'One Health´ approach to end zoonotic TB.

Mycobacterium bovis has a wide host range causing TB in animals, both in wildlife and cattle (bovine TB bTB), and in humans (zoonotic TB zTB). The real burden of bovine and zoonotic TB (b/zTB) remains unknown due to diagnostic challenges. Although progress has been made to reduce the burden of TB, b/zTB has been neglected in low- and middle-income countries (LMICs) with little improvement in prevention, diagnosis or treatment. Using Tanzania as a case study, because of its high TB burden, large wildlife diversity and wide reliance on livestock, we developed an approach to comprehensively estimate the burden and implement multidisciplinary actions against b/zTB. We performed a review of the literature on b/zTB, but there is a lack of available data on the b/zTB burden in Tanzania and, notably, on epidemiological indicators other than incidence. We propose a five-action programme to address b/zTB in Tanzania, and we believe our proposed approach could benefit other LMICs as it operates by implementing and strengthening surveillance and health delivery. The resulting knowledge and system organisation could further prevent and mitigate the effects of such conditions on human and animal health, livestock production, population livelihood and the economy.

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Informed patient consent for defaulter tracing: should we obtain it?

Active default tracing is an integral part of tuberculosis (TB) programmatic control. It can be differentiated into the tracing of defaulters (patients not seen at the clinic for > or =2 months) and 'late patients' (late for their scheduled appointments). Tracing is carried out to obtain reliable information about who has truly died, transferred out or stopped treatment, and, if possible, to persuade those who have stopped treatment to resume. This is important because, unlike routine care for non-communicable diseases, TB has the potential for transmission to other members of the community, and therefore presents the issue of the rights of the individual over the rights of the community. For this reason, default or 'late patient' tracing (defined together as default tracing in this article) has been incorporated into standard practice in most TB programmes and, in many industrialised countries, it is also a part of public health legislation. In resource-poor countries with limited access to phones or e-mails, default tracing involves active home visits. In this Unresolved Issues article, we discuss the need for patient consent within both the programmatic and the research context; we describe how this subject arose during operational research training at the Research Institute of Tuberculosis in Japan; we provide comments from individuals who are experienced and skilled at international and national TB control; and finally we offer some conclusions about the way forward. This is not an easy subject, and we welcome open debate on the issue.

Cardiopulmonary resuscitation in patients with the acquired immunodeficiency syndrome. A prospective study.

To study the outcome of cardiopulmonary resuscitation (CPR) in patients with acquired immunodeficiency syndrome (AIDS), data on CPR in hospitalized patients were collected prospectively during a one-year study period. Of 43 consecutive patients with AIDS who underwent CPR, 23% were revived in the initial attempt, whereas of 293 patients with other diseases 42% were revived. One (2.3%) of 43 patients with AIDS survived until hospital discharge, and his arrest was iatrogenic, as opposed to 19 (6.5%) of 293 patients with diseases other than AIDS. A respiratory mechanism for the arrest was significantly more common in patients with AIDS. The duration of the unsuccessful attempt did not vary significantly; a higher number of temporary pacemakers was used in patients with diseases other than AIDS indicating a more invasive approach. Survival until hospital discharge is minimal in our series of patients with AIDS, undergoing CPR. We recommend that informative discussions take place early in the course of the disease to provide patients with a better understanding of the available options in case of cardiorespiratory arrest.

Fatal toxic epidermal necrolysis during prophylaxis with pyrimethamine and sulfadoxine in a human immunodeficiency virus-infected person.

The combination of pyrimethamine and sulfadoxine (Fansidar) has been reported to cause severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Recently, this drug combination has been used for prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. After two months of weekly prophylaxis with pyrimethamine and sulfadoxine, a 48-year-old homosexual man who was antibody positive for human immunodeficiency virus developed severe widespread erythema, blisters, and loss of skin in sheets, and subsequently died. To our knowledge, this is the first reported case of fatal toxic epidermal necrolysis occurring in a patient with acquired immunodeficiency syndrome-related complex. The lack of absolute safety of prophylaxis with pyrimethamine and sulfadoxine is emphasized in our case, and mandates cautious use and the consideration of less toxic prophylactic measures such as therapy with the recently introduced aerosolized pentamidine.

Association of tuberculosis risk with the degree of tuberculin reaction in HIV-infected patients. The Gruppo Italiano di Studio Tubercolosi e AIDS.

