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.     

INDICATIONS FOR SURGICAL TREATMENT IN GENITO-URINARY TUBERCULOSIS

Proper methods of surgical treatment effect arrest of localized tuberculosis in 90 per cent of cases, but as early and latent renal tuberculosis can be controlled in 50 per cent of cases by conservative treatment, careful deliberation as to choice of method of treatment is necessary in each case. In some circumstances, operation is definitely contraindicated. These observations apply also to tuberculosis elsewhere in the urogenital tract. When surgical treatment is carried out, careful preoperative and postoperative medical care is an important factor.The primary site of urogenital tuberculosis is the kidney, from which organ the infection spreads to the ureter, the bladder and the prostate gland. The prostate gland is the initial site of invasion in the genital tract, extension to other genital structures following. This sequence of infection is an important consideration in determining the management of urogenital tuberculosis.     

CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance.     

Does the onset of tuberculosis in AIDS predict shorter survival? Results of a cohort study in 17 European countries over 13 years. AIDS in Europe Study Group.

OBJECTIVE--To assess the impact of tuberculosis on mortality in patients with AIDS. DESIGN--Community based cohort study. SETTING--52 centres in 17 countries (AIDS in Europe study). SUBJECTS--5249 patients who were alive and free of tuberculosis one month after the diagnosis of AIDS, enrolled between 1979 and 1989, and followed up until 1992. MAIN OUTCOME MEASURES--Onset of clinically active tuberculosis or death, or both. RESULTS--During a mean follow up period of 15 months 201 (4%) patients developed tuberculosis and 3889 (74%) died. Patients who developed tuberculosis survived significantly longer (median 22 months) than those who did not (median 16 months). This apparent survival advantage was due to patients who survived longer having more opportunity to develop tuberculosis (or any other disease). In models that took into account the time at which tuberculosis was diagnosed, the onset of tuberculosis was associated with a significant increase in mortality (adjusted relative hazard of death 1.34; 95% confidence interval 1.12 to 1.60). CONCLUSIONS--The onset of tuberculosis in patients with AIDS predicts a substantial increase in mortality. Whether this increased mortality is directly attributable to the tuberculosis remains uncertain. If the association is causal preventive chemotherapy and aggressive treatment of tuberculosis could improve survival in AIDS.     

Tuberculous peritonitis in a case receiving continuous ambulatory peritoneal dialysis(CAPD) treatment

Background

Tuberculosis continues to be an important health problem in the world. Besides pulmonary involvement extrapulmonary involvement becomes an affair in developing countries, even in developed countries.

Case presentation

A thirty-six year old male patient was admitted with abdominal pain, diarrhea, nausea, vomiting and fever which had started one week before. The patient had been followed up with predialisis Chronic Renal Failure(CRF) diagnosis for 4 years and receiving continuous ambulatory peritoneal dialysis (CAPD) treatment for 4 months. In peritoneal fluid, 1600/mm3 cells were detected and 70% of them were polymorphonuclear leukocytosis. The patient begun nonspesific antibiotherapy but no benefit was obtained after 12 days and peritoneal fluid bacterial cultures remained negative. Peritoneal smear was positive for Asid-fast basilli (AFB), and antituberculosis therapy was started with isoniazid, rifampicine, ethambutol and pyrazinamide. After 15 days his peritoneal fluid cell count was decreased and his symptoms were relieved. Peritoneal fluid tuberculosis culture was found positive.

Conclusion

Considering this case, we think that in patients with CAPD catheter and peritonitis; when peritoneal fluid leukocytes are high and PMNL are dominant, AFB and tuberculosis culture must be investigated besides bacterial culture routinely.     

An unusual presentation of primary male genital tuberculosis

Urogenital tuberculosis is a rare disease; however, it is the second most common location for tuberculosis after the lung. Currently, incidence of urogenital tuberculosis is increasing due to factors such as a higher prevalence of immunosuppression (especially that caused by human immunodeficiency virus infection) and drug abuse. Herein a new case of male genital primary tuberculosis is reported presenting as a scrotal tumor; the originality of this observation lies in its unusual pseudotumor form.     

