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TUBERCULOSIS

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Feb 2007 Vol 22 no 1
Australian
Respiratory
In this edition: Socio-political
issues, nursing, diagnosis of TB in
children from poor countries
M. tuberculosis E M Photo
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Editorial Advisory Group:
Editorial
Drs J Thompson, M Hurwitz, P Kelly, V
Krause, A Sleigh.
A recent report from the Austin Hospital in this edition) has the authors, Graham et al, welcomed, but should not exceed 400 words. proposing that BCG vaccination should be All communications, including letters to the routine for all medical students shown not be infected by M. tuberculosis. They believe that a combination of TST and an improved Dr John Thompson,
version of the original γ interferon test would 3 Banner St, O'Connor 2602 ACT
Background: Tuberculosis (TB) is a major
QuantiFERON-TB Gold/T-Spot, the test they propose, did not perform as well as hoped in countries. Following the disruption to health a recent South African series. In other words services in East Timor due to violent political conflict in 1999, the National Tuberculosis Control Program was established, with a local It is easy to understand why BCG vaccination agency. Within a few months the TB program was no longer offered to medical students in Methods and Findings: Using the East
disease in most of Australia, and multidrug Timor TB program as a case study, we have resistance was virtually unknown. Thus the risk of a student developing the disease did implementation of this type of communicable not justify vaccination. As Graham et al have disease control program in a post-conflict pointed out, the situation has now changed. undertaken, and semi-structured interviews outside Australia in poor countries where TB were conducted in 2003 with 24 key local and is rife, or even in Aboriginal communities in international stakeholders. Coordination, North Australia where the disease remains cooperation and collaboration were identified as major contributors to the success of the TB program. The existing local structure and exposed to multidrug resistant organisms at a rate far greater than their occurrence in organisation, the commitment among local Australia. These circumstances suggest that establishing an effective program, and the considered for all medical students. There is willingness of international advisers and local little point in giving INH chemoprophylaxis to counterparts to be flexible in their approach an infected student or graduate with resistant were also important factors. This success organisms, while current data show that the alternative, a combination of rifampicin plus including mass population displacement, lack of infrastructure and the competing interests into sick ones. It may be that the National of organisations working in the health sector. Conclusions: Five years after the conflict,
Australia wide guidelines on this issue., and the TB program continues to operate in all having done so, publicise them more widely districts with high notification rates, although challenge. Lessons learned in East Timor may be applicable to other post-conflict TB after major conflict: experiences and
settings where TB is highly prevalent, and lessons learned in East Timor
may have relevance to other disease control Martins et al Dili, East Timor, Darwin,
Comment: As well, the post-colonial nature
Australia
PLOS Med 2006; 3: e383
Socio-political Issues
Methods: We retrospectively reviewed all
reported cases of active tuberculosis in
Toronto between July 1 1999, and June 30, Counterfeit anti-infective drugs
2002. We obtained extensive clinical data on cases as well as information on the training Newton et al Vientiane Laos, Oxford UK,
and clinical experience of treating physicians. Atlanta USA, Bangkok Thailand.
associated with patient mortality in a survival Lancet Infect Dis 2006; 6: 602
Results: In a multivariable Cox regression
Summary: The production of counterfeit or
analysis involving 1154 patients, factors associated with all-cause mortality included patient age (in years) (hazard ratio [HR] 1.05, that contributes to morbidity, mortality and P<0.001), use of directly observed therapy reporting of resistance and toxicity and loss (HR 0.22, CI 0.13-0.39, p<0.001), receipt of tuberculosis (per case managed per year)(HR 0.98,CI O.97-0.99; p<0.01) Factors that were not associated with patient survival included analysis and simple field tests will enhance drug quality monitoring, improved access to foreign medical school, the physician's inexpensive genuine medicines, support of medical specialty and the number of years in reporting, vigorous law enforcement, and Interpretation: Physician experience with
tuberculosis and use of directly observed therapy positively influenced the survival of patients with active tuberculosis in our Comment: There seems to be a particular
problem with some multidrug antituberculosis Comment: Another example of the 'learning
The impact of physician training and
experience on the survival of patients with
Tuberculin reactivity among health care
active tuberculosis.
workers in nonhospital settings
Khan et al Toronto Canada
Shah et al Saskatoon, Canada,
Washington, Baltimore Md, Lubbock Tx
CMAJ 2006; 175: 749
Background:
Am J Infect Control 2006; 34: 338
influencing treatment outcomes of patients Background:
with tuberculosis. We conducted an analysis compensation data to identify health care workers at risk of tuberculosis exposure in the characteristics and their association with the rate of death among tuberculosis patients. Methods: We identified State Fund workers'
investigate the major determinants of grant tuberculin skin test (TST) conversion (size Methods: With information available publicly
>/=10mm) with a previous negative skin random-effects analysis to investigate the effect of grant characteristics, types of Results: Health care workers experienced an
primary recipient and local fund agent, and overall accepted workers' compensation country attributes ion disbursements that equivalent employees (FTEs) per year for one of Global Fund payments). To check the robustness of findings, regression results accounted for the largest number, with 18.4 % tuberculin reactivity claims. The number of tuberculin reactivity claims was the highest Findings: Grant characteristics-such as size
for offices and clinics of doctors of medicine of commitment, lag time between signature (3.7 per 10,000 FTEs), followed by medical and first disbursement, and funding round- Conclusion:
This study allowed implementation. Enhanced political stability characterization of employees in various was associated with high use of grants. Low- nonhospital health services locations with developed health systems for a given level of Comment: Not huge conversion rates: does
income, were more likely to have a higher reporting your tuberculin conversion now rate of grant implementation than nations with Interpretation: The higher rate of grant
implementation seen in countries with low support to proponents of major increases in Absorptive capacity and disbursements
health assistance for the poorest countries by the Global Fund to fight AIDS,
and argues that focusing resources on low- Tuberculosis and Malaria: analysis of
income countries, particularly those with grant implementation.
