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Neafsey D.E.,Cambridge Broad Institute | Lawniczak M.K.N.,Imperial College London | Park D.J.,Cambridge Broad Institute | Redmond S.N.,Imperial College London | And 16 more authors.
Science | Year: 2010

Mosquitoes in the Anopheles gambiae complex show rapid ecological and behavioral diversification, traits that promote malaria transmission and complicate vector control efforts. A high-density, genome-wide mosquito SNP-genotyping array allowed mapping of genomic differentiation between populations and species that exhibit varying levels of reproductive isolation. Regions near centromeres or within polymorphic inversions exhibited the greatest genetic divergence, but divergence was also observed elsewhere in the genomes. Signals of natural selection within populations were overrepresented among genomic regions that are differentiated between populations, implying that differentiation is often driven by population-specific selective events. Complex genomic differentiation among speciating vector mosquito populations implies that tools for genome-wide monitoring of population structure will prove useful for the advancement of malaria eradication.


BETHESDA, Maryland, 16 de febrero de 2017 /PRNewswire/ -- En un informe publicado hoy a través de The Lancet Infectious Diseases (Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed Malian adults: a randomised, double-blind trial), los investigadores indicaron que la vacuna Sanaria® PfSPZ protege frente a las infecciones naturales de Plasmodium falciparum, principal causa de fallecimientos por malaria, manteniendo la protección durante las 24 semanas de estudio en un área de Mali que cuenta con una intensa transmisión de la malaria. El estudio estuvo dirigido por medio del doctor Mahamadou Sissoko, del Malaria Research and Training Center (MRTC) de la University of Science, Techniques and Technologies, Bamako, Mali y también por la doctora Sara Healy, del Laboratory of Malaria Immunology and Vaccinology, del National Institute of Allergy and Infectious Diseases de los U.S. National Institutes of Health. Se administraron 5 dosis de vacuna PfSPZ a 44 sujetos y placebo en forma de solución salina a otros 44 sujetos. Los voluntarios se sometieron a seguimiento durante 6 meses para determinar la presencia de parásitos de malaria en la sangre. Una impresionante cantidad del 93% del grupo tratado con placebo tuvo una o más infecciones de malaria; solo el 66% de los sujetos vacunados adquirió una infección. Esto representa el 48% de la eficacia de protección por medio del análisis del tiempo para el evento y una eficacia de un 29% según el análisis proporcional. No se dieron diferencias en los efectos secundarios entre los grupos vacunados y los tratados con placebo. El consejero delegado de Sanaria, Stephen L. Hoffman, MD, explicó: "Estos son resultados esperanzadores que demuestran la protección destacada con el régimen de dosis que es sub-óptima. Los ensayos clínicos en marcha en Tanzania, Guinea Ecuatorial, Burkina Faso, Alemania, Estados Unidos y Mali está previsto establezcan un régimen de dosis de vacuna PfSPZ que proporcionará el nivel de protección que buscamos". La vacuna PfSPZ está formada por parásitos de malaria crio-preservados vivos y purificados de forma atenuada por la radiación y que son administrados en una inyección de 0,5 mL por medio de inoculación venosa directa rápida. Los niños de África son los más afectados a causa de la malaria. En 2015, la malaria causó 214 millones de episodios clínicos y 438.000 muertes en todo el mundo según la OMS. Este impacto tan devastador se produce a pesar de las inversiones de miles de millones de dólares en esfuerzos para el control de la malaria. La malaria es además una preocupación para los turistas, diplomáticos, viajeros de negocios, trabajadores de ayuda, trabajadores industriales y personal militar en todo el mundo. El profesor Ogobara Doumbo, MD, PhD y director de Mali MRTC, comentó: "Llevamos décadas esperando una vacuna contra la malaria que sea altamente eficaz. Hemos evaluado numerosas vacunas contra la malaria experimentales en Mali. Este es, de lejos, el mejor resultado que hemos logrado. Estamos orgullosos de haber albergado el primer ensayo de eficacia de campo de la vacuna PfSPZ en África, y estamos expectantes por conseguir los resultados del segundo ensayo". "Estos resultados proporcionan que las pruebas de la protección contra la infección, no solo contra la enfermedad, se pueden mantener durante al menos medio año. Esta es la piedra angular para nosotros en referencia al régimen de vacuna PfSPZ que proporcionará un elevado nivel y protección duradera a las personas que padecen malaria dentro de las áreas afectadas", indicó el profesor Marcel Tanner, director general de la Swiss Academy of Sciences y director emérito del Swiss Tropical and Public Health Institute. "Esta vacuna es una herramienta ideal para conseguir la eliminación. Estamos emocionados en relación a los ensayos clínicos que puede conseguir la vacuna PfSPZ en África desde Tanzania desde el este de Guinea Ecuatorial hasta el oeste". Acerca de Sanaria Inc.: La misión de Sanaria es comercializar vacunas para la malaria de parásito completo que confieran protección duradera y de alto nivel contra la malaria, además de usar estas vacunas para la prevención de la malaria en personas y eliminen la malaria en regiones completas. Sanaria (http://www.sanaria.com) tiene su sede en Rockville, Maryland. Este comunicado contiene determinadas declaraciones prospectivas que implican riesgos e incertidumbres conocidos y desconocidos, que pueden causar que los resultados reales difieran materialmente de los anticipados expresados o implícitos por las declaraciones efectuadas. Si desea más información contacte con Alexander Hoffman, press@sanaria.com, 301-339-0092.


