Blantyre

Researchers are studying HIV prevention among women in Blantyre, Malawi, focusing on choices and preferences between long-acting injectable PrEP and oral PrEP. The study aims to understand the impact of rolling out injectable PrEP alongside oral PrEP by tracing women who have stopped or lost contact with PrEP services within the past two years. It also seeks to explore reasons for discontinuation, user experiences, and preferences for re-engagement. Participants include women who have missed their PrEP visits by three months or more and whose outcomes are unknown. The study involves two groups one receiving standard care per national guidelines with counseling and follow-up messages, and another receiving standard care plus a tracing strategy to determine their PrEP status. The tracing strategy includes phone calls and, with consent, in-person home visits to reconnect participants with care. Women traced will complete surveys assessing their HIV outcomes and preferences, and a subset will participate in interviews alongside healthcare providers to better understand PrEP use and discontinuation. Researchers will measure the number of women who return to PrEP after tracing and assess drug levels through dried blood samples. The study lasts about two years and aims to inform better strategies for maintaining PrEP use and preventing HIV among women in Malawi.

Acute hypoxemia is a serious condition that commonly occurs in adults in resource-limited settings and can be deadly. This trial investigates whether high flow oxygen therapy leads to better survival outcomes compared to standard flow oxygen in adults with low blood oxygen levels treated in five hospitals in low or lower middle income countries. The study also aims to understand what helps or hinders the use of high flow oxygen in these settings and to measure how much oxygen each method uses. Participants will be randomly assigned to receive either high flow oxygen delivered through a large nasal cannula at up to 60 liters per minute, or standard flow oxygen delivered by nasal cannula, face mask, or non-rebreather mask at flows up to 15 liters per minute. Both treatment groups aim to maintain blood oxygen saturation between 90% and 94%. The study will compare outcomes between these two oxygen delivery methods throughout the hospital stay. During the study, participants will be monitored for survival in the hospital up to day 90, as well as functional status, need for mechanical ventilation, days requiring oxygen, and length of hospital and ICU stay. Researchers will also track the time until escalation to more intensive respiratory support if needed. The study will examine oxygen use and barriers to implementing high flow oxygen therapy. Participants involvement will include regular assessments and follow-up during hospitalization and up to 90 days after admission.

Researchers are evaluating a device called BreathAlert, developed by Rice University in collaboration with clinicians at Queen Elizabeth Central Hospital, to monitor apnea in infants and children at risk. This observational study aims to assess BreathAlerts ability to detect respiration and apneic episodes by comparing its performance to traditional vital sign monitors, which include measurements such as temperature, heart rate, EKG, respiratory rate, SPO2, and impedance pneumography. During the study, the BreathAlert device, a low-cost battery-powered respiratory rate and apnea monitor, is attached to patients in the neonatal or pediatric ward who are at risk for apnea or require respiratory rate monitoring. Data is collected simultaneously from both BreathAlert and standard vital signs monitors while the patient is being observed. Participants will have the BreathAlert device attached while they are at risk for apnea, and researchers will collect data from both the device and existing monitors. The main outcome measured is the accuracy of BreathAlert over a maximum period of one week. The study involves patients from newborns up to 17 years old, with caregiver consent required, and continues until study completion in June 2028.

Researchers are studying ambulatory antibiotic treatments for neonates with all-risk asymptomatic congenital syphilis in a randomized, open-label phase II trial called CARES-1. The study aims to evaluate the pharmacokinetics and safety of different antibiotic options to improve treatment approaches for this vulnerable newborn population. Participants are randomly assigned to one of three treatment groups a 10-day course of oral Linezolid given twice daily at 10 mgkg, a 10-day course of oral Amoxicillin given twice daily at 50 mgkg, or a single intramuscular dose of Benzathine Penicillin G at 50,000 IUkg. These treatments are provided in an ambulatory setting to assess their effectiveness and tolerability in newborns. During the study, infants will be monitored from enrollment through day 10 for antibiotic levels in blood and cerebrospinal fluid, and adverse events will be tracked for up to 24 weeks. Clinical outcomes will be evaluated through week 24 to assess treatment impact. This includes measuring time above minimum inhibitory concentrations and AUCMIC ratios in serum and CSF. Safety and treatment effects will be closely observed throughout the study duration.

