Clinical trial NCT04634695: Assessing to What Extent Dhps-431V Mutation May Influence the Protective Efficacy of IPTp-SP
Official title: Assessing the Prevalence and Impact of Dihydropteroate Synthase-431V Mutation on the Protective Efficacy of Intermittent Preventive Treatment During Pregnancy Using Sulphadoxine-pyrimethamine
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pregnancy Malaria
Keywords: Antimalarial drug
Sulphadoxine-pyrimethamine
SP-resistance
Malaria in Pregnancy
mutation
Intermittent Preventive treatment
Lead sponsor: Obafemi Awolowo University
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: London School of Hygiene and Tropical Medicine
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2020-11-18
Enrollment: 288
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO(16) will be followed in recruiting subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal clinics of Obafemi Awolowo University Teaching Hospitals complex, Ile-Ife

Brief summary: Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in moderate-to-high transmission settings. Evidence has recently become available supporting the emergence of a novel Pfdhps-431V mutation in Nigeria. This new mutation may further confound the existing SP-resistance; thus, the intended follow-on project aims to assess the influence of Pfdhps-431V mutation on the protective efficacy of SP during pregnancy.

The aims are to detect P. falciparum positivity at delivery and pregnancy outcome in participants who must have received three or more doses of IPTp_SP. We will attempt to check the presence of existing and new Pfdhps/Pfdhfr mutations in the samples positive for P. falciparum using a quantitative PCR (qPCR). The prevalence of novel Pfdhps-431V mutant and other Pfdhps/Pfdhfr resistance alleles among the study population will be estimated. The significance of the resistance genes on the efficacy of SP will be described by looking at its associations with the reported IPTp use, P. falciparum infection, maternal anaemia, low birth weight, and preterm delivery.

Detailed description: Malaria in pregnancy (MiP) is considered a major public health issue with substantial risks for mothers and their babies. Intermittent preventive treatment in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) is adopted as a part of antenatal care (ANC) to prevent malaria and reduce the risk associated with MiP. However, SP-resistance is increasing with the emergence of Plasmodium falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) resistant genes challenging the benefits and effectiveness of IPTp-SP. Still, evidence has become available supporting the emergence of a novel Pfdhps-I431V mutation. The I431V mutation is found only in West and Central African countries, however, its impact on SP resistance has not been evaluated. We are hypothesizing that the new mutation may confound the existing SP-resistance resulting in an apparent reduction in the protective effect of SP during pregnancy within the region.

The study will recruit adult pregnant women and will assess the presence of malaria infection at delivery. The study will seek new mutations in vivo using full sequencing. This molecular tool will also be used to look at the prevalence of novel Pfdhps-431V mutation among pregnant women undergoing monthly IPTp-SP. Attempts will be made to re-evaluate the prevalence of other Pfdhps and Pfdhfr resistance alleles among the study population. The significance of the resistance genes on the protective efficacy of SP will be described.

The present study is an observational study to be conducted among all booked pregnant women. The pregnant women must have received at least three therapeutic doses of sulphadoxine-pyrimethamine as part of routine antenatal care (ANC) before delivery. sion and Pregnant women who consented to participate will be tested for the presence of malaria parasite during the third trimester and at delivery. 80-100 µL blood samples will be saved as dried blood spot on Whatman® filter paper from the individual with P. falciparum malaria positivity Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO will be followed in enrolling subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal

Eligibility criteria: Inclusion Criteria:

* Pregnant women at 26 weeks of pregnancy who aged ≥ 18 years; Must have commenced IPTp-SP and intended to receive three or more therapeutic doses of SP before delivery; Readiness to give informed consent and comply with the study protocol.

Exclusion Criteria:

* Pregnant women during their first trimester as SP is not recommended during the first trimester; Severe or complicated malaria as the subject will require additional treatment and consideration; Presence of underlying chronic or severe diseases (e.g., cardiac, renal or hepatic diseases, HIV/AIDS); Individuals who are receiving co-trimoxazole for another disease condition (as SP is not usually recommended): Inability to swallow oral medication because of persistent nausea and vomiting

Primary outcomes:
measure: Malaria infection at the time of delivery
timeFrame: May 2021
measure: Dhps-431V mutation
timeFrame: May 2021
Secondary outcomes:
measure: Average maternal haematocrit
timeFrame: May 2021
measure: Birth weight of babies
timeFrame: May 2021
measure: Prevalence of placental malaria
timeFrame: May 2021
Other outcomes:
Locations:
city: Ile-Ife
country: Nigeria
facility: Obafemi Awolowo University Teaching Hospital
state: Osun State
city: Osogbo
country: Nigeria
facility: State Specialist Hospital, Asubiaro
state: Osun State
Study officials:
affiliation: Obafemi Awolowo University
name: Adebanjo Adegbola, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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