BETHESDA, Maryland, Feb. 16, 2017 /PRNewswire/ -- In a report published today in The Lancet Infectious Diseases, (Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed Malian adults: a randomised, double-blind trial) investigators reported that Sanaria® PfSPZ Vaccine protected against natural infections of Plasmodium falciparum, the leading cause of malaria deaths and protection was sustained for the 24 weeks of the study in an area of Mali with intense malaria transmission. The study was led by Dr. Mahamadou Sissoko, Malaria Research and Training Center (MRTC), University of Science, Techniques and Technologies, Bamako, Mali and by Dr. Sara Healy, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health. Five doses of PfSPZ Vaccine were administered to 44 subjects and saltwater placebo given to 44 subjects. Volunteers were followed for six months to determine presence of malaria parasites in the blood.  A staggering 93% of the placebo group had one or more malaria infections; only 66% of vaccinated subjects acquired an infection.  This represents 48% protective efficacy by time-to-event analysis and 29% efficacy by proportional analysis.  There were no differences in adverse events between the vaccinated and placebo groups. Sanaria CEO, Stephen L. Hoffman, MD said, "These are encouraging results which show significant protection with a dosage regimen that is sub-optimal. Ongoing clinical trials in Tanzania, Equatorial Guinea, Burkina Faso, Germany, the U.S., and Mali are intended to establish a PfSPZ Vaccine dosage regimen that will provide the high-level protection we seek." PfSPZ Vaccine is composed of live, radiation-attenuated purified, cryopreserved malaria parasites administered in a 0.5 mL injection by rapid direct venous inoculation. African children are hardest hit by malaria. In 2015 malaria caused 214M clinical episodes and 438,000 deaths worldwide according to WHO. This devastating impact occurs despite investment of billions of dollars in malaria control efforts. Malaria is also a concern for tourists, diplomats, business travelers, aid workers, industrial workers, and military personnel worldwide. Professor Ogobara Doumbo, MD, PhD, Director of the Mali MRTC, said, "We have been waiting decades for a highly effective malaria vaccine. We have assessed many experimental malaria vaccines in Mali. This is by far the best result we have ever obtained. We are proud to have hosted the first field efficacy trial of PfSPZ Vaccine in Africa, and are expectantly awaiting results of our second study." "These results provide evidence that protection against infection, not just disease, can be sustained for at least half a year.  This is a cornerstone for us to home in on a PfSPZ Vaccine regimen that will provide high level, lasting protection to people living in malaria affected areas," said Professor Marcel Tanner, President, Swiss Academy of Sciences and Director Emeritus, Swiss Tropical and Public Health Institute. "Such a vaccine is an essential tool to achieve elimination. We are excited about clinical trials of PfSPZ Vaccine that stretch across Africa from Tanzania in the East to Equatorial Guinea in the West." About Sanaria Inc.: Sanaria's mission is to commercialize whole-parasite malaria vaccines that confer high-level, long-lasting protection against malaria, and use these vaccines to prevent malaria in individuals and eliminate malaria from entire regions.  Sanaria (http://www.sanaria.com) is based in Rockville, Maryland. This news release contains certain forward-looking statements that involve known and unknown risks and uncertainties, which may cause actual results to differ materially from anticipated results or achievements expressed or implied by the statements made. For further information contact Alexander Hoffman, press@sanaria.com, 301-339-0092.


