Parasitic Infections of the Skin

Early Malnutrition And Parasitic Infections Reduce Cognitive Ability Later In Childhood

Parasitic Infections of the Skin | Johns Hopkins Medicine

Stunted growth caused by chronic malnutrition during the first two years of life has an adverse affect on a child’s cognitive ability later in childhood, according to researchers from the Johns Hopkins Bloomberg School of Public Health and the University of Maryland School of Medicine.

The researchers also concluded that early infection with the diarrhea-causing parasite, Giardia lambia, might be associated with diminished cognitive function later in childhood.

The study, which appears in the February 16 issue of The Lancet, suggests that efforts to improve cognitive function of school children in developing nations should focus on improving the nutrition and well being of children early in life.

“With this study, we were able to track the children as they developed from infancy through age 9. Children with severely stunted growth at age 2 scored 10 points lower on cognitive tests than their peers, which indicates that the detrimental effects of malnutrition linger through childhood,” explains Douglas S.

Berkman, ScM, lead author of the study. Berkman conducted his research while studying epidemiology at the Johns Hopkins Bloomberg School of Public Health and submitted the research as his master’s thesis.

Berkman is now a medical student at the Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey.

For the study, Berkman used data collected from an earlier nutritional study conducted from 1989 to 1991 by co-author, Robert H. Gilman, MD, professor of international health at the Johns Hopkins Bloomberg School of Public Health. In the initial study, researchers followed 234 children near Lima, Peru from birth to age 2.

At the time, the children were monitored for growth development and incidents of diarrhoeal disease and parasitic infection. In 1999, Berkman tracked down 143 of the original study participants for further evaluation.

The children were assessed using the Wechsler intelligence scale for children-revised (WISC-R), which is a widely accepted test for measuring cognitive ability and intelligence.

After adjusting for socio-economic status and schooling, the researchers found that by age 9, children who were severely stunted in the second year of life scored 10 points lower on the WISC-R cognitive test than children with better development. The researchers also looked closely at the impact of diarrhea, which is both a cause and an effect of malnutrition.

Children infected with the G. lamblia parasite that causes diarrhea, one or more times per year scored 4 points lower on WISC-R than children that were not infected with the parasite. However, the researchers found no decrease in test scores among children with a history of diarrhoeal disease in general or diarrhea caused by Cryptosporidium parvum infection.

“There is a high prevalence of stunted growth in children living in less developed countries. It is estimated to be as high as 40 percent in children younger than age 5. Our results can be used in designing intervention programs seeking to prevent the adverse effects of stunting later in life,” explains Dr. Gilman.

“This study illustrates the importance of attending to the nutritional needs of children under 3 years of age,” adds co-author Maureen Black, PhD, professor of pediatrics at the University of Maryland School of Medicine.

###The article “Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow up study” appears in the February 16, 2002 issue of The Lancet and was written by Douglas S. Berkman, Andres G. Lescano, Robert H. Gilman, Sonia L. Lopez, and Maureen M. Black.

The research was funded by an ITREID grant and a grant from the Fogarty Foundation at the National Institutes of Health.

For more information, visit the Johns Hopkins Bloomberg School of Public Health on the Internet at http://www.jhsph.edu.

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Source: https://www.sciencedaily.com/releases/2002/02/020215071338.htm

The Making of a Tropical Disease: A Short History of Malaria

Parasitic Infections of the Skin | Johns Hopkins Medicine

This publication is one of a series published by the Johns Hopkins University Press on biographies of disease. Earlier volumes were Mania: A Short History of Bipolar Disorder and Dropsy, Dialysis, and Transplant: A Short History of Failing Kidneys. Malaria is clearly a worthy subject in this ambitious series.

The preface sets the stage for the treatise on malaria and establishes the author’s interest and qualifications for writing the book.

The first chapter provides a reasonable scenario for establishing Africa as the place of origin of human malaria parasites and the probable movement of the organisms with movements of early humans from Africa through southern Asia and eventually to the Pacific Islands.

The reviewer was somewhat uncomfortable with the complete absence of any discussion of the evolution of Plasmodium species in nonhuman primates because those parasites are clearly closely related to those found in humans. The statement that there are 4 species of malaria parasites that infect humans is inaccurate.

