TB-Related News and Journal Items - Week of June 19, 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.
>******************************************************
>CALIFORNIA: "Tuberculosis Cases on Rise, County Reports"; Sacramento Bee
>(www.sacbee.com) (06/17/00) P. B1; Griffith, Dorsey.
>
> Sacramento County, California, is seeing a rise in new tuberculosis
>(TB) cases after two years of decline. Dr. Glennah Trochet said 84 new
>cases of active TB have been reported this year, compared to 89 cases for
>all of 1999. While staff shortages will delay the immediate analysis of the
>new cases, health officials have determined a link between six of the
>individuals, who had all taken part in services for the homeless in the
>downtown area. Dr. Glennah Trochet, the county's health officer, noted that
>none of the cases are multidrug resistant, crediting the county's aggressive
>directly observed therapy program.
>************************************************************
>TEXAS: Education Week (www.edweek.org) (05/31/00) Vol.19, No. 38, P. 28;
>Portner, Jessica.
>
> Along the Mexican border in Texas, schoolchildren are frequently
>sickened by diseases that are preventable. Mass inoculation campaigns have
>helped, but with the flow of people between Mexico, it is hard to keep
>illness at bay. The United States has successfully eradicated polio and
>reduced diphtheria, tetanus, and measles. However, hepatitis A, chicken
>pox, dengue fever, and tuberculosis (TB) rates along the counties on the
>Mexican border are high. Infections are rampant because of unsanitary and
>crowded living conditions, and endemic disease from Mexico is common. The
>polluted Rio Grande River also is a cause for cases of gastroenteritis.
>Unsanitary conditions in colonies along the border affect children in
>school, and immunization clinics are necessary to keep them healthy and
>alert for classes. The nurses inoculate for hepatitis A and B, chicken pox,
>measles, mumps, rubella, TB, diphtheria, pertussis, tetanus, and polio. In
>Webb County, over 30 per 100,000 people tested positive for TB exposure,
>which is three times the rate for the entire state, and all potential school
>employees are tested for the disease before being hired. The area has few
>pediatricians, however, and one doctor reports seeing 100 to 200 patients a
>day. A 1990 measles outbreak in Laredo took over five months to contain,
>involving the immunization of some 20,000 children. However, there has not
>been a major outbreak there in years, and the chicken pox rate has declined
>below the state average. The shots for most children are free, but migrant
>workers are hard to locate for repeated doses. Laurie Henfey of Texas
>immunization program notes, "It's a constant battle to get [children]
>vaccinated. There's never going to be a time where we can say, 'Oh, we're
>done."
>********************************
>
>"Drugs Show Promise in Tuberculosis Fight"; USA Today (www.usatoday.com)
>(06/22/00) P. 9D; Healy, Michelle.
>
> Researchers from PathoGenesis in Seattle have developed a potential
>treatment for drug-resistant tuberculosis (TB). The scientists report in
>the current issue of Nature that a family of drugs called nitroimidazopyrans
>has proven effective against TB in animal tests. Given sufficient funding
>and successful clinical tests, the drug could receive regulatory clearance
>in five to eight years, the researchers said, which would make it the first
>new anti-TB therapy in three decades.
>***********************************************************
>OTHER NEWS ITEMS:
>**************************************
>ALABAMA: Huntsviile Times: Madison County Commission...... June 7, 2000;
>STEVE DOYLE.
>
>Announced the county has purchased a $44,948 heating and ventilation system
>for the Wheeler Avenue jail annex. The Southern Center for Human Rights
>recently asked a federal judge to close the jail because of poor
>ventilation, which it said exposes inmates to insufferable heat, second-hand
>cigarette smoke and tuberculosis. U.S. District Judge U.W. Clemon toured the
>annex May 18 and gave county officials 10 days to figure out how to improve
>ventilation. County Attorney Julian Butler said the Trane ventilation system
>will improve air circulation in the old metal buildings. The equipment
>should be installed in early July.
>****************************************
>New weapon found for TB - Experimental treatment combats drug-resistant
>strains; MSNBC NEWS SERVICES.
>
>June 21 - An experimental drug shows promise in fighting tuberculosis at a
>time when TB is becoming increasingly resistant to existing antibiotics,
>especially in poor countries, researchers said Wednesday. If tests are
>successful and the compound, PA-824, is approved, it will be the first new
>TB-specific drug on the market in 30 years, said C. Kendall Stover, a
>scientist at the Seattle biotechnology company PathoGenesis Corp., where it
>was developed. Stover said it kills all of the drug-resistant forms of TB
>that have been tested to date, including the strains resistant to more than
>one drug. Tests on mice and guinea pigs indicate PA-824 is at least as
>potent as today's first-line anti-tuberculosis drug, isoniazid, he said. It
>also hits different molecular targets, affecting the bacteria's fatty cell
>wall and shutting down protein synthesis. "This drug is sort of a Trojan
>horse," Stover said. "The bacteria actually activates it and turns it into
>something that hits these targets and kills the bacteria." The findings were
>reported in this week's edition of the journal Nature.
>**********************************
>Mayo Foundation for Medical Education and Research. © 2000 Mayo Foundation
>for Medical Education and Research: ASK THE MAYO PHYSICIAN Category:
>Infectious diseases: What is "consumption?"; June 16, 2000.
>
>Question: I am currently reading the book "Angela's Ashes" by Frank McCourt.
>He often describes people dying or suffering from "the consumption". What is
>this? Is it a specific disease or a catch-all word for any unknown disease?
>Deborah / Colo. Answer: The word consumption used as a medical condition
>refers to wasting away of the body from a chronic illness, particularly
>pulmonary tuberculosis (TB of the lung). The term is not commonly used at
>the present time in that context. Sir William Osler in his classic medical
>text of 1892, "The Principles and Practice of Medicine," listed pulmonary
>tuberculosis with its synonyms: phthisis and consumption. A particularly
>virulent form of TB - tuberculous pneumonia - was called "galloping
>consumption." The other term, phthisis, is from the Greek word meaning, "to
>decay." Prior to the discovery of streptomycin and subsequent antibiotics
>effective against Mycobacterium tuberculosis, the germ that causes TB, it
>was common for the disease to lead to severe weight loss and other signs of
>chronic infection. In contrast to the term for bubonic plague, "The Black
>Death," TB was often referred to as "The White Death." Unfortunately,
>strains of the TB bacillus are now emerging that are resistant to many of
>the previously effective antibiotics so that many people, particularly those
>with immune deficiency, are still at risk of this serious, contagious
>disease that has been with us since antiquity. The evolution of medical
>terminology is both interesting and important to people seeking medical
>information in old family history records.
>****************************************
>LTIC NEWS SERVICE: FOREIGN DIPLOMATS WORRIED ABOUT SPREAD OF TUBERCULOSIS IN
>LATVIA; Baltic News Service - Estonia, Jun 13, 2000.
>
>Several foreign diplomats share with Latvian Welfare Minister Andrejs
>Pozarnovs their concern over large number of tuberculosis patients in
>Latvia, Pozarnovs told reporters Tuesday. According to the welfare
>minister, tuberculosis incidence in Latvia exceeds the average statistical
>figure in Europe several times. During informal talks with Pozarnovs the
>foreign diplomats said that this problem gained particular importance when
>considered in the context of Latvia moving towards the European Union (EU).