News Article | February 16, 2017
Site: www.chromatographytechniques.com

An investigational malaria vaccine given intravenously was well-tolerated and protected a significant proportion of healthy adults against infection with Plasmodium falciparum malaria--the deadliest form of the disease--for the duration of the malaria season, according to new findings published in the February 15th issue of the journal Lancet Infectious Diseases. The study participants live in Mali, Africa, where they are naturally exposed to the parasite. The investigational vaccine, known as the PfSPZ Vaccine, contains live but weakened sporozoites, the form of the parasite that infects humans, and was developed by scientists at Sanaria Inc., of Rockville, Maryland. The study was conducted by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the University of Science, Techniques, and Technologies of Bamako (USTTB), Mali, one of NIAID's International Centers of Excellence in Malaria Research. In 2015, 212 million cases of malaria occurred worldwide, and 429,000 people with malaria died, largely African children under five years old, according to the World Health Organization. Although only 1,500 to 2,000 cases of malaria are diagnosed in the United States each year, the disease is a concern for international travelers, aid workers and military personnel worldwide. "Considerable progress has been made in the global fight against malaria within the past decade, yet far too many people--particularly young African children--continue to become infected and die from the disease," said NIAID Director Anthony S. Fauci, M.D. "A safe, effective vaccine to protect against this mosquito-borne illness would greatly help efforts to bring the disease under control." Humans acquire malaria through the bite of infected mosquitoes, which inject parasites in the sporozoite stage of their life cycle into the bloodstream. The parasites travel to the liver, multiply, and then spread throughout the bloodstream causing malaria symptoms, including chills, fever, headache, nausea, sweating and fatigue. PfSPZ Vaccine uses live but weakened sporozoites of the malaria parasite species P. falciparum to generate an immune response to protect against malaria infection. Earlier research found that the experimental vaccine safe and protective against malaria infection for up to a year in healthy U.S. adults who had not been previously exposed to malaria. The Mali study was launched in January 2014 to provide additional safety data about PfSPZ Vaccine and determine if it could protect adults living in a malaria-endemic area against naturally occurring malaria infection. The study enrolled 109 healthy African men and non-pregnant women ages 18 to 35 years old. It was led by co-principal investigators Sara Healy, M.D., M.P.H., of NIAID's Laboratory of Malaria Immunology and Vaccinology, and Mahamadou Sissoko, M.D., M.P.H., of USTTB's Malaria Research and Training Center. Participants received either five doses of the intravenous PfSPZ Vaccine or five doses of placebo (saline) over five months of the dry season at the study's clinical site in the Donéguébougou village in rural Mali. Clinical staff then actively monitored the participants during the six-month rainy, malaria-transmission season for the presence of malaria parasites in the blood. The investigators report that the vaccine candidate was well-tolerated and safe with no serious adverse events. Among the 40 participants who received five placebo doses, 93 percent (37 participants) developed P. falciparum malaria infections; by comparison, 66 percent (27 participants) of the participants who received five doses of the PfSPZ Vaccine (41 participants) developed malaria infection. Based on the primary study analysis, PfSPZ Vaccine demonstrated a 48 percent protective efficacy by time-to-first positive malaria blood smear and 29 percent efficacy by proportion of participants with at least one positive malaria blood smear during a full 20-week malaria transmission season. By both measures of protective efficacy, there was statistically significant protection in the vaccine group as compared with the placebo group. "This level of sustained efficacy against malaria infection in a region with an intense transmission season has not been seen in previous malaria vaccine studies in Africa," said Dr. Healy. "It is a very encouraging finding that we can, hopefully, build upon." The vaccine-induced antibody response was considerably lower in the Mali study, however, than in the U.S. trial even though study participants received the same vaccine regimen. "The poor antibody response to PfSPZ Vaccine among Malians could have been because of the participants' lifelong exposure to P. falciparum," said Patrick E. Duffy, M.D., chief of NIAID's Laboratory of Malaria Immunology and Vaccinology. The investigators report that the intravenous delivery system for the PfSPZ Vaccine did not pose a problem to administer in a rural, malaria-endemic area--an initial concern about the experimental vaccine's unique design. "Direct venous inoculation is not currently used for any licensed vaccines to prevent an infectious disease," said Professor Ogobara Doumbo, M.D., Ph.D., senior scientist for the Mali malaria vaccine program and chair of the Department of Epidemiology of Parasitic Diseases at USTTB. "In this study, we administered 491inoculations in a rural setting without a problem, and the dosages were delivered in a matter of seconds. It shows that this approach is feasible from both a logistical and public health standpoint." According to the researchers, a preventive malaria vaccine employed in mass vaccination programs to eliminate P. falciparum from geographically defined areas would need to prevent malaria infection or transmission in at least 80 percent of recipients throughout the malaria transmission season. Clinical trials now underway in Africa, Europe and the United States have been designed to boost PfSPZ Vaccine's efficacy by increasing dosage levels and varying the timing and number of doses. The experimental vaccine is also being examined in demographic groups other than healthy adults, including adolescents, children and infants.


