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COHORT SUMMARY
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COHORT SUMMARY | |
Section Title | Description |
Source population | Pregnant women |
Study Location | Entebbe |
Study Period | 01/04/2003 – 30/04/2011 |
Protocol title | The effect of worm infections during pregnancy on immunisations and infections in infants |
Protocol serial number | 064693 |
Short Title | Entebbe Mother and Baby Study (EMaBS) |
Study design | Randomised controlled trial |
Sponsor | London School of Hygiene and Tropical Medicine (UK) |
Funder | Wellcome Trust (grant refs: 079110 and 095778) |
Implementing Institution | MRC/LSHTM &UVRI Uganda Research Unit |
Background /Rationale | The Entebbe Mother and Baby Study (EMaBS) was established in 2003 to investigate how worm infections during pregnancy and early childhood affect immune responses. The study examined whether these infections influence responses to immunisations, susceptibility to other infections, and the development of allergies in children. Researchers tested this by evaluating the effects of deworming treatments given during pregnancy and early childhood, with interventions continuing until the children reached five years of age. Follow-up studies have since tracked participants into adolescence and adulthood to understand long-term health effects. Over more than two decades, EMaBS has developed into a major research platform for studying how early-life exposures such as worms and malaria influence health later in life. Please see protocol paper: https://doi.org/10.1186/ISRCTN32849447
For more information on the study, please visit https://www.lshtm.ac.uk/research/centres-projects-groups/emabs
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Primary Objective | That helminth infection in pregnancy and in early childhood affects the immune response to childhood vaccines and susceptibility to disease in childhood. |
Intervention type | Drug |
Intervention | 1. Randomised, double-blind, placebo controlled trial of albendazole versus placebo and praziquantel versus placebo during pregnancy (all mothers treated with both six weeks after delivery) |
Drug / device / biological / vaccine name(s) | Albendazole, praziquantel |
Primary outcome measure(s) | Current primary outcome measure(s): |
Key secondary outcome measure(s) | Current secondary outcome measure(s): |
Study Site and infrastructure | Entebbe Grade A hospital |
Target Population | Pregnant women and their children |
Eligibility criteria | Inclusion criteria 1.Pregnant women (aged 14 to 47 years) in the second or third trimester
Exclusion criteria 1. Anaemia (more than or equal to 8 g/dl), bloody diarrhoea |
Recruitment and enrollment | 2500 |
Follow-up procedures | Children data: Age 1(one) – 5(five)years Clinical / Questionnaire data Enrolled infants in the Entebbe Mother and Baby Study attended clinic follow-up visits where comprehensive maternal and child health data were collected. Maternal status was documented as well, sick, or deceased (including date of death where applicable), while the child’s general health status was recorded. Anthropometric measurements, including weight, height or supine length, head circumference, and mid-upper arm circumference (MUAC) were taken, and stool and blood samples were collected for laboratory analysis. Immunisation history was reviewed, including completion of routine vaccines, number of BCG doses received (with 99 recorded if uncertain), presence, number, and size of BCG scars, and any BCG-related complications such as ulcers, abscesses, or lymphadenopathy. Information was also gathered on illnesses and treatments during the preceding year, including malaria (slide-confirmed), diarrhoea, pneumonia, measles, tuberculosis, worm treatment, and symptoms such as wheezing, itchy eyes, or itchy rash. At age five, additional data were collected on schooling (nursery/preschool attendance), use of cotrimoxazole preventive therapy (PCP prophylaxis), antiretroviral therapy (ART) status, frequency of sleeping under a mosquito net, other household mosquito control measures, frequency of contact with the lake, and history of treatment for bilharzia. Caregivers were also asked whether they consented to return the child for further growth and developmental assessment.
Laboratory data In addition to clinical and questionnaire data, detailed laboratory investigations were conducted. Full blood count parameters included white and red blood cell counts, haemoglobin, haematocrit, mean cell volume, mean cell haemoglobin, mean corpuscular haemoglobin concentration, platelet count, mean platelet volume, and differential counts (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), alongside CD4 and CD8 cell counts. Parasitological assessments covered detection and quantification of microfilariae (including Mansonella perstans), malaria slide results with parasite counts per 200 white cells and species identification, and stool examinations for Schistosoma mansoni, Ascaris, hookworm, Trichuris, Strongyloides, Trichostrongylus, and other worm infections, including composite indicators such as any worm infection and albendazole-susceptible worm infection. Immunological analyses measured cytokine responses—interferon-gamma (IFN-γ), interleukin-5 (IL-5), interleukin-13 (IL-13), and interleukin-10 (IL-10)—to crude culture filtrate proteins (cCFP) and tetanus toxoid, including raw, standardised, and log-transformed (log[standardised response +1]) values to support robust statistical analysis.