Management of vaginal dryness and dyspareunia in estrogen sensitive cancer patients

Cancer patients suffer from vaginal dryness and dyspareunia earlier and longer than the general population, with more severe and distressing symptoms. Life-style advices are the first step and vaginal lubricants can be tried, but they can't completely relieve atrophic symptoms. The most effective therapy is use of vaginal estrogens, but compliance and management are particularly difficult in estrogen sensitive cancer patients because of their systemic absorption. Compliance can be improved if they are begun at a very low dose and gradually increased until the lowest effective dose is reached. Promestriene only possesses an intramucosal effect, it can be used at very low doses in cancer patients suffering from urogenital symptoms.     

New approaches in the diagnosis and treatment of latent tuberculosis infection

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence.     

Population-based genetic epidemiologic analysis of Chlamydia trachomatis serotypes and lack of association between ompA polymorphisms and clinical phenotypes

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases worldwide. Urogenital strains are classified into serotypes and genotypes based on the major outer membrane protein and its gene, ompA, respectively. Studies of the association of serotypes with clinical signs and symptoms have produced conflicting results while no studies have evaluated associations with ompA polymorphisms. We designed a population-based cross-sectional study of 344 men and women with urogenital chlamydial infections (excluding co-pathogen infections) presenting to clinics serving five U.S. cities from 1995 to 1997. Signs, symptoms and sequelae of chlamydial infection (mucopurulent cervicitis, vaginal or urethral discharge; dysuria; lower abdominal pain; abnormal vaginal bleeding; and pelvic inflammatory disease) were analyzed for associations with serotype and ompA polymorphisms. One hundred and fifty-three (44.5%) of 344 patients had symptoms consistent with urogenital chlamydial infection. Gender, reason for visit and city were significant independent predictors of symptom status. Men were 2.2 times more likely than women to report any symptoms (P=0.03) and 2.8 times more likely to report a urethral discharge than women were to report a vaginal discharge in adjusted analyses (P=0.007). Differences in serotype or ompA were not predictive except for an association between serotype F and pelvic inflammatory disease (P=0.046); however, the number of these cases was small. While there was no clinically prognostic value associated with serotype or ompA polymorphism for urogenital chlamydial infections except for serotype F, future studies might utilize multilocus genomic typing to identify chlamydial strains associated with clinical phenotypes.     

Control and prevention of tuberculosis in Britain: an updated code of practice. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society.

A subcommitte was appointed by the Joint Tuberculosis Committee of the British Thoracic Society to review and bring up to date guidelines on control measures for tuberculosis. The updated code of practice emphasises that all cases of tuberculosis must be notified. A minority of patients need admission, and those with positive sputum smears should be regarded as infectious until they have received two weeks of chemotherapy. NHS staff at risk should be protected, and evidence of infectious tuberculosis should be sought as routine among certain prospective NHS employees, schoolteachers, and others. Contact tracing should be vigorously pursued, and all entrants to Britain from countries where tuberculosis is common should be screened. BCG vaccination should be offered in selected instances, and local organisation of tuberculosis services should be extended.     

T cell cytokine patterns in active tuberculosis patients in a northeastern area of Romania

Developing countries like Romania have a high incidence of tuberculosis. Literature data suggest that people in these countries have an important Th2-type immune background which prevents a protective Th1 response of the host against Mycobacterium tuberculosis. Our study is the first attempt in Romania to identify cytokine patterns in active tuberculosis. The study included 15 patients with active pulmonary tuberculosis and 11 healthy volunteers. Peripheral blood mononuclear cells (PBMC), stained with carboxyfluoresceine-diacetate-succinimidylester (CFSE), were incubated for 7 days with purified protein derivate (PPD) or with medium alone. Intracellular synthesis of IFNgamma and IL-4 in proliferated (CFSE(low)) T cells was detected by flowcytometry. The results showed that both Th1 (IFNgamma) and Th2 (IL-4) cytokines are produced in response to in vitro PPD-stimulation of PBMC from pulmonary tuberculosis patients and healthy controls. Moreover, the proportion between IFNgamma and IL-4 is tilted in favour of IL-4 in PPD-activated (CD3+ CFSE(low)) cells from healthy persons, who did not develop active tuberculosis during the two-year study time interval. This predominance of Th2 effectors points to the need to further investigate the role of IL-4 in the M. tuberculosis infection.     

