Typhoid Fever

Researchers are evaluating the safety, tolerability, and how the body processes (pharmacokinetics) single and multiple intravenous doses of a drug called BWC0977 in healthy adult volunteers. This Phase 1 study involves a total of 64 healthy adults aged 18 to 55 years and is designed as a randomized, double-blind, placebo-controlled trial with multiple dose groups. The study focuses on measuring any treatment-emergent adverse events and serious adverse events to understand the drug's safety profile. Participants will be divided into two main groups: single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. In the SAD phase, volunteers receive one intravenous infusion of BWC0977 or placebo over 2 hours at doses of 750 mg or 1500 mg. In the MAD phase, participants receive multiple intravenous infusions of BWC0977 or placebo over 30 minutes to 2 hours daily for 7 to 10 consecutive days. Dose levels will increase sequentially based on safety and tolerability data collected during the study. During the study, participants will undergo various assessments including physical exams, vital signs, ECGs, laboratory tests, and blood sampling at specific times before, during, and after infusions to monitor safety and measure drug levels in the body. Researchers will track adverse events for up to 8 days after single dosing and up to 16 days after multiple dosing. Volunteers must comply with study visits and requirements throughout the trial, which lasts until August 2026.

Researchers are investigating whether adding a rapid biomarker test to current clinical guidelines can better identify young children with fever who are at risk of serious infections in sub-Saharan Africa. This study compares standard care based on integrated management of childhood illness (IMCI) guidelines alone to an approach enhanced by measuring suPAR levels, a biomarker, during the first clinical assessment. The goal is to see if this combined strategy improves decisions about hospital admission or discharge and leads to better health outcomes for children aged 2 to under 60 months. The trial is a multi-country, open-label, randomized study with two groups: one receiving the standard IMCI-based care and the other receiving IMCI care plus a point-of-care suPAR test. Blood samples will be taken from all children, but only the intervention group will have their suPAR levels measured immediately. Clinicians will use these results along with IMCI guidelines to decide whether to admit or discharge each child during the first clinical visit. A second, more detailed clinical assessment will also be performed on all participants to confirm or adjust decisions and ensure safety. Children will be followed up on days 3 and 7 after enrollment with additional visits if clinical worsening occurs. A day 28 follow-up will collect information on serious events, hospitalizations, or deaths, with an optional extra interview at three months. Participants with respiratory symptoms may join a substudy involving lung exams and sample collections. The study team will measure outcomes like the appropriateness of discharge decisions, hospital admissions, severity of illness, and mortality to evaluate the new triage approach's effectiveness and safety over these timeframes.

Researchers are evaluating the need for antibiotic prevention in patients with chronic liver disease who have gastric varices and are treated with elective endoscopic injection of cyanoacrylate (GVO). Gastric varices can cause serious bleeding with a high chance of rebleeding and mortality. While endoscopic injection of tissue glue is effective in stopping acute bleeding, it still carries risks of rebleeding and infection, which are important concerns for patients with weakened immune systems due to liver conditions. The study compares two groups: one receiving an antibiotic called ertapenem injected intravenously before the endoscopic cyanoacrylate injection, and the other not receiving this antibiotic before the procedure. The trial is randomized and aims to clarify whether giving this antibiotic can help prevent infections and complications after GVO treatment. The treatment is delivered during an elective endoscopic procedure to manage gastric varices. Participants will be monitored for three years to evaluate key outcomes such as the prevention of sepsis, rebleeding rates, refractory bacterial infections, and mortality. Assessments will include tracking infections and bleeding events over time. The study is designed to provide long-term data on the benefits and risks of using antibiotic prophylaxis in this patient group, with ongoing safety monitoring throughout the follow-up period.

