Ignite Creation Date:
2024-05-06 @ 7:56 PM
Last Modification Date:
2024-10-26 @ 3:16 PM
Study NCT ID:
NCT06182176
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-20
First Post:
2023-12-05
Brief Title:
Effectiveness and Cost-effectiveness of Integrated Model for Malaria and Helminth Control
Sponsor:
London School of Hygiene and Tropical Medicine
Organization:
London School of Hygiene and Tropical Medicine
Study Overview
Official Title:
Evaluating the Effectiveness and Cost-effectiveness of Integrating Mass Drug Administration for Helminth Control With Seasonal Malaria Chemoprevention in Ghanaian Children
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MALHELMIN
Brief Summary:
Malaria remains a major health problem especially among children living in sub-Saharan Africa where more than 90 of the disease and deaths occur Adding to this high burden among the children is the co-existence of parasitic worms in their intestines and urinary tract The combined infection of malaria and parasitic worms in these children has additive adverse effects of anaemia poor physical and cognitive development and death Existing control programmes for the parasitic worms are operating sub-optimally despite the 2012 London Declaration on Neglected Tropical Diseases NTDs of achieving 75 treatment coverage by 2020 On the other hand a malaria prevention programme called Seasonal Malaria Chemoprevention SMC introduced in the same year as the London Declaration on NTDs has achieved more than 75 treatment coverage and prevented 75-85 of cases of uncomplicated and severe malaria in children The remarkable success of SMC has led to the recent WHO recommendation for its extension to other at-risk age groups and in highly seasonal malaria transmission settings outside the Sahel region This encouraging development supports the need to explore the possibility of integrating helminth control programmes with other successful delivery platforms such as SMC However limited empirical evidence exists on an integrated approach that integrated the control of malaria and parasitic worms in a safe acceptable easy-to-deliver and effective manner
To address this knowledge gap the investigators conducted a randomised controlled trial in the first stage of this project to establish the feasibility and safety of integrating helminth control with SMC among Senegalese children This second stage will assess the effectiveness and cost-effectiveness of using SMC platform to deliver deworming drugs to preschool and school-aged children living in communities where the burden of malaria and parasitic worms is high in central Ghana One thousand two hundred children aged 1-14 years will be randomly assigned equally to two study communities where antimalarial SMC drugs and deworming drugs will be administered in combination to the children living in one study community and antimalarial SMC drugs alone will be delivered to the children living in the second study community The effectiveness of the combined delivery will be determined by checking whether the combined antimalarial and deworming drugs prevent anaemia in the children who receive the combined drugs compared to the children who receive antimalarial drugs only We will also determine the cost and cost-effectiveness of this approach by estimating the incremental cost savings due to cases of moderate and severe anaemia averted by giving antimalarial and deworming drugs together to the children The findings of this study would provide evidence to boost public health recommendations for an integrated control of malaria and parasitic worms among children living in the poorest countries of the world The findings may also reinforce the empirical evidence that the future direction of healthcare systems in developing countries should be comprehensive health management rather than vertical management of a single disease
To address this knowledge gap the investigators conducted a randomised controlled trial in the first stage of this project to establish the feasibility and safety of integrating helminth control with SMC among Senegalese children This second stage will assess the effectiveness and cost-effectiveness of using SMC platform to deliver deworming drugs to preschool and school-aged children living in communities where the burden of malaria and parasitic worms is high in central Ghana One thousand two hundred children aged 1-14 years will be randomly assigned equally to two study communities where antimalarial SMC drugs and deworming drugs will be administered in combination to the children living in one study community and antimalarial SMC drugs alone will be delivered to the children living in the second study community The effectiveness of the combined delivery will be determined by checking whether the combined antimalarial and deworming drugs prevent anaemia in the children who receive the combined drugs compared to the children who receive antimalarial drugs only We will also determine the cost and cost-effectiveness of this approach by estimating the incremental cost savings due to cases of moderate and severe anaemia averted by giving antimalarial and deworming drugs together to the children The findings of this study would provide evidence to boost public health recommendations for an integrated control of malaria and parasitic worms among children living in the poorest countries of the world The findings may also reinforce the empirical evidence that the future direction of healthcare systems in developing countries should be comprehensive health management rather than vertical management of a single disease
Detailed Description:
This study has two components effectiveness and cost-effectiveness components The effectiveness study will be conducted in three stages The first stage will focus on pre-intervention surveys in Kintampo North Municipal and Pru East district This will be followed by an intervention stage which will be conducted in either Kintampo North or Pru East district depending on which of these districts has a higher prevalence of malaria STH and schistosoma infections The third stage will be a post-intervention cross-sectional survey in the communities where the intervention study is conducted
