TB or not TB: The role of immunodiagnosis

The evaluation of delayed‐type hypersensitivity immune responses by the tuberculin skin test and, more recently, by ex vivo IFN‐γ release assays (IGRAs) form the basis for the risk assessment for the development of tuberculosis (TB) in close contacts of infective index patients and in immunocompromised hosts. In contrast, immunodiagnosis has little value for the diagnosis of active TB so far. A report in this issue of the European Journal of Immunology [ Eur J Immunol 2012. 42: 2844–2850 ] provides new insight into the phenotypic characteristics and selective recruitment of Ag‐specific T cells to the site of the infection, as analyzed by flow cytometry, which may provide new opportunities for the immune‐based diagnosis of TB in the future.     

TB news

Tuberculosis (TB) requires several different treatment drugs, making daily treatment difficult to maintain. A study of 23 HIV-positive TB patients and 22 HIV-negative TB patients found twice-weekly therapy to be effective. The patients received either daily therapy or therapy three times per week. The therapy consisted of isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for seven months in HIV-positive patients and four months in HIV-negative patients. Compliance was defined as completing eighty percent of the required doses.     

结核感染T细胞斑点试验在结核诊断与筛查中的价值

目的 探讨结核感染T细胞斑点试验(T-SPOT.TB)在结核诊断与筛查中的价值.方法 对2013年1月至2016年12月在南通市第一人民医院就诊的266个患者分为结核组、非结核组及生物制剂组,抽取静脉血应用结核感染T细胞斑点试验进行检测,同时部分患者进行了结核菌素检测.结果 T-SPOT.TB法诊断TB患者的敏感度为87.9％,阳性预测价值和阴性预测价值分别是43.2％和88.5％,TB组T-SPOT.TB检测阳性率明显高于非TB组(P ＜0.001)和生物制剂组(P＜0.001)的阳性率.而TST试验结果中,TB组阳性率与非TB组、非TB组阳性率与生物制剂组差异均没有统计学意义(P＞0.05),而TB组阳性率与生物制剂组差异有统计学意义(P＜0.05).在所有受试者T-SPOT.TB检测和TST试验的一致性为70.3％(K =0.397),生物制剂组中两者一致性为59.5％ (K=0.313).在TB组和非TB组中,两种方法一致性更高,分别为83.7％(K=0.486)和77.1％ (K=0.437).T-SPOT.TB法中TB组的斑点数显著高于非TB组(P ＜0.001)和生物制剂组(P＜0.001),而非TB组和生物制剂组的斑点数差异没有统计学意义(P＞0.05).结论 T-SPOT.TB检测比结核菌素试验有更高的灵敏度及阴性预测价值,并且不受环境分枝杆菌和BCG接种的影响,使得T-SPOT.TB在结核感染的诊断与筛查中具有较好的临床应用价值.     

The campaign against TB: governments must commit themselves. TB in Africa

This article presents an interview with Pierre Chaulet on the campaign against tuberculosis (TB) in Africa. Chaulet noted during the 9th IUATLD Conference of the Africa Region that the national TB control programs have taken on a new commitment in Africa since the declaration of TB as a global emergency in the 1990s. The TB control program package consists of five principal components: 1) political will of the government and its commitment to support the program; 2) case detection; 3) initiation of short course chemotherapy among detected cases; 4) ensuring the regular supply of essential anti-TB drugs; and 5) establishing a registry and reporting system for program monitoring and evaluation. Of the 40 African countries participating in the conference, 30 have efficient programs. Comparing the management of National TB Control Programs in Francophone and Anglophone Africa, it is noted that both are complementary, although generally, public health issues are more easily integrated into the medical training in the Anglophone countries than they are in the Francophone. Anglophone uses a more comprehensive approach to public health while countries in the Francophone practiced a more traditional university centralization. Finally, Chaulet gives his comment on the role of WHO in addressing concerns over the financial issues involved in TB Control Programs, particularly in the mobilization of resources from nongovernmental organizations and international institutions.     

