Phosphorylation of Plasmodium berghei derived phosphoproteins associated with the host erythrocyte membrane by the spectrin kinase

Summary Plasmodium berghei derived phosphoproteins are associated with the host erythrocyte membrane. Effectors of the phosphorylation reaction regulate the phosphorylation of the P. berghei derived proteins and spectrin in a similar manner. The spectrin kinase also phosphorylates the P. berghei phosphoproteins in a reconstituted reaction at the same site(s) as the endogenously phosphorylated proteins. These results indicate that a host protein kinase may regulate parasite phosphoproteins during malaria.Abbreviations 2,3-DPG 2,3-diphosphoglyceric acid - SDS Sodium Dodecyl Sulfate     

Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon

Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range.     

Review: Natural Antimalarial Agents (1995-2001)

Malaria is one of the diseases for which even today not many suitable drugs are available. The rapid spread of resistance toward current drugs encourages the study for new active molecules. Ethnobotanical research can be of help to find new leads. Traditional remedies have always been a source of important antimalarial drugs and continue to provide novel and effective treatments, both where pharmaceuticals are not available and also where the disease is highly resistant to commonly prescribed drugs. This article provides a comparative compilation of various studies reported between 1995 and 2001 on natural compounds with antiplasmodial activity, with the goal of providing a basis for further in vitro and in vivo studies, as well as for clinical trials for the development of new antimalarial medicines. Referee: Dr. Robert Verpoorte, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, PO Box 9502, 2300 RA Leiden, The Netherlands     

Identification of microsatellite markers in Plasmodium mexicanum,a lizard malaria parasite that infects nucleated erythrocytes

Reptile and bird hosts of malaria parasites (Plasmodium) have nucleated erythrocytes. Infected blood thus contains a mix of abundant host and scant parasite DNA which has prevented identification of Plasmodium microsatellites. We developed a protocol for isolation of microsatellite markers for Plasmodium mexicanum, a parasite of lizards. The ATT repeat was common in the genome of P. mexicanum, but most (87%) of these repeats were exceptionally long (50–206 + repeats). Seven microsatellite markers with polymerase chain reaction primers are described. The protocol should allow discovery of microsatellites of malaria parasites (with AT‐rich genomes) infecting bird and reptile hosts.     

Mitochondrial genome sequences support ancient population expansion in Plasmodium vivax

Examination of nucleotide diversity in 106 mitochondrial genomes of the most geographically widespread human malaria parasite, Plasmodium vivax, revealed a level of diversity similar to, but slightly higher than, that seen in the virulent human malaria parasite Plasmodium falciparum. The pairwise distribution of nucleotide differences among mitochondrial genome sequences supported the hypothesis that both these parasites underwent ancient population expansions. We estimated the age of the most recent common ancestor (MRCA) of the mitochondrial genomes of both P. vivax and P. falciparum at around 200,000-300,000 years ago. This is close to the previous estimates of the time of the human mitochondrial MRCA and the origin of modern Homo sapiens, consistent with the hypothesis that both these Plasmodium species were parasites of the hominid lineage before the origin of modern H. sapiens and that their population expansion coincided with the population expansion of their host.     

Membrane proteins involved in the adherence of Plasmodium falciparum-infected erythrocytes to the endothelium.

Plasmodium falciparum (human malaria) infections are characterized by the attachment of erythrocytes infected with mature stage parasites to endothelial cells lining the post-capillary venules, a phenomenon known as sequestration. In the human body, the microvessels of the heart, lungs, kidneys, small intestine, and liver are the principal sites of sequestration. Sequestered cells that clog the brain capillaries may reduce blood flow sufficiently so that there is confusion, lethargy, and unarousable coma--cerebral malaria. This review considers what is known about the molecular characteristics of the surface proteins, that is, the red cell receptors and the endothelial cell ligands, involved in sequestration. Recent work from our laboratory on the characterization of the adhesive proteins on the surface of the P falciparum-infected red cell, and the ligands to which they bind on human brain endothelial cells is also discussed. Finally, consideration is given to the multifactor processes involved in sequestration and cerebral malaria, as well as the possible role of 'anti-adhesion therapy' in the management of severe malaria.     

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.