Posts Tagged 'endtheneglect'

New routes to Chagas…

On March 5th 2001, a 37 year old woman went into surgery to have a kidney and pancreas transplant from a donor that had already passed away. Once discharged, she returned to the hospital six weeks later to be treated for a sudden onset of fever (of unknown origin). She would die six months later, on the first week of October.

What turned out to be the first recognised case of a T. cruzi infection through solid-organ transplantation in the Unites States, came after the physician identified the parasites in a peripheral blood smear. Upon identification the physician immediately notified the Centre for Disease Control (CDC). Upon further investigation it was discovered that other patients had received infected organs from the same donor. A 32 year old woman who had received the liver, and a 69 year old woman who received the other kidney. Both organs were found to be infectious. The donor of the infected organs was an immigrant from Central America.

At the time, no protocol or policy was in place for the regular screening of organ donations for T. cruzi — something that was routinely done in Chagas endemic areas. And no test was licensed for screening organ or blood donors. Today, two Chagas tests are available, out of a full complement of 60 that are licensed and routinely used to screen organs and blood donation for a wide range of infectious agents (including HIV, hepatitis, and west nile virus).

After the infection was detected, all three women were treated with nifurtimox — a drug not available in the US at the time. And a drug, over ten years later, still only has a single manufacturer. Today, nifurtimox, a drug that dates back to 1960, is available for US$48 per treatment regimen — the equivalent of a month of a Bolivian miner’s salary.

Of the three women that were infected, it was only the 69 year old woman that would survive the parasitic infection. In the most severe case, it was death as a result of immunosuppression. The woman who received the kidney and pancreas transplants, was the most immunosuppressed of the three patients. She died even after completing a full course (4 months) of treatment with nifurtimox.

Dorsal view of the “kissing bug”, Triatoma infestans

The original organ donor, the immigrant from Central America, most likely acquired Chagas from the triatomine kissing bug. As it bites, the insect carrying the parasite deposits faeces on the victim’s skin, and when the person rubs the bite wound, the faeces containing the parasite enters the bloodstream.

Blood and organ donor screening programs across the Americas and North America have essentially eliminated transmission via this way. However, some cases still turn up. Add to that the lack of awareness of the disease among US healthcare providers complicates the issue.

Chagas, once thought of and regarded as an exotic disease, given little attention, is increasingly being diagnosed in non-endemic areas. In 2009 it was estimated that 300,000 people living in the US were chronically infected with the parasite. In Europe, Chagas has been reported from congenital transmission (from mother to infant), in a recipient of a bone marrow transplant, and among Brazilian immigrants of Japanese origin in Japan.

Patterns of emigration have drastically changed the epidemiology of this disease over the recent decades. Immigration is one reason, but not the only one.

A new study has shown that a high proportion of triatomine bugs collected in Arizona and California had fed on humans, while others were positive for T. cruzi parasite infection. This new study essentially indicates that the potential exists for vector transmission of Chagas disease in the US. Up until now, the most common result of a triatomine bite was an allergic reaction.

Featured image — source

Triatomine image — source

Originally appearing at Weir, E. (2006). Chagas disease: hidden affliction and visible neglect Canadian Medical Association Journal, 174 (8), 1096-1096 DOI: 10.1503/cmaj.051442 Machado, F., Jelicks, L., Kirchhoff, L., Shirani, J., Nagajyothi, F., Mukherjee, S., Nelson, R., Coyle, C., Spray, D., de Carvalho, A., Guan, F., Prado, C., Lisanti, M., Weiss, L., Montgomery, S., & Tanowitz, H. (2012). Chagas Heart Disease Cardiology in Review DOI: 10.1097/CRD.0b013e31823efde2 Stevens, L., Dorn, P., Hobson, J., de la Rua, N., Lucero, D., Klotz, J., Schmidt, J., & Klotz, S. (2012). Vector Blood Meals and Chagas Disease Transmission Potential, United States Emerging Infectious Diseases, 18 (4), 646-649 DOI: 10.3201/eid1804.111396

A Trojan Horse to fight disease…

Originally appearing at


From an ancient Latin poem comes the relatively simple concept — deliver the deadly blow within a Trojan horse. The Greeks used it to end the war against Troy after ten long years. In science it’s one of the new and unique ways scientists are coming up with to fight diseases in man. To fight the disease before it gets into the host — in the animals that transmit and spread such diseases. The goal to eliminate the disease within the fly by using something common to the fly — the bacteria that lies within. It’s a common theme that is gaining popularity. In science we call it paratransgenesis. A strategy that relies on weaponizing the simple bacteria that live inside the flies that transmit parasites.

New open access research published in BioMed Central’s Microbial Cell Factories uses such a trojan horse paratransgenesis technique that represents a new way researchers are looking to fight African sleeping sickness.

The same way there are bacteria within our gut and digestive system — aiding our digestion, providing the nutrients that we are unable to synthesize ourselves, and generally contributing to our being — the tsetse fly also contains bacteria (bacterial endosymbiont). Sodalis glossinidius is one such bacteria.

The bacterial endosymbiont of the tsetse fly can be found in many places within the tsetse fly. Both inter- and intracellularly in the fly midgut, muscle, fat body, milk glands, and salivary glands. They can be found everywhere in the fly, but more importantly, everywhere that counts — everywhere the trypanosome invades. That seems to be the great advantage of using this bacteria as a delivery mechanism.

With this bacteria, which naturally lives in the tsetse fly, the researchers working in Belgium have been able to turn the bacteria against the trypanosome. They modified the bacteria’s genome to secrete a single domain antibody. These antibodies, which bind to the surface of the parasite, are the first stage in producing targeted nanobodies which could kill, or block, trypanosome development.

The technique proved tricky, and a delicate one to get right. The most important factor was that the growth of the mutated bacteria was unaltered, increasing their chances of survival within the fly, and meaning the trypanosome had less of a chance to overcome the attack.

Such a technique has already been done for other diseases of note — dengue, malaria, and Chagas disease. More and more, the foundation is being laid for a new kind of disease prevention strategy.

Coutinho-Abreu, I., Zhu, K., & Ramalho-Ortigao, M. (2010). Transgenesis and paratransgenesis to control insect-borne diseases: Current status and future challenges Parasitology International, 59 (1), 1-8 DOI: 10.1016/j.parint.2009.10.002

De Vooght, L., Caljon, G., Stijlemans, B., De Beatselier, P., Coosemans, M., & Van Den Abbeele, J. (2012). Expression and extracellular release of a functional anti-trypanosome Nanobody(R) in Sodalis glossinidius, a bacterial symbiont of the tsetse fly Microbial Cell Factories, 11 (1) DOI: 10.1186/1475-2859-11-23

Durvasula RV, Gumbs A, Panackal A, Kruglov O, Aksoy S, Merrifield RB, Richards FF, & Beard CB (1997). Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria. Proceedings of the National Academy of Sciences of the United States of America, 94 (7), 3274-8 PMID: 9096383

The Mysterious Disease… Buruli ulcer

Repost: originally appearing at April 29, 2011…

Imagine for a moment you don’t live where you live. Let’s say you live in Benin, or Togo, or Côte D’Ivoire, or perhaps Ghana (we can even add Australia to the list). Perhaps one day you notice on your ankle a small, somewhat pointed elevation of the skin. A nodule. What you have is so painless you consider it inconsequential – it will clear up in a few days. You awake one morning with a slight fever. For this particular ailment it would be rare to have a fever, but not unheard of. Where you normally reside “man flu” is the worst-case scenario you can think of. In Contonou, Benin, you can name at least three diseases that start with fever-like symptoms and could end with your death. Your niece died from one of them – before her fifth birthday, and the other caused blindness in your uncle. But this isn’t any of those.

After a few days this nodule is now the size of a boil. In Washington DC, a boil can be excised. In Togo this is worse than a mere boil. Your foot has swollen – so much that its hard to stand upright. Even more disconcerting is that this all comes without any pain. What follows can only be described as horrific. A painless necrotizing skin lesion, followed by ulcer and scar formation. Before you know it, your foot is being eaten away from the inside. The lesion grows and grows, oozing fluid and puss. A wide painless ulcer now covers a large area of your lower limb.

