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BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GM

BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GM

BACKGROUND: Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana.METHODS: Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at - 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA.RESULTS: Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom.CONCLUSION: The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gam

BACKGROUND: Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana.METHODS: Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at - 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA.RESULTS: Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom.CONCLUSION: The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gam

Edem MA Tette,1 Ben A Gyan,2 Kwadwo A Koram3 1Department of Community Health, University of Ghana Medical School, Accra, Greater Accra Region, Ghana; 2Department of Immunology, Noguchi Memorial Institute for Medical Research University of Ghana, Accra, Greater Accra Region, Ghana; 3Department of Epidemiology, Noguchi Memorial Institute for Medical Research University of Ghana, Accra, Greater Accra Region, GhanaCorrespondence: Edem MA Tette Email edemenator@googlemail.comAbstract: The corona virus pandemic undoubtedly demonstrates the growing need for research in medical science. However, with the decline in physician scientists world-wide, innovative ways are needed to engender interest in research among medical students and young doctors to replenish the stock of physician investigators. One way of doing this is to create compulsory and elective projects for them. We describe research internships created for medical students at the Noguchi Memorial Institute for Medical Research to expose them to the rudiments of biomedical research and proposal development. We also describe research internships for doctors waiting for house job postings or keen to do research who needed mentorship. Though the response has been positive, the full impact will be realized with time. The recognition that training should be backed with a supportive environment, mentorship and clear career paths for physician scientists is also mentioned.Keywords: research, internship, medical students, doctors, physician scientist, investigator, extracurricular research, medical education

BACKGROUND: Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana.METHODS: Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at - 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA.RESULTS: Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom.CONCLUSION: The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gam

Background: Genetic polymorphisms in the complex gene cluster encoding human Fc-gamma receptors (Fc gamma Rs) may influence malaria susceptibility and pathogenesis. Studying genetic susceptibility to malaria is ideal among sympatric populations because the distribution of polymorphic genes among such populations can help in the identification malaria candidate genes. This study determined the distribution of three FcyRs single nucleotide polymorphisms (SNPs) (Fc gamma RIIB-rs1050519, Fc gamma RIIC-rs3933769 and Fc gamma RIIIA-rs396991) among sympatric Fulani and Dogon children with uncomplicated malaria. The association of these SNPs with clinical, malariometric and immunological indices was also tested. Methods: This study involved 242 Fulani and Dogon volunteers from Mali age under 15 years. All SNPs were genotyped with predesigned TaqMan (R) SNP Genotyping Assays. Genotypic and allelic distribution of SNPs was compared across ethnic groups using the Fisher exact test. Variations in clinical, malariometric and immunologic indices between groups were tested with Kruskal-Wallis H, Mann-Whitney U test and Fisher exact test where appropriate. Results: The study confirmed known malariometric and immunologic differences between sympatric Fulani and non-Fulani tribes. Parasite density was lower in the Fulani than the Dogon (p < 0.0001). The mutant allele of Fc gamma RIIC (rs3933769) was found more frequently in the Fulani than the Dogon (p < 0.0001) while that of Fc gamma RIIIA (rs396991) occurred less frequently in the Fulani than Dogon (p = 0.0043). The difference in the mutant allele frequency of Fc gamma RIIB (rs1050519) between the two ethnic groups was however not statistically significant (p = 0.064). The mutant allele of rs396991 was associated with high malaria-specific IgG1 and IgG3 in the entire study population and Dogon tribe, p = 0.023 and 0.015, respectively. Parasite burden was lower in carriers of the Fc gamma RIIC (rs3933769) mutant allele than no

Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974), total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P < 0.001), severe malarial anemia (OR = 0.18, P, 0.001), and cerebral malaria (OR = 0.39, P = 0.022). Levels of total IgE significantly differed among malaria phenotypes (P = 0.044) and rs3024974 genotypes (P = 0.037). Neither cytokine levels nor IL-6/IL-10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis.

