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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malarial infection in nonimmune pregnant women is a major risk factor for pregnancy failure. The biological mechanisms that underlie malaria-associated fetal loss, however, are poorly understood. Plasmodium chabaudi AS infection during early pregnancy results in midgestational embryonic loss in naive C57BL/6 mice. To define the immunopathogenesis of this malaria-induced pregnancy compromise, cytokine production in plasma, spleen, and placenta cell culture supernatants during the first 11 days of infection and gestation was studied. In infected pregnant mice, systemic interleukin-1beta and both systemic and splenic gamma interferon levels were elevated relative to those in uninfected pregnant mice, and gamma interferon was also robustly produced within the placenta 1 to 2 days before malaria-induced fetal loss. Although circulating tumor necrosis factor production was not affected by pregnancy or infection, circulating soluble tumor necrosis factor receptor II was highest in infected pregnant mice, particularly those undergoing abortion, but decreased at the placental level preceding abortion. Systemic levels of interleukin-10 were also high in infected mice at this time point, but this cytokine was not detected at the placental level. Histological examination revealed that trophoblast giant cells of aborting mice phagocytosed infected red blood cells and hemozoin. Furthermore, in vitro-cultured trophoblast cells isolated from embryos on day 7 of gestation phagocytosed P. chabaudi AS-infected red blood cells and secreted tumor necrosis factor. These results suggest that systemic and placenta-level proinflammatory antimalarial immune responses, in the absence of adequate and sustained counterregulatory mechanisms, contribute to pregnancy loss in this model.
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PMID:Association of malaria-induced murine pregnancy failure with robust peripheral and placental cytokine responses. 1968 96

The aim of this study was to investigate the incidence and causes of maternal deaths and stillbirths at the Hospital of Obstetrics and Gynecology at Wad Medani, Sudan, from 1 January 2003 through 31 December 2007. All maternal deaths and stillbirths during this period were reviewed and classified retrospectively. There were 146 maternal deaths and 33034 live births, giving a maternal mortality ratio of 442/100,000 live births. The age range was 18-42 years with a mean (standard deviation) of 30.57 (5.26) years. The most common cause of death was septicaemia following obstructed labour or abortion-related sepsis, followed by haemorrhage, pre-eclampsia/ecalampsia, viral hepatitis and malaria. The stillbirth rate was 29/1000 births; the majority of which (8/1000) were macerated stillbirths.
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PMID:High maternal mortality and stillbirth in the Wad Medani Hospital, Central Sudan, 2003-2007. 1976 81

Malaria, a parasitic infection transmitted by mosquitoes, is one of the most devastating infectious diseases, killing more than 1 million people annually. Pregnant women, children, and immunocompromised individuals have the highest morbidity and mortality, and Africa bears the heaviest burden. The World Health Organization defines malaria as a disease of poverty caused by poverty. Pregnant women infected with malaria usually have more severe symptoms and outcomes, with higher rates of miscarriage, intrauterine demise, premature delivery, low-birth-weight neonates, and neonatal death. They are also at a higher risk for severe anemia and maternal death. Malaria can be prevented with appropriate drugs, bed nets treated with insecticide, and effective educational outreach programs.
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PMID:Malaria and pregnancy: a global health perspective. 1982 76

