Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges

ABSTRACT

Introduction: Malaria in pregnancy continues to be a significant public health burden globally, with over 100 million women at risk each year. Sulfadoxine-pyrimethamine (SP) is the only antimalarial recommended for intermittent preventive therapy in pregnancy (IPTp) but increasing parasite resistance threatens its viability. There are few other available antimalarial therapies that currently have sufficient evidence of tolerability, safety, and efficacy to replace SP.

Areas covered: Novel antimalarial combinations are under investigation for potential use as chemoprophylaxis and in IPTp regimens. The present review summarizes currently available therapies, emerging candidate combination therapies, and the potential challenges to integrating these into mainstream policy.

Expert opinion: Alternative drugs or combination therapies to SP for IPTp are desperately required. Dihydroartemisinin-piperaquine and azithromycin-based combinations are showing great promise as potential candidates for IPTp but pharmacokinetic data suggest that dose modification may be required to ensure adequate prophylactic efficacy. If a suitable candidate regimen is not identified in the near future, the success of chemopreventive strategies such as IPTp may be in jeopardy.

KEYWORDS:

• Adverse outcomes
• azithromycin
• chemoprophylaxis
• dihydroartemisinin-piperaquine
• efficacy
• intermittent preventive treatment in pregnancy (IPTp)
• mefloquine
• pregnancy
• sulfadoxine-pyrimethamine

Article highlights

• There are 125 million pregnancies annually in women who are at risk of malaria, and it has been estimated that 200,000 infant and 10,000 maternal deaths result each year from malaria infection during gestation

• The conventional antimalarials chloroquine and sulfadoxine-pyrimethamine (SP) have been the mainstay of regular chemoprophylaxis and intermittent preventive therapy in pregnancy (IPTp), but increasing parasite resistance has had an adverse impact on their use

• SP is, nevertheless, the only antimalarial recommended for IPTp, its continued effectiveness in part reflecting activity against non-malarial infections that have potentially adverse obstetric outcomes

• Evaluation of alternatives in appropriately designed clinical studies can be hampered by teratogenicity and embryotoxicity concerns, which helps explain why there are few other available antimalarial therapies that have sufficient evidence of tolerability, safety, and efficacy to replace SP

• Dihydroartemisinin-piperaquine and azithromycin-based combinations are showing great promise as potential IPTp candidates, but dose modification may be required to ensure adequate prophylactic efficacy

• If a suitable candidate regimen is not identified in the near future, the success to date of chemopreventive strategies such as IPTp in endemic areas may be in jeopardy

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

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Funding

This manuscript has not been funded.