Researchers are investigating why the impact of SARS-CoV-2 in sub-Saharan African countries, specifically Malawi, appears milder compared to Europe and the Americas. The study aims to understand how innate immune responses, malaria, intestinal parasites, undernutrition, and anemia influence infection risk, symptom progression, transmission, and responses to SARS-CoV-2 vaccination. They are assessing immune responses and vaccine effects in various groups to better understand susceptibility and immunity in this population. The study includes up to 200 symptomatic individuals confirmed with SARS-CoV-2 infection, their household contacts about 700, and up to 600 vaccine recipients aged 5 to 75 years. Participants undergo multiple visits for blood and stool sample collection over a follow-up period of up to 1.5 years. Vaccine recipients receive either the AstraZeneca or Johnson and Johnson vaccines, with samples collected at specific intervals after vaccination to monitor immune responses. Participants will have blood drawn at baseline and multiple follow-up visits to measure antibody levels, cellular immune responses, and markers of inflammation. Stool samples will be collected to diagnose intestinal parasites. Researchers will also monitor infection rates, symptom duration, and vaccine responses. The study will track these measures over time to assess how infections and vaccinations affect immunity and disease outcomes, with the overall participation lasting up to 15 months after initial enrollment.

Researchers are studying the safety and effects of a drug called 6-diazo-5-oxo-L-norleucine DON in healthy adults, adults with uncomplicated malaria, and children aged 12 months to 14 years with cerebral malaria. The study aims to evaluate the safety of a single intravenous dose of DON, understand how the drug moves through the body, and assess if DON improves brain blood flow, reduces brain swelling, and changes brain activity patterns in children with cerebral malaria. This is a Phase 12a dose-escalation safety study involving dose increases in adults and children. The study has two parts. In Part 1, healthy adults and adults with uncomplicated malaria will receive one dose of DON intravenously at increasing doses from 0.1 mgkg up to 10.0 mgkg. Adults also receive the anti-nausea drug ondansetron, and adults with malaria receive standard malaria treatment per local guidelines. Part 2 involves children with cerebral malaria, who will be randomly assigned to receive either DON at different doses or a placebo, along with anti-nausea medication and recommended malaria therapies. Pediatric enrollment spans multiple malaria seasons with dose escalation through cohorts. Participants will be closely monitored over six months. Adults receive ondansetron before and after the DON dose and are observed for safety. Children will have brain scans MRI, brain blood flow assessments transcranial Doppler, and brain activity tests EEG along with routine clinical evaluations. Researchers will track side effects, drug levels in the blood, and brain function to assess safety and effects. The studys main safety assessments occur within 14 days of dosing, and pharmacokinetic measurements are taken up to 18 hours after infusion.

Researchers are investigating new treatment options for adults with newly diagnosed, drug-sensitive pulmonary tuberculosis through a phase 2BC open-label platform study. The trial compares several experimental drug regimens with a standard control treatment to assess efficacy and safety. Participants include adults aged 18 to 65 years with confirmed pulmonary tuberculosis sensitive to rifampicin and isoniazid. The study aims to optimize doses of existing drugs and introduce new medications to improve treatment outcomes. The study is divided into three stages. In stage 1, participants are randomly assigned to the control or one of two experimental arms containing high-dose rifampicin and other drugs for 12 to 17 weeks. Stage 2 adds an experimental arm including the drug BTZ-043, with participants allocated across four arms in varying ratios. Stage 3 begins after stages 1 and 2 complete enrollment, comparing the control arm with two new experimental arms involving novel drug combinations. Treatments are given once daily, with dosages adjusted by arm and weight. Participants will undergo sputum testing, chest X-rays, and molecular tests to confirm tuberculosis and drug sensitivity before enrollment. During the study, researchers will monitor participants through regular clinical assessments, laboratory tests, and electrocardiograms to track treatment response and safety. The main outcomes measured include time to stable culture conversion and changes in mycobacterial load. Safety is evaluated by recording adverse events and laboratory abnormalities over the treatment period, with follow-up continuing up to 12 months after randomization.

