Cutaneous Leishmaniasis, Lesions, and Sand flies and Morgellons

[tcmgpt13]

I think it's quite possible that bedbugs are insect vectors of disease. It has been known since the 1950's that bedbugs carry a large number of disease organisms. So far little is known about their possible role as vectors of disease. Current scientific thought sees them only as carriers of disease, but then there has not been a lot of study conducted on bedbugs either. There is some evidence that bedbugs may be a vector for chagas (see posts on this thread about that). Now three hospital patients in Canada have been found to have five bedbugs, three of which had MRSA while two had VRE, or vancomycin-resistant Enterococcus faecium . One microbiologist in the article says this is an intriguing finding and should be studied further. That seems what should be done, but who knows whether it will be. It is chilling to realize that hospitals which have rapidly become an unsafe environment as far as antibiotic resistant germ exposure but may even have insects which spread such diseases.

Scientists Discover Bedbugs Carrying MRSA Germ In Study

May 11, 2011 8:51 PM

NEW YORK (CBSNewYork/AP) — Hate insects? Afraid of germs? Researchers are reporting an alarming combination: bedbugs carrying a staph “superbug.”

Canadian scientists detected drug-resistant staph bacteria in bedbugs from three hospital patients from a downtrodden Vancouver neighborhood.

Al Jones of 1010 WINS spoke with some tourists in Times Square about the finding.

1010 WINS’ Al Jones Speaks With Tourists In Times Square

Marie, who was visiting from Kentucky, said the thought of bedbugs made her skin crawl.

“I thought..why should they scare us? Maybe I should start getting scared,” she said.

Sofia said looking for the creepy, crawly critters was all a part of her routine, which includes checking bedding carefully before her head hits the pillow.

“I think about them, but we haven’t encountered any. We haven’t found any, but I think about them when we go,” she said.

Bedbugs have not been known to spread disease, and there’s no clear evidence that the five bedbugs found on the patients or their belongings had spread the MRSA germ they were carrying or a second less dangerous drug-resistant bacteria.

However, bedbugs can cause itching that can lead to excessive scratching. That can cause breaks in the skin that make people more susceptible to these germs, noted Dr. Marc Romney, one of the study’s authors.

The study is small and very preliminary. “But it’s an intriguing finding” that needs to be further researched, said Romney, medical microbiologist at St. Paul’s Hospital in Vancouver.

The hospital is the closest one to the poor Downtown Eastside neighborhood near the city’s waterfront. Romney said he and his colleagues did the research after seeing a simultaneous boom in bedbugs and MRSA cases from the neighborhood.

Five bedbugs were crushed and analyzed. MRSA, or methicillin-resistant Staphylococcus aureus, was found on three bugs. MRSA is resistant to several types of common antibiotics and can become deadly if it gets through the skin and into the bloodstream.

Two bugs had VRE, or vancomycin-resistant Enterococcus faecium, a less dangerous form of antibiotic-resistant bacteria.

Both germs are often seen in hospitals, and experts have been far more worried about nurses and other health care workers spreading the bacteria than insects.

It’s not clear if the bacteria originated with the bedbugs or if the bugs picked it up from already infected people, Romney added.

The study was released Wednesday by Emerging Infectious Diseases, a publication of the U.S. Centers for Disease Control and Prevention.

Scientists Discover Bedbugs Carrying Drug-Resistant Staph Bacteria MRSA Germ In Study « CBS New York

[tcmgpt13]

I believe there will be many introduced co-infections which a parasite brings into the body discovered in future study into parasite infections. The more I learn about how little is known so far about parasites the more I believe that what is known about parasites is in its infancy. Since the attitude of developed nations appears to have been that parasites were very few among their populations the study of parasites was not that important for a long time.

An introduced viral infection makes a lot of sense to my own case, since it was readily apparent rather quickly that the viral medication I took for diagnosed reactivated viral infections dried up those lesions rather quickly while the lesions which IMHO contain parasites appeared to remain unaffected except perhaps for size as at the time they were smaller lesions. It was my herbal salves which drew out enough of the infection so that they would heal. Just as antibiotics do not work for every bacterial infection it is likely that viral medications do not work for every viral infections especially if it is a previously unknown virus.