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Key findings | 1.Antenatal albendazole treatment was associated with increased risk of infantile eczema. The authors suggested this may reflect a protective immune-regulatory effect of maternal helminth exposure during pregnancy, although a direct effect of albendazole could not be excluded
2. Maternal hookworm infection appeared protective against childhood eczema and modified allergy risk factors. Children born to mothers with hookworm had a lower incidence of eczema.
3. Deworming in pregnancy did not produce the expected improvements in childhood vaccine responses or common childhood infections. Apart from a few specific effects, there was little evidence of benefit for immunizations or infection outcomes.
4.Quarterly albendazole treatment in preschool children reduced clinical malaria incidence. This was an unexpected secondary benefit observed during follow-up.
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Publications | 1.Elliott AM, Kizza M, Quigley MA, Ndibazza J, Nampijja M, Muhangi L, Morison L, Namujju PB, Muwanga M, Kabatereine N, Whitworth JA. The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]. Clin Trials. 2007;4(1):42-57. doi: 10.1177/1740774506075248. PMID: 17327245; PMCID: PMC2643383.
3. Elliott AM, Namujju PB, Mawa PA, Quigley MA, Nampijja M, Nkurunziza PM, Belisle JT, Muwanga M, Whitworth JA; Mother and Baby study team. A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to Bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]. BMC Infect Dis. 2005 Dec 21;5:115. doi: 10.1186/1471-2334-5-115. PMID: 16371154; PMCID: PMC1352364.
4. Muhangi L, Woodburn P, Omara M, Omoding N, Kizito D, Mpairwe H, Nabulime J, Ameke C, Morison LA, Elliott AM. Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. Trans R Soc Trop Med Hyg. 2007 Sep;101(9):899-907. doi: 10.1016/j.trstmh.2007.03.017. Epub 2007 Jun 6. PMID: 17555783; PMCID: PMC1950430.
5. Tweyongyere R, Mawa PA, Emojong NO, Mpairwe H, Jones FM, Duong T, Dunne DW, Vennervald BJ, Katunguka-Rwakishaya E, Elliott AM. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial. BMC Infect Dis. 2009 Mar 18;9:32. doi: 10.1186/1471-2334-9-32. PMID: 19296834; PMCID: PMC2666740.
5. Ndibazza J, Muhangi L, Akishule D, Kiggundu M, Ameke C, Oweka J, Kizindo R, Duong T, Kleinschmidt I, Muwanga M, Elliott AM. Effects of deworming during pregnancy on maternal and perinatal outcomes in Entebbe, Uganda: a randomized controlled trial. Clin Infect Dis. 2010 Feb 15;50(4):531-40. doi: 10.1086/649924. PMID: 20067426; PMCID: PMC2857962.
6. Webb EL, Mawa PA, Ndibazza J, Kizito D, Namatovu A, Kyosiimire-Lugemwa J, Nanteza B, Nampijja M, Muhangi L, Woodburn PW, Akurut H, Mpairwe H, Akello M, Lyadda N, Bukusuba J, Kihembo M, Kizza M, Kizindo R, Nabulime J, Ameke C, Namujju PB, Tweyongyere R, Muwanga M, Whitworth JA, Elliott AM. Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jan 1;377(9759):52-62. doi: 10.1016/S0140-6736(10)61457-2. Epub 2010 Dec 20. PMID: 21176950; PMCID: PMC3018567.
7. Mpairwe H, Webb EL, Muhangi L, Ndibazza J, Akishule D, Nampijja M, Ngom-wegi S, Tumusime J, Jones FM, Fitzsimmons C, Dunne DW, Muwanga M, Rodrigues LC, Elliott AM. Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results. Pediatr Allergy Immunol. 2011 May;22(3):305-12. doi: 10.1111/j.1399-3038.2010.01122.x. Epub 2011 Jan 23. PMID: 21255083; PMCID: PMC3130136.
8. Tweyongyere R, Mawa PA, Kihembo M, Jones FM, Webb EL, Cose S, Dunne DW, Vennervald BJ, Elliott AM. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial. BMC Infect Dis. 2011 Sep 2;11:234. doi: 10.1186/1471-2334-11-234. PMID: 21888656; PMCID: PMC3176493.
9. Elliott AM, Ndibazza J, Mpairwe H, Muhangi L, Webb EL, Kizito D, Mawa P, Tweyongyere R, Muwanga M; Entebbe Mother and Baby Study Team. Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child? Parasitology. 2011 Oct;138(12):1499-507. doi: 10.1017/S0031182011001053. Epub 2011 Aug 3. PMID: 21810307; PMCID: PMC3178871.
10. Webb EL, Kyosiimire-Lugemwa J, Kizito D, Nkurunziza P, Lule S, Muhangi L, Muwanga M, Kaleebu P, Elliott AM. The effect of anthelmintic treatment during pregnancy on HIV plasma viral load: results from a randomized, double-blind, placebo-controlled trial in Uganda. J Acquir Immune Defic Syndr. 2012 Jul 1;60(3):307-13. doi: 11.1097/QAI.0b013e3182511e42. PMID: 22728750; PMCID: PMC3383620.
12. Kizito D, Tweyongyere R, Namatovu A, Webb EL, Muhangi L, Lule SA, Bukenya H, Cose S, Elliott AM. Factors affecting the infant antibody response to measles immunisation in Entebbe-Uganda. BMC Public Health. 2013 Jul 1;13:619. doi: 10.1186/1471-2458-13-619. PMID: 23816281; PMCID: PMC3733798.
13. Millard JD, Muhangi L, Sewankambo M, Ndibazza J, Elliott AM, Webb EL. Assessing the external validity of a randomized controlled trial of anthelminthics in mothers and their children in Entebbe, Uganda. Trials. 2014 Aug 6;15:310. doi: 10.1186/1745-6215-15-310. PMID: 25100338; PMCID: PMC4138365.
14. Nash S, Mentzer AJ, Lule SA, Kizito D, Smits G, van der Klis FR, Elliott AM. The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial. PLoS Negl Trop Dis. 2017 Feb 8;11(2):e0005213. doi: 10.1371/journal.pntd.0005213. PMID: 28178298; PMCID: PMC5298230.
15. Muriuki JM, Mentzer AJ, Kimita W, Ndungu FM, Macharia AW, Webb EL, Lule SA, Morovat A, Hill AVS, Bejon P, Elliott AM, Williams TN, Atkinson SH. Iron Status and Associated Malaria Risk Among African Children. Clin Infect Dis. 2019 May 17;68(11):1807-1814. doi: 10.1093/cid/ciy791. PMID: 30219845; PMCID: PMC6522755.
16.Sekitoleko I, Komata R, Ssali I, Kyasanku R, Nakyesige R, Sewankambo M, Akello F, Twinamasiko N, Namutebi M, Tumusiime J, Akantorana C, Akurut H, Balungi PA, Akello M, Atkinson SH, Niwaha A, Wajja A, Kyegombe N, Nyirenda M, Elliott AM, Walusimbi B, Webb EL. Early-life infectious and nutritional exposures and cardiovascular risk in early adulthood in Uganda: protocol for a new round of data collection in the Entebbe Mother and Baby Study birth cohort at 21 years (EMaBS@21). BMJ Open. 2026 Apr 7;16(4):e119342. doi: 10.1136/bmjopen-2026-119342. PMID: 41946545; PMCID: PMC13064186.
