Satakunta, Finland

Preparing for Maternal GBS Vaccine Trials in Africa

Two vaccines designed for pregnant women, to protect their unborn infant, are entering late phase development and will prevent infections from GBS and respiratory syncytial virus, respectively. For these vaccines to be approved, the vaccine must work effectively without causing any unwanted responses. To implement these vaccines in countries with low resources, healthcare systems must be strengthened by improving vaccine safety monitoring and surveillance of infection, and advancing vaccine delivery, vaccine confidence, and patient participation. The PROTECT study, funded by the EU Commission EDCTP, is three-fold: 1. Establishment of pregnancy exposure registries: The rapid rollout of electronic health records (EHR) in some East African countries offers an opportunity to use routine data to strengthen reporting of rates of adverse pregnancy, neonatal and infant outcomes, and any adverse events following immunisation; this will be imperative in informing and preparing for future large scale vaccination rollout campaigns. The approach will develop pregnancy registries embedded within national reporting systems to establish this data, including baseline rates of pregnancy and infancy outcomes for Tetanus and COVID19 vaccines currently in use. These reporting systems will allow monitoring of potential safety signals once new vaccines are introduced. 2. Developing sentinel site GBS microbiological surveillance: The investigators will conduct a prospective observational GBS surveillance study among infants less than 90 days old who are admitted with laboratory confirmed GBS. The investigators will develop and strengthen invasive bacterial disease (IBD) surveillance, with a focus on GBS in Kenya, Malawi, Mozambique and Uganda. Each of the proposed lead sites has access to microbiological capacity that will be leveraged to monitor microbiologically confirmed neonatal sepsis burden. In doing so, the investigators will improve the nations' ability to participate in late phase clinical trials and post-licensure effectiveness studies. 3. Vaccine Confidence: The aim of this study is evaluating the knowledge and practices of pregnant women and other key stakeholders around vaccination and factors influencing vaccine confidence during pregnancy. The investigators will also create tools and communication strategies to improve willingness of pregnant women to participate in vaccine trials and consequently increase confidence in vaccines and vaccine trials during pregnancy in Mozambique, Uganda, Malawi and Kenya. The investigators will work closely with the World Health Organization (WHO), African Medicines Agency and Country Stakeholders. This programme of work culminates in a network of maternal vaccine trial sites that can rapidly evaluate vaccines in pregnancy from late-stage trials through to introduction on a national level.

Multimodal Analgesia Utilization and Acute Postoperative Pain After Major Surgery At Mulago National Referral Hospital