Recent reports of the extensive occurrence of natural human infections with P. knowlesi in Borneo and the Philippines are an issue that warrants attention. (Experimental infections in humans with malaria parasites from nonhuman primates in Asia do not need to be detailed here.

) Fortunately, some weaknesses in the discussion of the evolution of primate malaria parasites do not seriously detract from the detailed and well-written story of malaria as a human disease.

The movement of malaria into northern areas and its eventual retreat back to the tropics is well told and clearly addresses the central theme of “the making of a tropical disease.

” The discussions of the long history of malaria control efforts directed toward the vector and, to a lesser extent, the parasite without what the author considers adequate attention to the social aspects of malaria occurrence are well structured.

The recounting of the disastrous Global Malaria Eradication effort is must reading for anyone interested in human malaria. The reviewer experienced this effort personally but continues to be fascinated with this extraordinary story.

The discussion of the current program, “Roll Back Malaria,” is an essential part of this story. This ongoing and massive effort to bring malaria under control is multifaceted and heavily funded, and its eventual outcome may well inspire Dr. Packard to write an addendum to this interesting book.

The author’s focus on poverty and its contribution to the continued presence of malaria in endemic areas, especially Africa, is well presented.

There is no doubt that war, famine, political upheaval, and human poverty are primary issues in the continued presence of malaria as a major cause of illness and death. Unfortunately, this book does not offer a solution to these issues.

This book should be read by and on the shelf of anyone working in or generally interested in the place of malaria in human history.

Suggested citation for this article: Warren M. The making of a tropical disease: a short history of malaria [book review]. Emerg Infect Dis [serial on the Internet]. 2008 Oct [date cited]. Available from http://www.cdc.gov/EID/content/14/10/1679.htm

Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2609898/

Ascaris

Parasitic Infections of the Skin | Johns Hopkins Medicine

— The first section of this topic is shown below —

  • Ascaris lumbricoides: largest intestinal nematode (roundworm) that is a human pathogen.
    • Soil-transmitted helminth
      • Ova develop on warm, humid soil (about 3 wks) before becoming infective.
      • Adult worms live in lumen of small intestine (up to 2 yrs).
      • Ova excreted in stool.
  • Life cycle: humans ingest infective ova that hatch and release larvae.

    Larvae invade intestinal mucosa and travel from portal to systemic circulation to lungs in about 4 days. Larvae penetrate through alveoli, ascend the trachea, and are reingested, then mature in intestines and live for 10 to 24 months.[3]

  • Ova are hardy.

    They can sustain freezing and live up to 6 years in moist soil. Adult female worms can produce 200,000 ova/day.

Epidemiology:

  • Endemic in warm, humid areas especially where human excreta is used as fertilizer, contaminated wastewater is used for irrigation, or geophagy (deliberate/regular consumption of soil) is practiced.
  • Infection most common in young, but affects all ages.
    • Heavy infections can cause malnutrition.[6]
  • Transmission: hand to mouth.
  • Ascariasis due to A. suum is a swine-associated zoonosis.[7]

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  • Ascaris lumbricoides: largest intestinal nematode (roundworm) that is a human pathogen.
    • Soil-transmitted helminth
      • Ova develop on warm, humid soil (about 3 wks) before becoming infective.
      • Adult worms live in lumen of small intestine (up to 2 yrs).
      • Ova excreted in stool.
  • Life cycle: humans ingest infective ova that hatch and release larvae.

    Larvae invade intestinal mucosa and travel from portal to systemic circulation to lungs in about 4 days. Larvae penetrate through alveoli, ascend the trachea, and are reingested, then mature in intestines and live for 10 to 24 months.[3]

  • Ova are hardy.

    They can sustain freezing and live up to 6 years in moist soil. Adult female worms can produce 200,000 ova/day.

Epidemiology:

  • Endemic in warm, humid areas especially where human excreta is used as fertilizer, contaminated wastewater is used for irrigation, or geophagy (deliberate/regular consumption of soil) is practiced.
  • Infection most common in young, but affects all ages.
    • Heavy infections can cause malnutrition.[6]
  • Transmission: hand to mouth.
  • Ascariasis due to A. suum is a swine-associated zoonosis.[7]

There's more to see — the rest of this entry is available only to subscribers.

