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Archive for December, 2009

Dec 28 2009

TB research findings raise concerns

Posted by: Paul Chinnock - Editorial Team

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Could some tuberculosis bacteria have evolved so that they have actually become dependent on one of the key drugs used in TB treatment? A case study (1) in China raises this disturbing possibility. Bacteria isolated from a TB patient in whom treatment had failed were found to grow poorly without the antibiotic rifampicin and to grow better in its presence. The authors of the report say that this case demonstrates the importance of drug susceptibility testing, and that doctors should be prepared to remove rifampicin from a patient’s treatment regimen if resistance to the drug has been demonstrated.

Another TB research article published in recent days reports disappointing findings. One of the reasons why it is so difficult to control this disease is the ability of the bacterium Mycobacterium tuberculosis to lie dormant for many years, then suddenly emerge to cause serious disease. It was proposed a few months ago by Swedish researchers that M. tb. might have the ability to turn into dormant, highly-resistant spores. If true, this would provide promising new avenues of research in the fight against TB. However, a new study (2) by US scientists has found no evidence that M. tb can actually form spores.

Working with the organism Mycobacterium marinum, often used in TB research, the researchers used genomic techniques to demonstrate that mycobacteria are unlikely to be able to form spores. They were also unable to detect the presence of spores by light microscopy or by testing for heat-resistant, colony-forming units in aged cultures of M. marinum. And they failed to recover heat-resistant colony-forming units from frogs chronically infected with M. marinum. So it may be back to the drawing board to find an explanation for TB dormancy.

References

1. Zhong M, Zhang X, Wang Y, Zhang C, Chen G, Hu P, Li M, Zhu B, Zhang W, Zhang Y (2010). An interesting case of rifampicin-dependent/-enhanced multidrug-resistant tuberculosis. Int J Tuberc Lung Dis; 14(1):40-44. Abstract on PubMed. (Full paper not open access.)

2. Traaga BA Driks A, Stragier P, Bitter W, Broussard G, Hatfull G, Chu F, Adams KN, Ramakrishnan L, Losick R (2009). Do mycobacteria produce endospores? Proc Natl Acad Sci USA; Abstract published online before print (Full paper not open access.) A summary is available on EurekAlert.

Dec 28 2009

Malaria vaccine uses nasal route

Posted by: Paul Chinnock - Editorial Team

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Japanese researchers have claimed to be the first to use a nasal vaccine to successfully block transmission of the malaria parasite from mosquitoes to mice. Their finding may lead on to the development of such a vaccine for use in the prevention of malaria in humans.

Malaria vaccines based on ookinete surface proteins (OSPs) of the malaria parasite are known to block oocyst development within feeding mosquitoes, thus disrupting the parasite’s life cycle. The Japanese team - based at the Tropical Biosphere Research Center, University of the Ryukyus - set out to investigate whether a nasally administered OSP vaccine could effectively block parasite transmission in vivo.

Writing in the journal Infection and Immunology, they report that mosquitoes that took a blood meal from nasally vaccinated mice were subsequently unable to pass on the parasite to other mice as the fertilization cycle had been interrupted.

Reference
Arakawa T, Tachibana M, Miyata T, Harakuni T, Kohama H, Matsumoto Y, Tsuji N, Hisaeda H, Stowers A, Torii M, Tsuboi T (2009). Malaria ookinete surface protein-based vaccination via the intranasal route completely blocks parasite transmission in both passive and active vaccination regimens in a rodent model of malaria infection.Infect Immun; 5496-500. Abstract on PubMed. (Full paper is not open access.)

Dec 23 2009

Dwindling funds for malaria could reverse recent gains

Posted by: Paul Chinnock - Editorial Team

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Patrick Adams writes…

A number of countries have made great strides in terms of malaria control, resulting in reductions of over 50% in the number of malaria cases in more than a third of affected countries.

According to the World Malaria Report 2009, the progress was made possible by major increases in donor country contributions to the Global Fund, leading WHO Director General Dr Margaret Chan to declare that “development aid for health is working”.

The report notes, however, that funds for malaria “are disproportionately concentrated on smaller countries with lower diseases burdens”. The report recommends that, in order to maintain the gains made to date, “more attention be given to ensuring success in large countries that account for most malaria cases and deaths”.