News Article | February 15, 2017
Site: www.prnewswire.co.uk

BETHESDA, Maryland, 16. Februar 2017 /PRNewswire/ -- In einem heute in der wissenschaftlichen Fachzeitschrift The Lancet Infectious Diseases veröffentlichten Bericht (Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed Malian adults: a randomised, double-blind trial) geben Prüfer an, dass der Sanaria® Impfstoff PfSPZ einen Schutz gegen alle Infektionen mit Plasmodium falciparum, der führenden Ursache für Todesfällen durch Malaria, biete. Laut den Angaben im Bericht konnte dieser Schutz zudem in einem Gebiet in Mali mit starker Malariaübertragung während der 24-wöchigen Studie aufrechterhalten werden. Die Leitung der Studie oblag Dr. Mahamadou Sissoko vom Malaria Research and Training Center (MRTC), University of Science, Techniques and Technologies, Bamako (Mali) und Dr. Sara Healy vom Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health. Fünf Dosen des Impfstoffs PfSPZ wurden 44 Studienteilnehmern verabreicht; die Placebogruppe aus 44 Studienteilnehmern erhielt eine Kochsalzlösung. Die freiwilligen Teilnehmer wurden sechs Monate lang beobachtet, um die Präsenz von Malariaparasiten im Blut zu ermitteln. Bei überragenden 93 % der Placebogruppe wurde mindestens eine Malariainfektion festgestellt; nur 66 % der geimpften Studienteilnehmer infizierten sich. Die durch eine Ereigniszeitanalyse ermittelte Schutzwirkung beträgt demnach 48 %; zudem liegt die verhältnismäßige Wirksamkeit bei 29 %. Im Hinblick auf Nebenwirkungen wurden zwischen der Impfstoff- und Placebogruppe keine Unterschiede verzeichnet. „Dies sind ermutigende Ergebnisse, die einen signifikanten Schutz bei suboptimaler Therapiedosis demonstrieren. Laufende klinische Studien in Tansania, Äquatorialguinea, Burkina Faso, Deutschland, den USA und Mali sollen die Entwicklung eines geeigneten Therapie- und Dosierungsplans für den Impfstoff PfSPZ, durch den der gewünschte hohe Schutz gewährleistet werden kann, ermöglichen", erklärte der CEO von Sanaria Stephen L. Hoffman, M.D. Der Impfstoff PfSPZ besteht aus kryokonservierten, hochreinen, lebensfähigen, durch radioaktive Strahlung attenuierten Malariaparasiten, die als intravenöse Impfinjektion (0,5 ml) direkt verabreicht werden. Afrikanische Kinder sind besonders stark von Malaria betroffen. Im Jahr 2015 wurden laut WHO weltweit 214 Mio. klinische Malariafälle und 438.000 Todesfälle verzeichnet. Diese katastrophalen Auswirkungen treten trotz Investitionen i. H. v. mehreren Milliarden Dollar in Malariaschutzmaßnahmen auf. Malaria stellt außerdem ein Risiko für Touristen, Diplomaten, Geschäftsreisende, Entwicklungshelfer, Industriearbeiter und Angehörige des Militärs aus der ganzen Welt dar. „Wir warten seit Jahrzehnten auf eine hochwirksame Malariaimpfung. Wir haben viele experimentelle Malariaimpfstoffe in Mali geprüft. Dies ist bei Weitem das beste Ergebnis, das wir je erreicht haben. Wir sind stolz, die erste im Feld durchgeführte Wirksamkeitsstudie des Impfstoffs PfSPZ in Afrika bei uns durchgeführt zu haben, und erwarten gespannt die Ergebnisse unserer zweiten Studie", erklärt Professor Ogobara Doumbo, M.D., Ph.D., Director des Mali MRTC. „Diese Ergebnisse bieten Evidenz, dass der Schutz vor Infektionen, nicht nur vor der Erkrankung, mindestens ein halbes Jahr aufrechterhalten werden kann. Dies ist ein wichtiger Meilenstein für uns, um einen Therapieplan für den Impfstoff PfSPZ, der einen hohen und langfristigen Schutz für Menschen in Malariagebieten bieten kann, einzugrenzen", erklärt Professor Marcel Tanner, President, Swiss Academy of Sciences und Director Emeritus, Swiss Tropical and Public Health Institute. „Ein solcher Impfstoff ist ein essentielles Instrument, um eine Ausrottung zu erreichen. Wir freuen uns auf die klinischen Studien für den Impfstoff PfSPZ, die sich über ganz Afrika, von Tansania im Osten nach Äquatorialguinea im Westen, erstrecken." Über Sanaria Inc.: Ziel von Sanaria ist es, Ganzparasiten-Malariaimpfungen auf den Markt zu bringen, die einen hohen und langfristigen Schutz vor Malaria bieten, und diese Impfungen einzusetzen, um sowohl Patienten vor Malaria zu schützen als auch eine Ausrottung von Malaria in ganzen Regionen zu erreichen. Sanaria (http://www.sanaria.com) hat seinen Hauptsitz in Rockville, Maryland. Diese Pressemitteilung enthält sogenannte „zukunftsbezogene Aussagen" (forward-looking statements), die bekannten sowie unbekannten Risiken und Unwägbarkeiten unterliegen, welche eine Abweichung der tatsächlichen Ergebnisse von den erwarteten Ergebnissen oder Leistungen, die implizit oder explizit in den hierin enthaltenen Aussagen kommuniziert werden, zur Folge haben können. Weiterführende Informationen: Alexander Hoffman, press@sanaria.com, 301-339-0092.