political stability, will not create difficulties of Lu et al Cambridge Ma USA
restricted to grant implementation, which is one part of the issue of absorptive capacity. The Lancet 2006; 368: 483
In the future, assessment of the effect of Background: The Global Fund to fight AIDS,
Tuberculosis was launched in 2002 to attract Comment: No doubt the researchers have
and rapidly disburse money to fight these factored in the enormous absorptive capacity believe that poor countries cannot effectively use such resources to increase delivery of their health programmes- referred to as a lack International standards for tuberculosis
care

Hopewell et al San Francisco CA USA
Lancet Infect Dis 2006; 6: 710
graduates about TB, particularly in countries of high incidence. One suspects that too Summary: Part of the reason for failing to
themselves with their duty to the patient and tuberculosis incidence worldwide is the lack of effective involvement of all practitioners - public and private - in the provision of high quality tuberculosis care. While health-care Can public - private collaboration promote
tuberculosis case detection among the
trained and are expected to have adopted poor and vulnerable?
health practices, the same is not likely to be Malmborg et al Nydalen Norway
true for non-programme providers. Studies of Bull World Health Org 2006; 84: 752
conducted in several different parts of the Summary: Private-public mix (PPM) DOTS is
widely advocated as a DOTS adaptation for common. The basic principles of care for promoting progress towards the international tuberculosis (TB) control targets of detecting 70 % of TB cases and successfully treating diagnosis should be established promptly; 85% of these. Private health care plays a standardised treatment regimens should be central role in health-care provision in many used with appropriate treatment support and developing countries that have a high burden supervision; response to treatment should be of TB. It is therefore encouraging that PPM projects are being set up in various countries responsibilities must be carried out. Prompt treatment are essential for good patient care programmes and other partners in the fight and tuberculosis control. All providers who The objective of this review was to use the patients with tuberculosis must recognise that published literature to assess the range of providers included in PPMs for their ability to individual, but they are also assuming an International Standards for Tuberculosis Care (ISTC) describe a widely endorsed level of elements of a pro-poor PPM model, namely, care that all practitioners should seek to cost-effectiveness from a patient perspective, achieve in managing individuals who have, or accessibility, acceptability and quality. The are suspected of having, tuberculosis. The review revealed that a very large part of the total spectrum of potential PPM-participating providers in delivering high quality care for partners has not yet been explored; current patients of all ages, including those with models focus private-for -profit health-care smear-positive, smear-negative, and extra- pulmonary tuberculosis, tuberculosis caused by drug-resistant Mycobacterium tuberculosis important to think critically about the type of complex, and tuberculosis combined with HIV private providers who are best suited to meeting the needs of the poor, and that more Comment: Familiarity with the contents of
socioeconomic status of patients accessing adequate education of medical students and Comment: All the more important after the
IMF and World Bank set about dismantling the state health systems of so many poor Rifampicin plus pyrazinamide versus
isoniazid for treatment of latent
tuberculosis infection: a meta-analysis
Prevention
Gao et al Chengdu, Sichuan, China

Should medical students be routinely
Int J Tuberc Lung Dis 2006; 10: 1080
offered BCG vaccination?
Setting: Six trials from Haiti, Mexico, the
Graham et al Melbourne Australia
USA, Brazil, Spain, Zambia and Hong Kong. Objective: To evaluate the efficacy and
MJA 2006; 185: 324
safety of rifampicin plus pyrazinamide(RZ) vs. Abstract: BCG vaccination is no longer
routinely offered to all medical students in without human immunodeficiency virus (HIV) Victoria. Practices in Australia's 15 medical vaccination and surveillance for tuberculosis controlled trials (RCTs) and quasi-RCTs that (TB) infection during the medical course. compared RZ for 2-3 months with INH for 6- Health care workers can be exposed to TB in 12 months. Endpoints were development of Australian hospitals, but the risk is much active TB, severe adverse effects and death. higher if they undertake work in countries with Treatment effects were summarised as risk student electives. BCG vaccination is safe , Results: Three trials conducted in HIV-
recipients from active TB, including multidrug- infected patients and three trials conducted in resistant TB. Protection is long-lasting, non-HIV-infected persons were identified. requires only a single dose, and there is new The rates of TB in the RZ group were similar infections, not just active disease. Although infected: pooled RD = 0%; 95 % CI -1-2, P = interpretation of the tuberculin test(TST), 0.89; non-infected persons; pooled RD = 0%; treatment groups ( HIV-infected patients; approach for all Australian medical students pooled RD = -1%, 95% CI -4-2, P=0.53; non- vaccination for students who test negative, incidence of all severe adverse events was provided they have not previously received HIV-infected persons (RD =29%, 95% CI 13- Comment: Such standardisation is long
46, P =0.0005 vs RD =7%, 95% CI 4-10,P< 0.0001).
Conclusion: RZ is equivalent to INH in terms
of efficacy and mortality in the treatment of latent tuberculosis infection. However, this regimen increases the risk of severe adverse Treatment for adult HIV infection: 2006
recommendations of the International
AIDS Society--USA Panel
Comment: There may still be a case to use
RZ in HIV-infected persons within populations Hammer et al USA
where multidrug resistance is very common, JAMA 2006; 296: 827
medical student who had been infected after Context: Guidelines for antiretroviral therapy
are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are A case for passiveimmunoprophylaxis
used. The International AIDS Society-USA against tuberculosis.
