Placental impression smears is a good indicator of placental malaria in sub-Saharan Africa.

INTRODUCTION: Placental malaria (PM) is an important predictor of infant morbidity and mortality in sub-Saharan Africa. Although placental histology is the gold standard test to diagnose PM, the placenta impression smears remains widely used in epidemiological studies. This study is set to evaluate the performance of placental impression smears to detect PM in pregnant women in southern Benin. METHODS: A cross-sectional analysis was performed on data collected in the framework a multicenter randomized clinical trial (Malaria in Pregnancy Preventive and Alternative Drugs). Samples from 491 pregnant women were examined in the district of Allada, Southern Benin. Plasmodium falciparum infections have been assessed in placental blood and placental biopsy. RESULTS: Placental malaria detected by placenta impression smears and histology were prevalent in 11.4% and 10.8%, respectively. Sensitivity and specificity of placental impression smears were 90.6% and 98.4%. Among 55 pregnant women tested positive by placenta impression smears, 48 were positive by the histology, while 7 were negative (positive predictive value: 87.3%). Four hundred and twenty four (424) of the 429 tested negative by the placenta impression smears, were also negative according to histology whereas the rest (5 of 429) of the women were positive (negative predictive value: 98.8%). CONCLUSION: Placenta impression smear is an accurate and easy method for the diagnosis of placental malaria.

Placental Schistosoma haematobium infection in a German returnee from Malawi.

Schistosomiasis is a widespread helminthic infection which sometimes may affect travelers to endemic areas. We report on a case of urogenital and placental schistosomiasis in a 28-year-old German woman who had been exposed to schistosomiasis in Lake Malawi one year earlier. She experienced painless macrohaematuria in her 21st week of pregnancy. Cystoscopy revealed vesical lesions typical for urogenital schistosomiasis. Histopathology confirmed ova of Schistosoma (S.) haematobium. The patient was treated with praziquantel 40 mg/kg/body weight/day for 3 days. After 285 days of gestation and 18 weeks post treatment, the patient delivered a healthy girl. Histopathology of placenta revealed eggs of S. haematobium in placental stroma. The infant proved negative for anti-Schistosoma spp. antibodies at the age of 15 months. This is the first report on placental schistosomiasis since 1980 and the first case occurring in a traveler.

Iron homeostasis in mother and child during placental malaria infection.

In malaria-endemic areas, iron deficiency and placental Plasmodium falciparum infection commonly coexist. In primigravidae and their newborns, hepcidin and other iron parameters were evaluated in groups and classified according to placental P. falciparum and maternal anemia status. Mothers had relatively high hepcidin levels considering their low iron status. In cord blood, levels of hepcidin, hemoglobin, and other iron parameters were also similar for groups. We conclude that maternal hepcidin is not significantly altered as a function of placental infection and/or anemia. Importantly, fetal hemoglobin and iron status were also unaffected, regardless of the presence of placental infection or maternal anemia.

Characterization of reproductive disorders in ewes given an intrauterine dose of Toxoplasma gondii tachyzoites during the intrauterine insemination.

The aim of this study was to characterize the reproductive disorders in the acute and chronic phases in ewes experimentally infected with different doses of Toxoplasma gondii during artificial insemination occurred. Animals (n=41) were divided into three experimental groups: in the group 1 (G1, n=15), animals were inseminated using contaminated semen containing 6.5×104 tachyzoites; in the group 2 (G2, n=15), animals were inseminated with contaminated semen containing 4×107 tachyzoites and in the group 3 (G3, n=11), animals were inseminated using tachyzoite-free semen, serving as control group. Parasitemia and seroconversion were observed in 28 of 30 and 20 of 30, respectively, from the seventh day after infection. Embryonic reabsorption was observed in the acute phase in ewes from G1 and G2. Persistent anestrus, hydrometra, mucometra and follicular cysts were observed in the second phase of the experiment in animals from G1 and G2. Histopathological lesions similar to those of toxoplasmosis were found in the placentas. In conclusion, artificial insemination using semen containing experimentally added tachyzoites can establish toxoplasmosis in ewes and cause reproductive pathologies during the acute and chronic phases of the disease.

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth.

Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP3(+) Treg and more generalized FOXP3(+) CD4(+) Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-gamma, TNF-alpha, IFN-gamma:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

Placental malaria and low birth weight in pregnant women living in a rural area of Burkina Faso following the use of three preventive treatment regimens.