Spacek, Lisa A. “Ascaris.” Johns Hopkins ABX Guide, The Johns Hopkins University, 2016. Johns Hopkins Guide, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/Ascaris. Spacek LA. Ascaris. Johns Hopkins ABX Guide. The Johns Hopkins University; 2016. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/Ascaris. Accessed May 18, 2020.Spacek, L. A. (2016). Ascaris. In Johns Hopkins ABX Guide. The Johns Hopkins University. Retrieved May 18, 2020, from https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/AscarisSpacek LA. Ascaris [Internet]. In: Johns Hopkins ABX Guide. The Johns Hopkins University; 2016. [cited 2020 May 18]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/Ascaris.* Article titles in AMA citation format should be in sentence-caseMLAAMAAPAVANCOUVERTY – ELECT1 – AscarisID – 540034A1 – Spacek,Lisa,M.D., Ph.D.Y1 – 2016/10/13/BT – Johns Hopkins ABX GuideUR – https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/AscarisPB – The Johns Hopkins UniversityDB – Johns Hopkins GuideDP – Unbound MedicineER –

Source: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540034/all/Ascaris

Johns Hopkins Bloomberg School of Public Health

Parasitic Infections of the Skin | Johns Hopkins Medicine

Click on the publication title to read it.

Flores-Garcia Y*, Nasir G*, Hopp CS, Munoz C, Balaban AE, Zavala F, & Sinnis P. Antibody-Mediated Protection against Plasmodium Sporozoites Begins at the Dermal Inoculation Site. mBio, 9(6), e02194-18, 2018 Publication selected for commentary “Shedding Light on the Role of the Skin in Vaccine-Induced Protection against the Malaria Sporozoite” by J.P. Daily, mBio.02555-18

Hopp CS, Bennett BL, Mishra S, Lehmann C, Hanson KK, Lin JW, Rousseau K, Carvalho FA, van der Linden WA, Santos NC, Bogyo M, Khan SM, Heussler V, Sinnis P. Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites. PLoS Pathog 13:e1006586, 2017.

Swearingen KE, Lindner SE, Shi L, Shears MJ, Harupa A, Hopp CS, Vaughan AM, Springer TA, Moritz RL, Kappe SH, Sinnis P. Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics. PLoS Pathog 12:e1005606, 2016.

Hopp CS, Chiou K, Ragheb DR, Salman A, Khan SM, Liu AJ, Sinnis P. Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition. Elife 4:doi:10.7554/eLife.07789, 2015. Publication selected for commentary “Looking for Blood” by P. Formaglio and R. Amino, Elife 4:2015.

Espinosa DA, Gutierrez GM, Rojas-López M, Noe AR, Shi L, Tse SW, Sinnis P, Zavala F. Proteolytic cleavage of the Plasmodium falciparum circumsporozoite protein is a target of protective antibodies. J Infect Dis, 212:1111-9, 2015.

Ejigiri I, Ragheb DRT, Pino P, Coppi A, Bennett BL, Soldati-Favre D and Sinnis P. Shedding of TRAP by a rhomboid protease from the malaria sporozoite surface is essential for gliding motility and sporozoite infectivity. PLoS Pathogens 8:e1002725, 2012.

Coppi A, Natarajan R, Pradel G, Bennett BL, James ER, Roggero MA, Corradin G, Persson C, Tewari R and Sinnis P. The malaria circumsporozoite protein has two functional domains each with distinct roles as sporozoites journey from mosquito to mammalian host. J Exp Med 208:341-36, 2011.

Hobbs CV, Voza T, Coppi A, Marsh K, Borkowsky W and Sinnis P. HIV protease inhibitors affect development of pre-erythrocytic stage Plasmodium. J Infect Dis 199: 134-141, 2009. Publication selected for cover image.

Li-Min T, Gissot M, Coppi A, Sinnis P and Kim K. Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity. Nature Med. 14: 954-58, 2008. Publication selected for commentary by C. Engwerda and M. Good, Nature Med. 14:912-913.

