Postpartum Primaquine in Breast Milk

• Status: Not yet recruiting
• Trial end date: 2025-10-31
• Target enrollment: 0
• Participant gender: Female

Summary

Plasmodium vivax and ovale infections both follow chronically relapsing courses, leading to cumulative morbidity and mortality. P. vivax is the second most common malaria worldwide, with an estimated 13.8 million cases annually, and there is increasing concern about severe illness and death in vulnerable populations.

Radical cure of P.vivax and P.ovale with 8-aminoquinolines is necessary to prevent relapse. The most widely 8-aminoquinoline is primaquine (7-14 day course), which has been used for almost 75 years. Its widespread use is hampered by the potentially severe haemolysis primaquine may trigger in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common red blood cell enzyme deficiency in the world. Safe administration of primaquine requires at least 30% of normal G6PD activity to avoid significant hemolysis.

Screening for malaria is routine in pregnancy, leading to improved detection of P. vivax infections, but primaquine and is contraindicated in pregnancy. As a result, relapses of P. vivax are common in postpartum and lactating women. Normal G6PD activity levels in infants less than 6 months old have only recently been described and have only been established along the Thailand-Myanmar border. Most low-resource settings are therefore unable to determine infant G6PD status. Uncertainty about infant G6PD status means that breastfeeding women are rarely offered radical cure because of theoretical concerns about drug exposure through breast milk triggering haemolysis in breastfed infants and children with G6PD deficiency. Though neonates generally have higher G6PD activity than adults, increased haemolysis for a neonate could theoretically contribute to neonatal jaundice and anaemia.

Understanding drug exposure to a breastfeeding neonate is operationally important, as interventions that can be safely offered before women leave the hospital postpartum have higher uptake. Current World Health Organization guidelines advise against prescribing primaquine to lactating women if they are breastfeeding infants less than 6 months old, or breastfeeding infants with G6PD deficiency or unknown G6PD status.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Oxford
• Collaborator: Mahidol Oxford Tropical Medicine Research Unit
• Treatments: Primaquine

Criteria

Inclusion Criteria: Mothers

• Lactating woman >= 18 years old

• Planning to breastfeed for the duration of the study

• Breastfeeding one infant 48 hours - 5 days old

• Willingness and ability to comply with the study protocol for the duration of the study

• Can understand information about the study and provide consent

Inclusion Criteria: Infants

• Healthy neonate 48 hours - 5 days old

Exclusion Criteria: Mothers

• Known hypersensitivity to Primaquine (PMQ), defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis

• Known Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in mother defined as G6PD activity <70% of normal male population median by spectrophotometry

• Presence of any condition which in the judgement of the investigator would place the participant at undue risk or interfere with the results of the study

• Screening Hct <33% by complete blood count (CBC)

• Known history of severe jaundice in a previous child

• Blood transfusion within the 3 months before screening

Exclusion Criteria: Infants

• Known Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in neonate defined as G6PD activity <70% of normal male population median by spectrophotometry

• Presence of any condition which in the judgement of the investigator would place the participant at undue risk or interfere with the results of the study

• Screening Hct <40% by CBC

• Estimated gestational age at birth < 38 weeks

• Evidence of birth asphyxia (5 min Apgar score <7)

• Moderate or severe jaundice as defined as total serum bilirubin above treatment line on day 1 (before maternal dose)