Study Objectives: Primary Objectives - To determine the prevalence of perioperative multimodal analgesia practices among adult patients undergoing elective major surgery at Mulago National Referral Hospital. - To determine the association between perioperative multimodal analgesia practices and acute postoperative pain among adult patients undergoing elective major surgery at Mulago National Referral Hospital. Secondary Objective - To determine factors associated with perioperative multimodal analgesia practices at Mulago National Referral Hospital. Study site: Mulago National Referral Hospital, the largest public hospital in Uganda with a bed capacity of 1500. Study area: Post Anaesthesia Care Units of the Main Operating Theatre Complex and five inpatient surgical units i.e., Colorectal, Upper Gastrointestinal/Hepatobiliary, Spine, Thoracic, Orthopaedic Study Population: All adult patients undergoing elective major surgeries in the five surgical units during the study period who meet the eligibility criteria. Sample size assessment: calculated using the Kish Leslie (1965) formula. Adjusted for a 10% loss to follow up rate and clustering with a design effect of 1.5. Sampling procedure: Based on monthly surgical averages, participants will be grouped as follows: Colorectal - 105 patients, Upper Gastrointestinal/Hepatobiliary - 84 patients, Spine - 112 patients, Orthopaedic - 126 patients, Thoracic - 22 patients. Consecutive sampling will be done in each of the surgical units until the desired sample size is attained. Study procedure: - The principal investigator or research assistants will visit the patients the evening before their scheduled surgery to screen for eligibility and obtain informed consent. - Data on patient socio-demographics, ASA status, clinical diagnosis, type of scheduled surgery, and performance of a preoperative anaesthetic assessment will be abstracted from the patient's chart. - Enrolled patients will be asked about any history of chronic (≥3 months) pain and use of analgesics. - The patient will be asked about the presence of preoperative pain. If in pain, a baseline assessment will be performed using the Numeric Rating Scale, which will be physically presented to the patient. The numbers on the scale and what levels of pain they represent will be explained to the patient. The patient will then be asked to choose a number on the scale that best represents their current level of pain. Either the patient or the research assistant will circle this. - All systemic analgesic medications (drug class, agent, dosage, frequency, route of administration, prescriber) and regional analgesic techniques (the name of the technique, cadre of the performer of the technique, and drug(s) given, including dosage and frequency) utilised in the preoperative period will be recorded. - Upon admission to the PACU after the surgery, all systemic analgesic medications, regional analgesic techniques, and medications utilised in the intraoperative phase will be abstracted from the patient's anaesthetic chart. Additional data collected will include the cadre of the anaesthesia provider, i.e. anaesthesiologist, anaesthetic officer or anaesthesia resident and their years of practice or year of training, type of anaesthetic used, i.e. general anaesthesia, spinal anaesthesia, epidural anaesthesia or a combination of spinal and epidural anaesthesia, peripheral nerve blocks, intravenous regional anaesthesia, type of surgery performed and duration of the surgical procedure. Postoperatively: - All the systemic analgesic medications and regional analgesic techniques utilised in the postoperative period will be abstracted from the patient's files. 9. Pain intensity after surgery will be measured using the Numeric Rating Scale. The nurse or doctor on duty will be informed if a patient is found with an NRS of ≥4. The research assistants will follow up to ensure that interventions to relieve the patient's pain have been instituted. Data collection and management Research assistants will undergo data collection training for three days. The abstraction form will be pre-tested before actual data collection on 10 participants who will not be part of the study. Questions will then be refined to ensure their clarity and relevance during the data collection process. All completed forms will be cross-checked for completeness by the Principal Investigator daily. Any errors, incompleteness, or incoherence will be addressed before data storage and entry. Data will be entered into REDCap electronic data capture software with programmed data checks. The database will be stored on a password-locked hard drive, and the principal investigator's Google Drive will be used as a backup. Data cleaning will be done weekly to ensure quality data is available for analysis. Data Analysis Data analysis will be carried out using Stata software (version 17). Univariable analysis will be achieved using frequencies with their proportions for categorical data, means with standard deviations for continuous variables with normal distribution, and medians with their interquartile ranges for continuous data with skewed distribution. Objective 1: To determine the prevalence of perioperative multimodal analgesia practices in adult patients undergoing elective major surgery at Mulago National Referral Hospital. Descriptive statistics will be used to describe the systemic and/or regional analgesic medications used in the perioperative period (multimodal analgesia practices). Frequencies with their proportions, means with standard deviations, and medians with their interquartile ranges will be reported appropriately. The results will be presented in tables, graphs and charts. Objective 2 and secondary objective Binary logistic regression will be used to evaluate the association between individual independent variables (including perioperative multimodal analgesia practices) and acute postoperative pain. Variables with a p-value of less than 0.2 in the bivariable analysis will be used in the multivariable analysis. Crude odds ratio (cOR) and their 95% confidence intervals will be reported. Multivariable logistic regression will be used to evaluate the association between perioperative multimodal analgesia practices and acute postoperative pain, adjusting for other independent variables and controlling for interaction and confounding. Adjusted odds ratios (aOR) and their 95% confidence intervals will be reported. The statistical significance in this study will be determined at a p-value less than 0.05.

Precision Imaging to Evaluate Kaposi Sarcoma

Introduction of Arpraziquantel Treatment for Schistosomiasis Control in Preschool-aged Children in Endemic Areas: a Small-scale Public Health Intervention Study

Earlier Prime-BOOST Schedule to Improve MEasles Protection in High Burden Settings

Two doses of measles containing vaccine (MCV) are recommended in young children with the first dose given at different times depending on the setting. In low-incidence settings the MCV1 is given at 12 months of age or later as more infants over 12 months of age respond to MCV1 due to the absence of maternal antibody interference and an overall better immune response due to the maturation of the infant immune system. In high measles incidence settings MCV1 is given earlier at 9 months of age as there is no remaining protection from maternal antibody at this age and risk of infection if unvaccinated can be high. However, in children born with low levels or rapid decay of maternal antibody, the 9-month timing for MCV1 means the infant may be susceptible to infection for some months prior to vaccination. Therefore, in settings of high infant measles incidence, an early first dose at 6 months of age may bridge this susceptibility gap. Our study will assess differences in protective levels of measles antibody in children randomised to receive early (6 months) or standard (9 months) MCV1 in a high incidence measles setting, and early (12 months) or standard (18 months) booster vaccines, in those who are given early MCV1. There will be 5 blood draws over 2 years. The study will compare children who received a) two doses of measles vaccine at 6 and 18 months with 9 and 18 months, and b) two doses of measles vaccine at 6 and 12 months compared with 6 and 18 months. The study is funded by the Bill & Melinda Gates Foundation (INV-048650)