Coppi A, Tewari R, Bishop JR, Bennett BL, Lawrence R, Esko J, Billker O and Sinnis P. Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade cells. Cell Host Microbe 2:316-327, 2007. Publication selected for cover image and commentary by M. Mota, Cell Host Microbe 2:286-288.

Yamauchi LM, Coppi A, Snounou G and Sinnis P. Plasmodium Sporozoites Trickle the Injection Site. Cell. Microbiol. 9:1215-1222, 2007.

Medica D and Sinnis P. Quantitative dynamics of Plasmodium yoelii sporozoite transmission by infected Anopheline mosquitoes feeding on vertebrate hosts. Infect Immun 73:4363-4369, 2005.

Coppi A, Pinzon-Ortiz C, Hutter C and Sinnis P. The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion. J Exp Med 201:27-33, 2005.Comment by S.M. Hurtley in “Editors Choice”, Science 307:319.

Pinzon-Ortiz C, Friedman J, Esko J and Sinnis P. The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for Plasmodium sporozoite attachment to target cells. J Biol Chem 276:26784-26791, 2001.

Source: https://sinnislab.johnshopkins.edu/

A Pinworm Medication Is Being Tested As A Potential Anti-Cancer Drug

Parasitic Infections of the Skin | Johns Hopkins Medicine

Generic drugs used for other conditions are being given a second look as cancer treatments.

Katherine Streeter for NPR

Cancer researchers are testing whether a generic drug that has been used for more than 40 years to treat parasitic infections may also help fight cancer.

The tests of mebendazole are part of a growing effort to take a fresh look at old medicines to see if they can be repurposed for new uses.

I first learned about mebendazole several years back when my son came home from camp with a gross but common infection: pinworms.

My pediatrician prescribed two doses of mebendazole, and two weeks later the infection was gone.

Flash-forward a couple of years, and I was surprised to find on clinicaltrials.gov, the federal database of medical trials, that mebendazole was being investigated as a potential cancer drug.

Curious, I contacted Gregory Riggins, a cancer researcher at Johns Hopkins University who is testing the safety of mebendazole as a potential cancer treatment. He invited me to his lab in Baltimore.

Gregory Riggins, a researcher at Johns Hopkins University, discovered that laboratory mice didn't develop cancer after being given a drug for pinworms.

Allison Aubrey/NPR

Riggins took me inside and showed me cages of cancer research mice. A few years back, he said, his idea to test mebendazole started here.

Some of the lab animals got infected with pinworms, the same parasite my son had. The veterinarian at Johns Hopkins treated the whole colony of mice with an animal version of mebendazole.

The drug staved off the parasite, but it also did something surprising. Before the mice were treated for pinworms, Riggins and his team had implanted cancer cells into the animals' brains.

But after the mice got the pinworm drug, the cancers never developed. “Our medulloblastoma stopped growing,” Riggins says. He found out that other researchers were conducting animal studies to see if the drug had effects on lung cancer and melanoma.

So he got funding to do two Phase 1 studies to test whether mebendazole is safe to use in brain cancer patients, one in children and another in adults. So far the drug appears to be safe and well tolerated by patients, Riggins says. That would be expected, given that it has been used for decades around the world to treat pinworms.

” the preclinical studies it looks it has promise,” says Tracy Batchelor, director of the division of neuro-oncology at Massachusetts General Hospital, who is not involved in the research.

“The next step is to look for a benefit in a Phase 2 trial.” That would test whether mebendazole has any effect on cancer in people.

Riggins hopes to conduct that sort of trial in adult brain cancer patients.

At a time when it can cost a billion dollars to develop a new drug, the idea of repurposing existing drugs is appealing, according to Bruce Bloom. He's the president and chief science officer of Cures Within Reach, which has helped to fund Riggins' research.

Bloom points to research on metformin, a diabetes drug that's being looked at as a potential treatment for a dozen different kinds of cancer and also tuberculosis. A common blood pressure drug, propranolol, is also being studied.

“It's not ly that mebendazole or any other single repurposed drug is ever going to cure cancer,” Bloom says. But he envisions the possibility that combinations of repurposed drugs might help the body to manage cancer.

