Vientiane

Researchers are evaluating the antiviral activity of multiple influenza drugs in adults with early symptomatic influenza infection. This Phase 2, randomized, open-label, controlled, adaptive platform trial aims to compare the effectiveness of currently licensed influenza antivirals and those with potential antiviral activity against a no-treatment control group. The study focuses on patients with uncomplicated influenza who have high viral loads, to better understand in-vivo antiviral effects and support guideline development and treatment prioritization. The trial includes several licensed antiviral drugs such as oseltamivir, peramivir, zanamivir, laninamivir, baloxavir, and favipiravir, along with molnupiravir, which has shown antiviral activity in pre-clinical studies. Treatments are administered in various forms including oral, inhaled, and intravenous routes, with dosing schedules ranging from single doses to multiple days of twice-daily dosing. Some treatment arms combine two antivirals. Randomization ensures at least 20% of participants receive no antiviral treatment, with equal allocation among available interventions. Participants will be involved from screening through treatment and monitoring up to five days, during which the rate of viral clearance will be measured. Assessments include symptom evaluation, rapid antigen or RT-PCR testing to confirm influenza infection, and safety monitoring. Participants must be able to walk unaided and adhere to study procedures, including follow-up visits. The overall study duration covers early infection and antiviral response measurement, focusing on understanding drug effects in uncomplicated flu cases.

Researchers are evaluating antiviral treatments for Respiratory Syncytial Virus (RSV) in low-risk adults aged 18 to under 65 years with early symptoms. This phase 2, randomized, open-label, controlled, adaptive platform trial compares licensed and potential antivirals against RSV, aiming to measure the rate of viral clearance within the first five days of treatment. The study addresses the urgent need for effective antiviral therapies as vaccines and preventive monoclonal antibodies primarily target other populations. Participants will be randomly assigned to receive one of several antiviral drugs or no antiviral treatment as a control. The drugs studied include ribavirin, given orally three times daily with doses based on body weight for five days; molnupiravir, taken orally twice daily for five days; and favipiravir, administered orally with a higher dose on the first day followed by a lower dose twice daily for four more days. Randomization ensures at least 20% of participants receive no antiviral treatment, with equal allocation among the active treatments. During the 28-day participation, patients will be monitored for viral clearance rates and safety. Assessments include symptom tracking, laboratory tests, and follow-up visits to evaluate the antiviral effects and any adverse events. Researchers will measure how quickly the virus clears from the body compared to no treatment, providing key information on the effectiveness of these interventions in early RSV infection.

Researchers are investigating the causes and clinical outcomes of acute febrile illness in patients older than 28 days living in rural areas of Laos, Myanmar, Thailand, the Thai-Myanmar border region, and Bangladesh. The study focuses on patients presenting with fever lasting 14 days or less, aiming to better understand the burden and factors affecting febrile illness in these low- and middle-income communities where infectious diseases remain a major health concern. This observational study is part of the South and Southeast Asian Community-based Trials Network and is funded by the UK Wellcome Trust. The study is conducted in two parts: Work Package A collects data from village health workers and local health facilities on the incidence and outcomes of febrile illness in the community, while Work Package B recruits patients from higher-level health facilities who are likely more severely ill. In Work Package B, a wide range of specimens, including blood and respiratory samples, will be collected for detailed diagnostic testing such as blood cultures, serology, molecular diagnostics, and host biomarker assays. These data will help create electronic decision-support tools to aid health workers in patient assessment and treatment. Participants will be closely monitored during their visit to health facilities where samples will be collected over approximately one month to determine the prevalence of pathogens causing febrile illness. Researchers will gather clinical data and laboratory results to analyze causes, incidence, and outcomes of fever in these rural settings. The study aims to improve future interventions by providing a rich understanding of febrile illness in these populations, with follow-up and safety monitoring incorporated in the study design.

