Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1.

The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase 125I-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion.     

Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model

Using an in vitro model of human lung endothelial cells, we studied different characteristics of Plasmodium falciparum isolates as potential factors for malaria severity in 2 Thai patient groups: 27 with complicated malaria and 42 with uncomplicated malaria. In regard to binding properties, no association existed between cytoadherence and rosette phenotypes (P = 0.1) and hypothrombocytemia increased the cytoadherence level (P = 0.007). Cytoadherence was significantly associated with malaria severity (P = 0.05) in contrast to rosette formation (P = 0.9). Intercellular adhesion molecule-1 and chondroitin-4-sulfate were major receptors of cytoadherence in those with complicated malaria compared with those with uncomplicated malaria (P < 10(-4)). Chondroitin-4-sulfate could act as a putative receptor for malaria complications in non-pregnant women. CD36 was the main receptor in patients with uncomplicated malaria (P < 10(-3)). Vascular cell adhesion molecule-1 and E-selectin played a minor role in 2 groups (P = 0.6). Qinghaosu derivatives were more efficient than other antimalarial drugs, but a positive correlation was observed between the 50% inhibitory concentrations of halofantrine and quinine and the number of adhesive parasitized red blood cells, suggesting their influence on cytoadherence.     

Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes

In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37 degrees C, but after heating to febrile temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance.     

Receptor specificity of clinical Plasmodium falciparum isolates: nonadherence to cell-bound E-selectin and vascular cell adhesion molecule-1

The pathogenicity of Plasmodium falciparum is due largely to the parasite's unique ability to adhere to capillary and postcapillary venular endothelium during the second-half of the 48-hour life cycle. The resulting sequestration of infected erythrocytes (IRBC) in deep vascular beds leads to tissue hypoxia, metabolic disturbances, and organ dysfunction which characterize severe falciparum malaria. Several endothelial receptors of cytoadherence have been identified, but their clinical relevance remains controversial. In the present report, the receptor specificity of 60 clinical P falciparum isolates was determined using transfectants each expressing one of CD36, intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). All isolates tested adhered to CD36 and ICAM-1, but the adherence to CD36 was at least 10-fold higher. Seven isolates adhered to E-selectin whereas none of 19 isolates adhered to VCAM-1. From a population standpoint, about 30% of IRBC in each isolate adhered to CD36, and 2% to 3% adhered to ICAM-1. The percentage adherent to E-selectin and VCAM-1 was negligible. IRBC selected on CD36 adhered almost exclusively to CD36 whereas 80% to 90% of IRBC selected on ICAM-1 could also adhere to CD36. Selected IRBC did not adhere to E-selectin or VCAM-1. These findings indicate that cytoadherence to multiple endothelial receptors is a rare occurrence with natural P falciparum isolates, but do not exclude a role for the adhesion molecules in promoting other IRBC-endothelial interactions such as rolling under flow conditions. Receptor specificity in vivo may be dictated by the ligand-receptor combination which provides the best survival potential for the parasite.     

Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria.

The ability of Plasmodium falciparum-infected red blood cells (RBC) to form spontaneous erythrocyte rosettes was studied in 130 fresh isolates from Gambian children with cerebral or uncomplicated malaria from August to November 1990. All isolates (24 of 24) from patients with cerebral malaria formed rosettes, but only 61 of 106 isolates from children with uncomplicated malaria formed rosettes. The mean rate of rosette formation in isolates from children with cerebral malaria (28.3%) was significantly greater than that in isolates from children with uncomplicated malaria (8.5%). Giant rosettes were more frequently formed in isolates from patients with cerebral malaria than in those from patients with uncomplicated malaria. Sera of children with cerebral disease generally lacked anti-rosette activity, while many sera from children with uncomplicated malaria showed strong anti-rosette activity when tested against the patients' ow parasites. Some sera that were devoid of autologous rosette-disrupting activity were able to disrupt rosettes formed in other isolates, indicating the presence of different rosette formation mechanisms. Forty percent (6 of 15) of the sera from patients with cerebral malaria caused microagglutination of the patients' own uninfected and infected RBC, while only 10% (3 of 31) of sera from children with uncomplicated disease caused microagglutination. The ability of infected RBC to bind to melanoma cells grown in vitro did not differ between patients with cerebral or uncomplicated malaria. The results of this study, taken in conjunction with our previous findings, establish a strong association between rosette formation in P. falciparum-infected RBC and cerebral malaria.     

Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1.