Vitamin D supplementation promotes macrophages' anti-mycobacterial activity in type 2 diabetes mellitus patients with low vitamin D receptor expression

The increasing number of people with type 2 diabetes (DM2) is alarming and if it is taken into account that the relative odds of developing tuberculosis in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients, thus in developing countries where these two diseases are encountering face to face, there is a need for prophylaxis strategies. The role of vitamin D has been widely implicated in growth control of Mycobacterium tuberculosis (Mtb) during primary infection mainly through the induction of certain antimicrobial peptides (AMPs). In this study we evaluated the vitamin D serum levels, CYP27B1-hydroxylase enzyme, vitamin D receptor (VDR) and AMPs gene expression in Healthy donors, DM2 and TB patients. Results showed that DM2 group has lower VDR and AMPs expression levels. When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis. This preliminary study suggests the use of vitamin D as prophylaxis for tuberculosis in high DM2 endemic countries.     

The Spectrum of Extrapulmonary Tuberculosis

The incidence of new cases of extrapulmonary tuberculosis has remained constant, despite the decline in new cases of active pulmonary tuberculosis. This might be due to a delay in recognition, and particularly a lack of consideration of tuberculosis when the presenting symptoms are other than respiratory. Extrapulmonary tuberculosis should be considered in the differential diagnosis of bone, joint, genitourinary tract and central nervous system (CNS) diseases.To determine factors that might delay recognition and identification, 62 patients having extrapulmonary tuberculosis during 1969-1972 at the Los Angeles County-University of Southern California Medical Center were studied.Three quarters of these patients had had CNS, skeletal or genitourinary tuberculosis in equal distribution or 25 percent each. CNS involvement was seen frequently in the disseminated form. Presenting symptoms were protean and not specific, such as fever, anorexia, weight loss, cough, lymphadenopathy and neurologic abnormalities. Roentgenograms of the chest were abnormal in most. When a roentgenogram of the chest suggests pulmonary tuberculosis, signs and symptoms in other body systems should suggest extrapulmonary tuberculosis. If no abnormalities are seen on a roentgenogram of the chest, however, this does not preclude the diagnosis of extrapulmonary tuberculosis. Neither does a negative tuberculin skin test exclude the condition.Abnormal laboratory findings are common, especially in disseminated tuberculosis. These include various anemias, bone marrow disorders, hyponatremia due to inappropriate antidiuretic hormone syndrome. Analyses of pleural, peritoneal, pericardial and joint fluid usually show an exudate high in lymphocytes and occasionally low in glucose. Similar findings are seen in spinal fluid. The histological features of caseous or noncaseous granulomas are suggestive of but not specific for tuberculosis. Only culture of mycobacteria from sputum, urine, spinal fluid, pleural and other effusions and tissue biopsy specimens will yield a definitive diagnosis.Physicians must have a high index of suspicion to diagnose extrapulmonary tuberculosis, as it can resemble any disease in any organ system. Immediate therapy in the disseminated variety, sometimes even before a definite diagnosis can be made, may be lifesaving.     

Which population level environmental factors are associated with asthma,rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here.In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution.Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence.The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.     