Elias Asuming-Brempong,1–3 Ben Gyan,2 Abena Serwaa Amoah,3,4 William van der Puije,3,4 Langbong Bimi,1 Daniel Boakye,3 Irene Ayi3 1Department of Animal Biology and Conservation Science, University of Ghana, Legon, Ghana; 2Immunology Department, 3Parasitology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana; 4Parasitology Department, Leiden University Medical Centre, Leiden, The NetherlandsBackground: Recent studies have shown the urine filtration and Kato-Katz techniques to significantly underestimate infection intensity in Schistosoma haematobium and Schistosoma mansoni infections, respectively. Infection intensity determination by these methods improves only with increasing number of samples collected per participant. This implies tedious and lengthy periods of sample processing and analysis by microscopy examination, hence the increased chances of experimental errors. This study sought to determine the relationship between levels of eosinophil cationic protein (ECP) and infection intensity by egg count both in S. haematobium and S. mansoni single and coinfections.Methods: This was a cross-sectional study carried out in Pakro, a periurban community in Ghana, involving a total of 308 participants. Each provided urine and stool samples, which were processed using the filtration and Kato-Katz techniques, respectively. Processed samples were examined by microscopy. Aliquots of urine from 73 participants were analyzed for levels of ECP using an ECP enzyme-linked immunosorbent assay kit.Results: Of the 308 urine samples examined, 59 (19.15%) were positive for S. haematobium. Significant association was observed between sex and S. haematobium infection intensity by egg count (P<0.05) as well as between age and infection intensity (P<0.001). Mean ECP levels were higher in S. haematobium-positive samples than in S. haematobium-negative samples (P<0.001). There was also

Kwame Adu-Bonsaffoh,1,2 Daniel Ansong Antwi,1 Samuel Amenyi Obed,3 Ben Gyan4 1Department of Physiology, University of Ghana Medical School, Accra, Ghana; 2Department of Obstetrics and Gynecology, Korle Bu Teaching Hospital, Accra, Ghana; 3Department of Obstetrics and Gynecology, University of Ghana Medical School, Accra, Ghana; 4Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana Background: Preeclampsia (PE) is still a disease of theories as the exact cause remains uncertain. Widespread vascular endothelial cell dysfunction is thought to mediate the generalized vasospasm and hypertension characteristic of PE. Altered nitric oxide (NO) production has been associated with the endothelial dysfunction in the pathogenesis of PE but conflicting results have emerged from previous studies. Objectives: To determine maternal serum levels of NO, a biomarker of endothelial function, in nonpregnant, normal pregnant, and preeclamptic women. Materials and methods: This was a cross-sectional case–control study of 277 women comprising 75 nonpregnant, 102 normal pregnant, and 100 preeclamptic women conducted at the Korle Bu Teaching Hospital between April and June 2011. About 5 mL of venous blood was obtained from the participants for the various investigations after meeting the inclusion criteria and signing to a written consent. Serum levels of NO were determined by Griess reaction. The data obtained were analyzed with SPSS version 20. Results: The study showed significantly elevated serum levels of NO in preeclamptic women (82.45±50.31 µM) compared with normal pregnant (33.12±17.81 µM) and nonpregnant (16.92±11.41 µM) women with P<0.001. The alteration in maternal serum NO levels was significantly more profound in early-onset (severe) PE (119.63±45.860 µM) compared to that of late-onset (mild) disease (62.44±40.44

Paul Winston Tetteh,1,4 Charles Antwi-Boasiako,1 Ben Gyan,3 Daniel Antwi,1 Festus Adzaku,1 Kwame Adu-Bonsaffoh,1,2 Samuel Obed21Department of Physiology, 2Department of Obstetrics and Gynecology, University of Ghana Medical School, Accra, Ghana; 3Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana; 4Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, The NetherlandsBackground: The cause of pre-eclampsia remains largely unknown, but oxidative stress (an imbalance favoring oxidant over antioxidant forces) has been implicated in contributing to the clinical symptoms of hypertension and proteinuria. Assessment of oxidative stress in pre-eclampsia using urinary isoprostane has produced conflicting results, and it is likely that renal function may affect isoprostane excretion. The aim of this study was to determine the role of oxidative stress in the pathophysiology of pre-eclampsia and to assess the effect of renal function on isoprostane excretion in pre-eclampsia in the Ghanaian population.Methods: This was a case-controlled study, comprising 103 pre-eclamptic women and 107 normal pregnant controls and conducted at the Korle-Bu Teaching Hospital between December 2006 and May 2007. The study participants were enrolled in the study after meeting the inclusion criteria and signing their written informed consent. Oxidative stress was determined by measuring urinary excretion of isoprostane and total antioxidant capacity using an enzyme-linked immunosorbent assay technique. Renal function was assessed by calculating the estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula.Results: The pre-eclampsia group had significantly (P = 0.0006) higher urinary isoprostane excretion (2.81 ± 0.14 ng/mg creatinine) than the control group (2.01 ± 0.18 ng/mg creatinine) and a significantly (P = 0.0008) lower total antioxidant power

