Diagnosis and Management of Malaria in Pregnancy

Introduction
Malarial infection in pregnant women is a leading cause of bad pregnancy outcomes like spontaneous abortion, preterm delivery, decreased growth, low birth weight, stillbirth, congenital infection, maternal death, and neonatal mortality. Plasmodium falciparum infection is dangerous for pregnant women because infected red blood cells can sequester in the placenta, causing negative fetal consequences. Suppose anti-malarial medications do not reach therapeutic levels in the placenta. In that case, parasites that have been sequestered there may be released sporadically into the peripheral circulation, resulting in recurrent maternal infection.

Pregnant women are vulnerable to malaria infection because of the immunological changes that occur during pregnancy and a fraction of P. falciparum parasites’ particular preference for sequestering in the maternal blood spaces of the placenta. This placental malaria infection aids the parasite in avoiding immune system clearance and, in particular, spleen filtration. On the red cell surface, P. falciparum parasites express a protein termed VAR2CSA, which binds to the placental receptor Chondroitin Sulphate A.

Antibodies to VAR2CSA have been linked to protection against placental malaria and poor birth outcomes. Moreover, a VAR2CSA-based vaccination is currently being tested in clinical trials.

Although P. vivax infection has been linked to adverse pregnancy outcomes such as low birth weight and maternal anemia, it does not cause placental sequestration. In addition, a recent study indicated low infection rates and morbidity in pregnant women affected by malaria due to P. vivax infection.

Consequences of malaria in pregnancy
The consequences of malaria during pregnancy depend on the aggressiveness of the transmission. Maternal anemia and low birth weight of newborns due to fetal growth restriction or early delivery are examples of the consequences of severe malaria in pregnant women.

Malaria infection in non-immune pregnant women in low-transmission areas can be severe and life-threatening, depending on the time to diagnose and provide proper treatment and care. Acute lung injury, severe hypoglycemia, pregnancy loss due to miscarriage or stillbirth, and coma are expected maternal consequences.

The severe complications associated with malaria in pregnant women include:

• Premature birth ( child takes delivery before 37 weeks of pregnancy)
• Low birth weight
• The growth of the baby decreases in the womb
• Stillbirth
• Miscarriage
• Death of the mother ( rare cases)

The diagnosis followed by treatment at the right time can prevent the consequences of malaria in pregnant women. This article briefly discusses the diagnosis, treatment, and preventive measures to help pregnant women and couples be safe from getting infected with malaria.

Diagnostic Tests to confirm malaria in pregnancy
Malaria during pregnancy is challenging to diagnose because the malarial parasites sequester in the placenta, and thus the blood tests show the negative presence of malarial parasites. Below are the different methods to diagnose malaria during pregnancy.

1. Blood Smear Microscopy Test and Rapid Diagnostic Test (RDT)
   The use of stained blood smear microscopy tests to diagnose malaria is considered the gold standard because of its use in clinical practice for a very long time. Rapid diagnostic tests (RDT) detect the specific parasite antigen or enzyme responsible for malaria. RDTs are particularly successful for diagnosing symptomatic malaria infection, which is often accompanied by high parasitemia, at the point of treatment. However, RDTs are less sensitive than blood smear microscopy tests and are also ineffective as screening tools because:
   RDTs may miss low parasitemia or low-density infection of the parasite, which is more likely in pregnant women. RDTs are relatively insensitive for diagnosing malaria caused by P. vivax.
2. Molecular diagnosis using PCR and qPCR
   PCR stands for Polymerase Chain reaction. Quantitative PCR may detect very-low-density malaria infection, demonstrating the sensitivity of polymerase chain reaction. However, the PCR assays are time-consuming and require a specialized laboratory with experienced personnel. LAMP (loop-mediated isothermal amplification) is similar to PCR in terms of sensitivity, but it is faster and more robust, and it might be used at the point of care. It is an alternative to PCR and qPCR. LAMP, PCR, and qPCR are currently only available in research settings.
3. Placental histology
   Intervillositis or leucocyte infiltrates, primarily monocytes, can accompany active infection, especially in first-time mothers with low pregnancy-associated malaria immunity. In addition, it is significantly linked to low birth weight and maternal anemia.
   
