As we have discussed at length in this blog, Chagas disease presents a formidable and increasingly serious public health challenge for Latin America, and is increasingly becoming a problem in the United States and other developed countries as well. Without increased funding for research, treatment and prevention efforts, the disease will continue to spread and to infect and kill millions of people. Because the disease mainly affects impoverished and rural areas, focus on developing new and better biotechnologies has been slow and limited by lack of funding. Although there has been recent progress it has been advancing very slowly. The new biotechnologies being developed for Chagas disease are exceptionally promising, but they require larger-scale international interest, backing, and research in order to be brought to completion and implemented effectively. This post will retrace our research into the characteristics of Chagas disease and its treatment and prevention, and will posit some further points of analysis and discussion.
Our exploration of Chagas disease began with a definition. A severe disease caused by the parasite trypanosoma cruzi, and spread by triatomine, or ‘kissing’ bugs, Chagas disease kills more people yearly in Latin America than does malaria. The bugs are endemic to Latin America, and they like to live in cracks in poor housing, particularly in adobe or mud houses. There are various means of infection, the most common of which occurs when the bugs defecate near an orifice or bite site into which the victim unknowingly rubs the feces, together with the parasite. The parasite can also be ingested with food or spread through blood contact, organ transplants or from mother to child. Although mild flu-like symptoms can present immediately after infection, often there are few or no symptoms. An exception to this trend is the sign of Romana, in which small children who are infected develop one red, puffy eye. Additionally, isolated incidents have yielded more severe symptoms, such as in a recent outbreak in Brazil, where bugs were crushed into sugar cane juice. Ten to twenty years after infection, with few other symptoms, the victims can develop serious heart disease or intestinal malformation, which are often fatal. Thus, the development and presentation of Chagas disease is particularly insidious.
While the modes of infection are known, the mechanism of the disease’s function remains nebulous. Authorities do not know, for example, why ingesting the parasite with sugar cane juice might have caused more severe symptoms, although they postulate that perhaps more parasite would enter the body if it the whole bug was crushed into food and ingested, or that some strains are more virulent than others. Nevertheless, the amount of time that the parasite can survive in feces is unknown, and methods to purify foods are not widely known or practiced. Another current hypothesis is that the reaction to the parasite is, in fact, an autoimmune reaction. There is evidence of an autoimmune response to the parasite, and some researchers also wonder if the chronic inflammation seen in advanced Chagas-caused heart disease is due to lingering antigens or to long-term anti-parasitic agents, and not from the living parasite itself. However, immunosuppressant therapies have demonstrated an increase, rather than a decrease in mortality, raising questions about the autoimmune hypothesis. It has also been suggested that perhaps the response is sometimes primarily autoimmune and sometimes primarily caused by the parasite itself, depending on the strain of the parasite and the genetics of the host. In order to accurately treat Chagas disease, more research into its mechanism is desperately needed.
Some such research on the parasitic mechanism has been conducted, and has demonstrated high levels of creativity (although at great cost). In 2000, several scientists decided to study the parasite in a low-gravity environment, space, in order to try to elucidate its mechanism. They focused on one particular, unnamed enzyme, and treated it with a variety of natural compounds to try to find one that inhibited its function. While this type of research is very innovative and seems to yield promising results, it is hard to imagine that it would be financially or practically sustainable in the long term.
This lack of understanding of the exact mechanism has contributed to there being only a handful of existing pharmaceuticals that show varying degrees of effectiveness. Funding for further research and drug development has been limited, due largely to the pharmaceutical industry’s reticence to devote the R&D resources to developing drugs that will not yield much in revenue. Thus, though companies have sometimes stumbled across compounds that show some efficacy in treating Chagas, few companies have brought these drugs to market. Happily, some non-profit organizations have filled this gap. Pharmaceutical companies have donated some of these promising compounds to non-profits, which are studying them further and hope to bring them to market. While this is not the most efficient way to find a treatment or cure, it certainly provides some progress. Development of new drugs would allow us to stop using bendizole which, while being the most common drug used to treat Chagas disease, is not always effective at killing the parasites.
One of the new drugs being researched is TAK-187, an anti-fungal agent which has been effective in treating Chagas disease in mice. It seems to work by blocking ergosterol, a steroid that is vital in the parasite’s development. The hope is that it will be more effective and have less harsh side effects than the current treatments. Another antifungal, ravuconazole, is also being researched thanks to the collaboration of Eisai Co. Ltd. and Drugs for Neglected Disease Initiative (DNDi). Eisai and DNDi have collaborated to enter final testing and to develop potentially affordable marketing of E1224, a pro-drug form of ravuconazole. The drug is currently in the late stages of the approval process and if this drug is approved the company hopes to create a two tired pricing scheme which will allow ravuconazole to be sold at a lower price in endemic countries and at a more expensive price in other areas. This would make the drug affordable where it is needed most, while still providing incentive for its production. There is less hope for TAK-187 because it is still in the early stages of development and drug testing is both a lengthy and expensive process. Because the main market for the drug would be poor areas in Latin America, even if it is proven to be effective there is no guarantee that it will be mass produced.
Besides the use of drugs, the other way that we currently treat the heart disease caused by the Chagas parasite is through heart transplants. However, this is a very complex and dangerous procedure and because Chagas disease largely affects those of low socioeconomic status, it is not feasible for the population that needs it most. The latest move has been to try to cure the disease by replacing the damaged heart cells with bone-marrow derived cells. Experiments in mice have successfully shown that this procedure lessens the inflammation and fibrosis in the heart and another trial in Brazil proved that this would be a safe procedure in humans. Because of the positive outcomes of this first trial in humans, researchers are currently working on a phase II trial to test for efficacy which will be larger randomized, double-blind and placebo controlled trial.
Some other novel treatment strategies have also been known to be effective in combating Chagas disease. Especially promising is use of genetically engineered organisms to alter the disease transmission patterns. As previously mentioned, this parasitic disease is propagated when the 'kissing bug' infects a host with the parasite. By targeting this insect population and the parasite, which act as the vectors for this condition, its spread might be halted and eradicated. Insecticides have been considered for use in this situation and in the similar malaria epidemic, which is propagated by mosquitos. Attempts to implement such measures, however, have not been entirely effective. Their lack of total success has led to the conclusion that interfering with the insect's ability to transmit the disease, rather than outright killing it, may be a better approach to take.
Armed with this new information, many researchers have turned to genetic engineering to provide a solution. This relatively new technology allows scientists to alter the genomic material of organisms, thus affecting their ability to produce certain proteins and to facilitate specific physiological functions on a molecular level. This alteration translates to a change in the organism's environmental fitness and abilities to perform functions and to survive. One model of genetic engineering has been applied to the 'kissing bug' itself. By tweaking the organism's genome such that it is unable to sexually reproduce, scientists are able to generate a cohort of sterile insects. The theory is that introducing these bugs into the wild will provide competition for fertile insects and will interfere with the species' ability to proliferate. Thus, genetically engineering the insects may decrease their survival in the natural environment and reduce the presence of the Chagas Disease vector.
Similarly, some researchers are focusing on genetic engineering that targets a bacterium upon which the disease-causing parasite depends for obtaining essential nutrients. In the natural life cycle, the parasite picks up bacterium from feces upon which it feeds, and the bacterium reside in its gut and function to facilitate nutrient absorption. This symbiotic relationship becomes vital to the parasite, and it would not be able to survive without the bacterium. Thus by interfering with this relationship, scientists can impact the disease-causing vector directly. Researchers have been successful in modifying the bacterium in such a way as is harmless to the bacterium, yet prevents its facilitation of nutrient reabsorption for the parasite. By introducing this type of genetically engineered organism into the wild, scientists hope to effect a huge reduction in the propagation of Chagas Disease.
While genetically engineered organisms may have potential to provide a halt to the Chagas Disease epidemic, several drawbacks exist to their implementation. Public sentiment is not universally supportive of such technology, which may function to alter an organism from its naturally occurring condition. Also, introducing an altered species into already balanced ecosystems may precipitate huge unforeseen changes. It is extremely difficult, if not impossible, for scientists to unravel the intricate interconnections that comprise an ecosystem. Affecting the reproductive patterns of just one part of a system, such as is proposed by genetic engineering aimed at decreasing 'kissing bug' populations, may create a huge imbalance in the predator/prey relationships that maintain current species populations. Furthermore, introducing new genetic materials into the environment may result in both vertical and horizontal transfer, which implies that the engineered genes may infiltrate unintended species. Thus while technology enables researchers to implement genetic engineering, it may not be advanced enough to do so safely.