With this disease early diagnosis makes all the difference – but it is often rare. Surgical excision of the infected tissue has long been the first port of call. Today, along with surgery, you are given the antibiotics streptomycin and rifampin for 8 full weeks. That is if it was caught at an early stage. Your doctor did not know what it is until it was too late, as there are four other diseases that cause skin lesions and ulcers.

With treatment lesions heal but with permanent scarring and contractures which limit movement in your limb. You have no outer skin on the right side of your foot. A skin graft, taking skin from another part of your body, to patch up the infected area is needed. Imagine a small child of less than 15 years of age needing a skin graft. The lesions are sometimes so large that finding enough healthy skin to graft on is impossible. Eventually it will invade your bones, leading to severe disabilities and deformities. Maybe they will have to amputate. Any pain you experience will be due to secondary infections. Secondary infections that might also kill you.

What you have is the second most common bacterial infection we know of — Mycobacterium ulcerans. The bacteria, produces a toxin — mycolactone. The toxin is necrotizing and immunosuppressive, permeabilising soft tissue — eating away until there’s nothing left. In Ghana, Togo, Benin, Washington DC, Côte D’Ivoire, or France, Buruli ulcer is not on the list of diseases you know about. It wouldn’t matter anyway as you would have no idea how you caught it. Was it a mosquito? Infected water? Aquatic bugs? In humans, transmission and infection of the bacteria is unknown. On the shores of Lake Volta, Ghana, some call the disease vengeance while others call it witchcraft. Social stigma is a phrase pregnant with so many definitions – but largely meaningless until it happens to you.

Buruli ulcer left ankle EID

For lack of a better metaphor – if there was a popularity contest for neglected tropical diseases, Buruli ulcer is probably the least popular of neglected diseases. Being unpopular at being neglected might sound like a contradiction in terms but Buruli ulcer hasn’t got a famous person or celebrity face attached to it. We’re still talking metaphors. George Clooney has bigger fish, or rather mosquitoes, to fry. Even in some parts of Europe chikungunya and Dengue fever get more column inches than Buruli ulcer.

“Significant progress has been made in the past 10 years in knowledge of Buruli ulcer, investments in related research, control of the disease, and improvement of tools for case diagnosis and development of treatment protocols. Substantial achievements have been made in diagnosis, treatment, immunology and epidemiology.”

This could have been the opening paragraph to any report on any neglected tropical disease. In fact, that was the second paragraph to the Contonou Declaration in March 2009. What sets Buruli ulcer apart from most other neglected diseases is the next line:

“Despite these achievements, little is known about the exact mode of transmission of the disease, and there is no simple diagnostic test usable in the field.”

All neglected tropical diseases suffer from lack of interest, but Buruli ulcer is a special case. At all levels not much is known. A mysterious disease indeed. The point is not that its a tiny little disease that we know almost nothing about – the point is that we know almost nothing about. It is an emerging disease, named after Buruli county in Uganda, which saw many cases during the 1960s – and only now given prominence after a former Director-General of WHO encountered the debilitating tropical disease. Rolling back the scourge of the diseases that are already endemic is as much a priority as combating those yet to emerge.

Significant first steps have been made in drawing the attention of the world to the suffering caused by this “mysterious” neglected disease. The Global Buruli Ulcer Initiative (GBUI) was established in 1998, dedicated to doing all those things international agencies do that is necessary to combat disease; raising awareness, improve access to early diagnosis and treatment, and promotion of research to develop better tools for treatment and prevention. The World Health Organisation has recently extended its agreement with the pharmaceutical company Sanofi-Aventis to provide free drugs to treat some of the most neglected tropical diseases as well as support for control programmes for Buruli ulcer.

Buruli ulcer is not a disease measured in the human death toll — rather the personal burden to the individual. Morbidity and disability.

“It may not kill but it destroys lives.”

