Different Species Of Plasmodium Research Articles

In vitro Evaluation and Molecular Dynamics, DFT Guided Investigation of Antimalarial Activity of Ethnomedicinally used Coptis teeta Wall.

Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of northeast India. In this study, the antimalarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification was carried out via in silico study. On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta. The IC50 of the methanol extract of Coptis teeta was reported to be 0.08 μg/ml in 3D7 strain and 0.7 μg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations, it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the bandgap energy of noroxyhydrastinine was found to be 0.186 Ha, indicating a favorable interaction. The in silico analysis as an addition to the in vitro results provides strong evidence of noroxyhydrastinine as an antimalarial agent.

Species of plasmodium (P. Falciparum and P. Vivax) involved in children with malaria: An experience from a tertiary childcare hospital.

Objective: To find out different species of plasmodium (P. falciparum and P. vivax) involved in children with malaria at a tertiary childcare hospital. Study Design: Descriptive, Cross-sectional study. Setting: Department of Paediatric Medicine, The Children’s Hospital and Institute of Child Health, Multan. Period: October 2019 to March 2020. Material & Methods: A total of 281 cases of either gender, aged 1 to 12 years and patients with malaria were enrolled. A special template was designed to record study information. Venous blood as five ml sample was drawn and dispatched to institutional laboratory for ICT malaria, complete blood count and giemsa stain smear and observed under light microscope. Data analysis was performed employing SPSS version 24.0. Results: Out of a total of 281 cases, 177 (63.0%) were male ande 104 (37.0%) female. Mean age of study participants was 4.29±2.48 years. A total of 135 (48.0%) children belonged to rural areas and 197 (70.1%) had monthly family income < 25000 rupees. Mean duration of illness was 4.21 ± 2.12 days. Previous history of use of anti-malarial drugs was noted in 62 (22.1%) of our study cases. Plasmodium falciparum was observed in 52 (18.5%) cases and plasmodium vivax in 229 (81.5%). Conclusion: Plasmodium vivax is predominantly more prevalent in our population as compared with plasmodium falciparum in children with malaria. Plasmodium falciparum and plasmodium vivax were significantly linked with age and disease duration. Malaria was noted to be more prevalent among poor families living in slum areas having inadequate sanitation facilities.

The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design.

The infection dynamics between different species of Plasmodium that infect the same human host can both suppress and exacerbate disease. This could arise from inter-parasite interactions, such as competition, from immune regulation, or both. The occurrence of protective, cross-species (heterologous) immunity is an unlikely event, especially considering that strain-transcending immunity within a species is only partial despite lifelong exposure to that species. Here we review the literature in humans and animal models to identify the contexts where heterologous immunity can arise, and which antigens may be involved. From the perspective of vaccine design, understanding the mechanisms by which exposure to an antigen from one species can elicit a protective response to another species offers an alternative strategy to conventional approaches that focus on immunodominant antigens within a single species. The underlying hypothesis is that certain epitopes are conserved across evolution, in sequence or in structure, and shared in antigens from different species. Vaccines that focus on conserved epitopes may overcome the challenges posed by polymorphic immunodominant antigens; but to uncover these epitopes requires approaches that consider the evolutionary history of protein families across species. The key question for vaccinologists will be whether vaccines that express these epitopes can elicit immune responses that are functional and contribute to protection against Plasmodium parasites.

Mefloquine binding to human acyl-CoA binding protein leads to redox stress-mediated apoptotic death of human neuroblastoma cells

Malaria is an infectious disease that is caused by different species of Plasmodium. Several antimalarial drugs are used to counter the spread and infectivity of Plasmodium species. However, humans are also vulnerable to many of the antimalarial drugs, including the quinoline-based drugs. In particular, the antimalarial mefloquine has been reported to show adverse neuropsychiatric effects in humans. Though mefloquine is known to be neurotoxic, the molecular mechanisms associated with this phenomenon are still obscure. In this study, we show that mefloquine binds to and inactivates the human acyl-CoA binding protein (hACBP), potentially inducing redox stress in human neuroblastoma cells (IMR-32). Mefloquine occupies the acyl-CoA binding pocket of hACBP by interacting with several of the critical acyl-CoA binding amino acids. This leads to the competitive inhibition of acyl-CoA(s) binding to hACBP and to the accumulation of lipid droplets inside the IMR-32 cells. The accumulation of cytosolic lipid globules and oxidative stress finally correlates with the apoptotic death of cells. Taken together, our study deciphers a mechanistic detail of how mefloquine leads to the death of human cells by perturbing the activity of hACBP and lipid homeostasis.

The Prevalence of Malaria in Soldiers, Zahedan, Iran

Background: Malaria is an infectious disease, which is caused by different species of plasmodium. It damages social and economic growth and is also one of the leading causes of morbidity and mortality. Malaria is transmitted by female anopheles mosquitoes. Studying the epidemiology of malaria is critical, and it has been poorly studied in asymptomatic individuals, especially in boundary soldiers. Objectives: This study aimed at evaluating the prevalence of malaria in veterans. Methods: In this cross-sectional study, a total of 300 blood samples were collected from the volunteers of a garrison in Zahedan City, Sistan and Baluchestan Province, Southeast of Iran during the spring and summer of 2017 and simultaneously, the questionnaires were completed by the subjects. Then, the samples were examined by microscopic examination and nested PCR method. Results: Of 300 studied samples, 4 samples (1.3%) were positive for P. vivax and had asymptomatic malaria, of which. Three samples were native to Sistan and Baluchistan and another one was native to Kerman. No species of Plasmodium was observed. Conclusions: A low prevalence (1.3%) of malaria indicated that it has decreased in Sistan and Baluchistan during the last years and also using the nested PCR technique is suggested to diagnose malaria in asymptomatic patients.

Novel molecular diagnostic technique for detecting the different species of Plasmodium

BackgroundSensitive diagnostic techniques are needed for timely detection of malaria parasite and disease control. Molecular diagnostic techniques involving Polymerase chain reaction (PCR) with 18 s rRNA as a known diagnostic target with an overall sensitivity of 10 parasites per microliter is used as a gold standard. Till date, no attempt has been undertaken to develop a technique for the identification of four Plasmodium species in a single step PCR combined with restriction digestion with enzymes. MethodPlasmodium species-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays have been developed, based on RFLP of amplified PCR product of mitochondrial gene as a target. This approach identifies Plasmodium species in two steps involving amplification of mitochondrial (Mt) gene by PCR followed by digestion with restriction enzymes. ResultA total of 36 clinical samples were subjected to PCR-RFLP for the diagnosis and detection of malaria parasites targeting mitochondrial gene (Mt). The findings of the method were compared with gold standard methods (Microscopy, RDTs and Nested PCR) and was able to detect mixed infection with a sensitivity of 100% and specificity of 93.8% with respect to nested PCR. The results obtained by PCR-RFLP were validated with Sanger sequencing (n = 32) and were found to be consistent with the method. ConclusionThis method identifies and distinguishes four species of human malaria parasite namely P. falciparum (Pf), P. vivax (Pv), P. malariae (Pm) and P. ovale (Po) in approximately 4 h. To overcome and address PCR difficulties, continuous efforts are needed for the development of newer diagnostic techniques.

Malaria parasites of long-tailed macaques in Sarawak, Malaysian Borneo: a novel species and demographic and evolutionary histories

BackgroundNon-human primates have long been identified to harbour different species of Plasmodium. Long-tailed macaques (Macaca fascicularis), in particular, are reservoirs for P. knowlesi, P. inui, P. cynomolgi, P. coatneyi and P. fieldi. A previous study conducted in Sarawak, Malaysian Borneo, however revealed that long-tailed macaques could potentially harbour novel species of Plasmodium based on sequences of small subunit ribosomal RNA and circumsporozoite genes. To further validate this finding, the mitochondrial genome and the apicoplast caseinolytic protease M genes of Plasmodium spp. were sequenced from 43 long-tailed macaque blood samples.ResultsApart from several named species of malaria parasites, long-tailed macaques were found to be potentially infected with novel species of Plasmodium, namely one we refer to as “P. inui-like.” This group of parasites bifurcated into two monophyletic clades indicating the presence of two distinct sub-populations. Further analyses, which relied on the assumption of strict co-phylogeny between hosts and parasites, estimated a population expansion event of between 150,000 to 250,000 years before present of one of these sub-populations that preceded that of the expansion of P. knowlesi. Furthermore, both sub-populations were found to have diverged from a common ancestor of P. inui approximately 1.5 million years ago. In addition, the phylogenetic analyses also demonstrated that long-tailed macaques are new hosts for P. simiovale.ConclusionsMalaria infections of long-tailed macaques of Sarawak, Malaysian Borneo are complex and include a novel species of Plasmodium that is phylogenetically distinct from P. inui. These macaques are new natural hosts of P. simiovale, a species previously described only in toque monkeys (Macaca sinica) in Sri Lanka. The results suggest that ecological factors could affect the evolution of malaria parasites.

