Risk Of Severe Malaria Research Articles

Cytokine Profiles at Birth Predict Malaria Severity during Infancy

BackgroundSevere malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood.Methods and FindingsCytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10) were measured at birth (cord blood; N=783) and during subsequent routine follow-up visits (peripheral blood) for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman’s rank correlation). Cord levels of IL-1β and TNF-α (but not other cytokines) correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05). Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE) method), with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression): adjusted hazard ratio (95% CI) 0.60 (0.39-0.92), P = 0.02.ConclusionIL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density.

Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway

SummaryThe clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.PaperClip

Intermittent Preventive Treatment in Pregnant Women Is Associated with Increased Risk of Severe Malaria in Their Offspring

BackgroundIn areas of widespread sulfadoxine-pyrimethamine resistance, intermittent treatment in pregnancy (IPTp) fails to prevent placental malaria (PM) and may exacerbate drug resistant infections. Because PM predicts increased susceptibility to parasitemia during infancy, we hypothesized that IPTp would also increase susceptibility to malaria infection and disease in the offspring.MethodsIn a birth cohort from NE Tanzania, we evaluated the association between maternal IPTp use and risk of parasitemia and severe malaria in the offspring. Using Cox Proportional Hazards Models as well as Generalized Estimating Equations, we evaluated the effects of IPTp on the entire cohort and on subgroups stratified by PM status at delivery.Results and ConclusionsOffspring of PM+ women who received IPTp had a dose-dependent decrease in time to first parasitemia (AHR = 2.13, p = 0.04 [95%CI: 1.04, 4.38]). Among all offspring, IPTp was associated with earlier first severe malaria episode (AHR = 2.32, p = 0.02 [95%CI: 1.12, 4.78]) as well as increased overall odds of severe malaria (AOR = 2.31, p = 0.03 [95%CI: 1.09, 4.88]). Cost-benefit analyses of IPTp regimens should consider the long term effects on offspring in addition to pregnancy outcomes.

Plasmodium falciparum Infection Patterns Since Birth and Risk of Severe Malaria: A Nested Case-Control Study in Children on the Coast of Kenya

Children in malaria endemic areas acquire immunity to severe malaria faster than to mild malaria. Only a minority of children suffers from severe malaria and it is not known what determines this. The aim of this study was to establish how P. falciparum infections during the first years of life affect the risk of severe malaria. A matched case-control study was nested within a large birth cohort set up to study the immunoepidemiology of pneumococci on the Kenyan coast. Infection patterns in three-monthly blood samples in cohort children admitted to hospital with severe malaria were compared to controls matched on age, residential location and time of sampling. P. falciparum detected at least once from birth conferred an increased risk of severe malaria and particularly if multiclonal infections, as characterized by genotyping of a polymorphic antigen gene, were ever detected. The results show for the first time that children with severe malaria have more infections early in life compared to community controls. These findings provide important insights on the immunity to severe disease, knowledge essential for the development of a vaccine against severe malaria.

Déterminants du neuropaludisme en milieu pédiatrique congolais

Malaria still constitutes a worrying problem of public health. It remains an important cause of infant mortality. To determine the determinants of severe malaria a case control study was carried out from July to December 2011 in the pediatric intensive care department of the university hospital of Brazzaville. The group included 230 children hospitalised for severe malaria, and the control group consisted of children followed up for non-severe malaria. Cases and controls were compared using statistical tests for matched group. The young age of the mother (OR=4.13), her poor education level (OR=2.36), the low socioeconomic level of parents (OR=5.90), the malnutrition (OR=2.67), the delay of consultation (OR=13.69) and parasitemia were associated with significantly higher risk of severe malaria. The importance of identified determinants imposes the implementation of primary prevention measures, which pass through the amelioration of socioeconomic and cultural conditions of populations, the reinforcement of sanitary education, and also a secondary prevention consisting of an early and accurate management of ordinary malaria.

Inflammatory Responses Associated with the Induction of Cerebral Malaria: Lessons from Experimental Murine Models

Inflammatory Responses Associated with the Induction of Cerebral Malaria: Lessons from Experimental Murine Models

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP's, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 1–10 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1α gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS, G6PD). It identifies two X-linked genes associated with altered risk of severe malaria in females, identifies mutations in ADCY9, IL1A and CD40L as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels, and also identifies novel genetic associations with severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are required to test the generality of these associations and to understand their functional consequences.

Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.

MALARIA AND HIV IN ADULTS: When The Parasite runs into The Virus

Malaria and HIV/AIDS are among the principal causes of morbidity and mortality worldwide, particularly in resource-limited settings such as sub-Saharan Africa. Despite the international community’s efforts to reduce incidence and prevalence of these diseases, they remain a global public health problem. Clinical manifestations of malaria may be more severe in HIV infected patients, which have higher risks of severe malaria and malaria related death. Co-infected pregnant women, children and international travelers from non-malaria endemic countries are at higher risk of clinical complications. However, there is a paucity and conflicting data regarding malaria and HIV co-infection, particularly on how HIV infection can modify the response to antimalarial drugs and about drug-interactions between antiretroviral agents and artemisinin-based combined regimens. Moreover, consulting HIV-infected international travelers and physicians specialized in HIV care and travel medicine should prescribe an adequate chemoprophylaxis in patients travelling towards malaria endemic areas and pay attention on interactions between antiretrovirals and antimalarial prophylaxis drugs in order to prevent clinical complications of this co-infection.This review aims to evaluate the available international literature on malaria and HIV co-infection in adults providing a critical comprehensive review of nowadays knowledge.

Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria

In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups.Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI95%: 0.273–0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group O was demonstrated with a decreased risk of severe malaria OR=0.743 (CI95%: 0.566–0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI95%: 1.128–2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype.We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.

Malaria in HIV/AIDS Patients at Different CD4+ T Cell Levels in Limbe, Cameroon

HIV infection has resulted in an increased risk of severe malaria and death, because the odds of parasitaemia and risk of malaria fever increase with decreasing CD4+ T cell count and increasing viral load. A cross-sectional study was conducted on 203 HIV/AIDS patients to determine the pattern of malaria infection, anaemic status and the outcome of ARV therapy vis-a-vis malaria treatment at different CD4+ T cell levels of the patient. Participants were HIV patients aged ≥ 20 years attending the HIV treatment centre of Limbe Regional Hospital, Cameroon. Clinical manifestations of malaria in patients were determined using a structured questionnaire. Their CD4+ T cell count and haemoglobin level were determined using the FACS count method. Malaria prevalence and density were determined from Giemsa-stained blood films. Clinical manifestations of malaria increased with decreasing CD4+ T cell counts. There was a negative correlation between malaria severity and decreasing CD4+ T cell counts. A significantly greater proportion (p<0.01) of patients had moderate anaemia. Cases of anaemia increased significantly (p<0.001) with decreasing CD4+ T cell counts. Declining immunity increases vulnerability to malaria infection and highly active ARV combination therapy has great potential to reduce HIV-related malaria.

Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

BackgroundMalaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.MethodsHRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.ResultsAmong 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X 2> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X 2< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.ConclusionUse of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.

Nitric oxide generation in children with malaria and the NOS2G-954C promoter polymorphism

Previous epidemiological studies have demonstrated a protective association between the NOS2G-954C (NOS2(Lambaréné)) polymorphism in inducible nitric oxide synthase and severe malaria. The polymorphism is commoner in children with uncomplicated compared with severe malaria. We now show that the likely mechanism for such protection is increased flux of nitrogen from arginine to nitric oxide (NO) during episodes of malaria. Forty-seven boys with uncomplicated malaria received an infusion of (15)N-arginine to measure directly whole body in vivo NO production. The NOS2G-954C genotype previously associated with reduced risk of severe malaria in Gabon was also assessed. Evaluable data were obtained from 40 boys, of whom 6 were NOS2G-954C heterozygotes. Heterozygotes had higher urinary (15)N nitrate enrichments, 2.3 ± 0.6 vs. 1.4 ± 0.5 atoms percent excess (P = 0.001) and higher ratios of (15)N between urine nitrate and plasma arginine (87 ± 11 vs. 57 ± 18%, P = 0.001) consistent with accelerated NO production. We also derived total NO production rates, combining data with total urine production rate and nitrate concentration; these showed no difference by genotype (0.62 ± 0.36, n = 6 vs. 0.83 ± 0.50 μmol/kg·h, n = 16; P = 0.36), but data were confounded by very high variability in measurements of urine output and nitrate concentrations. This study supports the idea that NOS2 genotype protects against severe malaria by increasing NO production during episodes of uncomplicated malaria.

Impact of HIV infection on severity of imported malaria is restricted to patients with CD4 cell counts &lt; 350 cells/μl

To study the relative impact of HIV-1 infection and associated immunodepression on the severity of Plasmodium falciparum malaria in adults returning from areas of endemic malaria. We conducted a cross-sectional study, based on data from 104 HIV-infected patients from the French Hospital Database on HIV cohort (FHDH-ANRS CO4) and 161 HIV-negative patients from Bichat hospital, with a diagnosis of imported P. falciparum malaria between 2000 and 2003. The severity of falciparum malaria episode was graded with World Health Organization (WHO) criteria 2000 or on 2007 French recommendations. Depending on criteria used, 40% (WHO) and 28% (2007 French recommendations) of episodes of imported P. falciparum malaria in HIV-infected patients were classified as severe, compared with 21% (WHO) and 11% (2007 French recommendations) of episodes among HIV-negative patients. Among HIV-infected patients, the episodes were severe in between 22 (CD4 cell counts > or =350/microl) and 51% (CD4 cell counts <350/microl) of cases using WHO criteria, and between 12 (CD4 cell counts > or =350/microl) and 41% (CD4 cell counts <350/microl) of cases using 2007 French recommendations criteria. Relative to HIV-negative patients, after adjusting for confounding factors, HIV-infected patients with severe immunodepression (CD4 cell counts <350/microl) were at a significantly higher risk of severe malaria than HIV-negative patients (odds ratio 3.2-4.7, depending on the criteria) contrary to HIV-infected patients with CD4 cell counts more than 350/microl (odds ratio 0.7-0.9). The association between HIV infection and severity of imported P. falciparum malaria is only observed for HIV-infected patients with severe immunodepression (CD4 cell counts <350/microl).

