TB-Related News and Journal Items - Week of June 5, 2000

>The CDC Center for HIV, STD, and TB Prevention provides the following
>information as a public service only. Providing synopses of key scientific
>articles and lay media reports on HIV/AIDS, other sexually transmitted
>diseases and tuberculosis does not constitute CDC endorsement. This update
>also includes information from CDC and other government agencies, such as
>background on Morbidity and Mortality Weekly Report (MMWR) articles, fact
>sheets, press releases, and announcements. Reproduction of this text is
>encouraged; however, copies may not be sold, and the CDC HIV/STD/TB
>Prevention News Update should be cited as the source of the information.
>*************************************************************
>"New Clues to How the TB Bacillus Persists"; Science (www.sciencemag.org)
>(05/26/00) Vol. 288, No. 5470, P. 1314; Wickelgren, Ingrid
>
> Tuberculosis (TB) kills around 2 million people a year and can remain
>latent for years before sickening the host. Two groups are studying how the
>tuberculosis bacterium can stay in the body so long. One group is being led
>by Stanford University's Stanley Falkow, while the other is being led by
>William Jacobs of Albert Einstein College of Medicine in New York City.
>They have both found genes that may be necessary for TB infection to
>persist. This discovery could allow for new drugs that target the genes in
>order to fight TB. Falkow and colleagues identified the Mycobacterium
>marinum genes using green fluorescent proteins and inserting DNA fragments
>into this latent infection in frogs similar to human TB. However, Ian Orme
>of Colorado State University does not know if the frog model of Stanford's
>group is accurate for humans, since M. marinum is harmless to people.
>Meanwhile, William Jacobs and colleagues looked for mutants two years ago in
>the genes and found that mutations in the BCG gene, or bacillus
>Calmette-Guerin, could prevent the bacteria from forming cords, when the
>microbes come together in long rope like structures in culture. This
>research is helping show that a mutated enzyme affects the ability of M.
>tuberculosis to endure. The new technology of creating TB mutants will
>greatly help the study of new drugs for this disease.
>*************************************************************
>"G8 to Unveil Plan to Curb Infectious Diseases in Poor Nations: Report";
>Agency France Presse (www.afp.com) (06/08/00)
>
> A report in the Yomiuri Shimbun newspaper indicates that the leaders at
>the Group of Eight summit in Japan next month will show their support for
>developing nations and their fight against AIDS, tuberculosis, and malaria.
>The leaders will call for financing nongovernmental groups and activities to
>improve the conditions in poor countries. The G-8 summit will be held in
>Okinawa from July 21 to 23.
>*************************************************************
>OTHER NEWS ITEMS:
>*************************************************************
>WHITE HOUSE STATEMENT; June 1, 2000; Office of the Press Secretary; The U.S.
>- EU Summit - Joint efforts on HIV/AIDS, malaria, tuberculosis and other
>infectious diseases.