Hyalournan Role in Pathophysiology of Different Species of Plasmodium

Background For years, Plasmodium vivax has been considered the cause of benign malaria. Nevertheless, it has been observed that this parasite can produce a severe disease comparable with Plasmodium falciparum. It has been suggested that some physiopathogenic processes might be shared by these 2 species, such as cytoadherence. Objective This study was conducted to demonstrate the severity of the disease with the hyaluronic acid (HA) level with different species of Plasmodium in patients complaining of fever of unknown origin, highly suspected clinically to be caused by malaria, which were diagnosed by microscopic examination, OptiMAL rapid antigen test, and serum level of HA and were assessed. Subjects and Methods A total of 32 expatriate patients attending King Faisal Specialized Hospital, Taif, Kingdom of Saudi Arabia, complaining of fever of unknown origin were examined for malaria parasites by microscopy of Giemsa-stained blood smears, OptiMAL rapid antigen test, and HA test. The diagnostic performance of these methods was statistically compared. Results Of 32 clinically suspected cases, 17 (53%) were positive for Plasmodium infection, and of these, 8 (47%) were infected by P. falciparum (G1) and 9 (53%) by P. vivax (G2). Fifteen (47%) were negative for Plasmodium species (G3). The differences in the level of HA were statistically significant in G1 as compared with G3 as well as G2 as compared with G3 and statistically insignificant in G2 as compared with G1 (P > 0.05). Conclusions The association of severity of anemia and the trend observed between adhesion to HA and increased parasite densities suggest their potential contribution to sequestration observed in P. vivax infections.

Immunological Cross-Reactivity between Malaria Vaccine Target Antigen P48/45 in Plasmodium vivax and P. falciparum and Cross-Boosting of Immune Responses.

In general, malaria immunity has been suggested to be species specific with very little, if any, known cross-reactivity between Plasmodium vivax and P. falciparum, both of which are responsible for >90% of human malaria, and co-endemic in many countries. It is therefore believed that species-specific immunity may be needed to target different species of Plasmodium. Pfs48/45 and Pvs48/45 are well established targets in the sexual stages of the malaria parasites, and are being pursued for the development of transmission blocking vaccines. Comparison of their sequences reveals 61% and 55% identity at the DNA and protein level, respectively raising the possibility that these two target antigens might share cross-reacting epitopes. Having succeeded in expressing recombinant Pfs48/45 and Pvs48/45 proteins, we hypothesized that these proteins will not only exhibit immunological cross–reactivity but also cross-boost immune responses. Mice were immunized with purified recombinant proteins using CFA, Montanide ISA-51 and alum as adjuvants, and the sera were analyzed by ELISA, Western blotting and indirect fixed and live IFA to address the hypothesis. Our studies revealed that Pvs48/45-immune sera showed strong cross-reactivity to full length Pfs48/45 protein, and the majority of this cross reactivity was in the amino-terminal and carboxyl-terminal sub-fragments of Pfs48/45. In cross-boosting experiments Pfs48/45 and Pvs48/45 antigens were able to cross-boost each other in mouse immunization studies. Additionally we also noticed an effect of adjuvants in the overall magnitude of observed cross-reactivity. These studies may have significant implications for immunity targeting transmission of both the species of malaria parasites.

Molecular characterization and phylogenetic analysis of Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium cynomolgi.