Group B Streptococcus GBS is a leading cause of sepsis and bacterial meningitis in newborns during the first 90 days of life, contributing significantly to newborn deaths. Researchers are preparing for maternal GBS vaccine trials in Africa to improve infection prevention through better data collection, surveillance, and vaccine confidence. The PROTECT project supports sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform pregnancy and infant health data, monitor GBS incidence, and understand factors affecting vaccine acceptance. The study consists of three main parts creating pregnancy exposure registries using electronic health records to track pregnancy and infant outcomes conducting a prospective observational GBS surveillance study among infants under 90 days with confirmed GBS infection at sentinel sites and assessing vaccine confidence through surveys and interviews with pregnant women, healthcare workers, and community leaders. These activities aim to strengthen healthcare systems for future vaccine trials and rollout. Participants include pregnant women and their infants up to hospital discharge for the registry infants under 90 days with confirmed GBS infection for surveillance and pregnant women, healthcare workers, and community stakeholders for vaccine confidence research. The study involves collecting and analyzing medical records, microbiological data, and survey responses over periods ranging from 12 months to two years. Researchers will monitor pregnancy and infant outcomes, GBS infection rates, and vaccine knowledge to prepare for vaccine safety monitoring and effective vaccine implementation.

Researchers are evaluating the RTS,SAS01 malaria vaccine through case-control studies embedded within the Malaria Vaccine Pilot Evaluation MVPE conducted in Ghana, Malawi, and Kenya. This observational study aims to assess the vaccines safety with focus on cerebral malaria, meningitis, and severe malaria, as well as its impact on all-cause mortality among children aged 6 months to 59 months. The study also supports the use of case-control methods in immunization and malaria control programs. The study involves two main case-control components clinical outcomes and mortality outcomes. For clinical outcomes, children living in MVPE areas who meet case or control definitions based on hospital surveillance are recruited, with each case matched to four controls. The mortality component recruits children who died from any cause excluding accidents or trauma and matches them with four live controls. Data collection includes administering questionnaires to caregivers at their homes and gathering information from hospital and community surveillance systems. Participants will be involved through consented data collection via questionnaires and surveillance records. Data on meningitis, severe malaria, cerebral malaria, and mortality by gender are collected and analyzed. Controls are recruited by canvassing households near cases to match age and location. The study spans 45 months, with ongoing monitoring of outcomes including hospital admissions and deaths. Findings will support vaccine safety and effectiveness assessments and inform policy decisions.

Researchers are evaluating new drug combinations for treating adults with drug-susceptible pulmonary tuberculosis TB in this Phase 2 randomized trial. The study aims to compare the early effectiveness and safety of these novel regimens against the current standard treatment, which includes isoniazid, rifampicin, pyrazinamide, and ethambutol. The main goal is to see if these new treatments improve early bacterial clearance and maintain acceptable safety over an 8-week period. Participants will be assigned to receive one of several drug regimens during the first 8 weeks. These include the standard treatment or experimental combinations containing bedaquiline, pretomanid, linezolid, TBI-223, or sutezolid at various doses. After the initial 8 weeks, all participants continue with standard therapy for an additional 18 weeks. Medication is taken orally daily, with dosing adjusted by weight and specific guidelines. During the 52-week study, which covers the full treatment and follow-up period, participants will have regular assessments including sputum tests to measure bacterial growth, blood tests to monitor safety, and clinical evaluations. The main outcomes measured are changes in bacterial growth over the first 6 weeks and the occurrence of significant side effects by week 8. Additional measurements include culture conversion rates, adverse events up to week 26, and overall cure rates at 52 weeks. Participants will be closely monitored throughout for safety and treatment response.