MODERN MANAGEMENT OF TUBERCULOSIS—The Public Health Implications of Recent Advances

Modern treatment for tuberculosis has greatly increased the problem of preventing spread of infection. BCG vaccination, for instance, would cause all persons to react to tuberculin test so that the possibility of tuberculosis could never be ruled out by this means. Streptomycin and more recently developed drugs may sterilize sputum so that diagnosis cannot be confirmed for some time after use of such drugs; when by use of these drugs the disease had been confined to caseous encapsulations, later breakdown of the encapsulations may release strains of bacilli resistant to the drugs both in the patient and in others infected with them. The temporary sterilization of sputum, coupled with the euphoria resulting in part from abrupt remission of the toxic state, may lead to premature discharge of patients from sanatoria and further spread of tuberculosis. Both the public and the profession must be impressed with these facts.For more profitable than minifilm surveys of normal populations are routine x-ray examination of all patients admitted to hospitals (by which two to five times as many cases have been found) and follow-up of persons who have had contact with tuberculosis patients (thirteen times as many cases found).A study being conducted by the California Tuberculosis and Health Association indicates that in many counties neither the number of x-rays made in public surveys nor the number of cases found is known or even to be estimated from existing records.Because of reduction in deaths due to tuberculosis some public officials are reluctant to spend for further treatment facilities. As the actual number of cases is increasing in many areas, however, expenditures will have to be increased.     

Antituberculous drug resistance in Manitoba from 1980 to 1989.

OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs. DESIGN: Comparison of drug-resistant and non-drug-resistant cases of tuberculosis. SETTING: Manitoba. PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989. MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described. RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem. CONCLUSION: Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease.     

The epidemic situation in relation to HIV infection in Ukraine (1987-1997)

The analysis of the dynamics of the epidemic process for 10 years made it possible to find out the presence of two separate epidemic waves of HIV infection. The first wave (1987-1994) was manifested as the slow type of the development of the epidemic, characterized mainly by sexual transmission. During this period 398 persons with HIV infection were detected, 24 persons were found to have AIDS; of these, 13 persons died. The second epidemic wave began in 1995 and was due to the spread of HIV among users of drugs introduced by injection. By the end of 1995 the number of HIV carriers was 34 times greater than that of 1994, reaching 1490 persons. In 1996-1997 this figure increased 8 times (annually). The number of AIDS patients rose to 420 persons. The most unfavorable regions with respect to HIV infection and AIDS morbidity were determined. The western regions of the Ukraine were noted to be in a more favorable situation in this respect with infection indices being lower more than 30 times. Up to 80% of all infected persons were found to be addicts introducing drugs intravenously. Growing morbidity in sexually transmitted disease, particularly in syphilis, contributed to the deterioration of the epidemiological situation. The conclusion was made on the necessity of introducing new prophylactic programs and expanding current ones. The signs of stabilization in Odessa and Nikolayev were observed; in these cities pilot programs aimed at the strategy of the "decrease of harm" have been introduced (in collaboration with UNAIDS) since 1996.     

HIV infection in the penitentiaries of Ukraine

In connection with a sharp increase of the number of HIV-infected persons in the Ukraine the natural growth of the number of such persons in penitentiary institutions was registered, starting from 1995 (455 persons in 1995, 2,937 persons in 1996, 2,779 persons in 1997 and 173 persons during 5 months of 1998). 83% of HIV infection persons were drug addicts introducing drugs intravenously. In 1997 the strategy of decreasing the risk of infection in penitentiary institutions was worked out in collaboration with UNAIDS experts: repressive and isolation measures were replaced with measures aimed at the "decrease of harm". Special attention is given to circumstances aggravating the epidemic situation in HIV infection, and particularly at the sharp growth of morbidity in tuberculosis and syphilis (10.6 and 10.3 times respectively in 1997 in comparison with 1993). In addition, in 1997 the number of person having drug addiction was noted to increase 2.3 times in comparison with 1993. The necessity of taking constant information and educational measures aimed at decreasing the risk of the spread of HIV infection is emphasized.     

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.     

The characteristics of HIV infection during a sharp activation of the epidemic process in Rostov Province

A considerable growth in cases of HIV infection in Rostov Province was registered in 1996-1997. Number of men was 525, number of women--196 cases, were registered. The highest index of HIV infection was noted in group of tested by epidemiological evidence (4494,4 per 100,000 tested persons), which was 57.2 times higher than the average level for this region. The growth in the number of infected persons was due to the import of HIV from the territory of Ukraine and the subsequent spread of the virus among drug addicts introducing drugs by intravenous injection.     