1. The placental blood film examination is worthy of routine application wherever aestivo-autumnal malaria is endemic. This type of malaria when associated with labor and the early days of the puerperium can be more easily and certainly diagnosed by the use of this film and a polychrome stain than by employing the usual films made from the mother's peripheral blood at the time of labor. The placental film in such an infection offers an abundance of adult parasites and far more evidence of the presence of pigment, while the peripheral blood film frequently offers but a scant number of the small ring or discoid forms of a parasite. The examination of the present series revealed positive placental films in nineteen cases, while but eight of these same cases were positive in the peripheral blood film examination. On the other hand, no peripheral blood films were found positive in which the associated placental films did not reveal a far more abundant evidence of the infection. 2. The early days of the puerperium can by this method be protected many times from a malarial outburst, and, as a rule, puerperal sepsis can be differentiated. 3. The intricate vascular architecture of the mature placenta rivals that of the spleen, liver, and bone marrow as a harbor for adult malarial parasites of this type and as a storage for pigment. 4. The localization of parasites in the placenta is unique. Here is the one vascular system which particularly favors the development of the parasites but which at the same time is so situated that it may be spontaneously discarded by the body at the climax of the attack. By this simple act late in pregnancy the prognosis for both mother and child may be improved. 5. The pregnant state encourages attacks of malaria by lowering bodily resistance and by furnishing an additional harbor for the development of parasites. A tenable theory in regard to most attacks of this nature, occurring in cases under professional care, would appear to be the development of latent malaria (malarial carriers) into acute attacks toward the close of the pregnant state. The women who expose themselves (as the negroes in this series) offer favorable conditions to the introduction of a primary infection. Malaria frequently interrupts the late stages of pregnancy and sometimes causes the death of the mother and the fetus, more often the latter. The records at Ancon indicate that it more frequently exerts a harmful influence than other types of infectious diseases in this locality. 6. Most of the children in this series that were delivered while malaria was present in the mother, were of a race that seems to possess a relative immunity to the ravages of malaria. This may account for the fact that the negro fetus more nearly approximates the full term of development when associated with this disease and is comparatively subjected to a less number of the accidents of pregnancy. Many of them revealed evidence of prematurity and were jaundiced, but, as a rule, they developed rapidly. The commonest mishap is miscarriage late in pregnancy. Occasional still-births occur and sometimes there is a fatal issue to both the mother and child. 7. Cases diagnosed as congenital malaria probably indicate that some accident occurred to the placenta, because it practically never happens that fetal blood is positive at the time of birth, regardless of the degree of infection in the mother. Many of the cases now reported in the literature as congenital malaria suggest immediate postnatal infection as their history, as our pathological and clinical records testify. 8. The size of the intervillous spaces of the placenta and their adaptability in the localization of parasites seem to disprove to a certain extent the old idea that the localization depends on the smallness of the capillary caliber. If this were the case the brain should be more often the seat of an extensive localization than the spleen, bone marrow, and placenta, yet our anatomical records will not support that theory. A sluggish blood sinus with a large endothelial surface, a higher internal body temperature, and red blood cells burdened with parasites of a certain age beyond the ring form seem to be important factors in the localization and development of the aestivo-autumnal parasite. 9. The racial disparity of malarial infections shown in this series is believed to be due to local conditions and a wrong impression is apt to be given by our statistics in regard to the relative immunity of the negro race. The white women on the Canal Zone avail themselves of all the opportunities the sanitary system affords; they live well and place the entire course of their pregnant state under competent professional care, while the negro woman is indifferent to her pregnant state, works as a domestic servant, and lives in the cheapest unprotected quarters that can be rented in the suburban divisions of Panama City where the malarial rate is highest and the sanitary control is difficult. It should be noted that these negro women can carry an infection with little manifestation of its presence that would produce serious results in the white women brought from the temperate zone regions of Europe and the United States.
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PMID:THE DIAGNOSTIC VALUE OF THE PLACENTAL BLOOD FILM IN AESTIVO-AUTUMNAL MALARIA. 1986 27

Apicomplexan protozoa are a phylum of parasites that includes pathogens such as Plasmodium, the causative agent of the most severe form of malaria responsible for almost 1 million deaths per year and Toxoplasma gondii causing toxoplasmosis, a disease leading to cerebral meningitis in immunocompromised individuals or to abortion in farm animals or in women that are infected for the first time during pregnancy. The initial immune reactions developed by the host are similar in response to an infection with Plasmodium and Toxoplasma in the sense that the same cells of the innate immune system are stimulated to produce inflammatory cytokines. The glycosylphosphatidylinositol (GPI) anchor is the major carbohydrate modification in parasite proteins and the GPIs are essential for parasite survival. Two immediate GPI precursors with the structures ethanolamine phosphate-6(Manalpha1-2)Manalpha1-2Manalpha1-6Manalpha1-4GlcN-PI and ethanolamine phosphate-6Manalpha1-2Manalpha1-6Man-alpha1-4-GlcN-PI are synthesized by P. falciparum. Two main structures are synthesized by T. gondii: ethanolamine phosphate-6Manalpha1-2Manalpha1-6(GalNAcbeta1-4)Manalpha1-4GlcN-PI and ethanolamine phosphate-6Manalpha1-2Manalpha1-6(Glcalpha1-4GalNAcbeta1-4)Manalpha1-4GlcN-PI. This review describes the biosynthesis of the apicomplexan GPIs and their role in the activation of the host immune system.
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PMID:Immunological reactions in response to apicomplexan glycosylphosphatidylinositols. 2037 10

Apicomplexans comprise some of the most life threatening parasites infecting human and livestock and includes Plasmodium and Toxoplasma, the causative agents of malaria and toxoplasmosis respectively, in humans as well as Neospora caninum (abortion in livestock, neosporosis in dogs), Cryptosporidium (Diarrheal cryptosporidiosis and opportunistic infections in AIDS patients) and Eimeria (poultry coccidiosis). These parasites are characterized by a complex life cycle usually alternating between sexual and asexual cycles in different hosts. The need to adapt to different host environments demands a tight regulation of gene expression during parasite development. Therefore, the understanding of parasite biology will facilitate the control of the infection and the disease. In this review we emphasize the progress made so far in gene regulation in two medically important parasites, namely Plasmodium falciparum and Toxoplasma gondii, as well as other less known apicomplexan. The genome of both Plasmodium and Toxoplasma has been sequenced and since then there has been a significant progress in understanding the molecular mechanisms that control stage specific gene expression in the two parasites. In addition, the information gained in each of the parasite can be used in studying mechanisms that are still elusive in the other apicomplexans that are not readily available. Additionally, they can serve as model system for other disease causing Apicomplexan parasites.
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PMID:Comparative analysis of stage specific gene regulation of apicomplexan parasites: Plasmodium falciparum and Toxoplasma gondii. 2042 66

Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.
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PMID:Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy. 2234 35

Placental malaria is a common clinical complication during pregnancy and is associated with abortion, premature delivery, intrauterine growth retardation and low birth weight. The present study was designed to delineate the underlying mechanism of placental pathology during malarial infection with special reference to oxidative stress and apoptosis. Experimentally, pregnant BALB/c mice were infected with Plasmodium berghei infected red blood cells on gestation day 10. The presence of malarial infection in placenta was confirmed by histopathological studies. It was observation that infected placenta had plugged placental sinusoids with parasitized red blood cells and malarial pigments. Interestingly, we found significant increase in the level of malondialdehyde, the index of oxidative stress and decreased activity of catalase, the antioxidant in infected placenta. Furthermore, in infected placenta the oxidative stress mediated apoptosis was determined by DNA fragmentation assay, ethidium bromide/acridine orange staining and caspase activity. It was observed that oxidative stress begin after second day of malarial infection. Interestingly, it was observed that there was down regulation of anti-apoptotic protein Bcl-2 and up regulation of pro-apoptotic protein Bax in infected placenta, suggesting the involvement of mitochondrial pathway of apoptosis which was further confirmed by activation of caspase 9. However, no change in the expression of Fas gene and caspase 8 activity, indicated the absence of death receptor pathway. Thus, it can be concluded that the placental pathology during malarial infection is mediated by mitochondrial pathway of apoptosis occurring due to augmented lipid peroxidation which may in turn jeopardise the materno-fetal relationship.
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PMID:Role of oxidative stress and apoptosis in the placental pathology of Plasmodium berghei infected mice. 2239 90

Obstetric use of the antimalarial drug mefloquine has historically been discouraged during the first trimester and immediately before conception owing to concerns of potential fetal harm. With the rise of resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP), mefloquine is now being considered as a replacement for SP for universal antenatal administration to women from malaria-endemic regions. Recent recommendations have also suggested that mefloquine may be used cautiously among pregnant travelers who cannot otherwise avoid visiting these areas. Mefloquine has been demonstrated to cause blockade of gap junction protein alpha 1 (GJA1) gap junction intercellular communication (GJIC), and recent evidence suggests that GJA1 GJIC is critical to successful embryonic implantation and early placental development. During routine use, mefloquine accumulates in organ and peripheral tissue, crosses the blood-placental barrier, and may plausibly accumulate in developing decidua and trophoblast at concentrations sufficient to interfere with GJA1 GJIC and, thus, cause deleterious effects on fetal outcomes. This conclusion is supported by epidemiological evidence that demonstrates use of the drug during early development is associated with an increased risk of miscarriage and stillbirth. Confirmatory studies are pending, but the available experimental and epidemiological evidence support renewed adherence, where feasible, to existing mefloquine package insert guidance that women avoid the drug during the periconceptional period.
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PMID:Mefloquine gap junction blockade and risk of pregnancy loss. 2283 76

Malaria in pregnancy is associated with increased risks of maternal anemia, spontaneous abortion, low birth weight, premature delivery and other adverse effects on health. In Brazil, disease transmission is highly concentrated in the multi-state region that constitutes the Brazilian Amazon (more than 99% of all cases). This study, conducted between the first bimesters of 2007 and 2008, aims to identify the local barriers to prompt and effective case management of malaria in pregnancy and was carried out in health facilities located in three endemic municipalities of the Brazilian Amazon (Manaus, Presidente Figueiredo and Porto Velho). The study design combined both qualitative and quantitative descriptive methods. The qualitative design involved semi-structured interviews with health personnel who routinely deal with malaria care. The quantitative design involved a review of medical records of pregnant women in the visited health facilities. Additionally, data were abstracted from SIVEP-Malaria Epidemiological Surveillance Information System (Brasil, 2007) and Primary Care Information System (SIAB) databases. Flaws were detected in diagnosis (only 6.8% of women tested for malaria) and treatment (for Plasmodium falciparum infections, only 44.8% of patients received recommended first-line therapy; 10.2% of prescription presented treatments were not found in national guideline and 7.3% of the prescriptions for Plasmodium vivax and 17.9% of the prescriptions for P. falciparum were not sanctioned by the official guidelines). Training (only 37.3% had had some training), knowledge and counseling were also sub-optimal. These results indicated the need to improve the health-worker performance through training. Close supervision and feedback on the health-worker performance are also needed. These findings also highlighted the need to put into practice a series of government recommendations that encourage close collaboration between the National Malaria Control Program and Primary Health Care actions in order to achieve safer pregnancies.
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PMID:Uncomplicated malaria among pregnant women in the Brazilian Amazon: local barriers to prompt and effective case management. 2317 20


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