First stage During community sensitisation and engagement meetings with parents and caregivers of potentially eligible children living in Kintampo North Municipal and Pru East district the Kintampo Health Research Centre KHRC study team will explain the need for this study using a simple picture to illustrate the integration of SMC and anthelminthic drugs the study rationale and informed consent procedure and the risks and benefits of allowing their children to participate in the study After these meetings an investigator from KHRC will identify parentscaregivers of potential child participants to explain the study further to them on an individual basis The parentscaregivers will be given a copy of the participant information sheet Parentscaregivers who feel that the study is appropriate for their child will be visited at home at a mutually agreed time For logistical purposes written informed consent will be obtained from a parentcaregiver one day before the planned start date of the pre-intervention survey in both districts along with positive assent from children aged 7 years where required Following this an investigator will provide a pre-labelled stool collection container to the parentcaregiver at this visit and encourage them to collect stool from their child and keep this safely for the research team who will visit them the following day Subsequently the investigator will confirm the parentcaregivers willingness to allow their childs continued participation in the study and administer a purpose-designed electronic questionnaire to the parentscaregivers The questionnaire will cover information such as socio-demographic data health and residence characteristics history of de-worming and malaria treatment Heightlength cm and weight kg of each child will be measured and anthropometric indices height-for-age weight-for-age weight-for-height and body mass index will be calculated using the WHO AnthroPlus software wwwwhointgrowthreftoolsen The study villages will be mapped by recording each study participants household global-positioning system GPS coordinates with a hand-held GPS device
Following administration of the questionnaire finger-prick blood samples will be collected from each child participant for thick and thin smear examination for malaria microscopy and blood spot filter papers will be collected for DNA isolation and PCR amplification for species determination Haemoglobin concentrations will be measured using the Haemocue method Freshly voided urine samples will also be collected from all study children Urine filtration test will be used to quantify S haemotobium according to standard laboratory guidelines Parallel testing for circulating cathodic antigens CCA will be used to complement the filtration test
Stool samples will be collected to detect intestinal helminths Duplicate Kato-Katz thick smears will be prepared from the stool samples and examined by experienced technicians using light microscopy to determine the egg counts for S mansoni and STH The number of eggs per slide will be used to obtain a measure of the number of helminth eggs per gram of faeces EPG The intensity of the helminth infection will be categorised according to standard guidelines A multiplex PCR assay will also be used for simultaneous detection of mixed infections of helminths Quality control will be performed by re-examining at least 10 of randomly selected blood slides urine filters and Kato-Katz smears by an experienced independent laboratory scientist Laboratory staff performing the analyses will be masked to the origin of the samples
Intervention stage The intervention stage will be implemented during SMC campaign in Bono East Region Results obtained from the laboratory analysis of the blood stool and urine samples collected from the children enrolled in the pre-intervention surveys in Kintampo North and Pru East districts will be used to determine which of the districts will host the intervention stage of the study Given that the focus of this project is to evaluate the effectiveness of the integrated SMC-NTD control programmes the intervention stage of the study will be conducted in the district with a higher prevalence of malaria STH and schistosomiasis Also the intervention stage will be implemented in conjunction with the SMC providers in the selected district The first day of starting the intervention stage Day 0 will correspond to the day prior to the commencement of the first cycle of SMC in the selected district On that day the communities in the selected district will be randomised at the community level and stratified on the basis of the malaria and helminth prevalence obtained from the pre-intervention surveys into two groups at a 11 ratio to receive either combined SMC and anthelminthic drugs intervention arm or SMC drugs only control arm Given that 4-aminoquinoline drugs are reported to have antagonistic pharmacological interactions with praziquantel the SMC partner drugs amodiaquine AQ a 4-aminoquinoline derivative and sulphadoxine-pyrimethamine SP will not be administered with anthelminthic drugs albendazole and praziquantel on the same day in this study Therefore eligible children randomised into the intervention communities will receive albendazole and praziquantel on Day 0 and those randomised into the control communities will receive Vitamin A and Zinc supplements as control drugs On the following day which corresponds to the start Day 1 of the first SMC cycle the children in the control and intervention communities will receive AQ and SP according to the WHO and Ghana SMC implementation guidelines This will be followed on the second and third day of the SMC cycle with all study children in the two groups receiving AQ in line with the SMC guidelines All children irrespective of the study arms will undergo safety assessment
