The treatment of infectious diseases: advances in the use of antimicrobial drugs

Twenty-eight patients with pulmonary tuberculosis in a small, tax-supported sanatorium were treated by primary pulmonary resection. In a comparison of results with those obtained in the same sanatorium by thoracoplasty and extrapleural pneumothorax, it was noted that in general the patients who had resection had earlier conversion of sputum to "negative" and had a shorter stay in hospital. Complications were not of sufficient frequency to contraindicate use of resection in cases in which there was doubt that thoracoplasty would be effective. The cost of hospitalization for surgical treatment and postoperative care was considerably less when resection was done than it was for either three-stage or two-stage thoracoplasty.     

PRIMARY PULMONARY RESECTION FOR TUBERCULOSIS—Medical and Economic Aspects in a Small Sanatorium

Twenty-eight patients with pulmonary tuberculosis in a small, tax-supported sanatorium were treated by primary pulmonary resection. In a comparison of results with those obtained in the same sanatorium by thoracoplasty and extrapleural pneumothorax, it was noted that in general the patients who had resection had earlier conversion of sputum to “negative” and had a shorter stay in hospital.Complications were not of sufficient frequency to contraindicate use of resection in cases in which there was doubt that thoracoplasty would be effective.The cost of hospitalization for surgical treatment and postoperative care was considerably less when resection was done than it was for either three-stage or two-stage thoracoplasty.     

Mass survey--Its future

Experience with a fast-tempo case finding survey in Seattle confirms the opinion expressed with regard to other areas, that the tools now are at hand to eradicate tuberculosis in Seattle in a 20-year period. The most important single factor in controlling tuberculosis is segregation and treatment of patients with active cases - sanatorium care that is sufficient in quantity and quality. Aggressive use of community-wide, mass x-ray program constitutes the second largest factor in controlling tuberculosis and has its greatest application in cities of over 100,000 population. The cost of such a mass survey program is trifling when compared with the cost of an adequate hospitalization program. The Seattle experience indicates that the cost of a mass survey program amortized over a five-year period is only 2 per cent of the cost of one year of hospital care.     

Mass Survey—Its Future

Experience with a fast-tempo case finding survey in Seattle confirms the opinion expressed with regard to other areas, that the tools now are at hand to eradicate tuberculosis in Seattle in a 20-year period.The most important single factor in controlling tuberculosis is segregation and treatment of patients with active cases — sanatorium care that is sufficient in quantity and quality.Aggressive use of community-wide, mass x-ray program constitutes the second largest factor in controlling tuberculosis and has its greatest application in cities of over 100,000 population.The cost of such a mass survey program is trifling when compared with the cost of an adequate hospitalization program. The Seattle experience indicates that the cost of a mass survey program amortized over a five-year period is only 2 per cent of the cost of one year of hospital care.     

Drug resistance patterns among hospitalized tuberculous patients in Rio de Janeiro, Brazil, 1993-1994.

The purpose of this study was to analyze the prevalence and risk factors for drug resistance among hospitalized patients in two tertiary care centers, an acquired immunodeficiency syndrome (AIDS) reference center and a sanatorium, in Rio de Janeiro, Brazil. From 1993-1994, 389 patients were diagnosed as having tuberculosis (TB). Isolates from 265 patients were tested for in vitro susceptibility to rifampin and isoniazid. Resistance to one or more drugs was detected in 44 patients (16.6%) and was significantly more common among recurrent cases in both hospitals (p=0.03 in the AIDS center and p=0.001 in the sanatorium). Twenty seven patients (10.2%) had isolates resistant to both isoniazid and rifampin. Multi-drug resistance was associated with human immunodeficiency virus (HIV) infection among patients who had never been treated for TB. In conclusion, drug-resistant TB is high in hospitalized patients in Rio de Janeiro, especially among HIV infected patients. Therefore, measures to control TB and prevent nosocomial transmission need urgently to be set up in the Brazilian hospitals.     

Tuberculosis: Hospitalization and Outpatient Treatment

Initial hospitalization terminated by discharge upon medical advice to continue with chemotherapy on an outpatient basis represents the treatment of choice for most patients with active pulmonary tuberculosis. Any departure from this plan for any patient should be accepted only after careful consideration of all the circumstances. Patients with active pulmonary tuberculosis who are to receive outpatient chemotherapy without adequate initial hospitalization should be carefully selected by the local or provincial department of public health. Approval in writing should be required from the appropriate public health authority before antituberculosis chemotherapy is provided at public expense for any such patient, except possibly for a limited period while awaiting formal approval. In all instances, the clinic which dispenses the antituberculosis drugs should have the patient under supervision with recall for follow-up examinations as required. Prophylactic antituberculosis chemotherapy may be provided to certain groups of persons without hospitalization.     

