Clinical trials

The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

The United Nations Conventions on the Rights of the Child UN General Assembly, 1989), outlawed violence against children worldwide. Yet, 75% of all children worldwide - experience violence while growing up (Know Violence in Childhood, 2017). In Low- and Middle-Income countries prevalence rates at home and at school are higher (Hoeffler, 2017), with particularly high rates in Africa (Hecker et al., 2018; Nkuba, Hermenau, \& Hecker, 2018; Hillis et al., 2016). Violence against children is related to negative mental health outcomes, lower quality in the child-adult relationship, lower cognitive functioning, and emotional and behavioural problems that begin in childhood and may persist through adolescence until adulthood (Berlin et al., 2009; Gershoff \& Grogan-Kaylor, 2016; Hecker et al., 2016; Kim \& Cicchetti, 2010; Majer et al., 2010; Mills et al., 2011; Newbury et al., 2018; Wilson et al., 2009). The present study focuses on violent discipline in schools, as (1) many children are subjected to violent discipline at school on a regular basis, and (2) teachers justify violent discipline since they want to encourage better academic performance and maintain children's discipline (Masath et al., 2022). As in other African countries (Hecker et al., 2018; Nkuba, Hermenau, \& Hecker, 2018; Hillis et al., 2016), violent discipline is prevalent in Zambian schools, despite its prohibition in 2022 (End Corporal Punishment, 2025). With this study we test the intervention Interaction Competencies with Children - for Teachers (ICC-T; Kirika \& Hecker, 2022) to alleviate violence against children. ICC-T is a manualised 5,5 days training workshop focusing on the basic competencies in the work with children, including non-violent action alternatives. Previous cluster randomized controlled trail studies on ICC-T in Tanzania and Uganda showed that teachers who participated in ICC-T, used significantly less violent discipline measures against children compared to teachers in the control group. The transferability of the intervention to and the effectiveness in the Zambian context remains unclear. Evidence from our research may guide policy makers to implement further measures aiming at ending violence against children.

The goal of this clinical trial is to learn if a program called Kupambana can improve mental health and HIV care outcomes in young people with HIV in Zambia by combining stigma-reduction support with financial and job-skills training. The main questions it aims to answer are whether Kupambana is feasible and acceptable to young people with HIV and whether it improves mental health, reduces stigma, and improves progress along the HIV care continuum, such as staying in care and taking HIV medicine as prescribed. Researchers will compare young people who participate in Kupambana with those who receive a one-time financial literacy training session (usual care) to determine whether Kupambana leads to greater improvements in stigma, mental health, and HIV care outcomes. Participants will complete a baseline questionnaire and then be randomly assigned to either the Kupambana program or the one-time financial literacy training. Those assigned to Kupambana will attend eight weekly peer-led support group sessions focused on reducing HIV- and poverty-related stigma, receive a voucher for technical and vocational education and training, and attend a one-time financial literacy session. Those assigned to the comparison group will attend only the one-time financial literacy session. All participants will complete follow-up surveys at the end of the program and again 3 and 6 months later.

Cognizant of the prevalence of complicated non communicable diseases (NCD) and the attendant capacity problems faced by the health workers in primary care settings, we propose to adapt and pilot the Package of Essential Non-communicable Diseases (PEN) Plus intervention using the Interactive Systems Framework (ISF) and then implement and monitor the impact. The ISF framework proposes and organizes several implementation strategies to achieve Evidence Based Implementation (EBI) adaptation. We will apply these strategies at 2 first level hospitals (Peri-Urban and Rural) to ensure local adaptation and work towards scaling up of the WHO-PEN Plus in the rest of Zambia. This process will be inclusive, involving a Stakeholder Consultation Group that shall include the Zambian Non-Communicable diseases and injuries (NCDI) Poverty Commission and shall report bi-annually to a Project Advisory Board (PAB) chaired by the Permanent Secretary of the Ministry of Health.