BACKGROUND: The virulence of Plasmodium falciparum malaria is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on dome-shaped protrusions called knobs on the IE surface is central to both. Differences in receptor specificity and affinity of expressed PfEMP1 are important for IE adhesiveness, but it is not known whether differences in the number and size of the knobs on which the PfEMP1 proteins are expressed also play a role. Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density. METHODOLOGY/PRINCIPAL FINDINGS: We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates from Ghanaian children with malaria and 10 P. falciparum isolates selected in vitro for expression of a particular PfEMP1 protein (VAR2CSA) were examined. Knob density increased from ~20 h to ~35 h post-invasion, with significant variation among isolates. The knob density ex vivo, which was about five-fold higher than following long-term in vitro culture, started to decline within a few months of culture. Although knob diameter and height varied among isolates, we did not observe significant time-dependent variation in these dimensions. CONCLUSIONS/SIGNIFICANCE: The density of knobs on the P. falciparum-IE surface depends on time since invasion, but is also determined by the infecting isolate in a time-independent manner. This is the first study to quantitatively evaluate knob densities and dimensions on different P. falciparum isolates, to examine ex vivo isolates from humans, and to compare ex vivo and long-term in vitro-cultured isolates. Our findings contribute to the understanding of the interaction between P. falciparum parasites and the infected host.

Eric Aidoo,1 Frederick K Addai,1 John Ahenkorah,1 Bismarck Hottor,1 Kwasi A Bugyei,2 Ben A Gyan31Department of Anatomy, 2Department of Pharmacology, University of Ghana Medical School, College of Health Sciences, Korle-Bu, Accra, Ghana; 3Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, GhanaPurpose: This study tested whether natural cocoa powder ingestion could mitigate hepatic injury coincident with murine malaria. Plasmodium berghei infection causes liver damage including hepatic sinusoidal distension, and elevated serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. According to literature, these pathologies largely result from activity of reactive oxygen species (ROS) and may be extenuated by antioxidants.Animals and methods: Thirty Balb/c mice were randomly assigned to three equal groups. One of two groups of mice inoculated with 0.2 mL of P. berghei-parasitized red blood cells (RBCs) was given unrestricted 24-hour access to a natural cocoa powder beverage (2% by weight) in place of water. The third group of mice were neither infected nor given cocoa. All mice were fed the same standard chow. After 6 days, mice were sacrificed and their livers processed for histomorphometric assessment of mean hepatic sinusoidal diameter as a quantitative measure of altered morphology. Serum ALT and AST were measured as a gauge of functional impairment.Results: Compared with uninfected mice, hepatic sinusoidal diameter in P. berghei-infected mice not given cocoa increased by 150%, whereas a smaller increase of 83% occurred in infected mice that ingested cocoa. Mean serum ALT increased by 127% in infected mice not given cocoa and 80% in infected mice that consumed cocoa, compared with the value for uninfected mice. Similarly, mean serum AST was raised by 141% in infected mice not given cocoa and 93% in infected mice that drank cocoa.Conclusion: Distension of hepatic sinusoidal diameter in P. berghe