Researchers are evaluating whether AI-enabled, nurse-led treatment planning can match or improve the quality of clinical reasoning and management compared to standard physician-led care in adults aged 18 years and older. The study focuses on patients in rural and semi-urban India presenting with hypertension, diabetes mellitus, fever, breathlessness, or musculoskeletal pain. It aims to determine if nurse consultations supported by a large language model (LLM) achieve clinical quality scores that are not worse than those of physician consultations and to assess patient acceptance and satisfaction with AI-assisted nurse care. Participants receive two consultations during the same visit: one led by a nurse using an AI-based clinical decision support tool and one by a physician providing standard care. The nurse-led consultation involves routine history taking and clinical assessment, with interaction through a digital interface to the LLM for assistance in diagnosis, reasoning, and treatment planning. The physician consultation follows usual clinical practice without AI support. The study compares these two approaches in a randomized order within each participant. Throughout the study visit, both consultations are audio recorded for blinded clinical quality evaluation. After the nurse + LLM consultation, participants complete an exit survey measuring communication, trust, and satisfaction. Researchers also gather nurse-reported feedback on acceptability and feasibility through interviews after nurses complete at least 10 AI-assisted consultations. The main outcome measured is the clinical quality of the consultations immediately after both visits, with additional assessments of patient experience and nurse perspectives over up to nine months.

This research evaluates the accuracy and consistency of an AI platform called OpenGenome that analyzes free-text symptom descriptions submitted voluntarily by adults. The study collects anonymous symptom data and matches it with real biomedical literature from PubMed and ClinicalTrials.gov to generate structured biological signal reports. It aims to assess how well the extracted signals align with sources, how confidence scores correlate with dataset size and symptom specificity, and the distribution of biological signals across a large population. Adults aged 18 or older can submit free-text symptom descriptions via the OpenGenome platform, which then uses an AI-assisted method to extract primary and secondary biological signals grounded in biomedical evidence. For each submission, the system retrieves up to 16 relevant sources and provides a confidence score and signal strength. No treatment or intervention is given, and no participant contact occurs during the observational registry. Participants are involved by voluntarily submitting symptom descriptions online through the platform, with all data anonymized at collection. The study continuously monitors the internal signal-source concordance rate over 12 months. There are no in-person visits or direct assessments, ensuring privacy and minimal burden. This ongoing data collection helps researchers understand the platform's accuracy and signal calibration in a broad anonymous population.

Researchers are studying acute febrile illness in patients older than 28 days who live in rural areas of Laos, Myanmar, Thailand (including the Thai-Myanmar border region), and Bangladesh. This observational study aims to describe the causes, clinical outcomes, and host biomarkers associated with these illnesses, which last 14 days or less. The study is part of a larger community-based network seeking to improve understanding and future interventions for febrile illness in low- and middle-income countries in South and Southeast Asia. The study involves two main parts: Work Package A collects data from village health workers and local health facilities to understand the incidence and outcomes of febrile illness at the community level. Work Package B recruits patients seeking care at higher-level health facilities who may be more severely ill. In Work Package B, researchers collect various samples including venous blood and respiratory specimens for detailed diagnostic testing such as blood cultures, serological assays, molecular diagnostics, and host biomarker assays. Participants will be monitored for about one month to measure the prevalence of pathogens and recovery status. The study will analyze the association between host biomarkers and clinical outcomes to help create electronic decision-support tools for village health workers. These tools and other interventions will be tested later to improve assessment, triage, and treatment of patients with febrile illness. The total duration of participation and follow-up is approximately one month.

This research aims to evaluate the effects of a multi-component chlorination intervention on maternal and neonatal health in public healthcare facilities in western Kenya. The trial focuses on reducing bacterial contamination and antibiotic-resistant infections in neonates born at these facilities. The study is a cluster randomized controlled trial involving 36 health facilities, with a goal to provide evidence on how chlorinated water supply and reliable chlorine disinfectant use impact bacterial contamination and infection rates. Health facilities will be randomly assigned either to a control group or to an intervention group. Intervention facilities will receive passive inline chlorine dosers that automatically treat water used in maternity wards, along with a steady supply of chlorine disinfectant. Half of the intervention sites will produce chlorine on-site using electrochlorinators, while the other half will receive bulk chlorine deliveries. Both intervention and control facilities will receive infection prevention and control messaging. Facilities will also get equipment like mops and spray bottles for surface cleaning. Participants include pregnant adults or mature minors giving birth at enrolled facilities and their newborns. Researchers will collect data over 24 months, assessing bacterial contamination in water, on hands, and on surfaces, as well as gut colonization by pathogenic and antibiotic-resistant bacteria in mothers and neonates. Health outcomes like possible serious bacterial infection and sepsis symptoms will be monitored during the first week after birth. The study will also track neonatal and maternal mortality up to 28 days postpartum to understand the intervention's impact on infection and health.