7例影像学表现为弥漫肺间质性病变的肺结核报道及文献复习

目的:通过对7例高分辨CT(High Resolution Computed Tomography,HRCT)表现为弥漫肺间质性病变的肺结核患者的相关资料进行分析,结合相关文献,提高对该类肺结核的认识。方法:分析本院2012.2~2015.3确诊的7例HRCT表现为弥漫肺间质性病变的肺结核的临床症状、体征、影像学资料及痰抗酸杆菌、结核菌素纯蛋白衍生物(Purified Protein Derivative,PPD)试验、T细胞斑点试验(T-SPOT.TB)、抗结核抗体、血常规、血沉(Erythrocyte Sedimentation Rate,ESR)等实验室检查、病理检查等资料。结果:6例经2次以上痰涂片阳性确诊为肺结核,1例抗结核治疗有效诊断为肺结核;弥漫肺间质性病变的肺结核患者HRCT上间质性病变的范围与抗酸杆菌的检出及发热症状的出现有关联;与盗汗、乏力、咯血等结核中毒症状及PPD、结核抗体、ESR等指标无明显相关关系。结论:弥漫肺间质性病变也可为肺结核的一种特殊表现,极易误诊为其他间质病变。当患者临床表现及实验室检查无特殊发现时,需考虑肺结核的可能并进行结核病相关检查,尤其是抗酸杆菌及肺组织病理检查,以尽早明确诊断。     

Complications of Antiretroviral Therapy Initiation in Hospitalised Patients with HIV-Associated Tuberculosis

Background

HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries.

Methods

Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded.

Results

Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm³ (IQR 31–106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%.

Conclusions

High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1^st three months following ART initiation.     

Extensively drug-resistant tuberculosis: current challenges and threats

Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis caused by a Mycobacterium tuberculosis strain that is resistant to at least rifampicin and isoniazid among the first-line antitubercular drugs (multidrug-resistant tuberculosis; MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second-line drugs, namely amikacin, kanamycin and/or capreomycin. Recent studies have described XDR-TB strains from all continents. Worldwide prevalence of XDR-TB is estimated to be c. 6.6% in all the studied countries among multidrug-resistant M. tuberculosis strains. The emergence of XDR-TB strains is a reflection of poor tuberculosis management, and controlling its emergence constitutes an urgent global health reality and a challenge to tuberculosis control activities in all parts of the world, especially in developing countries and those lacking resources and as well as in countries with increasing prevalence of HIV/AIDS.     

耐药性结核性脑膜炎研究进展

结核性脑膜炎是由结核杆菌引起的中枢感染性疾病,是肺外结核病中最严重的一种,其多侵袭脑膜,有时可累及脑实质、脊髓,有很高的致死率。结核病在发展中国家中的感染趋势尤为突出。我国为人口大国,抗结核治疗和预防的形势异常严峻。随着抗结核药物的广泛使用,耐药性结核性脑膜炎患者数量增加,严重影响了结核性脑膜炎的预后。在耐药性结核性脑膜炎患者的治疗中,早期诊断、经验性治疗、调整治疗方案对患者的预后尤为重要。本文对耐药性结核性脑膜炎的分布、临床诊断、基因检测、治疗方案及预后进行系统性的总结。     

伊曲康唑注射剂治疗伴有肺结核史的侵袭性真菌感染2例

目的报道2例伴有肺结核史的侵袭性真菌感染经伊曲康唑注射剂治疗经过,探讨伴有肺结核史患者的抗真菌治疗经验。方法例1为49岁＂支气管肺囊肿合并感染,陈旧性肺结核＂男性患者,诊断为侵袭性肺曲霉感染确诊病例。例2为51岁＂右侧自发性气胸,慢性阻塞性肺病,陈旧性肺结核＂男性患者,诊断为侵袭性肺念珠菌感染拟诊病例。均予伊曲康唑注射剂治疗2周结合抗细菌治疗,并作临床和真菌学疗效监测。结果治疗两周后两患者临床症状和体征均得到明显改善,标本真菌镜检转阴,培养仍为阳性。结论在有肺结核病史存在的侵袭性真菌感染抗真菌治疗时间可能需要延长。合理应用抗生素、激素,严格掌握用药指针、时机、剂量与疗程是控制真菌感染的重要因素。     

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.