Any use of mebendazole as a cancer drug would be years away, if it proves to work at all. Most drugs that emerge from Phase 1 trials never deliver the hoped-for benefits.

And in an odd twist to a complicated story, the cost of mebendazole in the U.S. has skyrocketed in recent years. Though it remains very affordable in most countries, the wholesale cost of a 100 mg tablet in the U.S. has risen from $4.50 in 2011 to $369 in 2016, according to Truven Health Analytics.

The dynamics that led to the price hike were in play before interest rose in the drug as a potential cancer treatment, analysts say. In 2013, Amedra Pharmaceuticals bought marketing rights to mebendazole from Teva Pharmaceuticals. It already owned rights to another key generic antiparasitic drug, albendazole.

“At that point, anyone who has had a high school or undergraduate economics course would be able to explain the price hike,” says Joey Mattingly, an assistant professor in the department of pharmacy practice and science at the University of Maryland School of Pharmacy who studies generic drug pricing.

That leaves people with pinworm infections with the choice of two expensive prescription medications or cheaper over-the-counter options.

“Pinworms are exceedingly common,” says Rachel Orscheln, an assistant professor of pediatric infectious diseases at Washington University and St. Louis Children's Hospital. The CDC estimates 40 million people are infected in the U.S. annually. Orscheln says the people most ly to be infected are children and people who are living in group settings such as nursing homes.

“There are certain cases where we do need to prescribe this medication,” says Orscheln. But at the higher price, she says, “I'm very disinclined to prescribe [it].” She says over-the-counter drugs such as Pin-X or pyrantel, can work just as well in children, so “I'm very ly to steer people in that direction.”

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Source: https://www.npr.org/sections/health-shots/2017/01/30/512400204/a-pinworm-medication-is-being-tested-as-a-potential-anti-cancer-drug

Parasitology

Parasitic Infections of the Skin | Johns Hopkins Medicine

Home > Departments > W. Harry Feinstone Department of Molecular Microbiology and Immunology > Research Programs > Parasitology

From its founding in 1916, the Johns Hopkins Bloomberg School of Public Health has made parasitology research a priority.

Malaria, yellow fever, amebiasis, trypanosomiasis and helminths were important public health problems, and hookworm was a major concern of the Rockefeller Foundation, the top donor to the School of Hygiene and Public Health.

Among the School's original departments, the Department of Protozology and Medical Entomology had four divisions—protozology, helminthology, medical entomology and later a division of virology.

Chair Robert William Hegner observed that “zoologists who are interested in parasitology usually direct their attention to the parasite [morphology, life history and systematics], whereas most physicians tend to emphasize the reactions of the host [symptomology, pathology and therapeutics].

Only when these two phases are brought together and when aspects of the subject peculiar to the public health activities are added is a complete program realized: then parasitology becomes the biology of host-parasite relationships.”

Research Groups

Dr. Peter Agre’s laboratory studies the influence of both human and malaria parasite aquaporins on malaria infection. During the rapid growth of malarial parasites within red blood cells, glycerol is taken up by the parasites and incorporated into lipids for membrane biosynthesis.

The glycerol must cross the red blood cell plasma membrane and the parasitic plasma membrane to become accessible for the parasite. The group has shown that aquaglyceroporins are expressed in both membranes in mice.

Host aquaporin 9 (AQP9) is expressed in the red blood cell plasma membrane and parasite aquaglyceroporin (PbAQP) is expressed in the parasite plasma membrane. The glycerol transport pathway contributes to the virulence of Plasmodium intraerythrocytic stages during malarial infection.

Host aquaporins are also being studied in brain, where AQP4 serves to protect against cerebral malaria. These efforts will provide better understanding of the biology of malaria and may lead to better methods to control or treat malaria.

The laboratory of Dr. Isabelle Coppens studies the adaptations of apicomplexan parasites to their host mammalian cells that lead to disease pathology.

The phylum of Apicomplexa includes human pathogens such as Plasmodium, the causative agent of malaria, Toxoplasma and Cryptosporidium, two leading opportunistic pathogens of immunocompromised individuals.

  By entering into the confines of a cell, these parasites assure themselves a ready source of nutrients and protection from immune confrontations.

