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Objective To evaluate the impact of malaria on maternal death through the analysis of the seasonal variations of crude and malaria-specific maternal mortality rates. Methods All maternal deaths and live births occurring at Maputo Central Hospital, located in an urban area, between January 2001 and December 2003, were retrospectively recorded. Clinical diagnoses of the causes of death and period of the year were analysed. Results Two hundred and seventy-eight deaths were recorded. The overall crude maternal mortality rate was 995/100 000 live births. Malaria was the most frequent cause of maternal death, accounting for 23%. Crude and malaria-specific maternal mortality rates showed a similar pattern of seasonal variation, with peaks at the beginning and the end of the malaria transmission season. The malaria-specific maternal mortality rate was significantly higher during the rainy seasons (rate ratio 1.919; 95% CI 1.061, 3.470; P = 0.031). Conclusions Malaria may contribute to maternal mortality in highly endemic countries in sub-Saharan Africa, at least in urban areas. Efforts to improve malaria control in pregnancy may have an impact on maternal mortality in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Presents information on a study which characterized the inflammatory infiltrates in the placenta immunohistochemically, using a broad panel of monoclonal antibodies in samples from women with different types of malarial infection. Discussion on malaria and plasmodium falciparium; Materials and methods; Results of the study.

Background: Leukoerythroblastosis, a non-specific and often short-lasting response of the bone marrow to different diseases such as malignancies or infections, is characterized by the presence in the peripheral blood of immature red and white cells.Methods: We present a case of leukoerythoblastosis occurring in a 24 months old Mozambican girl, in the context of a severe malaria episode and an associated urinary tract infection. Peripheral blood smear was used for diagnosis of malaria and leukoerythroblastosis. Enterobacter cloacae isolation and antibiotic susceptibility testing were performed by conventional microbiology.Results: Peripheral blood smear was positive for Plasmodium falciparum and showed a leukoerythroblastosis with red cell anisopoikilocytosis and left shifted neutrophils. Urine culture confirmed the presence of a multi-resistant E. cloacae. Treatment of underlying conditions resolved the leukoerythroblastic reaction.Conclusions: Leukoerythroblastosis may be related to different infectious diseases and may also appear in the context of severe malaria. Bacterial superinfection needs to be investigated. [ABSTRACT FROM AUTHOR]

Background: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. Methods: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a nonfalciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. Results: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. Conclusions: Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites. [ABSTRACT FROM AUTHOR]

Background: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. Methods and Findings: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. Conclusions: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. Trial Registration: ClinicalTrials.gov Pan African Clinical trials Registry [ABSTRACT FROM AUTHOR]

Background. Malaria and human immunodeficiency virus (HIV) infection during pregnancy affect the transplacental transfer of antibodies against several pathogens from mother to fetus, although the effect of malaria and HIV infection on the transfer of antimalarial antibodies remains unclear.Methods. Levels of total immunoglobulin G (IgG), immunoglobulin M (IgM), and IgG subtypes against the following Plasmodium falciparum antigens were measured in 187 pairs of mother-cord plasma specimens from Mozambique: 19-kDa fragment of merozoite surface protein 1 (MSP119), erythrocyte binding antigen 175 (EBA175), apical membrane antigen 1 (AMA1), and parasite lysate. Placental antibody transfer was defined as the cord-to-mother ratio (CMR) of antibody levels.Results. Maternal malaria was associated with reduced CMR of EBA175 IgG (P = .014) and IgG1 (P = .029), AMA1 IgG (P = .002), lysate IgG1 (P = .001), and MSP1 IgG3 (P = .01). Maternal HIV was associated with reduced CMR of MSP1 IgG1 (P = .022) and IgG3 (P = .023), lysate IgG1 (P = .027) and IgG3 (P = .025), AMA1 IgG1 (P = .001), and EBA175 IgG3 (P = .001). Decreased CMR was not associated with increased adverse pregnancy outcomes or augmented risk of malaria in the infant during the first year of life.Conclusions. Placental transfer of antimalarial antibodies is reduced in pregnant women with malaria and HIV infection. However, this decrease does not contribute to an increased risk of malaria-associated morbidity during infancy. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49–91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 19-year-old patient who experienced spleen rupture due to an untreated infection with Plasmodium vivax, a parasite that causes malaria. The study examined the patient's spleen and found high levels of the parasite in the red pulp. Additionally, the study observed an increase in plasmablasts, a type of immune cell, in the spleen. These findings suggest that P. vivax infections can cause changes in the spleen that resemble lymphoma and may impact the development of immunity against the parasite. [Extracted from the article]

The article presents a case study of a 19-year-old nonimmune patient with Plasmodium vivax monoinfection supported by polymerase chain reaction (PCR) in his peripheral blood and spline section. It states that the initial diagnosis revealed anemia and thrombocytopenia, and he was transferred to a tertiary-care infectious diseases reference center. The patient submits to splenectomy due to profuse intra-abdominal hemorrhage.

The histological study of the placenta is useful in the diagnosis of malaria during pregnancy. However, the scarcity of parasites and pigment in many malarial infections renders their identification difficult. We have tested the accuracy of standard and polarisation microscopy in the evaluation of 500 placental specimens from an area of high malarial endemicity in Tanzania. Standard microscopy showed a low sensitivity (50.3% for parasites, 40.5% for pigment), due to poor detection rates in cases with scant parasites (12.7% for <1%; 97.8% for >5% parasitised erythrocytes, P<0.001) or minimal pigment deposition (42.4% versus 84.5% when severe, P<0.001). The use of polarisation microscopy significantly increased the sensitivity of detection of pigment to 100% and parasites to 98.1% because of the marked birefringence of hemozoin present in mature stage parasites which accumulate in the placenta. Formalin pigment shares many properties with hemozoin, but the use of neutral buffered formalin prevented the formation of formalin pigment in placentas even after long periods of fixation. In conclusion, polarisation microscopy is a simple tool that markedly increases the sensitivity of the detection of malaria infection in the placenta and has good specificity when used on tissues fixed in neutral formalin. This method can be useful to investigators working in the malaria field. [Copyright &y& Elsevier]

Background: Difficulties to disentangle the protective versus exposure role of anti-malarial antibodies hamper the identification of clinically-relevant immune targets. Here, factors affecting maternal IgG and IgMs against Plasmodium falciparum antigens, as well as their relationship with parasite infection and clinical outcomes, were assessed in mothers and their children. Antibody responses among 207 Mozambican pregnant women at delivery against MSP119, EBA175, AMA1, DBLα and parasite lysate (3D7, R29 and E8B parasite lines), as well as the surface of infected erythrocytes, were assessed by enzyme-linked immunosorbent assay and flow cytometry. The relationship between antibody levels, maternal infection and clinical outcomes was assessed by multivariate regression analysis. Results: Placental infection was associated with an increase in maternal levels of IgGs and IgMs against a broad range of parasite antigens. The multivariate analysis including IgGs and IgMs showed that the newborn weight increased with increasing IgG levels against a parasite lysate, whereas the opposite association was found with IgMs. IgGs are markers of protection against poor pregnancy outcomes and IgMs of parasite exposure. Conclusions: Adjusting the analysis for the simultaneous effect of IgMs and IgGs can contribute to account for heterogeneous exposure to P. falciparum when assessing immune responses effective against malaria in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF, TNF-β was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR. Results: Higher concentrations of IL-6 and IL-1β were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1β and TNF strongly correlated among themselves (ρ > 0.5, p < 0.001). Higher production of IL-1β was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044). Conclusions: Complex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection. [ABSTRACT FROM AUTHOR]