Adherence of mature Plasmodium falciparum parasitized erythrocytes (PRBCs) to microvascular endothelium contributes directly to acute malaria pathology. We affinity purified molecules from detergent extracts of surface-radioiodinated PRBCs using several endothelial cell receptors known to support PRBC adherence, including CD36, thrombospondin (TSP), and intercellular adhesion molecule 1 (ICAM-1). All three host receptors affinity purified P. falciparum erythrocyte membrane protein 1 (PfEMP1), a very large malarial protein expressed on the surface of adherent PRBCs. Binding of PfEMP1 to particular host cell receptors correlated with the binding phenotype of the PRBCs from which PfEMP1 was extracted. Preadsorption of PRBC extracts with anti-PfEMP1 antibodies, CD36, or TSP markedly reduced PfEMP1 binding to CD36 or TSP. Mild trypsinization of intact PRBCs of P. falciparum strains shown to express antigenically different PfEMP1 released different (125)I-labeled tryptic fragments of PfEMP1 that bound specifically to CD36 and TSP. In clone C5 and strain MC, these activities resided on different tryptic fragments, but a single tryptic fragment from clone ItG-ICAM bound to both CD36 and TSP. Hence, the CD36- and TSP-binding domains are distinct entities located on a single PfEMP1 molecule. PfEMP1, the malarial variant antigen on infected erythrocytes, is therefore a receptor for CD36, TSP, and ICAM-1. A therapeutic approach to block or reverse adherence of PRBCs to host cell receptors can now be pursued with the identification of PfEMP1 as a malarial receptor for PRBC adherence to host proteins.     

Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand

The kinetic profiles of soluble chondroitin-sulphate A (CSA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin were investigated in 17 patients hospitalized with Plasmodium falciparum malaria. The aim was to see if these circulating adhesion molecules could be considered as markers for the severity of P. falciparum malaria. The levels of all the adhesion molecules were found to be higher in the sera from all the malaria cases, both severe and uncomplicated, than in those from uninfected controls. The elevation in plasma CSA, reported for the first time, was statistically very significant (P = 0.00001). However, when severe cases were compared with the uncomplicated, there were no significant differences in the level of any of the receptors except ICAM-1, which was highest in those with the severe disease (P = 0.01). The absence of any significant correlation between the plasma concentration of CSA and malaria severity indicates that this adhesion molecule could not be used to predict the severity of malaria, although its role in sequestration of the parasites in pregnant women is well established.     

Antibodies among men and children to placental-binding Plasmodium falciparum-infected erythrocytes that express var2csa

During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.     

Plasmodium falciparum-infected erythrocytes demonstrate dual specificity for adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive properties

Hyaluronic acid (HA) and chondroitin sulfate A (CSA) have been identified as receptors for adhesion of Plasmodium falciparum-infected erythrocytes (IEs) and appear to be involved in mediating parasite accumulation in the placenta. We demonstrate here that some, but not all, parasite populations can adhere to both receptors, and we identify distinguishing features of adhesion. Adhesion to HA and CSA was greatest among pigmented trophozoite-infected erythrocytes and at physiologic pH and was associated with a lack of rosette formation and little adhesion to CD36 and intercellular adhesion molecule-1. Adhesion to HA was sensitive to trypsin cleavage of the IE surface, whereas trypsin-resistant and trypsin-sensitive CSA adhesion were both observed. Soluble HA, but not CSA, could cause aggregation or clumping of IEs. Different HA types varied in adhesion-inhibitory activity, which was altered by physical treatment, suggesting that structural features of HA influence IE interactions. These findings have important implications for understanding the pathogenesis of malaria, particularly in pregnancy.     

Modifications in the CD36 binding domain of the Plasmodium falciparum variant antigen are responsible for the inability of chondroitin sulfate A adherent parasites to bind CD36

