The Seattle MCTC is recruiting for our next trial, which starts in October 2017. If you are interesting in participating or know someone who does, please direct them to www.fredhutch.org/en/labs/vaccine-and-infectious-disease/seattle-malaria-clinical-trials-center.html
The Seattle MCTC co-sponsored the 2017 SIFF and helped to spread the word about our clinical trials program to local Seattle residents. The Seattle MCTC uses a wide variety of media outlets to inform area residents about our need for healthy volunteers to participate in our clinical trials of drug and vaccine candidates. On several of the opening nights, Drs. Kublin, Murphy or Duke addressed the audiences just before the screenings about the work of the MCTC.
The last MCTC-sponsored opening was for "Frontieres" (Borders - www.siff.net/festival/borders), the story of a harrowing journey of several women across west Africa. Photo (left to right): SIFF Education Programs Manager Dustin Kaspar, Director Apolline Traoré, Actor Amélie MBaye and MCTC co-investigator Sean Murphy. Ms. Traoré is from Burkina Faso, a west African country of 18 million people. In 2015, at least 7 million cases of malaria occurred there. The work of the Seattle MCTC strives to reduce the burden of malaria in Burkina Faso and throughout the world. For more information on the Seattle MCTC, go to Seattle Malaria Clinical Trials Center.
Nothing completes a sunny afternoon malaria lab barbecue like mosquitoes...especially when there's only one mosquito and it is made out of puff pasty dough and surrounded by little puff pastry parasites! Strawberry-peach pie never tasted as good! Photo is from our recent lab party to celebrate two lab members accepted into graduate and professional training programs out east. Zac Billman will be heading to the University of North Carolina to pursue combined MD/PhD training in their MSTP program. Amelia Hanron will be heading to Yale University for their Masters of Public Health program with a focus on the Epidemiology of Infectious Disease. Congrats to both and thanks for the pie Amelia!
One-step method for gametocyte and erythrocyte stage parasite detection published in malaria journal
The large collaborative team's work on spliced gametocyte mRNAs as infection detection markers is now published in the Malaria Journal (http://rdcu.be/sbZ4). Gametocytes are sexual-stage parasites that cause no disease in humans but are rather the forms transmitted from humans back to mosquitoes during a mosquito bite. The male and female gametocytes mate in the mosquito and allow the lifecycle to continue (see Lifecycle page). Since people have no symptoms from gametocytes and since most treatments for malaria infection do not kill gametocytes, these forms can circulate for a long time in humans and this can aid onward transmission to mosquitoes. Normal molecular diagnostic tests (like our 18S rRNA RT-PCR assay) cannot be used to detect gametocytes because all malaria parasites make 18S rRNAs and because other genomic targets are not stage-specific. Instead, the usual approach has been to perform gametocyte mRNA-specific RT-PCR AFTER treating extracted nucleic acids with DNase to destroy genomic material that would otherwise confuse the test. Most gametocyte-specific mRNAs in common use are from single exon genes. However, we (and a few others) have identified spliced gametocyte specific mRNAs and designed RT-PCR reagents that specifically amplify regions across these splicing sites, thereby eliminating the need for DNase treatment. The bottom line is that our new assay can be combined with the existing 18S rRNA RT-PCR assay in a ultrasensitive, multiplex assay that may be useful for field studies, drug studies and other clinical trials. We thank our colleagues at UW, the Center for Infectious Disease Research, Medicines for Malaria Venture, University of California San Francisco, Infectious Diseases Research Collaboration (Uganda), the London School of Hygiene & Tropical Medicine, PATH and the Seattle Malaria Clinical Trials Center (Fred Hutch Cancer Research Center) for collaborating on this project.
If you are interested in a project requiring this type of testing, please contact us at firstname.lastname@example.org.
April 25 is World Malaria Day. The good news is that malaria morbidity and mortality continues to decline. The bad news is that without sustained investment, focus and creativity on the parts of scientists, clinicians, funders, politicians and just about everyone, the gains that we have made in the past 20 years could be undone. Malaria elimination and eradication efforts need a highly effective vaccine to augment the drugs and vector interventions being applied globally. Today Dr. Sebastian Mikolajczak and I spoke with a team from UW Medicine about the work going on in Seattle. See the Facebook Live feed below.
After completing training of diagnostic laboratory staff in Kisumu, Kenya, Amelia and Mariko took in the sights of Kenya!