Parasite's Virus Packs a Disease-Causing Punch
by Jennifer Welsh, LiveScience Staff Writer
Date: 11 February 2011 Time: 12:02 PM ET


The presence of the Leishmania RNA virus is revealed by staining the viral capsids red.
Science/AAAS

Viruses are usually bad for those they infect. But not for one parasite, which gets a competitive boost from carrying a virus, new research is showing.
The virus, called Leishmania RNA virus-1 (or LRV-1), infects parasitic protozoa, or single-celled organisms, of the genus Leishmania, which causes skin sores. When humans are infected by virus-carrying Leishmania, the virus activates the inflammation system, causing a much more virulent disease with big, destructive sores that can make it hard to eat and breathe.

"For the parasite, there is an advantage to having the virus," it only takes fewer virus-infected parasites to cause a lesion, lead author Nicolas Fasel, of the University of Lausanne in Switzerland, said. "It's the first description where a virus increased the virulence in the pathogenecity of a parasite."

This virulent type of disease is called mucocutaneous leishmania, and is most prevalent in South America. There are two other types of the disease that people can get, including a milder form of skin sores (cutaneous) or a dangerous whole-body infection that includes fever, anemia and organ swelling (visceral).

The disease comes from the subgenus Leishmania viannia, which can cause all three types of leishmania. The infection starts with the bite of a third parasite, the sand fly, which injects the immature parasite into its human host. These parasites infect the host's white blood cells and mature, where they kill the macrophage (the white blood cells) and can be sucked up from the bloodstream by another sand fly, where they reproduce and can infect others.

Leishmania infection, called leishmaniasis, affects about 12 million people worldwide, and is a major health problem in the Mediterranean, Asia, Africa, the Middle East, and Central and South America.

The researchers were particularly interested in mucocutaneous leishmaniasis, a particularly harmful form of the disease that destroys the soft tissues of the nose and mouth. This type of infection tends to be caused by the parasite Leishmania Viannia. They wanted to figure out why the mucocutaneous infections are much more virulent and are localized to South America. Only about 5 to 10 percent of the 12 million people infected with Leishmania get the mucocutaneous form of the disease.
"We knew there was a virus in these species, but nobody understood the role of this virus," Fasel told LiveScience. "People looked but nobody found it; they did not have the tools to do it like we have now."

Manipulating macrophages

Once inside a human, the infected protozoa makes its way into the immune system's macrophages, which normally gobble up invaders like viruses . Inside little compartments within the white blood cells, the protozoa get shuttled to the warm, wet and cozy mucous membranes that line parts of our bodies.

The researchers ran tests on hamsters and mice with strains of L. viannia, showing that only some viannia strains spread rapidly and cause high levels of damage similar to that seen in mucocutaneous leishmaniasis.
In subsequent experiments, the team discovered that the rapid, highly damaging form of the infection was linked to a protein called TLR3 found in the tiny compartment of the macrophages where the protozoa (parasite) live.

When Fasel infected mice that don't have this TLR3 receptor with virus-ridden parasites, they didn't develop the mucocutaneous version of the disease. The receptor-virus interaction is the key to the pathogen's virulence, he said,but how this interaction increases the pathogenicity, they aren't sure.

"TLR3 normally helps the immune system fight infections, but when we deleted it in mice and repeated the experiment, infections with virus-infected Leishmania were less harmful," Fasel said.

New therapies

The results have direct implications for public health, researchers say.
"So far, different clinical outcomes in infected humans have mostly been claimed to result from different genetic backgrounds of the individuals," Christian Bogden, a researcher from Friedrich-Alexander University Erlangen-Nürnberg in Germany who was not involved in the study, said in an e-mail.

