Association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection With Maternal Mortality and Neonatal Birth Outcomes in Botswana by Human Immunodeficiency Virus Status.

OBJECTIVE: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region. METHODS: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status. RESULTS: Of 20,410 individuals who gave birth, 11,483 (56.3%) were screened for SARS-CoV-2 infection; 4.7% tested positive. People living with HIV were more likely to test positive (144/2,421, 5.9%) than those without HIV (392/9,030, 4.3%) (P=.001). Maternal deaths occurred in 3.7% of those who had a positive SARS-CoV-2 test result compared with 0.1% of those who tested negative (adjusted relative risk [aRR] 31.6, 95% CI 15.4-64.7). Maternal mortality did not differ by HIV status. The offspring of individuals with SARS-CoV-2 infection experienced more overall adverse birth outcomes (34.5% vs 26.6%; aRR 1.2, 95% CI 1.1-1.4), severe adverse birth outcomes (13.6% vs 9.8%; aRR 1.2, 95% CI 1.0-1.5), preterm delivery (21.4% vs 13.4%; aRR 1.4, 95% CI 1.2-1.7), and stillbirth (5.6% vs 2.7%; aRR 1.7 95% CI 1.2-2.5). Neonates exposed to SARS-CoV-2 and HIV infection had the highest prevalence of adverse birth outcomes (43.1% vs 22.6%; aRR 1.7, 95% CI 1.4-2.0). CONCLUSION: Infection with SARS-CoV-2 at the time of delivery was associated with 3.7% maternal mortality and 5.6% stillbirth in Botswana. Most adverse birth outcomes were worse among neonates exposed to both SARS-CoV-2 and HIV infection.

High risk of adverse birth outcomes among adolescents living with HIV in Botswana compared to adult women living with HIV and adolescents without HIV.

BACKGROUND: Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents. METHODS: The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10-19 years of age) and adults (defined as 20-35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes. RESULTS: This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79). CONCLUSIONS: Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.

Pre-Exposure Prophylaxis (PrEP) Initiation and Retention Among Young Kenyan Women.

The DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, Safe) Initiative works to reduce HIV infection among adolescent girls and young women (AGYW) through prevention interventions including Pre-Exposure Prophylaxis (PrEP). Pamoja CBO in Kisumu, Kenya implemented DREAMS. We describe PrEP initiation and persistence in 549 AGYW who started PrEP through Pamoja and factors associated with discontinuation. Median persistence time was 308 days (95% CI 245, 382) with 59% of AGYW discontinuing by the end of the study. The most common reasons for stopping PrEP were lack of perceived risk (27.9%) and relocation (18.7%). In the multivariable model, only age < 18 was associated with stopping PrEP. Younger age was associated with shorter time to discontinuation. Implementing PrEP through DREAMS was successful in supporting initiation of PrEP for AGYW. However, low rates of persistence at 1 year emphasizes the need for strategies to support PrEP persistence if HIV elimination is to be achieved.

Nocardiosis in renal transplant patients.

Renal transplant patients are immunosuppressed and are at increased risk of opportunistic infections, including Nocardia infection. In renal transplant patients, information on the incidence and risk factors associated with nocardiosis is limited. To address the incidence and risk factors associated with nocardiosis in a large renal transplant population, we used the US Renal Data System (USRDS). Sequelae of allograft failure or rejection after infection were also examined. Demographics, clinical risk factors, Nocardia diagnosis, and allograft failure following Nocardia infection were queried in USRDS renal transplant patients using International Classification of Diseases, Ninth Revision (ICD-9) codes in billing claims and Centers for Medicare and Medicaid Services Form 2728. Generalized linear models were used to determine the risk factors associated with nocardiosis, and Cox proportional hazards models were used to examine the association of risk factors with graft failure among patients with Nocardia infection. Of 203,233 renal transplant recipients identified from 2001 to 2011, 657 (0.32%) were diagnosed with Nocardia infection. Pneumonia was the most frequent presentation (15.2%), followed by brain abscess (8.4%). Numerous factors associated with increased Nocardia infection included age >65 years (OR=2.10, 95% CI 1.71 to 2.59), history of transplant failure (OR=1.28, CI 1.02 to 1.60) or history of rejection (OR=4.83, CI 4.08 to 5.72), receipt of a deceased donor transplant (OR=1.23, CI 1.03 to 1.46), and treatment with basiliximab (OR=1.25, CI 1.00 to 1.55), cyclosporine (OR=1.30, CI 1.03 to 1.65), tacrolimus (OR=2.45, CI 2.00 to 3.00), or thymoglobulin (OR=1.89, CI 1.59 to 2.25). In patients with nocardiosis administration of antithymocyte globulin (HR=2.76), chronic obstructive pulmonary disease (HR=2.47), and presentation of Nocardia infection with brain abscess (HR=1.85) were associated with an increased risk of graft failure. This study provides new information to enhance early recognition and targeted treatment of nocardiosis in renal transplant patients.