Background and rationale:The World Health Organisation (WHO), estimates influenza global deaths at 290,000 to 650,000 annually. Although influenza is mostly associated with upper respiratory tract infections (URTIs), its role in lower respiratory tract infections (LRTIs) and the associated poor clinical outcomes have been overlooked in sub-Saharan Africa. A study conducted in eight SSA countries estimated that 8.2% of cases and 2.8% of deaths from LRTIs were due to primary infection with influenza. Pneumonia and influenza-associated illness are responsible for 8.5% of respiratory deaths in Zambia. However, in routine practice, testing to distinguish between bacterial and viral etiology of RTIs is seldom done outside sentinel surveillance due to the high cost and lack of available testing options. This consequently underestimates viral RTIs in the population. It is particularly important to diagnose flu early on in vulnerable populations so that they receive timely and appropriate medical care. Although Zambia is a high HIV burden country with a prevalence of 11%, there is presently no study that has described the burden of influenza in the HIV positive population. This research study will address gaps in current scientific knowledge, providing key insights about the prevalence, circulating types, seasonality and associated clinical outcomes of influenza, RSV and SARS-CoV-2 infection in Zambia in the post COVID-19 era. Objectives Primary To determine the prevalence of influenza (A and/or B) infections in a high HIV burden setting in Lusaka, Zambia over one or more influenza seasons. Secondary 1. To determine the prevalence of influenza co-infection with RSV and/or SARS-CoV-2 2. To determine the clinical outcomes of influenza (A and/or B) infection among Zambian adults, with and without co-infection with RSV and COVID-19, by HIV and COVID-19 vaccination status. 3. To evaluate the accuracy and yield of aerosol-based sampling for diagnosis of respiratory viruses (influenza, SARS-CoV-2, and RSV) compared to nasal/ nasopharyngeal swabs, for rapid diagnosis of infection among symptomatic individuals in Zambia. 4. To evaluate the acceptability of exhaled breath aerosol (XBA) sampling for diagnosis and screening of respiratory infections of pandemic potential. Study design and participants: Primary objective and secondary objective 1: Cross sectional surveillance study of individuals presenting with flu-like symptoms at two first level hospitals in Lusaka, Zambia. Recruitment of 594 participants will be done over the study period and participants will include both males and females presenting with 2-7 days of flu-like symptoms, able to provide informed consent, aged ≥18 years, with a known HIV status or willing to be tested, with a known COVID 19 vaccination status and available for symptom follow-up. Secondary objective 2: Prospective follow up of participants enrolled in aim 1 for 14 days will be done to document clinical symptom progression and outcomes. Appropriate care will be provided to all participants within routine care services. Secondary objective 3 \& 4: Mixed methods approach. All patients enrolled under aim 1 will be requested to provide in addition to the routine nasopharyngeal sample, an aerosol-based sample for diagnostic accuracy and yield evaluation. We will also conduct an investigator-administered questionnaire to ascertain end-user experience and preferences for either sampling method. Location Zambia (Kanyama and Chawama sub-districts) Duration April 2025 to November 2026 (Participant enrolment duration)

Cholera is a serious diarrheal disease that can be fatal within hours of onset. The current available cholera vaccines to prevent the disease are not very effective. Panchol is a new oral cholera vaccine that may be an improvement over the currently available vaccines in use. The goal of this study is to learn safety of this new oral cholera vaccine and the body's immune response to the vaccine. The researchers will compare the PanChol vaccine to placebo to see the side effects experienced in participants. The participants will be adults aged between 18 and 55 years and they will be required to: 1. Be admitted to hospital until they stop passing the cholera vaccine in their stool. During admission, all side effects will be recorded by the researchers. 2. After discharge, the participants will visit the research site every month for 3 months with an optional visit at the 4th month for the researchers to assess the participants' general health.

Adults who are hospitalized in Lusaka, Zambia, and found to have advanced HIV disease will be enrolled and randomly assigned to receive the ARC intervention or standard of care. All participants will then be followed through the end of the hospitalization and for up to 1 year after discharge from hospital.

While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

This study aims to characterize the pediatric cryptosporidiosis disease profile with respect to clinical presentation.

Purpose: The primary objective of this study is to assess the diagnostic accuracy of an AI-enabled ultrasound tool for estimating fetal weight Participants: 1,000 pregnant individuals Procedures (methods): This prospective diagnostic accuracy study will enroll 1,000 pregnant individuals within one week of anticipated delivery. At a single visit, each participant will undergo two ultrasound assessments: (1) standardized sweeps for AI analysis (performed by both specialist and nonspecialist users), (2) specialist-performed fetal biometry.