Bogden notes that there is still much work to be done on the relationship between the virus, parasite and host, but thinks the explanation is a good one. "This is an exciting study which for the first time provides a clear-cut explanation of why different strains of a Leishmania (Viannia) species can lead to differential courses of infection in humans," he told LiveScience.
There are a few drugs available to treat Leishmania, though researchers aren't sure how they work, and people's immune systems are already becoming resistant to the drugs, especially in South America. Vaccines are also in the works, but none are currently in trials.

Knowing how this virus regulates the parasite's virulence could help researchers develop new therapies to modulate the severity of this disease. Slowing down the body's inflammatory response could slow the progress of the disease, and increase the effectiveness of current drugs.
Fasel says that screening for this virus in the field could help determine correct treatment pathways for Leishmania infections, especially if they are at high risk for developing this mucocutaneous version of the disease. He is in the process of starting a clinical trial in Colombia to determine if this screening is helpful.

"There could be a link between inflammation and resistance," Fasel said. "We need to test in the field if by controlling inflammation, people respond better to the treatment."

The study appears today (Feb. 11) in the journal Science.

[tcmgpt13]

It's always good to hear about new parasite treatments for many of these infections are deadly and have no effective treatments. Possibly this new treatment for the Old World version of leishmaniasis might help related diseases such as New World visceral leishmania, mainly found in Brazil:

New Treatment for Kala Azar, the Most Deadly Parasitic Disease After Malaria

ScienceDaily (Sep. 23, 2011) — East Africa is fighting the worst kala azar outbreak in a decade. Collaboration across the region through the Leishmaniasis East Africa Platform (LEAP) has resulted in the development of a new combination therapy (SSG&PM) which is cheaper and nearly halves the length of treatment from a 30 day course of injections to 17 days. East African endemic countries are taking the necessary regulatory measures to use it in their programmes, but experts warn that without international funding or interest in supporting governments in the roll out, too few patients will benefit.

'The poorest of the poor, in the most remote villages are the ones who are wasting away from kala azar and who could benefit the most from a shorter more affordable treatment' said Dr. Monique Wasunna, Assistant Director, KEMRI, and Head, DNDi Africa. 'Neglected diseases and patients mean that even when there are new treatments and hope, they are too far from the headlines and donor priorities to get support to governments. This is why we are calling for urgent action.'

This week in Nairobi, over 100 clinical researchers and regional experts from Ministries of Health and drug regulatory authorities are meeting for the bi-annual LEAP -- Leishmaniasis East Africa Platform -- to see what is and is not working in the field and to find better ways to control the disease.

After 70 years of little improvement or change in the treatment of kala azar in Africa, LEAP and its partners have developed a new treatment: Sodium Stibogluconate & Paromomycin (SSG&PM) combination treatment. This is cheaper and nearly halves the length of treatment from the current 30 day course of injections to 17 days. It also cures the patient. Combination therapies help fight resistance to treatment. Countries around the region are in the process of registration and are ready to use the treatment, but need funding to control the disease.

Kala azar is another name given to visceral leishmaniasis (VL), a parasitic disease endemic in around 70 countries worldwide. South Sudan has the second highest number of cases after India. The disease is spread through the bite of a sandfly and is fatal without treatment. Approximately half a million people are infected with the disease and 50-60,000 die every year as a result of the infection. Patients suffer from irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia.

'I have spent fifty years treating kala azar patients and researching this killer parasite and I know first-hand how desperately these poor patients and overburdened health workers need shorter, cheaper, and easier-to-use treatment,' said Professor Ahmed Mohamed El Hassan, Emeritus Professor, Institute of Endemic Diseases University of Khartoum, Sudan. 'Ideally for patients in such conditions, we need an oral treatment, such as those being tested or completely new drugs, but we are a long way from there and we need to make the most of this existing better treatment and find the funds to roll it out,' he concluded.

In March 2010, the World Health Organization (WHO) Expert Committee on the Control of Leishmaniases recommended SSG&PM as first-line treatment for VL in East Africa. It is already being used to treat patients in the countries such as Sudan and South Sudan. Other affected countries are in the process of registering PM to combine it with the already registered SSG to get the treatment to patients.