>After integration into the EU there will not be any borders between Latvia
>and the EU, consequently, the number of tuberculosis patients may grow also
>in the European countries. The Latvian welfare minister did not specify
>countries represented by the diplomats, who were worried by the spread of
>tuberculosis in Latvia. He only said they were representatives from several
>Scandinavian states. Pozarnovs said that about 200,000 lats (USD 333,000)
>have been allocated for fight against tuberculosis under the next year's
>Latvian budget, although the allocations still required an approval by the
>government. The World Health Organization (WHO) warned Monday that the fight
>against communicable diseases could be lost in the next 10 to 20 years if
>proper use is not made of current resources, AFP news agency reported. "The
>world may only have a decade or two to make optimal use of many of the
>medicines presently available to stop infectious diseases," David Heymann,
>executive director of WHO's program on communicable diseases stressed, as he
>presented a report on drug-resistant diseases. "We are literally in a race
>against time to bring levels of infectious diseases down worldwide, before
>the diseases wear the drug down first," he added. For example, in Estonia,
>Latvia, and certain parts of Russia, more than 10 percent of tuberculosis
>viruses are now resistant to the two most effective medicines for the
>disease, the report said.
>******************************
>NIH-National Institute of Allergy and Infectious Diseases; 21 JUNE 2000;
>NIAID-industry partnership leads to promising new tuberculosis drug.
>
>Tuberculosis (TB), the world's leading killer among infectious diseases, has
>not faced an effective new class of drugs for more than 30 years. Now, a
>promising new weapon in the fight against that disease -- which kills one
>person every 15 seconds across the globe -- has been reported in the current
>issue of Nature. The candidate drug, developed by scientists at PathoGenesis
>Corporation in Seattle, has unique properties that may make it superior to
>current anti-TB compounds. Collaborative studies performed with scientists
>at the National Institute of Allergy and Infectious Diseases (NIAID)
>determined how the drug works. Because TB hits hardest in impoverished
>regions where people cannot afford drug treatment, pharmaceutical companies
>have been reluctant to invest in research on new drugs. "Infectious diseases
>like TB, AIDS and malaria exact a devastating toll worldwide, particularly
>in developing countries," states Anthony S. Fauci, M.D., director of NIAID.
>"Public-private collaborations like this can effectively accelerate research
>on new ways to treat and prevent these diseases." The incidence of TB, a
>chronic bacterial infection caused by Mycobacterium tuberculosis (MTB), has
>been increasing for several years, in part because HIV infection increases
>susceptibility to MTB. In addition, multi-drug resistant (MDR) strains of
>the bacteria are spreading throughout the globe, making new TB drugs
>necessary. Even MTB strains that are susceptible to current drugs are often
>difficult to eliminate because they can enter a latent state similar to
>hibernation where they hide away in low-oxygen regions of the lungs. To
>facilitate TB drug development, NIAID and PathoGenesis established a
>research collaboration focused on developing a new class of anti-TB agents
>that attack the protective cell wall of MTB. "The company's expertise in
>chemistry and molecular biology meshed well with our expertise in cell wall
>biochemistry," says Clifton E. Barry III, Ph.D., chief of the tuberculosis
>research section in NIAID's Laboratory of Host Defenses. "Our collaboration
>demonstrates the value of combining complementary efforts to find creative
>solutions to global disease." The idea for the newest drug candidate arose
>when the scientists scoured the literature for unrecognized compounds with
>anti-TB activity. They noted that a compound -- originally investigated by
>another company for use in the treatment of cancer -- also was reported to
>have activity against MTB. This compound had not been pursued, however,
>because it tended to cause mutations. PathoGenesis chemists made 328
>chemical variants of the original compound, which the team then tested for
>anti-TB activity in the test tube and in mice. Many of the new compounds
>destroyed MTB as well as or better than the original drug but lacked its
>undesirable mutation-causing properties. In laboratory assays, these
>variants also killed all MDR strains of MTB tested. One of these compounds,
>called PA-824, was selected for further study because it showed promising
>activity in animal models of TB. "At the time, we were collaborating with
>Dr. Barry's laboratory on another project involving bacterial cell walls,"
>says Dr. Kendall Stover, senior director of research biology at
>PathoGenesis. "Therefore, we redirected some of our efforts to figure out
>how PA-824 worked. Dr. Barry's laboratory assisted us in investigating
>PA-824's novel mechanism for killing M. tuberculosis. We discovered that the
>new drug acts in part by preventing MTB from forming an important fatty acid
>component of its cell walls. We were quite fortunate to collaborate with Dr.
>Barry's lab, because NIAID's cell wall biochemistry expertise nicely
>complemented ours." The researchers discovered another advantage of PA-824
>over existing agents. Most anti-TB drugs must first be activated by MTB
>itself, and MDR strains can resist these agents by blocking their entrance
>into the bacteria or preventing their activation. PA-824, however, may use a
>'Trojan horse' approach to bypass the MTB sentries, allowing the drug to
>target the cell wall and kill the bacteria. "We continue to study this
>property as an important element of other new anti-TB compounds," says Dr.
>Barry. The partnership with PathoGenesis was arranged through a Cooperative
>Research and Development Agreement (CRADA) from NIAID. CRADAs do not award
>money to drug companies but rather are research agreements through which
>public and private organizations share resources. RADAs therefore provide
>one way for companies to pursue promising but "low-profit" drugs -- such as
>those for TB, AIDS and malaria -- without spending huge amounts of money
>starting up new laboratories. NIAID is a component of the National
>Institutes of Health (NIH). NIAID conducts and supports research to prevent,
>diagnose, and treat illness such as HIV disease and other sexually
>transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an
>agency of the U.S. Department of Health and Human Services. Press releases,
>fact sheets and other NIAID-related materials are available on the NIAID Web
>site at http://www.niaid.nih.gov. Reference: Stover, CK et al. A
>nitroimidazopyran drug candidate for the treatment of active and latent
>tuberculosis. Nature 2000;405:926-66.
>*************************
>June 23, 2000; Bankrolling Colombia's War on Drugs: House and Senate Will
>Now Reconcile Bills; CHRISTOPHER MARQUIS.
>
>WASHINGTON, June 22 -- Nearly a year after President Andrés Pastrana of
>Colombia asked the United States for emergency aid to battle narcotics
>traffickers and their rebel allies, the Senate cleared the way today for a
>package of $1.3 billion........... The Senate also increased spending by
>$30 million to $255 million for international efforts to fight AIDS, and
>added $10 million for a total of $66 million to battle the global spread of
>tuberculosis. But it provided only $75 million in assistance to the world's
>poorest countries, a reduction from the administration's $262 million
>request.
>*******************************************************
>OTHER JOURNAL ITEMS:
>******************************************************
>International Journal of Tuberculosis and Lung Disease: 2000; 4 (6):
>491-195; Pyrazinamide is not active against Mycobacterium tuberculosis
>residing in cultured human monocyte-derived macrophages; L Heifets, M.
>Higgins, B. Simon.
>
>Authors sought to evaluate the antimicrobial activity of pyrazinamide
>against Mycobacterium tuberculosis in cultured human monocyte-derived normal
>and activated macrophages. They incubated monocytes separated from human
>blood (in plastic plates) for seven days to mature into macrophage
>monolayers. After activation with TNF-a or IFN-g or without prior treatment,
>they infected the macrophages with M. tuberculosis. The next day they added
>various concentrations of pyrazinamide (PZA), morphazinamide (MZA) or
>isoniazid (INH), and the viable counts of the intracellular bacteria were
>determined at days 0, 4, and 8. They report no inhibitory activity of PZA at
>any concentration was detected, while clear dose-dependent bacteriostatic
>and bactericidal activities were demonstrated by MZA and INH in the same
>experimental model. They conclude PZA has neither bacteriostatic nor
>bactericidal activity against M. tuberculosis persisting or multiplying in
>cultured monocyte-derived human macrophages, and it might be that the
>well-known effectiveness of this drug in tuberculosis patients is not
>related to its supposed activity against intracellular bacterial
>subpopulations.
>*******************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>496-503; Patient and disease characteristics, and outcome of treatment
>defaulters from the Singapore TB control unit-a one-year retrospective
>survey; C. B. E. Chee, I. C. Boudville, S. P. Chan, Y. K. Zee, Y. T. Wang.