Panel has updated its recommendations as warranted by new developments in the field. Reljic et al London UK
Objective: To provide physicians and other
Lancet Infect Dis 2006; 6: 813
clinicians with current recommendations for the use of antiretroviral therapy in HIV- Summary: HIV-associated tuberculosis is
infected adults in circumstances for which escalating ominously in Africa and south east there is relatively unrestricted access to drugs and monitoring tools. The recommendations Therefore, new approaches to tuberculosis are centered on 4 key issues: when to start control need to be explored. We discuss the antiretroviral treatment; what to start; and potential use of passive immunoprophylaxis what to change. Antiretroviral therapy in with antibodies in tuberculosis control. special circumstances is also described. Although the predominant type of active host Data sources and study selection: A 16-
resistance is T-cell mediated, recent results in monoclonal antibodies to certain antigens research and patient care internationally. (eg, Acr or lipoarabinomannan) can impart scientific conferences from mid 2004 through tuberculous infection. These results are May 2006 were identified and reviewed by corroborated by data from other laboratories on passive vaccination against a number of Conclusions: Antiretroviral therapy in adults
intracellular microbial pathogens. Further continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation humanised) antibody reagents, to increase of therapy continues to be recommended in their protective efficacy, and to expand our all symptomatic persons and in asymptomatic understanding of the mechanisms of antibody persons after the CD4 cell count falls below 350/µL and before it declines to 200/µL. A Comment: Let us hope that this approach is
nonnucleoside reverse transcriptase inhibitor more successful than that using antibodies as or a protease inhibitor boosted with low dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is
TB and HIV
the individual patient profile. Therapy should corticosteroids, if necessary; BIII). Efforts antituberculous and antiretroviral therapy patients with treatment failure is now a although this goal can be difficult to achieve plasma HIV-1 RNA level below 50 copies /ml. Adherence to antiretroviral therapy in the reconstitution inflammatory syndrome overlap short term and the long term is crucial for those that can occur with hypersensitivity treatment success and must be continually reactions to 1 or more of the agents in use Mycobacterium tuberculosis
infection:
Comment: We are still not sure how long to
The use of antiretroviral therapy in patients delay ART following the institution of TB with active Mycobacterium tuberculosis infection is complicated by interactions inflammatory syndrome in patients in whom treatment for the 2 infections is started in Effect of tuberculosis preventive therapy
patients. These reactions usually occur in the on HIV disease progression and survival
in HIV-infected adults.
antiretroviral therapy and reflect reconstituted immunity to M tuberculosis. They may include Lim et al Milwaukee WIS USA
systemic manifestations, such as fever and HIV Clin Trials 2006; 7: 172
malaise, or local reactions in organs, such as Purpose: To determine whether tuberculosis
(TB) preventive therapies alter the rate of disease progression to AIDS or death and to Recommendations
identify significant prognostic factors for HIV simultaneously, treatment for tuberculosis Method: In a randomized placebo-controlled
trial in Kampala, Uganda, 2,736 purified Antiretroviral therapy should not be delayed protein derivative (PPD)-positive and anergic for patients with low CD4 cell counts but a HIV-infected adults were randomly assigned precise CD4 cell count threshold at which to four and two regimens respectively. PPD- positive patients were treated with isoniazid (INH) for 6 months (6H; n=536), INH plus rifampicin for 3 months (3 HR; n=556), INH established in controlled clinical trials (BIII). All HIV-1-infected patients with tuberculosis should be treated with a rifamycin-based months (n=464). Anergic participants were regimen. Drug selections and dosages for treated with 6H (n= 395) or placebo (n= 323). their antiretroviral regimens should be made Results: During follow-up, 404 cases
with considerations for the interactions between rifamycins and antiretroviral agents occurred. The cumulative incidence of the AIDS progression was greater in the anergic pronounced for rifampin than for rifabutin. cohort compared to the PPD-positive cohort Immune reconstitution inflammatory syndrome reactions are best managed with (p <.0001). Among PPD-positive patients, efavirenz-based antiretroviral regimen. No the relative risk of the AIDS progression with INH alone was 0.95 (95% CI 0.68-1.32); with necessary. Nevirapine can be an alternative 3HR it was 0.83 (95% CI 0.59-1.17; and with to efavirenz in this situation. For patients who cannot take efavirenz, either due to controlling for significant baseline predictors. resistance or intolerance, rifabutin and a Among anergic patients, the relative risk of the AIDS progression was 0.81(95% CI 0.52- adjustments. No definite recommendations can be given regarding the optimal timing of Conclusion: The number of signs or
antiretroviral therapy, but a delay of two months after initiation of antituberculosis morbidity and mortality. Even though the therapy would be advisable and seems safe effective in reducing the incidence of TB for Comment: A reasonably simple guide to the
HIV-infected adults, their benefit of delaying Comment: Yet we know that the presence of
TB causes HIV-infection to progress more Microbiology
Automatic identification of Mycobacterium
tuberculosis by Gaussian mixture models
Antiretroviral therapy in AIDS patients
Forero et al Birmingham UK
with tuberculosis
J Microscopy 2007; 223: 120
Moreno et al Madrid Spain
Summary: Tuberculosis and other kinds of
AIDS Rev 2006; 8: 115
mycobacteriosis are serious illnesses for which early diagnosis is critical for disease Summary: Tuberculosis associated with HIV
bacillus detection but current sample-analysis techniques are time-consuming, very tedious, subject to poor specificity and require highly concomitant treatment for tuberculosis has pattern-recognition are appropriate tools for improving the manual screening of samples. problems faced by clinicians include the Here we present a new technique for sputum image analysis that combines invariant shape rifamycins, a cornerstone in antituberculosis features and chromatic channel thresholding. therapy, and protease inhibitors, which are Some feature descriptors were extracted from an edited bacillus data set to characterize combination regimens, as well as the best moment to initiate antiretroviral therapy in patients with tuberculosis. The therapy of model representation and a minimal error choice for patients with no previous antiretroviral experience includes an antituberculosis regimen with rifampin and an employed for the last identification stage. nosocomial fungal pathogen can survive up This technique constitutes a step towards automating the process and providing a high other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or Comment: We look forward to further
shorter (Candida parapsilosis,14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. How long do nosocomial pathogens
as astrovirus, HAV, polio-or rota virus, persist persist on inanimate surfaces? A
systematic review.