Yet more worrying, some experts say, is the possibility that donor contributions may have peaked. Last February, it was announced that the Global Fund faces a $5 billion shortfall through 2010. In order to address the gap, the fund would impose a series of “efficiency cuts”, “uncertainty cuts” and “delays”. Reporting on the Global Fund’s 20th board meeting in Addis Ababa last month, policy analyst David Wendt speculated that these measures could put at risk more than US$ 1 billion of the US$ 2.64 billion of approved Round 9 budgets.

“The prospects for increasing donor contributions to the Global Fund are small,” says Dr Matthew Lynch, director of the Global Program on Malaria at the Johns Hopkins Bloomberg School of Public Health. “Given the delays associated with Rounds 9 and 10, even maintaining the current GFATM funding levels is going to be a stretch.” And though the funding level for Round 10 has yet to be determined, he says, “it’s not likely to be huge”.

Lynch adds that while the US government “is doing a lot,” and the President’s Malaria Initiative (PMI) is “fully-funded and doing a very good job,” these bilateral contributions represent just a fraction of Global Fund amounts. The global recession may be partly to blame, he says. But even so, the basic donor-recipient paradigm has to change.

“I do still believe ‘cautious optimism’ is appropriate,” says Lynch, referring to WHO Director General Dr Margaret Chan’s reaction to the global report findings. “Mortality levels are declining. There are two more years to run on Round 8 funds. And I think we will demonstrate some substantial returns-on-investment. But countries are going to have to recognize those returns-on-investment and start shouldering more of the financial load.”

Richard Tren, director of Africa Fighting Malaria, has been among the more vocal advocates calling for more domestic funding for malaria. He has said that external funding alone will not be sufficient, and, along with many others, he’s questioned the distribution of limited aid dollars on wealthy countries like China and India.

China is the third-richest nation overall, India the fifth. In the Global Fund’s 9th round of funding since 2002, China’s total funding request for a malaria “National Strategy Application” (NSA) was roughly $ 176.5 million. (An NSA is a funding channel that allows countries to request support for strong existing national HIV/AIDS, TB and/or malaria strategies). Meanwhile, India requested more than US$ 113 million for malaria.

But are these countries indeed “rich”? In per person terms, China is poorer than 132 countries; India is poorer than 166. Both have space programmes, but both also have extreme poverty.

Regardless, says Lynch, it’s clear that relying on donors will be increasingly risky for endemic country governments. It’s also likely, he says, that even households will need to make contributions as well. “Malaria elimination is a long-term goal, which means a long haul for maintaining high net coverage. The era of the free nets campaign may be rapidly drawing to a close.”

Dec 23 2009

Recommended holiday reading

Posted by: Paul Chinnock - Editorial Team

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The findings of research are often difficult to put into practice. Advances in health care and prevention often fail to live up to expectations when attempts are made to implement programmes in developing countries.

The Alliance for Case Studies for Global Health has collected case studies that provide information on current practices and the lessons learned - both positive and negative. The result is an attractively presented 210-page book, freely available online.

Drug and vaccine discovery, preventive initiatives and health systems strengthening all feature in the book. Infectious diseases - including malaria, TB and neglected tropical diseases (NTDs) - are the subject of many of the case studies reported. Whilst it is hard to single out individual case studies as being of particular importance, the descriptions of efforts to improve medical laboratory services in Malawi and Tanzania are definitely worth reading. So are the accounts of integrated NTD programmes in Rwanda, Burundi, Niger and Tanzania.

Expensively packaged publishing projects like this one can sometimes focus entirely on the positive, creating a false impression of what has been achieved. Whilst there is certainly good news to be found in the pages of this book, it adopts a realistic perspective throughout. There is much here to be learned.

Dec 23 2009

Nigeria’s “last case” of guinea worm

Posted by: Paul Chinnock - Editorial Team

Comments (1)

Earlier this year, as reported on TropIKA.net, former Nigerian head of state Yakubu Gowon, who has been intensely involved in the campaign to rid his country of dracunculiasis (guinea worm disease) predicted that 2009 would be the first year in which no guinea worm cases were reported there. As the year draws to a close, it looks like he was right.