>
>The U.S. and the EU today announced a joint response to the critical global
>infectious disease threats of HIV/AIDS, malaria and tuberculosis (TB),
>especially as they impact Africa. Infectious diseases are the leading cause
>of death worldwide, causing nearly half of all deaths among people under age
>45. The developing world, especially Africa, bears an enormous burden from
>these diseases, which not only destroy lives, but also perpetuate the cycle
>of sickness and poverty. HIV/AIDS, malaria, and TB, together killing over 5
>million people worldwide each year, are threatening recent gains in economic
>growth, education and life expectancy. In Africa where HIV/AIDS is now the
>leading cause of death, the disease claimed 2.3 million lives last year
>alone - more than ten times the number who died in armed conflict. TB and
>malaria claim millions more, with malaria causing one in five childhood
>deaths in Africa. The U.S./EU Joint Response on HIV/AIDS, Malaria and TB The
>U.S. and EU today agreed to: - Seek increased government and private sector
>resources dedicated to combating HIV/AIDS, TB, and malaria; - Support an
>increase in World Bank and regional development bank resources devoted to
>health care system development; - Encourage Highly Indebted Poor Countries
>(HIPC) to use funds made available under the Cologne Debt Relief Initiative
>to build health systems to combat AIDS and fight other diseases; - Develop
>new financial investment incentives and public/private partnerships to make
>drugs and vaccines more available and affordable following the models of the
>Global Alliance for Vaccines and Immunization and the proposal for a tax
>incentive to companies who develop new vaccines for AIDS, malaria and TB; -
>Accelerate disease information and education campaigns in cooperation with
>political leaders in Africa; - Increase diplomatic engagement with national
>leaders to intensify joint action and encourage attention at the highest
>levels in the battle against HIV/AIDS, malaria and TB; and - Encourage the
>G-8 nations to address these issues as a priority at the upcoming summit in
>Okinawa...... Today's announcement builds on the U.S. Administration's
>aggressive response to these global disease challenges. In his State of the
>Union address, President Clinton announced a significant multi-part proposal
>to accelerate the development of malaria, TB and AIDS vaccines - vaccines
>for which there is huge need, but little market incentive for industry to
>develop. This included: - $50 million to the Global Alliance for Vaccines
>and Immunization to purchase existing state-of-the-art vaccines for
>developing countries; - a sharp increases in NIH vaccine research; - a $1
>billion tax credit for sales of vaccines for malaria, TB and AIDS when they
>are developed; and - a call to the World Bank to dedicate an additional
>$400-900 million in concessionary loans for health; and - a campaign to
>mobilize the EU, G-8, and other countries to increase funding and provide
>leadership on these issues. President Clinton is also asking Congress for
>$325 million to fight international AIDS - more than doubling the nation's
>commitment in two years. Investment in AIDS research to find a cure exceeds
>$1.8 billion this year, including over $200 million to find a vaccine - the
>most effective long-term solution for Africa. This year, the Administration
>has committed over $70 million for TB prevention, control and research, and
>over $100 million for malaria.,,,,,
>*********************************
>Clinton Remarks to the Duma; U.S. Newswire; 5 Jun 8:56; Transcript of
>Clinton Remarks to the Duma
>To: National and International Desks. June 5 /U.S. Newswire/ - Remarks made
>by President Clinton today to the Duma in Russia: The Duma Moscow, Russia. ;
>
>Let me say that this whole debate on missile defense and the nature of the
>threat reflects a larger and, I think, more basic truth. As we and other
>nation states look out on the world today, increasingly we find that the
>fundamental threat to our security is not the threat that we pose to each
>other, but instead, threats we face in common -- threats from terrorist and
>rogue states, from biological, chemical and nuclear weapons which may be
>able to be produced in increasingly smaller and more sophisticated ways.
>Public health threats, like AIDS and tuberculosis, which are now claiming
>millions of lives around the world, and which literally are on the verge of
>ruining economies and threatening the survival of some nations. The world
>needs our leadership in this fight as well. And when President Putin and I
>go to the G-8 meeting in July, I hope we can support a global strategy
>against infectious disease.
>*********************************
>Korea Times; June 5, 2000; Int'l Bicycle Rally Set to Raise Aid for NK
>Children Suffering TB.
>
>A civic group and two companies will launch a 2,000-kilometer bicycle race
>beginning in Paris and ending in Berlin on June 18 to raise funds for North
>Korean children suffering from tuberculosis (TB). The Korean Sharing
>Movement (KSM) yesterday announced that it is organizing the seven-day fund
>raising event in cooperation with Korea Telecom Hitel Co. and Netpia Korea.
>The movement has already selected 50 Koreans and another 50 Europeans as
>participants in the race. The participants and civic group members are
>scheduled to stage fund raising events in major European cities in France,
>Belgium, the Netherlands and Germany. The international event is set to be
>wrapped up on June 24 when the rallying teams arrive at the German capital.
>KSM estimates that about 200,000 children currently suffer from TB in North
>Korea. Korean health authorities said that an estimated total three to four
>million North Koreans are TB patients. The communications network firm
>Hitel and Internet domain company Netpia donated $20,000 each for the fund
>raising event. The two corporations plan to set aside 100 won for every
>visit to their Web pages' donation sites for needy North Korean children
>from today until June 13. For international Web domains, Netpia will
>accumulate $1 for English registrations and 5,000 won for Korean beginning
>Tuesday. The firm will also earmark 1,000 won for the registration of local
>domains for medical aid to suffering children in the North. KSM and the
>companies will hold a public campaign in Taehangno, central Seoul to
>celebrate the charity rally and encourage people to join the donation
>movement.
>*************************************************************
>OTHER JOURNAL ARTICLES:
>********************
>
>American Journal of Respiratory Cell and Molecular Biology; Volume 22,
>Number 6, June, 2000; Natural Resistance-Associated Macrophage Protein Gene
>in African Americans w/Sarcoidosis. Mary J. Maliarik, Kang Mei Chen, Roberta
>G. Sheffer, Benjamin A. Rybicki, Marcie L. Major, John Popovich Jr., and
>Michael C. Iannuzzi.
>
>Report notes the histologic and clinical similarities between tuberculosis
>and sarcoidosis suggest a shared underlying pathophysiology. The report also
>notes the human natural resistance-associated macrophage protein (NRAMP1),
>which is closely related to the mouse gene, has been associated with
>susceptibility to tuberculosis in some human populations. Given the
>importance of the Nramp1 gene in animal models of granulomatous disorders,
>the association with human tuberculosis, and the possible role of NRAMP1 in
>macrophage activation and function, authors hypothesized that human NRAMP1
>plays a role in susceptibility to sarcoidosis. They analyzed several NRAMP1
>gene polymorphisms in a case-control study of 157 African American patients
>with sarcoidosis and 111 African American control subjects. Their results,
>in contrast to those in tuberculosis patients, showed that the less common
>genotypes were found more often in control subjects than in case patients
>(odds ratio, 0.48; 95% confidence interval, 0.28-0.81). In particular, they
>found one polymorphism, a (CA)n repeat in the immediate 5' region of the
>gene, to have a protective effect (P = 0.014). Whereas NRAMP1 polymorphisms
>have been associated with increased susceptibility to tuberculosis, they
>report their results suggest that at least one NRAMP1 polymorphism may
>decrease susceptibility in sarcoidosis.
>*************************
>Journal of the American Medical Association: Vol. 283 No. 21; June 7, 2000;
>MEDICAL NEWS AND PERSPECTIVES: IOM Report a Blueprint for Elimination of TB;
>Joan Stephenson, PhD.
>
>Writer notes the new report calling for the elimination of tuberculosis (TB)
>in the United States warns that the potential cost of not making such an
>effort is a resurgence of the disease. She notes the report, prepared for
>the Institute of Medicine (IOM) by a panel of experts, recommends aggressive
>measures to stamp out lingering traces of the disease in hard-to-reach,
>high-risk populations. She says one key component of the panel's blueprint
>for TB elimination involves screening would-be immigrants for latent
>infection before allowing them to enter this country. She notes the report
>opens with a quotation from philosopher George Santayana, "Those who cannot
>remember the past are condemned to repeat it;" the report urgently describes
>the need to avoid the complacency that contributed to TB's resurgence in the
>United States in the 1980s. She observes that, after the introduction of
>effective treatment in 1953 resulted in dramatic declines in TB rates,
>public health leaders dared to envision wiping out the disease in this
>country - yet instead of heeding the calls for TB elimination, what was
>eliminated instead was federal support, as categorical federal funding for
>the disease was ended in 1972. She says as local TB control efforts
>withered, infection rates surged during the late 1980s, and treatment
>efforts were complicated by the emergence of deadly, multidrug-resistant
>strains of Mycobacterium tuberculosis, and the result was an epidemic that
>cost billions of dollars to control. She acknowledges that although TB rates
>in the United States are now at an all-time low, the IOM panel of 13 experts
>warned that efforts must be intensified to prevent another resurgence:
>"Despite the falling number of cases in the United States, this country has
>entered a dangerous phase in which the disease has retreated to specific
>communities where it can lie dormant and resist detection," said Morton N.
>Swartz, MD, of Massachusetts General Hospital, Boston, who served as chair
>of the report committee. "Without decisive steps to identify and treat the
>undetected cases, the disease could come back with a vengeance and exact a
>heavy price." The writer says continued vigilance is also needed because the
>global epidemic, which claims 2 to 3 million lives each year, is a potential
>source of new infections, and in some of the hardest-hit countries in Africa
>and Asia, more than half the population is now infected with TB. She notes
>43% of UN cases occurred among immigrants from countries with high rates of
>the disease, compared with 27% of cases in 1992, and, if this trend
>continues, foreign-born residents soon could account for the majority of new
>TB cases here. Because of this, she points out the panel concluded that
>efforts to prevent a resurgence of the disease should include screening for
>latent infection in people applying for permanent residency visas (green
>cards). She notes the IOM report calls for adding a new measure: requiring
>tuberculin skin tests for people from countries where more than 35% of the
>population is infected (the average infection rate worldwide) before they
>enter the United States; most countries with high rates of the disease are
>in Africa and Asia, said panel member Ronald Bayer, PhD, of Columbia
>University. The writer comments that prospective immigrants from Mexico,
>which has a TB prevalence of 17%, would also be screened for latent
>infection because of the disproportionately large number of new immigrants
>from that country. She notes under the new proposal, those with positive
>skin test results would be allowed to enter the United States, but documents
>granting permanent residency status would be withheld until they received
>further evaluation and treatment of latent infection. She reports the effort
>would involve administering skin tests to about 250,000 people a year and
>treating those with latent infection, at a cost of about $23 million - in
>the long run - this would be cheaper than the cost of treating the
>individuals and others they infect," said Swartz. She notes the report
>outlines the need for increased outreach efforts in immigrant communities,
>as well as among such other high-risk groups as prison inmates, homeless
>persons, intravenous drug abusers, and people infected with HIV. She quotes
>IOM panel member, Pat Chaulk from the Annie E. Casey Foundation: "As the
>number of TB cases goes down, the proportion of hard-to-reach and
>hard-to-serve are increasing," and he said what is needed to reach such
>individuals is investing "in local capacity for retraining and hiring
>additional staff who can work across cultural issues and in diverse
>neighborhoods where TB may be more prevalent."
>
>TYhe IOM Report also recommends: (1) assisting other countries in fighting
>the infection and increasing research funding for tuberculosis; (2) the
>federal government should develop better tools to fight TB, including better
>diagnostic tests and treatments for both latent infection and active
>disease, as well as a more effective vaccine; (3) development of better
>tests to identify latent infection; (4) developing shorter, simpler, and
>less toxic regimens for treating the disease; (5) development of better ways
>to treat infection with multidrug-resistant M tuberculosis..... Regarding
>the need for better tools, panel member Philip C. Hopewell, MD, of San
>Francisco General Hospital says "We need better tests to identify latent
>infection, and with new information about Mycobacterium tuberculosis
>resulting from recent sequencing of the pathogen's genome, there's reason to
>be optimistic about the prospects for developing a better diagnostic test."
>The IOM report, Ending Neglect: The Elimination of Tuberculosis in the
>United States, is posted online at
>http://books.nap.edu/books/0309070287/html/10.html.
>
>*************************
>Journal of the American Medical Association: Vol. 283 No. 21; June 7, 2000;
>RESEARCH LETTER: False-Positive Tuberculin Skin Test Results Among Health
>Care Workers; Henry M. Blumberg, MD; Nancy White, RN; Patricia Parrott, RN;
>Wanda Gordon, RN; Mary Hunter, MD and Susan Ray, MD.