News Article | February 16, 2017
Site: www.eurekalert.org

An investigational malaria vaccine given intravenously was well-tolerated and protected a significant proportion of healthy adults against infection with Plasmodium falciparum malaria--the deadliest form of the disease--for the duration of the malaria season, according to new findings published in the February 15th issue of the journal Lancet Infectious Diseases. The study participants live in Mali, Africa, where they are naturally exposed to the parasite. The investigational vaccine, known as the PfSPZ Vaccine, contains live but weakened sporozoites, the form of the parasite that infects humans, and was developed by scientists at Sanaria Inc., of Rockville, Maryland. The study was conducted by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the University of Science, Techniques, and Technologies of Bamako (USTTB), Mali, one of NIAID's International Centers of Excellence in Malaria Research. In 2015, 212 million cases of malaria occurred worldwide, and 429,000 people with malaria died, largely African children under five years old, according to the World Health Organization. Although only 1,500 to 2,000 cases of malaria are diagnosed in the United States each year, the disease is a concern for international travelers, aid workers and military personnel worldwide. "Considerable progress has been made in the global fight against malaria within the past decade, yet far too many people--particularly young African children--continue to become infected and die from the disease," said NIAID Director Anthony S. Fauci, M.D. "A safe, effective vaccine to protect against this mosquito-borne illness would greatly help efforts to bring the disease under control." Humans acquire malaria through the bite of infected mosquitoes, which inject parasites in the sporozoite stage of their life cycle into the bloodstream. The parasites travel to the liver, multiply, and then spread throughout the bloodstream causing malaria symptoms, including chills, fever, headache, nausea, sweating and fatigue. PfSPZ Vaccine uses live but weakened sporozoites of the malaria parasite species P. falciparum to generate an immune response to protect against malaria infection. Earlier research found that the experimental vaccine safe and protective against malaria infection for up to a year in healthy U.S. adults who had not been previously exposed to malaria. The Mali study was launched in January 2014 to provide additional safety data about PfSPZ Vaccine and determine if it could protect adults living in a malaria-endemic area against naturally occurring malaria infection. The study enrolled 109 healthy African men and non-pregnant women ages 18 to 35 years old. It was led by co-principal investigators Sara Healy, M.D., M.P.H., of NIAID's Laboratory of Malaria Immunology and Vaccinology, and Mahamadou Sissoko, M.D., M.P.H., of USTTB's Malaria Research and Training Center. Participants received either five doses of the intravenous PfSPZ Vaccine or five doses of placebo (saline) over five months of the dry season at the study's clinical site in the Donéguébougou village in rural Mali. Clinical staff then actively monitored the participants during the six-month rainy, malaria-transmission season for the presence of malaria parasites in the blood. The investigators report that the vaccine candidate was well-tolerated and safe with no serious adverse events. Among the 40 participants who received five placebo doses, 93 percent (37 participants) developed P. falciparum malaria infections; by comparison, 