Early detection of Pre-XDR TB with line probe assay in a high TB burden country

BackgroundWorldwide, tuberculosis (TB) is one of the top 10 causes of death. Drug resistant tuberculosis has lately become a major public health problem that threatens progress made in Tuberculosis (TB) care and control worldwide. The aim of this study was to determine the prevalence of Pre-extensive drug resistant TB among MDR TB in North Central of Nigeria.MethodsThis study was conducted from October, 2018 to August, 2019 with 150 samples. In Nigeria, guidelines for DR-TB as recommended by WHO is followed. All the samples from the patients who gave their consent were transported to a zonal reference TB laboratory (ZRL).ResultsMean age was 38.6 ± 13.4 years with peak age at 35–44. Out of these 103 samples processed with LPA, 101(98%) were rifampicin resistant and 2 were rifampicin sensitive, 99(96%) were INH resistant and 4 (4%) were INH sensitive, 5(5%) were fluoroquinolone resistant, 98(95%) were fluoroquinolone sensitive, 12 (12%) were Aminoglycoside + Capreomycin resistant, 91(83%) were Aminoglycoside + Capreomycin sensitive.ConclusionMultidrug resistant TB and its severe forms (Pre-extensive & extensively drug resistant TB) can be detected early with rapid tool- Line Probe Assay rapid and prevented timely by early initiation on treatment.     

Modification of Clearview Tuberculosis (TB) Enzyme-Linked Immunosorbent Assay for TB Patients Not Infected with HIV

Diagnosis of active tuberculosis by detection of urinary lipoarabinomannan (uLAM) from Mycobacterium tuberculosis is an attractive approach. Concentrating urine 100-fold allowed quantitation of uLAM at levels equal to picograms/ml of nonconcentrated urine. The approach of concentrating urine 100-fold improved the clinical sensitivity of the Clearview TB enzyme-linked immunosorbent assay (ELISA) from 7% to 57% yet impaired its specificity from 97% to 89%. (This study has been registered at University Hospital of Turku under registration no. 47/180/2009, Helsinki University Central Hospital under 149/2010, University Hospital of Kuopio under 105/2010, and China Medical University Hospital, Taichung, under DMR-99-IRB-075-2.)     

Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family

The human T-cell recognition of the low-molecular-mass culture filtrate antigen TB10.4 was evaluated in detail. The molecule was strongly recognized by T cells isolated from tuberculosis (TB) patients and from BCG-vaccinated donors. The epitopes on TB10.4 were mapped with overlapping peptides and found to be distributed throughout the molecule. The broadest response was found in TB patients, whereas the response in BCG-vaccinated donors was focused mainly toward a dominant epitope located in the N terminus (amino acids 1 to 18). The gene encoding TB10.4 was found to belong to a subfamily within the esat-6 family that consists of the three highly homologous proteins TB10.4, TB10.3, and TB12.9 (Rv0288, Rv3019c, and Rv3017c, respectively). Southern blot analysis combined with database searches revealed that the three members of the TB10.4 family were present only in strains of the Mycobacterium tuberculosis complex, including BCG, and M. kansasii, whereas other atypical mycobacteria had either one (M. avium, M. intracellulare, and M. marinum) or none (M. scrofulaceum, M. fortuitum, and M. szulgai) of the genes. The fine specificity of the T-cell response to the three closely related esat-6 family members was markedly different, with only a few epitopes shared between the molecules. Minimal differences in the amino acid sequence translated into large differences in recognition by T cells and secretion of gamma interferon. In general, the peptides from TB10.4 stimulated the largest responses, but epitopes unique to both TB10.3 and TB12.9 were found. The relevance of the findings for TB vaccine development and as a potential mechanism for immune evasion is discussed.     

Apoptosis in the skeletal muscle of untreated children with juvenile dermatomyositis: impact of duration of untreated disease

Juvenile dermatomyositis (JDM) is the most common myopathy in children with characteristic skin rash and muscle weakness, in which longer duration of untreated disease was associated with less muscle weakness. The duration of untreated inflammation may alter the apoptotic pathways involved in skeletal muscle damage. Diagnostic muscle biopsies from 14 untreated patients were stained for apoptosis markers. TUNEL-positive nuclei and caspase 3 were detected within the laminin layer, indicating apoptosis of skeletal muscle nuclei. Untreated JDM disease duration greater than 2 months ("long"), was associated with higher Fas-positive cell counts in the perivascular region compared with the "short" disease duration group, 2 months or less. Within the "long" duration group, higher Fas-positive cell counts were positively associated with increased TUNEL-positive nuclei and caspase 3. We conclude that the duration of untreated disease (chronic inflammation) influences the mode of continuing cell damage and death in children with JDM.     

TB vaccines: progress and problems

Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a situation worsened by the advent of the HIV epidemic and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. The existing vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has proven inefficient in several recent field trials. There is currently intense research using cutting-edge vaccine technology to combat this ancient disease. However, it is necessary to understand why BCG has failed before we can rationally develop the next generation of vaccines. Several hypotheses that might explain the failure of BCG and the strategies designed to address these shortcomings are discussed.