18S ribosomal RNA gene sequences of different species of Plasmodium were aligned and analyzed to determine the molecular diversity among different species of Plasmodium. AT content of P. cynomolgi, P. ovale, P. falciparum, P. vivax and P. malariae ranged from 62.30 to 63.15, 63.90 to 65.29, 66.67 to 68.40, 61.66 to 63.25 and 64.09 to 76.36 in case respectively. GC content of P. cynomolgi, P. ovale, P. falciparum, P. vivaxand P. malariae ranged from 36.85 to 37.70, 34.71 to 36.43, 31.60 to 33.27, 23.64 to 35.91 and 36.75 to 38.34 respectively. Molecular weight (Da) of P. cynomolgi, P. ovale, P. falciparum, P. vivax and P. malariae ranged from 1,160,127.00 to 1,400,332.00, 437,273.00 to 481,438.00, 668,021.00 to 685,243.00, 540,378.00 to 1,176,962.00 and 132,788.00 to 305,211.00 respectively. Relative melting temperature (Tm) of P. cynomolgi and P. ovale varied from 0.36799 to 0.36837 and 0.36712 to 0.36814 respectively. In P. falciparum and P. vivax relative Tm ranged from 0.36545 to 0.36626 and 0.36802 to 0.36866 respectively. Relative Tm of P. malariae varied from 0.36174 to 0.36790.

Seroepidemiology of Plasmodium species infections in Zimbabwean population.

BackgroundIndividuals living in malaria-endemic regions may be exposed to more than one Plasmodium species; there is paucity of data on the distribution of the different species of Plasmodium in affected populations, in part due to the diagnostic method of microscopy, which cannot easily differentiate between the species. Sero-epidemiological data can overcome some of the shortcomings of microscopy.MethodsThe specificity of IgG antibodies to recombinant merozoite surface protein 1 (MSP-119) derived from four human Plasmodium species (Plasmodiumfalciparum, Plasmodiumvivax, Plasmodiummalariae, Plasmodiumovale) was investigated using competition enzyme-linked immunosorbent assay. Subsequently, these antigens were used to determine the exposure prevalence to the different Plasmodium species in serum samples of participants. One-hundred individuals, aged five-18 years, from each of the three Plasmodium meso-endemic Zimbabwean villages (Burma Valley, Mutoko, Chiredzi) were recruited in the study.ResultsThe study demonstrated that the host serum reactivity to MSP-119 antigens was species-specific and that no cross-reactivity occurred. The overall prevalence of antibody response to MSP-119 antigens was 61 % in Burma Valley, 31 % in Mutoko and 32 % in Chiredzi. Single species IgG responses to MSP-119 were most frequent against P. falciparum, followed by P. malariae and P. ovale, with responses to P. vivax being the least prevalent. Interestingly, 78–87 and 50 % of sera with IgG responses to P. malariae and P. ovale MSP-119, respectively, also had IgG specific response for P. falciparum MSP-119 antigens, indicating that exposure to these species is a common occurrence in these populations. Single species IgG responses to the non-falciparum species were at a very low frequency, ranging between 0 and 13 % for P. malariae.ConclusionsThere is evidence of a higher exposure to the non-falciparum parasite species than previously reported in Zimbabwe. The recombinant MSP-119 antigens could be used as additional diagnostic tools in antibody assays for the detection of exposure to the different Plasmodium species. The results also introduce an interesting concept of the co-infection of non-falciparum Plasmodium almost always with P. falciparum, which requires further validation and mechanistic studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1325-3) contains supplementary material, which is available to authorized users.

Clinical profile and complications of acute malaria caused by different species of Plasmodium

Introduction: Malaria is more severe in children than in adults and 78% of all deaths due to malaria occur in children under 5years. Plasmodium vivax has long been considered to have benign course. However during past few years several studies reported severe complicated cases of vivax malaria. Methodology: Children in the age group of 6 months to 15 years admitted in the Department of Pediatrics with clinical malaria were tested for malaria using peripheral smear, QBC and rapid diagnostic test. Children with positivity of any of these tests were enrolled in the study. Complete clinical profile is noted. Investigations like complete blood counts, LFT, RFT etc., were done. Results: Out of 150 children enrolled in the study 80 had Plasmodium vivax monoinfection. 61 had Plasmodium falciparum monoinfection and 9 had mixed infection. 41% of them were under 5years of age. The incidence of complications like severe anemia (10% vs. 18%), jaundice (10% vs. 44%), transaminitis (6% vs.13%), azotemia (6% vs. 36%) and thrombocytopenia (12.5% vs. 26%) were more common in P falciparum than in P vivax malaria with statistical significance (p < 0.05). There was no statistically significant difference in the incidence of hypoglycemia and cerebral malaria in P vivax and P falciparum malaria. Conclusion: The incidence of severe malaria in P. vivax infection is comparable to that in P. falciparum infection and it is no more benign. Hence robust efforts are required for reduction and elimination of P vivax transmission.