Adhesion of mature Plasmodium falciparum parasitized erythrocytes to microvascular endothelial cells or to placenta contributes directly to the virulence and severe pathology of P falciparum malaria. Whereas CD36 is the major endothelial receptor for microvasculature sequestration, infected erythrocytes adhering in the placenta bind chondroitin sulfate A (CSA) but not CD36. Binding to both receptors is mediated by different members of the large and diverse protein family P falciparum erythrocyte membrane protein-1 (PfEMP-1) and involves different regions of the molecule. The PfEMP-1-binding domain for CD36 resides in the cysteine-rich interdomain region 1 (CIDR-1). To explore why CSA-binding parasites do not bind CD36, CIDR-1 domains from CD36- or CSA-binding parasites were expressed in mammalian cells and tested for adhesion. Although CIDR-1 domains from CD36-adherent strains strongly bound CD36, those from CSA-adherent parasites did not. The CIDR-1 domain has also been reported to bind CSA. However, none of the CIDR-1 domains tested bound CSA. Chimeric proteins between CIDR-1 domains that bind or do not bind CD36 and mutagenesis experiments revealed that modifications in the minimal CD36-binding region (M2 region) are responsible for the inability of CSA-selected parasites to bind CD36. One of these modifications, mapped to a 3-amino acid substitution in the M2 region, ablated binding in one variant and largely reduced binding of another. These findings provide a molecular explanation for the inability of placental sequestered parasites to bind CD36 and provide additional insight into critical residues for the CIDR-1/CD36 interaction.     

Association of msp-1, msp-2 and pfcrt genes with the severe complications of Plasmodium falciparum malaria in children

The pathogenesis of severe malaria is still not clearly understood and there are few substantial data describing the association of specific parasite genotypes with the severity of Plasmodium falciparum infection in humans. The merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) of P. falciparum play a crucial role in the parasite's invasion of the human host and the subsequent manifestation of the complications of severe malaria. Attempts at associating msp-1 and msp-2 genotypes with the severity of P. falciparum malaria therefore appear worthwhile. In the present study, based in the malaria-endemic district of Sundergarh, in the Indian state of Orissa, the msp-1, msp-2 and pfcrt genotypes of P. falciparum infecting children were investigated and compared against the severity of malaria in each donor child. The two major complications seen in the subjects, cerebral malaria and severe anaemia, were each found to be significantly associated with the RO33 subtype of msp-1 and the 3D7 subtype of msp-2. Although the study isolates showed a high degree of multiclonicity (multiplicity of infection = 1.9) and of polymorphism in msp-1 and -2, almost all (95%) of the isolates had the K76T mutation in their pfcrt genes.     

Cytoadherence of Plasmodium falciparum-infected erythrocytes in the human placenta

In Plasmodium falciparum-parasitized pregnant women, erythrocytes infected by mature stages of the parasite sequester into placental intervillous spaces. The presence of parasites in the placenta causes maternal anaemia and low birth weight of the infant. In-vitro studies suggest placental sequestration may involve the cytoadherence of infected erythrocytes to chondroitin sulphate A (CSA) and/or intercellular adhesion molecule 1 (ICAM-1) expressed by human placental syncytiotrophoblast. We identified P. falciparum receptors expressed on the surface of human syncytiotrophoblast using immunofluorescence of placental biopsies from Cameroon, a malaria-endemic area. In all placentas, a strongly positive staining was observed on the syncytiotrophoblast for CSA, but not for ICAM-1, vascular endothelium cell adhesion molecule-1, E-selectin, nor CD36. The cytoadherence ability of parasites from pregnant women and nonpregnant subjects was assessed on in-vitro cultured syncytiotrophoblast. Parasites from pregnant women bound to the trophoblast via CSA but not ICAM-1. Parasites from nonpregnant hosts either did not bind to the trophoblast culture or bound using ICAM-1. Our data support the idea that placental sequestration may result from cytoadherence to placental trophoblast and that pregnant women are parasitized by parasites that differ from parasites derived from nonpregnant host by their cytoadherence ability.     

Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence

Two potential malaria virulence factors, parasite multiplication rate (PMR) and red blood cell selectivity (measured as selectivity index [SI]), were assessed in Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not differ significantly between uncomplicated and severe malaria cases. Malian isolates from hyperparasitemic patients had significantly lower PMRs (median = 1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n = 23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test). Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98; Mali geometric mean SI = 1.6, n = 104), and there was no significant association between the SI and malaria severity. Therefore, in contrast to previous results from Thailand, we found no association of PMR and SI with malaria severity in African children. This raises the possibility of differences in the mechanisms of malaria virulence between sub-Saharan Africa and Asia.     

