Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Prevalence of Caesarean sections in Enugu, southeast Nigeria: Analysis of data from the Healthy Beginning Initiative.

BACKGROUND: In order to meet the Sustainable Development Goal to decrease maternal mortality, increased access to obstetric interventions such as Caesarean sections (CS) is of critical importance. As a result of women's limited access to routine and emergency obstetric services in Nigeria, the country is a major contributor to the global burden of maternal mortality. In this analysis, we aim to establish rates of CS and determine socioeconomic or medical risk factors associated with having a CS in Enugu, southeast Nigeria. METHODS: Data for this study originated from the Healthy Beginning Initiative study. Participant characteristics were obtained from 2300 women at baseline via a semi-structured questionnaire. Only women between the ages of 17-45 who had singleton deliveries were retained for this analysis. Post-delivery questionnaires were used to ascertain mode-of-delivery. Crude and adjusted logistic regressions with Caesarean as the main outcome are presented. RESULTS: In this sample, 7.22% women had a CS. Compared to women who lived in an urban setting, those who lived in a rural setting had a significant reduction in the odds of having a CS (aOR: 0.58; 0.38-0.89). Significantly higher odds of having a CS were seen among those with high peripheral malaria parasitemia compared to those with low parasitemia (aOR: 1.54; 1.04-2.28). CONCLUSION: This study revealed that contrary to the increasing trend in use of CS in low-income countries, women in this region of Nigeria had limited access to this intervention. Increasing age and socioeconomic proxies for income and access to care (e.g., having a tertiary-level education, full-time employment, and urban residence) were shown to be key determinants of access to CS. Further research is needed to ascertain the obstetric conditions under which women in this region receive CS, and to further elucidate the role of socioeconomic factors in accessing CS.

What do You Need to Get Male Partners of Pregnant Women Tested for HIV in Resource Limited Settings? The Baby Shower Cluster Randomized Trial.

Male partner involvement has the potential to increase uptake of interventions to prevent mother-to-child transmission of HIV (PMTCT). Finding cultural appropriate strategies to promote male partner involvement in PMTCT programs remains an abiding public health challenge. We assessed whether a congregation-based intervention, the Healthy Beginning Initiative (HBI), would lead to increased uptake of HIV testing among male partners of pregnant women during pregnancy. A cluster-randomized controlled trial of forty churches in Southeastern Nigeria randomly assigned to either the HBI (intervention group; IG) or standard of care referral to a health facility (control group; CG) was conducted. Participants in the IG received education and were offered onsite HIV testing. Overall, 2498 male partners enrolled and participated, a participation rate of 88.9%. Results showed that male partners in the IG were 12 times more likely to have had an HIV test compared to male partners of pregnant women in the CG (CG = 37.71% vs. IG = 84.00%; adjusted odds ratio = 11.9; p < .01). Culturally appropriate and community-based interventions can be effective in increasing HIV testing and counseling among male partners of pregnant women.

Prevalence of Sickle Cell Trait and Reliability of Self-Reported Status among Expectant Parents in Nigeria: Implications for Targeted Newborn Screening.

BACKGROUND/AIMS: Sickle cell disease (SCD) is a life-threatening, autosomal recessive blood disorder prevalent in sub-Saharan Africa. We identified the prevalence of sickle cell trait (SCT) among pregnant women and their male partners in Enugu State, Nigeria, and determined the accuracy of self-reported sickle cell status and its reliability for identifying high-risk newborns for targeted screening. METHODS: We conducted a nested cohort study of expectant parents enrolled in the Healthy Beginning Initiative (HBI). The HBI is a cluster-randomized trial of a congregation-based approach designed to increase HIV testing. Participants completed a survey regarding self-awareness of their sickle cell genotype and consented to genotype screening by cellulose acetate electrophoresis. RESULTS: SCT prevalence (HbAS) was 22% (746/3,371). Only 50% of participants provided an accurate self-report. Self-report accuracy was significantly different (p < 0.0001) between individuals who reported having SCT or SCD (61% accuracy) versus those who reported not having SCT or SCD (86% accuracy). Demographic variables including gender, age, household size, employment, education, and home location were significantly associated with providing an accurate self-report. CONCLUSIONS: Low numbers of accurate parental self-reports, coupled with a high SCT prevalence in Nigeria, could limit the efficacy of targeted newborn screening. However, our data indicate that it is feasible to integrate sickle cell screening for pregnant women with existing, community-based health care programs developed by the President's Emergency Plan for AIDS Relief (PEPFAR), such as the HBI. Expanding screening programs could enable the development of targeted newborn screening based on maternal genotype that could identify all newborns with SCD in resource-limited settings.