Although it is endemic to Latin America, Chagas disease is spreading rapidly due to globalization, travel, and blood transfusions. With this level of mobility, CD is only going to become more prevalent in the United States, not less, which is why it is necessary for developed countries to allocate funding towards CD treatment. It needs to be recognized that this problem is no longer isolated to Latin America, as it once was. Gemma Ortiz, head of the Chagas campaign for Doctors Without Borders commented, “One hundred years later, the disease continues to be transmitted to lots of people. And as people move around and the world is becoming a more global place, we see it in North America, Japan, Europe, and Australia”. According to the most recent data available, 300,000 people in the United States have Chagas, and one out of every 300 Latino blood donors in Los Angeles County tests positive for Chagas, and this number has been increasing since the 1990s. This serves only to drive up health care costs, with all of the blood screening necessary, as well as hospital stays and deaths due to the heart, liver, and other problems caused by CD.
In order to prevent these costs and this extra burden on the health care system, it is a worthwhile endeavor to put money and resources towards R&D to develop and distribute vaccinations for this disease. Improving vaccinations/prevention, early detection (as the disease is much more curable in the acute phase than in the chronic phase), and drug development is necessary in order to prevent future costs associated with CD. As Dr. Sheba Meymandi, director of cardiovascular research and invasive cardiology at the Olive View- UCLA Medical Center (the only place is the country that treats CD) said, “The goal (for surveillance and better treatment) is to catch it, and treat it before it becomes an expensive medical condition. If you can decrease the risk, that’s a huge success.” CD is no longer an isolated problem faced only by developing countries, and unless the US supports the development of prevention, early detection, and treatment, the burden on the health care system will only increase.
The fact that there is such little awareness, understanding, and research of a disease that afflicts over sixteen million people worldwide is astounding. Few effective treatments exist for the disease, due to the fact that it primarily burdens impoverished peoples and thus provides little financial incentive for pharmaceutical companies to invest in drug development. Failures in the attempts to elucidate the exact mechanism make finding an effective treatment even more of a challenge. Yet despite these enormous roadblocks, collaboration between some pharmaceutical companies, community organizations, and organizations that focus on neglected diseases, has generated some hope and allowed for some much-needed research to be conducted on the disease mechanism and treatment. New pharmaceuticals have been developed that show promise, but many are in the early stages of development and must endure a lengthy testing process before they can go to market. Exciting advances have also been made in creating genetically engineered organisms to reduce disease transmission, yet this practice raises many controversial issues that must be addressed before it is implemented on a larger scale. As Chagas disease continues to traverse national borders and become more prevalent in wealthier countries like the United States, we can only hope that this will stir awareness and incentivize more investment in development of new technologies to combat the disease. The growing prevalence has already prompted physicians in the United States to create better surveillance methods and created an urge for better research and treatment options. CD has the potential to place an enormous burden on the American healthcare system unless we invest now in technologies to prevent more expensive consequences later.
Thursday, December 3, 2009
Monday, November 23, 2009
Sunday, November 22, 2009
Why do I care about Chagas?
When I traveled to rural Honduras in the summer of 2008, I had never heard of Chagas disease. By the end of my trip, I was terrified of Chagas, even though I slept underneath a mosquito net in a concrete building. The gruesome mode of transmission was enough to scare me, as horror story might, but it was the silent progression of the disease that most frightened me. I was volunteering with a clinic, and most of the homes we visited were adobe or wood homes that the kissing bug loves to infest. Surely a huge segment of the population had been infected, and wouldn’t know it for years to come, until suddenly organ failure ripped them from their families.
The community we were in was very isolated from most medical care and much medical knowledge. The town our little ill-equipped clinic was in was located literally at the end of the road (which was unpaved). To get to the nearest hospital, a three-hour drive over bumpy, unpaved roads was required. The nearest big city was six or seven hours away. Villagers hiked sometimes for hours from their unmapped, tucked-away homes just to come to our clinic. I don’t know if our clinic checked people regularly for Chagas (I believe it did not), but even if it did, treatment would be nearly impossible, since the clinic was not equipped for it, and the villagers were too poor to pay much for it. Add on top of these difficulties a cultural distrust of medicine, and the toxic effects and limited efficacy of available drugs, and the challenge Chagas poses worsens.
We saw multiple children there with one red, puffy eye. We figured they had pink-eye or something innocuous until we found out that this is Romana’s sign, which sometimes pops up in children who have been infected via the eye by the Chagas parasite. Their parents, oblivious to the meaning of such a seemingly harmless symptom, and busy tending to a whole family brood, were not even alarmed enough to ask us about it. While they lived in ignorance, and we stood essentially unable to help, the disease worked silently to deteriorate these kids’ organs.
Chagas poses a huge public health challenge for some of the poorest countries in Latin America. Largely overlooked by the international community (although its spread into the U.S. blood supply may increase interest), the disease kills thousands every year while drug companies try only half-heartedly to help. While non-profits have played a large role in spurring research into treatment, and improving patient care and teaching, they do not have the resources necessary to effect large-scale improvements in public health. Considerable money needs to be invested in methods of prevention (for example, knocking down adobe houses and building concrete ones instead, or genetically modifying the disease vectors), awareness (public health outreach efforts to teach communities about how to identify and fight infestations), and treatment (developing better drugs or vaccines, or improving stem cell therapy). Yet, while Chagas continues to affect only the poorest citizens of the poorer countries, this money appears unobtainable, and the disease's horror will persist.
- Joanna Sharpless
A Neglected Infection of Poverty
Dr. Sheba Meymandi discusses her attempts to raise Chagas awareness.
Developing World's Parasites, Disease Hits US
The Wall Street Journal
Stephanie Simon and Betsy McKay
22 August 2009
To complement some other posts focusing on the issue of Chagas in a broader sense, here's a story of the disease through the eyes of one woman doctor battling the disease in poor communities in California.
Dr. Sheba Meymandi, a physician who runs the first Chagas clinic opened in the U.S., has committed her life to improving health in underserved communities where Chagas disease runs rampant. One weekend per month, Dr. Meymandi travels by car to impoverished Latino communities near the LA clinic and uses churches as makeshift clinics in order to test and treat patients for Chagas.
One of her biggest challenges is convincing people to get tested, as many don’t care to be tested for an “exotic” disease. Another problem is the bad reputation of the treatment regimen; the treatment therapy is associated with a slew of unfortunate side effects including memory loss and lack of sensation in the limbs. Many illegal immigrants are also unwilling to obtain treatment because they don’t want to draw attention to themselves.
Dr. Meymandi asserts that Chagas should no longer be considered an exotic disease, as it is highly prevalent particularly in shanty towns lining the U.S.-Mexico border where overcrowding, malnutrition, poor sanitation, and much animal-to-human contact are present. Poor drainage systems are cesspools for breeding of Chagas bugs, and a lack of window screens allows for easy transmission to humans.
Raising awareness of the disease burden has become a major goal, and already health care legislation is pending for a full report to congress on Chagas along with several other diseases dubbed (very appropriately) “neglected infections of poverty”. This article and video gives us another look at issues raised in many other posts in this blog regarding the social causes of Chagas, the extremely poverty associated with Chagas, and public's lack of knowledge on the issue of Chagas. Yet examining the issue through the eyes of one doctor who has made battling Chagas her life's work gives us insight that we can't see in other news reports. We can use the issue of Chagas as a lens through which we can view broader controversies in society, such as debates about healthcare and the health and human rights (or lack therof) in illegal immigrant populations in the United States. Decisions made on these broader issues will greatly influence the future impact of Chagas disease in the U.S.
Find the article at http://online.wsj.com/article/SB12
5090339313750961.html
CD: Acute and Chronic Phase
Flow chart showing phases of CD, and at what phases which symptoms present
Chagas R&D
New, Improved Treatments for Chagas Disease: From the R&D Pipeline to the Patients
Isabela Ribeiro et al, 2009
Public Library of Science Journal- Neglected Tropical Diseases
This article discusses the need for new and improved treatments for Chagas disease, and sets up short term, medium term, and long term goals for this process. Shorter term goals include better use of existing treatments through new formulations and expanding access. Longer term goals include development of new drugs. The article discusses the 2 current treatments available (that have been mentioned in previous articles)- nifurtimox and benznidazole. However, these are limited to treating the acute phase of the disease, not the chronic phase. The article mentions that no promising new drugs are expected anytime soon, although according to other articles there is one- Ravuconazole, discovered and developed by Eisai Co.
There are many barriers to developing treatments, including the fact that there is little standardization among the protocols and parasites used by researchers in assays. Thus reproducibility has been difficult to achieve. Few rigorous trials have been conducted in CD, particularly to test drug efficacy in patients with chronic CD, since such patients often do not present any clinical disease manifestation until a very advanced stage. CD research is often deemed “too difficult” by many.
