Assessing to What Extent Dhps-431V Mutation May Influence the Protective Efficacy of IPTp-SP

NCT04634695 | Unknown

• 1 other identifier: DEEM-FIT
• Study Type: observational
• Target: 288
• Locations: 1 country
• Sites: 2

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.

Conditions

Pregnancy Malaria

Keywords

Antimalarial drug; Sulphadoxine-pyrimethamine; SP-resistance; Malaria in Pregnancy; mutation; Intermittent Preventive treatment

Outcome Measures

Primary Outcomes (2)

• Malaria infection at the time of delivery

  P. falciparum malaria positivity will be confirmed using microscopy

  May 2021

• Dhps-431V mutation

  Point mutation at codon dhps-I431V will be carried out

  May 2021

Secondary Outcomes (3)

• Average maternal haematocrit

  May 2021

• Birth weight of babies

  May 2021

• Prevalence of placental malaria

  May 2021

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Obafemi Awolowo University: lead
• University of Copenhagen: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (2)

Obafemi Awolowo University Teaching Hospital

Ile-Ife, Osun State, +234, Nigeria

RECRUITING

State Specialist Hospital, Asubiaro

Osogbo, Osun State, +234, Nigeria

RECRUITING

Related Publications (3)

• van Eijk AM, Larsen DA, Kayentao K, Koshy G, Slaughter DEC, Roper C, Okell LC, Desai M, Gutman J, Khairallah C, Rogerson SJ, Hopkins Sibley C, Meshnick SR, Taylor SM, Ter Kuile FO. Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2019 May;19(5):546-556. doi: 10.1016/S1473-3099(18)30732-1. Epub 2019 Mar 25.

  PMID: 30922818 BACKGROUND

• Oguike MC, Falade CO, Shu E, Enato IG, Watila I, Baba ES, Bruce J, Webster J, Hamade P, Meek S, Chandramohan D, Sutherland CJ, Warhurst D, Roper C. Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):220-229. doi: 10.1016/j.ijpddr.2016.08.004. Epub 2016 Sep 29.

  PMID: 27821281 RESULT

• Alifrangis M, Nag S, Schousboe ML, Ishengoma D, Lusingu J, Pota H, Kavishe RA, Pearce R, Ord R, Lynch C, Dejene S, Cox J, Rwakimari J, Minja DT, Lemnge MM, Roper C. Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia. Emerg Infect Dis. 2014 Aug;20(8):1280-6. doi: 10.3201/eid2008.131897.

  PMID: 25061906 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood will be collected and DNA will be extracted for malaria parasite genomic analysis

Study Officials

• Adebanjo Adegbola, PhD

  Obafemi Awolowo University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adebanjo J Adegbola, PhD

CONTACT

+2348035816301; banjogbola@yahoo.com

Adebimpe O Ijarotimi, FMCOG

CONTACT

+2348034002812; tadeolar@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 18, 2020
• Study Start: August 10, 2020
• Primary Completion: May 31, 2021
• Study Completion: July 1, 2021
• Last Updated: November 18, 2020

Record last verified: 2020-11

Locations

NG (2)