S J Rogerson

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..VAR2CSA appears to be the main ligand responsible for adhesion to chondroitin sulphate A (CSA). Whether other PfEMP1 molecules can also mediate placental adhesion, independent of CSA binding, is unclear...

..This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure...

..This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation...

..Improved understanding of the relationship between pathogenesis, immunity, and pregnancy outcome will allow better targeting of our interventions to prevent the consequences of malaria in pregnancy...

..0001), number of ANC visits (P = 0.002), and recent febrile symptoms (P = 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development...

..02). Placental histology is the most sensitive method for the diagnosis of malaria in pregnancy. Methods for preparation of placental films may affect the density, but not the prevalence, of P. falciparum infection detected...

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..Such approaches would greatly increase our knowledge on the pathogenesis of this disease and may provide new avenues for intervention strategies...

..Prevention of pregnancy malaria by vaccination may also become possible, but targets must be closely defined, and strategies developed to test candidates against meaningful end points...

..With increasing malaria control efforts worldwide, declining population immunity might alter drug response profiles. Improved methods for assessing antimalarial immunity will strengthen malaria control efforts...

..Placental production of TNF-alpha, but not of IFN-gamma, may be implicated in impaired fetal growth in Malawian women...

..The prevalence of agglutinating antibodies to pregnancy isolates was generally low, but it was highest in multigravidae who are likely to have had the greatest exposure...

..falciparum erythrocyte membrane protein 1 as the parasite ligand paves the way to a more detailed understanding of the pathogenesis of placental infection and potential therapeutic strategies targeting the interaction...

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..falciparum antigens is more likely to account for the age-dependent prevalence of parasitaemia observed...

..falciparum-erythrocyte membrane protein 1 (PfEMP1)...

..002), and both formed fewer rosettes than isolates cultured from children (range, 0 to 56%; P < 0.0001). Rosette formation is common in infections of children but uncommon in pregnancy and rarely detected in placental isolates...

..The results of recent research indicating an interaction between HIV and malaria in pregnancy are summarized. Ten questions for basic researchers are posed. The answers may help direct future efforts to control malaria in pregnancy...

..Intermittent presumptive treatment with SP is having a positive impact on some, but not all indicators of malaria infection and morbidity in Malawi. Improved implementation and continued surveillance are essential...

..Fixed Giemsa-stained smears allow long-term storage and re-examination, without fluorescence microscopy...

..We propose that the differential timing of binding provides a mechanism for the temporal repression of rif genes. In addition, we find that transcription profiles of upsA var genes and their neighbouring rif genes are unlinked...

..These findings do not support the hypothesis that cerebral malaria is caused by cerebral sequestration of certain virulent types...

..The lack of novel genotypes emerging suggests that among children with severe malaria the dominant clones sequestered in deep organs are usually the same as those in peripheral circulation...

..Furthermore, we found that the prevalence of the SAO trait was lower among pregnant women than among non-pregnant controls...

..Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual...

..CONCLUSION: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections...

..The diversity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy...

..However, our observation that low-dose iRBCs initiate functional DC maturation warrants reevaluation and further investigation of DC interactions with blood-stage P. falciparum...

..The mechanism of mother-to-child transmission (MTCT) of HIV-1 is not well described...

..We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR...

..005) was lower in HIV-infected women than in HIV-uninfected women. HIV infection has a broad impact on variant-specific immunity, which may explain the susceptibility of infected individuals to clinical malaria episodes...

..005; for MSP-2, P< .05) or SMA (for MSP-1 and MSP-2, P<.001; for AMA-1, P< .005). These distinct IgG patterns might reflect differences in age, exposure to P. falciparum, and/or genetic factors affecting immune responses...

..These assays have the advantage over other malaria phagocytosis assays in that they are rapid, simple and specific to malaria-infected cells and avoid potential bias associated with manual counting...

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..falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis...

..These data suggest a role for CD16(+) monocytes in the pathogenesis of maternal malaria and HIV-1 infections...

..Together these data suggest that a single P. falciparum infection can be sufficient to induce antibodies reactive with several PfEMP1 variants, although the repertoire of target epitopes they recognize may still be restricted...

..Although these nonhydrolyzable GTP analogs reduced erythrocyte invasion efficiency and partially retarded growth of the intracellular parasite, they appeared to have little direct effect on PfEMP1 trafficking...

..03). CONCLUSION: Placental malaria infection is associated with an increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child transmission of HIV...

..Comparisons between antibodies suggest that adhesion-inhibitory antibodies and those to PRBC variant antigens have distinct and overlapping epitopes, may be acquired independently, and have different roles in immunity...

..In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta...

..Neither OptiMAL nor PCR testing of peripheral blood is adequately sensitive to detect all placental malaria infection, but a positive result by OptiMAL testing identifies women with a high proportion of low-birth-weight babies...

..These findings demonstrate prominent selective accumulation of mature asexual-stage IEs but infrequent accumulation of ring stages in the placental blood spaces, consistent with an important role for mature-stage IE adhesion...

..These findings have important implications for understanding and evaluating interactions between P. falciparum and hyaluronic acid that may be involved in disease pathogenesis...

..Transplacental infection before term, and clearance of maternal infection, is postulated...

..These results indicate the need for reevaluation of previous assumptions of a minimal overlap between var gene repertoires from different parasite isolates...

..The impairment is greatest in the most immunosuppressed women and could explain the increased susceptibility to malaria seen in pregnant women with HIV infection...

..Almost 30% of HIV-infected children died, compared with 8.9% of uninfected children, and HIV-infected children constituted over 40% of in-patient deaths...

..In this paper, we attempt to improve our understanding of the disease and its mechanisms from observed differences and similarities between contrasting areas of transmission, and to identify priorities for future research...

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..Conclusions. Immunity may be mediated by a repertoire of antibodies to diverse and common epitopes. Strategies based on vaccination with a single domain or isolate might be hindered by antigenic diversity...

..Between 25% and 35% of infants born to HIV-infected mothers become HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could be through a breakdown in the placental barrier (i.e., maternal-fetal microtransfusions)...

..The dihydrofolate reductase 164-Leu mutation, which confers resistance to both pyrimethamine and chlorproguanil, was found in 4.7% of the samples. Previously unreported mutations in dihydropteroate synthase were also found...

..CONCLUSIONS: The HIV and CAM were the major infections associated with PTD in this study. CAM, but not malaria, causes PTD via its effect on proinflammatory cytokines...

..They may function by blocking parasite adhesion to placental CSA, but given their cytophilic nature, they might also opsonize malaria-infected erythrocytes for interaction with Fc receptors on phagocytic cells...

..These data are consistent with the hypothesis that var2csa encodes a PfEMP1 expressed on the surface of IE, which mediates adhesion to CSA and is relatively conserved between genetically distinct strains of P. falciparum...

..Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription...

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..There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women...

..We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi...

..If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa...