Archive for February, 2012

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

Hope and health behind bars…

Prison winter

“without hope, a man in prison is nothing.”

Those were the words declared and despaired by Clarence Norris while serving a life sentence in an Alabama jail. Clarence had a long and torturous ordeal. He was arrested in Alabama in 1931, sentenced to the electric chair three times, had his sentence commuted once, released on parole twice, broke his parole the same number of times — the final time he managed to remain free until his death from Alzheimer’s in 1989.

The trials and tribulations of Clarence Norris, the last of the nine Scottsboro defendants, serves as an example to the fact that the eternal optimist not only lasts longer in prison, but survives prison.

In contrast to the growing regard for the psychological construct of hope in medical and psychological arenas, hope has not yet found a place in the field of criminology or in relation to the general health of imprisoned populations.

Not only is hope an essential requirement in prison, it is ambiguously important in prison for health. As prison populations increase, so does the associated medical care… and in countries like the US, that imprisons more and more of its citizens, that cost becomes substantial. So it makes sense to attack the problem at the root of the cause.

Inmates usually have a wide variety of health problems ranging from arthritis, asthma, and backaches, to more serious diseases such as hepatitis, HIV, and tuberculosis. Not to mention the cases of infection that break out as a direct result of incarcerated populations. This is as a result of the lifestyle of inmates as much as anything else (prevalence of drug and alcohol abuse, and associated health problems, is high among offenders). And sometimes, unfortunately, getting ill in prison can be a death sentence.

In a sample of 501 jail inmates, physical health concerns were evaluated in their relation to optimism. Examining if physical health concerns increased or decreased over the period of incarceration, and whether optimism was associated with physical health. The results, obviously with something like this, were inconclusive. To tease apart optimism in itself is a hard task.

Generalities in associating the eternal optimist with employing more effective and adaptive coping strategies, and being able to distinguish controllable situations from those that are uncontrollable and thus are more likely to demonstrate acceptance in the face of events that they cannot control, largely have no merit based on the data observed.

One fact is certain; that the realisation of policy makers and those charged with running correctional communities of the full extent of health problems within prisons pose a clear public health opportunity… and a unique opportunity to confront it.

Heigel, C., Stuewig, J., & Tangney, J. (2010). Self-Reported Physical Health of Inmates: Impact of Incarceration and Relation to Optimism Journal of Correctional Health Care, 16 (2), 106-116 DOI: 10.1177/1078345809356523

Wilper AP, Woolhandler S, Boyd JW, Lasser KE, McCormick D, Bor DH, & Himmelstein DU (2009). The health and health care of US prisoners: results of a nationwide survey. American journal of public health, 99 (4), 666-72 PMID: 19150898

This is exactly how super-villains are created…

via BBC News

A group of researchers has created the first community-run biology laboratory in New York City.

The lab is an effort to provide a home for amateur scientists, as well as professionals looking for a space away from academia and business.

The co-founder of Genspace says it is “crucial that this lab exists” in order to foster creativity in the sciences.

A group of scientists not content with the status quo, angry how academia doesn’t recognise their genius, breaking away to form their own society where they can do what ever experiment takes their fancy? Yeah… the end is nigh.

“It’s a boy!” A phrase less common among Black Women…?

20070401 It's a Boy

More boys are born than girls. For every 100 girls born, 105 boys occur. An odd quirk of nature that occurs throughout the world. Except, that is, when it comes to women of sub-Saharan African descent.

Right from birth, men across the spectrum suffer a high attrition rate — leading to the tendency of more females surviving than males. By age 65 and over, the trend is set — there are substantially more females than males in most countries. Women survive. Men don’t.

It seems, from a point-of-view, that from birth the boy is fighting a losing battle. The boy is three to four times more likely than the girl to have developmental disorders like autism and dyslexia. The girl will learn language earlier and develop richer vocabularies. The list of handicaps do not end there. The girl will demonstrate insight and judgment earlier in adolescence, not to mention the girl hears better. Teenage boys are more likely to commit suicide than girls and are more likely to die violent deaths before adulthood.

You would think that after all of this the tendency for more boys to be born would be a futile attempt by mother nature.

To some this is merely a question of numbers and statistics, but to others the numbers hold questions about societies, lives, and the unapparent deep-seated socio-economic differences between us. In every country the end statistic is the same. More males. Except women in sub-Saharan Africa give birth to more females than non-Black women in all other parts of the world. A curious fact that seems to fore-go national or continental boundaries, as similar trends have also been observed in the United States among the African-American population.

In general, across a population, trends in sex ratio cannot be attributed to any single set of risk factors. And dozens of factors, too numerous to list, can be attributed to the central question of why more males are born and why there seems to be a decline. Even events occurring after conception may perhaps skew the outcome of a male.

So, is it really a case of Black Women giving birth to more females? Or does it just seem that way? The fact that fertility is generally and substantially higher in sub-Saharan African women as well as African-American women could just simply point to the fact that the more you give birth the less likely it is that it will be a boy.

Perhaps it takes more calories to create a boy than it does a girl. Lower caloric intake might cause an unequal sex ratio at birth as foetal sex and maternal diet are linked. The exact nature of that link is as of yet unidentified.

A study of 740 British women showed that a majority of those who had the highest energy intake gave birth to boys. A statistic like this can easily be extrapolated and compared to those mothers in less developed nations that consume fewer calories, but easily breaks down when you displace it to Black Women in the US.

In the end the answer, it seems, is yet to reveal itself. But one thing is certain — we are approaching parity. A 1 to 1 sex ratio seems to be the overwhelming trend that we are heading to. The shrinking sex ratio. Black Women represent the first racial group where this trend can be seen evidently. For what reason and as a result of what stimulus still remains to be seen.

Davis, D., Webster, P., Stainthorpe, H., Chilton, J., Jones, L., & Doi, R. (2007). Declines in Sex Ratio at Birth and Fetal Deaths in Japan, and in U.S. Whites but Not African Americans Environmental Health Perspectives, 115 (6), 941-946 DOI: 10.1289/ehp.9540

Amadu Jacky Kaba (2008). Sex Ratio at Birth and Racial Differences: Why Do Black Women Give Birth to More Females Than NonBlack Women? African Journal of Reproductive Health, 12

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

What had I twaught…

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