Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda.

Infectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings.

Pre-positioned Outbreak Research: The Joint Medical Emerging Diseases Intervention Clinical Capability Experience in Uganda.

The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.

HIV incidence rates and risk factors for urban women in Zambia: preparing for a microbicide clinical trial.

OBJECTIVES: A preparedness study was conducted to evaluate the suitability of sites and populations following the same study procedures intended for a larger scale microbicide efficacy trial. In the process the study evaluated human immunodeficiency virus (HIV) incidence, prevalence, and risk profiles for HIV-acquisition among young women in urban Zambia. METHODS: Women aged 16 to 49 years were screened for participation in the study that involved HIV/sexually transmitted infection testing and the assessment of sexual behavioral characteristics. Two hundred thirty-nine eligible women were enrolled and followed up for 12 months. RESULTS: Baseline HIV prevalence at screening was 38.7% (95% CI: 34.2%-43.3%). The highest age-specific prevalence of HIV was 54.1% (95% CI: 46.3%-61.8%) seen in women aged 26 to 34 years. HIV incidence was 2.6% per 100 woman years. Pregnancy rates were high at 17.4 per 100 woman years (95% CI: 12.2-24.1). CONCLUSION: It was concluded that our general population sample, characterized by high HIV prevalence and ongoing incidence rates despite receiving regular risk reduction counseling and free condoms qualifies for future microbicide studies.A microbicide preparedness study conducted in Lusaka, Zambia found high HIV prevalence and appreciable HIV incidence in a population of women in an urban setting.

Safety and acceptability of cellulose sulfate as a vaginal microbicide in HIV-infected women.

OBJECTIVES: Few studies of topical microbicides have assessed their safety in HIV-infected women. We conducted this study to evaluate the safety and acceptability of 6% cellulose sulfate (CS) gel as a vaginal microbicide in sexually abstinent and active HIV-infected women. METHODS: Fifty-nine HIV-infected women were enrolled in a randomized double-blind placebo-controlled study comparing 6% CS to placebo gel used for 14 days. Sexually abstinent women applied gel once or twice daily and sexually active women used gel once daily. RESULTS: CS gel was safe with no reported severe or life-threatening adverse events (AE). Thirty-nine (66%) of the participants experienced urogenital AE judged as probably or possibly related to gel. The majority (51%) of these participants reported only mild events. Fewer women (62%) who used CS experienced urogenital AE than those assigned to placebo gel (70%) (P = 0.59). Eleven (19%) women experienced intermenstrual bleeding judged to be probably or possibly related to gel use (four in the CS and seven in the placebo gel group). There was no increase in AE by frequency of gel use or sexual activity with the exception of abdominal/pelvic pain which was noted more frequently with twice daily use among sexually abstinent women. Women and men found the gel highly acceptable. CONCLUSIONS: This Phase I study demonstrated that CS vaginal gel was safe, well tolerated and acceptable by HIV-infected women and their male partners. Thus, further development of CS is warranted as a potential method to prevent HIV transmission and acquisition.

Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women.

OBJECTIVES: To establish the highest practical dose and frequency (HPDF) of 0.3% or 1% tenofovir vaginal gel applied once or twice daily by sexually abstinent HIV-uninfected women, and to evaluate the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women. METHODS: Eighty-four women, enrolled in sequential cohorts, used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were carried out during five study visits, with colposcopy at enrollment and on day 14. Samples for pharmacokinetics were collected before and after the initial tenofovir gel use and at day 13. RESULTS: The 1% tenofovir gel used twice daily was as well tolerated as other regimens used by the 48 HIV-negative sexually abstinent women, establishing the HPDF. Although 92% of the women reported at least one adverse event, the majority were mild (87%) and involved the genitourinary tract (70%). One possibly product-related severe adverse event involving lower abdominal cramping was reported by a sexually abstinent woman who used 0.3% gel twice daily. Serum tenofovir levels were low but detectable in 14 of the 25 women. No new HIV RNA resistance mutations were detected after 2 weeks of tenofovir gel in the 24 HIV-infected participants. No significant systemic toxicity was detected. CONCLUSION: A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted.