Ascariasis
Conditions
Keywords
soil-transmitted helminths, Ascaris lumbricoides, anthelminthic, ivermectin, albendazole
Brief summary
The goal of this prospective follow-up study nested within an open-label randomized controlled trial is to investigate the unexpectedly high prevalence of Ascaris lumbricoides infection observed 3-4 months after school-based mass drug administration with ivermectin plus albendazole (IVM-ALB) or albendazole alone (ALB) in Kisoro District, South-Western Uganda. By assessing initial treatment response and subsequent infection dynamics, the study will help clarify whether reduced drug efficacy, suboptimal treatment coverage, reinfection, or a combination of these factors may explain the previous findings. The main questions the study aims to answer are: * How effective are IVM-ALB and ALB against A. lumbricoides at 3 weeks, based on egg reduction and cure rates? * How often do A. lumbricoides and other soil-transmitted helminth infections recur by 3 months? * How effective are the treatments against Trichuris trichiura and hookworm? * What can genetic characterization of Ascaris eggs reveal about parasite populations and potential drug resistance markers? The study will enrol 450 pupils aged 5-14 years from three primary schools, which participated in the previous mass drug administration evaluation. In each school, 150 pupils will be randomly assigned equally to receive a single oral dose of: * ivermectin (200 µg/kg) plus albendazole (400 mg); or * albendazole (400 mg) alone. Each treatment arm will include 225 pupils overall. Children will be included regardless of baseline infection status, following parental/guardian informed consent and child assent. Other pupils will receive routine albendazole under national deworming guidelines. Stool samples will be collected before treatment and at 3 weeks and 3 months. Duplicate Kato-Katz thick smears will quantify A. lumbricoides, T. trichiura and hookworm eggs. The primary outcome is the arithmetic mean egg reduction rate for A. lumbricoides at 3 weeks. Secondary outcomes include cure rates at 3 weeks, reinfection rates at 3 months, egg reduction and cure rates for T. trichiura and hookworm, and genetic characterization of Ascaris populations and potential resistance markers. Adverse events will be recorded through passive safety monitoring.
Interventions
Albendazole 400mg manufactured and donated by GlaxoSmithKline (GSK) to WHO
DRUGIvermectin 3 mg
World Health Organization Pre-Qualification (WHO PQ) recommended ivermectin 3mg tablets will be used together with albendazole 400mg tablets as provided by WHO for Neglected Tropical Disease (NTD) programs.
Sponsors
Jennifer Keiser
Vector Borne & Neglected Tropical Disease Control Division, Ministry of Health, Uganda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The study team members involved in the treatment will be aware of the treatment allocation of the study participants (also due to the nature of the treatment with a single tablet (ALB arm) vs several tablets of IVM plus one ALB tablet according to height category), the outcome assessors, however, will not know which samples belong to which arm.
Intervention model description
Prospective follow-up study nested within an open-label randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
5 Years to 14 Years
Healthy volunteers
Yes
Inclusion criteria
* Informed consent provided by parent/guardian and assent provided by pupil * School-aged children (5-14 years) enrolled in the respective study schools * Able and willing to provide a stool sample before and 3 weeks and 3 months post-treatment
Exclusion criteria
* Presence or signs of major systemic illness * Recent use of anthelmintic drugs in the 4 weeks before treatment * Known allergy to study medication (i.e. benzimidazoles or ivermectin) * Participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Egg Reduction Rates (ERRs) for A. lumbricoides infection at 3 weeks post-treatment | 3 weeks after treatment | Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the duplicate Kato-Katz thick smears and multiplying this number by a factor of twelve. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment. Egg reduction for A. lumbricoides infection will then be calculated as change in egg counts from baseline to 3 weeks post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants A. lumbricoides egg negative at 3 weeks post-treatment (cured) | 3 weeks after treatment | The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR). |
| Number of participants egg negative at 3 weeks with soil-transmitted helminth infections 3 months post-treatment (reinfected) | 3 months after treatment | Number of participants that converted from egg negative with Ascaris lumbricoides, Trichuris trichiura and/or hookworm infections at 3 weeks post-treatment to egg positive after 3 months. |
| Number of participants with concomitant soil-transmitted helminth infections egg negative at 3 weeks post-treatment (cured) | 3 weeks after treatment | Number of participants that converted from egg positive with Trichuris trichiura and/or hookworm infections to egg negative after 3 weeks. |
| Egg-reduction Rates (ERRs) against concomitant soil-transmitted helminth infections | 3 weeks after treatment | Percent change in arithmetic and geometric mean eggs per gram of stool from before to after treatment. ERRs will be calculated for Trichuris trichiura and hookworm infections as described in outcome 1. |
Countries
Uganda
Contacts
CONTACTJennifer Keiser, Prof.
CONTACTPeter Steinmann, Dr.
PRINCIPAL_INVESTIGATORJennifer Keiser, Prof.
Swiss Tropical & Public Health Institute
Outcome results
None listed