Evidence of transmission of Burkholderia cepacia, Burkholderia multivorans and Burkholderia dolosa among persons with cystic fibrosis

Previous studies have identified specific Burkholderia cepacia complex strains that are common to multiple persons with cystic fibrosis (CF). Such so-called epidemic strains have an apparent enhanced capacity for inter-patient spread and reside primarily in Burkholderia cenocepacia (formerly B. cepacia complex genomovar III). We sought to identify strains from B. cepacia complex species other than B. cenocepacia that are similarly shared by multiple CF patients. We performed genotype analysis of 360 recent sputum culture isolates from 360 persons residing in 29 cities by using repetitive extragenic palendromic polymerase chain reaction (rep-PCR) and pulsed field gel electrophoresis. The results indicate that sharing of a common Burkholderia multivorans strain occurs relatively infrequently; however, several small clusters of patients infected with the same strain were identified. A cluster of seven patients infected with the same B. cepacia (genomovar I) strain was found. We also identified a large group of 28 patients receiving care in the same treatment center and infected with the same Burkholderia dolosa strain. These observations suggest that B. cepacia complex strains in species other than B. cenocepacia may be spread among CF patients.     

Does fear of immigration authorities deter tuberculosis patients from seeking care?

Physician groups are concerned that legislation requiring physicians to report illegal immigrants to immigration authorities will delay curative care. In particular, patients with tuberculosis may delay seeking care for infectious symptoms and spread the disease. We surveyed 313 consecutive patients with active tuberculosis from 95 different facilities to examine the relationship of immigration-related variables, symptoms, and delay in seeking care. Most patients (71%) sought care for symptoms rather than as a result of the efforts of public health personnel to screen high-risk groups or to trace contacts of infectious persons. At least 20% of respondents lacked legal documents allowing them to reside in the United States. Few (6%) feared that going to a physician might lead to trouble with immigration authorities. Those who did were almost 4 times as likely to delay seeking care for more than 2 months, a period of time likely to result in disease transmission. Patients potentially exposed an average of 10 domestic and workplace contacts during the course of the delay. Any legislation that increases undocumented immigrants'' fear that health care professionals will report them to immigration authorities may exacerbate the current tuberculosis epidemic.     

上海口岸2014-2015年入境人员肺结核筛查情况

为了解上海口岸入境人员肺结核的筛查情况及后续处理,防止结核病通过口岸跨境传播,本研究于2014年1月—2015年12月对所有在上海口岸办理入境体检的14岁以上人员进行结核病筛查,通过病史、体格检查和胸部X线摄影筛查疑似肺结核患者;对疑似肺结核患者进行痰细菌学检测、T‐SPOT ．TB和 Xpert MTB／RIF检测。结果显示,2014—2015年上海口岸入境人员共检出疑似肺结核患者215例,总检出率为229．76／10万;确诊肺结核患者33例,总检出率为35．27／10万,确诊率为15．3％。对210例疑似肺结核患者进行痰细菌学检测,结果显示结核分枝杆菌培阳率为14．3％,非结核分枝杆菌培阳率为17．1％。有95例和78例疑似肺结核患者分别接受 T‐SPOT ．TB和 Xpert MTB／RIF 检测,以痰细菌学检测为“金标准”,T‐SPOT ．TB的灵敏度为100％,特异度为49．4％;Xpert MTB／RIF的灵敏度为87．5％,特异度为96．8％。33例确诊肺结核患者中,25例（75．8％）离境,15例（45．5％）在离境前接受抗结核治疗,8例（24．2％）失访。本研究显示,上海口岸入境人员中肺结核确诊率仍有待提高。筛查与诊断中,T‐SPOT ．TB具备较高灵敏度, Xpert MTB／RIF具备较高特异度,两种方法均有较高应用价值,两者联用可提高检出率,缩短检出时间。对确诊病例或未确诊的可疑病例应加强后续监管。     