BACKGROUND: The weekly chemoprophylaxis of malaria during pregnancy with chloroquine (CQ) has become problematic with the increasing resistance of Plasmodium falciparum to this drug. There was a need to test the benefits of new strategies over the classical chemoprophylaxis. This study was conducted to provide data to the National Malarial Control Programme for an evidence-based policy change decision making process. It compares the efficacy of two IPT regimens, using chloroquine (CQ) or sulphadoxine/pyrimethamine (SP), with the classical chemoprophylaxis regimen using CQ in reducing the adverse outcomes of malaria infection, for the mother and the foetus. METHODS: Pregnant women attending the first antenatal care visit were randomly assigned to one of the three treatment regimens. They were subsequently followed up till delivery. Maternal, placental and cord blood samples were obtained upon delivery to check for P. falciparum infection. RESULTS: A total of 648 pregnant women were enrolled in the study. Delivery outcome were available for 423 of them. Peripheral maternal P. falciparum infection at delivery was found in 25.8% of the women. The proportion of women with maternal infection was significantly lower in the IPTp/SP group than in the CQ group (P << 0.000). The prevalence of placental malaria was 18.8% in the CWC/CQ group; 15.9% in the IPTp/CQ group and 10.6% in the IPTp/SP group. The incidence of LBW (weight < 2,500 g) was significantly higher among infants of mothers in the CWC/CQ group (23.9%) as compared with those of mothers in the IPTp/CQ (15.6%) and IPTp/SP (11.6%) groups (p = 0.02) CONCLUSION: Intermittent preventive treatment with SP has shown clear superiority in reducing adverse outcomes at delivery, as compared with intermittent preventive treatment with CQ and classical chemoprophylaxis with CQ.

A cohort study of haemoglobin and zinc protoporphyrin levels in term Zambian infants: effects of iron stores at birth, complementary food and placental malaria.

OBJECTIVE: To examine zinc-protoporphyrin (ZPP) and haemoglobin levels, and to determine predictors of iron deficiency anaemia (IDA) in Zambian infants. SUBJECTS AND METHODS: Ninety-one women and their normal birth weight (NBW) infants were followed bi-monthly during the first 6 months of life, and iron status, food intake, malaria parasitaemia and growth were monitored. At 4 months, the infants were divided into two groups, and the data were analysed according to whether or not they were exclusively breastfed. RESULTS: Almost two-third of infants were born with low iron stores as defined by ZPP levels, and this proportion increased with age. Over 50% had developed IDA by 6 months. Exclusive breastfeeding at 4 months could be a protective factor for IDA (odds ratio (OR): 0.2; 95% confidence interval (CI): 0.0-1.1). Exclusively breastfed infants had higher haemoglobin values at 4 and 6 months (mean difference 0.6; 95% CI: 0.1-1.2 g/dl and mean difference 0.9; 95% CI: 0.2-1.7 g/dl, respectively), compared with infants with early complementary feeding. In univariate analysis, past or chronic placental malaria appeared to be a predictor of IDA at 4 and 6 months, but the significance was lost in multivariate analysis. CONCLUSIONS: Zambian NBW infants are born with low iron stores and have a high risk to develop IDA in the first 6 months of life. Continuation of exclusive breastfeeding after 4 months is associated with a reduction of anaemia. The effect of placental malaria infection on increased risk of infant IDA could not be proven.

Decline of placental malaria in southern Ghana after the implementation of intermittent preventive treatment in pregnancy.

BACKGROUND: Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) has been adopted as policy by many countries in sub-Saharan Africa. However, data on the post-implementation effectiveness of this measure are scarce. METHODS: Clinical and parasitological parameters were assessed among women delivering at a district hospital in rural southern Ghana in the year 2000 when pyrimethamine chemoprophylaxis was recommended (n = 839) and in 2006 (n = 226), approximately one year after the implementation of IPTp-SP. Examinations were performed in an identical manner in 2000 and 2006 including the detection of placental Plasmodium falciparum infection by microscopy, histidine-rich protein 2, and PCR. RESULTS: In 2006, 77% of the women reported to have taken IPTp-SP at least once (26%, twice; 24%, thrice). In 2006 as compared to 2000, placental P. falciparum infection was reduced by 43-57% (P < 0.0001) and maternal anaemia by 33% (P = 0.0009), and median birth weight was 130 g higher (P = 0.02). In 2006, likewise, women who had taken > or = 1 dose of IPTp-SP revealed less infection and anaemia and their children tended to have higher birth weights as compared to women who had not used IPTp-SP. However, placental P. falciparum infection was still observed in 11% (microscopy) to 26% (PCR) of those women who had taken three doses of IPTp-SP. CONCLUSION: In southern Ghana, placental malaria and maternal anaemia have declined substantially and birth weight has increased after the implementation of IPTp-SP. Likely, these effects can further be increased by improving IPTp-SP coverage and adherence. However, the remnant prevalence of infection in women having taken three doses of IPTp-SP suggests that additional antimalarial measures are needed to prevent malaria in pregnancy in this region.