The development of the RTS,S malaria vaccine candidate: challenges and lessons

RTS,S is the world's most advanced malaria vaccine candidate and is intended to protect infants and young children living in malaria endemic areas of sub-Saharan Africa against clinical disease caused by Plasmodium falciparum. Recently, a pivotal Phase III efficacy trial of RTS,S began in Africa. The goal of the programme has been to develop a vaccine that will be safe and effective when administered via the Expanded Program for Immunization (EPI) and significantly reduce the risk of clinically important malaria disease during the first years of life. If a similar reduction in the risk of severe malaria and other important co-morbidities associated with malaria infection can be achieved, then the vaccine could become a major new tool for reducing the burden of malaria in sub-Saharan Africa. Encouraging data from the ongoing phase II programme suggest that these goals may indeed be achievable. This review discusses some of the unique challenges that were faced during the development of this vaccine, highlights the complexity of developing new vaccine technologies and illustrates the power of partnerships in the ongoing fight against this killer disease.

Increased Risk for Severe Malaria in HIV-1–infected Adults, Zambia

To determine whether HIV-1 infection and HIV-1-related immunosuppression were risk factors for severe malaria in adults with some immunity to malaria, we conducted a case-control study in Luanshya, Zambia, during December 2005-March 2007. For each case-patient with severe malaria, we selected 2 matched controls (an adult with uncomplicated malaria and an adult without signs of disease). HIV-1 infection was present in 93% of case-patients, in 52% of controls with uncomplicated malaria, and in 45% of asymptomatic controls. HIV-1 infection was a highly significant risk factor for adults with severe malaria compared with controls with uncomplicated malaria (odds ratio [OR] 12.6, 95% confidence interval [CI] 2.0-78.8, p = 0.0005) and asymptomatic controls (OR 16.6, 95% CI 2.5-111.5, p = 0.0005). Persons with severe malaria were more likely to have a CD4 count <350/microL than were asymptomatic controls (OR 23.0, 95% CI 3.35-158.00, p<0.0001).

Intrahousehold Allocation of Free and Purchased Mosquito Nets

For some health goods, intrahousehold allocation may be more important in determining outcomes than household-level consumption. An example is the use of mosquito nets to prevent malaria. Malaria kills over one million people annually, 90 percent of them children under the age of five. The use of insecticide treated mosquito nets (ITNs) is considered the most costeffective available strategy for control of the disease. In 2000, 44 of the 50 malaria affected countries in Africa committed themselves to increasing the use of ITNs by vulnerable populations, in particular children under five years of age and pregnant women. Adults in malarious regions have typically acquired some immunity to the disease through repeated exposure over the course of their lives. The risk of severe malaria resulting in lifelong disability or death is highest for young children and pregnant women across transmission environments (Robert W. Snow et al. 2003). On the other hand, lost labor time often accounts for the largest portion of the private cost of the disease. This implies a trade-off between minimizing the income lost to malaria and minimizing the risk that a household member dies or is permanently disabled. Despite public health messages emphasizing the importance of using mosquito nets to protect young children from malaria, nets are often used by adults when a household does not have enough nets to cover all members (Eline L. Korenromp et al. 2003; Frederick Mugisha and Jacqueline Arinaitwe 2003). Determining the welfare-maximizing allocation of nets is Intrahousehold Allocation of Free and Purchased Mosquito Nets

The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection

To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and microsatellite (MS) of the promoter region of inducible nitric oxide synthase (iNOS) gene which are known to enhance the NO production in vivo. A total of 428 (204 severe, 224 mild) adult patients living in the eastern part of India were analyzed. The single nucleotide substitutions -954G-->C was found to be very rare, and -1173C-->T was absent in this population. But interestingly, longer forms of MS were found to be significantly associated with severe malaria (OR = 2.89, 95% CI = 1.955-4.295, P < 0.0001), and the linear regression analysis revealed that the risk of severe malaria significantly increases as the summed repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the median plasma level of nitrate/nitrite (NOx) was observed to be high in mild patients compared to severe patients, and the level of parasitemia was significantly low among mild patients than severe ones. These findings suggest that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe malaria.

Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

BackgroundHost adhesion molecules play a significant role in the pathogenesis of Plasmodium falciparum malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, ICAM1, PECAM1 and CD36, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.MethodsThe frequency distribution of seven selected SNPs of ICAM1, PECAM1 and CD36 was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.ResultsAssociation of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the PECAM1 gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.ConclusionThe data highlights the significance of variations in the ICAM1, PECAM1 and CD36 genes in the manifestation of falciparum malaria in India. The PECAM1 exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.

Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan

Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.