Post-intervention stage All child participants enrolled in the intervention study will be evaluated one month after the last course of SMC cycles which corresponds to the end of malaria transmission season to measure their haemoglobin concentration and to obtain a further blood film dried blood spot stool and urine samples to test for malaria-helminth co-infections using parasitological methods such as microscopy Kato-Katz urine filtration test and improved diagnostic tools including molecular methods qPCR as described above
Data collection for the cost and cost-effectiveness analyses The incremental financial and economic costs of delivering the integrated SMC-anthelminthic drugs programme in the intervention stage of this study will be estimated from a health service Ministry of Health and donor perspective compared to the counterfactual of giving SMC drugs alone Financial cost data including all direct expenditures on the trial including salaries and economic costs donated goods or services such as time of salaried health workers will be collected through reviews of project records and semi-structured key informant interviews KIIs at district health facility and community health workers CHW levels Detailed costs will be captured for disaggregated cost categories including SMC and MDA drugs drug supply chain CHW delivery of doses supervision training planning meetings sensitisation and supplies Incremental costs required for the integrated delivery of anti-helminth MDA with SMC above what would be required for SMC delivery alone will be identified The cost of diagnosis and treatment of moderate and severe anaemia from the health service perspective will be estimated using a combination of primary and secondary data Cost per outpatient visit and cost per inpatient day excluding diagnosis and treatment will be obtained from existing data sources Costs of diagnostic tests medicines and provider time for treating cases of moderate and severe anaemia will be captured through KIIs with health staff at facilities providing outpatient and inpatient services in the study area These parameters will be used to estimate incremental cost savings due to cases of moderate and severe anaemia averted by SMC plus MDA compared to SMC alone
For the cost-effectiveness analysis CEA the main measure of the effects will be disability-adjusted life-years DALYs averted DALYs combine mortality years of life lost YLLs and morbidity years lived with disability YLDs into a single measure of effect allowing the impact of SMC MDA to be compared with the impact of different types of health interventions The effect measure used to calculate DALYs will be moderate and severe anaemia cases averted where anaemia is the primary outcome for the CEA which is where the main incremental health benefit from co-delivery is expected derived from unadjusted results of the trial calculated on the basis of intention-to-treat DALYs will be modelled using a 3 discount rate in the base case no age weighting standard DALY weights and life tables and other secondary data eg duration of an episode of anaemia The CEA results will be expressed as an incremental cost-effectiveness ratio ICER The ICER is calculated as the difference in costs between MDA SMC versus SMC alone divided by the difference in effects between those strategies
First stage During community sensitisation and engagement meetings with parents and caregivers of potentially eligible children living in Kintampo North Municipal and Pru East district the Kintampo Health Research Centre KHRC study team will explain the need for this study using a simple picture to illustrate the integration of SMC and anthelminthic drugs the study rationale and informed consent procedure and the risks and benefits of allowing their children to participate in the study After these meetings an investigator from KHRC will identify parentscaregivers of potential child participants to explain the study further to them on an individual basis The parentscaregivers will be given a copy of the participant information sheet Parentscaregivers who feel that the study is appropriate for their child will be visited at home at a mutually agreed time For logistical purposes written informed consent will be obtained from a parentcaregiver one day before the planned start date of the pre-intervention survey in both districts along with positive assent from children aged 7 years where required Following this an investigator will provide a pre-labelled stool collection container to the parentcaregiver at this visit and encourage them to collect stool from their child and keep this safely for the research team who will visit them the following day Subsequently the investigator will confirm the parentcaregivers willingness to allow their childs continued participation in the study and administer a purpose-designed electronic questionnaire to the parentscaregivers The questionnaire will cover information such as socio-demographic data health and residence characteristics history of de-worming and malaria treatment Heightlength cm and weight kg of each child will be measured and anthropometric indices height-for-age weight-for-age weight-for-height and body mass index will be calculated using the WHO AnthroPlus software wwwwhointgrowthreftoolsen The study villages will be mapped by recording each study participants household global-positioning system GPS coordinates with a hand-held GPS device
Following administration of the questionnaire finger-prick blood samples will be collected from each child participant for thick and thin smear examination for malaria microscopy and blood spot filter papers will be collected for DNA isolation and PCR amplification for species determination Haemoglobin concentrations will be measured using the Haemocue method Freshly voided urine samples will also be collected from all study children Urine filtration test will be used to quantify S haemotobium according to standard laboratory guidelines Parallel testing for circulating cathodic antigens CCA will be used to complement the filtration test