Facilitators and barriers to HIV pre-exposure prophylaxis (PrEP) uptake through a community-based intervention strategy among adolescent girls and young women in Seme Sub-County, Kisumu, Kenya.

BACKGROUND: While the introduction of HIV Pre-Exposure Prophylaxis (PrEP) as an HIV prevention strategy has allowed women to exercise more control over the reduction of HIV transmission rates, adolescent girls and young women in Sub-Saharan Africa continue to experience higher rates of HIV infections and bear the greatest disease burden. Understanding progress in PrEP uptake among adolescent girls and young women would enhance risk reduction in this vulnerable population. The Determined, Resilient, AIDS-Free, Mentored and Safe women (DREAMS) Initiative plays a key role in this risk reduction strategy. METHODS: We performed a qualitative study to explore facilitators and barriers to PrEP implementation and assess factors effecting initiation and persistence on PrEP among adolescent girls and young women enrolled in the DREAMS Initiative at Pamoja Community Based Organization in Kisumu, Kenya. We conducted key informant interviews (n = 15) with Pamoja Community Based Organization staff, health care providers and community leaders. Additionally, we conducted focus group discussions with young women receiving PrEP and peer mentors (n = 40). We performed a directed content analysis using the Consolidated Framework for Implementation Research to organize the identified facilitators and barriers. RESULTS: We found that the use of the safe space model, decentralization of PrEP support and delivery, peer mentors, effective linkage to local health care facilities, the sensitization of parents and male sexual partners, disclosure of PrEP use by beneficiaries, active stakeholder involvement and community engagement were among some of the facilitators to PrEP uptake. Barriers to PrEP implementation, initiation and persistence included stigma associated with the use of anti-retroviral drugs, drug side effects, frequent relocation of beneficiaries, limited resources for routine screening and medication monitoring, and a limited number of qualified health care workers for PrEP distribution and administration. CONCLUSION: Overall, the community roll-out of PrEP within the DREAMS Initiative was successful due to a number of key facilitating factors, which ultimately led to successful PrEP implementation, increased PrEP initiation and enhanced persistence among adolescent girls and young women. The identified barriers should be addressed so that a larger scale-up of PrEP roll-out is possible in the future.

Design, Synthesis, and Evaluation of (2-(Pyridinyl)methylene)-1-tetralone Chalcones for Anticancer and Antimicrobial Activity.

BACKGROUND: Chalcones, natural products produced by plants as a natural defense mechanisms against various pathogens, are molecules with structures that include two aromatic rings joined by an α, ß unsaturated carbonyl system. Previous research has demonstrated that chalcones exhibit a wide variety of biological activities, including anticancer, antifungal, and antibiotic properties. OBJECTIVE: Our goal is to synthesize novel heterocyclic-containing chalcones and have their biological activities evaluated. Methods Sixteen chalcones were synthesized by the crossed aldol condensation of substituted tetralones with substituted pyridinylaldehydes. The products were purified by recrystallization in MeOH/H2O and characterized by 1H NMR, 13C NMR, and HRMS. Anticancer assays were performed by NCI (National Cancer Institute) against the NCI-60 panel of 60 different human cancer cell lines, including leukemia, non-small-cell lung cancer, colon, central nervous system, melanoma, ovarian, renal, prostate, and breast cancer. Antimicrobial assays were performed by COADD (Community for Open Antimicrobial Drug Discovery) against Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Cryptococcus neoformans var. grubii, and Candida albicans. RESULT: Chalcone 3d had demonstrated growth inhibition greater than 60% against a variety of cancers: leukemia (MOLT-4, SR), non-small cell lung cancer (NCI-H522), colon cancer (HCT- 116), prostate cancer (DU-145), and breast cancer (MCF7, MDA-MB-468) and was also cytotoxic to three different cell lines (CCRF-CEM, RPMI-8226, and KM12). 5c was active against leukemia (CCRF-CEM, RPMI-8226, SR) and breast cancer (MCF7) and 5e was active only against leukemia (RPMI-8226, SR). 5h was partially active and the best compound with growth inhibition of MRSA by 75%. 3b was the best compound against EC, KP, and PA and 3f had the greatest activity against AB. For fungi, 3f and 3e demonstrated the best growth inhibition. CONCLUSION: A small library of heterocyclic-containing chalcones was developed and initial screening demonstrates modest activity against cancers, bacteria, and fungi.