Post-Trial Tuberculosis Case Finding: A Substudy of CoVPN 3008

This observational substudy will involve participants from the CoVPN 3008 trial, regardless of their HIV status, to study tuberculosis (TB). At the start, all participants will be screened for TB, even if they have no symptoms. They will receive chest x-rays and provide sputum samples for TB testing using Xpert Ultra, smear microscopy, and culture. The study has two main groups. Group 1 includes participants with confirmed TB, and Group 2 includes participants without TB who will act as controls. Participants with confirmed TB will start treatment and have a first follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. A second follow-up visit will take place at week 26 to evaluate their treatment progress, clinical outcomes, and TB status, ensuring they receive the necessary care. Participants without TB will have a single follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. The study aims to identify potential biomarkers of TB by analyzing blood samples from both cases and controls, focusing on gene expression linked to TB, including hidden (subclinical) TB.

Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline

This will be a double-blind randomized block stratified clinical trial. Participants will be enrolled if they have advanced drug sensitive TB evidenced by infiltrates/lesions in at least 2 zones on a chest X-ray, among other inclusion criteria. Participants will receive 100mg of doxycycline or matching placebo once a day for 12 weeks in addition to standard anti TB therapy. Participants will undergo baseline high resolution CT scans to evaluate lung parenchyma involvement and repeat CT scans at 12 months to score TB associated fibrosis. Lung function assessment with spirometry will be done at 6 and 12 months after enrolment to assess trends of lung function in the control and intervention study arms. Profibrotic cytokines (TGFbeta) and Matrix metalloproteinases (1, 3 ,8,9) will be measured at baseline , 3 and 6 months after enrolment.

Study To Evaluate Safety, Tolerability, and Pharmacokinetics of MAM01 in African Population

This is a Phase 1b, age de-escalation/dose escalation trial that will be conducted in a setting of perennial Plasmodium falciparum (malaria parasite) transmission in Africa. The study will be conducted in 2 parts: Part A (Dose Escalation in Adults); Part B (Age De-escalation/Dose Escalation in Younger Children).