'After 20 years, WHO has updated the guidelines for the control of leishmaniasis. This shows that there is greater collaboration and progress. Now countries need support to translate this into lives saved on the ground,' said Dr. Mercé Herrero, Disease Prevention and Control, Leishmaniasis National Control Programme, WHO Ethiopia.

The development of SSG&PM is the result of a collaborative partnership over a period of six years between DNDi, LEAP, and other partners including the National Control Programmes of Kenya, Sudan, Ethiopia, and Uganda, as well as Médecins Sans Frontières (MSF) and the World Health Organization (WHO).

wwwsciencedaily.com/releases/2011/09/110923102525.htm

[posey]

What I don't understand is why, when all this is going on, is M dismissed as dellusional? With all the information and links posted here, it stands to reason that when a person walks into a Drs. office with sores al over their body, someone would investigate. I have never had the lesions but have seen pics of those suffering with them. Any prudent Dr. would know something is not right.

This is why I think it gives cause to believe that something is being hidden and if I am right, how could we possibly expect to get credible research done? No one is going to fund something they do not want people to know about.

Maybe I am just paranoid but something about the whole picture stinks. I can sincerely say I hope I am wrong and am just being suspicious.

[tcmgpt13]

Posey, my theory about why Morgellons is not studied is that in the Western world if a particular parasite or other infection was discovered and it was known that it would prove very expensive to treat or there was no effective treatment for it that information would hidden. The government might not want that information revealed. Far better to label a potentially large group of patients DOP. People in developed nations tend to demand more and not less medical treatment. What better way to avoid additional medical care expenses and the funding of more research since the government (as currently headed these days) wants to take over all medical care and ration it. In such a scenario those in government would not want anything known about what was really causing the illness. Anti-depressants and tranquilizers are cheaper to dole out. And it keeps the patient quiet. Just think of what they did in countries to those who caused trouble of any sort. Such individuals were often drugged and thrown into hospitals for the insane.

The other possibility is that agrobacterium is an issue for those genetically disposed. Again many individuals, governments and corporations would not want this known. Of course none of this is fact, just a guess. Also I feel that governments as run now in the developed Western world seem to favor treating poor folks in the developing world as opposed to treating folks who live in their own countries.

[tcmgpt13]

Those of us who believe some type of parasite may be connected to Morgellons might enjoy reading about this research into how the trypanosomes which cause sleeping sickness can fool the human immune system by blocking its ability to fight off these parasites.

New research shows how disease-causing parasite gets around human innate immunity

August 30, 2010

Writer: Philip Williams

Biochemistry and Molecular Biology, Department of Franklin College of Arts and Sciences

Athens, Ga. - Trypanosomes are parasites responsible for many human and animal diseases, primarily in tropical climates. One disease these parasites cause, African sleeping sickness, results from the bite of infected tsetse flies, putting over 60 million Africans at risk in 36 sub-Saharan countries. The recent 1998-2001 sleeping sickness epidemics in South Sudan, Angola, Democratic Republic of Congo and Uganda killed tens of thousands of people and resulted in over a half million infected individuals.

A team of researchers at the University of Georgia and Glasgow University has now shown, for the first time, just how one species of these parasites evades the human innate defenses. The finding could open the way for new classes of drugs and more in-depth studies about how parasites manage to kill so many and cost governments billions of dollars to fight.

'We believe this research represents a paradigm shift and causes us to think more broadly about how pathogens avoid host defense mechanisms,' said Stephen Hajduk, professor and head of the department of biochemistry and molecular biology at UGA and one of the leaders of the research. 'It turns out that African trypanosomes have evolved a diversity of ways to avoid human innate and acquired immune systems.'

The research, published today in the Proceedings of the National Academy of Sciences, was a joint effort between UGA and a group led by Annette Macleod at the University of Glasgow in Scotland. Other authors of the paper include Rudo Kieft, a research professional in Hajduk's lab at UGA; Paul Capewell and Nicola Veitch in the Macleod lab in Wellcome Center for Molecular Parasitology in Glasgow; and Michael Turner of the Biomedical Research Center at the University of Glasgow. The department of biochemistry and molecular biology at UGA is part of the Franklin College of Arts and Sciences. Hajduk also is a member of the Center for Tropical and Emerging Global Diseases at UGA.