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Summary of the sub-study (if any) | TB042
Each visit recorded core administrative identifiers alongside clinical assessments: vital signs, graded local injection-site reactions (pain, warmth, swelling, itching, scaling) at 30 and 60 minutes post-vaccination, systemic reactions (fever, malaise, headache, myalgia, nausea, and others) on a 0–3 scale, physical examinations across seven body systems, medical history across fourteen systems, and concomitant medications. Vaccinations were given at Day 0 (all groups) and Day 56 (second dose), documenting the product used—ChAdOx1 85A, BCG, or MVA85A—along with site, route, dose, and lot details, followed by a 60-minute post-vaccination examination. Intercurrent vaccinations (e.g. HPV, tetanus, hepatitis B, yellow fever) were tracked at interim visits, and participants completed diary cards after each vaccination recording temperature, symptom severity, and medication use, reviewed at Days 14 and 63. Extensive biological sampling supported the immunology and safety endpoints: blood for ELISpot and exploratory immunology at every visit, plus haematology, biochemistry, malaria testing, gene expression, Mansonella perstans, urine pregnancy tests, and stool for Kato-Katz. Laboratory work spanned screening tests (HIV, hepatitis B/C, malaria, urinalysis, ELISpot), full haematology and biochemistry panels, detailed immunological assays (ELISpot, ICS, and innate-immunity stimulant panels), parasitology, and a urine dipstick panel—all feeding into a final eligibility determination and group assignment, with investigator comments logged throughout. Co-Host study: Participants enrolled in the CoHost study attended screening, enrolment, and follow-up visits where clinical, laboratory, and socio-demographic data were collected. Screening data included participant identifiers, visit dates, informed consent and assent (with dates), consent for sample storage, eligibility criteria, and prior study participation. Demographic characteristics included age, sex, schooling status, education level, and contact information. Clinical assessment included vital signs (temperature, blood pressure, pulse, height, weight, and oxygen saturation). Detailed symptom data were collected, including history of COVID-19–like illness (fever, cough, sore throat, headache, breathlessness, loss of taste/smell, fatigue, and muscle aches), duration, severity, impact on daily activities, hospitalization, oxygen requirement, testing, and vaccination status. Current symptoms were assessed individually with duration, and participants reported healthcare-seeking behaviour and activity limitation. Medical history was recorded by body system, including respiratory, cardiovascular, gastrointestinal, neurological, allergic, and surgical conditions, alongside physical examination findings. Participants were issued symptom diary cards to record ongoing symptoms, which were reviewed at follow-up for completeness and frequency of symptom episodes. Biological samples collected included stool for PCR and blood samples (EDTA plasma, EDTA whole blood, and heparinised blood) for analysis and storage. Baseline data included immunisation history, deworming and malaria treatment, residential and housing characteristics, water and sanitation, household assets, parental background (tribe, education, occupation), and dietary practices. Follow-up visits (telephone and clinic) captured ongoing symptoms, COVID-19 exposure risks, diary data, repeat clinical assessments, and sample POPVAC C study: Participants enrolled in the POPVAC C study attended screening, enrolment, and follow-up visits where clinical, laboratory, and socio-demographic data were collected. Screening data included participant identifiers (PVCID and initials), visit dates, informed consent and assent (with dates) for study participation, sample storage, and genetic testing, emancipated minor status, and eligibility assessment outcomes. Demographic characteristics included age (restricted to 9–17 years), sex, and school name. Clinical assessment included vital signs (temperature, blood pressure, pulse, height, and weight), BCG scar status, and a calculated cumulative blood volume limit based on weight. Medical history was recorded by body system, including skin, respiratory, cardiovascular, gastrointestinal, neurological, allergic, and surgical conditions, with ongoing status and details captured where applicable. Physical examination findings were recorded across the same body systems. Eligibility was assessed through structured inclusion and exclusion criteria reviews. Inclusion criteria covered EMABS study membership, age range, written consent and assent, willingness to avoid pregnancy, provision of locator information, and ability to comply with study requirements. Exclusion criteria captured concurrent trial enrolment, clinically significant medical or psychiatric history, acute illness, use of immunosuppressive agents, vaccine or food allergies, prior receipt of study vaccines, keloid tendency, use of investigational products, recent blood product administration, and current lactation or pregnancy. Computed eligibility outcomes were generated separately for inclusion, exclusion, and laboratory criteria and combined into a final enrolment outcome. Biological samples collected included stool for PCR and storage, and blood samples (EDTA plasma, EDTA whole blood, heparinised blood, and Tempus tube whole blood) for immunological analysis and storage. Urine samples were collected for pregnancy testing, yellow fever vaccine viral load assessment, and lactulose/mannitol ratio testing. Laboratory tests performed included a full blood count (RBC, haemoglobin, haematocrit, MCV, MCH, MCHC, white cell differential, platelets, and MPV), malaria rapid diagnostic test with microscopy if indeterminate, Mansonella filarial count, and HIV serology using three platforms with a final result recorded. Immunology laboratory data captured sample condition on receipt, availability of plasma and whole blood fractions, ELISpot assay