A new vaccine to protect against tuberculosis is urgently needed. Nowhere is the need greater than for HIV-infected people, who face very high risks of developing TB. A clinical trial in Tanzania has found that a new TB vaccine reduced TB infection rates by 39% amongst 2,000 HIV-infected patients.

The seven-year trial - a collaboration between Dartmouth Medical School, USA and Muhimbili Medical School, Dar es Salaam - employed a whole cell vaccine of the organism Mycobacterium vaccae, closely related to M. tuberculosis the disease agent responsible for TB. Patients in the trial had already received the standard BCG vaccination for TB.

The trial - known as the DarDar Study (Dartmouth-Dar es Salaam) - has already created considerable interest. The next steps are to improve manufacturing methods to support the production of the larger quantities of the vaccine needed for further studies and subsequent clinical use. Development work on manufacturing will be conducted by the Aeras Global TB Vaccine Foundation in Maryland, USA, in conjunction with the London-based manufacturer, Immodulon Therapeutics.

Reference
1. von Reyn CF, Mtei L, Arbeit RD, Waddell R, Cole B, Mackenzie T, Matee M, Bakari M, Tvaroha S, Adams LV, Horsburgh CR, Pallangyo K; the DarDar Study Group (2010). Prevention of tuberculosis in Bacille Calmette-Guérin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS; 2010 Jan 28. [Epub ahead of print]

The Internet allows open discussion to take place on a huge range of topics, including the implementation of programmes to control the infectious diseases of poverty. The excellent Topnaman blog on malaria presents a discussion of an article [1] in the Bulletin of WHO that criticised some aspects of the President’s Malaria Initiative’s (PMI) work in Angola. The intervention in question was the use of indoor residual spraying (IRS) of insecticide.

The core of the criticisms made is that intervention areas were selected on the basis of reported clinical diagnoses of malaria, unsupported by laboratory findings, and that this led to expensive control efforts taking place in areas where they were not necessary.

Published on the blog are a response from PMI to the original Bulletin article, followed by a comment on this from one of the article’s authors, Bill Jobin.

PMI say that the work conducted in a low-transmission area provided “experience and confidence” to enable subsequent activities in higher transmission areas. But Bill Jobin argues the case for programmes that are based on data from microscopic diagnoses in appropriate sentinel populations. “Then we will know what the problem really is, and where to put our efforts”, says Jobin.

Reference
1. Somandjinga M, Lluberas M, Jobin WR (2009). Difficulties in organizing first indoor spray programme against malaria in Angola under the President’s Malaria Initiative. Bull World Health; 87(11):871-874.

A US doctor working in Cape Town, South Africa says that TB infection rates of children are “at the highest levels ever recorded since the onset of TB chemotherapy in the middle of the last century”. He calls for more research to develop new ways of treating the disease.

Dr Robin Wood is Director of the Desmond Tutu HIV Centre at the University of Cape Town. In a blog in the Huffington Post he speaks of the high TB rates his research team have identified during a clinical trial: “By the time children enter school at age 5, 20 percent are already infected with TB. By the time they reach the age of sexual maturity, 13 years, 50 percent are infected. And between the ages of 24 and 28 - the years of peak prevalence of HIV - 80 percent are infected”. Also serious is the growing number of cases of drug-resistant forms of TB.

He contrasts current funding for TB with efforts being made against H1N1 and expresses concern that the global economic crisis could lead to cuts in research budgets. He want to see “increased research of all the stages of TB development”.

In the good old days, most cases of malaria responded to chloroquine (CQ) treatment and there was a high level of public awareness as to the name of this drug. However, as an editorial in the Tanzanian online newspaper ThisDay points out, in this era of CQ resistance, very few people have a clear idea of what drug they or their children need when they suspect they have malaria.

Referring to a 2008 study [1] the article stresses that a high proportion of the antimalarials on sale in Africa are likely to be ineffective. The situation is confusing and people need guidance. ThisDay says, “There is need for the government to make an aggressive effort to remove all inappropriate and ineffective drugs (most of which are counterfeit products) from the shelves, while at the same time we look into the way of bringing down the costs of other effective drugs”. Governments also need to provide more information to assist the public in their efforts to choose effective drugs from the range of products now available to them.

Reference
1. Bate R, Coticelli P, Tren R, Attaran A (2008) Antimalarial Drug Quality in the Most Severely Malarious Parts of Africa – A Six Country Study. PLoS ONE 3(5): e2132.

Research aimed at developing new treatments for the infectious diseases of poverty (IDPs) has generally been of very little interest to the pharmaceutical industry. The people with these diseases are, by definition, poor and would be unable to afford expensive new drugs. Hence there is no profit to be made.

However, the economies of some of some countries with high rates of IDP incidence are now growing rapidly. China is a case in point. Tuberculosis is the country’s number one infectious cause of death, claiming some 160,000 lives annually. China has the world’s second highest number of TB cases, after India.

But thanks to its economic success China can now pay for TB drugs. A study by the market research group ResearchAndMarkets says that China’s demand for TB drugs has grown at a fast pace in the past decade. It predicts that, in the next five years, both production and demand will continue to grow. The study examines China’s economic trends, investment environment, industry development, supply and demand, industry capacity, industry structure, marketing channels and major industry participants. (Unfortunately the full report is only available for a very high fee - around $6,000.)

What impact will economic growth in IDP-endemic countries have on the research priorities of the pharmaceutical industry? Certainly countries that have both IDPs and money become a more interesting prospect. Many countries with growing economies are, for example, afflicted by dengue fever and by malaria. Will industry come to regard these as more attractive areas for research than previously?

Some of the highest rates of infectious diseases, however, are in Africa where economies are still struggling. The profit motive for addressing their disease burden is still lacking.

A report in Business News says that drug giant Novartis has had no success in trying to raise funds from the public and philanthropic sectors to to finance development of drugs against neglected illnesses including dracunculiasis (guinea-worm disease), malaria and tuberculosis.

Novartis wants to raise about $1 billion annually for 10 years to create a fund that companies and institutions could draw on to develop treatments for diseases that get little drug-development interest because they wouldn’t be profitable. The US and European governments, the Bill & Melinda Gates Foundation and the Wellcome Trust have all apparently been approached without success.

Paul Herrling, head of Novartis corporate research says, “It’s two years I’ve been working on this thing, and I don’t have a cent”.

An intriguing report from Ecuador says that scientists have been given government backing to attempt to transform a vaccine used to protect against yellow fever so that it becomes active against malaria and dengue.

Researchers from the University of Guayaquil will apparently use the transformed vaccine in a study based in a military hospital - see report from SperoNews.

One reason why research is needed to develop new antimalaria drugs is the the appearance of resistance to drugs currently in use. The mainstay of malaria treatment is now artemisinin combination therapy (ACT) but many ACTs in circulation are faked or substandard versions. These products tend to contain low doses of active drugs, and when the malaria parasite is exposed to such doses the development of resistant strains is more likely to occur.

Action against fakes has generally been inadequate. News that fakes have been intercepted and seized by the authorities is always welcome therefore. AllAfrica.com reports that Nigeria’s National Agency of Food and Drugs Administration and Control (NAFDAC) has impounded a consignment of nine packages of the antimalarial Lonart (artemether plus lumafantrine) valued at Naira 10 million ($67 million). NAFDAC made the discovery during routine checks at Lagos airport and employed their recently acquired drug testing equipment to establish that the drugs were faked.

While the story is encouraging, one can only speculate as to how many fake antimalarials (and other drugs) are still entering countries like Nigeria undetected.

Tuberculosis control efforts in China are claimed to have saved over three-quarters of a million deaths and prevented 20 million new cases of the disease over the last eight years.

According to the Xinhua.net news service, the figures were given at a joint meeting of China’s health ministry with the World Bank and the UK Department for International Development, which supported the TB control programme based on DOTS (directly observed treatment, short course).

China’s population of TB patients was estimated as 4.5 million in 2009, the world’s second largest after India.

Arguing that the burden of neglected tropical diseases (NTDs) is not just dependent on climate, but mainly related to incidence of poverty, an editorial [1] in PLoS Neglected Tropical Diseases details the large number of neglected infections of poverty in the Arctic region and calls for greater research into these devastating, debilitating and sometimes deadly diseases.

“One of the most dramatic illustrations of poverty as the single most important determinant of neglected infections among human populations is the observation that these conditions occur among the poorest people in the Arctic region,” states the paper’s author, Dr Peter Hotez, President of the Sabin Vaccine Institute and Distinguished Research Professor at George Washington University. He says there are a dozen neglected infections of poverty in the region, most of which are food-borne.

There are seven countries with significant territory in the Arctic, including Canada, Finland, Greenland, Norway, Russia, Sweden and the United States (Alaska). Iceland is also sometimes included in the definition of the Arctic. Approximately two million people live north of the Arctic Circle, with 60% living in Arctic Russia. A high percentage of these populations represent aboriginal or indigenous peoples. In Canada, the most indigenous people of the Arctic are the roughly 50,000-60,000 Inuit.

Dr Hotez notes that it is not surprising that neglected infections of poverty are found in the Arctic given the region’s socioeconomic deprivation, stress, and environmental degradation. Indigenous people living in the Arctic region suffer disproportionately from high rates of chronic conditions such as smoking, drinking and obesity and have a life expectancy 8-12 years shorter than the non-indigenous population. “Indeed, overall the world’s indigenous people in general suffer from high rates of infections such as ectoparasitic skin infestations, upper and lower respiratory track infections, and central nervous system infections from bacterial invasive organisms and tuberculosis, childhood illnesses, diarrheal and intestinal helminth infections, urinary tract infections, bone and musculoskeletal infection and in some cases, HIV/AIDS and malaria,” Hotez writes.

Many of the parasitic infections are food-borne and transmitted through uncooked or inadequately prepared meats from polar bear and sea mammals such as walrus or seal. Other infections are zoonoses (diseases that can be transmitted from animals to humans) transmitted from livestock unique to the Arctic region such as reindeer and elk.

Toxoplasmosis is one of the neglected infections of poverty endemic to the Arctic region. In terms of prevalence and diseases burden, toxoplasmosis is probably the most important parasitic infection in the North American Arctic. Toxoplasmosis can seriously impact people with a weakened immune system. The parasite can also cause encephalitis, neurologic diseases and can also affect the heart, liver and eyes. “Given the high rates of toxoplasmosis, a program of newborn screening for these populations would identify at-risk infants eligible for antiprotozoan chemotherapy,” Hotez concludes.

Dr Hotez also calls for further study of neglected infections of poverty throughout the Arctic region, including among the indigenous populations living in Russia and Siberia. “Ultimately, programs for prevention of neglected infections may need implementation for all of the indigenous people living in the Arctic region,” Hotez states.

Reference
1. Hotez PJ (2010) Neglected Infections of Poverty among the Indigenous Peoples of the Arctic. PLoS Negl Trop Dis 4(1): e606.