IL-12 producing monocytes and IFN-gamma and TNF-alpha producing T-lymphocytes are increased in placentas infected by Plasmodium falciparum.

Placental Plasmodium falciparum sequestration is associated with dysregulated immune function. Placental inflammatory responses via IFN-gamma and TNF-alpha are implicated in functional damage. However, they are needed during placental infection to control asexual stage parasites. To test the hypothesis that placental immunomodulation associated with malaria disturbs cytokine secretion differently in monocytes and lymphocytes, we have determined the proportion of monocytes and/or lymphocytes secreting IFN-gamma, TNF-alpha, IL-10 and IL-12. Intervillous and peripheral blood monocyte (CD14+) and lymphocyte (CD3/CD4+; CD3/CD8+) cytokine production was compared between 17 P. falciparum-infected and 12 non-infected Senegalese women. After culture with phorbolmyristate acetate/ionomycin (PMA/iono), lipopolysaccharide (LPS) or P. falciparum-infected erythrocytes (IE), the intracellular expression of cytokines in lymphocytes (IFN-gamma, TNF-alpha) and monocytes (IL-10, IL-12, TNF-alpha), was detected. In response to IE, CD4+ and CD8+ T-cells produced IFN-gamma and TNF-alpha at similar rates in both compartments. In response to PMA/iono, the frequencies of CD4+ and CD8+ T-cells producing IFN-gamma and TNF-alpha were similar in both compartments, but increased in P. falciparum-infected placentas. In response to LPS or IE, IL-12 secreting monocytes were increased in infected women, while the frequency of TNF-alpha secreting monocytes was decreased compared to that in non-infected placenta. The monocyte IL-12 response is not impaired in infected women. IL-12 is an important factor for inducing IFN-gamma in T-cells. Thus, IL-12 and IFN-alpha responses may synergistically allow a protective immune response in placental malaria. TNF-alpha production by CD4+ and CD8+ T-cells is up-regulated in P. falciparum-infected placentas, suggesting that T-cells actively participate to inflammatory responses.

Granulomatous villitis formed by inflammatory cells with maternal origin: a rare manifestation type of placental toxoplasmosis.

We present a case of placental toxoplasmosis with granulomatous villitis. The patient was a 26-year-old gravida 1 female with the findings of intrauterine death at 16th week of gestation. The pregnancy was terminated. Pathological examination revealed an autolysed fetus and a placenta with necrotizing granulomas within the villous stroma. Encysted Toxoplasma gondii was rarely observed within the granulomas and serologic examination of the mother confirmed acute toxoplasmosis. A fluorocein in situ hybridization examination, using sex chromosome probes, revealed that the villous granulomas were formed by inflammatory cells, originated from the maternal immune system. In conclusion, T. gondii should be taken into consideration as a rare cause of placental granulomatous inflammation. To the best of our knowledge, this is the first case of granulomatous villitis due to toxoplasmosis, in which formation by maternal inflammatory cells has been demonstrated.

Lack of an association between antibodies to Plasmodium falciparum glycosylphosphatidylinositols and malaria-associated placental changes in Cameroonian women with preterm and full-term deliveries.

Sequestration of Plasmodium falciparum parasites within the placenta often leads to an accumulation of macrophages within the intervillous space and increased production of tumor necrosis factor alpha (TNF-alpha), a cytokine associated with placental pathology and poor pregnancy outcomes. P. falciparum glycosylphosphatidylinositol (GPI) anchors have been shown to be the major parasite component that induces TNF-alpha production by monocytes and macrophages. Antibodies against P. falciparum GPI (anti-PfGPI), however, can inhibit the induction of TNF-alpha and inflammation. Thus, the study was undertaken to determine whether anti-PfGPI antibodies down-regulate inflammatory-type changes in the placentas of women with malaria. Anti-PfGPI immunoglobulin M (IgM) and IgG levels were measured in 380 pregnant women with or without placental malaria, including those who delivered prematurely and at term. Results showed that anti-PfGPI antibody levels increased with gravidity and age and that malaria infection boosted anti-PfGPI antibodies in pregnant women. However, no association was found between anti-PfGPI antibodies and placental TNF-alpha levels or the presence of acute or chronic placental malaria. Furthermore, anti-PfGPI antibody levels were similar in women with preterm and full-term deliveries and were not associated with an increase in infant birth weight. Thus, these results fail to support a strong role for anti-PfGPI antibodies in the prevention of chronic placental malaria infections and malaria-associated poor birth outcomes.