The US Carter Center which has been at the heart of guinea worm eradication efforts says there have been no known cases since November 2008. According to the Center, the last person to have had the disease (a villager in the southeast of the country) has become a “minor celebrity”.

Two more years must pass without further cases before Nigeria is officially accredited as being free of the disease. Nevertheless, the achievement of the eradication efforts, which began in 1988, have been nothing short of astonishing. According to 1987 figures, there were 650,000 guinea worm cases in some 6,000 villages across Nigeria.

Nigeria joins 15 other countries that have rid themselves of Guinea worm disease since 1986. It is estimated that in 2009, fewer than 3,500 cases of the disease remain in four African countries: Ethiopia, Ghana, Mali and Sudan. It has hard to believe that just 20 years ago the total number of cases worldwide was approaching three million.

In Ghana there have been calls for opinion leaders to support community-based surveillance volunteers who are a key part of the plan to eradicate the disease there by 2014 - see Ghana News Agency report.

A recent report on Afrika.com notes that it is now six years since Uganda had any cases; WHO’s country director there has handed over an official certificate saying the coutry is guinea worm free.

Dec 23 2009

The role of temperature in infectious disease: a call for more research

Posted by: Paul Chinnock - Editorial Team

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The TropIKA.net Blog welcomes contributions from guest bloggers. We publish below a viewpoint from Guey Chuen (Oscar) Perng, Associate Professor, Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, USA: gperng@emory.edu. As always, we encourage comments on the views expressed in the blog. Please use the ‘Leave a Reply’ function at the end of the blog.

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Inconsistent results are common in investigations of human diseases. In addition to differences attributable to individuals’ genetic background, environment or food consumption, temperature may also be an important factor.

Temperature plays a critical role in the macro-environment; trees or flowers grow in defined geographical zones, and so do infectious diseases. Temperature also plays, perhaps, an even more critical role in the micro-environment, such as in the physiology of a cell.

Fever is a form of body response to a change in physiology. This may be the reason why most pathogenic infections are febrile - i.e. they induce a fever. In some infections, fever can last for several days and occasionally up to a week. In reality, such a long duration of fever is rare as, upon sensing fever, most people self-medicate or seek professional medical help; the majority of patients seek help when their fever lasts more than two or three days.

Most parents seek help for their febrile children promptly but, due to inattentiveness, some children may be feverish for several days before assistance is sought. In adults, tolerance levels for fever may be stronger and delays in seeking help are common. Thus, investigations on samples collected during the febrile period and results derived from these specimens must be interpreted cautiously. Fruitful and important information may be gained, especially when searching for biomarkers with a system biology approach, in structure-based drug design, or in the evaluation of diagnostic kits, but such investigations are based on normal temperature conditions.

Yes, fever involves only a change in body temperature of a couple of Celsius degrees. However, if we feel our body temperature rising to 38 degrees C, we may feel a little too hot; at 39 C we feel unwell, feverish and anxious; and at 40 C we we feel very concerned, even desperate. Thus, a change of a few degrees is sufficient to cause a noticeable effect on our physiology, which may have a much greater impact on cells or pathogens within our body. Cell physiology may have been changed significantly, the structure of proteins from host or pathogens may alter, and the specific antigens used for diagnostic kits (which are mainly based on the detection of antigen at normal temperature) may not be present.

Additionally, temperature is among the most important of the parameters that free-living microbes monitor. Microbial physiology needs to be readjusted in response to sudden temperature changes. Virtually every
biomolecule responds to temperature shifts by performing conformational changes, and this can be exploited for direct temperature sensing mechanisms to control the expression of heat shock, cold shock or virulence genes. Importantly - since the tertiary and quaternary structures of proteins are susceptible to temperature changes, and particularly to heat - several protein-dependent thermometers have evolved in nature.

Perhaps we need to give serious attention to the importance of temperature in the drug treatment of infectious diseases. Most drugs for pathogenic infections are given to the patient within febrile periods. The crystal structure of a particular pathogen protein derived at normal temperature may be similar to that derived at a higher temperature. However, it is possible that the dynamic space on which the drug is targeted may differ significantly. Drugs are designed to fit within gaps in crystal structure at normal temperature; they may not fit perfectly in structures at a higher temperature. Consequently, the efficacy of drug treatment may not live up to expectation. This may also favour the selection of parasite strains resistant to the drug and consequently the development of more virulent pathogens.

I urge a thorough and systemic investigation of the role that temperature plays in the search for specific biomarkers with a system biology approach, in structured-based drug design, and perhaps in the re-evaluation
the diagnostic kits with antigens prepared at different temperatures.

Dec 22 2009

Leishmaniasis research in Ethiopia

Posted by: Paul Chinnock - Editorial Team

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One of the most neglected of the infectious diseases of poverty, visceral leishmaniasis (kala azar), will be the subject of a new research project in Ethiopia.

The project, entitled “Studies on the ecology and transmission dynamics of visceral leishmaniasis in Ethiopia”, will seek to determine the drivers of transmission of the disease, of which there an estimated 500,000 cases worldwide annually. The worst affected region in Africa is southern Sudan and northwest Ethiopia.

The research will be carried out by the Hebrew University of Jerusalem Kuvin Center for the Study of Infectious and Tropical Diseases, supported by a $5 million grant from the Bill & Melinda Gates Foundation. For further information see press release.

Dec 22 2009

Call to introduce vaccine that could cut child death rates

Posted by: Paul Chinnock - Editorial Team

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Extensive research has demonstrated the effectiveness of rotavirus vaccination in reducing death rates in children. It is believed that rotavirus is the most common cause of severe diarrhoea and dehydration in under-fives, leading to some 527,000 deaths every year – 85% of them in Africa and Asia. WHO has recommended the inclusion of the vaccine in national immunization programmes worldwide. So far, however, many governments have been slow to act.

A report from IRIN News describes a meeting - held earlier this month in Dakar, Senegal - of the West African Rotavirus Advisory Board, at which health experts urged national governments in the region to introduce the vaccine with minimum delay. Professor George Armah,of Ghana’s Noguchi Memorial Institute for Medical Research, said that the evidence from research was clear and policymakers should now act: “Rotavirus is one of the major causes of diarrhoea deaths and hospital admissions. There are vaccines that are very effective and can radically reduce mortality and morbidity from rotavirus infection”.

Two rotavirus vaccines are available - one of them from GlaxoSmithKline which sponsored the Dakar meeting. Following a similar meeting in Kenya, a number of countries in southern and eastern Africa applied to the GAVI Alliance - the global public-private partnership to increase vaccine access – for assistance in introducing both rotavirus and pneumococcal vaccines.

Dec 22 2009

Good news from Ghana: TB treatment and cure rates are approaching target levels

Posted by: Paul Chinnock - Editorial Team

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By 2015, as part of the Millennium Development Goals, 85% of new cases of pulmonary tuberculosis should be successfully treated (using directly-observed treatment, short course [DOTS]). There are fears that many developing countries, particularly in Africa, will fail to hit this target. But Ghana is nearly there according to a report from the Ghana Broadcasting Corporation.

A forum in Kumasi heard that the present coverage rate is “almost 80%”.

Dec 22 2009

Dengue vaccine research expands in Latin America

Posted by: Paul Chinnock - Editorial Team

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Dengue fever was considered to be virtually absent from most parts of Latin America until the late 1960s, but since then case numbers have increased and the region is now one of the most badly affected parts of the world for this mosquito-borne viral disease.

Sanofi Pasteur, the vaccines division of the sanofi-aventis Group, has announced that it will be expanding its dengue vaccine clinical programme in Latin America with a new multicentre study in children and adolescents in Mexico, Colombia, Honduras and Puerto Rico.

The company’s candidate vaccine has been evaluated in clinical trials (Phase I, II) in adults and children from non-endemic (US) and endemic countries (Mexico, Philippines). Sanofi Pasteur reports that a balanced immune response against all four dengue serotypes was observed after three doses, and that the vaccine appears to be well tolerated. There are ongoing clinical studies with adults and children in Mexico, Colombia, Honduras, Puerto Rico, Peru, the Philippines, Vietnam, Singapore, and Thailand.

Further details are available in a company press release.