Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance.

Background: Malaria rapid diagnostic tests (RDTs) have greatly improved access to diagnosis in endemic countries. Most RDTs detect Plasmodium falciparum histidine-rich protein 2 (HRP2), but their sensitivity is seriously threatened by the emergence of pfhrp2-deleted parasites. RDTs detecting P.

Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergens and B. microti.

Apicomplexan parasites include those of the genera Plasmodium, Cryptosporidium, and Toxoplasma and those of the relatively understudied zoonotic genus Babesia In humans, babesiosis, particularly transfusion-transmitted babesiosis, has been emerging as a major threat to public health. Like malaria, the disease pathology is a consequence of the parasitemia which develops through cyclical replication of Babesia parasites in host erythrocytes. However, there are no exoerythrocytic stages in Babesia, so targeting of the blood stage and associated proteins to directly prevent parasite invasion is the most desirable option for effective disease control.

Human Babesiosis: Pathogens, Prevalence, Diagnosis and Treatment.

Human babesiosis is a zoonotic disease caused by protozoan parasites of the genus, primarily in the Northeastern and Midwest United States due to , and Western Europe due to . Parasites are transmitted by the bite of the ixodid tick when the vector takes a blood meal from the vertebrate host, and the economic importance of bovine babesiosis is well understood. The pathology of human disease is a direct result of the parasite's ability to invade host's red blood cells.

Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria vaccine design.

With drug resistance to available therapeutics continuing to develop against Plasmodium falciparum malaria, the development of an effective vaccine candidate remains a major research goal. Successful interruption of invasion of parasites into erythrocytes during the blood stage of infection will prevent the severe clinical symptoms and complications associated with malaria. Previously studied blood stage antigens have highlighted the hurdles that are inherent to this life-cycle stage, namely that highly immunogenic antigens are also globally diverse, resulting in protection only against the vaccine strain, or that naturally acquired immunity to blood stage antigens do not always correlate with actual protection.

Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America.

Background: Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations.

Identification and characterization of the RouenBd1987 Babesia divergens Rhopty-Associated Protein 1.

Human babesiosis is caused by one of several babesial species transmitted by ixodid ticks that have distinct geographical distributions based on the presence of competent animal hosts. The pathology of babesiosis, like malaria, is a consequence of the parasitaemia which develops through the cyclical replication of Babesia parasites in a patient's red blood cells, though symptoms typically are nonspecific. We have identified the gene encoding Rhoptry-Associated Protein -1 (RAP-1) from a human isolate of B.

A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein.

Background: The Plasmodium falciparum protein RH5 is an adhesin molecule essential for parasite invasion of erythrocytes. Recent studies show that anti-PfRH5 sera have potent invasion-inhibiting activities, supporting the idea that the PfRH5 antigen could form the basis of a vaccine. Therefore, epitopes recognized by neutralizing anti-PfRH5 antibodies could themselves be effective vaccine immunogens if presented in a sufficiently immunogenic fashion.

Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia.

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area.

A community-randomized evaluation of the effect of intermittent preventive treatment in infants on antimalarial drug resistance in southern Tanzania.

Background: Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance.

Methods: Twenty-four areas were randomly assigned to receive or not receive IPTi.

Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP.

Introduction: Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia.

Analysis of polymorphisms in the merozoite surface protein-3α gene and two microsatellite loci in Sri Lankan Plasmodium vivax: evidence of population substructure in Sri Lanka.

The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3α (Pvmsp-3α) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3α, 11 alleles were found with an expected heterozygosity (H(e)) of 0.

High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children.

Background: Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP).

Methods: The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné.

Epidemic of Plasmodium falciparum malaria involving substandard antimalarial drugs, Pakistan, 2003.

Because of instability in eastern Afghanistan, new refugees crossed into the federally administered tribal areas of northwestern Pakistan in 2002. In 2003, we investigated an epidemic of Plasmodium falciparum malaria in 1 of the camps. Incidence was 100.

Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola.

Objectives: To assess the extent of drug resistance in Uige through molecular genetic analysis and to test whether the dhfr triple mutant alleles present in Angola are of southeast Asian origin.