One development to help deal with these issues is the creation of non-profit product development partnerships (PDPs) which work to fill in the gaps for neglected diseases. These PDPs offer a different model, since R&D is no longer financed by a product’s sale price. A PDP is currently working on developing a better CD portfolio to address the needs of patients. They aim to deliver more effective treatment for acute, indeterminate, and chronic CD and are working on a pediatric formulation of benznidazole.
http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000484
Isabela Ribeiro et al, 2009
Public Library of Science Journal- Neglected Tropical Diseases
This article discusses the need for new and improved treatments for Chagas disease, and sets up short term, medium term, and long term goals for this process. Shorter term goals include better use of existing treatments through new formulations and expanding access. Longer term goals include development of new drugs. The article discusses the 2 current treatments available (that have been mentioned in previous articles)- nifurtimox and benznidazole. However, these are limited to treating the acute phase of the disease, not the chronic phase. The article mentions that no promising new drugs are expected anytime soon, although according to other articles there is one- Ravuconazole, discovered and developed by Eisai Co.
There are many barriers to developing treatments, including the fact that there is little standardization among the protocols and parasites used by researchers in assays. Thus reproducibility has been difficult to achieve. Few rigorous trials have been conducted in CD, particularly to test drug efficacy in patients with chronic CD, since such patients often do not present any clinical disease manifestation until a very advanced stage. CD research is often deemed “too difficult” by many.
One development to help deal with these issues is the creation of non-profit product development partnerships (PDPs) which work to fill in the gaps for neglected diseases. These PDPs offer a different model, since R&D is no longer financed by a product’s sale price. A PDP is currently working on developing a better CD portfolio to address the needs of patients. They aim to deliver more effective treatment for acute, indeterminate, and chronic CD and are working on a pediatric formulation of benznidazole.
http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000484
Breakthroughs in the Quest for a Vaccine
Researchers at UGA provide first look at protein expression in Chagas disease-causing parasites
Innovations Report
15/07/2005
Major advances have been made in elucidating the genetic processes of Trypanosoma cruzi, the parasite that causes Chagas. This article highlights findings from a study at the University of Georgia, where a research team successfully conducted a survey of protein expression in the four lifecycle stages of the parasite. Their results show distinct protein expression abundance and specificity during different stages of the life cycle.
The research is useful because it could hold the key to a new drug or vaccine target. As touched on in previous posts, current treatments for Chagas aren’t always effective and no vaccine has yet been developed. The problem with developing a vaccine lies in the complexity of this four-stage parasite lifecycle, as it complicates attempts to create an effective therapy that can target and eliminate the parasite in all its different stages. But by examining protein expression along with the recently developed gene map, scientists may be able to make decisions on the viability of specific large gene families as candidates for a vaccine.
This article shows thad advances in bioinformatics such as these are integral to drug and vaccine development for Chagas. Yet we already know that the biggest barrier to Chagas’ vaccine development is not scientific. As Chagas disease afflicts mainly impoverished peoples, there is little financial incentive for drug manufacturers to work invest in R&D for a treatment. Public-private partnerships and market commitments need to be formed in order to ensure that the different private and public goals are aligned towards finding a vaccine.
Nevertheless, these genetic breakthroughs are a hopeful sign in the pursuit of a vaccine for a life-threatening disease that afflicts more than 20 million people around the globe.
Article found at http://www.innovations-report.com/html/reports/life_sciences/report-46584.html
More on Buggy Blood: Transfusing the Disease
An ongoing map record showing confirmed cases of donor blood being infected with Chagas disease 07-09. Put out by the AABB (see below). These AABB labs account for 65% of the total blood collected in the U.S.
“Blood Donations in the U.S. testing positive for Chagas’ Disease”
Associated Content
21 Oct 2007
Is blood donated to aid people in life-saving transfusions safe from being buggy? Probably, according to the CDC. Yet discoveries of blood donations infected with the Chagas parasite have highlighted not only the higher-than-anticipated prevalence of Chagas in the U.S. but also the need for better screening to ensure blood donation recipients aren’t getting infected. We know from the last "Buggy Blood" post that blood donations in the U.S. are infected with the Chagas parasite, but another eye-opening article really elaborates on the extent of the problem, the barriers to better screening, and what steps have been taken to ensure blood donations are safe.
An October ‘07 article recounts the release of info from the American Association of Blood Banks (AABB) indicating that about 241 blood donations in the U.S. had tested positive for Chagas disease since the advent of an FDA-licensed blood detection method in January ‘07. Within the year Chagas-positive blood donations had been spotted in 34 states, prompting Dr. James Maguire, former head of the CDC’s parasitic diseases division, to describe the results as “surprising”.
Yes, the results suggest the horrifying possibility that an unknown number of patients receiving untested blood donations may have been exposed to and possibly infected by transfusions containing the deadly T.cruzi parasite. Blood safety experts and the Red Cross were looking into new disease cases that may have involved transmission via blood transfusions with infected blood, but details were not disclosed in the article. Experts estimated that roughly 70% of blood donations were being screened for Chagas--- meaning that about a third of all blood donations in the country are being used in transfusions without being screened for infection. Meaning that for a third of blood donations, you run the risk, if not minuscule, of being infected with a potentially fatal disease without even knowing it.
…..yeah, that’s not very reassuring to me either. And the 2009 CDC Q&A factsheet on screening blood donations for Chagas is even less helpful. In response to a blood donors’ question “Will I be tested automatically (for Chagas)?” the CDC states “Probably. Most blood banks are testing for Chagas disease”. I’m guessing any person about to receive a blood transfusion would prefer the answer regarding the infection status of the blood they’re receiving to be a little more definitive than “probably”.
The good news from this: we now possess an effective blood test for detecting Chagas’ (the T.cruzi ELISA test, developed by Ortho boasts 100% sensitivity and 99.99% sensitivity), and it seems that we have taken the first steps towards developing a biovigilance network and screening blood for Chagas in blood donors as a medical standard. Plus, the donors who test positive are now becoming aware of their own infection status, allowing for them to take any precautionary measures and contributing to the growing pool of evidence on the true prevalence of Chagas in the U.S. Info put out by the AABB includes an ongoing biovigilance map where you can see confirmed cases where donor blood tested positive for Chagas.
Building on the last "Buggy Blood" post, this article really is eye-opening in terms of infected blood donations. Yet more emphasis needs to be put on screening ALL donors for Chagas, rather than just some. How can we do this? Educating the public and publicizing the issue.
CDC factsheet http://www.cdc.gov/chagas/factsheets/screening.html
AABB Biovigiliance Network http://www.aabb.org/Content/Programs_and_Services/Data_Center/Chagas
Article: http://www.noblood.org/news-hot-topics-such-hepatitis-c-sars-aids/3907-us-blood-donations-testing-positive-chagas-disease.html
Saturday, November 21, 2009
Community Communication and Insecticide Distribution
La participación ayuda en la lucha contra el Mal de Chagas (Participation helps in the fight against Chagas disease).
ClarÃn
Valeria Román
Feb. 10, 2007
A strong partnership between rural communities and the government is critical to controlling infestations of the ‘kissing bug’ that causes Chagas, the Argentine newpaper ClarÃn reports. Fumigation or widespread insecticide use in at-risk homes has been effective in controlling the insect populations and in limiting cases of Chagas disease. The kissing bugs prefer to live in adobe or wood huts, which are easily accessible from the outside. Therefore, as soon as insecticides wear off, the bugs are free to move back in and infect their victims.
Currently, there is generally poor communication between government agencies that organize insecticide distribution and the communities that need it. Community members do not report re-infestations and disorganized, poor, bureaucratic governments are slow to monitor bug populations and fumigate as needed. This article reports on a combined American-Argentine study, which found that increasing public awareness of Chagas, encouraging communities to remain vigilant for the kissing bug, and facilitating reporting pathways from the communities to the government decreased the number of Chagas cases.
Creating community discussions and networks to watch out for Chagas is the first step in prevention. Chagas most devastatingly affects communities that are not reached by public health publicity efforts. Many of these communities are poor enough that most people will not have television, internet or radio access to tell them what to look out for. Thus, word of mouth is crucial to spreading awareness of the disease. Thus, community members must create a discussion network to track the spread of the insect population. Only then can the government accurately determine where fumigation is needed.
While community awareness and organization can be fostered by government or non-profit public health outreach programs, it is much more difficult to improve government responsiveness. Many of the countries most affected by Chagas are poor, and lack resources to easily manufacture and distribute large amounts of insecticide to rural communities that are often scattered, unmapped, and hard to access. Some kind of efficient reporting system that takes into account the citizens’ limited means of communication must also be developed.
