A Case of Toxoplasmosis in Pregnancy
Meera Chand, John Holton in Case Studies in Infection Control, 2018
If T. gondii DNA had been detected in amniotic fluid, it would have indicated that foetal infection was likely to have taken place. As spiramycin does not cross the placenta, the treatment of choice in this situation would be an oral combination regimen of pyrimethamine (an antagonist of dihydrofolate reductase) and sulfadiazine (a sulfonamide drug), along with folinic acid supplementation to prevent bone marrow suppression. This treatment should be continued in the mother through pregnancy. Trimethoprim-sulfamethoxazole has also been used. Clindamycin is an alternative agent if there has been a history of sulfonamide allergy. Other options are azithromycin, dapsone, and atovaquone, but experience of their use in this context is limited. Pyrimethamine is generally felt to be the pivotal drug in the treatment regimen but should not be given in the first trimester as it is teratogenic.
Toxoplasma gondii
Peter D. Walzer, Robert M. Genta in Parasitic Infections in the Compromised Host, 2020
Pyrimethamine is a folic acid antagonist and when used in anti-Toxoplasma doses may cause significant bone marrow suppression. Folinic acid (leucovorin) is transported across human cell membranes but not across Toxoplasma cell membranes and therefore may be a useful adjunct to prevent the bone marrow toxicity of pyrimethamine but maintain its therapeutic efficacy. In contrast, folic acid seems to have an adverse effect on the action of pyrimethamine and sulfadiazine (380). Folinic acid at a dose of 5-10 mg/day should be given orally or parenterally along with pyrimethamine. Other less serious side effects with pyrimethamine include gastrointestinal distress, headaches, and a bad taste in the mouth.
Antimicrobials during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
These agents are used primarily to treat toxoplasmosis. Pyrimethamine, a folic acid antagonist, is also used to treat malaria. There are no adequate scientific studies of its use during pregnancy, but Hengst (1992) reported no increase in the malformation rate in 64 newborns whose mothers had taken this drug during the first half of pregnancy. Spiramycin has been used extensively in Europe during the first trimester with no apparent adverse fetal effects. Sulfadiazine, a sulfonamide, has not been reported to be teratogenic when used in the first trimester. However, as with all sulfonamides, it could potentially be related to hyperbilirubinemia in the newborn, especially in the premature infant.
High prevalence of dihydrofolate reductase gene mutations in Plasmodium falciparum parasites among pregnant women in Nigeria after reported use of sulfadoxine-pyrimethamine
Published in Pathogens and Global Health, 2018
Olusola Ojurongbe, Christian N. Nguetse, Samuel A. Fayemiwo, Catherine O. Falade, Taiwo A. Ojurongbe, Bolaji N. Thomas, Christian G. Meyer, Thirumalaisamy P. Velavan
An important observation is the poor adherence of pregnant women to the WHO recommended SP for malaria prevention. Other drugs like dihydroartemisinin, chloroquine, and pyrimethamine that are not recommended for treatment or prevention of malaria in pregnancy are still commonly used by pregnant women in this study area. Pyrimethamine was the most commonly prescribed drug for malaria prevention during pregnancy in Nigeria [44] before the advent of ITPp-Sp. It was also previously recommended for weekly use of non-immune individuals traveling to malaria endemic regions [24,25]. Pyrimethamine, as monotherapy, is no longer recommended due to widespread resistance to the drug [47]. Mutations in the pfdhfr gene may reduce the effectiveness of pyrimethamine [48]. These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase via loss of hydrogen bonds and steric interactions [49]. Its continual use, as evidenced by study subjects in our study, reveals it remains a major contributory factor to the high rate of resistance and triple mutations among pregnant women specifically and the region in general. This observation is highlighted by the recent report of significant oral artemisinin monotherapy in Nigeria, contrary to policy, as a significant contributor to drug resistance and treatment failures [50]. We recommend stringent monitoring policies as well as improvement in import guidelines regarding what antimalarials can be imported and from which countries.
The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation
Published in Journal of Drug Targeting, 2018
Chun Y. Wong, Hani Al-Salami, Crispin R. Dass
Lactoferrin is a natural polypeptide in milk, which is well-documented with potent anti-microbial effects against bacteria, viruses, parasite and fungi [71]. Toxoplasma gondii is one of the deadly intracellular parasites that invades nucleated cell in human and animals, which cause toxoplasmosis and severe complications especially in pregnant women and immunocompromised patients [51]. Standard regime, such as sulfadiazine and pyrimethamine causes gastric-related problems, weight loss and headache [72]. In order to overcome the side-effects, alternative natural drugs, which can target the infected organs, modulate immune response and cause no side-effects, are preferred. A nanocapsule formulation (alginate/chitosan/calcium phosphate) was developed to load bovine lactoferrin for toxoplasmosis treatment [51]. The study found that the nanoformulation enhanced the stability of lactoferrin, increased reactive oxygen species (ROS) and cytokines (Th1) production in liver and spleen cells and reduced the number of infected macrophages in vitro. It was concluded that lactoferrin-loaded nanoparticles interrupted parasite multiplication and improved the lifespan of mice.
Infection-related stillbirth: an update on current knowledge and strategies for prevention
Published in Expert Review of Anti-infective Therapy, 2021
Samia Aleem, Zulfiqar A. Bhutta
IPT with sulfadoxine-pyrimethamine (SP) during pregnancy is recommended year-round with a 3 dose regimen in areas that are malaria endemic, starting in the second trimester [14]. This recommendation is based on a systematic review and meta-analysis of trials that compared regimens containing three or more doses for IPT, versus the previous standard of two doses [15]. Seven trials comprising 6281 pregnancies in sub-Saharan Africa were included in the study, which found that IPT with 3 or more doses of SP was associated with a higher birth weight and a lower risk of low birth weight compared to 2 doses [15]. This study however did not assess the effect on rates of stillbirth. A Cochrane review from 2014 which included 17 chemoprevention trials, enrolling 20,256 pregnant women found that malaria chemoprevention reduced the risk of antenatal parasitemia by nearly 61%, and reduced low birthweight by nearly 27% [16]. Notably, no effect was seen on perinatal mortality, spontaneous abortions, or stillbirths; these analyses, however, were underpowered to detect clinically significant differences [16].
Related Knowledge Centers
- Bone Marrow Suppression
- Dapsone
- Malaria
- Toxoplasmosis
- Allergy
- Folinic Acid
- Isosporiasis
- Pneumocystis Pneumonia
- HIV/AIDS
- Oral Administration