We are analyzing the microbial genes and pathways involved in the co-option of host cell processes and organelles by Apicomplexa including the host cytoskeleton and membrane traffic during infection, the salvage of host lipids and the remodeling of the parasitophorous vacuole to support parasite differentiation and replication. We focus on the pathogenic mechanisms at the host-parasite interface that represent interesting targets for the development of therapeutic strategies against Apicomplexa infections.

Dr. Monica Mugnier’s laboratory studies antigenic variation in the African trypanosome, Trypanosoma brucei. These deadly parasites evade recognition by the immune systems of the humans and animals they infect by “switching” a dense surface coat made up of a protein known as variant surface glycoprotein, or VSG. T.

brucei can extend its repertoire of VSGs beyond those encoded in the genome through recombination events that create new, antigenically distinct variants. This diversification of the VSG repertoire to create new antigen coats is critical for the parasite to maintain a chronic infection.

 The Mugnier lab uses bioinformatics and other high-throughput approaches to better understand the dynamics of antigenic variation and the mechanisms driving VSG diversification in vivo.

Malaria parasites contain two organelles, the apicoplast and the mitochondrion, which are thought to have arisen through the incorporation of other cells into the parasite.  Due to the prokaryotic origin of these organelles, they contain a range of metabolic pathways that differ significantly from those of the human host. Dr.

Sean Prigge’s laboratory is investigating biochemical pathways found in these organelles, particularly those that are dependent on the enzyme cofactors lipoate, biotin and iron-sulfur clusters.

We are interested in these three cofactors, how they are acquired, how they are used, and whether they are essential for the growth of malaria parasites.

At any given time, helminth parasites (nematodes, trematodes, tape worms) infect over a third of the human population. These long-lived multicellular parasites, which typically establish infection that last for months to decades, induce immune responses that result in a fundamental change the immune status of infected individuals. Dr.

Alan Scott investigates the impact of parasitic nematodes on host immunity with special emphasis the function of macrophages in the lungs. In addition, Dr. Scott investigates the role of lung macrophages in regulating the inflammatory response induced against malaria-infected red blood cells that sequester in the pulmonary environment.

 

Schistosomes are unique parasites of the blood system that occupy a niche in the venous capillaries draining the small intestine (Schistosoma mansoni or S. japonicum) and the bladder (S. haematobium). These parasites cause severe pathology in the liver in the case of the first two and the bladder in the case of the third.

In fact in the bladder, the infection is associated with the development of bladder cancer. Dr. Clive Shiff is interested in the mechanisms in the development of this cancer resulting from chronic infection, detecting changes in early stages of the infection and also in methods to improve the diagnosis of these infections by using DNA detection.

The objective is to improve epidemiological method to assess the public health impact of the parasite.

Dr. Photini Sinnis and her group are focused on understanding the fundamental biology of the pre-erythrocytic stages of malaria. This includes sporozoites, the infective stage of the malaria parasite, and the liver stages into which they develop.

This is an understudied yet critically important area of investigation as this is when malaria infection is established in the mammalian host.

The goals of their research are to: 1) elucidate the molecular interactions required for the sporozoite’s journey from mosquito midgut to mammalian liver; 2) understand the events involved in hepatocyte invasion; 3) translate their findings to develop drugs and a vaccine that target these stages of the malaria parasite.

Research in Dr. Prakash Srinivasan’s laboratory is focused on understanding the molecular basis of host cell invasion by the human pathogen Plasmodium falciparum. Clinical disease is caused by the exponentially growing malaria parasites within the red blood cell (RBC).

This blood stage infection begins when merozoites (invasive forms) make contact with RBCs through specific ligand-receptor interactions that activate intracellular signaling, both in the parasite and the RBC, to facilitate parasite entry.

Many of these signaling pathways are conserved and function also during sporozoite (another invasive form) invasion of hepatocytes (liver).

We use complementary approaches such as conditional genome editing techniques, live cell imaging, small molecule inhibitors and quantitative proteomics to study the function of invasion determinants in this complex process. We leverage this knowledge to develop and validate new antimalarial vaccine and drug targets using in vitro and in vivo model systems.