Immunity to placental malaria. I. Elevated production of interferon-gamma by placental blood mononuclear cells is associated with protection in an area with high transmission of malaria.

In areas in which malaria is holoendemic, primigravidae and secundigravidae, compared with multigravidae, are highly susceptible to placental malaria (PM). The nature of gravidity-dependent immune protection against PM was investigated by measuring in vitro production of cytokines by placental intervillous blood mononuclear cells (IVBMC). The results demonstrated that interferon (IFN)-gamma may be a critical factor in protection against PM: production of this cytokine by PM-negative multigravid IVBMC was elevated compared with PM-negative primigravid and secundigravid and PM-positive multigravid cells. Low IFN-gamma responsiveness to malarial antigen stimulation, most evident in the latter group, was balanced by increased interleukin (IL)-4 production, suggesting that counter-regulation of these two cytokines may be a crucial determinant in susceptibility to PM. A counter-regulatory relationship between IL-10 and tumor necrosis factor-alpha was also observed in response to malarial antigen stimulation. These data suggest that elevated production of IFN-gamma, as part of a carefully regulated cytokine network, is important in the control of PM.

[Placental infection in Rwanda: comparison an HIV infected population and a control population]. / Infection placentaire au Rwanda: comparaison entre une population infectée par le VIH et une population contrôle.

We report an histological study from term placentas of 286 HIV positive women born in Rwanda. We observed chorioamnionitis without any pathogen in 15% of the cases, cocci Gram positive infection in 12 observations and malaria infection in 75% of placentas. We noted 71 cases of active malaria infection with Plasmodium falciparum trophozoites in the erythrocytes of the intervillous spaces, and 135 cases of chronic infection with malaria pigment without any parasite. An ultrastructural study performed in 8 cases of active malaria infection showed characteristic features of trophozoites and schizontes, and malaria pigment. No viral particle were seen. We did not observe any significative difference concerning the incidence of chorioamnionitis and of malaria infection in 275 HIV negative placentas. In the literature as well as in the present study, the main lesions observed in the placentas of AIDS patients were chorioamnionitis. Opportunistic infections and neoplasias of the placenta are exceptional. Detection of HIV proteins by immunochemistry or in situ hybridization is possible, but the HIV could not be identified in the trophoblast by electron microscopy. Mechanisms of the materno-fetal transmission for HIV are currently unknown.

[The value of anatomo-pathologic examination of the placenta in areas of endemic malaria and low socio-cultural levels]. / Intérêt de l'examen anatomo-pathologique du placenta dans les zones d'endémie palustre et de faible niveau socio-culturel.

OBJECTIVES: Determine the sensitivity of the pathology examination of the placenta as a screening examination for malaria and the consequences of this infection on prematurity and birth-weight. METHODS: Eighty placentas were examined at the Mjunga, Madagascar dispensary at the beginning of the rainy season. The aspect of the placenta was compared with a malaria index and to malaria disease state as a function of parity and anti-malarial prophylaxis used by the mother as well as with the state of the infant. RESULTS: Among the placentas examined, 41.3% were considered normal and abnormal or clearly pathological in 58.7%. Estimating the gestational age on the basis of the histological examination of the amniotic cells was in agreement with the gestational age calculated from the last cycle in 53 cases and in disagreement in 8 cases. The percentage of cases of malaria discovered by the pathology examination (20%) was greater than that after thick swab screening (10%). 75% of the mothers has Plasmodium falciparum infection at the time of delivery and 13.8% of the mothers with negative thick drops had malaria lesions of the placenta. The parity of infected mothers was similar to non infected mothers. All the premature newborns had pathological placentas included 12.5% with malarial lesions. 90% of the hypertrophic newborns had pathological placentas included 50% with malarial lesions. No case of congenital malaria was observed. CONCLUSION: Pathology examination of the placenta is as sensitive as blood drop tests for screening for malaria. The histological examination of amniotic cells can give a good estimation of gestational age in developing countries.

[Toxoplasmosis in pregnancy. Prevention, diagnosis, and therapy]. / La toxoplasmosi in gravidanza. Prevenzione, diagnosi e terapia.