66 percent (27 participants) of the participants who received five doses of the PfSPZ Vaccine (41 participants) developed malaria infection. Based on the primary study analysis, PfSPZ Vaccine demonstrated a 48 percent protective efficacy by time-to-first positive malaria blood smear and 29 percent efficacy by proportion of participants with at least one positive malaria blood smear during a full 20-week malaria transmission season. By both measures of protective efficacy, there was statistically significant protection in the vaccine group as compared with the placebo group. "This level of sustained efficacy against malaria infection in a region with an intense transmission season has not been seen in previous malaria vaccine studies in Africa," said Dr. Healy. "It is a very encouraging finding that we can, hopefully, build upon." The vaccine-induced antibody response was considerably lower in the Mali study, however, than in the U.S. trial even though study participants received the same vaccine regimen. "The poor antibody response to PfSPZ Vaccine among Malians could have been because of the participants' lifelong exposure to P. falciparum," said Patrick E. Duffy, M.D., chief of NIAID's Laboratory of Malaria Immunology and Vaccinology. The investigators report that the intravenous delivery system for the PfSPZ Vaccine did not pose a problem to administer in a rural, malaria-endemic area--an initial concern about the experimental vaccine's unique design. "Direct venous inoculation is not currently used for any licensed vaccines to prevent an infectious disease," said Professor Ogobara Doumbo, M.D., Ph.D., senior scientist for the Mali malaria vaccine program and chair of the Department of Epidemiology of Parasitic Diseases at USTTB. "In this study, we administered 491inoculations in a rural setting without a problem, and the dosages were delivered in a matter of seconds. It shows that this approach is feasible from both a logistical and public health standpoint." According to the researchers, a preventive malaria vaccine employed in mass vaccination programs to eliminate P. falciparum from geographically defined areas would need to prevent malaria infection or transmission in at least 80 percent of recipients throughout the malaria transmission season. Clinical trials now underway in Africa, Europe and the United States have been designed to boost PfSPZ Vaccine's efficacy by increasing dosage levels and varying the timing and number of doses. The experimental vaccine is also being examined in demographic groups other than healthy adults, including adolescents, children and infants. Sanaria was the regulatory sponsor of the trial; NIAID supported the development of the vaccine through the Small Business Innovation Research award 5R44AI055229. Additional information about the PfSPZ Vaccine trial in Mali is available at ClinicalTrials.gov using the identifier NCT01988636. A follow-up study examining a three-dose PfSPZ Vaccine regimen with higher dosage levels has just been completed by the same clinical team in Mali, Africa. Results from that study will be available in mid-2017. Additional information about that research is also available at ClinicalTrials.gov using the identifier NCT02627456. Reference: MS Sissoko et al. Safety and efficacy of PfSPZ vaccine against Plasmoidum falciparum via direct venous inoculation in healthy malaria-exposed Malian adults: a randomized, double-blind trial. The Lancet Infectious Diseases DOI: 10.1016/S1473-3099(17)30104-4 (2017). NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www. .