Dr. David Sullivan and his laboratory work on Plasmodium molecular biology related to iron metabolism, which also intersects with heme crystallization, the target of the antimalarial quinolone drugs.

and Bioavailable iron also plays a critical role in the activation of the another class of antimalarial drug, the artemisinins. Work on cerebral malaria and severe anemia involves the human endothelial response to Plasmodium and contribution of Plasmodium hemolysins to anemia.

A general principle of infectious diseases is accurate diagnosis and effective treatment and the laboratory works on novel saliva or urine malaria diagnostics as well as new malaria uses for already existing FDA approved drugs.

An epidemiologic study in Bangladesh is probing the role of hemoglobin E on outcome and transmission risk amongst other human, parasite and vector factors. Ongoing work on helminthes includes filiariasis and schistosomiasis.

Source: https://www.jhsph.edu/departments/w-harry-feinstone-department-of-molecular-microbiology-and-immunology/research-programs/parasitology/

Kiran T. Thakur, MD

Parasitic Infections of the Skin | Johns Hopkins Medicine

Samuel G, DiBartolo-Cordovano R, Taj I, Merriam A, Lopez JM, Torres C, Lantigua RA, Morse S, Chang BP, Gyamfi-Bannerman C, Thakur KT. A survey of the knowledge, attitudes and practices on Zika virus in New York City. BMC Public Health. 2018 Jan 2;18(1):98. doi: 10.1186/s12889-017-4991-3.

Ho NT, Hoang VMT, LE NNT, Nguyen DT, Tran A, Kaki D, Tran PM, Thompson CN, Ngo MNQ, Truong KH, Nguyen HT, Ha TM, Nguyen CVV, Thwaites GE, Thakur KT, Hesdorffer D, Baker S. A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam. Epidemiol Infect. 2017 Oct 24:1-11. doi: 10.1017/S095026881700228X.

Thompson H, Thakur K. Infections of the Central Nervous System in Returning Travelers and Immigrants. Curr Infect Dis Rep. 2017 Oct 3;19(11):45. doi: 10.1007/s11908-017-0594-5.

Mezochow A, Thakur K, Vinnard C. Tuberculous Meningitis in Children and Adults: New Insights for an Ancient Foe. Curr Neurol Neurosci Rep. 2017;17(11):85.

Zucker J, Neu N, Chiriboga CA, Hinton VJ, Leonardo M, Sheikh A, Thakur K. Zika Virus-Associated Cognitive Impairment in Adolescent, 2016. Emerg Infect Dis. 2017;23(6):1047-1048.

Rimmer K, Shah H, Thakur K. Expanding medicines for neurological disorders on the World Health Organization Model List. Neurology 2017;88(10):e87-e91.

Miller E, Becker Z, Shalev D, Lee C, Cioroiu C, Thakur K. Probable Zika virus-associated Guillain-Barré syndrome: Challenges with clinico-laboratory diagnosis. Journal of Neurological Sciences 2017;375:367-370.

Roth W, Tyshkov C, Thakur K, Vargas W. Encephalomyelitis Following Definitive Zika Virus Infection. Neurology Neuroimmunology and Neuroinflammation 2017;4(4):e349.

Merkler AE, Reynolds AS, Gialdini G, Morris NA, Murthy SB, Thakur K, Kamel H. Neurological Complications after Tuberculous Meningitis in a Multi-state cohort in the United States. J Neurol Sci. 2017;375:460-463.

Savic RM, Ruslami R, Hibma JE, Hesseling A, Ramachandran G, Ganiem AR, Swaminathan S, McIlleron H, Gupta A, Thakur K, van Crevel R, Aarnoutse R, Dooley KE. Pediatric tuberculous meningitis: model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children. Clin Pharmacol Ther. 2015 Aug 11.

Thakur KT, Lyons JL, Smith BR, Shinohara RT, Mateen FJ. Stroke in HIV-infected African Americans: a retrospective cohort study. J Neurovirol. 2015 Jul 9

Saylor D, Thakur K, Venkatesan A. Acute encephalitis in the immunocompromised individual. Curr Opin Infect Dis. 2015;28(4):330-6

Hardy SJ, Benavides DR, Thakur KT, Probasco JC, Pardo CA. A longitudinally extensive myelopathy in a patient with AIDS. Pract Neurol. 2015 Jun 2

Thakur KT, Mateyo K, Hachaambwa L, et al. Lumbar puncture refusal in sub-Saharan Africa: a call for further understanding and intervention. Neurology 2015;84(19):1988-90.