Genetic Analysis and Species Specific Amplification of the Artemisinin Resistance-Associated Kelch Propeller Domain in P. falciparum and P. vivax.

Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong Subregion and now poses a threat to malaria control and prevention. Recent work has identified mutations in the kelch propeller domain of the P. falciparum K13 gene to be associated artemisinin resistance as defined by delayed parasite clearance and ex vivo ring stage survival assays. Species specific primers for the two most prevalent human malaria species, P. falciparum and P. vivax, were designed and tested on multiple parasite isolates including human, rodent, and non- humans primate Plasmodium species. The new protocol described here using the species specific primers only amplified their respective species, P. falciparum and P. vivax, and did not cross react with any of the other human malaria Plasmodium species. We provide an improved species specific PCR and sequencing protocol that could be effectively used in areas where both P. falciparum and P. vivax are circulating. To design this improved protocol, the kelch gene was analyzed and compared among different species of Plasmodium. The kelch propeller domain was found to be highly conserved across the mammalian Plasmodium species.

Computational Study of Quinolone Derivatives to Improve their Therapeutic Index as Anti-malaria Agents: QSAR and QSTR.

Malaria is a parasitic disease caused by five different species of Plasmodium. More than 40% of the world's population is at risk and malaria annual incidence is estimated to be more than two hundred million, malaria is one of the most important public health problems especially in children of the poorest parts of the world, annual mortality is about 1 million. The epidemiological status of the disease justifies to search for control measures, new therapeutic options and development of an effective vaccine. Chemotherapy options in malaria are limited, moreover, drug resistant rate is high. In spite of global efforts to develop an effective vaccine yet there is no vaccine available. In the current study, a series of quinolone derivatives were subjected to quantitative structure activity relationship (QSAR) and quantitative structure toxicity relationship (QSTR) analyses to identify the ideal physicochemical characteristics of potential anti-malaria activity and less cytotoxicity. Quinolone with desirable properties was built using HyperChem program, and conformational studies were performed through the semi-empirical method followed by the PM3 force field. Multi linear regression (MLR) was used as a chemo metric tool for quantitative structure activity relationship modeling and the developed models were shown to be statistically significant according to the validation parameters. The obtained QSAR model reveals that the descriptors PJI2, Mv, PCR, nBM, and VAR mainly affect the anti-malaria activity and descriptors MSD, MAXDP, and X1sol affect the cytotoxicity of the series of ligands.

Identification and expression of maebl, an erythrocyte-binding gene, in Plasmodium gallinaceum

Avian malaria is of significant ecological importance and serves as a model system to study broad patterns of host switching and host specificity. The erythrocyte invasion mechanism of the malaria parasite Plasmodium is mediated, in large part, by proteins of the erythrocyte-binding-like (ebl) family of genes. However, little is known about how these genes are conserved across different species of Plasmodium, especially those that infect birds. Using bioinformatical methods in conjunction with polymerase chain reaction (PCR) and genetic sequencing, we identified and annotated one member of the ebl family, merozoite apical erythrocyte-binding ligand (maebl), from the chicken parasite Plasmodium gallinaceum. We then detected the expression of maebl in P. gallinaceum by PCR analysis of cDNA isolated from the blood of infected chickens. We found that maebl is a conserved orthologous gene in avian, mammalian, and rodent Plasmodium species. The duplicate extracellular binding domains of MAEBL, responsible for erythrocyte binding, are the most conserved regions. Our combined data corroborate the conservation of maebl throughout the Plasmodium genus and may help elucidate the mechanisms of erythrocyte invasion in P. gallinaceum and the host specificity of Plasmodium parasites.