>
>In this letter to the editor, the writers comment that two different
>commercial tuberculin reagents are available in the United States. They
>point out that Villarino et al1 concluded that "both Aplisol and Tubersol
>will correctly classify comparable numbers of persons not infected with M.
>tuberculosis and that the choice of product used for [tuberculin] skin
>testing has little effect on test performance." These writers report on an
>experience at their institution with false-positive tuberculin skin test
>(TST) results among a group of health care workers associated with the use
>of Aplisol, contradicts these conclusions. They investigated a marked
>increase in TST conversions among health care workers at the Grady Health
>System that began in mid-September 1999. They say tuberculin skin tests are
>mandatory for all their health care workers every 6 months unless there is
>documentation of a previously positive result; tests are placed and read by
>the hospital's employee health service using the Mantoux method;
>self-reading is not permitted; two-step testing is required for newly hired
>employees; and a positive TST is defined as induration of 10 mm or greater.
>They report in the three 6-month periods before September 1999, baseline
>conversion rates were as follows: 4 (0.09%) of 4670 health care workers
>tested between January and June 1998; 8 (0.2%) of 4363 tested from July
>through December 1998; and 5 (0.1%) of 4358 tested from January through June
>1999. They note that between September 15 and October 15, 1999, 11 (1.2%)
>health care workers had a new TST conversion (median, 12-mm induration;
>range, 10-20 mm) among 914 individuals tested, a marked increase compared
>with the previous 1.5 years (P<.001). All 11 health care workers were
>subsequently found to have chest radiographs that showed no evidence of
>tuberculosis. The writers report their pharmacy had switched from Tubersol,
>which had been used exclusively for the prior 6 years, to Aplisol because of
>lower price. They say, beginning in mid-September 1999, the employee health
>service staff (which remained the same during this period) stopped using
>Tubersol and began using Aplisol purified protein derivative (PPD) reagent
>(lot numbers 01739P and 00159P). They retested with Tubersol PPD (lot number
>2515-11) all 11 health care workers who tested positive with Aplisol with )
>and they found negative TST results (10 individuals with 0-mm induration and
>1 individual with 3-mm induration). They say an additional individual who
>had a positive baseline TST with Aplisol had a positive repeat TST with
>Tubersol (20-mm induration). They conclude their experience indicates that
>there may not be equivalency between different PPD products although they
>point out the difference between our findings and those of Villarino et al
>may reflect lot-to-lot variation of tuberculin. They note Villarino et al
>evaluated only 2 different lots of Aplisol tuberculin reagent, and the
>Aplisol lot associated with false-positive test results at their institution
>was not one of those. The writers comment that previous studies have also
>found false-positive TST results associated with Aplisol and say their
>experience demonstrates the need for a better and more reliable test for
>detection of tuberculosis infection.
>***********************
>Science 2000 June 2; 288: 1647-1651; Essential Role for Cholesterol in Entry
>of Mycobacteria into Macrophages; John Gatfield, Jean Pieters.
>
>Report notes that mycobacteria are intracellular pathogens that can invade
>and survive within host macrophages, thereby creating a major health problem
>worldwide; the molecular mechanisms involved in mycobacterial entry are
>still poorly characterized. Here authors report that cholesterol is
>essential for uptake of mycobacteria by macrophages. They point out
>cholesterol accumulated at the site of mycobacterial entry, and depleting
>plasma membrane cholesterol specifically inhibited mycobacterial uptake.
>They report cholesterol also mediated the phagosomal association of TACO, a
>coat protein that prevents degradation of mycobacteria in lysosomes. Thus,
>they conclude, by entering host cells at cholesterol-rich domains of the
>plasma membrane, mycobacteria may ensure their subsequent intracellular
>survival in TACO-coated phagosomes.
>*************************
>British Medical Journal; 2000;320:1551-1552 ( 10 June ); Editorials; Cheaper
>antiretrovirals to treat AIDS in South Africa; They are at their most cost
>effective in preventing mother to child transmission, Karen Zwi, Neil
>Söderlund, Helen Schneider.
>
>Editorial notes that many countries in sub-Saharan Africa are overwhelmed by
>a pandemic of HIV and AIDS that is reducing life expectancy by two decades,
>reversing gains made in infant mortality and increasing the burden on health
>resources that are already overstretched; South Africa is no exception.
>Writers note the government, AIDS activists, healthcare professionals, and
>communities are desperate to find a universal solution or "magic bullet."
>The writers point out triple combination therapy has dramatically widened
>the gulf in people's experience of HIV and AIDS, depending on whether they
>live in the North or the South, and not surprisingly, activists, both local
>and international, have persistently called for a substantial lowering of
>the prices of antiretroviral and other expensive drugs needed to treat
>people with AIDS. In addition, the writers point out that cure rates of
>tuberculosis are poor even by the standards of developing countries (57% for
>patients with newly positive smears) and the whole infrastructure for
>treatment needs substantial overhaul. The writers say the government is
>probably right about its position on the secondary importance of
>antiretrovirals, but for the wrong reasons, and say real solutions to the
>AIDS epidemic in South Africa are a lot less glamorous - they consist of
>incremental improvement in basic health services, including antenatal care,
>prophylaxis and treatment of opportunistic infections, and tuberculosis and
>sexually transmitted disease care, improved status for women in society,
>support to community based palliative care providers, and improved
>cooperation between government and non-governmental organizations. The
>writers conclude that lowering the price of antiretrovirals has a role to
>play, but is not in itself a solution.
>***********************
>LANCET: 2000; 355: 2077 - 2080: Correspondence; Mycobacterium tuberculosis
>transmission and HIV status; Stefano Bonora, Ercole Concia, Benedetta
>Allegranzi, Alberto Biglino, Giovanni Di Perri
>
>These writers comment that Marcos Espinal and co-workers (Jan 22, p 275 )
>provided evidence that HIV-positive patients with tuberculosis are less
>likely than HIV-negative patients to transmit Mycobacterium tuberculosis
>infection to contacts. This article sheds light on the debated subject of
>infectiousness of HIV-associated tuberculosis. However, they comment immune
>status of the HIV-positive patients is a crucial issue not focused on by
>Espinal et al. Features of HIV-associated tuberculosis are known to change
>according to the patient's immune deterioration. They point out clinical
>and pathological findings in tuberculosis developing in HIV-positive
>patients with a relative conserved immune status (represented by CD4+ T-cell
>count) are virtually indistinguishable from those seen in tuberculosis in
>HIV-negative individuals. However, by contrast, they comment the knowledge
>of tuberculosis acquired in non-HIV individuals may not apply to the most
>severely immunosuppressed AIDS patients, in whom the clinical and
>pathological picture is often atypical; opinions differ on the infectious
>potential of these patients. They say that pulmonary evidence of a greater
>than usual number of viable bacilli interspersed in poorly competent and
>unspecific tissue reactions suggested a potential for greater
>infectiousness. Writers comment in some hospital settings transmission of M
>tuberculosis infection and disease from AIDS patients to health-care workers
>was significantly more likely than in comparable HIV-negative settings,
>while on the other hand, the immuno-deficiency-related tendency to a higher
>bacillary count seems to be counterbalanced by a lower ability to generate
>open lesions (the ones accounting for infectiousness) in the respiratory
>tract. They question Espinal and colleagues' report - might the reduced
>infectiousness be attributable to the fraction of most immunosuppressed
>patients rather than being a characteristic of all HIV-positive tuberculous
>individuals? They point out the weakened cough (suggested by the authors as
>an explanation for the reduced infectiousness) seems to be clinically
>reasonable only in very compromised HIV-positive patients. They point out
>the issue has clinical and epidemiological implications too and the belief
>that all HIV-positive patients with tuberculosis, rather than just a
>proportion of them, are potentially less infectious could lead to
>underestimates of the risk in many settings.
>********************
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