viruses, such as HBV or HIV can persist for more than one week. Herpes viruses, such Kramer et al Greifswald, Berlin,
Hamburg, Germany
shown to persist from only a few hours up to BMC Infect Dis 2006; 6: 130
Conclusion: The most common nosocomial
pathogens may well survive or persist on Background: Inanimate surfaces have often
surfaces for months and can thereby be a been described as the source for outbreaks of nosocomial infections. The aim of this regular preventive surface disinfection is Comment:
Methods:The literature was systematically
restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of a Microscopic-observation drug-
nosocomial pathogen on any type of surface susceptibility assay for the diagnosis of
Results: Most gram-positive bacteria, such
Moore et al London UK, Lima Peru,
Staphylococcus aureus (including MRSA), or Baltimore Md, New Orleans Lo, USA
Streptococcus pyogenes, survive for months N E J Med 2006; 355: 1539
Escherichia coli, Klebsiella spp., Background: New diagnostic tools are
Pseudomonas aeruginosa, Serratia urgently needed to interrupt the transmission of tuberculosis and multi-drug tuberculosis. survive for months. A few others, such as Rapid, sensitive detection of tuberculosis and Bordetella pertussis, Haemophilus influenzae, multi-resistant tuberculosis in sputum has Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including studies of the microscopic-observation drug- Mycobacterium tuberculosis and spore susceptibility(MODS) assay, in which broth forming bacteria, including Clostridium difficile cultures are examined microscopically to can also survive for months on surfaces. Methods: In an occupational setting in Peru,
Current evidence on diagnostic accuracy
of commercially based nucleic acid
amplification tests for the diagnosis of
susceptibility testing in three target groups: pulmonary tuberculosis
tuberculosis, prescreened patients at high Greco et al Rome Italy
risk for tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized Thorax 2006; 61: 783
Background:
nucleic acid amplification tests (NAATs) have reference methods: automated mycobacterial become the most frequently used molecular culture and culture on Lowenstein-Jensen tests for laboratory diagnosis of pulmonary tuberculosis (TB), published studies report Results: Of 3760 sputum samples, 401
Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89% pulmonary TB in smear positive and smear for automated mycobacterial culture, and negative respiratory samples using culture as (P<0.001); the median time to culture Methods: English language studies reporting
positivity was 7 days, 13 days and 26 days, data sufficient for calculating sensitivity and respectively (P<0.001),and the median time specificity of commercial NAATs on smear to the results of susceptibility tests was 7 positive and/or smear negative respiratory days, 22 days, and 68 days, respectively. samples were included. Meta-regression was The incremental benefit of a second MODS used to analyse associations with reference culture was minimal, particularly in patients at test quality, the prevalence of TB, sample and test type. Predictive values for different resistant tuberculosis. Agreement between levels of pre-test probability were quantified susceptibility was 100% for rifampin, 97% for Results: Sixty three journal articles published
isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance), criteria. Pooled sensitivity and specificity omycin (kappa values, 1.0,0.89,0.93,0.71 and Conclusions: A single MODS culture of a
media used as reference test, the inclusion of bronchial samples, and the TB prevalence multidrug-resistant tuberculosis than the accuracy. The test type had no effect on the Comment: As I understand it a positive
correlated with sensitivity or sensitivity, culture is determined by the presence of 'cording' and other known characteristics. Conclusions: Commercial NAATs can be
But 'cording' will not distinguish members of confidently used to exclude TB in patients M. tuberculosis complex from each other. environmental mycobacterial is suspected and to confirm TB in a proportion of smear characteristics of primary studies have a P=.001). Linear regression analysis revealed considerable effect on the reported diagnostic presence of DM (P=.06), and plasma glucose Comment: We could believe there is no
concentration (P=.016) were correlated with longer any place for "in house" NAAs. Conclusion: Exposure (AUC 0-6h) to
patients with TB and DM, compared to patients with TB only. Patients with TB and Pharmacology
Exposure to rifampicin is strongly
Comment: It is interesting that the presence
reduced in patients with tuberculosis and
of DM alone does not correlate with lower type 2 diabetes
exposure to rifampicin. Are we to conclude that such low exposure is limited with poorly Nijland et al Jakarta Indonesia
Clin Infect Dis 2006; 43: 848
Background: Type 2 diabetes (DM) is a
strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Pulmonary tuberculosis in infants:
radiographic and CT findings
compared the pharmacokinetics of rifampicin Kim et al Seoul Korea
in patients with TB, with and without DM. Methods: Seventeen adult Indonesian
AJR 2006; 187: 1024
sex-matched patients with TB and without Objective: As complications of tuberculosis
DM were included in the study during the are frequent in infancy, correct diagnosis of tuberculosis in infants is important. The patients received 450 mg of rifampicin (10 radiographic and CT findings of pulmonary weekly. Steady-state plasma concentrations tuberculosis in infants and to determine the radiologic features frequently seen in infants desacetylrifampicin were assessed at 0, 2, 4, Conclusion: Frequent radiologic findings of
Results: Geometric means of rifampicin
exposure (AUC 0-6 h) were 12.3 mg x h/L ( mediastinal or hilar lymphadenopathy with 95% CI, 8.0-24.2) in patients with TB and central necrosis and airspace consolidations, DM, and 25.9 mgxh/L (95% CI, 21.4-40.2) in especially masslike consolidations with low- attenuation areas or cavities within the concentration of rifampicin. No significant nodules and airway complications are also differences in time to maximum concentration frequently detected in this age group. CT is a of rifampicin were observed. The AUC 0-6 h useful diagnostic technique in infants with of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only (geometric mean, 0.6 vs 3.2 mg xhL; radiography. CT scans can also be helpful when chest radiographs are inconclusive or A randomized controlled trial of two
complications of tuberculosis are suspected. treatment programs for homeless adults
Comment: Despite the increased ionizing
with latent tuberculosis infection
radiation exposure there is a case to be made for all chest Xray negative infants with Nyamathi et al Los Angeles, San
strongly positive tuberculin tests to have non Francisco, CA USA
contrast CT studies of the mediastinum at the Int J Tuberc Lung Dis 2006; 10: 775
Setting: Few studies have examined
strategies for optimizing adherence to latent Tuberculous pericardial effusion after
Objectives: 1) To compare the effectiveness
