Why are pregnant women at high risk?
Immunological changes
Hormonal changes
Sequestration to the placental site
Increases susceptibility to bites
Infected erythrocytes in pregnant women are immunologically distinct from infected erythrocytes found in nonpregnant individuals: they express a specific class of variant surface antigen (pregnancy-associated malaria variant surface antigen [VSA-PAM]) that mediates adhesion of infected erythrocytes to chondroitin sulfate A (CSA) on the syncytiotrophoblast lining the intervillous space.
Adherence of erythrocytes expressing VSA-PAMs to the surface of syncytiotrophoblast appears to stimulate an inflammatory response. This results in monocyte migration and release of humoral factors, such as tumor necrosis factor-alpha (TNF-alpha), into the intervillous circulation that may promote preterm labor.
Clinical presentation
Presentation depends on transmission rates of the area(holoendemic vs mesoendemic) and gravidity.
The clinical manifestations of malaria are nonspecific and variable.
Fever(temperature ≥37.5°C),chills, sweats, headache, myalgias, fatigue, nausea, abdominal pain, vomiting, diarrhea, jaundice, and cough. Hypoglycemia is a common complication of severe malaria, pulmonary edema, acute respiratory distress syndrome.Anemia is a common complication of malaria in pregnancy.The anemia is generally normocytic and normochromic, with a striking absence of reticulocytes.
Diagnosis
Dx of malaria is based on clinical presentation, hx of travel to endemic areas and microscopic detection of parasites.
1. microscopy
Detection of parasites on Giemsa-stained blood smears by light microscopy is the standard tool for diagnosis of malaria.
Microscopy allows identification of the Plasmodium species as well as quantification of parasitemia. It also enables diagnosis of hematologic abnormalities and other infectious diseases such as filariasis, trypanosomiasis, babesiosis, and others.
Two types of blood smears are used in malaria microscopy: thin and thick smears
Thin smears allow identification of the infecting parasite species and can be used to measure parasite density.
Thick smear preparation involves mechanical lysis of red blood cells so that malaria parasites can be visualized independent of cell structures. Thick smears allow the microscopist to review a relatively large quantity of blood and are typically used to screen for presence or absence of the malaria parasite.
2. Rapid diagnostic test
RDTs provide a qualitative result but cannot provide quantitative information regarding parasite density.
3. Assay types
RDTs based on antigen detection detect one or more of the following: histidine-rich protein 2 (HRP2), Plasmodium lactate dehydrogenase (pLDH), and aldolase. Depending on the target antigen(s), an RDT may identify Plasmodium genus only or may distinguish P. falciparum and/or P. vivaxinfections.
HRP2 — Histidine-rich protein 2 (HRP2) is part of a family of P. falciparum histidine-rich proteins. It is only produced by P. falciparum; therefore, use of HRP2-based RDTs is appropriate in regions where P. falciparum is the predominant species.
However, detectable HRP2 antigen may persist in the bloodstream for anywhere from a few days to several weeks after parasitemia is no longer present. In the absence of good quality confirmatory microscopy, there is currently no way to distinguish HRP2 antigenemia resulting from a new infection or persistent infection (ie, resulting from treatment failure) from antigenemia persisting from a recently treated infection.
Rarely, false-negative HRP2 results may occur at very high levels of antigenemia or parasitemia due to a prozone-like effect.Prozone effect is defined as false-negative or false-low results in antigen-antibody immunological reactions, due to an excess of either antigens or antibodies.
Use of molecular tests for malaria detection is generally limited to reference laboratories and is primarily for research and epidemiologic purposes
Oral regimens for treatment of Plasmodium falciparum malaria in pregnant women
| Type of infection | Trimester | Drug and dose |
Chloroquine-resistant P. falciparuminfection¶
All malarious regions except those specified as chloroquine sensitive listed in the box below.
Middle Eastern countries with chloroquine-resistant P. falciparum include Iran, Oman, Saudi Arabia, and Yemen. | First trimester | Quinine PLUS clindamycin |
| Quinine: 542 mg base (= 650 mg salt) orally three times daily for seven days.Δ |
| Clindamycin: 20 mg base/kg/day (up to 1.8 grams) orally divided three times daily for seven days. |
| OR |
| Artemisinin combination therapy (doses below) can be used as alternate therapy in first trimester if quinine + clindamycin is unavailable or treatment failure. |
| Second or third trimester | Artemisinin combination therapy: One of the following:◊ |
| Artemether-lumefantrine: 1 tablet = 20 mg artemether and 120 mg lumefantrine. A three-day treatment schedule with a total of six oral doses is recommended based on weight (25 to 34 kg: 3 tablets per dose; ≥35 kg: 4 tablets per dose). The patient should receive the initial dose, followed by the second dose 8 hours later, then 1 dose orally twice daily for the following two days. Take after a full meal or whole milk. |
| Artesunate-amodiaquine: 1 tablet = 100 mg artesunate and 270 mg amodiaquine. Dosing for patients ≥36 kg consists of 2 tablets per day orally for three days. |
| Artesunate-mefloquine: 1 tablet = 100 mg artesunate and 220 mg mefloquine hydrochloride per tablet. Dosing for patients ≥30 kg consists of 2 tablets per day orally for three days. |
| Dihydroartemisinin-piperaquine:§ 1 tablet = 40 mg of dihydroartemisinin and 320 mg of piperaquine phosphate. Dosing for patients 36 to <60 kg consists of 3 tablets per day for three days. Dosing for patients 60 to <80 kg consists of 4 tablets per day for three days. |
Chloroquine-sensitive P. falciparum infection
Central America west of Panama Canal; Haiti; the Dominican Republic; and most of the Middle East.
Infections acquired in the Newly Independent States of the former Soviet Union and Korea to date have been uniformly caused by Plasmodium vivax and should therefore be treated as chloroquine-sensitive infections. | Any trimester | Chloroquine |
| 600 mg base (= 1000 mg salt) orally immediately, followed by 300 mg base (= 500 mg salt) orally at 6, 24, and 48 hours. Total dose: 1500 mg base (= 2500 mg salt).¥ |
| OR |
| Hydroxychloroquine |
| 620 mg base (= 800 mg salt) orally immediately, followed by 310 mg base (= 400 mg salt) orally at 6, 24, and 48 hours. Total dose: 1550 mg base (= 2000 mg salt). |
Despite its decreasing efficacy against P. falciparum, chloroquine continues to be used widely because of its low cost and good tolerability. It remains the drug of first choice for treating P. vivax malaria. Pruritus is a common adverse effect in African patients.
Sulfadoxine/pyrimethamine is well tolerated as treatment and when used as intermittent preventive treatment in pregnant African women.
Quinine is the mainstay for treating severe malaria in many countries. Cardiovascular or CNS toxicity is rare, but hypoglycaemia may be problematic and blood glucose levels should be monitored.
ALU::CONCLUSIONS: These data suggest that exposure to AL in pregnancy, including first trimester, is not associated with particular safety risks in terms of perinatal mortality, malformations, or developmental impairment. However, more data are required on ALU use during the first trimester.
In general, parasitemia typically clears within 48 to 72 hours with appropriate therapy.Iron deficiency appears to be protective against malaria;
Malaria (severe), treatment:
Artesunate::IV: 2.4 mg/kg/dose at 0 hours, 12 hours, and 24 hours. Assess parasite density 4 hours after last dose of artesunate and proceed with therapy as follows, based on parasite density.
If parasitemia ≤1% and patient able to tolerate oral therapy:Transition to full treatment course with oral regimen.
If parasitemia ≤1% and patient unable to tolerate oral therapy: Continue with artesunate 2.4 mg/kg/dose once daily for up to 6 additional days or switch to IV doxycycline or clindamycin for up to 6 additional days. After 7 total days of IV therapy, proceed with full treatment course with an oral regimen.
If parasitemia >1%: Continue with artesunate 2.4 mg/kg/dose once daily until parasitemia ≤1% (maximum of 7 days IV treatment). Proceed with full treatment course with an oral regimen as soon as parasitemia ≤1% and patient is able to tolerate oral therapy.
Complications
●Miscarriage
●Preterm birth (<37 weeks of gestation)
●Low birth weight (LBW; <2500 g at birth)
●Fetal growth restriction
●Perinatal mortality
●Congenital malaria infection, but congenital disease is most often associated with P. falciparum and P. vivax
●Maternal anemia
●Maternal mortality,Maternal death may be related to cerebral malaria, acidosis, organ failure (pulmonary, renal, hepatic), and/or severe anemia.
Hypoglycemia
Pulmonary edema
Prevention.
1. Use of insecticide-treated bed nets.
2. Travels to endemic areas
3. Intermittent preventive treatment in pregnancy (IPTp)
●Sulfadoxine-pyrimethamine (SP) – For HIV-negative pregnant women who live in malaria-endemic areas in Africa, we agree with WHO recommendations for administration of at least three doses of SP for IPTp, ideally at a minimum of three antenatal care visits starting early in the second trimester and at least four weeks apart . The dose of IPTp-SP is 1500 mg sulfadoxine/75 mg pyrimethamine; administration consists of three tablets (each containing 500 mg sulfadoxine/25 mg pyrimethamine); ideally IPTp should be administered as directly observed therapy.
WHO recommends the administration of folic acid at a dose of 0.4 mg daily; this dose may be safely used in conjunction with SP. Folic acid at a daily dose equal or above 5 mg should not be given together with SP as this counteracts its efficacy as an antimalarial
each SP dose suppresses or clears asymptomatic placental infection and provides up to six weeks of posttreatment prophylaxis.
Sulfadoxine-pyrimethamine should be avoided in the first weeks of life because it could aggravate neonatal hyperbilirubinemia.
●For HIV-infected pregnant women in malaria endemic areas, we are in agreement with the WHO recommendation for cotrimoxazole prophylaxis, regardless of CD4 cell count and throughout all trimesters of pregnancy. Prophylaxis consists of a daily dose of sulfamethoxazole 800 mg and trimethoprim 160 mg. This provides protection against malaria as well as HIV-related opportunistic infections
Antimalaria drugs
1. 4-aminoquinolines
Chloroquine
Amodiaquine
Piperaquine
2. 4-methanolquinolines
Quinine
Quinidine
Mefloquine
3. 8-aminoquinolines
Primaquine
4. ANTIFOLATES
Sulfadoxine and pyrimethamine target enzymes involved in folate synthesis; pyrimethamine targets dihydrofolate reductase (DHFR), and sulfadoxine acts on dihydropteroate synthase (DHPS).
sulfadoxine can precipitate hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
5. Artemisinin.
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