Question: How effective is fortified iodized salt with folic acid (FISFA) in increasing serum and red blood cell folate in non-lactating, non-pregnant women of reproductive age in the country of Zambia who do not have active food fortification with a folic acid program? Participants will: * Consume salt with folic acid instead of their regular salt for 6 months * Have a blood draw 4 times * Fill out surveys

CHIME is a randomized, parallel-arm, double-blind, placebo-controlled trial focused on infants with hypoxic ischemic encephalopathy (HIE). The trial will recruit neonates who are diagnosed with HIE within six hours after birth based on physiologic criteria (acidosis noted on an umbilical cord or early \[\<1 hour\] postnatal blood sample) and neurologic criteria (modified Sarnat exam consistent with encephalopathy). Following informed consent, and by six hours after birth, neonates with HIE will be randomized to one of two treatment arms and subsequently receive one 20 mg/kg dose of oral caffeine followed by two additional 10 mg/kg doses at 24-hour intervals or placebo of the same regimen (three total doses). The goal of this clinical trial is to compare the incidence of all-cause mortality OR moderate to severe neurodevelopmental impairment (NDI) at 18-22 months between neonates with HIE who are randomized to oral caffeine or placebo. Our hypothesis is that neonates with HIE who receive oral caffeine will have 10% lower incidence of all-cause mortality or moderate to severe NDI at 18-22 months compared to placebo.

The goal of this clinical trial is to learn if extended admission to the Kangaroo Mother Care (KMC) ward helps to prevent postpartum depression in mothers of low birthweight infants in a low-resource setting whose newborns were admitted to the neonatal intensive care unit (NICU) more than standard of care KMC. The main questions it aims to answer are: * Does longer KMC decrease the incidence of postpartum depression in mothers of low birthweight infants in a low-resource setting? * Does longer KMC improve neurodevelopmental outcomes of low birthweight infants at 6, 12, and 18 months in a low-resource setting? * What are the barriers to practicing KMC in low birthweight infants following hospital discharge in a low-resource setting? * What is the prevalence of paternal depression in a low resource setting? * Is it cost effective to admit preterm mother-infant dyads to the KMC ward following NICU discharge? Researchers will compare (extended admission to the KMC ward) to (standard of care KMC) to see if extended KMC decreases PPD in mothers of preterm infants in low-resource settings. Participants (infants) will: * At time of discharge from the NICU, when clinically stable, spend either \< 2 days in the KMC ward with their mothers or spend longer in the KMC ward until discharge. * Return to clinic at routine follow-up visits (at 2 weeks and at 6-8 weeks) where mothers will be screened for postpartum depression and fathers will be screened for depression. * Return to clinic for neurodevelopmental screening at 6, 12, and 18 months where mothers will be screened for postpartum depression and perceived social support and fathers will be screened for depression.

The goal of this clinical trial is to learn if caffeine citrate prevents apneic events that result in sick visits in moderately preterm infants after discharge from the hospital. It will also learn if the use of caffeine leads to better developmental outcomes at 12 months of age. Our research questions are: 1. Does continued treatment of moderately preterm newborns with caffeine citrate after hospital discharge prevent or decrease apneic events that result in sick visits? 2. Will the continued use of caffeine citrate lead to improved developmental outcomes among infants at 12 months of age? Researchers will compare caffeine citrate to a placebo (a look-alike substance that contains no drug) to see if caffeine citrate prevents apneic spells which result in healthcare visits. Parents of participants will: 1. Administer caffeine citrate 20mg/kg/day or a placebo (equivalent volume of sterile water) orally every day for up to 28 days after hospital discharge 2. Keep a diary of symptoms and any apneic events 3. Check in with researchers via telephone call once a week 4. Return to clinic for infant physical examination at 28 days 5. Return to the clinic for infant physical examination at 2 months 5\. Return to clinic for infant neurodevelopmental examination with Ages and Stages Questionnaire at 12 months of age

Access to quality antenatal care (ANC) and postnatal care (PNC), including maternal, newborn, and infant services, is integral to reducing adverse pregnancy-related health outcomes and promoting positive birth experiences. The World Health Organization (WHO) recommends a total of eight ANC visits for pregnant women. However, the ANC coverage rate remains considerably lower among more vulnerable populations, and the quality of care that women receive is inconsistent, often poor, and frequently fails to detect risks in a timely fashion or adequately prepare women for the birth process. While rates of facility-based delivery are on the rise worldwide, disparities persist and the quality of care across facilities remains uneven. Even less information is available on PNC, where services beyond routine immunizations may not be widely available, especially in resource-poor regions. Additionally, limited evidence exists on innovative service delivery approaches and how to effectively scale tested maternal and newborn health (MNH) interventions. This coupled with the fragmented datasets from smaller studies limit our ability to advocate for policy change. The Pregnancy Risk Stratification Innovation and Measurement Alliance (PRiSMA) is implementing a harmonized open cohort study that seeks to evaluate pregnancy risk factors and their associations with adverse pregnancy outcomes, including stillbirth, neonatal mortality and morbidity, and maternal mortality and severe morbidity. The goals are to develop a harmonized data set to improve understanding of pregnancy risk factors, vulnerabilities, and morbidity and mortality and to estimate the burden of these risk factors and outcomes in LMICs. Ultimately, these data will inform development of innovative strategies to optimize pregnancy outcomes for mothers and their newborns.