While the ideas proposed in this article are logical, their implementation is much more difficult. Improvements might be more consistent and sustainable if countries were to finance the one-time destruction of adobe/wood housing and replace it with concrete buildings that the bugs do not prefer to infest.
Apologies to those who don’t speak Spanish, but for those who do, check out the article at:
http://www.clarin.com/diario/2007/10/02/sociedad/s-03203.htm
Finding a Cure with Hit-and-Miss
Pfizer enters tropical disease drug partnership
The Associated Press, Business Week
Nov 18, 2009
Pfizer and Merck and Co. have both recently started a partnership with the nonprofit group Drugs for Neglected Diseases (DNDi) to try to find a treatment for Chagas disease. Pfizer agreed in November to give DNDi access to test 150,000 of their current drug candidates for effectiveness against the disease.
This again demonstrates the importance of non-profit groups in fostering and securing interest in treating Chagas disease. It also highlights how slow progress in treating Chagas disease is, since investigation of new drugs consists of a hit-or-miss strategy of testing thousands of existing compounds.
Not surprisingly, Pfizer has made a big deal of this partnership, presumably since it benefits their public image (not to say that it isn’t generous).
http://www.businessweek.com/ap/financialnews/D9C20TV80.htm
Also read: http://www.pharmabiz.com/article/detnews.asp?articleid=52715§ionid=
The Associated Press, Business Week
Nov 18, 2009
Pfizer and Merck and Co. have both recently started a partnership with the nonprofit group Drugs for Neglected Diseases (DNDi) to try to find a treatment for Chagas disease. Pfizer agreed in November to give DNDi access to test 150,000 of their current drug candidates for effectiveness against the disease.
This again demonstrates the importance of non-profit groups in fostering and securing interest in treating Chagas disease. It also highlights how slow progress in treating Chagas disease is, since investigation of new drugs consists of a hit-or-miss strategy of testing thousands of existing compounds.
Not surprisingly, Pfizer has made a big deal of this partnership, presumably since it benefits their public image (not to say that it isn’t generous).
http://www.businessweek.com/ap/financialnews/D9C20TV80.htm
Also read: http://www.pharmabiz.com/article/detnews.asp?articleid=52715§ionid=
Sunday, November 15, 2009
Genetic Engineering to Exterminate the Parasite
Bugs in the System? Issues in the science and regulation of genetically modified insects
A Report Prepared by the Pew Initiative on Food and Technology
January 2004
This report gives a very in-depth analysis of genetically modified insects and the issues surrounding their development, approval, employment, and regulation. As mentioned in a previous blog post, genetically modified insects may be a potentially successful strategy to combat the spread of Chagas' disease. Currently the most supported method is to create paratransgenic kissing bugs, in which the actual insect remains unchanged but its gut symbionts - the bacteria that it depends upon to get essential nutrients from its food - would be altered in such a way as to kill the insect as they travel through the digestive tract. This type of genetically modified organism can be created by giving the insect a substrate with bacteria that carry the desired transgenes, which may be lethal or may function to make the insects sterile or unable to infect hosts. While the use of genetically modified insects may appear a solution with a high potential to halt the Chagas disease epidemic, the use of this type of technology does not have a large precedent and raises several complex and possibly dangerous concerns.
Use of genetically modified insects in a variety of realms has a wide range of potential benefits. This article recounts several instances in which employing these organisms may be economically beneficial, such as eradicating a cash crop pest. In the context of Chagas' disease, creating a paratransgenic kissing bug would directly interfere with disease propagation and thus should cause a reduction in incidence. This result would obviously bring about a huge public health benefit, improving the quality of life for many people especially in endemic areas. It would also provide an economic benefit by easing the financial burden of treating this disease and losing part of the workforce to its symptoms.
Introduction of genetically modified insects into the environment is not risk-free, however. Altering a characteristic of the organism to change one trait may affect other parts of the insect's biological fitness as well. Changing the genetic make-up of the insect may alter its tolerance to certain environmental conditions, its ability to reproduce, its interactions with other animals, etc. Thus not only could genetically modifying an insect change one targeted trait, but it might throw off the delicate enviornmental balance and affect an entire ecosystem. Introducing this type of organism to an environment may have unintended consequences on non-target flora and fauna, both direct and indirect. Also, the stability of the introduced genetic construct is important to consider. Both horizontal and vertical gene transmission may occur, transferring the material within the original species and among other species as well. If the construct is more prone to mutation or recombination, serious consequences may ensue.
Also, regulation of genetically modified insects poses a challenge. In the history of genetic modification, the precedent established has been to regulated the altered material as the original product would have been regulated based on its intended function and not on its origin. For instance, a genetically modified crop would be subject to the same regulations as an unaltered crop. For insects, however, it is more difficult to find an analogous unaltered form for comparison. Current thought suggests that different genetically modified insects, depending on their potential uses, may be subject to regulation by the Environmental Protection Agency, the Food and Drug Administration, and the United States Department of Agriculture. Unlike other genetically modified products, insects are not neatly confined within national boundaries, so international legislation and regulation may be necessary.
Thus while genetically modified insects may have potential to effectively combat the Chagas' disease epidemic, the use of this biotechnology raises several important concerns about public health, environmental effects, and regulation. These issues must all be addressed adequately and thoroughly before implementing this type of measure, as recalling the introduction of a genetically modified insect into an environment would be extremely difficult, if not entirely impossible.
http://www.pewtrusts.org/uploadedFiles/wwwpewtrustsorg/Reports/Food_and_Biotechnology/pifb_bugs_012204.pdf
A Report Prepared by the Pew Initiative on Food and Technology
January 2004
This report gives a very in-depth analysis of genetically modified insects and the issues surrounding their development, approval, employment, and regulation. As mentioned in a previous blog post, genetically modified insects may be a potentially successful strategy to combat the spread of Chagas' disease. Currently the most supported method is to create paratransgenic kissing bugs, in which the actual insect remains unchanged but its gut symbionts - the bacteria that it depends upon to get essential nutrients from its food - would be altered in such a way as to kill the insect as they travel through the digestive tract. This type of genetically modified organism can be created by giving the insect a substrate with bacteria that carry the desired transgenes, which may be lethal or may function to make the insects sterile or unable to infect hosts. While the use of genetically modified insects may appear a solution with a high potential to halt the Chagas disease epidemic, the use of this type of technology does not have a large precedent and raises several complex and possibly dangerous concerns.
Use of genetically modified insects in a variety of realms has a wide range of potential benefits. This article recounts several instances in which employing these organisms may be economically beneficial, such as eradicating a cash crop pest. In the context of Chagas' disease, creating a paratransgenic kissing bug would directly interfere with disease propagation and thus should cause a reduction in incidence. This result would obviously bring about a huge public health benefit, improving the quality of life for many people especially in endemic areas. It would also provide an economic benefit by easing the financial burden of treating this disease and losing part of the workforce to its symptoms.
Introduction of genetically modified insects into the environment is not risk-free, however. Altering a characteristic of the organism to change one trait may affect other parts of the insect's biological fitness as well. Changing the genetic make-up of the insect may alter its tolerance to certain environmental conditions, its ability to reproduce, its interactions with other animals, etc. Thus not only could genetically modifying an insect change one targeted trait, but it might throw off the delicate enviornmental balance and affect an entire ecosystem. Introducing this type of organism to an environment may have unintended consequences on non-target flora and fauna, both direct and indirect. Also, the stability of the introduced genetic construct is important to consider. Both horizontal and vertical gene transmission may occur, transferring the material within the original species and among other species as well. If the construct is more prone to mutation or recombination, serious consequences may ensue.
Also, regulation of genetically modified insects poses a challenge. In the history of genetic modification, the precedent established has been to regulated the altered material as the original product would have been regulated based on its intended function and not on its origin. For instance, a genetically modified crop would be subject to the same regulations as an unaltered crop. For insects, however, it is more difficult to find an analogous unaltered form for comparison. Current thought suggests that different genetically modified insects, depending on their potential uses, may be subject to regulation by the Environmental Protection Agency, the Food and Drug Administration, and the United States Department of Agriculture. Unlike other genetically modified products, insects are not neatly confined within national boundaries, so international legislation and regulation may be necessary.
