Dye kills malaria parasites at speed not seen before -- ScienceDaily

Research shows that the dye methylene blue is a safe antimalarial that
kills malaria parasites at an unprecedented rate. Within two days,
patients are cured of the disease and no longer transmit the parasite if
they are bitten again by a mosquito. This discovery was made by Radboud
university medical center scientists and international colleagues
during a research project conducted in Mali. The results are
published in The Lancet Infectious Diseases .

Bacterial infection in mosquitoes renders them immune to malaria parasites

"Scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have established an inheritable bacterial infection in malaria-transmitting Anopheles mosquitoes that renders them immune to malaria parasites. Specifically, the scientists infected the mosquitoes with Wolbachia, a bacterium common among insects that previously has been shown to prevent malaria-inducing Plasmodium parasites from developing in Anopheles mosquitoes. Before now, researchers had been unable to create mosquitoes with a stable Wolbachia infection that passed consistently from mother to offspring."

Complement Receptor 1 Variants Confer Protection from Severe Malaria in Odisha, India.

In Plasmodium falciparum infection, complement receptor-1 (CR1) on erythrocyte's surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue.

METHODS:

Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database.

RESULTS:

The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria.

CONCLUSIONS:

The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.

No antibodies, no problem: Researchers identify how mosquito immune system attacks specific infections

Researchers at the Johns Hopkins Bloomberg School of Public Health have determined a new mechanism by which the mosquitoes' immune system can respond with specificity to infections with various pathogens, including the parasite that causes malaria in humans, using one single gene. Unlike humans and other animals, insects do not make antibodies to target specific infections. According to the Johns Hopkins researchers, mosquitoes use a mechanism known as alternative splicing to arrange different combinations of binding domains, encoded by the same AgDscam gene, into protein repertoires that are specific for different invading pathogens.

Evidence for additive and interaction effects of host genotype and infection in malaria

The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8,C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children’s ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.

Evidence for additive and interaction effects of host genotype and infection in malaria

The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8,C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children’s ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.

'Benign' malaria key driver of human evolution in Asia-Pacific

The malaria species rampant in the Asia-Pacific region has been a significant driver of evolution of the human genome, a new study has shown. An international team of researchers has shown that Plasmodium vivax malaria, the most prevalent malaria species in the Asia-Pacific, is a significant cause of genetic evolution that provides protection against malaria.

Read more at: http://medicalxpress.com/news/2012-09-benign-malaria-key-driver-human.html#jCp

MicrobeWorld - Symbiotic Bacteria Halt Malaria Life Cycle in Mosquitoes

Allowing mosquitos to feed on engineered strains of the symbiotic bacteria that naturally live in their midguts may provide the answer to preventing the malarial parasite Plasmodium from completing the relevant stages of its life cycle in the airborne host and being transmitted to humans, researchers claim. A team at the Johns Hopkins Bloomberg School of Public Health’s Malaria Research Institute has generated engineered strains of a common symbiotic bacterium Pantoea agglomerans that resides in the midgut of the anopheles mosquito. The bacterium is modified to secrete proteins that directly block development and survival of the Plasmodial ookinetes and oocysts developing in the midgut, which would normally give rise to the sporozoites that are transmitted into humans through the mosquito’s saliva.

Futurity.org – How malaria outsmarts immune system memory

YALE (US) — The parasite that causes malaria creates its own version of a human immune hormon (Macrophage migration inhibitory factor) a trick that keeps the body from remembering the infection and developing immunity.

Related articles

 Functional characterization of the Plasmodium falciparum and P. berghei homologues of macrophage migration inhibitory factor. Augustin et al, 2007

'Protein microarrays' may reveal new weapons against malaria

'

Researchers link cerebral malaria to epilepsy, behavior disorders

• Cerebral malaria 
• Epilepsy

High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India.

Complement receptor 1 is a receptor for Plasmodium falciparium, the malaria vector

Combating malaria with spiroindolones : SciBX: Science-Business eXchange

Combating malaria with spiroindolones : SciBX: Science-Business eXchange

Related articles

• Malaria vaccine close to reality (news-medical.net)