Toxoplasmosis is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity or in subclinical neonatal infection; most subclinical cases will develop ocular and neurological sequelae. Fetal infection and clinical outcome is related to when in pregnancy toxoplasmosis was acquired. The risk of transmission increases from 14% in the first trimester to 29% in the second and 59% in the third. Conversely, clinical damage decreases from about 80% in the first to 10% in the third trimester, but up to 50% of patients with subclinical congenital toxoplasmosis will develop neurologic and ocular sequelae. Congenital toxoplasmosis can be prevented by identification of non immune women at the beginning of pregnancy, by giving information on how to avoid the infection and by a serological follow-up until the delivery. Serological follow-up is based on repeated testing for specific IgG and IgM, but other serologic methods are necessary to differentiate between acute and chronic infections and possibly on a single serum sample. Procedures to detect fetal infection are ultrasound examination, cordocentesis and amniocentesis; prenatal diagnosis relies on demonstration of toxoplasma in fetal blood or amniotic fluid by mouse inoculation. Very promising results have recently obtained by the PCR-method applied to amniotic fluid samples. All strongly suspected cases of acquired toxoplasmosis in pregnancy have to be treated.

El examen de strout modificado usado como prueba de detección sistemática de la enfermedad de Chagas transplacentaria: I. Recolección y conservación de la sangre de cordón umbilical del recién nacido / The modified strout test used as systematic detection test of the transplacental Chagas'disease: I. Collection and preservation of the newborn's umbilical cord blood

A modified strout test used as a probe for the transplacental Chagas disease systemic diagnosis. I. Collection and preservation of the newborn`s umbilical cord blood

Estudio prospectivo de la enfermedade de Chagas en recien nacidos con infección placentaria por Trypanosoma cruzi (Santa Cruz, Bolivia) / Prospective study of Chagas disease in newborn children with placental infection caused by Trypanosoma cruzi (Santa Cruz, Bolivia)

Para conocer la significancia de la infección placentária por T. cruzi, 820 recien nacidos (RN) con peso ó 2500grs fueron examinados por los métodos del Strout y cortes histopatológicos de placenta, 35 RN presentaron infección placentária por T. cruzi, pero con el examen parasitológico directo en sangre del cordon umbilical negativo. A estos RN se les hizó el seguimiento parasitologico (microhematocrito y xenodiagnóstico) para detectar una eventual positivación en el post-parto. El seguimiento fué a los 7, 15, 30 y 60 dias después del nacimiento y con xenodiagnóstico a los 15 dias. En 27 RN se pudo completar el seguimiento observandose una positivación parasitária a T. cruzi en todos los casos. En el grupo control constituido por RN negativos a ambos, no hubo ninguna positivación durante el seguimiento. Estas observaciones nos permiten proponer, que un recien nacido con infección placentária por T. cruzi es un caso congênito y establecer un esquema práctico de diagnóstico precoz de la enfermedad de Chagas congênito

Transplacental Neospora caninum infection in cats.

Transplacental transmission of Neospora caninum was studied in 2 pregnant cats (queens). Queen 1 was inoculated subcutaneously with 2 x 10(6) cell culture-derived N. caninum tachyzoites on day 47 of gestation. She gave birth to a full-term kitten on the 17th day after inoculation. The kitten died the second day after birth due to generalized N. caninum infection. The mother cat was killed on the third day after parturition and was found to have a macerated kitten in the uterus. Severe placentitis, metritis, hepatitis, and nephritis due to N. caninum were seen in tissues from the queen. Queen 2 was fed N. caninum tissue cysts and mated 111 days later. She gave birth to 3 healthy full-term kittens. The kittens were necropsied at 2, 22, and 30 days of age. Neospora caninum was recovered from the organs and was seen in histologic sections in 1 of the 3 kittens. Results indicate that N. caninum can be transplacentally transmitted in cats during acute and chronic stages of infection. Neospora caninum-specific IgG antibodies were demonstrated in the sera of inoculated cats and nursing kittens.

Toxoplasma gondii cysts in placentas of experimentally infected sheep.

To determine the presence of tissue cysts in ovine placentas, 6 ewes were inoculated orally with 10,000 Toxoplasma gondii oocysts at 60 days of gestation. The ewes were euthanatized and necropsied 21, 52, 56, 57, 57, and 62 days after T gondii inoculation, and placental cotyledons from each ewe were collected and homogenized. To distinguish between the presence of tachyzoites that are killed by acid pepsin solution and bradyzoites (from cysts) unaffected by this solution, a portion of each homogenate was inoculated into mice and another portion was inoculated into mice after digestion in acid pepsin solution. Toxoplasma gondii was isolated in 26 of 34 (76.4%) of mice inoculated with nondigested placentas of all 6 ewes and in 16 of 34 (47%) mice inoculated with digested placenta of 5 of 6 ewes. Seemingly, cysts do occur in placental tissue, but the digestion method was inferior, compared with the nondigestion method for recovery of T gondii from placenta.