Researchers are evaluating antiviral treatments in adults aged 18 to 60 with early symptomatic COVID-19 who have high viral loads but are otherwise healthy. This phase 2, multi-center, adaptive platform trial aims to measure the antiviral effects of several interventions compared to no treatment, focusing on how quickly the virus clears from the body within the first five days. The study includes small molecule drugs, monoclonal antibodies, and dose-finding for parts of nirmatrelvir/ritonavir to understand their effectiveness in vivo. The trial investigates multiple antiviral treatments including small molecule drugs such as nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir, and metformin; monoclonal antibodies like sotrovimab, tixagevimab/cilgavimab, and casirivimab/imdevimab; and combination therapies. Participants are randomly assigned to receive one of these treatments or no antiviral treatment (with at least 20% assigned to no treatment). Dosages and schedules vary by treatment, for example, nirmatrelvir/ritonavir is given twice daily for five days, while monoclonal antibodies are given once on day 0. Participants will be involved in assessments including viral clearance measurements over days 0 to 5. Researchers will monitor for viral load reduction as the primary outcome, comparing treated groups to controls. Participants must be able to walk unaided, have oxygen saturation of at least 96%, and agree to follow-up visits. Safety and treatment adherence are monitored throughout, with the study supported by the Wellcome Trust and conducted under controlled conditions to ensure accurate evaluation of antiviral effects.

Researchers are evaluating how national medical oxygen strategies impact health systems and policy contexts in Africa and Asia. This study focuses on understanding the challenges and solutions related to medical oxygen access in six countries participating in the MOXY program: Uganda, Nigeria, Rwanda, Liberia, Lao PDR, and Cambodia. The research aims to inform national and global policy by involving stakeholders such as policymakers, implementers, and oxygen users, and by analyzing the costs and impacts of these strategies over four years. The study uses a mixed-methods approach with three embedded sub-studies: stakeholder analysis to understand the policy environment; policy-implementation gap analysis to examine differences between policy goals and actual practices; and comparative country case studies to identify unique challenges and solutions across different contexts. Researchers will employ co-design methods and annual stakeholder meetings to adapt the study to each country's needs. Participants, who are key informants from government, non-governmental agencies, professional groups, private sector, and civil society, will be interviewed at national, provincial, and local levels. Data collection includes interviews, policy reviews, program data, and surveys on facility readiness and clinical practices. The study will provide lessons and validated findings through national stakeholder dialogues and aims to improve medical oxygen service coverage and program implementation across countries.

Researchers are studying febrile illness in rural communities across South and Southeast Asia, including Cambodia, Laos, Myanmar, and Bangladesh. This extensive study aims to understand how common febrile illness is, what causes it, and what effects it has on people living in these areas. The research is funded by the UK Wellcome Trust and seeks to gather information on febrile illness on a scale never before attempted in these regions. The study focuses on Work Package A (WP-A), which operates at the community level by involving village health workers and small health centers. Patients who show signs of fever are recruited and assessed for symptoms. Since collecting specimens for diagnosis is challenging in these rural settings, the study uses finger-prick blood tests similar to existing rapid diagnostic tests, while also collecting dried blood spots for further testing. This approach helps identify various pathogens causing the febrile illness. Participants will be observed over time to track the incidence and outcomes of febrile illness. Researchers will measure how often febrile illness occurs locally and overall during the two-year period, as well as mortality and morbidity within one month after the patient first presents to a health worker or facility. The study involves clinical assessments and specimen collection to help improve future diagnosis and treatment of febrile illnesses in these communities.

In Lao People's Democratic Republic, tobacco smoking is common among adult men and women, creating an urgent need for effective and sustainable quitting methods. This study is evaluating a mobile health (mHealth) intervention designed to help adults quit smoking cigarettes. The project includes two phases: an initial phase to adapt the intervention to local culture and language, and a second phase to test the intervention's effectiveness through a randomized controlled trial (RCT) with adult smokers from two hospitals in Laos. The intervention involves two treatment groups. One group receives standard care, which includes brief advice, self-help materials based on WHO guidelines, and a two-week supply of nicotine patches. The other group receives the same standard care plus a fully automated smartphone program delivering personalized messages, images, and videos designed to boost motivation, coping skills, and reduce withdrawal symptoms over 26 weeks. The first phase also includes formative research like interviews and focus groups to tailor the intervention content. Participants complete baseline assessments via tablet and receive training on smartphone use if needed. They will be followed for 12 months, with treatment lasting 6 months. Researchers will monitor smoking status, using biochemical confirmation of abstinence at 12 months as the main outcome. Weekly smartphone assessments will track participants' motivation and smoking behaviors. The study also aims to build local research capacity and improve tobacco cessation services in Laos.

Murine typhus is a disease caused by Rickettisa typhi, an obligate intracellular bacterium transmitted by rodent fleas. The disease has a worldwide distribution; however the true burden is unknown, related to its non-specific presentation and lack of access to diagnosis in many regions. A systematic review of untreated murine typhus based on observational studies of a total of 239 patients has estimated the mortality associated with the disease at between 0.4% and 3.6%. Scrub typhus is caused by Orientia tsutsugamushi and transmitted by the larval stage of chigger mites (Trombiculidae family). It has been estimated to affect at least one million people each year. A systematic review found varying reports of the mortality associated with untreated scrub typhus ranging from 0-70% (median 6%). Polymerase chain reaction (PCR) based diagnosis of rickettsial infections is only available in one centre (Mahosot Hospital) in Vientiane. A number of hospitals use a variety of point-of-care antibody tests to diagnose rickettsial infections however many of these have not been validated and they are of uncertain sensitivity and specificity. In 2006 results of a two year prospective study of 427 patients presenting to Mahosot Hospital with a febrile illness and negative blood cultures showed that 115 (27%) patients had an acute rickettsial infection, confirmed by serological testing. Among these patients, 41 were diagnosed with murine typhus and 63 with scrub typhus. Antibacterial agents with activity against rickettsial pathogens include doxycycline, azithromycin, chloramphenicol and rifampicin. Azithromycin is often reserved for pregnant women or children below the age of 8 years due to lasting concerns after the tetracycline-associated staining of growing bones and teeth in the past. Evidence is accumulating that doxycycline is superior to azithromycin for the treatment of rickettsial disease. Clinical treatment failures have occurred following azithromycin treatment of murine typhus. The relationship between rickettsial bacteria load and both disease severity and response to treatment has not been characterised. Rickettsial concentrations in blood are generally low, of the order of 210 DNA copies/mL blood for R. typhi and 284 DNA copies/mL blood for O. tsutsugamushi. At present, there is no standard antibiotic susceptibility testing (AST) method for R. typhi and O. tsutsugamushi. The gold standard method for AST for Rickettsia pathogens is the plaque assay which determines minimal inhibitory concentration (MICs) from the smallest antimicrobial concentration inhibiting rickettsial plaque forming unit formation. This method is laborious and time consuming, taking approximately 14-16 days based on species to yield a result. Molecular detection methods are useful for diagnosing patients infected with rickettsial pathogens and has been applied for antibiotic susceptibility testing. Antibiotic susceptibility testing based on DNA synthesis inhibition detecting by quantitative PCR (qPCR) for O. tsutsugamushi clinical isolates has been reported. However, the relationship between antibiotic susceptibility profiles and treatment response has not been studied. There is a need to develop a reliable ex vivo method to characterize the treatment response and compare susceptibility of R. typhi and O. tsutsugamushi to different agents.

Researchers are evaluating the optimal dose of tafenoquine for the radical cure of Plasmodium vivax malaria in Southeast Asia. Tafenoquine is a recently approved drug that targets the dormant liver stage of P. vivax and offers the advantage of a single-dose treatment compared to the 14-day course of primaquine. The study aims to compare the currently recommended tafenoquine dose of 300 mg to a 50% higher dose to determine which provides better efficacy in this region, where higher doses of primaquine are typically needed for cure. A total of 700 participants will be randomly assigned to receive either the standard 300 mg dose or a higher 450 mg dose of tafenoquine, given as a single dose based on weight bands. Participants will also receive a schizonticidal agent, either chloroquine or artemether-lumefantrine, depending on the study site. Drug administration will be directly observed by study staff. Follow-up visits will occur daily until malaria parasites are cleared, then on days 7, 14, 21, 28, and monthly up to month 4. Participants will be monitored for adverse events, medication adherence, and parasite recurrence during this period. Throughout the study, participants will undergo medical history review, vital sign checks, physical exams, blood sampling, and laboratory testing, including glucose-6-phosphate dehydrogenase levels and pregnancy tests for eligibility. Researchers will track malaria recurrence by microscopy up to four months after treatment to assess efficacy. Safety will be monitored continuously, and participants with adverse events will receive appropriate follow-up care. The total study duration for each participant is four months from enrollment, regardless of any malaria recurrence episodes.