coronary artery bypass graft
of an intervention program employing nurse case management and incentives (NCMI) vs. Tuladhar et al London UK
a control program with standard care and incentives on completion of LTBI treatment; Ann Thor Surg 2006; 82: 1519
Summary: We describe a case of a recurrent
pericardial effusion after coronary artery Design: A prospective, two-group, site-
bypass grafting. This was initially considered to be due to post-pericardiotomy syndrome homeless adults residing in the Skid Row tuberculosis. After definitive surgery for this immunohistochemistry confirmed the change in TB knowledge. diagnosis of tubercular pericarditis. At 4 Results: Using intent-to-treat analysis, 62%
of participants in the intervention program, tuberculous therapy and corticosteroids, the compared with 39% of controls, completed the full 6-month course of LTBI treatment with without further recurrence of his tuberculous INH. Logistic regression modeling revealed pericarditis. Local reactivation of tuberculosis that intervention had three times greater odds after pericardiotomy has not been previously of completing INH treatment than controls. reported and merits careful consideration in population groups in which tuberculosis is intervention participants (P<0.0001). Comment: A successful outcome, although
Conclusions: Nurse case management
there could be concerns in giving high dose combined with education, incentives, and cortico-steroids to someone with tracking dramatically improves both atherosclerotic disease. knowledge in homeless persons compared to Comment: Whether TB control agencies can
afford the extra costs involved in this
Int Nurs Rev 2006; 53: 253
Aim: To identify the forms and means of
emotional support that nurses provide to Educational competencies to strengthen
patients living with multidrug-resistant tuberculosis curricula in undergraduate
nursing programs.
Background: A fundamental role of nurses is
to provide emotional support, defined as all Fair et al Houston TX USA
the strategies that a health team employs to Int J Nurs Educ Scholarsh 2006; 3: Art 23
well-being of the patient. However, neither
the forms of emotional support nor the means Summary: Worldwide, at least two million
people die annually from tuberculosis (TB), paper describes a qualitative study of a team with projections of 36 million more global of seven nurses working in a programme that provides individualized MDR-TB treatment to help nursing faculty strengthen TB curricula patients in Lima, Peru. It describes the and standardize TB content in national and international undergraduate nursing support that facilitated the ability of patients programs, the Nurse Discipline Group of the National Tuberculosis Curriculum Consortium economic difficulties, social stigma, drug side- effects, problems related to different stages of treatment and concurrent illnesses/special Methods: Qualitative study methods were
knowledge, ability, and/or skills required for an undergraduate nursing student to provide observe nurses and patients in an MDR-TB qualified holistic care for patients, families, observation sessions of nurses with their multidisciplinary health care educators in the patients and focus groups with seven nurses. United States, with the primary mission to Conclusion: Through theme and content
instill knowledge, skills, and appropriate analysis of qualitative data, ten situations attitudes in the management of active and latent TB among undergraduate health care These ten issues served as an analytical framework used to identify and discuss the Comment: We know that Australian nursing
various types of emotional support provided undergraduates have a very steep learning by both formal and informal means. This type curve for TB when they graduate and work in of support focused on problems related to far northern Australia and in surrounding different stages of treatment, social stigma of the illness, treatment adherence, side-effects, concurrent illnesses/special situations. Practice Implications: The essential role of
Nurses as providers of emotional support
the nurse as a provider of emotional support to patients with MDR-TB.
similar programmes with MDR-TB should, in Chalco et al Lima Peru
Comment: This study certainly emphasizes
the role of the nurse as individual patient
advocate and counsellor rather than as agent tuberculosis with a strong ability to boost prior of the community in controlling a disease Comment: This may be a genuine advance.
Immunology
Mucosal administration of Ag85B-ESAT-6
Antigen-specific CD8 + T cells and the
protects against infection with development of central memory during
Mycobacterium tuberculosis and boosts
Mycobacterium tuberculosis infection
prior bacillus Calmette-Guerin immunity.
Kamath et al Boston MA USA
Dietrich et al Copenhagen Denmark
J Immunol 2006; 177: 6361
J Immunol 2006; 177: 6353
Summary: Whether true memory T cells
Summary: We have examined the intranasal
develop in the face of chronic infection such as tuberculosis remains controversial. To Mycobacterium tuberculosis(Mtb) consisting address this question, we studied CD8 (+) T of the mucosal adjuvant LTK63 and the AG Ag85B-ESAT-6. Vaccination with tuberculosis ESAT6-related Ags TB10.3 and LTK63/Ag85B-ESAT-6 gave a strong and (20-28) is presented by H-2 K(d), and 20-30% lasting protection against tuberculosis, chronically infected mice are specific for this equivalent to that observed observed with Ag following respiratory infection with M tuberculosis. These TB 10.3/10.4 (20-28)- specific CD8(+) T cells produce IFN-gamma bromide/monophophoryl lipid A. Because a and TNF and express CD 107 on their cell crucial element of novel vaccine strategies is surface, which indicates their likely role as the ability to boost BCG-derived immunity, we CTLL in vivo. Nearly all of the AG-specific CD8(+) T cells in the lungs of chronically infected mice had a T effector cell phenotype vaccinated mice. We found that vaccinating based on their low expression of CD 62L and with LKT63/Ag85B-ESAT-6 strongly boosted TB10.3/10.4 (20-28)-specific CD8 (+) T cells was identified in the lymphoid organs that observed that infection with M.tb led to a express high values of CD62L and CD45RB. significant increase in anti-M.tb-specific CD4 Antibiotic treatment to resolve the infection T cells in the lungs of LKT63/Ag85B-ESAT-6- led to a contraction of the Ag-specific CD* (+) T cell population and was accompanied by an significant increase in the protection against increase in the proportion of CD8(+) T cells M.tb in LKT63/Ag85B-ESAT-6-boosted mice, with a central memory phenotype. Finally, significant expansion of TB10.3/10.4(20-28)-specific CD8(+) T cells, which suggests that these cells are in fact functional memory T Comment:
derived IFN-gamma differentially regulates T- function in M. tuberculosis infection and suggest that this response could serve as an NK cell-derived IFN-(gamma) differentially
important barrier in AIDS patients or other regulates innate resistance and neutrophil
individuals with compromised CD4(+) T cell response in T cell-deficient hosts infected
with Mycobacterium tuberculosis.
Comment: A fascinating revisit to the natural
Feng et al Bethesda MD USA
J Immunol 2006; 177: 7086
Treatment
Summary: Although it is known that IFN-
gamma-secreting T cells are critical for Rifapentine for the treatment of pulmonary
tuberculosis.
contribution of IFN-gamma produced by NK cells to host resistance to the pathogen is Munsiff et al New York NY USA
deficient RAG (-/-) mice, we showed that M Clin Infect Dis 2006; 1468
tuberculosis stimulates NK cell-dependant Summary: Rifapentine is a recently approved
cultures and in lungs of infected animals. antituberculosis drug that has not yet been More importantly, common cytokine receptor widely used in clinical settings. Clinical data gamma-chain(-/-) RAG(-/-) animals deficient support intermittent use of rifapentine with in NK cells, p40(-/-)RAG (-/-), or anti-IFN- isoniazid during the continuation phase of tuberculosis treatment. Patients with culture- displayed significantly increased susceptibility positive, noncavitary, pulmonary tuberculosis to M. tuberculosis infection compared with whose sputum smear is negative for acid-fast untreated NK-sufficient RAG (-/-) controls. bacilli at the end of the two month intensive Studies comparing IL-12 p40-P 35-deficient treatment are eligible for rifapentine therapy. RAG (-/-) mice indicated that IL12 plays a immunodeficiency virus-infected patients, mediated antimycobacterial effector functions given their increased risk of developing than IL 23 or other P40-containing IL-12 family members. The increased susceptibility of IL-12 deficient or anti-IFN-gamma mAb- currently recommended for children aged <12 treated RAG (-/-) mice was associated with not only elevated bacterial loads, but also with the development of granulocyte-enriched extrapulmonary tuberculosis. Rifapentine foci in lungs. The tissue response correlated (600mg) is administered once weekly with with increased expression of the granulocyte isoniazid (900 mg) during the continuation chemotactic chemokines KC and MIP-2 in NK phase of treatment. This combination should only given under direct observation. As with Interestingly, depletion of granulocytes further rifampin, drug-drug interactions are common, increased bacterial burdens and exacerbated and regular patient monitoring is required. attractive both for tuberculosis-control neutrophils in the absence of IFN-gamma. The above observations indicate that NK cell- Comment: Rifapentine seems inferior to
six-month regimen was effective regardless rifampin unless you follow the guidelines laid of HIV infection. The potential benefits from adjunctive corticosteroids in the management of effusive tuberculous pericarditis could not be demonstrated in this three-year study. Comment: A convincing study, even though
Experience with adjunctive
corticosteroids in managing tuberculous
pericarditis.
Reuter et al Cape Town South Africa
Cardiovasc J S Afr 2006; 17: 233
A diagnostic review: children of the
third world.
Objectives: To compare the efficacy of
intrapericardial corticosteroid therapy to either A refined symptom-based approach to
oral corticosteroid therapy or intrapericardial diagnose pulmonary tuberculosis in
placebo in addition to closed children.
Marais et al Cape Town South Africa
Methods: Patients with large pericardial
Pediatrics 2006; 118: 1350
effusions requiring pericardiocentesis were included. A short-course anti-tuberculous Background: Tuberculosis control programs
place an almost exclusive emphasis on adults randomized to one of three treatment groups: with sputum smear-positive tuberculosis , because they are most infections. However, children contribute a significant proportion of experience considerable tuberculosis-related Patients were followed up for at least one morbidity and mortality, but few children in Results: Fifty seven patients were included
antituberculosis treatment. The diagnostic in the study; 21 tested HIV positive (36.8%). difficulty experienced in endemic areas with Forty (70.0%) had microbiological and/or limited resources has been identified as a histological evidence of tuberculosis, and 17 major factor contributing to poor treatment (30.0%) had a diagnosis based on clinical and laboratory data. All patients responded scepticism regarding the potential value of well to initial pericardiocentesis. However, nine patients (16.0%) were lost to follow up. because current diagnostic approaches are The hospitalisation duration for the steroid often poorly validated. The natural history of groups was shorter than for the placebo. The childhood tuberculosis demonstrates that difference was not significant. Complications symptoms may offer good diagnostic value if they are well defined and if appropriate risk Conclusions: Intrapericardial and systemic
stratification is applied. This study aimed to corticosteroids were well tolerated but did not improve the clinical outcome. The standard symptoms to diagnose childhood pulmonary tuberculosis in a tuberculosis-endemic area. Methods: A prospective, community-based
tuberculosis, or (3) probable tuberculosis (as defined), excluding isolated pleural effusion. Africa. Specific well-defined symptoms were Results: In total, 1024 children were referred
documented in all children < 13 years of age reporting a persistent,nonremitting cough of > 2 weeks duration; study participants were (41.8%) children with persistent nonremitting thoroughly evaluated for tuberculosis. In symptoms at evaluation were investigated for addition, all of the children who received tuberculosis. Pulmonary tuberculosis was antituberculosis treatment during the study period were reviewed by the investigator, categorized as bacteriologically confirmed tuberculosis, 75 as radiologically certain concurrent disease surveillance provided a nonremitting cough of > 2 weeks duration, disadvantages associated with this symptom- preceding 3 months), and fatigue provided based diagnostic approach. In the absence of an acceptable gold standard test optimal uninfected children (sensitivity: 62.6%; case definition is an important consideration. specificity, 89.8%; positive predictive value: Children were characterized as 83.6%); the performance was better in the "bacteriologically confirmed tuberculosis", low risk group (> or= 3 years; sensitivity : "radiologically certain tuberculosis", "probable 82.3%; specificity: 90.2%; positive predictive tuberculosis", or "not tuberculosis". value: 82.3%) than in the high risk group ( < 3 Bacteriologically confirmed tuberculosis was years; sensitivity: 51.8%; specificity: 92.5%; defined as the presence of acid-fast bacilli on positive predictive values: 90.1%). In children with an uncertain diagnosis at presentation, tuberculosis cultured from a respiratory clinical follow-up was a valuable diagnostic specimen. Radiologically certain tuberculosis accuracy, particularly in the low-risk group. radiograph indicated certain tuberculosis in diagnostic value in HIV-infected children. the absence of bacteriological confirmation. Three (15%) of the 20 HIV-infected children Probable tuberculosis was defined as the diagnosed with pulmonary tuberculosis failed presence of suggestive radiologic signs and to report symptoms of sufficient duration to good clinical response to antituberculosis treatment in the absence of bacteriologic reported persistent, nonremitting symptoms in confirmation or radiologic certainty. Good the absence of tuberculosis. In addition, the clinical response was defined as complete tuberculin skin test was positive in < 20% of symptom resolution and weight gain of > or = 10% of body weight at diagnosis, within 3 months of starting antituberculosis treatment. Discussion: The combined presence of 3
Not tuberculosis was defined as spontaneous (persistent, nonremitting cough of > 2 weeks antituberculosis therapy in the absence of duration,objective weight loss [documented bacteriologic confirmation or radiologic signs failure to thrive] during the preceding 3 months; and reported fatigue) provided good tuberculosis was defined as a symptomatic child with (1) bacteriologically confirmed children > or = 3 years of age, with clinical tuberculosis, (2) radiologically confirmed follow-up providing additional value. The approach performed less well in children < 3 years. However, the presence of a persisting Conclusions: Pulmonary tuberculosis can be
nonremitting cough together with diagnosed with a reasonable degree of documented failure to thrive still provided a accuracy in HIV-uninfected children using a fairly accurate diagnosis (sensitivity: 68.3%; simple symptom-based approach. This offers specificity: 80.1%; positive predictive value: the exciting prospect of improving treatment 82.1%), illustrating the importance of regular access for children, particularly in resource weight monitoring in young children. Clinical limited settings where current access to follow-up also offered additional diagnostic value, but caution is required, because very Comment: An important study in its
young children have an increased risk of relevance to poor countries with high TB performed badly in HIV-infected children. group has enormous expertise in childhood Recent household contact with an adult index tuberculosis. Whether their findings are reproducible in other countries remains to be value than a positive tuberculin skin test, bul T-cell-based assays may offer the only real improvement in sensitivity to diagnose M. tuberculosis infection in HIV-infected children. The variable diagnostic value offered by this illustrates the importance of risk stratification, as demonstrated by the fact that 11 (91.7%) Extensively drug-resistant tuberculosis as
a cause of death in patients co-infected
manifestations who failed to meet the entry with tuberculosis and HIV in a rural area of
criteria were < 3 years of age or HIV-infected. South Africa.
Particular emphasis should be placed on the provision of preventive chemotherapy after Gandhi et al New Haven CT USA
these high-risk children. Study limitations Lancet 2006; 368: 1575
include the small number of HIV-infected children, but on the positive side, the large Background: The epidemics of HIV-1 and
number of HIV-uninfected children permitted tuberculosis in South Africa are closely adequate evaluation in this important group. related. High mortality rates in co-infected It is often forgotten that HIV-uninfected patients have improved with antiretroviral children constitute the majority of child therapy, but drug-resistant tuberculosis has tuberculosis cases, even in settings where HIV is endemic. This study demonstrates the assessed the prevalence and consequences importance of ascertaining a child's HIV status before symptom-based diagnosis is extensively drug-resistant (XDR) tuberculosis attempted. Because children were recruited in a rural area in KwaZulu Natal, South Africa. at both the clinic and hospital level, some Methods:
selection bias may have been introduced; surveillance for drug-resistant tuberculosis however, the only significant difference with sputum culture and drug susceptibility between the 2 groups was the proportion of testing in patients with known or suspected HIV-infected children. Pulmonary tuberculosis. Genotyping was done for tuberculosis was diagnosed with different isolates resistant to first-line and second-line levels of certainty differences were recorded Results: From January 2005, to March 2006,
sputum was obtained from 1539 patients.