Researchers are evaluating the clinical and antibacterial effects, safety, and pharmacokinetics of the drug Fluorothiazinone compared to a placebo for preventing hospital-acquired gram-negative bacterial infections in patients who are on mechanical ventilation. The study is a randomized, double-blind, placebo-controlled clinical trial conducted by the Gamaleya Research Institute of Epidemiology and Microbiology. Participants are randomly assigned to receive either Fluorothiazinone tablets or a matching placebo. Those in the treatment group take 2400 mg per day (4 tablets twice daily) for the first two days, then 1800 mg per day (3 tablets twice daily) from day three onward for up to 14 days or until ventilator-associated pneumonia caused by gram-negative bacteria develops. Tablets are taken twice daily, 12 hours apart, 30 minutes after meals. The placebo group follows the same dosing schedule with inactive tablets. During the study, participants are monitored for the development of pneumonia, bloodstream infections, and urinary tract infections associated with mechanical ventilation over a 14-day therapy period. Researchers track the time to infection onset, the proportion of patients affected by infections or septic complications, and any fatal outcomes. Safety, tolerability, and blood levels of Fluorothiazinone are also evaluated. The study includes adult patients in intensive care units who have been on mechanical ventilation for no more than 12 hours and are at high risk of requiring ventilation within 72 hours.

Researchers are evaluating a telemedicine system designed for continuous monitoring of body temperature in adults who have fever. This pilot study is nonrandomized and conducted at a single center, aiming to assess both the effectiveness and safety of the device. Up to 40 adults hospitalized for infections or other conditions causing temperature changes will participate, with no randomization or stratification of participants. The investigational device will be placed in the armpit area and connected to a mobile phone to continuously record temperature readings. Study staff will also manually measure skin temperature in the opposite armpit using a gallium thermometer every 30 to 60 minutes, increasing frequency if the temperature rises or if temperature-lowering drugs are administered. The device will stay in place for up to 72 hours, followed by an additional 72-hour monitoring period after removal to observe for any side effects. Participants will be monitored closely by research staff during device placement and after removal, with temperature checks and safety evaluations continuing throughout the six-day period. The main measurement is the correlation between the telemedicine device readings and standard thermometer measurements over 72 hours. Researchers will also track any adverse events related to the device or procedures during the entire monitoring period.

Access to safe drinking water remains a major challenge in rural households of developing countries, leading to millions of deaths annually due to unsafe water sources. This research evaluates a program that provides coupons for free dilute chlorine solution to improve child health by reducing diarrhea, fever, and cough incidents. The study is a large-scale randomized controlled trial conducted at health clinics, assessing the sustained health impacts and behavior related to chlorine use and health clinic visits. Participants are randomly assigned to receive coupons redeemable for a monthly supply of a 150ml bottle of dilute chlorine solution at registered health facilities for 12 months or to a control group that receives no coupons after enrollment. The intervention is delivered via SMS with an ID for coupon redemption after enrollment over a phone call. The study is conducted in collaboration with the Kenya Medical Research Institute at Health and Demographic Surveillance Systems sites. Participants are monitored for chlorine use in drinking water at 6-month intervals up to 36 months, along with assessments of child illness occurrences like diarrhea and fever. Data collection also includes child mortality and verbal autopsies for deceased children, providing valuable information for future studies on the mortality impact of chlorine distribution. The study involves ongoing data collection on self-reported health facility visits and objective measures of chlorine use over the study period.