Short course chemotherapy for tuberculous lymphadenitis in children.

OBJECTIVE--To assess the efficacy of a short course chemotherapy regimen for treating tuberculosis of the lymph nodes in children. DESIGN--Open, collaborative, outpatient clinical trial. SETTING--Outpatient department of the Tuberculosis Research Centre, paediatric surgery departments of the Institute of Child Health and Hospital for Children and the Government Stanley Hospital, Madras, South India. PATIENTS--Children aged 1-12 years with extensive, multiple site, superficial tuberculous lymphadenitis confirmed by biopsy (histopathology or culture). INTERVENTIONS--Patients were treated with a fully supervised intermittent chemotherapy regimen consisting of streptomycin, rifampicin, isoniazid, and pyrazinamide three times a week for two months followed by streptomycin and isoniazid twice a week for four months on an outpatient basis. Surgery was limited to biopsy of nodes for diagnosis and assessment. MAIN OUTCOME MEASURES--Response to chemotherapy was assessed by regression of lymph nodes and healing of sinuses and abscesses during treatment and follow up. Compliance with treatment and frequency of adverse reactions were also estimated. RESULTS--197 Patients were admitted to the study and 168 into the analysis. The regimen was well tolerated and compliance was good with 101 (60%) patients receiving the prescribed chemotherapy within 15 days of the stipulated period of six months. Those whose chemotherapy extended beyond that period received the same total number of doses. Clinical response was favourable in most patients at the end of treatment. Sinuses and abscesses healed rapidly. Residual lymphadenopathy (exceeding 10 mm diameter) was present in 50 (30%) patients at the end of treatment; these nodes were biopsied. Fresh nodes, increase in size of nodes, and sinuses and abscesses occurred both during treatment and follow up. After 36 months of follow up after treatment only 5 (3%) patients required retreatment for tuberculosis. CONCLUSION--Tuberculous lymphadenitis in children can be successfully treated with a short course chemotherapy regimen of six months.     

TUBERCULOSIS—Recent Trends in Infection,Disease and Deaths in California

Although fewer patients with tuberculosis are reported in a far advanced stage of the disease than ever before, the proportion of persons dying of tuberculosis whose disease had not previously been diagnosed appears to be increasing. The average length of sanatorium treatment, and the intramural case fatality rates have not shown much decrease. Tuberculosis mortality rates fall during economic depressions and rise with business booms. Epidemics of influenza do not always increase tuberculosis death rates. Common claims to the contrary are not sustained by recent California data.     

Incidence of Undiscovered Adult Diabetes in a Tuberculosis Sanatorium

The frequent occurrence of tuberculosis in patients with diabetes mellitus is well known. The object of this study was to find the incidence of undiscovered diabetes mellitus in patients with known tuberculosis. A total of 118 sanatorium patients over the age of 15 years were tested with one-hour postcibal blood sugar determinations in February 1961. True blood sugars were used. Nine patients had a value of 148 mg. % or higher. Glucose tolerance tests were carried out on eight of the nine patients with levels of 148 mg. % or higher. Five of these were shown to have diabetes. The incidence of undiscovered diabetes was 4.2% of the patients over 15 years of age in the sanatorium. It is predicted from the shape of the frequency distribution curve that this figure could be as high as 10% if the glucose tolerance tests were done at a level of 130 mg. % or higher.Routine one-hour p.c. blood sugar tests are recommended in all tuberculous patients and glucose tolerance tests in all of those patients with a level of 130 mg. % or higher.     

定西市2007—2010年外出务工人员肺结核线索调査情况分析

目的为了了解外出务工人群的结核病疫情状况,进一步加强对这部分人群结核病的控制工作。方法利用大多外出务工人员春节前集中返乡与家人团聚的时机,对有咳嗽、咳痰超过3周等可疑肺结核病症状者进行摸底调查和造册登记,并由县(区)疾控中心组织免费检查,对确诊患者进行免费抗结核治疗。结果 4年中调查返乡务工人员102万余人次,有可疑肺结核症状者占2.56%,共确诊活动性肺结核患者346例,其中涂阳108例,初治涂阴238例,男女之比为2.15∶1,以青壮年人群为主,20～39岁占73.99%;年均涂阳和活动性肺结核登记率分别为10.59/10万和33.92/10万,涂阳比例为31.21%,其中初治涂阳比例为95.37%。结论外出务工人员是结核病的高发人群,应加强外出务工人员的结核病防治工作,利用外出务工人员春节集中返乡的有利时机开展肺结核病线索调查是主动发现病人的有效方法。     

Tuberculosis; recent trends in infection,disease and deaths in California

Although fewer patients with tuberculosis are reported in a far advanced stage of the disease than ever before, the proportion of persons dying of tuberculosis whose disease had not previously been diagnosed appears to be increasing. The average length of sanatorium treatment, and the intramural case fatality rates have not shown much decrease. Tuberculosis mortality rates fall during economic depressions and rise with business booms. Epidemics of influenza do not always increase tuberculosis death rates. Common claims to the contrary are not sustained by recent California data.     

