Tuberculin Reaction Research Articles

Microbiological and genetic typing of atypical mycobacteria identified in the Novosibirsk region

219 samples of biological material from animals and 54 samples of environmental objects from farms in the Novosibirsk region, which are free from bovine tuberculosis, were examined for isolation of the tuberculosis pathogen, microbiological and genetic typing of isolated cultures of atypical mycobacteria. Microbiologic diagnosis included culture method, biochemical tests and biological assay. During the treatment of animal biomaterial 50 cultures were isolated, and 20 cultures were isolated from the environmental objects. The isolated cultures were classified as mycobacteria on the basis of their culture and morphological properties and bacterioscopy. According to biochemical characteristics, out of 70 cultures studied, 27 isolates (38.6%) belonged to atypical mycobacteria of different species. Of these, 26 cultures (96.3%) were categorized as Group III and 1 culture (3.7%) as Group IV according to Runyon's classification. Next, a biological assay was performed by infecting nonlinear white mice with suspensions of 27 identified cultures of atypical mycobacteria. At autopsy and pathological-anatomical study of laboratory animals, changes in internal organs characteristic for tuberculosis were not found, which confirms that the cultures under study belong to atypical mycobacteria. Molecular systematization of the isolated cultures revealed the presence of Mycobacterium avium (20 cultures, 74%), M. nonchromogenicum (5 cultures, 18.5%), M. intracellulare (1 culture, 3.7%) and M. fortuitum (1 culture, 3.7%). Thus, based on the results of a comprehensive study of 70 cultures of atypical mycobacteria isolated from animal biomaterial and environmental objects from the territory of farms in the Novosibirsk region, free from bovine tuberculosis, 27 isolates belonging to atypical mycobacteria of groups III and IV were identified according to Runyon’s classification. On the basis of typing, it was found that the leading role among the identified pathogens is occupied by atypical mycobacteria of group III, in particular M. avium. The etiology of nonspecific tuberculin reactions in tuberculosis-free herds of cattle can be explained by the isolation of atypical Mycobacterium tuberculosis groups III and IV according to Runyon classification from environmental objects and their persistence in the organism of healthy animals.

Tuberculin responses after BCG vaccination predict amyotrophic lateral sclerosis risk

BackgroundT cell infiltration around dying motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS). It is not known if this immune response represents a cause or a consequence of the disease. We aimed to establish whether individual variation in regulation of a T cell driven immune response is associated with long-term ALS risk. MethodsTuberculin skin test (TST) following BCG vaccination represents a standardized measure of a secondary T cell driven immune response. During a Norwegian tuberculosis screening program (1963–1975) Norwegian citizens born from 1910 to 1955 underwent TST. In those previously BCG vaccinated (median 7 years prior to TST), we related tuberculin skin tests to later ALS disease identified through validated Norwegian health registers. We fitted Cox proportional hazard models to investigate the association between tuberculin reactivity and ALS risk. ResultsAmong 324,629 participants (52 % women) with median age 22 (IQR 10) years at tuberculosis screening, 496 (50 % women) later developed ALS. Hazard ratio for ALS was 0.74 (95% CI 0.57–0.95) for those who remained TST negative compared to those who mounted a positive TST. The association was strongest when time between BCG immunization and TST was short. The associations observed persisted for more than four decades after TST measurement. ConclusionsNegative TST responses after BCG vaccination is associated with decreased long-term risk for ALS development, supporting a primary role for adaptive immunity in ALS development.

CASES OF DETECTION OF BOVINE TUBERCULOSIS IN KARAGANDA AND ULYTAU REGIONS

The article presents data from our own research on the epizootic situation of tuberculosis in the Karaganda and Ulytau regions for 2021-2024. In 2024, two foci of cattle tuberculosis were identified in the Karaganda region, one of which in the Nurinsky district is the rural district of Akhmetauyly, KH "Kugabaev N." and the other in the Bukhar-Zhyrau district is the rural district of Kokpekty, LLP "Janat". Two foci of cattle tuberculosis were also identified in the Ulytau region, one of which is in the Zhana-Arkinsky district - the rural district of M. Zhumazhanov, KH "Dias" and one in the city of Karazhal - KH "Peshkovets". Based on a veterinary and sanitary examination of the carcasses and internal organs of the slaughtered animals, the diagnosis of tuberculosis was confirmed. The qualified conduct of allergic studies by animal veterinary specialists, as well as differential diagnosis of nonspecific tuberculin reactions, make it possible to accurately determine the epizootic situation of tuberculosis. Strict adherence to the instructions for the diagnosis and prevention of tuberculosis, along with the implementation of the developed veterinary and sanitary and organizational and economic measures, contributes to the improvement of the epizootic situation of tuberculosis. Ultimately, this leads to a reduction in the risk of tuberculosis among people