Livelihoods Intervention With Urban Refugee Youth in Kampala, Uganda

As of March 2021, the prevalence of HIV among Ugandan youth aged 15-24 years was estimated at almost 2%, with young women and adolescent girls having an HIV prevalence over three times that of young men and adolescent boys (2.9% vs. 0.8%). The prevalence of HIV among youth living in Kampala's slums is even higher, at an estimated 13.9-37.2%. This high prevalence may be driven by factors such as food scarcity, limited infrastructure, lack of social support, stigma, and gender norms, which may limit the condom negation and use of HIV testing services among youth. Uganda hosts over 1.5 million refugees, 8% of which reside in Kampala, and many living within slums or informal settlements. While the UNAIDS Gap report identified displaced persons and adolescent girls and young women as populations at high-risk for HIV infection, the HIV prevalence among Uganda's refugees is largely unknown due to the lack of standardized surveillance of refugees. One approach to improve HIV testing among displaced persons in Uganda is through HIV self-testing (HIVST). HIVST involves a person collecting their own specimen (blood or saliva), conducting the test, and interpreting the results. HIVST has the potential to reduce testing barriers such as stigma and privacy, while enhancing confidentiality and convenience, which are important considerations for adolescents and young people. Innovative HIVST delivery strategies are urgently needed to link persons with positive HIVST results to confirmatory testing and HIV care. As such, identifying strategies to promote linkage to HIV care is essential to realize the public health impact of HIVST. Since there is a dearth of knowledge regarding efficacious interventions in refugee camps/settlements to engage young people in HIV testing and linkage to care, the investigators will harness various health promotion techniques including mHealth, comics, and the Creating Futures livelihoods intervention to address the urgent needs for: 1) HIV testing interventions with refugee/displaced adolescent and young people in Kampala, and 2) innovative HIVST delivery strategies to increase linkage to confirmatory testing and HIV care. The investigators will evaluate the feasibility and effectiveness of: 1) HIVST alone; 2) HIVST in combination with mHealth; and 3) HIVST, mHealth and Creating Futures in combination in increasing routine HIV testing, HIV status knowledge, and linkage to confirmatory testing and HIV care. The investigators aim to examine if adding a livelihoods program to HIV self-testing improves HIV prevention outcomes and other facets of well-being among urban refugee youth in Kampala. Mobile health (mHealth) can be used to facilitate HIVST adherence among displaced youth through mobile phone (mHealth) reminders. mHealth approaches are germane to low and middle-income countries (LMIC), where cell phone ownership is rising rapidly, but access to health care is often limited. In Uganda, over 13 million persons have access to mobile phones, and data suggest that HIV prevention messages through mobile phones are beneficial to supplement traditional modalities such as schools for adolescents. Educational comics offer a youth-friendly, low-cost, scalable approach for providing education and health promotion on health topics such as HIV, sexually transmitted infections, vaccines, and dementia. Comics have been used to educate both the general population and healthcare providers to improve care and patient experiences, as they are accessible, do not require high levels of literacy, and can encourage participants to envision and share solutions to sexual violence through facilitating dialogue around emotionally difficult and often stigmatized issues. Creating Futures is a group intervention that aims to help young people build their livelihoods and was designed for use with youth in urban informal settlements in South Africa. Previous researchers have implemented the Creating Futures intervention in South Africa and found that after the intervention, men's earnings increased, women's experiences of intimate partner violence decreased, men and women scored better on gender attitudes, and depression and suicidal thoughts decreased amongst men. The investigators will conduct a three-arm cluster randomized controlled trial (cRCT) to evaluate the effectiveness of HIVST delivery methods among youth living in Kampala. The five informal settlements in Kampala will be randomized in a 1:1:1 approach to one of the three study arms. The five informal settlements will be grouped into three sites based on close geographic proximity (1: Kabalagala and Kansanga, 2: Katwe and Nsambya, and 3: Rubaga). The investigators used the following criteria to select informal settlements: 1) settlements that host a large number of refugees or displaced persons; 2) communities with similar measures of socioeconomic status, healthcare access, languages, and living conditions; and 3) evidence of a high prevalence of depressive symptoms among urban refugee youth. Participants will be allocated to a study arm based on their informal settlement of residence. Youth living in slums and informal settlements have shared socio-physical environments. As such, except for individual-level outcome data, the investigators will use a cluster-randomized approach to limit challenges posed by experimental contamination and threats to internal validity. Data collection will be performed at baseline, and 3- and 6-months post-intervention implementation. The investigators are working with study collaborators from Young African Refugees for Integral Development (YARID), a nongovernmental youth refugee organization in Kampala, who have been involved since the initial research question and focus development stage. The study protocol was developed after a formative qualitative research phase (Phase 1), which included semi-structured interviews with peer navigators and other key informants (e.g., refugee health professionals, migrant workers, teen mothers). Refugee youth aged 18-24 years (12: 6 men, 6 women), living in the same informal settlements who are trained in research methods and ethics will act as peer navigators and enroll other youth in the study after obtaining written informed consent. The investigators employed purposive methods to recruit participants, such as word-of-mouth and venue-based sampling at community events and refugee agencies, beginning with participants who belonged to the Tushirkiane cohort and participated in previous trials on HIVST, COVID-19 prevention, and mental health interventions. The investigators will refresh the cohort with additional purposive recruitment of 16- and 17-year-old participants. The use of SMS and WhatsApp reminders from peer navigators and outreach events allows for the continued engagement and retention of study participants. Data collection will be conducted by research assistants trained by the Ministry of Health in pre- and post-test counselling. Data will be collected using a structured survey accessed via mobile phones or tablets in all study languages via the SurveyCTO app (Dobility). This app houses a secure platform and automatically encrypts data, which are then uploaded with a Secure Sockets Layer (SSL) certificate to a password-protected server. The use of SurveyCTO allows for multilingual and offline data collection with branching logic and consistency checks. All participants are assigned a unique ID number without any personal identifying information to enhance confidentiality. The analysis and reporting of this study will be conducted following the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The study analyst will be blinded to group allocation. Participant flow (screening, randomization, allocation, follow-up) will be illustrated using a flow diagram. The investigators will report baseline data for all groups summarized using mean (standard deviation) or median (first and third quartiles) for continuous variables and counts and frequencies (percent) for categorical variables. The investigators will use an intention-to-treat approach with a complete data set whereby participants will be analyzed according to their initial group allocation irrespective of whether they received said intervention.

Shortened Regimen for Drug-susceptible TB in Children

In previously untreated individuals with presumed drug-susceptible pulmonary and or peripheral lymph node TB treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (2HPZM), all given daily throughout, the proportion of participants who experience absence of cure (unsuccessful outcome) will not be inferior to that observed in participants who are treated with the standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide, with or without ethambutol followed by 8 to 16 weeks of rifampin plus isoniazid depending on disease severity) all given daily throughout.