A Theoretical Assessment of the Effects of Smoking on the Transmission Dynamics of Tuberculosis

Smoking has long being associated with tuberculosis. We present a tuberculosis dynamics model taking into account the fact that some people in the population are smoking in order to assess the effects of smoking on tuberculosis transmission. The epidemic thresholds known as the reproduction numbers and equilibria for the model are determined and stabilities analyzed. Qualitative analysis of the model including positivity and persistence of solutions are presented. The model is numerically analyzed to assess the effects of smoking on the transmission dynamics of tuberculosis. Numerical simulations of the model show that smoking enhances tuberculosis transmission, progression to active disease and in a population of smokers, tuberculosis cannot be controlled even when treatment success is assumed to be as high as 88%. Further, analysis of the reproduction numbers indicates that the number of active tuberculosis cases increases as the number of smokers increase.     

Serodiagnosis of extrapulmonary tuberculosis by enzyme-linked immunosorbent assay (ELISA)

Antibodies against Mycobacterium tuberculosis antigenic glycolipids were determined by enzyme-linked immunosorbent assay (ELISA). The 720 sera were collected from adult patients under investigation, suspected with extrapulmonary tuberculosis. The test performance was estimated according to definitive diagnosis in terms of specificity, sensitivity, positive predictive value and negative predictive value. These parameters calculated on 142 sera from patients with extrapulmonary tuberculosis and on 578 sera from patients with different nontuberculosis diseases were 92%, 81.6%, 70.9% and 95.1%, respectively. The specificity decreased to 85% when tuberculosis was associated with cancer or hepatic cirrhosis. In reactivated tuberculosis the sensitivity and the positive predictive value were 86.9% and 83.3%, respectively. Our results showed that ELISA was conclusive for patients with active tuberculosis, before the initiation of the treatment. The sensitivity decreased to 30% in inactive forms. It was demonstrated that ELISA was positive in cases with negative microscopy genitourinary tuberculosis. ELISA could be used as a supporting test in the laboratory diagnosis of active extrapulmonary tuberculosis in adults, disregarding the site involved.     

Tuberculous Enteritis

Tuberculous enteritis occurs in about 2 percent of patients with pulmonary tuberculosis. Although it is uncommon in the United States, tuberculous enteritis should be considered in any patient with active pulmonary tuberculosis and abdominal complaints.Eight cases of T. enteritis have been treated at Harbor General Hospital in the last 25 years. Associated pulmonary disease was shown radiologically to be present in seven of eight patients. Findings on contrast studies of the gastrointestinal tract showed disease in six of six patients examined.In five patients, surgical operation was required for diagnosis or complications. Resection of diseased bowel with primary anastomosis was done in five patients. Although medical therapy is the mainstay in the treatment of both pulmonary and intestinal tuberculosis, one staged resection of diseased bowel with primary anastomosis is the procedure of choice for complications such as obstruction, hemorrhage or perforation.     

Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states

T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p?=?0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.     

纤维支气管镜局部注药治疗耐药支气管内膜结核

目的:探讨和评价经纤维支气管镜局部注药对耐药肺结核合并支气管内膜结核患者的可行性和疗效.方法:对120例确诊为耐药肺结核合并支气管内膜结核患者,在进行全身抗结核治疗的同时依据患者志愿,随机分为两组,一组即单纯化疗者,另一组化疗+支气管镜注药组.比较两组病人在临床症状、痰菌阴转、影像学及纤维支气管镜下的疗效差异.结果:耐药肺结核合并支气管内膜结核经全身抗结核治疗辅以支气管镜局部给药,疗效显著优于单纯全身抗结核治疗.结论:使用支气管镜治疗耐药支气管内膜结核,可明显提高疗效、缩短病程,值得在临床上广泛应用.     

