Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Seroprevalence and burden of hepatitis E viral infection among pregnant women in central Nigeria attending antenatal clinic at a Federal Medical Centre in Central Nigeria.

Introduction: HEV infection may be life threatening in pregnant women and has been linked with 20-30% mortality, especially in the third trimester of pregnancy. HEV infection leads to elevated levels of preterm labour and other immunological parameters. It is vertically transmitted and could lead to poor feto-maternal outcomes. especially in fulminating viral hepatitis where both the mother and foetus could be lost. There is currently no known treatment or vaccine for HEV. There is therefore a need to study HEV seroprevalence and burden among vulnerable groups, such as pregnant women and their newborns in Nigeria, where maternal mortality is highly significant. Methods: A total of 200 samples were collected from pregnant women attending antenatal clinic at Federal Medical Centre (FMC) Keffi, in central Nigeria, of which (156/200) samples were from HIV-negative pregnant women and (44/200) were from HIV-positive pregnant women, using a simple random sampling method. Results: In total, 200 pregnant women [78.0% (156/200) HIV-negative pregnant women and 22.0% (44/200) HIV-positive pregnant women] were recruited for this study. The ages of the pregnant women ranged from 15-49 years, with a mean age of 26.4 years (± 6.23). The overall HEV IgG seropositivity in the study population was 31.5% (63/200); 95% CI (30-33). Conclusion: This study highlighted an unexpectedly high seroprevalence of HEV and poor feto-maternal outcomes in pregnant women residing in a rural and urban setting of central Nigeria. The study showed that the inherently high HEV seropositivity and poor feto-maternal outcomes may not be attributed to HEV viral hepatitis only but may be a combination of extrinsic and intrinsic factors.

Live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: randomized controlled phase I trial in the Philippines.

A recombinant live attenuated tetravalent dengue vaccine (TDV) is safe and immunogenic in adults and children in dengue-naïve populations. Data are needed in dengue endemic populations. In a phase I, randomized, controlled, blind-observer study in the Philippines, groups of participants aged 2-5, 6-11, 12-17, and 18-45 years received either three TDV vaccinations at months 0, 3.5, and 12 (TDV-TDV-TDV group) or licensed typhoid vaccination at month 0 and TDV at months 3.5 and 12 (TyVi-TDV-TDV group) and were followed for safety (including biological safety and vaccine virus viremia) and immunogenicity. No serious adverse vaccine related events and no significant trends in biological safety parameters were reported. Injection site pain, headache, malaise, myalgia, fever, and asthenia were reported most frequently, as mild to moderate in most cases and transient. Reactogenicity did not increase with successive vaccinations and was no higher in children than in adults and adolescents. Low levels of vaccinal viremia were detected in both groups after each TDV vaccination. After three TDV vaccinations, the seropositivity rates against serotypes 1-4 were: 91%, 100%, 96%, 100%, respectively, in 2-5 year-olds; 88%, 96% 96%, 92% in 6-11 year-olds; 88%, 83%, 92%, 96% in adolescents; and 100% for all serotypes in adults. A similar response was observed after two doses for the TyVi-TDV-TDV group. The safety profile of TDV in a flavivirus endemic population was consistent with previous reports from flavivirus naïve populations. A vaccine regimen of either three TDV vaccinations administered over a year or two TDV vaccinations given more than 8 months apart resulted in a balanced antibody response to all four dengue serotypes in this flavivirus-exposed population, including children.