patients, of whom 53 had XDR tuberculosis. Methods: Data on drug susceptibility testing Prevalence among 475 patients with culture for four antituberculosis drugs-isoniazid, rifampicin, ethambutol, and streptomycin- were gathered in the third round of the Global tuberculosis. Only 55% (26 of 47) of patients Project (1999-2002) from surveys or ongoing surveillance in 79 countries or geographical treated for tuberculosis; 67% (28 0f 42) had a recent hospital admission. All 44 patients those from the first two rounds of the project with XDR who were tested for HIV were co- participated followed a standardised set of tuberculosis died, with median survival of 16 among the 42 patients with confirmed dates of death. Genotyping of isolates showed that resistance to any of the four antituberculosis 39 of 46 (85%, 95% CI 74-95) patients with drugs in new cases of tuberculosis identified in 76 countries or geographical settings was Conclusions: MDR tuberculosis is more
prevalent than previously realised in this prevalence of multidrug resistance in new transmitted to HIV co-infected patients and is Karakalpakstan (Uzbekistan), Estonia, Israel, observations warrant urgent intervention and the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported prevalence of Comment: We now know that XDR bacilli are
analysis showed a significant increase in the easily passed to the immunosuppressed and prevalence of multidrug resistance in new seem to be virulent. Will they be as virulent cases in Tomsk Oblast (p<0.0001). Hong reported significant decreasing trends in Epidemiology of antituberculosis drug
resistance ( the global project on
antituberculosis drug resistance tuberculosis control in countries of the former
surveillance): an updated analysis
Soviet Union and in some provinces of China. Gaps in coverage of the Global Project are Aziz et al Antwerp Belgium, Atlanta GA
substantial, and baseline information is USA, Geneva Switzerland
urgently required from several countries with The Lancet 2006; 368: 2142
Comment: This is where the "political will" of Background: The burden of tuberculosis is compounded by drug-resistant forms of the disease. This study aimed to analyse data on antituberculosis drug resistance gathered by Case Report
Superficial thrombophlebitic tuberculide
Project on Anti-tuberculosis Drug Resistance Surveillance. Comment: Yes, although since PCR the
Motswaledi et al Limpopo South Africa
whole issue of what is a tuberculide and what Int J Dermatol 2006; 45: 1337
`````````````````````````````````````````````````````JT Background: Tuberculides are the result of
components of Population Studies
Mycobacterium tuberculosis. There are three The influence of previous exposure to
tuberculide, erythema induratum of Bazin, environmental mycobacteria on the
and lichen scrofulosorum. In 1997, in Japan, interferon-gamma response to bacille
Hara and coworkers reported five patients Calmette-Guerin vaccination in southern
with what they called "nodular granulomatous England and northern Malawi.
phlebitis" which they proposed was a fourth type of tuberculide. We describe a patient Weir et al London UK
who presented features identical to those Clin Exp Immunol 2006; 146: 390
attention to the previous report and to support the concept of a fourth tuberculide which Summary: We report a large study of the
effect of BCG vaccination on the in vitro 6- Methods: A black South African man
superficial veins on the antero-medial aspects schoolchildren in south-eastern England, of the lower legs. Nodular swellings were palpable along the course of these veins. vaccination is highly protective against vaccination is not protective. In the UK increase in IFN-gamma response to antigens culture and polymerase chain reaction (PCR). Results: Histologic examination showed a
granulomatous infiltrate localized to the veins relatedness of the species to Mycobacterium in the subcutaneous fat. Stains for acid-fast bovis BCG, and provides further evidence of bacilli and culture were negative but PCR the cross-reactivity of mycobacterial species was positive for M. tuberculosis DNA. The lesions responded promptly to gamma responses to purified protein derivatives (PPDs) from M.tuberculosis and Conclusions: Our patient showed features
identical to those of cases described by Hara prevalent in the Malawian than in the UK and coworkers and assigned as a fourth type group prior to vaccination; BCG vaccination of tuberculide. As the lesions clinically increased the prevalence of responses to resemble superficial thrombophlebitis, we these PPDs in the UK group to a level similar to that in Malawi. There was no evidence thrombophlebitic tuberculide" rather than " virulent MTB release large amounts of TDM magnitude of the initial response of the during growth as a pellicle within cavities. individual to environmental mycobacteria in activation of the toxicity and antigenicity of observations should assist the development TDM at the air interface and that presence of and interpretation of human clinical trials in Comment: Does this mean that TDM is partly
Comment: On the other hand, this study may
``````````````````````````````````````````````````````JT Extra Pulmonary Tuberculosis
Pathogenesis
Mycobacterium tuberculosis presenti-ng
as chronic red eye.
Multiple roles of cord factor in the
pathogenesis of primary, secondary and
Jennings A et al Westmead Sydney
cavitary tuberculosis, including a revised
description of the pathology of secondary
Cornea 2006; 25: 1118
disease.
Purpose: To report a case of tuberculosis of
Hunter et al Houston TX USA
Methods: Case report with pathologic
Ann Clin Lab Sci 2006; 36: 371
relocated to Australia from Liberia presented Summary: Tuberculosis, once thought to
have been controlled, is now resurgent in Results: The diagnosis was not initially
many parts of the world. Many gaps exist in polymerase chain reaction testing. Definitive cavitary disease. Evidence presented here diagnosis was made after repeated histologic suggests that cord factor (trehalose 6,6'- dimycolate, TDM) is a key driver of these resulted in prompt resolution of all ocular processes. It is the most abundant lipid released by virulent M.tuberculosis (MTB) Conclusion: Tuberculous conjunctivitis is
and can switch between two sets of activities. now a very rare condition in the developed On organisms, TDM is non-toxic and protects world. Definitive diagnosis requires the them from killing by macrophages. On lipid identification of Mycobacterium tuberculosis surfaces, it becomes antigenic and highly organisms in conjunctival biopsy specimens- toxic. Caseating granulomas, the hallmark of either through microscopic detection of acid- Comment: The data reported suggests that a
secondary tuberculosis begins as a lipid tuberculide is a more appropriate diagnosis pneumonia that accumulates mycobacterial antigens and host lipids in alveoli before developing conditions for activation of the toxicity and antigenicity of TDM. This rapidly produces cavities or leads to cavities. Finally, Treatment P 11 - 12
CONTENTS
Diagnostic Review: P 12 - 13
Editorial P 1 - 2
MDR-TB P 13 - 14
Disease Control P 2
Case Report P 14
Socio-Political Issues P 2 - 4
Population Studies P 15
Prevention P 4 - 5
Pathogenesis P 15
TB and HIV P 5 - 6
Extrapulmonary TB P 15 - 16
Microbiology P 6 - 8
RFLP in contact tracing
Pharmacology P 8 - 9

Imaging P 9
Surgery P 9
Nursing P 9 -10
Immunology P 10 - 11

Source: http://www.thearc.org.au/Resources/Uploaded/Newsletter/22-1-feb07.pdf