The determinants of the spread of HIV among injection drug addicts in Ukraine

The main tendencies in the development of drug addiction in the Ukraine, the dynamics of the spread of HIV among drug addicts introducing drugs intravenously, epidemiological data on HIV, AIDS and drug addiction, as well as prognoses on the development of HIV infection are presented. Since 1995 the number of HIV-infected persons grew 34-fold, the number of cases of HIV infection resulting from the intravenous use drugs rose to 70% simultaneously with the rise (about 34-fold) of the number of persons infected with HIV through sexual contacts (about 13 fold). In 1996-1997 such tendency increased. On the whole, the proportion of drug addicts introducing drugs by intravenous injection was 83% in the Ukraine. By April 1, 1998, official registration covered 18,800 HIV-infected persons, including 270 foreign nationals, as well as 499 AIDS patients, including 487 Ukrainian citizens, among them 28 children. Out of 18,800 HIV-infected persons, 78.3% were drug addicts, most of them young people aged 15-30 years; about 18% were young people under 20 years of age, 80% being males. According to the model the rapid spread of HIV from the group of drug addicts to the heterosexual population, the total number of HIV-infected persons reaching 1,500,000 is expected in the country by 2014.     

Successful use of an inhalational phytochemical to treat pulmonary tuberculosis: a case report.

Multi-drug resistant strains of tuberculosis pose a serious threat in many third- and first-world countries. The aim of this case report is to describe a potential new method for treating those with primary pulmonary tuberculosis using phytochemicals via inhalation. We report the first case of using inhaled phytochemicals in treating primary pulmonary tuberculosis. A 28-year-old female presented with symptoms suggestive of primary pulmonary tuberculosis, and she was found to be positive via chest X-ray and sputum culture. She subsequently underwent treatment with conventional DOTS treatment. Ten days post-inhalation of the phytochemical, the patient is tuberculosis negative (via sputum culture), with no clinical symptoms. This may be a potential new method and type of treatment for pulmonary tuberculosis.     

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India.     

Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study

Background

The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients.

Methods and Findings

This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases.A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting.

Conclusions

The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.     

The prevalence of previously undiagnosed leprosy in the general population of northwest bangladesh

Background

The prevalence of previously undiagnosed leprosy (PPUL) in the general population was determined to estimate the background level of leprosy in the population and to compare this with registered prevalence and the known PPUL in different levels of contacts of leprosy patients.

Methodology and Principal Findings

Multistage cluster sampling including 20 clusters of 1,000 persons each in two districts with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the cluster sample was 27 (19 SLPB, 8 PB2-5), giving a PPUL rate of 15.1 per 10,000.

Conclusions and Significance

PPUL in the general population is six times higher than the registered prevalence, but three times lower than that in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. Full village or neighbourhood surveys may be preferable to contact surveys where leprosy is highly endemic.     

Molecular epidemiology of drug-resistant tuberculosis in Sweden

Drug-resistant tuberculosis (TB), including the more severe forms of multidrug- and extensively drug-resistant forms, is an increasing public health concern globally. In Sweden the majority of patients with TB are immigrants from countries with a high incidence of TB including the drug-resistant forms. In this study, the spread of resistant TB in Sweden was investigated by molecular fingerprinting. Isolates resistant to at least one of the drugs, isoniazid, rifampicin, ethambutol or streptomycin, from 400 patients collected between 1994 and 2005, were studied by restriction fragment length polymorphism (RFLP) and by spoligotyping. Thirty-five clusters of patients infected with strains with identical RFLP and spoligotyping patterns (2-96 patients per cluster), comprising a total of 203 patients, were found. One large outbreak of isoniazid resistant tuberculosis was identified, involving 96 patients, mainly from the Horn of Africa. To identify chains of transmission, molecular epidemiological characterization of TB isolates should, if possible, be performed on isolates from all new TB patients.     

Changes in serum selenium, copper, zinc levels and Cu/Zn ratio in patients with pulmonary tuberculosis during therapy

The effectiveness and success of antituberculosis therapy is mainly measured by its ability to identify the organism in the sputum. In certain cases, available tuberculosis tests are not satisfactory and do not provide enough information on the effectiveness of antituberculosis therapy. Copper (Cu), zinc (Zn), and selenium (Se) are the essential elements that play a crucial role in the immune system. The serum levels of these elements vary in many diseases including tuberculosis. In this study, we investigate whether the serum levels of Cu, Zn, and Se change during antituberculosis therapy. We have included 22 pulmonary tuberculosis cases that were newly diagnosed with positive sputum and 18 healthy subjects. At the beginning and 2 mo after therapy, serum levels of Cu, Zn, and Se were measured by atomic absorption spectrometry. Despite Se and Cu levels not being affected during the treatment, we found that there was a significant increase in the levels of Zn and a decrease in the Cu/Zn ratio. Serum Zn levels and the Cu/Zn ratio could be used as a valuable laboratory tool for the clinicians to assess response to therapy or effectiveness of the ongoing antituberculosis therapy.     