Plasmodium falciparum antigenic variation: relationships between in vivo selection, acquired antibody response, and disease severity

BACKGROUND: Variant surface antigens (VSA) on Plasmodium falciparum-infected erythrocytes are potentially important targets of immunity to malaria. We previously identified a VSA phenotype--VSA with a high frequency of antibody recognition (VSA(FoRH))--that is associated with young host age and severe malaria. We hypothesized that VSA(FoRH) are positively selected by host molecules such as intercellular adhesion molecule 1 (ICAM1) and CD36 and dominate in the absence of an effective immune response. Here, we assessed, in 115 Kenyan children, the potential role played by in vivo selection pressures in either favoring or selecting against VSA(FoRH) among parasites that cause malaria. METHODS: We tested for associations between VSA(FoRH) and (1) the repertoire of VSA antibodies carried by children at the time of acute malaria and (2) polymorphisms in ICAM1 (K29M) and CD36 (T188G) that could potentially reduce the positive selection of VSA(FoRH). RESULTS: An expected negative association between VSA antibody repertoire and VSA(FoRH) was observed in children with nonsevere malaria. However, this association did not extend to children with severe malaria, many of whom apparently had well-developed VSA antibody responses despite being infected by parasites expressing VSA(FoRH). There was no evidence for involvement of CD36 or ICAM1 in positive selection of VSA(FoRH). On the contrary, a weak positive association between carriage of the CD36 (T188G) allele and VSA(FoRH) was observed in children with severe malaria. CONCLUSION: The association between the VSA(FoRH) parasite phenotype and severe malaria cannot be explained simply in terms of the total repertoire of VSA antibodies carried at the time of acute disease.     

Involvement of CD36 on erythrocytes as a rosetting receptor for Plasmodium falciparum-infected erythrocytes.

Plasmodium falciparum-infected erythrocytes (parasitized red blood cells [PRBCs]) can adhere to uninfected erythrocytes (RBCs) to form rosettes, and adhere to the endothelial cell (EC) surface antigen CD36. These adherence phenomena have previously been considered quite different. We show that anti-CD36 monoclonal antibodies (MoAbs) reverse rosetting of PRBCs from both a culture-adapted line (Malayan Camp [MC] strain) and a natural isolate, GAM425. Three MoAbs that block adherence of PRBCs to ECs or C32 melanoma cells also reversed rosetting by greater than 50% at levels of less than 1 microgram/mL (OKM5, OKM8, and 8A6). Two other MoAbs that react with purified CD36 (1D3 and 1B1), but do not react with the surface of C32 cells, failed to reverse rosetting. When rosettes were disrupted and the RBCs and PRBCs were pretreated separately with antibodies before mixing to allow rosette reformation, only pretreatment of RBCs had an effect. MoAb 8A6 pretreatment of RBCs blocked rosette reformation, while MoAb 1B1 pretreatment did not. Rosetting was also reversed by purified human platelet CD36. In conjunction with evidence that CD36 is expressed on normal human erythrocytes (van Schravendijk et al, Blood 80:2105, 1992), we conclude that this CD36 is able to act as a host receptor for rosetting in the MC strain and some natural isolates of P falciparum.     

A longitudinal investigation of Plasmodium falciparum malaria in children in northern India

A group comprising 27 young children (1-4 y of age) suffering from uncomplicated falciparum malaria were studied to characterize the isolates and to measure humoral immune responses during acute infection and after recovery. Finger prick blood from each individual was collected on d 1. After treatment with chloroquine, a further blood sample was collected from each child on d 7, 30, 90 and 180 for assay of antibody responses to P. falciparum antigens. Isolates from individual patients were incubated in vitro for demonstration of rosette formation, assay of plasmodial growth rate and analysis of Pfcrt gene polymorphism. Out of 27 isolates of P. falciparum, 20 showed formation of rosettes in vitro. The growth rate at 96 h varied widely among the isolates. In Pfcrt gene analysis at 76-codon site, 14 showed wild-type Lys 76, 7 showed mutant type Thr 76 and 6 had mixed type. 14 children, all with anaemia on d 7, showed a positive direct antiglobulin test (DAT). Sera positive by ELISA IgG on d 90 also showed parasite growth inhibitory activity in vitro. Significant levels of IgG, IgG1 and IgG3 subclass antibodies against MSP1 were detected in 14 sera collected on d 90. On d 180, there was a decline in IgG and its subtypes. These findings suggest that a variability in isolates may occur in one and the same seasonal area, making children prone to infection. As a consequence, they develop antibodies during recovery phase from an acute attack, which remain in circulation for a period of 4-5 months. After that, a decline in antibody level may again make them susceptible to the disease. Prevalence of different serotypes in a small area may suggest the complexity of malaria transmission.     