BACKGROUND: The virulence of Plasmodium falciparum malaria is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on dome-shaped protrusions called knobs on the IE surface is central to both. Differences in receptor specificity and affinity of expressed PfEMP1 are important for IE adhesiveness, but it is not known whether differences in the number and size of the knobs on which the PfEMP1 proteins are expressed also play a role. Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density. METHODOLOGY/PRINCIPAL FINDINGS: We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates from Ghanaian children with malaria and 10 P. falciparum isolates selected in vitro for expression of a particular PfEMP1 protein (VAR2CSA) were examined. Knob density increased from ~20 h to ~35 h post-invasion, with significant variation among isolates. The knob density ex vivo, which was about five-fold higher than following long-term in vitro culture, started to decline within a few months of culture. Although knob diameter and height varied among isolates, we did not observe significant time-dependent variation in these dimensions. CONCLUSIONS/SIGNIFICANCE: The density of knobs on the P. falciparum-IE surface depends on time since invasion, but is also determined by the infecting isolate in a time-independent manner. This is the first study to quantitatively evaluate knob densities and dimensions on different P. falciparum isolates, to examine ex vivo isolates from humans, and to compare ex vivo and long-term in vitro-cultured isolates. Our findings contribute to the understanding of the interaction between P. falciparum parasites and the infected host.

Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM.

Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM.

Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM.

Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most of the world's attention. However, in rural and impoverished urban areas, a number of unfectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight agaisnt infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective. © 2008 Boraschi et al.

Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most of the world's attention. However, in rural and impoverished urban areas, a number of unfectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight agaisnt infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective. © 2008 Boraschi et al.

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Udgivelsesdato: 2002-Aug, Severe malarial anaemia (SA) is a major complication of malaria and an important cause of child mortality and morbidity. However, the pathogenesis behind SA is poorly understood. Nitric oxide (NO) is known to play a protective role against clinical malaria but is also suggested to have a pathogenic role in cerebral malaria (CM). Erythrophagocytosis by splenic macrophages has been implicated in the pathogenesis of SA. In this study, plasma levels of NO, neopterin, haptoglobin and C-reactive protein (CRP) were measured in paediatric patients with CM, n=77, SA (n=28) and uncomplicated malaria (UM n=53). Haptoglobin levels were significantly lower in SA (median (interquartile range) 25 (17-59) mg/l) than in both CM and UM (40 (24-80) mg/l and 110 (60-160) mg/l, respectively, P<0.001). In contrast, NO levels were higher in SA (38 (28-51) micromol/l) than in CM and UM (21 (15-32) micromol/l and 10.3 (5.6-17) micromol/l, respectively, P<0.001). A significant negative correlation between haptoglobin and NO was seen in the SA group. No such correlation was observed within the UM or CM groups. No significant differences in neopterin levels were observed between any of the three groups, neither was there any correlation between parasitaemias and neopterin levels. The low haptoglobin and high levels of NO in this SA group may contribute to haemolysis. Taken together our results support the hypothesis that immune-mediated erythrocyte destruction is involved in the pathogenesis of malarial anaemia.

Udgivelsesdato: 2002-Aug, Severe malarial anaemia (SA) is a major complication of malaria and an important cause of child mortality and morbidity. However, the pathogenesis behind SA is poorly understood. Nitric oxide (NO) is known to play a protective role against clinical malaria but is also suggested to have a pathogenic role in cerebral malaria (CM). Erythrophagocytosis by splenic macrophages has been implicated in the pathogenesis of SA. In this study, plasma levels of NO, neopterin, haptoglobin and C-reactive protein (CRP) were measured in paediatric patients with CM, n=77, SA (n=28) and uncomplicated malaria (UM n=53). Haptoglobin levels were significantly lower in SA (median (interquartile range) 25 (17-59) mg/l) than in both CM and UM (40 (24-80) mg/l and 110 (60-160) mg/l, respectively, P<0.001). In contrast, NO levels were higher in SA (38 (28-51) micromol/l) than in CM and UM (21 (15-32) micromol/l and 10.3 (5.6-17) micromol/l, respectively, P<0.001). A significant negative correlation between haptoglobin and NO was seen in the SA group. No such correlation was observed within the UM or CM groups. No significant differences in neopterin levels were observed between any of the three groups, neither was there any correlation between parasitaemias and neopterin levels. The low haptoglobin and high levels of NO in this SA group may contribute to haemolysis. Taken together our results support the hypothesis that immune-mediated erythrocyte destruction is involved in the pathogenesis of malarial anaemia.