Ouologuem D.T.,University of Pennsylvania | Ouologuem D.T.,Malaria Research and Training Center | Roos D.S.,University of Pennsylvania
Journal of Cell Science | Year: 2014

Unlike most cells, protozoa in the phylum Apicomplexa divide by a distinctive process in which multiple daughters are assembled within the mother (schizogony or endodyogeny), using scaffolding known as the inner membrane complex (IMC). The IMC underlies the plasma membrane during interphase, but new daughters develop in the cytoplasm, as cytoskeletal filaments associate with flattened membrane cisternae (alveolae), which elongate rapidly to encapsulate subcellular organelles. Newly assembled daughters acquire their plasma membrane as they emerge from the mother, leaving behind vestiges of the maternal cell. Although the maternal plasma membrane remains intact throughout this process, the maternal IMC disappears -is it degraded, or recycled to form the daughter IMC? Exploiting fluorescently tagged IMC markers, we have used live-cell imaging, fluorescence recovery after photobleaching (FRAP) and mEos2 photoactivation to monitor the dynamics of IMC biogenesis and turnover during the replication of Toxoplasma gondii tachyzoites. These studies reveal that the formation of the T. gondii IMC involves two distinct steps - de novo assembly during daughter IMC elongation within the mother cell, followed by recycling of maternal IMC membranes after the emergence of daughters from the mother cell. © 2014. Published by The Company of Biologists Ltd.


Manyando C.,Tropical Diseases Research Center | Kayentao K.,Malaria Research and Training Center | Dalessandro U.,Institute of Tropical Medicine | Dalessandro U.,Medical Research Council Unit | And 3 more authors.
Malaria Journal | Year: 2012

Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of antimalarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to treat uncomplicated falciparum malaria with quinine plus clindamycin in early pregnancy and ACT in later pregnancy. © 2012 Manyando et al.; licensee BioMed Central Ltd.


Vernet G.,Fondation Merieux | Altmann D.M.,Imperial College London | Doumbo O.,Malaria Research and Training Center | Bhutta Z.A.,Aga Khan University | And 2 more authors.
Emerging Infectious Diseases | Year: 2014

Antimicrobial drug resistance is usually not monitored in under-resourced countries because they lack surveillance networks, laboratory capacity, and appropriate diagnostics. This accelerating problem accounts for substantial number of excess deaths, especially among infants. Infections particularly affected by antimicrobial drug resistance include tuberculosis, malaria, severe acute respiratory infections, and sepsis caused by gram-negative bacteria. Nonetheless, mapping antimicrobial drug resistance is feasible in under-resourced countries, and lessons can be learned from previous successful efforts. Specimen shipping conditions, data standardization, absence of contamination, and adequate diagnostics must be ensured. As a first step toward solving this problem, we propose that a road map be created at the international level to strengthen antimicrobial resistance surveillance in under-resourced countries. This effort should include a research agenda; a map of existing networks and recommendations to unite them; and a communication plan for national, regional, and international organizations and funding agencies.


Tshefu A.K.,University of Kinshasa | Gaye O.,Cheikh Anta Diop University | Kayentao K.,Malaria Research and Training Center | Thompson R.,National Health Research Institute | And 9 more authors.
The Lancet | Year: 2010

Background There is a need for new artemisinin-based combination therapies that are convenient, eff ective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. Methods This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemetherlumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre. Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate; control tablets contained 20 mg artemether and 120 mg lumefantrine. Both treatments were given according to bodyweight. The primary effi cacy outcome was PCR-corrected adequate clinical and parasitological response (ACPR) rate at day 28 in the per-protocol population. Non-inferiority was shown if the lower limit of the twosided 95% CI for the diff erence between groups was greater than-5%. This study is registered with ClinicalTrials.gov, number NCT00422084. Findings 1272 patients were randomly assigned to treatment (pyronaridine-artesunate, n=849; artemether-lumefantrine, n=423). The per-protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group. PCR-corrected ACPR rate at day 28 was 99·5% (780 patients; 95% CI 98·7-99·9) in the pyronaridine-artesunate group and 99·2% (383 patients; 95% CI 97·7-99·8) in the artemether-lumefantrine group (treatment diff erence 0·3%, 95% CI-0·7 to 1·8; p=0·578). There were 509 (60·0%) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 (57·0%) in 423 patients assigned to artemether-lumefantrine. The most frequent drug-related adverse event was eosinophilia (pyronaridine-artesunate, 53 events [6·2%]; artemether-lumefantrine 24 events [5·7%]). 21 (2·5%) patients in the pyronaridine-artesunate group and seven (1·7%) in the artemetherlumefantrine group discontinued study drugs or were withdrawn from the study. Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group. Interpretation Effi cacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. Funding Shin Poong Pharmaceutical and the Medicines for Malaria Venture.

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