Mycobacteria’s Antibodies Search: Serology, an Important Neglected Means to Establish a Diagnosis and a Prognosis

The WHO has banned the use of blood tests for the diagnostic and prognostic of tuberculosis. This is a monumental error that it never corrected. The current ban deprives the mycobacterial community of a tool that is essential to combat the disease. Serology estimates the humoral immune status of a patient or a population. It is not a substitute to antigen detection, but it is comparable to the tuberculin test which estimates the cellular immune status. Both give an evocative expression of the tubercle bacillus immunosuppressive activity and indicate the mobilization level of the infected patients’ immune defense. In opposition to the tuberculin reaction which makes the cutaneous test devoid of interest after a positive turn, the serology fluctuates according to the antigenic load.

Divergent proinflammatory immune responses associated with the differential susceptibility of cattle breeds to tuberculosis.

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines (bovine TB, bTB) due to M. tuberculosis- indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bTB prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), tank binding kinase-1 (TBK-1), and nitric oxide (NO) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1β transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to bTB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.

Lichen scrofulosorum- A rare case report

Lichen scrofulosorum, other name “tuberculosis cutis lichenoides” which is present as lichenoid eruption of minute papules, a rare tuberculid commonly seen in children and adolescents with tuberculosis. Mostly positive tuberculin reaction strongly associated with eruption. Diagnosis can be difficult in this type of lesion which is closely resemble to other type of dermatological conditions that are often primarily considered. Here we report a case of lichen scrofulosorum in a twenty year- old female having typical grouped lichenoid papules on the neck, hand and leg associated with itching.

TREC И KREC – ПЕРСПЕКТИВНЫЕ МАРКЕРЫ АКТИВНОСТИ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

Scientists around the Globe are making deliberate attempts to develop the new methods for predicting and diagnosing tuberculosis, but these measures are not enough to end its epidemic. The purpose of the study was to evaluate the excisional rings of the T-cell receptor (TREC) and K-deletion element of B-cells (KREC) in infants and preschool children at high risk of tuberculosis as a promising prognostic marker for tuberculosis infection activity. A cross-sectional study was conducted in Jan. - Sept. 2022. The observation group consisted of 87 children aged 1 to 7 [6 (5‒7)] y/o, of which 13 (14.9%) aged 1 to 3 y/o and 74 aged 4 to 7 y/o; 53 (60.9%) boys/34 (39.1%) girls. The three groups were formed: G1 (n=27) with an established diagnosis of tuberculosis (TB), G2 (n=34) with TB infection diagnosis made based on the results of tuberculin diagnosis and without signs of a local specific process, and [control] G3 (n=26) without signs of TB infection according to the results of specific skin tests and without signs of TB, i.e., conditionally healthy. All children, in addition to methods to confirm or exclude TB and methods of specific immunodiagnostics, have undergone a molecular genetic study: DNA extraction from a dry blood spot and quantitative determination of TREC and KREC by real-time PCR in values of TREC and KREC copies per 105 cells. In order to build the reference values of TREC and KREC quantitative indicators in dry blood spots, the results obtained in G3 were analyzed as well. Results: the reference values of TREC and KREC were established for children of early and preschool ages when extracting DNA from a dry blood spot. When assessing tuberculosis infection in children of early and preschool ages, statistically significant criteria were determined, such as: anti-tuberculosis therapy (F=42.001; p<0.001), positive or negative reaction to the recombinant tuberculosis allergen during an intradermal test (F=39.394; p<0.001), high blood TREC level (F=12.707; p<0.001), tuberculin reaction (F=10.625; p<0.001), and KREC level (F=3.182; p=0.039). Conclusion: high level of TREC can be considered as a marker for the activity or a personalized predictor for the risk of progression of TB infection in children of early and preschool ages with high risk of TB.