Top: Great Rift Valley viewpoint
Bottom: Nairobi Giraffe Center
UW Lab members head to Kisumu, Kenya to train colleagues on the plasmodium 18S rRNA RT-PCR assay in support of clinical trials in kenya
Mariko Seilie and Amelia Hanron are in Kisumu, Kenya this week to work with colleagues at the KEMRI-CDC site. The UW team will formally train our Kenyan colleagues on the UW-developed Plasmodium 18S rRNA biomarker RT-PCR assay that is used as a infection detection tool in malaria clinical trials. This site is the first facility in a malaria-endemic country to bring up the biomarker assay. The UW and KEMRI-CDC anticipate that this collaboration will enhance the ability to conduct clinical trials in the Kisumu region, including at the main field site in Siaya. The UW and Kisumu sites will be able to exchange materials, provide quality assurance for one another and eventually lead the development of a larger multi-center network equipped to run the molecular malaria assays.
The Center for Infectious Disease Research in collaboration with the Fred Hutch Cancer Research Center and the University of Washington published the findings of the GAP3KO Phase 1 vaccine study on January 4 in Science Translational Medicine (link to paper: https://doi.org/10.1126/scitranslmed.aad9099). This study showed that a P. falciparum strain with three genes deleted with safe, well-tolerated and immunogenic in ten human volunteers at a study we conducted in Seattle in 2014. Now on to the efficacy study planned for later in 2017...!!!
BBC article: http://www.bbc.com/news/health-38509736
Science Now article link: http://www.sciencemag.org/news/2017/01/promising-malaria-vaccine-disables-key-parasite-genes
Rapid diagnostic tests (RDTs) are a critical component of WHO's "test and treat" approach to malaria. Over 70% of malaria diagnoses in Africa are made by RDTs. A commonly targeted antigen in these lateral flow diagnostic devices is the P. falciparum histidine rich protein 2 (HRP2). However, a recent study from the University of North Carolina reports that 1 in 15 P. falciparum-infected children was infected by a P. falciparum strain with a pfhrp2 deletion. These parasites are undetectable by HRP2-based RDTs. The study was covered by the Science Daily News and was published in the Journal of Infectious Diseases. The finding of pfhrp2 deletions is not a completely new revelation (it was first reported in the Peruvian Amazon in 2010 but has now been observed globally in multiple reports). However, this was the first cross-sectional study on a national scale. The authors tested 7,137 children in the Democratic Republic of Congo and found 783 with discrepant RDT-/PCR+ results. PCR is more sensitive than RDTs so many of these results simply reflect samples where HRP2+ parasites were present at concentrations detectable only by PCR. However, 149 of these discrepant results turned out to be due to pfhrp2 deleted parasites, which are not detected by the RDT. These 149 samples account for 6.4% of the P. falciparum positives in the overall nationwide study.
While non-HRP2-based RDTs are in development to combat this problem, PCR and RT-PCR methods that target the essential 18S rRNA or coding genes have been used to find even pfhrp2-deleted parasites. Our lab's pan-Plasmodium 18S rRNA RT-PCR method can detect P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi as well as Plasmodium species that only infect mice like P. yoelii and P. berghei. This high rate of conservation within and between Plasmodium species and the critical role of 18S rRNAs in eukaryotic biology make it less likely that field strains will evade an 18S rRNA RT-PCR based approach. Currently-approved RDTs detect parasites at densities down to ~100,000-200,000 parasites/milliliter, whereas 18S rRNA RT-PCR can detect parasites down to 10-20 parasites/milliliter. Thus, the RT-PCR approach is thousands of time more sensitive than currently-approved RDTs. However, next-generation RDTs are rapidly improving and this is a good thing because they can be used right at the point of patient care. We are actively using our RT-PCR tests to support field studies whose goals include improvement of new and better RDTs. Perhaps one day, RDTs will be able to find nearly all of the malaria parasites lurking in asymptomatic patients worldwide regardless of their pfhrp2 status.
Reference to the UNC paper: Parr et al. 2016. Pfhrp2 -deleted Plasmodium falciparum parasites in the Democratic Republic of Congo: A national cross-sectional survey. Journal of Infectious Diseases. jiw538 DOI: 10.1093/infdis/jiw538
After nearly eradicating malaria decades ago and then experiencing a deadly resurgence, Sri Lanka has now succeeded in malaria eradication and has been certified by WHO. Congrats! (See article in the Wall Street Journal) for more info.
But wait there's more...In addition, the WHO also certified Kyrgyzstan's malaria elimination, which makes Europe the first WHO region to interrupt indigenous malaria transmission!!! More progress!