   A histological study of placental tissue at birth is a sensitive approach for detecting ongoing or prior malaria infection. When the malarial parasites digest hemoglobin, they produce a polymerized heme called hemozoin. The malaria pigment hemozoin, which is most typically found in fibrin deposits, can detect past infections.
   
   The hemozoin is detected either by using polarized light or laser desorption mass spectrometry (LDMS). LDMS has been considered a reliable tool for diagnosing malarial pregnancy as it can detect malarial parasites in the range of 100–1000/μl blood in samples collected from pregnant women.

Prevention
To prevent getting infected with malaria, pregnant women, adults, and children must follow necessary guidelines and precaution measures. These include:

1. Apply insect repellent on your skin and wear full sleeve shirts and pants when moving out of the house.
2. Always use mosquito nets on your bed before going to sleep.
3. Parents should make sure the newborn and children below five years are sleeping under a mosquito net.
4. Cover windows and doors with nets to prevent the entry of mosquitoes.
5. Permethrin is an insect repellent used on clothing, mosquito nets, tents, sleeping bags, and other materials to prevent the bite from mosquitoes.
6. Keep your nearby environment clean and get rid of old tyres, cups, plates, and other things where rainwater gets stored and becomes stagnant.
7. Spray DDT on stagnant water and near the drains to prevent the breeding of the mosquitoes.

Treatment of malaria in pregnancy

1. Intermittent preventive treatment (IPTp)
   IPTp, which uses sulphadoxine-pyrimethamine, is currently exclusively approved in Africa. In addition, Mefloquine and an azithromycin-chloroquine combination have recently been under study for malaria prophylaxis in pregnant women. Although mefloquine reduced parasite prevalence at delivery, however, it showed poor tolerance. As a result, the experiment of azithromycin and chloroquine was abandoned due to futility.
2. Indoor residual spraying and insecticide-treated nets (ITNs)
   ITNs help prevent malaria in pregnant women and reduce adverse pregnancy outcomes, according to evidence mostly from African trials. Unfortunately, the data on the study of ITNs in the Asian population is scarce, as the mosquito vectors and biting behavior differ, and malaria from P. vivax are common. Nonetheless, ITNs are a reasonably inexpensive and likely successful technique for malaria control in pregnancy in India.

Conclusion
Malaria in pregnant women is a matter of grave concern. The best malaria prophylaxis depends on the level of transmission; in places with greater transmission levels, ITNs have shown to be effective. The ongoing investigations will determine if preventative therapy approaches like IPTp or ITNs will find a positive outcome outside of Africa. Women in low-transmission areas may lack malaria immunity, putting them in danger of suffering a severe, perhaps deadly sickness or losing their kids due to miscarriage or stillbirth. Therefore, they need to be diagnosed and treated at the right time to prevent the consequences of malaria. Identifying the symptoms, carrying out diagnosis at the right time, providing optimal treatment and care, and educating the patients & pregnant women to follow malarial precaution measures will help curb the infection and prevent the negative consequences of malaria in pregnant women.

References

1. WHO Guidance for Prevention and Treatment of Malaria in Pregnancy. Accessed at https://www.mchip.net/sites/default/files/03.%20%20WHO%20Guidance%20for%20MIP%20Prevention%20and%20Treatment.pdf
2. Rogerson S. J. (2017). Management of malaria in pregnancy. The Indian journal of medical research, 146(3), 328–333. https://doi.org/10.4103/ijmr.IJMR_1304_17
3. The diagnosis and treatment of malaria in pregnancy, Royal College of Obstetricians and Gynaecologists. Accessed at https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_54b.pdf
4. Fried, M., Muehlenbachs, A., & Duffy, P. E. (2012). Diagnosing malaria in pregnancy: an update. Expert review of anti-infective therapy, 10(10), 1177–1187. https://doi.org/10.1586/eri.12.98
5. Malaria in pregnancy. Accessed at https://www.nhs.uk/conditions/malaria/complications/