Can Follow-Up Examination of Tuberculosis Patients Be Simplified? A Study in Chhattisgarh,India

Background

Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely.

Objectives

To assess the incremental yield of the second sputum sample in the follow-up of tuberculosis patients under the Revised National Tuberculosis Control Programme (RNTCP) in Chhattisgarh, India.

Methodology

A record review of tuberculosis (TB) patients registered in 2009 using a structured proforma from two sources, Tuberculosis and Laboratory Register, was undertaken in the six districts of Chhattisgarh, India.

Results

In smear positive cases, of 10,048 follow-up examinations, 45 (0.5%) were found to be smear positive only on the second sputum when the result of the first sample was negative. In smear negative pulmonary and extra pulmonary TB patients, of 6,206 follow-up smear examinations, 11(0.2%) were found to be smear positive.

Conclusions

The incremental yield of a second smear examination was very low, indicating that examination of one sputum sample is enough during follow-up among TB patients. There is insufficient yield to support sputum smear microscopy for monitoring smear negative pulmonary TB and extra pulmonary TB patients. These results indicate that the follow-up smear microscopy can be substantially simplified with favourable resource implications.     

Surveillance of Elderly Hospital Patients for Pulmonary Tuberculosis

A restrospective study of pulmonary tuberculosis in a general hospital showed that the diagnosis had been frequently overlooked in the middleaged or elderly because the patient also suffered from a more acute condition which preoccupied the attention of the doctor. The commonest error was to discount chest x-ray abnormalities by omitting sputum culture or serial radiography.Surveillance was carried out on all patients aged 60 or over admitted to a large general hospital whose routine chest radiograph showed signs of possible pulmonary tuberculosis whether apparently active or inactive. Three sputum samples from each patient were examined for Mycobacterium tuberculosis without reference to the clinical presentation. In a nine-month period six out of 81 patients proved to have active pulmonary tuberculosis (7·4%). It is suggested that this may be a useful method of screening the elderly hospital population for pulmonary tuberculosis.     

肺结核患者血清IFN-γ、Il-1β和TNF-α水平的临床检测价值分析

目的:研究肺结核患者血清γ干扰素(IFN-γ)、白介素-1β(Il-1β)以及肿瘤坏死因子-α(TNF-α)水平的临床检测价值。方法:选择2015年1月～2018年12月在北京市顺义区医院治疗的25例肺结核患者作为肺结核组,并且选择同期在该院进行体检的25例健康人作为对照组。采用酶联免疫吸附法(ELISA)检测并且比较肺结核组以及对照组研究对象的血清IFN-γ、Il-1β和TNF-α水平,比较痰菌阴性组(n=14例)以及痰菌阳性组(n=11例)、无空洞组(n=15例)以及有空洞组(n=10例)的血清IFN-γ、Il-1β、TNF-α水平。结果:肺结核组患者的血清IFN-γ、Il-1β、TNF-α水平均明显高于对照组(P0.05);痰菌阳性组肺结核患者的血清IFN-γ、Il-1β、TNF-α水平均明显高于痰菌阴性组患者(P0.05);有空洞组肺结核患者的血清IFN-γ、Il-1β、TNF-α水平均明显高于无空洞组患者(P0.05)。结论:肺结核患者的血清IFN-γ、Il-1β和TNF-α水平明显高于健康者,有助于判断疾病进程,这些细胞因子可能在结核病的发病中发挥着重要的作用。     

The characteristics of the course of tuberculosis in HIV-infected patients and prophylactic measures

Morbidity in HIV infection and tuberculosis in persons having these two infections in association was analyzed. According to the data for the end of the first quarter of 1997 the presence of association of HIV infection with tuberculosis was found in 91 patients. In 70.3% of cases HIV infection was contacted before the appearance of tuberculosis and in 18.7% of cases, after it; in 11% of cases the order of appearance of these two diseases could not be established. The study revealed that the markedness of the clinical picture of tuberculosis was determined by the progress of HIV infection.