BACKGROUND: The risk of developing active tuberculosis associated with a different size of induration to purified protein derivative (PPD) has not been prospectively assessed among individuals infected with human immunodeficiency virus (HIV). The quantification of this risk is important to more appropriately identify candidates for preventive therapy for tuberculosis. METHODS: A prospective, multicenter, cohort study on tuberculosis in HIV-infected patients was conducted in 23 infectious disease units in public hospitals in Italy. Two thousand six hundred ninety-five HIV-infected patients were enrolled in the study. Of these, 1054 patients who were nonanergic at the time of entry were included in the present analysis. The median duration of follow-up was 102 weeks. The main outcome measure was a diagnosis of active tuberculosis confirmed by the isolation of Mycobacterium tuberculosis in culture. RESULTS: Among the 252 patients with PPD reactivity, patients with an induration to PPD of 2 to 4 mm had a median CD4+ lymphocyte count of 0.34 x 10(9)/L (interquartile [IQ] range, 0.14 x 10(9)-0.56 x 10(9)), those with a response of 5 to 9 mm had a median count of 0.38 x 10(9)/L (IQ range, 0.24 x 10(9)-0.56 x 10(9)), and those with a response of 10 mm or higher had a median count of 0.37 x 10(9)/L (IQ range, 0.23 x 10(9)-0.52 x 10(9)) (P = .38). Compared with the 802 nonanergic PPD-negative patients, hazard ratios of tuberculosis were 2.1 (95% confidence interval [CI], 0.2-18.3) among the 55 patients with a response to PPD of 2 to 4 mm, 5.7 (95% CI, 1.6-19.8) among the 128 patients with a response to PPD of 5 to 9 mm, and 23.1 (95% CI, 7.8-68.6) among the 69 patients with a response to PPD of 10 mm or higher. CONCLUSIONS: Among nonanergic HIV-infected patients, the degree of response to tuberculin does not appear to reflect the degree of immunosuppression and is strongly correlated with the subsequent incidence of tuberculosis. To identify HIV-infected patients who are at an increased risk of tuberculosis and may benefit from preventive therapy, a response to PPD of 5 mm appears to be an appropriate cutoff point.

Tuberculosis and HIV: current status in Africa.

PIP: Having radically and permanently altered the face of tuberculosis (TB) in Africa, HIV/AIDS is the major threat to TB control programs in Africa. As HIV prevalence rises, so will TB rates. TB rates will plateau once HIV infection does. The control of TB therefore partly depends upon the control of HIV transmission. The current epidemiological situation is described with regard to TB case notification, incidence estimates, and projections; TB and HIV co-infection; and evidence of the interaction between TB and HIV. The impact of HIV upon the clinical management of TB with regard to diagnostic obstacles and treatment complications is considered, followed by an examination of the threats and opportunities for National Tuberculosis Program activities in Africa in the context of HIV/AIDS. Community-based TB care approaches and the role of isoniazid preventive therapy in HIV-infected people are also considered.^ieng

Preventive chemotherapy for HIV-associated tuberculosis in Uganda: an operational assessment at a voluntary counselling and testing centre.

OBJECTIVE: To assess the operational aspects of isoniazid preventive chemotherapy (IPT) for tuberculosis in persons dually infected with HIV and Mycobacterium tuberculosis identified at an independent HIV voluntary counselling and testing centre in Kampala, Uganda. DESIGN: HIV-infected persons were counselled, had active tuberculosis excluded by medical examination, and were offered purified protein derivative (PPD) skin testing. PPD-positive persons were offered isoniazid 300 mg daily for 6 months. Drugs were supplied, and toxicity and compliance were assessed monthly. Utilization of service, cost, and sustainability were also assessed. RESULTS: Between 14 June 1991 and 30 September 1992, 9862 persons tested HIV-positive. Of 5594 HIV-infected clients who returned to collect test results, only 1524 (27%) were enrolled. Of those, 1344 were tuberculin-tested (88%); 180 were not tested because of active tuberculosis, serious illnesses, refusal, and other reasons. Of the 1344, 250 (19%) did not return for test reading and 515 were negative (47% of tests read). Of 579 tuberculin-positive persons, 59 (10%) were excluded from preventive chemotherapy because of tuberculosis and other respiratory illnesses. Of 520 persons given isoniazid, 62% collected at least 80% of their drug supplies. No major toxicity was observed. One case of tuberculosis occurred in the first month of treatment. Cost of HIV counselling and testing was US $18.54 per person and cost of follow-up counselling and social support was US $7.89. CONCLUSIONS: Important factors were identified which caused attrition, such as limited motivation by counsellors to discuss tuberculosis issues during HIV pre- and post-test counselling, insufficient availability of medical screening, shifting of sites to collect pills, and frequent tuberculin-negative tests. Active tuberculosis among 6% of persons screened suggests that voluntary counselling and testing sites may be important for tuberculosis case finding and underscores the need to exclude tuberculosis carefully before starting IPT. In developing countries, further studies assessing the feasibility of IPT within tuberculosis and HIV/AIDS programme conditions are needed. Cost-effectiveness of IPT, compared with passive case finding, and its sustainability should be assessed before national policies are established.