Linkage to Care, Early Infant Diagnosis, and Perinatal Transmission Among Infants Born to HIV-Infected Nigerian Mothers: Evidence From the Healthy Beginning Initiative.

BACKGROUND: In 2014, Nigeria accounted for 33% of all new childhood HIV infections that occurred among the 22 Global Plan priority countries where 80% of HIV-infected women reside. Even with a vertical HIV transmission rate of 27%, only 6% of infants born to HIV-infected women in Nigeria receive early infant diagnosis (EID). This article reports rates of antiretroviral prophylaxis, EID, and mother-to-child transmission in a congregation-based Healthy Beginning Initiative (HBI) designed to increase HIV testing among pregnant women in southeast Nigeria. METHODS: This is a nested cohort study of HIV-exposed infants (HEI) within the HBI trial originally designed as a 2-arm cluster randomized trial. HIV-infected mothers and infants were followed between January 2013 and August 2014. RESULTS: Across both arms of the study, 72 HIV-infected women delivered 69 live infants (1 set of twins) and 4 had miscarriages. Of the 69 live-born HEI, HIV status was known for 71% (49/69), 16% (11/69) died before sample collection, and 13% (9/69) were lost to follow-up. Complete information was available for 84% of HEI (58/69), of which 64% (37/58) received antiretroviral prophylaxis. Among the 49 infants tested for HIV, 88% (43/49) received EID within 2 months and 12% (6/49) received antibody testing after 18 months. The mother-to-child transmission rate was 8.2% (4/49). CONCLUSIONS: EID was higher and HIV transmission rate was lower among the HBI participants compared to reported rates in 2014. However, further progress is needed to achieve goals of elimination of infant HIV infection.

Attitudes and beliefs about mental illness among church-based lay health workers: experience from a prevention of mother-to-child HIV transmission trial in Nigeria.

Common mental disorders are prevalent in Nigeria. Due to stigma and a limited number of trained specialists, only 10% of adults with mental illness in Nigeria receive any care. The Healthy Beginning Initiative is a community-based maternal/child health program that includes screening for perinatal depression and was implemented by lay, volunteer, church-based health advisors (CHAs). The aim of the study was to assess the beliefs and attitudes about mental illness among the CHAs. The study used a cross-sectional survey of 57 CHAs, who completed a 43-item, self-administered questionnaire that assessed their beliefs and attitudes about mental illness. The response rate was 71%. Respondents were mostly female (79%), married (83%) and aged 40-49 years (M = 41.16 SD = 10.48). Most endorsed possession by evil spirits (84%), traumatic events (81%) and witchcraft (60%) as causes of mental illness. A majority (69%) believed that people with mental illness were a nuisance, and less than half (46%) believed that mental disorders were illnesses like any other illness. It is concluded that stigmatizing attitudes and beliefs about mental illness are common among the CHAs. Training for lay health workers in Nigeria should include education on the known bio-psycho-social basis of mental disorders and the role of social inclusion in recovery.

Effect of a congregation-based intervention on uptake of HIV testing and linkage to care in pregnant women in Nigeria (Baby Shower): a cluster randomised trial.

BACKGROUND: Few effective community-based interventions exist to increase HIV testing and uptake of antiretroviral therapy (ART) in pregnant women in hard-to-reach resource-limited settings. We assessed whether delivery of an intervention through churches, the Healthy Beginning Initiative, would increase uptake of HIV testing in pregnant women compared with standard health facility referral. METHODS: In this cluster randomised trial, we enrolled self-identified pregnant women aged 18 years and older who attended churches in southeast Nigeria. We randomised churches (clusters) to intervention or control groups, stratified by mean annual number of infant baptisms (<80 vs ≥80). The Healthy Beginning Initiative intervention included health education and on-site laboratory testing implemented during baby showers in intervention group churches, whereas participants in control group churches were referred to health facilities as standard. Participants and investigators were aware of church allocation. The primary outcome was confirmed HIV testing. This trial is registered with ClinicalTrials.gov, identifier number NCT 01795261. FINDINGS: Between Jan 20, 2013, and Aug 31, 2014, we enrolled 3002 participants at 40 churches (20 per group). 1309 (79%) of 1647 women attended antenatal care in the intervention group compared with 1080 (80%) of 1355 in the control group. 1514 women (92%) in the intervention group had an HIV test compared with 740 (55%) controls (adjusted odds ratio 11·2, 95% CI 8·77-14·25; p<0·0001). INTERPRETATION: Culturally adapted, community-based programmes such as the Healthy Beginning Initiative can be effective in increasing HIV screening in pregnant women in resource-limited settings. FUNDING: US National Institutes of Health and US President's Emergency Plan for AIDS Relief.

Impact of male partner's awareness and support for contraceptives on female intent to use contraceptives in southeast Nigeria.

BACKGROUND: Despite the growing body of evidence on use of modern contraceptives among women in sub-Saharan African countries, little is known about the broader context in which female decision-making concerning contraceptive use occurs, particularly the role of their male partners' awareness and support of modern contraceptives. METHODS: We conducted a cross-sectional survey of 2468 pregnant women and their male partners enrolled in the Healthy Beginning Initiative (HBI), an intervention to increase HIV testing among pregnant women in Enugu, southeast Nigeria. The aims of this study were to determine: 1) male partners' awareness of, and support for, female contraceptive methods, and 2) influence of male partners' contraceptive awareness and support on pregnant women's expressed desire to use contraception. We used logistic regression models to examine the association between male partners' awareness and support of modern contraceptives on their spouses' desire to use contraceptives. RESULTS: Men's awareness of, and support for, use of modern contraceptives were significantly associated with their female partners' desire to use contraception. A majority of the men who were aware of modern contraceptives (66.5 %) and those who supported their spouses' use of contraception (72.5 %) had partners who expressed a desire to use contraception. Men who were aware of female contraception were 3 times more likely to have spouses who desired to use contraception (AOR = 3.17, 95 % C.I: 2.70-3.75). In addition, men who showed support for their spouses' use of contraception were over 5 times more likely to have spouses who indicated a desire to use contraception (AOR = 5.76, 95 % C.I: 4.82-6.88). Living in a household of 5 or more people (AOR = 1.45, 95 % C.I: 1.23-1.72) and residing in an urban area (AOR = 0.81, 95 % C.I: 0.67-0.97) were also significantly associated with women's expressed desire to use modern contraception. CONCLUSION: Men's awareness of, and support for, use of modern contraceptives were markedly associated with their spouses' desire to use contraception. This underscores the need for men's involvement in programs that seek to address women's uptake of contraception in low and middle income countries.

Impact of HIV testing and counseling (HTC) knowledge on HIV prevention practices among traditional birth attendants in Nigeria.

Nigeria is second in the world for the number of people with HIV and has a high rate of mother-to-child transmission (MTCT). Over 60% of births in Nigeria occur outside of health care facilities, and because of this, Traditional Birth Attendants (TBAs) play a significant role in maternal and child health. It is important that TBAs be knowledgeable about HIV prevention. The purpose of this study was to determine the impact of HIV testing and counseling (HTC) knowledge on the HIV prevention practices among TBAs in Nigeria. Five hundred TBAs were surveyed. Chi-square and logistic regression were used to assess differences in HIV prevention practices between TBAs with and without HTC knowledge. TBAs with HTC knowledge are significantly more likely to engage in HIV prevention practices than TBAs without HTC. Prevention practices included: wearing gloves during delivery (p < 0.01), sterilization of delivery equipment (p < 0.01), participation in blood safety training (p < 0.01), and disposal of sharps (p < 0.01). As long as a high percent of births occur outside health care facilities in Nigeria, there will be a need for TBAs. Providing TBAs with HTC training increases HIV prevention practices and can be a key to improve maternal and child health.