Stool samples will be collected to detect intestinal helminths Duplicate Kato-Katz thick smears will be prepared from the stool samples and examined by experienced technicians using light microscopy to determine the egg counts for S mansoni and STH The number of eggs per slide will be used to obtain a measure of the number of helminth eggs per gram of faeces EPG The intensity of the helminth infection will be categorised according to standard guidelines A multiplex PCR assay will also be used for simultaneous detection of mixed infections of helminths Quality control will be performed by re-examining at least 10 of randomly selected blood slides urine filters and Kato-Katz smears by an experienced independent laboratory scientist Laboratory staff performing the analyses will be masked to the origin of the samples
Intervention stage The intervention stage will be implemented during SMC campaign in Bono East Region Results obtained from the laboratory analysis of the blood stool and urine samples collected from the children enrolled in the pre-intervention surveys in Kintampo North and Pru East districts will be used to determine which of the districts will host the intervention stage of the study Given that the focus of this project is to evaluate the effectiveness of the integrated SMC-NTD control programmes the intervention stage of the study will be conducted in the district with a higher prevalence of malaria STH and schistosomiasis Also the intervention stage will be implemented in conjunction with the SMC providers in the selected district The first day of starting the intervention stage Day 0 will correspond to the day prior to the commencement of the first cycle of SMC in the selected district On that day the communities in the selected district will be randomised at the community level and stratified on the basis of the malaria and helminth prevalence obtained from the pre-intervention surveys into two groups at a 11 ratio to receive either combined SMC and anthelminthic drugs intervention arm or SMC drugs only control arm Given that 4-aminoquinoline drugs are reported to have antagonistic pharmacological interactions with praziquantel the SMC partner drugs amodiaquine AQ a 4-aminoquinoline derivative and sulphadoxine-pyrimethamine SP will not be administered with anthelminthic drugs albendazole and praziquantel on the same day in this study Therefore eligible children randomised into the intervention communities will receive albendazole and praziquantel on Day 0 and those randomised into the control communities will receive Vitamin A and Zinc supplements as control drugs On the following day which corresponds to the start Day 1 of the first SMC cycle the children in the control and intervention communities will receive AQ and SP according to the WHO and Ghana SMC implementation guidelines This will be followed on the second and third day of the SMC cycle with all study children in the two groups receiving AQ in line with the SMC guidelines All children irrespective of the study arms will undergo safety assessment
Post-intervention stage All child participants enrolled in the intervention study will be evaluated one month after the last course of SMC cycles which corresponds to the end of malaria transmission season to measure their haemoglobin concentration and to obtain a further blood film dried blood spot stool and urine samples to test for malaria-helminth co-infections using parasitological methods such as microscopy Kato-Katz urine filtration test and improved diagnostic tools including molecular methods qPCR as described above
Data collection for the cost and cost-effectiveness analyses The incremental financial and economic costs of delivering the integrated SMC-anthelminthic drugs programme in the intervention stage of this study will be estimated from a health service Ministry of Health and donor perspective compared to the counterfactual of giving SMC drugs alone Financial cost data including all direct expenditures on the trial including salaries and economic costs donated goods or services such as time of salaried health workers will be collected through reviews of project records and semi-structured key informant interviews KIIs at district health facility and community health workers CHW levels Detailed costs will be captured for disaggregated cost categories including SMC and MDA drugs drug supply chain CHW delivery of doses supervision training planning meetings sensitisation and supplies Incremental costs required for the integrated delivery of anti-helminth MDA with SMC above what would be required for SMC delivery alone will be identified The cost of diagnosis and treatment of moderate and severe anaemia from the health service perspective will be estimated using a combination of primary and secondary data Cost per outpatient visit and cost per inpatient day excluding diagnosis and treatment will be obtained from existing data sources Costs of diagnostic tests medicines and provider time for treating cases of moderate and severe anaemia will be captured through KIIs with health staff at facilities providing outpatient and inpatient services in the study area These parameters will be used to estimate incremental cost savings due to cases of moderate and severe anaemia averted by SMC plus MDA compared to SMC alone
For the cost-effectiveness analysis CEA the main measure of the effects will be disability-adjusted life-years DALYs averted DALYs combine mortality years of life lost YLLs and morbidity years lived with disability YLDs into a single measure of effect allowing the impact of SMC MDA to be compared with the impact of different types of health interventions The effect measure used to calculate DALYs will be moderate and severe anaemia cases averted where anaemia is the primary outcome for the CEA which is where the main incremental health benefit from co-delivery is expected derived from unadjusted results of the trial calculated on the basis of intention-to-treat DALYs will be modelled using a 3 discount rate in the base case no age weighting standard DALY weights and life tables and other secondary data eg duration of an episode of anaemia The CEA results will be expressed as an incremental cost-effectiveness ratio ICER The ICER is calculated as the difference in costs between MDA SMC versus SMC alone divided by the difference in effects between those strategies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None