The need for a clearer understanding of how these parasites evade human immune systems is at the heart of a serious public health problem, Hajduk said. During the recent epidemics of African sleeping sickness, as many as half the occupants in some African villages were infected with trypanosomes. The geographical isolation of these villages and ongoing civil wars contributed to what many believe were the worst epidemics of sleeping sickness in five decades.

This led to the realization that many of the existing therapies now available to fight African sleeping sickness are often ineffective and have extreme toxicity, frequently causing death. Additionally, there is increasing evidence that while new therapeutics may cure the disease, long-lasting neurological damage can be caused by infection.

The World Health Organization reports that the recent introduction of aggressive population screening in rural areas and distribution of more effective drugs has dramatically reduced the number of deaths, however.

Several species of African trypanosomes infect non-primate mammals and cause important veterinary disease yet are unable to infect humans. The trypanosomes that cause human disease, Trypanosoma brucei gambiense and T. b. rhodensiense, have evolved mechanisms to avoid the native human defense molecules in the circulatory system that kill the parasites that cause animal disease.

Two of the major challenges faced by scientists studying human sleeping sickness have been the identification of the naturally occurring human defense molecules that are active against the trypanosomes causing animal disease, and the identification of the strategies used by the human sleeping sickness parasites to avoid the action of these molecules.

Human innate immunity against most African trypanosomes is mediated by a subclass of HDL (high density lipoprotein, which people know from blood tests as "good cholesterol&quot called trypanosome lytic factor-1, or TLF-1. This minor subclass of human HDL further contains two proteins, apolipoprotein L-1 and haptoglobin-related protein, which are only found in primates. These proteins work together, in the lipid environment of the HDL particle, as a specific and highly active toxin against the trypanosomes that infect non-primate mammals. Despite its activity against some African trypanosomes, the toxin is completely nontoxic to the human sleeping sickness parasites.

The parasite that causes fast-onset, acute sleeping sickness in humans, T. b. rhodensiense, is able to cause disease because it has evolved an inhibitor of TLF-1 called Serum Resistance Associated (SRA) protein. Another species, T. b. gambiense, causes slow onset, chronic sleeping sickness and is responsible for over 95 percent of the human deaths caused by these parasites. Until the just-published research by Hajduk, Macleod and their colleagues, nothing was known about TLF-1 resistance in T. b. gambiense. Hajduk and Macleod report, for the first time, that T. b. gambiense resistance to TLF-1 is caused by a marked reduction of TLF-1 uptake by the parasite.

So how is this happening?

To survive in the bloodstream of humans, these parasites have apparently evolved mutations in the gene encoding a surface protein receptor. These mutations result in a receptor with decreased TLF-1 binding, leading to reduced uptake and thus allow the parasites to avoid the toxicity of TLF-1.

'Humans have evolved TLF-1 as a highly specific toxin against African trypanosomes by tricking the parasite into taking up this HDL because it resembles a nutrient the parasite needs for survival,' said Hajduk, 'but T. b. gambiense has evolved a counter measure to these human ‘Trojan horses' simply by barring the door and not allowing TLF-1 to enter the cell, effectively blocking human innate immunity and leading to infection and ultimately disease.'

The parasite may pay a price for blocking the uptake of a nutrient, but still the strategy works and the parasite can infect humans. Now that researchers know how the parasite survives, this may provide an intervention target that could keep the parasites from evading the human defense system. The result could be a newly strengthened innate defense system that halts the parasites in their paths.

The research was supported by grants from the National Institutes of Health and the Burroughs-Wellcome Fund.

news.uga.edu/releases/article/new-research-shows-how-disease-causing-parasite-gets-around-human-innate-im/

[tcmgpt13]

Leishmaniasis is a neglected tropical disease so the military has been doing some research to find effective treatments for diseases which are not being heavily researched by civilian pharmaceutical companies. They began this study due to the demoralizing effect disfiguring cutaneous lesions have on our troops, something with which we are all too familiar. Besides the mentioned drug which is topical and in stage III trials (it will be used on uncomplicated leishmania lesions) there are also some developments for better and more sensitive testing to diagnose leishmaniasis.

Here's the paragraph which discusses the current leishmania program:

'The Leishmaniasis program, which is part of the Military Infectious Disease Program (MIDRP), is vertically integrated with full-spectrum capabilities that include basic science, drug discovery and development, pre-clinical optimization, and clinical trials expertise for early Phase 1 testing of drugs for safety up to Phase 4 studies conducted after a drug is first put on market. The program particularly excels at “translational research” to discover and move a new product from the technology base to a level where a commercial partner will take the product on to licensure and marketing to the U.S. military and civilians. Some recent successful products developed by the program include: a Cepheid SmartCycler PCR assay which has recently received FDA 510(k) approval, a disposable point-of-care dipstick test for infection (transitioned to InBios International Inc.), a skin antigen test to detect delayed-type hypersensitivity to Leishmania, (transitioned to Allermed Laboratories Inc.) and WR279,396, a new topical formulation for the treatment of uncomplicated cutaneous leishmaniasis, (manufactured under contract by Teva Pharmaceutical Industries Ltd.) which is currently in a large scale, multicenter Phase 3 clinical trial in Tunisia.'

For those interested here is the entire article:

Drug Discovery at Walter Reed Army Institute of Research

Written by Lt. Col. Mark Hickman, Capt. J.R. Managbanag and Col. Max Grogl

MMT 2011 Volume: 15 Issue: 5 (August)

Drug Discovery at Walter Reed

Cutaneous leishmaniasis is a skin infection that afflicts approximately 12 million people worldwide in 98 countries on five continents, with as many as 2 million estimated new cases emerging each year. Most cases of leishmaniasis are caused by the transmission of parasites from the bite of infected sand flies. Human infection is caused by 21 of 30 Leishmania species that infect mammals. It is mostly an endemic disease with epidemic outbreaks occurring in both sedentary and mobile populations (military personnel, refugees, travelers). Cutaneous leishmania transmission concentrates in so-called “hot spots” in the field that are impossible to predict, with infection rates of up to 100 percent in humans. Cutaneous leishmaniasis is probably the “most neglected of neglected diseases” due to the fact that it does not result in death; however, the true socioeconomic impact of cutaneous leishmaniasis cannot be quantified. Severe disfigurement, disability, and social/ psychological stigma often results from cutaneous leishmaniasis infections. In addition, there is a potential for latent infections primarily from Leishmania infantum, a visceral disease that could appear later in life as an opportunistic infection in immunocompromised individuals.

Cutaneous leishmaniasis prevention is limited to personal protective measures such as insect repellent, bed nets, portable tent air conditioners, and control of disease reservoirs such as rodents and dogs. There are no vaccines or chemoprophylactic drugs to prevent leishmaniasis, and there are no drugs approved by the FDA for treatment. Cutaneous leishmaniasis has afflicted an unknown number of U.S. military members stationed in Iraq and Afghanistan. Exact numbers are not available for a variety of reasons: the disease was not parasitologically confirmed, clinically suspicious cases are usually not reported, most cases are noted from passive case detection versus an active process, soldiers won’t come forward as they don’t want to leave their unit, and elite units such as the special forces treat themselves and their infection data is difficult to capture. At the Walter Reed Army Institute of Research (WRAIR) Leishmaniasis Diagnostic Laboratory, more than 2,832 U.S. members of the armed forces have been diagnosed with cutaneous leishmaniasis from April 2003 to April 2011. Of the OIF/OEF cases, about 850 were evacuated to CONUS at a cost of $35,000 and 60-90 lost duty days per servicemember infected. The treatment time specified from the MEDCOM Guidance for the Management of Cutaneous Leishmaniasis (November 2010) is 10-20 days for each event plus follow-up. The impact on individual and unit morale is hard to quantify but not insignificant. Soldiers with large ulcerative lesions caused by a parasite have a demoralizing effect on other troops who fear the infection they may acquire. U.S. forces must be able to protect themselves, allied/coalition forces, DoD civilians and DoD contractors against infectious disease threats during deployments, sustainment operations and redeployments, especially to tropical and subtropical regions of the world where leishmaniasis is endemic. The U.S. military will no doubt be involved in leishmania endemic areas in the USCENTCOM, USAFRICOM and USSOUTHCOM areas of responsibility for the foreseeable future.

The Walter Reed Army Institute of Research (WRAIR) is a DoD-administered biomedical research organization that is tasked with delivering lifesaving products that sustain the combat effectiveness of soldiers. The Experimental Therapeutics Division of WRAIR has been engaged in antiparasitic drug discovery and development research since 1965. WRAIR scientists are engaged in developing antiparasitic drugs for malaria prophylaxis and also for treatment of cutaneous leishmaniasis. WRAIR and our associated research partners have the only complete bench to bedside drug discovery and development program for cutaneous leishmaniasis. This therapeutic area is generally not interesting to a pharmaceutical company as developing drugs for neglected diseases is not profitable. This DoD research effort is necessary to provide the impetus to develop a drug to the point where a pharmaceutical company can take over the final FDA approval process and production of a drug.

The Leishmaniasis program, which is part of the Military Infectious Disease Program (MIDRP), is vertically integrated with full-spectrum capabilities that include basic science, drug discovery and development, pre-clinical optimization, and clinical trials expertise for early Phase 1 testing of drugs for safety up to Phase 4 studies conducted after a drug is first put on market. The program particularly excels at “translational research” to discover and move a new product from the technology base to a level where a commercial partner will take the product on to licensure and marketing to the U.S. military and civilians. Some recent successful products developed by the program include: a Cepheid SmartCycler PCR assay which has recently received FDA 510(k) approval, a disposable point-of-care dipstick test for infection (transitioned to InBios International Inc.), a skin antigen test to detect delayed-type hypersensitivity to Leishmania, (transitioned to Allermed Laboratories Inc.) and WR279,396, a new topical formulation for the treatment of uncomplicated cutaneous leishmaniasis, (manufactured under contract by Teva Pharmaceutical Industries Ltd.) which is currently in a large scale, multicenter Phase 3 clinical trial in Tunisia.

As the spectrum of cutaneous disease caused by Leishmania parasites is extremely broad and diverse, clinicians need a full array of therapeutic options. Today, the largest gap in the treatment of cutaneous leishmaniasis is the lack of an oral drug for complicated cutaneous leishmaniasis that is safe, effective against all forms of cutaneous leishmaniasis, has superior cosmetic results, is available at low-cost and is adaptable for use in rural areas.

Anti-parasitic drug discovery and development at WRAIR is an essential element in providing FDA-licensed drugs for soldiers who are infected with tropical diseases not present in the U.S. Cutaneous leishmaniasis is a neglected disease which merits drug discovery and development where pharmaceutical companies are likely not willing on their own to pursue. ♦

Lt. Col. Mark Hickman, Chief, In Vitro Screening, Experimental Therapeutics Division, Walter Reed Army Institute of Research, Capt. J.R. Managbanag, Chief, Leishmania Diagnostic Research, Experimental Therapeutics Division, Walter Reed Army Institute of Research, Col. Max Grogl, Division Director, Experimental Therapeutics Division, Walter Reed Army Institute of Research

This report was supported by the United States Army Medical Research and Materiel Command. The opinions or assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.

kmimediagroup.com/mmt-home/341-mmt-2011-volume-15-issue-5-august/4596-drug-discovery-at-walter-reed-army-institute-of-research.html

[tcmgpt13]

The visceral form of leishmaniasis has been very hard to treat as well as control. Since there have been a few members who have been diagnosed with some form of leishmaniasis this article may interest them and others here too. This appears to be a breakthrough for future research into ways to more effectively treat this difficult form of the disease.

