Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward

Abstract

Malaria infection during pregnancy is an important driver of maternal and neonatal health in endemic countries. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention at each scheduled antenatal care visit, starting at the second trimester, in areas of high and moderate transmission. However, the increased resistance to SP in some endemic areas challenges its effectiveness. Furthermore, SP is contraindicated in the first trimester of pregnancy and in HIV-infected women on co-trimoxazole prophylaxis due to potential drug–drug interactions. Thus, in recent last decades, several studies evaluated alternative drugs that could be used for IPTp. A comprehensive literature review was conducted to summarize the evidence on the efficacy and safety of antimalarial drugs being evaluated for IPTp. Chloroquine, amodiaquine, mefloquine and azithromycin as IPTp have proven to be worse tolerated than SP. Mefloquine was found to increase the risk of mother-to-child transmission of HIV. Dihydroartemisin-piperaquine currently constitutes the most promising IPTp drug alternative; it reduced the prevalence of malaria infection, and placental and clinical malaria in studies among HIV-uninfected women, and it is currently being tested in HIV-infected women. Research on effective antimalarial drugs that can be safely administered for prevention to pregnant women should be prioritized. Malaria prevention in the first trimester of gestation and tailored interventions for HIV-infected women remain key research gaps to be addressed.

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

“…Revisiting existing drugs with safe clinical use is an alternative to the development of new molecules. In vitro studies have shown that mefloquine, a well-known molecule widely used in the treatment of malaria [ 209 ], acts as an efflux pump inhibitor in P. aeruginosa [ 210 ]. Trimethoprim, a drug used in combination with sulfamethoxazole to treat various infections, also has efflux pump inhibitory activity.…”

Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

“…For example, the total molecular weight, cLogP (octanol/water coefficient, solubility estimation), and the number of sp3 atoms (stereochemical complex-ity estimation) were calculated and statistically analyzed (Table S2). The results suggest that 3-nitroimidazopyridines derivatives (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), metronidazole hybridized derivatives , and quinoline-metronidazole derivatives (63a-63m) have high molecular weights compared with other 5-NI derivatives. These kinds of compounds are in the upper recommended limit to be considered "drug-like" compounds, according to the empirical rules proposed by Lipinsky [70].…”

“…Currently, drugs used as malaria treatment are divided into four categories (Figure 3): quinolines or aminoquinolines (e.g., chloroquine and primaquine); antifolates (e.g., sulfadoxine and pyrimethamine); artemisinin derivatives; and macrocycles, such as tetracycline and doxycycline [11]. However, although there are different types of drugs and novel poly-drug therapies, a growing concern is the emergence of drug-resistant Plasmodium strains [10,12].…”

Malaria in Pregnancy, Current Challenges, and Emerging Prevention Strategies in a Warming Climate

“…33 Chloroquine was not well tolerated in pregnancy trials nor were attempts at substituting SP with mefloquine, amodiaquine or azithromycin. [34][35][36] IPTp with dihydroartemisin-piperaquine (DP) is the most promising alternative to IpTP-SP perhaps because of the long half-life of piperaquine that may serve as prophylaxis against future mosquito bites as well as clearing any parasites sequestered in the placenta at the time of administration. Compared with IPTp-SP, IPTp-DP was associated with a lower risk of clinical malaria, peripheral parasitemia during pregnancy, and placental malaria at delivery.…”

“…SP resistance has led researchers to evaluate alternative antimalarials for chemoprophylaxis in pregnancy, including the reintroduction of chloroquine, an early antimalarial with widespread resistance whose efficacy in Africa reappeared after years of not recommending its use 33 . Chloroquine was not well tolerated in pregnancy trials nor were attempts at substituting SP with mefloquine, amodiaquine or azithromycin 34–36 . IPTp with dihydroartemisin-piperaquine (DP) is the most promising alternative to IpTP-SP perhaps because of the long half-life of piperaquine that may serve as prophylaxis against future mosquito bites as well as clearing any parasites sequestered in the placenta at the time of administration.…”