Stienstra Y, van der Graaf WT, Asamoa K, & van der Werf TS (2002). Beliefs and attitudes toward Buruli ulcer in Ghana. The American journal of tropical medicine and hygiene, 67 (2), 207-13 PMID: 12389949

Walsh DS, Portaels F, & Meyers WM (2011). Buruli ulcer: Advances in understanding Mycobacterium ulcerans infection. Dermatologic clinics, 29 (1), 1-8 PMID: 21095521

Trypanosomiasis has kept Africa green…

Originally appearing at, Dec 14 2011…

“Trypanosomiasis has kept Africa green…”

The quote above comes from a book I can’t remember by an author whose name escapes me. In essence, it alludes to the inextricable relationship and balance that exists between all things on our planet, particularly the relationship between man and his environment. For a long time, we have known about the influence diseases can have on us, but we are only now beginning to realise its full extent.

The delicate relationship and inter-connected influence between human populations, climate, and the ecology of disease (vector-borne or otherwise) has unfolded over evolutionary time.

Genetically, some populations are predisposed to particular diseases. A study published in Science last year, showed African-Americans have higher rates of kidney disease than European-Americans. The reason, as postulated by the researchers, was due to variants of a gene (APOL1), common in African chromosomes but absent from European chromosomes. The gene codes for a serum factor that lyses (or harms) trypanosomes. It seems the evolution of a critical survival factor in Africa now contributes to the high rates of kidney disease in African-Americans.

Changes in African climate in the last 5-6 million years are thought to have mediated important modifications in the African environment and in the animals that live there. As the rivers changed, and as plant and animal species adapted to a changing climate, disease was brought to areas where it wasn’t before. These phenomena have marked important milestones in the evolution of humans and their predecessors.

The expansion of savannah grasslands influenced the evolution and behaviour of early humans, as well as representing a turning point in the relation between apes and primate-infective trypanosomes. The two diseases of trypanosomiasis (rhodesiense and gambiense) perhaps drove early man ‘out of Africa’ — in an attempt to avoid tsetse infested areas of the Rift Valley.

Then came colonisation — disrupting the balance between parasite, fly, people, flora and fauna. Which, for the sake of brevity, leads us to where we are today. After witnessing the fall and rise of trypanosomiasis, we are now witnessing the fall. The question is if a rise will follow — a rise due to anthropogenic climate change. With the COP17 talks in Durban in full swing, the subject is what to do with the ever-warming world that we live in. How to combat the man-made climate change, and how to prepare for its irreversible effects. The hope is to secure a new legally binding agreement to succeed the Kyoto protocol. CO2 emissions last year were the highest on record, as shown by the International Energy Agency and without increased action, the cost of a 2-4°C rise in temperature will no longer be measured in dollars and cents, and instead in human lives.

The next decades are crucial to climate change, as we approach, closer and closer, the point of no return. Major environmental and human modifications are occurring in an Africa already ripe with neglected diseases.

Furthermore, the ongoing environmental changes as well as changes in human population will have drastic repercussions on the epidemiology and the spatial distribution of sleeping sickness in the region.

The question for the now and for the future — in particular relating to health and disease — is how to mitigate for an ever changing climate. And to understand how climate, human population dynamics and environmental changes will continue to influence not just trypanosomiasis, but other neglected diseases over time.

Genovese, G., Friedman, D., Ross, M., Lecordier, L., Uzureau, P., Freedman, B., Bowden, D., Langefeld, C., Oleksyk, T., Uscinski Knob, A., Bernhardy, A., Hicks, P., Nelson, G., Vanhollebeke, B., Winkler, C., Kopp, J., Pays, E., & Pollak, M. (2010). Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans Science, 329 (5993), 841-845 DOI: 10.1126/science.1193032

Cecchi G, Courtin F, Paone M, Diarra A, Franco JR, Mattioli RC, & Simarro PP (2009). Mapping sleeping sickness in Western Africa in a context of demographic transition and climate change. Parasite (Paris, France), 16 (2), 99-106 PMID: 19585887

What had I twaught…


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