>
>This study in the Singapore Tuberculosis Control Unit. Was conducted to 1)
>To identify any demographic, social, disease or treatment-related
>characteristics which may be predictive of patients defaulting from
>treatment; 2) to assess the effectiveness of home visits as a means of
>defaulter recall; and 3) to ascertain outcome in these patients. The study
>was a retrospective, case-controlled study of TB treatment defaulters,
>defined as patients who missed their scheduled appointments and required a
>home visit to recall for treatment; controls were randomly selected,
>non-defaulting patients who started treatment on the same dates as the
>defaulters. Authors report forty-four patients required home visits in
>1996.- compared to controls, defaulters were more likely to be non-Chinese,
>and to live on their own or with friends. They say there was no significant
>association of defaulting with age, sex, marital or employment status,
>disease characteristics, or treatment-related factors. They report seventy
>per cent defaulted during the continuation phase of treatment; home visits
>did not result in contact with the patient (or any other person) 41% of the
>time and, although 48% of the defaulters remained lost to follow-up at the
>time of the survey, all but one of the sputum-positive patients had
>bacteriologically converted by the time of default. They conclude 1)
>non-Chinese ethnicity and lack of family support were found to be factors
>strongly predictive of default and, 2) age, sex, marital and employment
>status, treatment-related factors and disease characteristics were not
>significant in distinguishing those at risk for defaulting.
>********************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>504-512; Twenty-five years of tuberculosis in a French university hospital:
>a laboratory perspective; J. Robert, D. Trystram, C. Truffot-Pernot, E.
>Cambau, V. Jarlier, J. Grosset.
>
>This is a report of a descriptive study of all 4549 culture-positive
>tuberculosis cases hospitalized at Pitié-Salpêtrière Hospital between 1972
>and 199, to determine the impact of recent changes in the epidemiology of
>tuberculosis in France and other industrialized countries on the primary
>trends of tuberculosis case rates in a French university hospital. Authors
>report that from 1972, there was a decline of 5% per year in the
>tuberculosis case rate, which leveled off in 1983. They note the proportion
>of tuberculosis patients who were human immunodeficiency virus (HIV)
>positive increased from 2% in 1983 to 28% in 1990, and thereafter remained
>stable; the proportion of foreign-born tuberculosis patients also increased,
>from 40% in 1972 to 55% in 1985. They note these two changes affected drug
>resistance patterns and drug resistance was more common among foreign-born
>than among French-born patients, whether previously treated or not. They
>observed resistance to rifampicin and multidrug resistance among previously
>untreated patients was highly related to HIV co-infection and
>extra-pulmonary sites of tuberculosis were more often smear-positive in
>HIV-positive than in non-HIV-positive patients (22.8% vs. 12.6%), and
>bacteraemia was diagnosed almost exclusively in HIV-positive patients. They
>sum up saying the changes in clinical and bacteriological tuberculosis
>patterns at the hospital level over the last 25 years have paralleled those
>observed at national and international level in industrialized countries,
>including a slowing in the decrease in the case rate, due in part to the HIV
>epidemic, a higher proportion of foreign-born patients and an increase in
>drug resistance.
>*********************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>513-518; Trial-of-antibiotic algorithm for the diagnosis of tuberculosis in
>a district hospital in a developing country with high HIV prevalence; D.
>Wilkinson, W. Newman, A. Reid, S. B. Squire, A. W. Sturm, C. F. Gilks.
>
>This study was conducted in adult medical wards in Hlabisa Hospital, South
>Africa, 1996-1997, in order to evaluate a diagnostic algorithm for pulmonary
>tuberculosis based on smear microscopy and objective response to trial of
>antibiotics. Authors report adults with chronic chest symptoms and abnormal
>chest X-ray had sputum examined for Ziehl-Neelsen stained acid-fast bacilli
>by light microscopy and those with
> negative smears were treated with amoxycillin for 5 days and assessed;
>those who had not improved were treated with erythromycin for 5 days and
>reassessed, and response was compared with mycobacterial culture. They
>found of 280 suspects who completed the diagnostic pathway, 160 (57%) had a
>positive smear, 46 (17%) responded to amoxycillin, 34 (12%) responded to
>erythromycin and 40 (14%) were treated as smear-negative tuberculosis. They
>noted the sensitivity (89%) and specificity (84%) of the full algorithm for
>culture-positive tuberculosis were high. However, they point out 11 patients
>(positive predictive value [PPV] 95%) were incorrectly diagnosed with
>tuberculosis, and 24 cases of tuberculosis (negative predictive value [NPV]
>70%) were not identified. They say NPV improved to 75% when anaemia was
>included as a predictor and algorithm performance was independent of human
>immunodeficiency virus status. They conclude sputum smear microscopy plus
>trial of antibiotic algorithm among a selected group of tuberculosis
>suspects may increase diagnostic accuracy in district hospitals in
>developing countries.
>****************************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>519-527; HIV testing among tuberculosis patients in the era of
>antiretroviral therapy: a population-based study in Brazil; K. DeRiemer, E.
>C. C. Soares, S. M. O. Dias, S. C. Cavalcante.
>
>This study was carried out in Rio de Janeiro, Brazil, a city with 29 862
>cases of tuberculosis (TB) reported between January 1995 and June 1998 and
>the purpose of the investigation was to evaluate the counseling and testing
>practices for human immunodeficiency virus (HIV) infection among TB
>patients, and to identify the patient characteristics associated with HIV
>screening as antiretroviral therapy was introduced. This was a
>cross-sectional study of patients with TB who were reported to the health
>department and who initiated anti-TB treatment and the main outcome measure
>was screened versus not screened for HIV. Authors report te proportion of
>TB patients who received HIV screening increased from January 1995 through
>June 1998 (P < 0.001); among young adults aged 20-49 years with TB, the
>independent predictors of HIV screening were a diagnosis of both pulmonary
>and extra-pulmonary TB (odds ratio [OR] = 2.4, 95% confidence interval [CI]
>2.1-2.8); TB meningitis (OR = 13.5, 95%CI 6.5-31.5); disseminated TB (OR =
>8.2, 95%CI 5.3-12.9); lymphatic TB (OR = 5.6, 95%CI 4.7-6.6); and male sex
>(OR = 1.4, 95%CI 1.3-1.6). They report patients with newly diagnosed TB who
>were women, lived in a low income neighborhood (OR = 0.7, 95%CI, 0.6-0.7),
>and sought TB treatment in their own residential neighborhood (OR = 0.3,
>95%CI 0.3-0.4) were less likely to receive HIV counseling and testing. They
>sum up saying health care providers in Rio de Janeiro selectively offered
>HIV counseling and testing to persons they perceived to be at risk for HIV
>and those with advanced stages of TB. Authors recommend HIV counseling and
>testing should be expanded and offered to all TB patients.
>********************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>528-536; Quantitative sputum bacillary load during rifampin-containing short
>course chemotherapy in human immunodeficiency virus infected and
>non-infected adults with pulmonary tuberculosis; M. L. Joloba, J. L.
>Johnson, A. Namale, A. Morrissey, A. E. Assegghai, R. D. Mugerwa, J. J.
>Ellner, K. D. Eisenach.
>
>This report is from the National Tuberculosis (TB) Treatment Center, Mulago
>Hospital and Joint Clinical Research Center, Kampala, Uganda where
>investigators sought to compare the quantitative sputum bacillary load
>between TB patients infected with the human immunodeficiency virus (HIV) and
>those non-infected, during treatment with standard short course chemotherapy
>(SCC). They compared clinical characteristics and quantitative sputum
>bacillary load as measured by quantitative acid-fast bacilli (AFB) smears,
>colony forming unit (cfu) assay and time until positive culture in the
>BACTEC® radiometric liquid system between 14 HIV-infected and 22
>non-HIV-infected adults with initial episodes of smear-positive
>pulmonary TB at baseline and during treatment with standard four-drug SCC.
>They report that, other than cavitation (P=0.042) and adenopathy (P=0.03),
>which were more common among non-HIV-infected and HIV-infected patients,
>respectively, there were no significant differences in baseline demographic,
>clinical, radiological and laboratory characteristics between the groups.
>They noted mean pretreatment sputum bacillary burden (6.5 0.51 log10
>AFB/ml, 5.91 0.91 log10 cfu/ml and 1.8 1.7 days until positive BACTEC®
>culture for HIV-infected patients and 6.32 0.85 log10 AFB/ml, 5.58 0.68
>log10 cfu/ml and 1.9 1.2 days until positive BACTEC® culture for
>non-HIV-infected patients) were comparable between HIV-infected and
>non-HIV-infected patients. They say clinical and bacteriological responses
>to standard SCC and treatment outcome did not differ between the groups.
>They conclude quantitative sputum bacillary load at baseline and during SCC
>did not differ significantly between HIV-infected and non-HIV-infected
>adults with initial episodes of smear-positive TB.
>***************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>537-543; Human immunodeficiency virus-related tuberculosis and primary drug
>resistance in Bangkok, Thailand; J. Punnotok, N. Shaffer, T. Naiwatanakul,
>U. Pumprueg, P. Subhannachart, A. Ittiravivongs, C. Chuchotthaworn, P.
>Ponglertnapagorn, N. Chantharojwong, N. L. Young, K. Limpakarnjanarat, T. D.
>Mastro.
>
>This study in the Central Chest Hospital, a 500-bed referral hospital near
>Bangkok with a large out-patient department, was carried out to determine
>human immunodeficiency virus (HIV) seroprevalence among patients with
>pulmonary tuberculosis (TB), and compare HIV-positive and HIV-negative TB
>patients. This cross-sectional study was conducted from July 1995 through
>June 1996, among newly registered adults ( 16 years old) with suspected
>pulmonary TB. Authors report, of 2587 newly registered patients with
>suspected pulmonary TB, 2019 (78%) received HIV pretest counseling and 1816
>(90%) consented to testing; of these, 364 (20%) were HIV-seropositive and
>among 1091 patients with bacteriologically confirmed TB, HIV seroprevalence
>was 22%. They found HIV-positive patients were more likely to be young,
>unemployed, single men and to have a history of injection drug use. They
>observed HIV-positive patients with first-episode TB were more likely to
>have Mycobacterium tuberculosis strains resistant to isoniazid (10.9% vs.
>3.5%; P < 0.001), rifampicin (9.4% vs. 2.9%; P < 0.001), and at least
>isoniazid and rifampicin (multidrug-resistant TB [MDR-TB]; 5.2% vs. 0.4%; P
>< 0.001). They sum up that HIV prevalence is high among TB patients at
>this Bangkok hospital and is associated with drug resistance, including a 12
>times higher risk of MDR-TB. They point out their findings underscore the
>urgent need to assure adherence to complete, effective TB treatment regimens
>for all patients, including persons who are potentially difficult to manage
>such as injection drug users.
>*******************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>544-549; Prevalence of drug-resistant Mycobacterium tuberculosis and
>monitoring therapy in tuberculosis patients in Tehran; A. R. Bahrmand, A. A.
>Velayati, V. V. Bakayev.
>
>This is a report of a prospective study of 257 patients undergoing treatment
>for whom data were collected on drug susceptibility testing and outcome as
>well as age, sex and history of treatment by health care clinics and private
>practitioners in Tehran. The purpose of the study was to analyze rates of
>drug resistance and response to treatment in tuberculosis patients. Authors
>report that, of 774 initially diagnosed patients, 380 were female and 394
>were male; 520 (67%) of the cases had pulmonary disease; the overall rate
>of primary drug resistance among Mycobacterium tuberculosis isolates
>resistant to at least one drug was 87/563 (15.5%); twenty-three patients
>were multidrug-resistant. They observed that, among 215 patients with
>drug-susceptible cultures recruited for follow-up, rapid response to
>short-course chemotherapy was observed in 190 (88%) who were successively
>both smear and culture negative after 2 and 4 months of treatment. They
>report that, after 6 months of treatment, 12 of the 25 patients with slow
>response to treatment had positive cultures; one was smear-positive, and of
>the 42 patients with drug-resistant isolates, satisfactory bacteriological
>response was observed after 6 months of treatment in 30 (71%). They conclude
>their observations support regional recommendations for short-course
>treatment regimens. They say culture rather than smear result could be a key
>parameter for individually guiding the duration of treatment in patients
>with poor response to treatment.
>****************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>550-554; A randomized controlled trial of lay health workers as direct
>observers for treatment of tuberculosis; M. Zwarenstein, J. H. Schoeman, C.
>Vundule, C. J.
>
>This study conducted in a suburb of Cape Town, South Africa, and involved a
>comparison of successful tuberculosis treatment outcome rates between self
>supervision, supervision by lay health worker (LHW), and supervision by
>clinic nurse. This was an open, randomized, controlled trial with
>intention-to-treat analysis. Authors report all groups (n =156) achieved
>similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95%
>confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI
>-3.7-33.6). They say new patients benefit from LHW supervision (LHW vs.
>clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision
>39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%,
>95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7). They sum
>up saying LHW supervision approaches statistically significant superiority,
>but fails to reach it most likely due to the study's limitation, the small
>sample size. They say it is possible that subgroups (new and female
>patients) do well under LHW supervision and suggest LHW supervision could
>be offered as one of several supervision options within TB control programs.
>******************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>555-561; Effect of anti-tuberculosis treatment on the tuberculin interferon-
>response in tuberculin skin test (TST) positive healthcare workers and
>patients with tuberculosis; R. L. Stuart, D. Olden, P. D. R. Johnson, A.
>Forbes, P. M. Bradley, J. S. Rothel, M. L. Grayson.
>
>This is a report of a study in a public hospital, Victoria, Australia
>conducted to evaluate the effect of multidrug treatment and isoniazid (INH)
>chemoprophylaxis on the tuberculin interferon-g assay (QIFN) in 19 patients
>with culture-confirmed Mycobacterium tuberculosis and 119 health care
>workers (HCWs) with tuberculin skin tests (TST) > 15 mm. Authors report the
>patients with M. tuberculosis were treated with standard medication and
>tested with QIFN at diagnosis and at regular intervals over a 12-month
>period. They say all HCWs, 59 (50%) of whom were prescribed INH
>chemoprophylaxis, were tested with QIFN at baseline, 2, 4, 6 and 12 months.
>They found QIFN results in patients with tuberculosis were consistent and
>reproducible. They report at the initial time point QIFN assays were
>positive for M. tuberculosis in 67%, and once positive, the QIFN assay
>remained so over the 12-month period. They relate that in the HCWS, initial
>QIFN assays were positive in 73 (61%)and, during the 12-month study, 91 HCWs
>had a QIFN assay on at least two occasions. They say the overall
>reproducibility between tests was fair (kappa statistic = 0.45), and was
>little affected by administration of INH. They sum up saying their data
>suggest that although the QIFN assay is generally positive in patients with
>proven tuberculosis, it does not provide clinically useful information
>during the first 12 months of treatment with multidrug chemotherapy or INH
>chemoprophylaxis.
>*******************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>562-569; Antibody response to culture filtrate antigens of Mycobacterium
>tuberculosis during and after treatment of tuberculosis patients; M. S.
>Imaz, E. Zerbini.
>
>This report notes that many authors have shown rising titres of
>anti-mycobacterial antibodies after a few months of anti-tuberculosis
>treatment; this humoral response might persist for years, making the
>discrimination between current and old disease difficult. Authors looked at
>characterization of the humoral response to culture filtrates of
>Mycobacterium tuberculosis before and after treatment of tuberculous
>patients in order to identify those antigens that could provide information
>about disease activity. They determined anti-mycobacterial IgG response
>during and after treatment of tuberculous patients by ELISA and immunoblot;
>serum was taken from 71 active tuberculous patients (59 newly acquired and
>12 relapse), 15 old tuberculous patients and 45 non-tuberculous control
>subjects. They report that, by antibody, response increased after 2 months
>of treatment. They say after chemotherapy was completed, the estimated
>number of antibodies remained at the same level and the level of specific
>antibodies in patients seems to reach the same level as that of control
>subjects 3 years after initiation of treatment. They report in Western blot,
>although each patient serum had its own characteristic banding pattern,
>differences between tuberculous patients and control subjects were found in
>the area below 20 kDa. They report serum from tuberculous patients showed
>high levels of antibodies at the 14 kDa region. They noted after the
>beginning of treatment, the intensity of the 14 kDa region band and the
>percentage of positive recognition tended to decrease and, therefore, one
>year after initiation of treatment, seven of 13 cases who demonstrated
>antimycobacterial antibodies in ELISA revealed a mild but still positive
>reaction at the 14 kDa region; this reactivity disappeared 2 years after
>initiation of chemotherapy. They conclude the 14 kDa region antigen seems
>to induce a humoral response that evolves in relation with the disease
>activity.
>*******************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>570-576; Efficacy of common antiseptics against mycobacteria; T. Rikimaru,
>M. Kondo, S. Kondo, K. Oizumi.
>
>Report notes that antiseptics are frequently used to prevent mycobacterial
>infection; however, the reported activities of a number of antiseptics
>against mycobacteria are not always consistent and the aim of this study was
>to determine those antiseptics that are useful against mycobacteria. Authors
>examined the effects of different antiseptics on mycobacteria (Mycobacterium
>avium, M. kansasii and M. tuberculosis). They report at concentrations of
>0.05%, povidone-iodine (PVP-I) killed 99% or more of all strains tested
>within 15 seconds, while 0.5% chlorhexidine gluconate and 0.1% benzalkonium
>chloride showed no bactericidal activity against mycobacteria. They say M.
>kansasii and M. tuberculosis were killed after exposure to cresol for 60
>seconds at concentrations of 1.0%, but M. avium was unaffected even after 60
>seconds. They observed that while M. kansasii and M. tuberculosis were
>killed by treatment with 2.0% glutaraldehyde for 5 minutes, M. avium was
>highly resistant to this agent. They conclude PVP-I seems to be a useful
>antiseptic against mycobacteria but they caution the measured activity of
>antiseptics should be interpreted carefully, due to the potential for
>interference by artifacts.
>**********************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>577-580; 3'UTR polymorphisms in the NRAMP1 gene are associated with
>susceptibility to tuberculosis in Koreans; S. Ryu, Y.-K. Park, G.-H. Bai,
>S.-J. Kim, S.-N. Park, S. Kang.
>
>This study from the Korea University and the Korean Institute of
>Tuberculosis, Seoul, Korea, was conducted to determine whether polymorphisms
>in the 3' untranslated region (UTR) of the NRAMP1 gene are associated with
>susceptibility to tuberculosis in Koreans. Authors report a significant
>association was found between the Korean tuberculosis patients and
>polymorphisms in the 3'UTR of the NRAMP1 gene (odds ratio [OR] 1.845; 95%
>confidence interval 1.097-3.104; 2 =5.424; P =0.020). They say their
>findings showed that genetic variations in the human NRAMP1 gene are
>associated with susceptibility to smear-positive tuberculosis in Korean
>patients. They comment the 3'UTR variant allele associated with
>susceptibility to tuberculosis is very uncommon in Caucasians, but is
>present in Koreans and West Africans. They say their observations may
>explain in part why African Americans and Koreans have greater
>susceptibility to tuberculosis than Caucasians.
>************************************
>International Journal of Tuberculosis and Lung Disease; 2000; 4 (6):
>581-583; Time between sputum examination and treatment in patients with
>smear-negative pulmonary tuberculosis; F. M. L. Salaniponi, F. Gausi, J. H.
>Kwanjana, A. D. Harries.
>
>Report notes the time between sputum examination and commencement of
>treatment in patients registered with smear-negative pulmonary tuberculosis
>(PTB) in four hospitals in Malawi was investigated. Authors obtained
>information on 701 of 887 patients who were registered over a 12-month
>period between 1997 and 1998: 86% were started on treatment within 3 weeks
>of sputum examination, 14% were started after a 3-week interval and 6% after
>a 6-week interval. They comment that such delays are unacceptable and say
>recommendations will go to program staff to repeat sputum examination in PTB
>suspects with an abnormal chest radiograph whose negative sputum smears were
>examined more than 3 weeks previously.
>*************************
>International Journal of Tuberculosis and Lung Disease: 2000; 4 (6):
>584-587; DNA fingerprinting of a national sample of Mycobacterium
>tuberculosis isolates, Botswana, 1995-1996; S. Lockman, J. D. Sheppard, M.
>Mwasekaga, T. A. Kenyon, N. J. Binkin, C. R. Braden, C. L. Woodley, D. W.
>Rumisha, J. W. Tappero.
>
>Authors comment that DNA fingerprinting may be useful to elucidate
>tuberculosis (TB) transmission in community settings, but its utility is
>limited if only few fingerprint patterns are observed or band numbers are
>low. They performed DNA fingerprinting on a national, population-based
>sample of Mycobacterium tuberculosis isolates from Botswana and during
>1995-1996, a random sample of 213 isolates, representing 5% of all
>smear-positive TB cases, underwent DNA fingerprinting using restriction
>fragment length polymorphism (RFLP) IS6110 analysis. They report eighty-two
>(38%) of the 213 isolates belonged to one of 18 clusters, with 2-9 isolates
>per cluster; the median number of bands was 10 (range 1- 9); 183 (86%) had
>six or more bands; sixty-three (49%) of 128 patients tested were infected
>with the human immunodeficiency virus (HIV). They conclude the degree of
>RFLP pattern heterogeneity and high band number support the feasibility of a
>prospective DNA fingerprinting study in Botswana.
>*******************************
>International Journal of Tuberculosis and Lung Disease: 2000; 4 (6); Study
>of the in vitro susceptibility of M. tuberculosis to ofloxacin in Spain; M.
>Casal, P. Ruiz, A. Herreras, and the Spanish Study Group of M. tuberculosis
>Resistance.
>
>Report notes the aim of this study was to determine the proportion of
>antituberculosis ofloxacin resistance among Mycobacterium tuberculosis
>strain isolates in Spain and, over a period of one month, 213 M.
>tuberculosis strains collected from 14 different hospitals were studied,
>including strains both susceptible and resistant to primary
>anti-tuberculosis drugs. Authors report in 28.1% of the strains, a minimum
>inhibitory concentration (MIC) for ofloxacin of 0.25 mg/ml was obtained; in
>43.6% the MIC was 0.5 mg/ml; in 22.06% it was 1 mg/ml; and in 6.1%it was >=
>2 mg/ml. They comment that ofloxacin currently seems to be an effective
>antimicrobial in vitro against susceptible or multiresistant strains of M.
>tuberculosis in human immunodeficiency virus (HIV)-negative or HIV-positive
>patients in Spain.
>*****************************
>PEDIATRICS Vol. 105 No. 6 June 2000, ELECTRONIC ARTICLE:: Mycobacterium
>bovis as a Significant Cause of Tuberculosis in Children Residing Along the
>United States-Mexico Border in the Baja California Region; Wayne M. Dankner*
>and Charles E. Davis. ,
>
>Authors sought to determine the role of Mycobacterium bovis in active
>pediatric tuberculosis (TB) in a United States-Mexico border region by
>reviewing all new cases of pediatric (<15 years old) TB presenting to San
>Diego hospitals and clinics from 1980 to 1997; patients were categorized by
>age, ethnicity, country of origin, culture results, and disease
>manifestations; case definitions were similar to those used by the Centers
>for Disease Control and Prevention; M bovis was distinguished from
>Mycobacterium tuberculosis by standard biochemical tests. They found the
>median age of the 563 identified patients was 4.1 years old; the yearly
>incidence began rising in 1989 and peaked in the mid-1990s; Hispanics
>constituted 78.9% of the patients, but they were less likely to be
>foreign-born (21.6%) than were black children and Asian/Pacific Islanders.
>Overall, they found M bovis caused 10.8% of all TB during this period, but
>of the 180 patients with positive culture results, M bovis accounted for
>33.9% and M tuberculosis 66.1%. They say the high percentage of M bovis
>infections was largely attributable to its contribution to extrapulmonary TB
>(55.2% of all culture-positive specimens). They noted M bovis patients were
>also even more likely to be Hispanic (90.2%), to present with extrapulmonary
>disease (95.1%), and to be older than 12 months (96.8%). They conclude
>their data demonstrate the dramatic impact of this underappreciated cause of
>zoonotic TB on US children at the Mexican border and underscore the need for
>cross-collaboration to enforce existing Mexican pasteurization laws.
>********************************
>PEDIATRICS Vol. 105 No. 6 June 2000; ELECTRONIC ARTICLE: Health of Children
>Adopted From China; Laurie C. Miller and Nancy W. Hendrie.
>
>Report notes since 1989, American parents have adopted 18 846 Chinese
>children and this study assesses the health and developmental status of
>these children after their arrival in the United States. Authors report a
>total of 452 children (443 girls) in 2 groups were evaluated; the clinic
>group children (n = 192) included all Chinese adoptees seen in an
>international adoption clinic between 1991 and 1998; the travel group
>comprised 260 of 325 Chinese children placed by a single Massachusetts
>adoption agency between 1991 and 1996 whose adoptive parents and American
>physicians responded to mailed questionnaires. Authors found growth and
>developmental delays were frequent in the clinic group; Z scores were found
>in 39% of children for height, 18% for weight, and 24% for head
>circumference. They say duration of orphanage confinement was inversely
>proportional to the linear height lag ® = .9), with a loss of 1 month of
>height age for every 2.86 months in the orphanage; 75% had significant
>developmental delay in at least 1 domain: gross motor in 55%, fine motor in
>49%, cognitive in 32%, language in 43%, social-emotional in 28%, activities
>of daily living in 30%, and global delays in 44%. They report the incidence
>of medical problems was similar in both groups of children (travel group and
>clinic group). Overall, among the 452 children, they found elevated lead
>levels in 14%, anemia in 35%, abnormal thyroid function tests in 10%,
>hepatitis B surface antigen in 6%, hepatitis B surface antibody in 22%,
>intestinal parasites (usually Giardia) in 9%, and positive skin test results
>for tuberculosis in 3.5%. They report one child each had hepatitis C
>exposure and congenital syphilis but none had human immunodeficiency virus
>infection. They found unsuspected significant medical diagnoses, including
>hearing loss, orthopedic problems, and congenital anomalies, in 18% (81/452)
>of the children. They sum up saying Chinese adoptees display a similar
>pattern of growth and developmental delays and medical problems as seen in
>other groups of internationally adopted children; an exception is the
>increased incidence of elevated lead levels (overall 14%). Although
>serious medical and developmental issues were found among the children, they
>say their overall condition was better than expected based on recent
>publicity about conditions in the Chinese orphanages.
>*****************************
>Journal of Clinical Investigation; June 2000, Volume 105, Number 12,
>1675-1677; American Society for Clinical Investigation; The cells that knew
>too much; Alan G. Baxter.
>
>Writers note that in the June issue of the JCI, Ikehara et al. report a
>novel function for an unusual population of lymphocytes - natural killer T
>(NKT) cells. They note these cells were originally identified as CD4-CD8-
>(double negative, DN) T cells responsible for rapid production of large
>amounts of IL-4, a cytokine that plays a critical role in supporting
>immunoglobulin production and inhibiting some inflammatory responses. They
>observe NKT cells are now usually identified either by the coexpression of
>the NK cell marker NKR-P1 (NK1.1 in mice) and the T-cell antigen receptor
>(TCR), or by the presence of unusually restricted TCR chains (termed V24JQ
>in humans and V14J281 in mice and rats; refs. They say although these cells
>may either be DN or express intermediate levels of the CD4 accessory
>molecule (CD4int), the fact that most NKT cells in humans, mice, and rats
>use similar TCR chains has led to the suggestion that they recognize a
>restricted range of targets; consistent with this hypothesis, many NKT-cell
>clones appear to be stimulated by the MHC class I-like molecule CD1, and NKT
>cells are severely depleted in mice carrying a targeted deletion of CD1d.
>They point out NKT cells play an important role in immunoregulation but NKT
>cells cannot be viewed simply as immune suppressor cells, since they also
>play a proinflammatory role in host resistance to tumors and infection;
>probably the best-established role for NKT cells is in immune responses to
>mycobacterial lipid antigens. They say the only member of the CD1 family of
>molecules expressed in mice is CD1d, and the NKT cells present in mice also
>respond to mycobacterial antigens; they predominate in the granulomatous
>reaction to Mycobacterium tuberculosis cell wall preparations, and such
>granulomas do not form in NKT cell-deficient J281 TCR-targeted deletion
>mice; the NKT cells of normal mice respond to mycobacterial infection by
>decreasing IL-4 production and increasing IFN- production, changes highly
>likely to aid the host response to mycobacteria, since IFN- plays a critical
>role in pathogen clearance.
>************************
>American Journal of Roentgenology; AJR 2000; 175:121-128; American Roentgen
>Ray Society; Pictorial Essay: Tuberculous Colitis - Radiologic-Colonoscopic
>Correlation; Seong Jin Park, Joon Koo Han, Tae Kyoung Kim, Joo Sung Kim,
>Hyun Chae Jung, In Sung Song and Byung Ihn Choi.
>
>Authors note until recently, intestinal tuberculosis was considered a rare
>chronic disease, occurring mainly in people of Third World countries, but
>researchers have noted a sharp increase in incidence of tuberculosis in
>young adults in association with recent epidemics of AIDS and patients with
>AIDS frequently have a greater incidence of extrapulmonary tuberculosis;
>therefore, it is necessary for radiologists to recognize the colonoscopic
>findings of various colonic diseases, including inflammatory bowel diseases
>and tumorous conditions. Authors observe that in the past, the radiologic
>diagnosis of intestinal tuberculosis was made with barium contrast studies,
>and although colonoscopy and colonoscopic biopsy have gained wide popularity
>and have supplanted the primary diagnostic role of radiologic studies, the
>double-contrast barium enema can provide detailed information on the mucosal
>pattern and early staging features of intestinal tuberculosis. They
>speculate with a better understanding of the early features of tuberculous
>colitis, early diagnosis with double-contrast barium enema might be
>possible. They note intestinal tuberculosis is diagnosed when histologic
>tests reveal caseating granulomas or acid-fast bacilli, but the sensitivity
>of revealing acid-fast bacilli or granulomas with caseating necrosis is low
>(approximately 32% and 50%, respectively). Therefore, they say the clinical
>diagnosis of intestinal tuberculosis depends on the presence of colonic
>mucosal lesions that are suggestive of intestinal tuberculosis on
>double-contrast barium enema or endoscopy - a clinical diagnosis of
>intestinal tuberculosis can also be made with a therapeutic trial of
>antituberculous treatment, especially in endemic areas. They observe the
>early features of intestinal tuberculosis are spasm, hypersecretion,
>increased motility, lymphoid hyperplasia, thickened folds, and shallow
>ulcers. They comment the ulcer in a patient with tuberculosis colitis is
>not considered an important finding because it does not appear on
>single-contrast barium enema and comment that on double-contrast barium
>enema, multifocally scattered shallow ulcers are frequently revealed on the
>ascending and transverse colon, correlating colonic aphthous ulcers with
>surrounding mucosal edema on colonoscopy. They note small aphthous ulcers
>are considered specific for Crohn's disease and, although uncommon, small
>aphthous ulcers have been described in tuberculous colitis.
>*******************
>The New England Journal of Medicine; June 22, 2000; Vol. 342, No. 25;
>Tuberculosis in a Child in North Dakota; Letter To the Editor; William W.
>Stead, M.D.
>
>Dr. Stead refers to the informative report where Curtis et al. describe
>extensive transmission of tuberculosis by an adopted nine-year-old child
>(Nov. 11 NEJM issue). Dr. Stead believes the authors of the paper and the
>author of the accompanying editorial overlooked a factor that probably was
>involved in the development of tuberculosis in this child. It seems clear to
>Dr. Stead that the child was not infected in North Dakota, where the
>tuberculosis case rate is about 2 per 100,000 population, but rather in his
>native Marshall Islands, where the case rate is 104 per 100,000 population.
>Curtis et al. noted a tuberculin skin test was performed shortly after his
>arrival in North Dakota in 1996, but unfortunately the result was not
>assessed, since the child was apparently was well at that time, and his
>tuberculosis developed two years later. Dr. Stead points out tuberculosis
>is common among persons from the Indian subcontinent who immigrate to the
>United Kingdom, in part because in the winter months dark-skinned people may
>be deficient in 1,25-dihydroxyvitamin D3, an important immunoregulatory
>hormone. He explains the Marshall Islands lie in the Pacific Ocean at a
>latitude of only 9 degrees north, where it is never cold enough to require
>staying indoors or dressing warmly, while North Dakota is at about 46
>degrees north, so there is a great difference in sunlight between the two
>locations for several months each year. Dr. Stead further comments that
>Douglas et al. have shown that the peak incidence of tuberculosis among
>persons with dark pigmentation who immigrate to the United Kingdom is in
>July (the month in which the tuberculosis of the source case was found), in
>contrast to the winter peak for other respiratory diseases. He speculates
>the reason for the delayed development of tuberculosis after the winter
>nadir of vitamin D3 is that it takes several months for a dormant
>tuberculosis infection to reactivate and produce sufficient symptoms for the
>illness to be diagnosed. Dr. Stead comments this experience should teach us
>that when dark-skinned people immigrate to northern states or Canada from
>areas where tuberculosis is common and sunshine abundant year round, we
>should be sure that they have adequate vitamin D to enable their immune
>system to function properly year round.
>******************************
>Journal of the American Medical Association; Vol. 283 No. 23; June 21, 2000;
>Public Health Law in a New Century - Part III: Public Health Regulation: A
>Systematic Evaluation; Lawrence O. Gostin, JD, LLD
>
>In this third article of a series, Gostin says public health interventions
>need justification because they intrude on individual rights and incur
>economic costs. He says coercive interventions can be justified in only 3
>cases: to avert a risk of serious harm to other persons, to protect the
>welfare of incompetent persons, and, most controversially, to prevent a risk
>to the person himself/herself. He proposes a systematic evaluation of public
>health regulation and recommends that public health authorities should bear
>the burden of justification and, therefore, should demonstrate (1) a
>significant risk based on scientific evidence; (2) the intervention's
>effectiveness by showing a reasonable fit between means and ends; (3) that
>economic costs are reasonable; (4) that human rights burdens are reasonable;
>and (5) that benefits, costs, and burdens are fairly distributed.
>*********************
>Lancet 2000; 355: 2223 - 2230; New class of drugs provides hope for future
>of tuberculosis treatment; Zoë Mullan.
>
>Writer notes that, after a 30-year void that saw no significant advances in
>antituberculosis drug development, scientists report the successful
>preliminary testing of a set of compounds that act via a completely new
>mechanism. Mullan notes these compounds, the nitroimidazopyrans, are
>structurally similar to the antibiotic metronidazole and, according to
>Kendall Stover (PathoGenesis Corporation, Seattle, WA, USA) and colleagues,
>who developed the drugs, the lead compound, PA-824, is bactericidal against
>Mycobacterium tuberculosis (including multidrug-resistant strains), is
>highly specific for the M tuberculosis complex, and, unlike current
>antituberculosis drugs, is active against growing and
>static organisms alike. He points out experiments in mice and guinea pigs
>showed that orally administered PA-824 was as effective as similar doses of
>isoniazid (Nature 2000; 405: 962-66 [PubMed]). Mullan reports that despite
>being excited by the new development, Stephen Gillespie (Royal Free and
>University College Medical School, London, UK) warns that there are many
>obstacles to overcome before the compound can be introduced into clinical
>practice. Not least of these is the reluctance of some drug companies to
>pursue the development of antituberculosis drugs because of their poor
>perceived profitability. He quotes Stover "Clinical trials could
>theoretically go ahead within the time-frame recommended by the Global
>Alliance for TB Drug Development..... but whether they're done by us or by
>someone else depends on funding. We're currently trying to figure out ways
>to go forward, maybe through licensing or collaborations". He notes
>Gillespie predicts that if such ways can be found, "the nitroimidazopyrans,
>alongside the oxazolidinones and new quinolones, give some reason for
>optimism for the future".
>*******************
>Lancet 2000; 355: 2256; Diagnosis of tuberculosis in Africa; Anthony
>Harries, Nicola Hargreaves, Julia Kemp, John Kwanjana, Felix Salaniponi.
>
>Writers reference the well-done and informative study about adult pneumonia
>in Kenya by J A G Scott and colleagues (LANCET: April 18, p 1225 ) that
>showed that patients with pulmonary tuberculosis can present with a short
>duration of illness; 8% of patients in the study who had respiratory
>illness for less than 2 weeks were found to be smear positive for acid-fast
>bacilli (AFB) from sputum specimens. Writers note this result is similar to
>results obtained in Malawi where 6% of patients who had a cough for less
>than 2 weeks had smear-positive pulmonary tuberculosis and they note in the
>Kenyan study, mycobacterial cultures were also done, and nearly 40% of
>patients with positive cultures had evidence of associated pneumococcal
>infection. They say this finding may explain reported observations that
>patients with pulmonary tuberculosis can improve temporarily on antibiotics,
>a factor which may lead to delays in diagnosis. The writers speculate that
>the difficult question to answer in the real world of tuberculosis control
>in resource-poor countries in Africa, is how patients with pulmonary
>tuberculosis with short duration of illness are to be diagnosed. They point
>out Scott and colleagues suggest that all patients with pneumonia should be
>screened for tuberculosis, and should have sputum cultures for Mycobacterium
>tuberculosis because sputum smears identified only half of the patients with
>tuberculosis in their study. They comment that doing sputum cultures on all
>patients presenting with pnuemonia would be an impossible task for any
>tuberculosis control program in sub-Saharan Africa and say international
>guidelines recommend that sputum smears are done on those suspected as
>having tuberculosis who have a cough for more than 3 weeks. They believe
>doing sputum smears for patients with a short history of coughing would also
>place an intolerable burden on an already overstretched laboratory system.
>These writers suggest patients with pneumonia should be treated with
>antibiotics, and those improving should be encouraged to go home. However,
>they also note the development of recurrent cough should give cause for
>investigation for tuberculosis, usually with sputum-smear examination and
>both patients and healthcare workers need to be made aware of this, and
>tuberculosis programs should include this recommendation in their
>case-finding guidelines. They believe there should be a lower threshold for
>carrying out relevant tuberculosis investigations in patients with pneumonia
>who are very sick, or in patients with a short duration of cough who present
>in closed institutions such as prisons. They comment early diagnosis of
>tuberculosis in such settings is crucial for transmission interruption, and
>in such situations sputum-smear examination in patients with a short history
>of coughing is justified.
>******************
>British Medical Journal; 2000;320:1726 ( 24 June ); Letters - Misconceptions
>about tuberculosis among immigrants to the United States; Susan T Cookson.
>
>Cookson wrote to say Charatan's story in BMJ's news extra about tuberculosis
>among foreign born people in the United States requires clarification
>because the term "immigrant" is not used accurately noting an immigrant to
>the United States is a person who is admitted as a lawful permanent resident
>or who becomes a permanent resident while living there. She says about 400
>000 people qualify in each category annually; about 70 000 refugees enter
>annually. She explains that within the Public Health Service, the Division
>of Quarantine of the Centers for Disease Control and Prevention writes the
>guidelines for the medical examination required for all immigrants and
>refugees and notifies receiving health departments of those who may have
>tuberculosis; potential immigrants and refugees who have infectious
>tuberculosis must be treated until they are not infectious; they are then
>allowed into the country on condition that they are followed up by the local
>health department. She notes those with possible non-infectious tuberculosis
>are also referred to local health departments; over 90% are evaluated.
>Cookson points out the United States Immigration and Naturalization Service
>has estimated that five million people born outside the United States were
>living in the country unlawfully in October 1996 and INS has responded to
>this with increased screening of those who are apprehended and detained. She
>points out roughly 155 000 people were placed in Immigration and
>Naturalization Service detention during fiscal year 1999. She notes the
>Public Health Service's Division of Immigration Health provides healthcare
>support to the immigration service by screening detainees for tuberculosis
>and in the last fiscal year the division screened over 52 000 detainees who
>were held for at least 48 hours or had symptoms of tuberculosis. She says
>other detainees might have been screened for tuberculosis while in
>correctional systems not covered by the division. She points out the total
>number of people born outside the United States who had tuberculosis in the
>country actually fell from 7930 in 1995 to 7591 in 1998 while during the
>same period the rates of tuberculosis in people born in the United States
>and people born outside the United States fell to 4.4/100 000 and 28/100
>000, respectively. She points out the Centers for Disease Control and
>Prevention has made it a priority for state and local health departments to
>follow up and treat immigrants and refugees identified as possibly having
>tuberculosis and for the Division of Quarantine to continue forwarding their
>medical documentation to relevant health departments. She says the recent
>decline in tuberculosis among people born outside the United States probably
>reflects successes in tuberculosis screening and follow up and says more
>effort is needed to address the problem of tuberculosis among the roughly
>five million undocumented people living in the United States to ensure that
>all segments of the population receive screening and treatment.
>*************************
>British Medical Journal; 2000;320:1726 ( 24 June ); Letters - Reforms to the
>health sector must retain vertical programs like those for tuberculosis;
>John Crofton.
>
>Crofton writes that health sector reform has become the policy urged on poor
>countries in the developing world and comments it basically it entails
>transferring responsibility for health services and health budgets to local
>communities. He is sympathetic to this approach but is concerned its
>uncritical application by governments has a dangerous obverse. He says in
>the vertical programs, central coordination and monitoring of the World
>Health Organization's DOTS (directly observed treatment short course)
>program for control of tuberculosis may be discouraged and the program may
>be suddenly abolished. He points out the economy of scale resulting from
>national bulk buying of antituberculous may drugs disappear, the
>tuberculosis experts in the Ministry of Health, who provide leadership and
>coordination and who monitor the program, are dispersed to other jobs; and
>suddenly there are no drugs for tuberculosis, either centrally or at the
>periphery, and no control program. Dr. Crofton says he was told that this
>has already occurred in Zambia and Ethiopia, it almost occurred in
>Bangladesh, and it is threatening to occur in many other countries. Dr.
>Crofton says it is essential to retain the economies of scale offered by the
>central purchase of drugs and basic diagnostic equipment and it is essential
>to retain control of central monitoring and coordination and gradually to
>hand over the major responsibility of the
>service to local communities as their skill develops. He comments that, just
>as in community development projects in the United Kingdom, professionals
>continue to be needed in the background to pick up the bits when a local
>administration fails. He says when he raised this problem at a recent
>symposium on global health, the representative of Save the Children
>supported him. He comments that he recently visited the School of Tropical
>Medicine in Liverpool and had discussions with people working on tropical
>disease problems in poor countries. Although he says they are sympathetic
>with the concept of health service reform, many are disturbed by the
>possibility of the sudden abolition of vertical programs with no real
>provision for their effective replacement.
>******************
>OTHER
>******************
>Project HOPE is recruiting a TB Physician to be based in Tashkent,
>Uzbekistan.
>
>WHERE: National Tuberculosis Program in Uzbekistan, Turkmenistan
>POSITION: TB Educator
>DURATION: One Year
>REPORTS TO: Administrative, at HOPE Center: Tom Kirby, Regional Director,
>N.I.S. Administrative, On-Site: Dr. Michael E. Zeilinger, Program Director.
>GOAL: Assist in the development of National TB program and pilot sites based
>on World Health Organization Directly Observed Treatment (WHO DOTS)
>diagnosis and treatment methodology in Uzbekistan and Turkmenistan.
>Collaborate with WHO, World Bank, USAID and CDC in the expansion of
>diagnostic services and case definition of tuberculosis in the
>aforementioned Central Asian countries.
>SPECIFIC RESPONSIBILITIES: 1. Act as Medical Consultant to expand the Uzbek
>and Turkmen National TB program and DOTS pilot sites building on Project
>HOPE pilot program in a various regions of the countries. The TB Physician
>will be based in Tashkent, Uzbekistan. 2. Review current case definition for
>TB and develop strict case definition criteria for national TB programs,
>according to WHO guidelines. Assist counterparts to further develop local
>technical capabilities to accurately diagnose and manage tuberculosis. 3.
>Provide oversight for the development of National TB Reference labs in
>Uzbekistan and Turkmenistan. 4. Collaborate in the development,
>implementation and evaluation of a cost effectiveness study of the WHO DOTS.
>5. Provide technical assistance to government counterparts in developing
>Tuberculosis policy as it pertains to adults and children. 6. Collaborate
>with Ministry of Health, other local partners, and international agencies in
>the development of a national procurement system for anti-tuberculosis
>pharmaceuticals in the Central Asian Republics. 7. Working with the
>existing Sanitary Epidemiological Service, strengthen the community-based
>program of surveillance and contact tracing. 8. Provide training/curricula
>development to medical staff in the National TB Institutes in Central Asian
>Republics. Encourage training of medical staff in pilot Oblasts and Raions
>to implement the WHO DOTS program 9. Provide quarterly reports of all
>activities to HOPE Center. 10. Participate in the development and meetings
>of a steering council for TB which will include: Ministry of Health,
>Ministry of Finance, TB Institutes, State Medical Universities, and other
>international organizations. 11. Prepare with the Ministries of Health and
>Finance and the TB Institutes a plan for rationalizing medical facilities
>and improving out patient services based on an expanded WHO DOTS model. 12.
>Develop proposals to seek additional funding to expand Project HOPE
>activities to additional Oblasts and to the prison populations in
>conjunction with the Central Asian Republics Program Director. 13. Act as
>Program Director, when the Program Director is out of country. 14. Perform
>other related duties as assigned. PREREQUISITES: 1. MD, Board Certified in
>Pulmonary Medicine or Infectious Disease, with particular focus on TB
>management. 2. Experience in Treatment of Pediatric Tuberculosis. 3.
>Experience in an international setting in developing and implementing
>curriculum for health care professionals. 4. Experience in DOTS
>implementation at a national level 5. Ability to work in a team atmosphere.
>6. Understanding of microbiological and radiological diagnosis of
>tuberculosis. 7. Epidemiological skills. 8. Computer skills. 9. Excellent
>training and communication skills. 10. Proficiency in English Language. 11.
>Proficiency in Russian language highly desirable. 12. Experience in
>materials and curricula development. Dr. Michael E. Zeilinger Program
>Director - Central Asian Republics Project HOPE
>CONTACT: Michael E. Zeilinger, mailto:Mzprojhope@kaznet.kz
>
>