Thus while genetically modified insects may have potential to effectively combat the Chagas' disease epidemic, the use of this biotechnology raises several important concerns about public health, environmental effects, and regulation. These issues must all be addressed adequately and thoroughly before implementing this type of measure, as recalling the introduction of a genetically modified insect into an environment would be extremely difficult, if not entirely impossible.
http://www.pewtrusts.org/uploadedFiles/wwwpewtrustsorg/Reports/Food_and_Biotechnology/pifb_bugs_012204.pdf
Going Beyond Insecticide
Don't Let the Bugs Bite
Ben Harder
Aug. 14, 2004
Science News, Vol. 166, No. 7
This article discusses the possibility of genetic engineering to defeat different diseases spread by insects. In the mid 20th century there were many efforts to eliminate diseases by spraying insecticides. They were able to eliminate malaria in the US and Europe with the use of insecticides (together with other methods) but many insects, especially in the tropical regions of the world have proved to be too strong to be easily eradicated simply by spraying chemicals. Researchers have since realized that they are not going to be able to get rid of mosquitoes and other insects so they have moved on to genetic engineering, which will either leave the insects incapable of spreading illness or at least curtail some vector populations. One example of this kind of disease control is the release of sterilized insects into the population. These insects then compete with fertile populations for mates, thereby reducing the number of offspring.
In the case of Chagas disease, researchers are using the bacterium Rhodococcus rhodnii, which typically lives in the soil and the guts of certain species of “kissing bugs”, several species of insects which carry the Chagas parasite. The insects cannot live without the nutrients made by the bacteria and young insects acquire it by eating the feces of older insects so it contains enormous potential. In July of 2003, CDC experiments showed that an inserted test gene was passed down through at least 100 generations in 8 out of 9 strains of the engineered bacteria.
In previous experiments, researchers had genetically modified the bacteria by inserting a gene that encodes a peptide which is harmless to the insect but toxic to the Chagas parasite. They found that the gene eliminated most to all of the insects parasites. In another experiment researchers built a mock hut inside of a lab and deposited genetically engineered bacteria in fake feces throughout the enclosure. They found that the majority of the insects picked up the engineered bacteria. They are now working on a way to translate this approach to insects living in the wild. Furthermore, they must determine if all species of insects which carry Chagas can pick up the bacterium.
Although these experiments show a lot of potential there are several large obstacles to their use. One of them is the general fear of genetic engineering, which may mean that the general population and many governments will be resistant to allowing these genetically modified insects or bacteria be released. Furthermore, researchers will need to continuously monitor the modified insects after releasing them in order to make sure they are properly controlling the disease and not further mutating. However, because of the money currently available for studying infectious disease, such as from the Gates Foundation, this science has a chance to progress quite rapidly.
Ben Harder
Aug. 14, 2004
Science News, Vol. 166, No. 7
This article discusses the possibility of genetic engineering to defeat different diseases spread by insects. In the mid 20th century there were many efforts to eliminate diseases by spraying insecticides. They were able to eliminate malaria in the US and Europe with the use of insecticides (together with other methods) but many insects, especially in the tropical regions of the world have proved to be too strong to be easily eradicated simply by spraying chemicals. Researchers have since realized that they are not going to be able to get rid of mosquitoes and other insects so they have moved on to genetic engineering, which will either leave the insects incapable of spreading illness or at least curtail some vector populations. One example of this kind of disease control is the release of sterilized insects into the population. These insects then compete with fertile populations for mates, thereby reducing the number of offspring.
In the case of Chagas disease, researchers are using the bacterium Rhodococcus rhodnii, which typically lives in the soil and the guts of certain species of “kissing bugs”, several species of insects which carry the Chagas parasite. The insects cannot live without the nutrients made by the bacteria and young insects acquire it by eating the feces of older insects so it contains enormous potential. In July of 2003, CDC experiments showed that an inserted test gene was passed down through at least 100 generations in 8 out of 9 strains of the engineered bacteria.
In previous experiments, researchers had genetically modified the bacteria by inserting a gene that encodes a peptide which is harmless to the insect but toxic to the Chagas parasite. They found that the gene eliminated most to all of the insects parasites. In another experiment researchers built a mock hut inside of a lab and deposited genetically engineered bacteria in fake feces throughout the enclosure. They found that the majority of the insects picked up the engineered bacteria. They are now working on a way to translate this approach to insects living in the wild. Furthermore, they must determine if all species of insects which carry Chagas can pick up the bacterium.
Although these experiments show a lot of potential there are several large obstacles to their use. One of them is the general fear of genetic engineering, which may mean that the general population and many governments will be resistant to allowing these genetically modified insects or bacteria be released. Furthermore, researchers will need to continuously monitor the modified insects after releasing them in order to make sure they are properly controlling the disease and not further mutating. However, because of the money currently available for studying infectious disease, such as from the Gates Foundation, this science has a chance to progress quite rapidly.
Treating with Transplants
Cell Therapy in Chagas Disease
Antonio C. Campos de Carvalho, Regina C. S. Goldenberg, Linda A. Jelicks,Milena B. P. Soares, Ricardo Ribeiro dos Santos, David C. Spray, and Herbert B. Tanowitz
May 2009
Interdisciplinary Perspectives on Infectious Diseases
Chagas disease, which is caused by the parasite Trypanosoma cruzi, can lead to cardiomyopathy and eventually to congestive heart failure. This is a large problem because the disease is endemic in all Latin American countries except for those in the Caribbean, and there are no effective treatments currently available. According to the article, 16–18 million individuals are infected with the parasite and this number continues to grow as more and more people are infected yearly. It is estimated that 10%–30% of all infected individuals will acquire chronic chagasic cardiomyopathy, which means that there are anywhere between 1.6 to 5.4 million patients with chronic chagasic cardiomyopathy in Latin America. Because of this, Chagas disease is one of the most important causes of heart disease in this region.
In the past heart transplants have been attempted as a cure for the disease but this procedure comes with many problems. The latest move has been to try to cure the disease by replacing the damaged heart cells with bone-marrow derived cells – experiments in mice have shown that that the transplantation of bone-marrow-derived cells ameliorates the inflammation and fibrosis in the heart caused by the Chagas infection.
In the most recent notable experiment, investigators in Brazil “initiated a clinical trial to examine the feasibility and safety of autologous bone marrow cell transplantation in patients with congestive heart failure due to chronic chagasic cardiomyopathy.” These patients have a 40% mortality rate within the first 2 years of onset. The study was only conducted on people who were at the stage of the infection where their only option is a heart transplant. Bone marrow aspiration was performed on the day of the injection and then the cell suspension was injected into the coronary arteries. This trial was not meant to show efficacy but it did show that, in general, this kind of therapy is feasible and safe. Furthermore, they had positive results such as a significant improvement in a 6 minute walking test as well as an improvement in quality of life. Furthermore, there was no detectable increase in arrhythmias. Because of the positive outcomes of this first trial, they are currently working on a phase II trial to test for efficacy which will be larger randomized, double-blind and placebo controlled trial.
It is very possible that this will be an effective therapy for patients with end-stage chagasic heart disease. However, we still have a long way to go. In addition to proving efficacy, researchers still do not know which cell type(s) is/are responsible for the effects observed in the animal and the preliminary human experiments. This will be important for further improving the therapy. My personal worry is that because this disease is generally concentrated in poorer populations, the people who need it most will not benefit from these scientific breakthroughs. It seems unlikely to me that this type of treatment will ever be an inexpensive or easy procedure, which means that it may be impossible to deliver in poor, remote areas, rendering it useless for many of the people who need it.
http://www.hindawi.com/journals/ipid/2009/484358.html
Antonio C. Campos de Carvalho, Regina C. S. Goldenberg, Linda A. Jelicks,Milena B. P. Soares, Ricardo Ribeiro dos Santos, David C. Spray, and Herbert B. Tanowitz
May 2009
Interdisciplinary Perspectives on Infectious Diseases
Chagas disease, which is caused by the parasite Trypanosoma cruzi, can lead to cardiomyopathy and eventually to congestive heart failure. This is a large problem because the disease is endemic in all Latin American countries except for those in the Caribbean, and there are no effective treatments currently available. According to the article, 16–18 million individuals are infected with the parasite and this number continues to grow as more and more people are infected yearly. It is estimated that 10%–30% of all infected individuals will acquire chronic chagasic cardiomyopathy, which means that there are anywhere between 1.6 to 5.4 million patients with chronic chagasic cardiomyopathy in Latin America. Because of this, Chagas disease is one of the most important causes of heart disease in this region.
In the past heart transplants have been attempted as a cure for the disease but this procedure comes with many problems. The latest move has been to try to cure the disease by replacing the damaged heart cells with bone-marrow derived cells – experiments in mice have shown that that the transplantation of bone-marrow-derived cells ameliorates the inflammation and fibrosis in the heart caused by the Chagas infection.