Placental chondroitin sulfate A-binding malarial isolates evade innate phagocytic clearance

Pregnancy-associated malaria is characterized by the accumulation of parasitized erythrocytes (PEs) and monocytes in the placenta, and they are believed to directly contribute to adverse birth outcomes. Although most parasite isolates adhere to CD36, placental isolates express novel variant surface antigens (VSAs) and bind to chondroitin sulfate A (CSA). CSA-binding PEs are rarely observed outside of pregnancy, and most primigravid women lack immunity and must rely on innate immune mechanisms to clear these placental parasite variants. We hypothesized that differences in VSA expression and adhesive phenotype between pregnancy-associated (CSA-binding) and non-pregnancy-associated (CD36-binding) isolates may have direct implications for the failure of primigravid women to control the placental parasite burden through innate phagocytic pathways. We demonstrate here, both in vitro and in vivo, that there is a nonopsonic phagocytic defect for CSA-binding PEs. The ability of CSA-binding PEs to evade innate clearance pathways may contribute to the parasite accumulation and recruitment of monocytes that characterize placental malaria.     

Normal human erythrocytes express CD36, an adhesion molecule of monocytes, platelets, and endothelial cells.

We have recently shown that rosetting of Plasmodium falciparum (MC R+ line)-infected erythrocytes (parasitized red blood cells [PRBCs]) with uninfected erythrocytes (RBCs) is blocked by coating of the RBCs with anti-CD36 monoclonal antibodies (MoAbs; Handunnetti et al, Blood 80:2097, 1992). Adult RBCs have previously been considered negative for CD36. However, using fluorescence-activated cell sorter analysis with the anti-CD36 MoAbs 8A6, OKM5, and OKM8, which reverse rosetting, we consistently detect CD36 on the majority of normal adult RBCs. Absorption of the MoAb solutions with CD36-transfected Chinese hamster ovary (CHO-CD36) cells removed the reactivity against both CHO-CD36 cells and RBCs, whereas absorption with CHO cells had no effect. By comparison with staining for glycophorin A, LFA-3, and CR1, the level of expression of CD36 appeared to be low. Nevertheless, normal RBCs were capable of adhering to plastic coated with anti-CD36 MoAbs. RBCs from one African malaria patient were identified as deficient in CD36 and these RBCs did not rosette with the patient's own P falciparum PRBCs, even though these PRBCs were capable of rosetting with RBCs from a normal donor in a CD36-dependent manner. Therefore, the level of expression of CD36 on normal RBCs is sufficient to be important in cell adherence, and may have a biologic role in normal individuals as well as in the pathology of P falciparum malaria.     

Substance Abuse and Medication Adherence Among HIV-Positive Women with Histories of Child Sexual Abuse

Substance abuse increases the risks for infections and impairs medication adherence among HIV/AIDS patients. However, little is known about the characteristics of substance abuse and its impact on medication adherence among HIV-positive women with a history of child sexual abuse (CSA). In the present study, 148 HIV-positive women with a history of CSA completed a structured interview assessing CSA severity, psychological status, substance abuse, medication adherence, and sexual decision-making. Severity of CSA was significantly associated with substance use but not with adherence. Participants who had used hard drugs and who had lower self-esteem and adherence self-efficacy reported significantly lower levels of adherence. Additional research on how CSA experiences impact health behaviors is needed to help develop culturally congruent interventions to reduce risk behaviors and facilitate better medication adherence for this vulnerable population.     

CD36 deficiency protects against malarial anaemia in children by reducing Plasmodium falciparum-infected red blood cell adherence to vascular endothelium

Objective  CD36 is a receptor that occurs on the surface of activated immune cells, vascular endothelial cells and participates in phagocytosis and lipid metabolism. CD36 is known to be the major endothelial receptor molecule for field isolates of Plasmodium falciparum. A T1264G mutation in exon X of the gene leads to deficiency of CD36. This study aimed at determining associations between CD36 deficiency, P. falciparum in vitro adherence on purified CD36 and anaemia among children in an endemic area.
Methods  Genotypes were determined by nested polymerase chain reaction of isolated DNA from filter blood spots followed by Restriction Fragment Length Polymorphism (RFLP). Plasmodium falciparum adherence assays were performed on immobilized purified CD36.
Results  The data indicate that CD36 is an important cytoadherence receptor that mediates adherence to most P. falciparum field isolates. Our findings also suggest that mutations causing CD36 deficiency may confer significant protection against malarial anaemia (MA) in children (χ² = 8.58, P  < 0.01).
Conclusion  That the protective role that CD36 deficiency may confer against MA in children seems to be mediated through reduced cytoadherence of infected red blood cells to vascular endothelium.