PIP: Those infected with human immunodeficiency virus (HIV) have a 5-10% risk per year of developing active tuberculosis, and this disease may accelerate the clinical course of HIV infection. Thus, a study was conducted in Uganda to assess the cost-effectiveness and acceptability of isoniazid preventive chemotherapy (IPT) for patients dually diagnosed with HIV and Mycobacterium tuberculosis. Of the 1344 HIV-infected patients at an independent HIV testing and counseling center in Kampala who were initially screened for participation in this study, 6% had signs of active tuberculosis. Selected for participation in the study were 520 subjects with no signs of active tuberculosis. Of these, 322 (62%) were considered compliant with the treatment regimen on the basis of their appearance for all scheduled appointments for pill distribution. One case of active tuberculosis occurred during the first month of IPT and most likely represented a case that went undetected in the screening process. No treatment-associated toxicity was reported. The cost of the HIV testing and counseling was US$18.54 per patient; that of follow-up counseling and support was $7.89. When administrative costs for the study were included in the calculation, the cost of IPT increased to $60.19 per person. Although reactivation of tuberculosis may have been prevented in up to 62% of subjects who received IPT, numerous factors mitigate against the routine implementation of such a treatment program, most notably its high cost and a shortage of voluntary HIV centers in developing countries. Needed are studies that evaluate the long-term community health, social, and economic benefits of such a program as well as further investigations of the impact of tuberculosis on the pace of progression from HIV to acquired immunodeficiency syndrome (AIDS).

Pneumocystis carinii infection of the thyroid in a hypothyroid patient with AIDS: diagnosis by fine needle aspiration biopsy.

A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver strain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A repeated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of hypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients.

Infections associated with Hickman catheters in patients with acquired immunodeficiency syndrome.

PURPOSE: Hickman catheters are frequently used as convenient long-term venous access in patients with acquired immunodeficiency syndrome (AIDS). These patients seem to be at increased risk for bacterial infections of intravenous devices. The aim of our study was to determine the frequency of Hickman catheter infection in patients with AIDS as compared with that in other patients. PATIENTS AND METHODS: We analyzed the records of 69 patients who underwent 71 consecutive Hickman catheter placements during a one-year study period. RESULTS: Forty-six Hickman catheters were inserted in 44 patients with AIDS, and 25 Hickman catheters were placed in 25 other patients. There were 18 infections: 16 occurred in patients with AIDS, and two developed in the control group (p less than 0.05). The 16 infections in AIDS were as follows: five exit site, five septicemias, two tunnel, one septic phlebitis, and three probable Hickman catheter-related. Staphylococcus aureus was responsible for 14 cases (87%); Staphylococcus epidermidis was responsible for four cases (25%). Mean onset of infection was 32 days, but seven patients were diagnosed in the first eight days after Hickman catheter insertion. Fever occurred in all patients with early infection, leukopenia was present only in three; infusion of parenteral nutrition did not increase the risk. Two early infections were fatal. The rate of Hickman catheter infection in patients with AIDS was 0.47 per 100 catheter days, as compared with 0.09 in the control group. CONCLUSION: Our findings underscore the need for using Hickman catheters only when absolutely indicated in patients with AIDS, since the risk of serious infectious complications appears to be high.

Pleural Pneumocystis carinii infection.

Extrapulmonary Pneumocystis carinii infection is a rare occurrence in patients with AIDS. Pleural involvement has been demonstrated in only one case, and this occurred after pneumothorax. This is a case report of pleural pneumocystosis in a patient with AIDS who did not have a pneumothorax.

High Staphylococcus aureus nasal carriage rate in patients with acquired immunodeficiency syndrome or AIDS-related complex.

Staphylococcus aureus has been reported to cause a high number of infections and septicemias, often related to intravenous catheters, in patients with acquired immunodeficiency syndrome (AIDS). Our objective was to assess the frequency of S. aureus nasal carriage among patients with AIDS or AIDS-related complex (ARC). The nasal carriage rate of S. aureus was determined within 24 hours of admission in 64 consecutively hospitalized patients with AIDS or ARC. Intravenous drug abusers were excluded. A control group of 64 patients with other diseases was also tested. Of 64 patients with AIDS or ARC, 35 (55%) were nasal carriers of S. aureus, compared with 18 (28%) of 64 control patients. Recent hospitalization did not influence carriage rate, nor did the recent use of antibiotics or zidovudine. The significant S. aureus carriage rate in patients with AIDS or ARC may contribute to the high incidence of intravenous catheter-related S. aureus infections in this population.

The burden of drug-resistant tuberculosis and mechanisms for its control.

Drug resistance in tuberculosis is largely a man-made phenomenon caused by erroneous prescribing practices on the part of physicians and noncompliance on the part of patients. The global epidemiology of drug-resistant TB, the impact of standardized short-course chemotherapy (SSC), and the potential future evolution of MDR TB are discussed in this chapter.

Group G streptococcal meningitis and sepsis in a patient with AIDS. A method to biotype group G streptococcus.

Lancefield group G streptococcus is now recognized as a pathogen and has been reported to cause severe infections, including meningitis. We describe the first case of meningitis caused by this organism in a patient with acquired immunodeficiency syndrome (AIDS) and the direct transmission of the pathogen to a technologist accidentally exposed to the cerebrospinal fluid. To prove the identity of the two strains, we have tested them employing the Vitek system. We have also tested 13 other strains of group G streptococci obtained from different sources. Our results yielded 14 different biotypes with the 15 strains tested. The only identical ones were the two suspect strains from the index case and the technologist. We conclude that the biotyping system employed in our study appears to be a useful epidemiological tool for marking group G streptococci.

Clinical features and management of severe dermatological reactions to drugs.

Cutaneous adverse drug reactions are a frequent occurrence and have been reported in more than 2% of hospitalised patients. Among the most commonly involved drugs are sulphonamides, penicillins, anticonvulsants and non-steroidal anti-inflammatory drugs. Two groups of mechanisms are involved in the pathogenesis of drug reactions: immunological, with all 4 types of hypersensitivity reactions described; and non-immunological, accounting for at least 75% of all drug reactions. Besides minor skin reactions like urticaria, maculopapular rash, fixed eruptions or erythema nodosum, which are generally self-limited, severe life-threatening manifestations also occur. Erythema multiforme is secondary to drugs in half the cases; the minor form is characterised by typical target and iris lesions and is usually benign. However, a much more severe condition, erythema multiforme major or Stevens-Johnson syndrome, is associated with mucosal, ocular and visceral involvement, and carries a mortality of 5 to 15% if untreated. Toxic epidermal necrolysis, which could represent an even more dramatic form of the same disease, is characterised by severe widespread erythema, blisters and loss of skin in sheets, with denudation of more than 10% of the body surface area. This entity is frequently due to drugs. Mortality is 25 to 70%, and 90% of the survivors will have sequelae. Exfoliative dermatitis is an erythematous scaling disease often produced by drugs and carrying significant mortality. Photodermatitis may at times present with severe eczematous features. For clinical and epidemiological reasons it is important to try to identify the culprit drug following an approach based on previous experience with the drug, timing of events, patient reaction to dechallenge, patient reaction to rechallenge (if feasible), alternative aetiological candidates, and drug concentration or evidence of overdose. Management of severe skin reactions to drugs should require admission to a burn unit, where patients should be placed in warmed air-fluidised beds, receive excellent nursing care, analgesics and tranquillisers. Peeling necrotic epidermis should be removed and denuded dermis covered with biological grafts or synthetic dressings. Fluid balance must be adequately maintained; nutritional support and careful monitoring of early signs of skin infections is mandatory to ensure immediate antimicrobial treatment. Ocular care must be excellent to avoid serious sight-threatening sequelae. Steroids are presently not recommended. With these therapeutic modalities, morbidity and mortality can be markedly decreased.