Methods: Seventy-one samples of blood from children admitted to the Pediatric Emergency Unit of Uige Provincial Hospital in 2004 were screened for resistance mutations at pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6.

Results: Mutations in pfcrt (codon76), pfmdr1 (codon86), pfdhfr (codons 51, 59, 108) and pfdhps (codons 436, 437) were common.

Randomized trial of artesunate+amodiaquine, sulfadoxine-pyrimethamine+amodiaquine, chlorproguanal-dapsone and SP for malaria in pregnancy in Tanzania.

Background: Malaria in pregnancy is serious, and drug resistance in Africa is spreading. Drugs have greater risks in pregnancy and determining the safety and efficacy of drugs in pregnancy is therefore a priority. This study set out to determine the efficacy and safety of several antimalarial drugs and combinations in pregnant women with uncomplicated malaria.

High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581.

Background: Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6-59 month children with uncomplicated malaria and in asymptomatic 2-10 month old infants.

ama1 genes of sympatric Plasmodium vivax and P. falciparum from Venezuela differ significantly in genetic diversity and recombination frequency.

Background: We present the first population genetic analysis of homologous loci from two sympatric human malaria parasite populations sharing the same human hosts, using full-length sequences of ama1 genes from Plasmodium vivax and P. falciparum collected in the Venezuelan Amazon.

Methodology/principal Findings: Significant differences between the two species were found in genetic diversity at the ama1 locus, with 18 distinct haplotypes identified among the 73 Pvama1 sequences obtained, compared to 6 unique haplotypes from 30 Pfama1 sequences, giving overall diversity estimates of h = 0.

Cluster of falciparum malaria cases in UK airport.

A cluster of 6 cases of Plasmodium falciparum malaria occurred in a UK airport among 30 travelers returning to the United States from East Africa. Molecular genotyping analysis indicated that all had been exposed to different parasites. The travelers' use of chemoprophylaxis was poor; their perception of risk was limited.

Seasonal carriage of pfcrt and pfmdr1 alleles in Gambian Plasmodium falciparum imply reduced fitness of chloroquine-resistant parasites.

Background: Observations in natural Plasmodium falciparum populations after removal of failing drugs suggest that there is a fitness cost of drug resistance.

Methods: To examine the effect of transient removal of drug pressure, we analyzed seasonal changes in the prevalence of chloroquine (CQ)-resistant parasite genotypes in The Gambia. Parasite isolates from 441 children presenting with uncomplicated falciparum malaria over 5 seasons (1998-2002) were linked to weekly rainfall data.

Comparison of the therapeutic efficacy of chloroquine and sulphadoxine-pyremethamine in children and pregnant women.

Objective: To compare the parasitological failure rates of under-fives and pregnant women with parasitaemia treated with chloroquine (CQ) or sulphadoxine-pyrimethamine (SP).

Methods: During a clinical trial of CQ, SP, amodiaquine (AQ) and SP plus AQ combination for malaria treatment in pregnant women in Ghana, a parallel study of treatment of children below 5 years of age with symptomatic malaria with CQ and SP was undertaken. Four hundred and fifty pregnant women with malaria parasitaemia and 203 children with malaria parasitaemia were randomized to receive CQ or SP.

Plasmodium malariae in Haitian refugees, Jamaica.

Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P.

Children in Burkina Faso who are protected by insecticide-treated materials are able to clear drug-resistant parasites better than unprotected children.

Background: It has been suggested that reducing exposure to malaria by vector control might impair the development of naturally acquired immunity to malaria. It is also thought that an individual's ability to clear drug-resistant malarial parasites after treatment is enhanced by acquired immunity.

Methods: To investigate the hypothesis that insecticide-treated materials may affect the acquisition of immunity to malaria, we compared the ability of children living in villages in which insecticide-treated curtains (ITCs) had been used for 6-8 years to clear resistant parasites after treatment with chloroquine (CQ) with that of children living in unprotected villages.

P. vivax malaria complicated by shock and ARDS.

We report a case of Plasmodium vivax malaria complicated by shock and ARDS. The patient responded to oral chloroquine and primaquine and PCR was positive for P. vivax DNA and negative for P.