The Rotavirus SpatioTrasncriptomics (Rota-Omics) study is a multidisciplinary research project aimed at understanding why oral rotavirus vaccines perform less effectively in some low- and middle-income countries, including Zambia. Rotavirus remains one of the leading causes of severe diarrheal disease in infants and young children worldwide, despite the widespread introduction of vaccines such as Rotarix® and Rotavac®. Although these vaccines have greatly reduced childhood deaths in many countries, vaccine effectiveness is often lower in settings where the burden of disease is highest. Understanding the reasons behind this reduced protection is critical for improving child health globally. A major focus of the study is Environmental Enteropathy (EE), also known as Environmental Enteric Dysfunction (EED), a chronic inflammatory condition of the small intestine that is common in low-resource settings. EE is associated with damage to the intestinal lining, chronic immune activation, poor nutrient absorption, and impaired gut barrier function. These changes are thought to interfere with the body's ability to respond effectively to oral vaccines, which rely on strong intestinal immune responses. The RotaOmics study uses a systems biology approach to investigate how the immune system, gut microbiome, nutrition, and intestinal inflammation interact to influence rotavirus vaccine responses. The term "omics" refers to advanced technologies that allow researchers to study genes, proteins, microbes, and other biological processes at a large scale. By combining these approaches, the study aims to identify biological markers and immune pathways associated with strong or weak vaccine responses. The study involves the collection of samples such as blood, stool, saliva, and breast milk from mothers and infants at different time points before and after vaccination. These samples are analysed using laboratory methods including antibody testing, molecular pathogen detection, microbiome sequencing, and immune profiling. The study also evaluates markers of gut inflammation and intestinal health. One important goal of the project is to identify correlates of protection, which are measurable biological indicators that predict whether a vaccine is likely to protect against disease. Identifying these markers could help guide the development of improved vaccines or supportive interventions to enhance vaccine performance in vulnerable populations. The study also contributes to a broader understanding of mucosal immunity, which refers to immune responses occurring in the gastrointestinal tract. Since many enteric infections begin in the gut, understanding intestinal immune function is important not only for rotavirus vaccines but also for other oral vaccines and diarrheal diseases. In addition to its scientific objectives, RotaOmics includes a strong capacity-building component. The project supports training for local scientists, clinicians, and laboratory personnel in areas such as molecular biology, immunology, genomics, bioinformatics, and data analysis. By strengthening local research expertise and infrastructure, the study aims to support long-term scientific development and improve regional capacity for infectious disease research and outbreak response. Overall, the RotaOmics study seeks to generate new insights into why oral rotavirus vaccines underperform in some settings and to identify strategies that may improve vaccine effectiveness and child health outcomes in Zambia and similar regions worldwide.

In Zambia, an estimated 20% of HIV-positive clients continue to present for first-time antiretroviral therapy (ART) initiation or re-initiation with advanced HIV disease (AHD). The Zambia Ministry of Health (MOH) and other key stakeholders lack information about the characteristics and behaviors of AHD clients, including how they are defined and diagnosed (e.g. low CD4 count v. clinical condition), their demographic and socioeconomic profiles, their HIV care histories, what services they receive, and their short-term outcomes (achieve viral suppression, remain AHD, disengage from care, die) and the timing of these outcomes. The Retain6 project aims to improve HIV treatment outcomes during clients' first six months on ART, when disengagement from care and mortality are highest. This protocol, called Advanced HIV disease during the first six months on antiretroviral therapy in Zambia (AHD Zambia), describes an observational study that will describe the experiences of clients who are diagnosed with AHD upon ART initiation (or re-initiation) in Zambia. Data collected will include clinical and socioeconomic characteristics, clinical and non-clinical needs, services delivered and received, and clients' and providers' concerns and preferences. The study's overall goal is to provide information to the Zambia MOH, treatment program partners, providers, and other stakeholders to better understand who is presenting with AHD in Zambia, how they are currently managed, and their treatment outcomes after starting ART. This information will be useful in determining interventions and guideline changes that might improve short- and long-term outcomes for AHD patients. The study, which will be conducted in collaboration with the Zambia MOH, will include retrospective file reviews, prospective quantitative surveys with outpatient and inpatient clients, qualitative focus group discussions (FGDs) and interviews with clients, and provider surveys and interviews.