In the most recent notable experiment, investigators in Brazil “initiated a clinical trial to examine the feasibility and safety of autologous bone marrow cell transplantation in patients with congestive heart failure due to chronic chagasic cardiomyopathy.” These patients have a 40% mortality rate within the first 2 years of onset. The study was only conducted on people who were at the stage of the infection where their only option is a heart transplant. Bone marrow aspiration was performed on the day of the injection and then the cell suspension was injected into the coronary arteries. This trial was not meant to show efficacy but it did show that, in general, this kind of therapy is feasible and safe. Furthermore, they had positive results such as a significant improvement in a 6 minute walking test as well as an improvement in quality of life. Furthermore, there was no detectable increase in arrhythmias. Because of the positive outcomes of this first trial, they are currently working on a phase II trial to test for efficacy which will be larger randomized, double-blind and placebo controlled trial.
It is very possible that this will be an effective therapy for patients with end-stage chagasic heart disease. However, we still have a long way to go. In addition to proving efficacy, researchers still do not know which cell type(s) is/are responsible for the effects observed in the animal and the preliminary human experiments. This will be important for further improving the therapy. My personal worry is that because this disease is generally concentrated in poorer populations, the people who need it most will not benefit from these scientific breakthroughs. It seems unlikely to me that this type of treatment will ever be an inexpensive or easy procedure, which means that it may be impossible to deliver in poor, remote areas, rendering it useless for many of the people who need it.
http://www.hindawi.com/journals/ipid/2009/484358.html
Promising Drug, Closer to Market
Bitten by the ‘Kissing Bug’
Lloyd Dunlap
November 2009
Drug Discovery News
This article provides an extremely current rationale for the need to develop a treatment for Chagas’ disease, and it discusses a newly emerging pharmaceutical. According to the World Health Organization, this potentially fatal condition, which is endemic to 21 Latin American countries, has been appearing in other regions of the world as population mobility continues to increase. This increased incidence of Chagas disease presents a potential threat of further spread through blood transfusions, organ transplants, and congenital infection.
Thus the treatment of this disease has become an issue of vital importance. Prompted by these recent trends, Eisai Co. Ltd. has partnered with the Drugs for Neglected Disease Initiative (DNDi) to develop a novel pharmaceutical treatment that is currently in late stages of the approval process. Several years ago, the former company produced ravuconazole as an antifungal agent, and it was found to have potentially therapeutic effects for Chagas’ disease. Eisai Co. Ltd. continued to develop the drug while DNDi conducted Phase I trials. At this point, the two have collaborated to enter final testing and potentially affordable marketing of E1224, a pro-drug form of ravuconazole that is metabolized to the active form upon administration.
If final testing of the drug yields efficacious results, the companies intend to sell it at a cheaper price in endemic countries and a more expensive price in non-endemic areas. Hopefully this two-tiered pricing scheme will make the drug most affordable where it is most needed, while still allowing the drug companies to produce it in a sustainable fashion.
http://www.drugdiscoverynews.com/index.php?newsarticle=3352
Lloyd Dunlap
November 2009
Drug Discovery News
This article provides an extremely current rationale for the need to develop a treatment for Chagas’ disease, and it discusses a newly emerging pharmaceutical. According to the World Health Organization, this potentially fatal condition, which is endemic to 21 Latin American countries, has been appearing in other regions of the world as population mobility continues to increase. This increased incidence of Chagas disease presents a potential threat of further spread through blood transfusions, organ transplants, and congenital infection.
Thus the treatment of this disease has become an issue of vital importance. Prompted by these recent trends, Eisai Co. Ltd. has partnered with the Drugs for Neglected Disease Initiative (DNDi) to develop a novel pharmaceutical treatment that is currently in late stages of the approval process. Several years ago, the former company produced ravuconazole as an antifungal agent, and it was found to have potentially therapeutic effects for Chagas’ disease. Eisai Co. Ltd. continued to develop the drug while DNDi conducted Phase I trials. At this point, the two have collaborated to enter final testing and potentially affordable marketing of E1224, a pro-drug form of ravuconazole that is metabolized to the active form upon administration.
If final testing of the drug yields efficacious results, the companies intend to sell it at a cheaper price in endemic countries and a more expensive price in non-endemic areas. Hopefully this two-tiered pricing scheme will make the drug most affordable where it is most needed, while still allowing the drug companies to produce it in a sustainable fashion.
http://www.drugdiscoverynews.com/index.php?newsarticle=3352
Struggling Towards New and Better Drugs
Drug shows promise against Chagas’ disease
Los Angeles Times
Charles Piller
Mar. 31, 2005
http://proquest.umi.com/pqdweb?index=0&did=814907681&SrchMode=1&sid=5&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335271&clientId=7344
A few new drugs to treat Chagas disease are currently being studied. Among them is the compound TAK-187, which has shown remarkable success in treating Chagas in mice. Moreover, TAK-187 might be more effective and have fewer dangerous side-effects than existing medications.
The most common currently used drug is benznidazole, which is not always effective at killing the parasites. Moreover, it can have toxic effects on the body, and can cause nerve and bone marrow damage.
TAK-187, an anti-fungal agent, seems to block production of ergosterol, a steroid that is vital in the parasite’s development. The drug has the potential to be an oral drug, rather than an ingestible one, which would make its delivery easier and possibly cheaper. Additionally, it is effective at one-tenth the blood concentration that benznidazole is and could be administered less frequently. Scientists postulate that this may be because the new compound is not as easily metabolized and excreted by the body.
Of course, this drug is in very early stages of study. As of 2005, they had not yet begun large-animal testing. Because drug approval moves so slowly, it is hard to say whether this drug will ever make it to market at all. Again, this is a drug intended as a systemic anti-fungal agent that unintentionally demonstrates effectiveness against Chagas. Even if further study shows that it is indeed successful in fighting Chagas, and that it is better at doing so than the existing drugs, there is no guarantee that it can be mass-produced and brought to market in order to benefit the millions of Chagas victims.
Los Angeles Times
Charles Piller
Mar. 31, 2005
http://proquest.umi.com/pqdweb?index=0&did=814907681&SrchMode=1&sid=5&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335271&clientId=7344
A few new drugs to treat Chagas disease are currently being studied. Among them is the compound TAK-187, which has shown remarkable success in treating Chagas in mice. Moreover, TAK-187 might be more effective and have fewer dangerous side-effects than existing medications.
The most common currently used drug is benznidazole, which is not always effective at killing the parasites. Moreover, it can have toxic effects on the body, and can cause nerve and bone marrow damage.
TAK-187, an anti-fungal agent, seems to block production of ergosterol, a steroid that is vital in the parasite’s development. The drug has the potential to be an oral drug, rather than an ingestible one, which would make its delivery easier and possibly cheaper. Additionally, it is effective at one-tenth the blood concentration that benznidazole is and could be administered less frequently. Scientists postulate that this may be because the new compound is not as easily metabolized and excreted by the body.
Of course, this drug is in very early stages of study. As of 2005, they had not yet begun large-animal testing. Because drug approval moves so slowly, it is hard to say whether this drug will ever make it to market at all. Again, this is a drug intended as a systemic anti-fungal agent that unintentionally demonstrates effectiveness against Chagas. Even if further study shows that it is indeed successful in fighting Chagas, and that it is better at doing so than the existing drugs, there is no guarantee that it can be mass-produced and brought to market in order to benefit the millions of Chagas victims.
Negotiating Barriers to Treatment
Nonprofits work with drug firms to treat diseases in third world
Los Angeles Times
Paul Elias
Feb. 9, 2004
http://proquest.umi.com/pqdweb?index=0&did=541501611&SrchMode=1&sid=2&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335139&clientId=7344
A world of difference; A nonprofit drug company works to wipe out diseases that plague developing nations but are ignored by Western pharmaceutical giants
Los Angeles Times
Linda Marsa
Oct. 25, 2004
http://proquest.umi.com/pqdweb?index=1&did=723100691&SrchMode=1&sid=3&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335178&clientId=7344
Too often, pharmaceutical companies avoid investing research and development in diseases that mostly affect the poor. Chagas disease is not an exception to this disappointing trend. Even though Chagas kills more people in Latin America than malaria does, no new drugs have been developed to treat it in the last forty years. These two articles suggest that this lack of progress is due mostly to the drug companies’ concerns that treatments for Chagas will not be very profitable, since they will be marketed only to the poorest citizens of the poorer countries in Latin America.
OneWorld Health, a non-profit organization that identifies as a drug company, is trying to close the gap between pharmaceuticals and Chagas victims. Celera Genomics Group, a “gene-mapping pioneer” had discovered a compound, K-777, that preliminarily demonstrated efficacy in treating Chagas. They were not willing, however, to develop the compound through to the treatment stage. Approached by OneWorld Health, they agreed to donate the rights to K-777 so that the non-profit could develop the drug and hopefully implement it in Latin America. Asked to comment by the Los Angeles Times, the Celera spokesman said, “It made sense for us to donate it…. They were well-positioned to move it forward and we weren’t.”