completion, innate whole blood stimulation assay (with antigens including PAM3, FSL, LPS, Curdlan, Mannan, CpG, and PHA), and supernatant storage. Baseline socio-demographic data included immunisation history before and after school entry (BCG, polio, DPT, Hepatitis B/HiB, measles, tetanus boosters, and other vaccines), deworming and malaria treatment history (albendazole, mebendazole, praziquantel, and Coartem), and residential history at birth, early childhood, and currently. Housing characteristics captured included number of rooms, predominant wall, roof, and floor materials, toilet type, sources of drinking and washing water, lighting sources, and household assets (including car, boat, motorbike, bicycle, television, radio, mobile phone, and bed). Animal ownership and animals entering the household were recorded. Parental background data included tribe, occupation, and educational attainment for both mother and father. Dietary practices were captured through frequency of consumption of fruit, vegetables, fish, and meat, oil type used in meal preparation, and frequency of meals eaten outside the home. Vaccine administration data were recorded at each relevant visit for BCG, Yellow Fever, HPV, Oral Typhoid (three doses), and Tetanus-Diphtheria vaccines, capturing batch number, expiry date, volume, route, injection site, time of administration, and whether the vaccine was administered. Concomitant medications were recorded with drug name, dose, unit, route, start and stop dates, and reason for use. Praziquantel and albendazole administration were documented separately, including number of tablets given and reasons if not administered. Adverse events were recorded at every visit, capturing event type, onset and stop dates and times, outcome, severity, relationship to study drug or vaccine, action taken, treatments given, study withdrawal status, and escalation to a serious adverse event. Protocol deviations and violations were classified, dated, and supported by uploaded documentation. A study termination form captured completion status and, where applicable, the reason for early withdrawal, including adverse events, exclusion criteria met, loss to follow-up, death with date, consent withdrawal, or physician or sponsor decision. All instruments included administrative fields capturing staff initials and login (auto-populated via REDCap), timestamps, and form completion status at each visit across eight study events spanning screening and enrolment through to Week 52. EMaBS@21 study; Participants enrolled in the EMaBS @21 study attended screening and data collection visits where clinical, laboratory, and socio-demographic data were collected. Screening data included participant identifiers, visit dates, informed consent (with dates), consent for sample storage and genetic testing, and eligibility criteria based on prior EMaBS participation, willingness to comply, and exclusion of significant medical conditions or recent pregnancy. Clinical assessment included vital signs (temperature, blood pressure, and pulse rate) and anthropometric measurements (height, weight, waist and hip circumference). Body composition was assessed by bioelectrical impedance analysis, providing basal metabolic rate, whole-body and segmental fat percentage and mass, fat-free mass, visceral fat rating, total body water, and muscle mass for the trunk, arms, and legs, alongside reactance and resistance values at 50 kHz across multiple electrode configurations. Blood pressure was recorded in triplicate, with the mean of the second and third readings used to guide clinical action. Medical history was recorded by body system, including skin, respiratory, cardiovascular, gastrointestinal, neurological, allergic, and surgical conditions, with whether each condition was ongoing and physical examination findings where history was abnormal. Regular medication use was also documented. Biological samples collected included stool for PCR and storage, and blood samples (EDTA whole blood and plasma, heparinised blood and plasma, sodium fluoride, and SST serum) for analysis and storage. HIV testing was conducted with pre- and post-test counselling, and positive results triggered referral for HAART initiation. Sample receipt, condition, processing, and storage of derived components (EDTA pellet, EDTA plasma, heparin plasma, PBMCs, and serum) were recorded by the immunology laboratory. Laboratory investigations included fasting glucose, insulin, HbA1c, lipid profile (HDL, LDL, total cholesterol, and triglycerides), and a full blood count with differential (haemoglobin, red cell indices, platelets, total white cell count, and absolute and relative counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils). Out-of-range results triggered a clinical significance flag and were reviewed by a named clinician. Socio-demographic data included age, sex, schooling and education level, employment and occupation, additional sources of income in the past three months, household composition, housing materials, biomass fuel use and exposure, sanitation and water sources, lighting, and household assets. Participant-reported outcome data covered physical activity across work, travel, and leisure domains using the GPAQ, sedentary time, functional disability across six domains, depressive symptoms (PHQ-9), anxiety (GAD-2), and insomnia severity (ISI). Dietary practices were captured as weekly serving frequencies across ten food groups, cooking oil type, and meals eaten outside the home. Alcohol use was assessed using the full AUDIT, alongside tobacco smoking frequency and quantity, and use of substances including khat and marijuana. Participants who were temporarily ineligible were followed up via a participant status and contact form at each clinic contact until eligibility was confirmed or the participant exited the study. Exit data recorded whether the study was completed, and if not, the reason (lost to follow-up, death, withdrawal of consent, investigator decision, or other), with relevant dates and details.
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