Thakur KT, McArthur JC, Venkatesan A. CNS Infections in 2014: guns, germs, and will. Lancet Neurology 2015;14(1):20-2.

Sutter R, Kaplan PW, Cervenka MC, Thakur KT, Asemota AO, Venkatesan A, Geocadin RG. Electroencephalography for diagnosis and prognosis of acute encephalitis. Clin Neurophysiol. 2014 Nov 15.

Lyons JL, Thakur KT, Lee R, et al. Utility of measuring (1,3) β-D-glucan in cerebrospinal fluid for the diagnosis of fungal central nervous system infection. J Clin Microbiol. 2014;53(1):319-22

Mikita K, Thakur K, Anstey N, et al. Quantification of Plasmodium Falciparum histidine-rich protein 2 in the cerebrospinal fluid from cerebral malaria patients. American Journal of Tropical Medicine and Hygiene 2014;91(3):486-92

Nelson G, Fermo O, Thakur K, et al. Resolution of a fungal mycotic aneurysm after a contaminated steroid injection: a case report. BMC Research Notes 2014;7:327

Fugate JE, Lyons JL, Thakur KT, et al. Infectious causes of stroke-a review. Lancet Infectious Diseases 2014. S1473-3099(14);70755-8

Thakur K, Probasco JC, Hocker SE, et al. Ketogenic Diet for Adults in Super-Refractory Status Epilepticus. Neurology 2014;82(8):665-70

Berkowitz A, Thakur K. Acute Inflammatory Demyelinating Polyradiculoneuropathy Following Malaria: Case Report and Review of the Literature. Journal of Clinical Neurosciences 2014;21(4):704-6.

Kirsch H, Thakur K, Birbeck G. Central Nervous System infections in returning travelers. Current Infectious Disease Reports 2013.15(6):600-11

Litvintseva AP, Lindsley MD, Gade L, Smith R, Chiller T, Lyons JL, Thakur KT, Zhang SX, Grgurich DE, Kerkering TM, Brandt ME, Park BJ. Utility of (1-3)-β-D-glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of fungal meningitis and other infections. Clinical Infectious Diseases 2013;58(5):622-30

Thakur K, Motta M, Asemota A, et al. Predictors of Outcome in Acute Encephalitis. Neurology 2013;81(9):793-800

Maynard BF, Bass C, Katanski C, Thakur K, Manoogian B, Leader M, Nichols R. Structure-Activity Relationships of FMRF-NH2 Peptides Demonstrate A Role for the Conserved C Terminus and Unique N-Terminal Extension in Modulating Cardiac Contractility. PLoS One 2013;8(9):e75502

Lyons J, Roos K, Marr K, Neumann H, Trivedi J, Kimbrough D, Steiner L, Thakur K, Harrison D, and Zhang S. Cerebrospinal fluid (1,3) β-D-glucan detection as an aid to diagnose iatrogenic fungal meningitis. J Clin Microbiol. 2013;51(4):1285-7

Thakur K, Zunt J. Neurologic parasitic infections in immigrants and travelers. Semin Neuro. 2011;31(3):231-44

Book chapters/non-peer reviewed manuscripts:

World Health Organization toolkit for the care and support of people affected by complications associated with Zika virus. World Health Organization 2017.

Identification and management of Guillain Barre syndrome in the context of Zika virus. Interim Guidance. World Health Organization 2016.

Assessment of infants with microcephaly in the context of Zika virus. Interim Guidance. World Health Organization 2016.

Thakur KT, Albanese E, Giannakopoulos P, Jette N, Linde M, Prince MJ, Steiner TJ, Dua T. Neurological disorders. Disease Control Priorities, World Bank 2016.

For a complete list of publications, please visit PubMed.gov

Source: https://www.columbianeurology.org/profile/thakurt