Observational cohort of adults with acute and chronic hepatitis B infection in Zambia, with and without HIV coinfection. Participants join the study at the time of diagnosis and before or at the time when they are starting antiviral treatments and then they are followed up over multiple years to assess changes to their liver and evolution of HBV (and HIV if applicable) infection. All treatments for HBV and HIV are standard per local Ministry of Health guidelines.

The study aims 1) to adapt, 2) to develop implementation strategies for and 3) to evaluate the effect of implementing a practice guideline for acute abdomen at primary care level in Zambia. We employ a sequential exploratory mixed method study design. Qualitative and quantitative data from health care workers will be used to adapt a practice guideline developed in a high-income into a low- and middle-income (LMIC) context and to develop strategies for successful implementation. The primary outcome of interest is the prospective change in length of stay in hospital among patients presenting with acute abdomen in the intervention site compared to the control site. The study will address the scarcity of literature on practice guidelines for acute abdomen in the LMIC context. The implementation of an adapted guideline may contribute to a reduction of the morbidity and mortality rates associated with acute abdomen in this setting by increasing management capacity at the primary care level.

To reduce the burden of TB worldwide through more accurate, faster, simpler, and less expensive diagnosis of TB Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) brings together experts in TB care, technology assessment, diagnostics development, laboratory medicine, epidemiology, health economics and mathematical modeling with highly experienced clinical study sites in 10 countries.

The Long-Covid (LC)-Revitalize clinical study is testing repurposed drug treatments for Long Covid, involving adult participants from Brazil, Canada, Italy, Uganda, the United States, and Zambia. To qualify, participants must have had Covid-19 and experienced Long Covid symptoms for at least three months. The main goal of the study is to determine whether the drug treatments can improve symptoms in five key areas: 1) fatigue, 2) breathing, 3) memory, thinking, and communication, 4) muscle and joint pain, and 5) circulation. A secondary goal is to assess changes in the body, such as reducing inflammation, as well as to confirm the safety and tolerability of the treatments. In the first phase, 348 participants will take either one of two existing medications (upadacitinib or pirfenidone) or a placebo (a pill with no active ingredient) for three months. Although these medications are not yet approved for Long Covid, they are authorized for use in treating other health conditions. This study is adaptive, meaning it may adjust based on early results. In the second phase, the study could continue testing the most effective drug(s) against a placebo with new participants, explore combinations of drugs to see if they improve results, or discontinue the drugs if they prove ineffective or unsafe and test alternative treatments.

The purpose of this study is to evaluate whether antibiotic treatment of non-dysentery Shigella associated watery diarrhea (NDSD) cases improves clinical outcomes and growth in children. Children with NDSD seeking care for diarrhea at the study hospitals in Bangladesh and Zambia will be enrolled and randomized to receive Azithromycin or placebo (a look-alike substance that contains no drug). Enrolled children will be followed for three months with household visits. The investigators will determine whether antibiotic treatment of NDSD reduces the duration of diarrhea and time to microbiological cure (shedding of Shigella in stool), and whether it improves growth in children compared with the placebo group.

The goal of this study is to compare the immune response of the single dose of the CERVAVAC vaccine with the single dose of Gardasil vaccine in girls/women aged 9 to 20 and boys aged 9 to 14 at 6 months, 12 months and 24 months post vaccination. The vaccine will be given randomly to the boys and girls/women in these age group and they will be followed up to check the immune status developed in them after vaccination. The status of immune response developed by the two differnet vaccines will be compared in these group of participants of the study.

The Decide-TB project aims to generate evidence for the implementation of a comprehensive Treatment Decision Algorithms (TDA) based approach for TB in children living in high TB burden and resource-limited countries, at District Hospital (DH) and Primary Health Centre (PHC) levels, and to facilitate the integration of this evidence within practices and policies. This programmatic pilot led by the National TB Programs (NTP) will test a TDA-based approach integrating TB screening, diagnosis, treatment decision-making, and disease severity assessment for shorter treatment eligibility, for use at a lower level of healthcare. This TDA-based approach will be evaluated in a hybrid effectiveness implementation study based on a pragmatic stepped wedge cluster-randomized trial. The Decide TB project will be implemented at the district level, targeting five districts in each country. Each cluster in a district will be made up of one district hospital and six primary health centers. The study will develop a Clinical Decision Support System (CDSS) to operationalize the use of TDAs, and strengthen District Health Information Systems (DHIS2) to collect individual data, which will contribute to monitoring and evaluation, clinical mentoring, and supervision by the country's NTPs.

Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) study seeks to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests.