What are the implications of Plasmodium vivax (P. vivax) infection in pregnancy?

From the Guidelines

Plasmodium vivax infection during pregnancy requires prompt treatment with chloroquine as the first-line treatment, unless the infection is acquired in a chloroquine-resistant area, in which case artemisinin-based combination therapies (ACTs) are recommended, with artemether-lumefantrine being preferred in the second and third trimesters, as supported by the most recent evidence from 2024 1. The treatment regimen for chloroquine is 600mg base initially, followed by 300mg base at 6,24, and 48 hours. In areas with chloroquine resistance, ACTs such as dihydroartemisinin-piperaquine or artemether-lumefantrine can be used, with the latter being preferred in the second and third trimesters due to its safety profile, as indicated by studies such as 1 and 1. For radical cure to prevent relapses, primaquine should be avoided during pregnancy due to potential fetal harm and unknown safety profile, and instead, weekly chloroquine prophylaxis (300mg base) should be continued until delivery, as suggested by 1 and 1. After delivery, if G6PD status is normal, primaquine can be given (0.5mg/kg daily for 14 days or 0.75mg/kg weekly for 8 weeks) to eliminate liver hypnozoites. Some key points to consider in the treatment of P. vivax malaria in pregnancy include:

• The importance of prompt treatment to protect both mother and fetus
• The use of chloroquine as the first-line treatment, unless the infection is acquired in a chloroquine-resistant area
• The preference for artemether-lumefantrine in the second and third trimesters in areas with chloroquine resistance
• The need to avoid primaquine during pregnancy and instead use weekly chloroquine prophylaxis until delivery
• The importance of regular fetal monitoring and the use of insecticide-treated bed nets, appropriate antimalarial prophylaxis, and prompt diagnosis and treatment of any suspected malaria infection. P. vivax in pregnancy is associated with maternal anemia, low birth weight, and preterm birth, though typically less severe than P. falciparum, as noted in studies such as 1 and 1. Regular fetal monitoring is essential, and all pregnant women in endemic areas should use insecticide-treated bed nets, receive appropriate antimalarial prophylaxis, and undergo prompt diagnosis and treatment of any suspected malaria infection, as recommended by 1 and 1.

From the Research

P vivax in Pregnancy

• P vivax malaria in pregnancy can be treated with chloroquine, which has been shown to be safe and effective in preventing relapse 2.
• A study found that chloroquine prophylaxis completely prevented P vivax episodes in pregnant women, with no difference in the proportions of reported side effects between the chloroquine and placebo groups 2.
• However, another study found that chloroquine is commonly under-dosed in the treatment of vivax malaria, and increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given 3.
• Primaquine is currently the only licensed hypnozoitocidal treatment for P vivax, but it requires long treatment courses and its effectiveness in different endemic settings remains largely unknown 4.
• A systematic review and meta-analysis found that adding primaquine to chloroquine reduced the risk of recurrence to 4.9% by day 42, which is lower than with chloroquine alone 3.

Treatment Options

• Chloroquine is the mainstay of treatment for P vivax malaria, but its efficacy is compromised in some areas due to resistance 4.
• Primaquine is used to prevent relapse, but it requires a 14-day course and can cause hemolytic anemia in people with G6PD deficiency 5.
• Alternative primaquine regimens, such as a 5-day or 7-day course, have been shown to be less effective than the standard 14-day course in preventing relapse 5.
• New-generation artemisinin combination therapies (ACTs) have shown potent efficacy against the erythrocytic stages of both drug-resistant P vivax and Plasmodium falciparum 4.

Safety and Efficacy

• Chloroquine has been shown to be safe and effective in preventing relapse in pregnant women with P vivax malaria 2.
• Primaquine is generally well-tolerated, but it can cause hemolytic anemia in people with G6PD deficiency 5.
• A study found that primaquine was safe and effective in preventing relapse in people with P vivax malaria, with no serious adverse events reported 5.
• The addition of primaquine to chloroquine has been shown to be highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax 3.