This apparent generosity still benefits the drug companies. They can receive large tax credits for donating rights to new compounds. Moreover, such seemingly selfless actions improve their image and can be used in public relations.
OneWorld Health is funded through grants, and has received substantial amounts of money from the Gates Foundation to work on treatment development for Chagas and similarly overlooked diseases. While the grants they receive are generous, they are insignificant compared to the research and development budgets of for-profit pharmaceutical companies.
While this partnership is certainly a positive step in the fight against Chagas disease, it does not maximize chances for finding better treatment options, immunizations or a cure. Pharmaceutical companies are not using their immense financial reserves to actively invest in or focus on research to treat Chagas and other similar diseases. Rather, their discoveries and advances in doing so are usually products of other lines of research. This is happily serendipitous for Chagas sufferers, but it is not the most effective or efficient way to help them.
Los Angeles Times
Paul Elias
Feb. 9, 2004
http://proquest.umi.com/pqdweb?index=0&did=541501611&SrchMode=1&sid=2&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335139&clientId=7344
A world of difference; A nonprofit drug company works to wipe out diseases that plague developing nations but are ignored by Western pharmaceutical giants
Los Angeles Times
Linda Marsa
Oct. 25, 2004
http://proquest.umi.com/pqdweb?index=1&did=723100691&SrchMode=1&sid=3&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258335178&clientId=7344
Too often, pharmaceutical companies avoid investing research and development in diseases that mostly affect the poor. Chagas disease is not an exception to this disappointing trend. Even though Chagas kills more people in Latin America than malaria does, no new drugs have been developed to treat it in the last forty years. These two articles suggest that this lack of progress is due mostly to the drug companies’ concerns that treatments for Chagas will not be very profitable, since they will be marketed only to the poorest citizens of the poorer countries in Latin America.
OneWorld Health, a non-profit organization that identifies as a drug company, is trying to close the gap between pharmaceuticals and Chagas victims. Celera Genomics Group, a “gene-mapping pioneer” had discovered a compound, K-777, that preliminarily demonstrated efficacy in treating Chagas. They were not willing, however, to develop the compound through to the treatment stage. Approached by OneWorld Health, they agreed to donate the rights to K-777 so that the non-profit could develop the drug and hopefully implement it in Latin America. Asked to comment by the Los Angeles Times, the Celera spokesman said, “It made sense for us to donate it…. They were well-positioned to move it forward and we weren’t.”
This apparent generosity still benefits the drug companies. They can receive large tax credits for donating rights to new compounds. Moreover, such seemingly selfless actions improve their image and can be used in public relations.
OneWorld Health is funded through grants, and has received substantial amounts of money from the Gates Foundation to work on treatment development for Chagas and similarly overlooked diseases. While the grants they receive are generous, they are insignificant compared to the research and development budgets of for-profit pharmaceutical companies.
While this partnership is certainly a positive step in the fight against Chagas disease, it does not maximize chances for finding better treatment options, immunizations or a cure. Pharmaceutical companies are not using their immense financial reserves to actively invest in or focus on research to treat Chagas and other similar diseases. Rather, their discoveries and advances in doing so are usually products of other lines of research. This is happily serendipitous for Chagas sufferers, but it is not the most effective or efficient way to help them.
Buggy Blood: Tranfusing the Disease
Chagas disease a growing concern
Susan Abram
September 2009
LA Daily News
Chagas disease, pervasive in South America, is now showing up more and more in the United States, due to globalization and travel, and also presumably, due to lack of initial symptoms, as mentioned in a previous article. As the world is becoming a more global place, it is showing up in North America, Japan, Europe, and Australia. And it is increasingly becoming a problem in blood donation in the United States.
In this article a woman named Maria Gutierrez donates blood, and then received a phone call three days later telling her the blood she donated was useless, because she has Chagas disease. Gutierrez went to several specialists, with no one able to provide her with very much information, and one doctor even saying there was nothing she could do, which in the early phase of Chagas is certainly untrue.
The only place to treat Chagas disease, and where Gutierrez was eventually treated as well, is at Olive View UCLA Medical Center in Sylmar. Patients at the clinic receive a full cardiac work-up, and this early detection has helped to identify nearly 80 cases. Citing the CDC, Doctors Without Borders says there are about 300,000 people living with Chagas in the United States, and in Los Angeles County, one out of every 300 Latino blood donors tests positive for Chagas.
Chagas is truly a neglected disease and remains challenging due to the length of time it remains dormant, making it difficult to treat. Most infections are not discovered until the chronic phase, when treatment is the most challenging. The Drugs for neglected Diseases Initiative is working to develop the first pediatric formulation of a drug to treat the disease, as well as researching possible use of existing drugs originally developed for other diseases to treat Chagas.
http://www.dailynews.com/search/ci_13288979
Susan Abram
September 2009
LA Daily News
Chagas disease, pervasive in South America, is now showing up more and more in the United States, due to globalization and travel, and also presumably, due to lack of initial symptoms, as mentioned in a previous article. As the world is becoming a more global place, it is showing up in North America, Japan, Europe, and Australia. And it is increasingly becoming a problem in blood donation in the United States.
In this article a woman named Maria Gutierrez donates blood, and then received a phone call three days later telling her the blood she donated was useless, because she has Chagas disease. Gutierrez went to several specialists, with no one able to provide her with very much information, and one doctor even saying there was nothing she could do, which in the early phase of Chagas is certainly untrue.
The only place to treat Chagas disease, and where Gutierrez was eventually treated as well, is at Olive View UCLA Medical Center in Sylmar. Patients at the clinic receive a full cardiac work-up, and this early detection has helped to identify nearly 80 cases. Citing the CDC, Doctors Without Borders says there are about 300,000 people living with Chagas in the United States, and in Los Angeles County, one out of every 300 Latino blood donors tests positive for Chagas.
Chagas is truly a neglected disease and remains challenging due to the length of time it remains dormant, making it difficult to treat. Most infections are not discovered until the chronic phase, when treatment is the most challenging. The Drugs for neglected Diseases Initiative is working to develop the first pediatric formulation of a drug to treat the disease, as well as researching possible use of existing drugs originally developed for other diseases to treat Chagas.
http://www.dailynews.com/search/ci_13288979
Cosmic Chagas
From Jungle to Space in Pursuit of New Drugs
Dina Eng
November 2000
NY Times
This story, made widely available to the public via the New York Times, discusses a unique approach to finding an effective treatment for Chagas’ Disease. Around the turn of the century, two men of very different scientific backgrounds collaborated to bring together seemingly disparate disciplines in addressing this parasitic problem annually responsible for the deaths of nearly 45,000 people in the Latin American countries to which it is endemic.
Dr. Frank Chang-Diaz, a NASA astronaut with physicist training, and Dr. Jose Zaglul, head of the Earth Institute and several agricultural courses, postulated that an effective treatment compound might be found in the vast vegetation of the Amazon Rainforest in South America. To better target their search, the scientists needed to gain more information about the pathological mechanisms of the parasite itself. They decided that an outer space scientific laboratory would provide an optimal environment to explore such important issues due to its pure conditions, such as microgravity, that cannot easily be simulated on Earth.
After recruiting a band of supporters, the scientists made this endeavor a reality. Experiments on several space shuttle missions attempted to isolate proteins involved in the parasite’s mechanism of action, as well as focusing on a particular enzyme to elucidate its structure and function. They also tested various compounds for efficacy in inhibiting this enzyme (which was unnamed in the article). The most promising compound was derived from a rainforest tree called the Gumbo-Limbo tree, or Bursera simaruba.
Aside from potentially making inroads into finding a novel treatment for Chagas’ disease, this scientific investigation tied together several disciplines in an unprecedented manner. It made a connection between the space frontier, biodiversity, biomedicine, and more fields. The impact of these new connections may be felt in non-scientific realms as well, such as connecting South America to the space missions.
http://www.nytimes.com/2000/11/28/health/from-jungle-to-space-in-pursuit-of-new-drugs.html
Dina Eng
November 2000
NY Times
This story, made widely available to the public via the New York Times, discusses a unique approach to finding an effective treatment for Chagas’ Disease. Around the turn of the century, two men of very different scientific backgrounds collaborated to bring together seemingly disparate disciplines in addressing this parasitic problem annually responsible for the deaths of nearly 45,000 people in the Latin American countries to which it is endemic.
Dr. Frank Chang-Diaz, a NASA astronaut with physicist training, and Dr. Jose Zaglul, head of the Earth Institute and several agricultural courses, postulated that an effective treatment compound might be found in the vast vegetation of the Amazon Rainforest in South America. To better target their search, the scientists needed to gain more information about the pathological mechanisms of the parasite itself. They decided that an outer space scientific laboratory would provide an optimal environment to explore such important issues due to its pure conditions, such as microgravity, that cannot easily be simulated on Earth.
After recruiting a band of supporters, the scientists made this endeavor a reality. Experiments on several space shuttle missions attempted to isolate proteins involved in the parasite’s mechanism of action, as well as focusing on a particular enzyme to elucidate its structure and function. They also tested various compounds for efficacy in inhibiting this enzyme (which was unnamed in the article). The most promising compound was derived from a rainforest tree called the Gumbo-Limbo tree, or Bursera simaruba.
Aside from potentially making inroads into finding a novel treatment for Chagas’ disease, this scientific investigation tied together several disciplines in an unprecedented manner. It made a connection between the space frontier, biodiversity, biomedicine, and more fields. The impact of these new connections may be felt in non-scientific realms as well, such as connecting South America to the space missions.
http://www.nytimes.com/2000/11/28/health/from-jungle-to-space-in-pursuit-of-new-drugs.html
Unraveling the Mechanism of Chagas
The Significance of Autoimmunity in the Pathogenesis of Chagas Heart Disease
Juan S. Leon and David M. Engman
May, 2003
Frontiers in Bioscience
Although we have been studying it for nearly half a century, we are still unsure of the exact mechanism of Chagas heart disease. One of the long standing hypotheses is that it could be an autoimmune disease. This hypothesis came from early observations of cardiac pathology and the discovery of antibodies that were reactive to the T. cruzi parasite as well as host proteins in patients with chronic Chagas heart disease. It is important that we figure out whether or not it is an autoimmune disease because it would change the way we treat the disease; if it is an autoimmune disease treatments must be targeted towards autoimmune mechanisms and not just the parasite.
It is clear that autoimmunity can be induced by T. cruzi in humans and animals but according to the authors there is no proof that autoimmunity directly contributes to Chagas heart disease. Several observations allow for other possibilities. One of these is the possibility that it is not live parasites that cause the inflammation. It may be that antigens from destroyed T. Cruzi remain in the heart tissue and cause ongoing inflammation. Other possibilities include that the Chagas parasite causes tissue ischemia and subsequent inflammation, or that it is caused an overly aggressive anti-parasite inflammatory response to the chronic presence of the parasite. There is nothing to disprove the autoimmunity hypothesis but there are also still many other possible hypotheses that need to be ruled out.
According to the authors there is “strong evidence in support of the hypothesis that Chagas disease can be explained by persistent parasite and anti-parasite immunity.” Although there is strong evidence that the parasite can induce autoimmunity the authors make the specific point that there is no well documented proof that this autoimmunity is “pathogenic” meaning that it might not be causing Chagas heart disease. One of the pieces of evidence against the autoimmunity hypothesis is that immunosuppressants have been documented to increase mortality, instead of decreasing it as one would expect. Immunosuppressants might simply make it easier for the parasites to cause disease. Furthermore anti T. cruzi chemotherapy has been shown to reduce heart disease. One interesting suggestion, based on the fact that Chagas disease outcomes are so varied, is that “T. cruzi may induce autoimmunity and/or disease depending on host immunogenetics and parasite genetics” which may make the particular strain autoimmunity-inducing or not.
http://cruzi.pathology.northwestern.edu/engmanlab/pdf/ReprintFBS.pdf
Dangerous Kisses
Lessons of the Kissing Bug’s Deadly Gift
Lawrence K Altman
April 12, 2005
NY Times
Chagas disease, which exists only in the Americas, has infected approximately 16 million people and causes about 50,000 deaths a year. It is a parasitic infection transmitted through the kissing bug (also known as the reduviid bug or the triatomine bug). The insect lives in cracks and crevices in poor housing where it bites people on the face, often while they are sleeping. It can also be transmitted via food contamination, blood transfusions, organ transplants, and from mother to child at birth.
The initial symptoms of Chagas disease are usually mild or nonexistent, so they are either construed as something else or simply go unnoticed. It usually takes decades for the disease to cause death by slowly damaging heart muscle, the esophagus, and colon, and by that time drugs cannot reverse the damage. The exact mechanism of the disease are still under investigation, although scientists have several hypotheses, including that it might be an autoimmune disease, or that the parasite causes an overly aggressive anti- parasite inflammatory response due to chronic presence of the parasite, as described in a later article.
However, in this particular outbreak described by the article in Brazil, symptoms did present themselves within a few days of the outbreak, which was apparently transmitted orally through contaminated sugar juice. The juice was pulled off the market and people who were anywhere in southern Brazil at the time were advised to get medical checkups if they drank sugar cane juice. The symptoms included fever, headache, muscle aches, vomiting, and a rash. Many people also experienced swollen lymph glands and spleen, abdominal pain, intestinal bleeding, jaundice, and encephalitis.
There are 2 drugs currently available—Benzonidazol, made by Roche, and Nifurtimox, made by Bayer. These drugs seem to be effective for treating Chagas disease in its early stages. Doctors are not sure why symptoms in this outbreak are more immediate and severe. One theory is more parasites entered the body through food than would have found their way to blood from a bite. Another theory is it might be an usually virulent strain of the Chagas parasite.
More research is needed to see how the bugs were deposited in the sugar cane, how long the parasite can survive in feces outside the kissing bug, as well as strategies to prevent oral transmission.
http://www.nytimes.com/2005/04/12/health/12docs.html
Lawrence K Altman
April 12, 2005
NY Times
Chagas disease, which exists only in the Americas, has infected approximately 16 million people and causes about 50,000 deaths a year. It is a parasitic infection transmitted through the kissing bug (also known as the reduviid bug or the triatomine bug). The insect lives in cracks and crevices in poor housing where it bites people on the face, often while they are sleeping. It can also be transmitted via food contamination, blood transfusions, organ transplants, and from mother to child at birth.
The initial symptoms of Chagas disease are usually mild or nonexistent, so they are either construed as something else or simply go unnoticed. It usually takes decades for the disease to cause death by slowly damaging heart muscle, the esophagus, and colon, and by that time drugs cannot reverse the damage. The exact mechanism of the disease are still under investigation, although scientists have several hypotheses, including that it might be an autoimmune disease, or that the parasite causes an overly aggressive anti- parasite inflammatory response due to chronic presence of the parasite, as described in a later article.
However, in this particular outbreak described by the article in Brazil, symptoms did present themselves within a few days of the outbreak, which was apparently transmitted orally through contaminated sugar juice. The juice was pulled off the market and people who were anywhere in southern Brazil at the time were advised to get medical checkups if they drank sugar cane juice. The symptoms included fever, headache, muscle aches, vomiting, and a rash. Many people also experienced swollen lymph glands and spleen, abdominal pain, intestinal bleeding, jaundice, and encephalitis.
There are 2 drugs currently available—Benzonidazol, made by Roche, and Nifurtimox, made by Bayer. These drugs seem to be effective for treating Chagas disease in its early stages. Doctors are not sure why symptoms in this outbreak are more immediate and severe. One theory is more parasites entered the body through food than would have found their way to blood from a bite. Another theory is it might be an usually virulent strain of the Chagas parasite.
More research is needed to see how the bugs were deposited in the sugar cane, how long the parasite can survive in feces outside the kissing bug, as well as strategies to prevent oral transmission.
http://www.nytimes.com/2005/04/12/health/12docs.html
What is Chagas disease?
The purpose of this blog is to examine the biotechnology involved in the treatment and prevention of Chagas disease. Chagas disease is a parasitic infection endemic to and very prevalent in Latin America. It is caused by Trypanosoma cruzi, a microscopic parasite spread by triatomine bugs, commonly called “kissing bugs” or “assassin bugs.” The disease is spread when the bugs’ feces are rubbed into a bodily orifice or into a cut or abrasion of the skin. The parasites can also be transmitted through blood or food. While no severe symptoms manifest immediately after exposure, a significant portion of Chagas sufferers will develop severe heart disease or intestinal malformation about 20 years after infection.
It is estimated that 8-11 million people in Central and South America are infected, and that approximately 50,000 people die annually because of Chagas. There are few good treatment options, and development of new ones has been slow.
This blog will explore these as well as other issues concerning Chagas disease. The mechanism of the disease is still not completely understood, and it may be an autoimmune disease, or involve a strong inflammatory response, a theory that we will discuss. We will also explore treatment options for Chagas disease, including heart transplants, bone marrow cell transplants, and current and future drug options. Another possible solution involves genetic engineering of bugs, which could curtail or prevent the bugs from spreading the illness.
Chagas disease is concentrated in areas of poverty, thus it is not one of the more lucrative problems to solve, which perhaps accounts for the few drug options currently available, and with new drugs being developed, pricing and access will be significant issues.
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