone. This publication describes study implementation methodology and the key lessons learned. Challenges encountered during implementation included unforeseen duration of follow-up, complexity of interpreting and communicating laboratory results to survivors, and the urgency of translating research findings into public health practice. Strong community engagement helped rapidly implement the study during the epidemic. The study was conducted in two phases. The first phase was initiated within five months of initial protocol discussions and assessed persistence of Ebola virus in semen of 100 adult men. The second phase assessed the persistence of virus in multiple body fluids (semen or vaginal fluid, menstrual blood, breast milk, and urine, rectal fluid, sweat, saliva, tears), of 120 men and 120 women. CONCLUSION/SIGNIFICANCE: Data from this study informed national and global guidelines in real time and demonstrated the need to implement semen testing programs among Ebola virus disease survivors. The lessons learned and study tools developed accelerated the implementation of such programs in Ebola virus disease affected countries, and also informed studies examining persistence of Zika virus. Research is a vital component of the public health response to an epidemic of a poorly characterized disease. Adequate resources should be rapidly made available to answer critical research questions, in order to better inform response efforts.

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Final Report.

BACKGROUND: Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS: We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS: Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS: These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).

The Non-linear Health Consequences of Living in Larger Cities.

Urbanization promotes economy, mobility, access, and availability of resources, but on the other hand, generates higher levels of pollution, violence, crime, and mental distress. The health consequences of the agglomeration of people living close together are not fully understood. Particularly, it remains unclear how variations in the population size across cities impact the health of the population. We analyze the deviations from linearity of the scaling of several health-related quantities, such as the incidence and mortality of diseases, external causes of death, wellbeing, and health care availability, in respect to the population size of cities in Brazil, Sweden, and the USA. We find that deaths by non-communicable diseases tend to be relatively less common in larger cities, whereas the per capita incidence of infectious diseases is relatively larger for increasing population size. Healthier lifestyle and availability of medical support are disproportionally higher in larger cities. The results are connected with the optimization of human and physical resources and with the non-linear effects of social networks in larger populations. An urban advantage in terms of health is not evident, and using rates as indicators to compare cities with different population sizes may be insufficient.

Comparison of contact patterns relevant for transmission of respiratory pathogens in Thailand and The Netherlands using respondent-driven sampling.

Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in The Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in The Netherlands and Thailand.

Online respondent-driven sampling for studying contact patterns relevant for the spread of close-contact pathogens: a pilot study in Thailand.

BACKGROUND: Information on social interactions is needed to understand the spread of airborne infections through a population. Previous studies mostly collected egocentric information of independent respondents with self-reported information about contacts. Respondent-driven sampling (RDS) is a sampling technique allowing respondents to recruit contacts from their social network. We explored the feasibility of webRDS for studying contact patterns relevant for the spread of respiratory pathogens. MATERIALS AND METHODS: We developed a webRDS system for facilitating and tracking recruitment by Facebook and email. One-day diary surveys were conducted by applying webRDS among a convenience sample of Thai students. Students were asked to record numbers of contacts at different settings and self-reported influenza-like-illness symptoms, and to recruit four contacts whom they had met in the previous week. Contacts were asked to do the same to create a network tree of socially connected individuals. Correlations between linked individuals were analysed to investigate assortativity within networks. RESULTS: We reached up to 6 waves of contacts of initial respondents, using only non-material incentives. Forty-four (23.0%) of the initially approached students recruited one or more contacts. In total 257 persons participated, of which 168 (65.4%) were recruited by others. Facebook was the most popular recruitment option (45.1%). Strong assortative mixing was seen by age, gender and education, indicating a tendency of respondents to connect to contacts with similar characteristics. Random mixing was seen by reported number of daily contacts. CONCLUSIONS: Despite methodological challenges (e.g. clustering among respondents and their contacts), applying RDS provides new insights in mixing patterns relevant for close-contact infections in real-world networks. Such information increases our knowledge of the transmission of respiratory infections within populations and can be used to improve existing modelling approaches. It is worthwhile to further develop and explore webRDS for the detection of clusters of respiratory symptoms in social networks.

Knowledge of tuberculosis and associated health-seeking behaviour among rural Vietnamese adults with a cough for at least three weeks.

AIMS: Good general lay knowledge of tuberculosis (TB), its cause and treatment is considered important for both prompt healthcare seeking and adherence to treatment. The main aim of this study was to describe the knowledge of TB among med and women with a cough for more than three weeks and to see how their health seeking related to TB knowledge. METHODS: A population-based survey was carried out within a demographic surveillance site in Vietnam. The study population included 35,832 adults aged 15 years or over. Cough cases were identified at household level and structures interviews were carried out with all cases of cough in person. RESULTS: A total of 559 people (1.6%) reported coughing with a duration of three weeks or longer (259 men and 300 women). A large proportion of individuals with a cough for more than three weeks had limited knowledge of the causes, transmission modes, symptoms, and curability of TB. Men had a significantly higher knowledge score than women (3.04 vs 2.55). Better knowledge was significantly related to seeking healthcare and seeking hospital care. More men than women did not take any health care action at all. DISCUSSION: Health education for TB thus seems to be useful, but efforts must be made to ensure that both men and women in different socioeconomic contexts can access the information.