Evaluation of Voice Disorders in Patients with Active Laryngeal Tuberculosis

IntroductionLaryngeal tuberculosis (LTB) is the most frequent larynx granulomatous disease. In general there is lung involvement, but in an important proportion of cases you can find LTB without pulmonary disease. The lesions observed in LTB, such as ulceration and fibrosis, can interfere in the process of voice production. The involvement of the mucous lining of the vocal folds can change their flexibility and, consequently, change voice quality, and the main symptom is dysphonia present in almost 90% of cases.ObjectiveTo describe the anatomical characteristics and voice quality in LTB patients.ResultThe most frequently affected sites were vocal folds in 87.5% patients, vestibular folds in 66.7%, epiglottis in 41.7%, arytenoid in 50%, aryepiglottic folds in 33.3%, and interarytenoid region in 33.3% patients. We found 95.8% cases of dysphonia. The voice acoustic analysis showed 58.3% cases of Jitter alterations, 83.3% of Shimmer and 70.8% of GNE.ConclusionVoice disorders found in active laryngeal tuberculosis are similar to those reported after clinical healing of the disease, suggesting that sequelae and vocal adjustments may install during the active phase of the disease, negatively impacting the process of vocal quality reestablishment.     

Adverse events among HIV/MDR-TB co-infected patients receiving antiretroviral and second line anti-TB treatment in Mumbai, India

Background

Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.

Methods

Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE.

Results

Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen.

Conclusions

AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.     

The coexistence of tuberculosis infection and lung cancer in patients treated in pulmonary department of Medical Academy in Lublin during last ten years (1990-2000)

The coexistance of tuberculous infection (TB-infection) and lung cancer in patients treated in Pulmonary Department of Medical Academy in Lublin during last ten years (1990-2000) has been evaluated. Inclusion criteria involved: aging from 50 to 80 years, tobacco smoking, tuberculous infection in present or in past, lung cancer. All analyzed patients (32 males, 13 females) were heavy smokers (from 10 to 70 cigarettes per day, during at least 5 years). 27 patients were suffered from lung tuberculosis in past, the rest of them had active tuberculous infection. In 19 cases we detected carcinoma planoepitheliale, in 13 cases carcinoma macrocellulare, in 7 cases carcinoma microcellulare and in 6 cases adenocarcinoma. We concluded, that increased occurrence of lung cancer in TB reinfected patients may be connected with immunodepression caused by chronic TB infection. In patients with new active TB-infection in whom the clinical status and chest X-ray were getting worse in spite of antituberculotic treatment recommended procedures for cancer diagnosis were performed. We suggest that bad results of anti-tuberculotic treatment in TB-infected patients are not always caused by bactericidal resistance. In these cases, the proper diagnosis of lung cancer should be considered.     

Spectrum of tuberculosis in patients with HIV infection in British Columbia: report of 40 cases.

OBJECTIVE: To review the clinical features, treatment and outcome of all known cases of tuberculosis in patients with human immunodeficiency virus (HIV) infection in British Columbia between 1984 and 1990. DESIGN: Retrospective case review. SETTING: Provincial tuberculosis registry and university-affiliated HIV clinic. PATIENTS: All people with HIV infection in whom active tuberculosis was diagnosed during the study period. RESULTS: All 40 patients identified were men; their mean age was 38 years. Of the subjects 30 (75%) were homosexual, 6 (15%) were homosexual and used intravenous drugs, 2 (5%) just used intravenous drugs, and 1 (2%) had had heterosexual contact with prostitutes; for the remaining subject the risk factor for HIV infection was not established. In all cases cultures of specimens from 15 body sources yielded Mycobacterium tuberculosis. Thirty-five of the patients had acquired immunodeficiency syndrome (AIDS), and five had HIV infection uncomplicated except for tuberculosis. In 28 (70%) of the cases no AIDS-defining disease had previously been diagnosed, and in 23 (58%) extrapulmonary tuberculosis represented the AIDS-defining disease. Symptoms at presentation included weight loss (in 80% of the cases), fever (in 75%), cough (in 70%) and night sweats (in 55%). The mean CD4 lymphocyte count was 0.2 x 10(9)/L (in 15 cases). Tuberculin skin test results were positive in 8 of 16 cases. The most striking radiologic finding was intrathoracic adenopathy. All except one of the 36 patients who received appropriate treatment responded favourably at first. Adverse reactions necessitating changes in treatment occurred in 12 (33%) of the cases. Relapse occurred after completion of therapy in two cases (one at 3 weeks and the other at 9 months after treatment was stopped). Tuberculosis was the cause of death in five cases. CONCLUSIONS: Tuberculosis in people with HIV infection commonly presents as extrapulmonary disease and precedes or coincides with other AIDS-defining opportunistic infections. In most cases tuberculosis is the AIDS-defining disease. Even though radiologic findings are often unusual physicians should suspect tuberculosis. A careful examination for evidence of disease at multiple sites should be done. The duration and choice of therapy must be adequate to avoid relapse.