Overproduction of some immune suppressing cytokines such as IL-10 are being implicated in the persistence of certain parasitic and microbial diseases. Those mentioned infections are as follows: Leishmania spp., Plasmodium spp. (malaria), Mycobacterium tuberculosis, Chlamydia pneumoniae, Candida albicans, lymphocytic choriomeningitis virus (LCMV), and cytomegalovirus (CMV).

IL-10 Neutralization Promotes Parasite Clearance in Splenic Aspirate Cells From Patients With Visceral Leishmaniasis

Shalini Gautam1,a, Rajiv Kumar1,a, Radheshyam Maurya1,2,a, Susanne Nylén3,4, Nasim Ansari4, Madhukar Rai1, Shyam Sundar1 and David Sacks4

Abstract

The mechanisms underlying the failure to contain the growth of Leishmania parasites in human visceral leishmaniasis (VL) are not understood. L donovani amastigotes were quantified in cultured splenic aspirate cells to assess the function of IL-10 in lesional tissue ex vivo. In 67 patients with active VL, IL-10 neutralization promoted parasite killing in 73% and complete clearance in 30%, while 18% had more parasites and 9% did not change. The splenic cells secreted increased levels of both tumor necrosis factor α (TNFα) and interferon γ (IFNγ) under IL-10-neutralizing conditions. These findings provide direct support for targeting IL-10 as an approach to therapy in human VL.

For those interested some of the article (too lengthy to post all of this discussion):

Interleukin-10 (IL-10) is an important immunosuppressive cytokine that, in addition to dampening potentially harmful inflammatory responses during chronic infection, can contribute to pathogen persistence [1]. IL-10 suppresses the activation of macrophages and dendritic cells for microbicidal and antigen presentation functions, and can inhibit T-cell activation directly [2]. Infection models in mice have produced unequivocal evidence that IL-10 is responsible, at least in part, for pathogen persistence. Thus, genetic ablation of IL-10 or IL-10 receptor blockade results in more effective clearance of a broad spectrum of microbial pathogens, including Leishmania spp., Plasmodium spp., Mycobacterium tuberculosis, Chlamydia pneumoniae, Candida albicans, lymphocytic choriomeningitis virus (LCMV), and cytomegalovirus (CMV; reviewed in [1]).

In humans, elevated levels of IL-10 are correlated with important chronic infectious diseases, including malaria [3, 4], tuberculosis [5, 6], and human immunodeficiency virus (HIV) [7]. An association between elevated IL-10 and an advanced stage of disease is especially well documented in patients with visceral leishmaniasis (VL) or kala-azar, who have high concentrations of IL-10 in serum as well as strongly elevated IL-10 mRNA in target organs such as spleen and bone marrow (reviewed in [8]). The evidence that IL-10 contributes to the chronicity of infection in humans is nonetheless indirect and confined to the enhancement of immune correlates of protection when IL-10 function is blocked in vitro [9, 10]. There is so far no direct evidence in any clinical setting that IL-10 inhibition will promote pathogen clearance. In the present studies, we have used the number of viable amastigotes present in splenic aspirate cells from VL patients as a readout to explore the effect of IL-10 neutralization on parasite killing ex vivo. The findings are the first to demonstrate a host protective effect of IL-10 neutralization in lesional tissue, and provide compelling evidence that overproduction of IL-10 directly contributes to the pathogenesis of human VL.

jid.oxfordjournals.org/content/204/7/1134.full?sid=32d4637b-9e95-4e8a-8fa4-c35ee70aa4e9 (October 1, 2011)

[csidegalNH]

Link to new treatment:


Potential new treatment identified for leishmaniasis | e! Science News

[sammy]

tcm This article makes a lot of sense. No one will admit this that this is being brought in by a fly from another country and is very transmitable from one person to another Iam sure my husband has m now he went to doc yesterday his face is a complete rash and itching yet he thinks m doesnt exist. I have been out of the country we both have and I think thats where this was picked up. sammy