Plasmodium falciparum in different age groups in Karachi-Pakistan

Background: Malaria is a parasitic disease caused by different species of Plasmodium showing symptoms of high fever, chill, flu like condition, headache and anemia, spread by the transfer of pathogens by female Anopheles mosquitoes, transfusions of blood and blood products. There are four species of Plasmodium, such as Plasmodium falciparum, P. vivax, P. ovale and P. malaria, but in Pakistan there is no any evidence of last two species except P. falciparum and P. vivax. The severity of the diseases not only depends on the species of Plasmodium but also on age, sex, immunity, nutritional values, general health and socio-economic condition whereas P. falciparum malaria or cerebral malaria is dangerous among four Plasmodium species because it increase the mortality rates throughout the world. Methods: The study area was located in Karachi region, on the coast of Arabian Sea, which based on different districts including district South, East, West, Central and Malir. The Performa was provided and filled at the time of survey. Each house was visited once a week and participants having high temperature and history with severe headache and chill were thoroughly examined and blood smear was taken. Thick and thin blood smears were examined and the thin blood smears were fixed in 100% methanol and stained in 2% Giemsa. Different stages of Plasmodium species especially P. falciparum and P. vivax were investigated under the oil immersion and the number of parasites/200 white blood cells (WBCs) were counted. Results: Total 1400 people were examined between the age of 2-12 years and 1762 for above 12 years during 2002 to 2004, in which 326 and 164 were found infected with P. falciparum respectively. In 2002 infection were recorded (32.7%) and (6.3%), in 2003 (20.9%) and (9.5%), while during 2004 infection were recorded (18.1%) and (11.6%). in age 2-12 years and above 12 years likewise. Conclusion: Early detection of the parasite on thick and thin films may help to reduce the morbidity and mortality associated with falciparum malaria, it is also concluded that patients between the ages of 2-12 years are more infected than those above 12 years.

Development of Humanized Mouse models to Study Human Malaria Parasite Infection

Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future.

Toward fast malaria detection by secondary speckle sensing microscopy

Diagnosis of malaria must be rapid, accurate, simple to use, portable and low cost, as suggested by the World Health Organization (WHO). Despite recent efforts, the gold standard remains the light microscopy of a stained blood film. This method can detect low parasitemia and identify different species of Plasmodium. However, it is time consuming, it requires well trained microscopist and good instrumentation to minimize misinterpretation, thus the costs are considerable. Moreover, the equipment cannot be easily transported and installed. In this paper we propose a new technique named “secondary speckle sensing microscopy” (S3M) based upon extraction of correlation based statistics of speckle patterns generated while illuminating red blood cells with a laser and inspecting them under a microscope. Then, using fuzzy logic ruling and principle component analysis, good quality of separation between healthy and infected red blood cells was demonstrated in preliminary experiments. The proposed technique can be used for automated high rate detection of malaria infected red blood cells.

The SLC4A1 gene is under differential selective pressure in primates infected by Plasmodium falciparum and related parasites

Malaria is a disease caused by Plasmodium parasites and is responsible for high mortality in humans. This disease is caused by four different species of Plasmodium though the main source of mortality is Plasmodium falciparum. Humans have a number of genetic adaptations that act to combat Plasmodium. One adaptation is a deletion in the SLC4A1 gene that leads to Southeast Asian ovalocytosis (SAO). There is evidence that SAO erythrocytes are resistant to multiple Plasmodium species. Here we analyze SLC4A1 in 23 primates and mammals to test for differential selective pressures among different primate lineages. Because primates are infected with both human Plasmodium parasites and their relatives, this analysis can be used to test which human Plasmodium parasite is the likely target of SAO. A significantly different pattern of molecular evolution was found in humans and African apes, species that are infected by P. falciparum and its relatives. This effect was restricted to the cytosolic domain of the SLC4A1 gene. The evidence is consistent with a different selective regime operating on this gene domain in humans and African apes, when compared to other primates and mammals. Alternatively, this pattern is consistent with a relaxation of selection or weak adaptive evolution operating on a small number of amino acids. The adaptive interpretation of the results is consistent with the SAO allele of the SLC4A1 gene interacting with P. falciparum in humans, rather than other Plasmodium parasites. However, additional investigation of the relationship between SLC4A1 variants and Plasmodium in humans and African apes is required to test whether the different selective regime in humans and African apes is due to natural selection or relaxed constraint.

Clinical and molecular aspects of malaria fever

Although clinically benign, malaria fever is thought to have significant relevance in terms of parasite growth and survival and its virulence which in turn may alter the clinical course of illness. In this article, the historical literature is reviewed, providing some evolutionary perspective on the genesis and biological relevance of malaria fever, and the available molecular data on the febrile-temperature-inducible parasite factors that may contribute towards the regulation of parasite density and alteration of virulence in the host is also discussed. The potential molecular mechanisms that could be responsible for the induction and regulation of cyclical malaria fevers caused by different species of Plasmodium are also discussed.