Eitt sindur um tuberklasmittuna

This paper is part of a treatise dealing with the clinical features of primary tuberculous infection, and the purpose of the present work is to contribute to the clinic of primary tuberculosis. Some literature about the theme is surveyed. The material used has been collected at the Tuberculosis Station of the Faroe Islands at Hoydal during the author's time of service there from 1939 to 1947. An account is given of the working plan of this tuberculosis station, where besides ordinary station work special attention is paid to the tuberculin register. The tuberculin reaction used has been Pirquet 's test. The material comprises a total of 430 cases of initial fever. The fever curve for adults was typically continual, while with children it vas irregular; the duration of the fever was similar for children and adults, generally 2 or 3 weeks; in l/4 of the cases it lasted more than one month. Maximum temperature generally about 39 degrees C might, however, be higher, especially with children. The duration and height of the fever had no prognostic significance. Slow pulse was a constant symptom witli adults, but was seldom noticed with children. This relative bradycardiagenerally lasted till the middle of ihe fever period. Krythema nodosum was a frequent symptom ot' initial fever and occurred 76 times among the 430 cases of initial fever. Sedimentation rate practically always increased, as a rule moderately, and decreased as the fever fell, but more slowly. X-rays examinations have been made during initial fever in 146 cases. X-rays changes were stated in all the children and in more than % of the adults. The changes stated were chifly enlarged hilar shadows, some had also infiltrations. Rather more than *4 had subjective symptoms, a number which is undoubtedly too low. The most frequent symptoms where retrosternal pain and soreness of the lower end of sternum, a stitch in the side, and pain between the shoulderblades. The mentioned symptoms must be supposed to bi' caused by tlie pathologic anatomic changes.

Can more information be extracted from bovine TB skin test outcomes to inform animal risk management? A retrospective observational animal-level study

Continual tailoring of control programmes of endemic pathogens during long-term eradication campaigns requires detailed analysis of surveillance data to inform evidence-based policy. Bovine tuberculosis is a disease where long-term control and eradication programs are in train in several countries. The primary diagnostic tool, the intradermal tuberculin test, used to identify infected animals can be interpreted using different criteria and cut-offs, facilitating flexibility in its use as a basis to inform interventions.We investigated the comparative risk of animals failing a single intradermal comparative tuberculin test (SICTT) based on their previous tuberculin test result following a higher risk test-type (reactor retest of an infected herd). The study was a retrospective cohort design, and the primary exposure was the test status following a reactor retest classified as mutually exclusive categories based on bovine and avian tuberculin reactions: standard interpretation inconclusive (Sdi), severe interpretation inconclusive (Svi), single intradermal test (SIT) reactors (SITr), SIT inconclusive (SITi), avian tuberculin reactors (Ar), and test negative animals. Random effects multivariable logistic regression was used to investigate future risk. Cross-validation and downscaling was used to explore model performance. Alternate models with differing outcome test types were also explored.The models were trained on 844,207 observations from June 2018 to June 2021. Sdi, Svi, SITr, SITi and Ar were associated with the following odds ratios 12.242 (95 %CIs: 5.236–28.625; p < 0.001), 4.101 (95 %CIs: 3.423–4.913; p < 0.001), 2.503 (95 %CIs: 1.878–3.338; p < 0.001), 1.741 (95 %CIs: 1.195–2.538; p = 0.004) and 1.065 (95 %CIs: 0.833–1.361; p = 0.616) for failing the next test, respectively. High model performance was achieved with inclusion of random effects for both training and test evaluation datasets (AUC: 0.94; Balanced accuracy: 0.84), but fixed-effects only predictions exhibited moderate performance (AUC: 0.70; Balanced accuracy: 0.69). This reflects that 55 % of the risk of test failure relates to between herd heterogeneity based on intra-class correlation, while controlling for fixed effects. Other factors that were associated with increasing risk included age (older cohorts were at greater risk than the youngest cohort), breakdown history of the herd (greater number of breakdowns prior to the study period), and the time between exposure test and outcome test.These results provide further evidence to inform risk-based management policies for TB, including the removal of Sdi animals in higher risk situations, supplementary testing of cattle based on tuberculin responses and the provision of risk management advice to herd owners. The results characterise the future animal-level risk posed by Svis and suggest this risk may require policy led interventions.

Comparative diagnosis of bovine tuberculosis using single intradermal cervical tuberculin technique, conventional methods, enzyme-linked immunosorbent assay, and the gamma-interferon assay.

Background and Aim:Bovine tuberculosis (TB) is a zoonotic disease that causes huge economic losses. This study aimed to compare the result obtained from the single intradermal test, conventional methods (culture and microscopy), gamma-interferon (IFN-γ) assay, and indirect enzyme-linked immunosorbent assay (ELISA) to diagnose bovine TB.Materials and Methods:This study evaluated 2913 animals from milk farms in Cairo, El-Sharkia, and El-Qalyubia Governorates by single intradermal cervical tuberculin technique (SICTT), ELISA, and IFN-γ assay.Results:Of the 2913 dairy cows surveyed, 3.7% yielded positive results. Culture prepared samples on Lowenstein-Jensen and Middlebrook 7H10 agar media yielded 52 (1.85%) isolates of Mycobacterium spp. from 2805 milk samples that yielded negative tuberculin reactions and 56 (51.85%) isolates of Mycobacterium spp. were recovered from 108 lymph node samples from positive cases. ELISA analysis of the sera of 108 positive SICTT reactors revealed that 94 (87.03%) and 97 (89.81%) animals were positive for bovine purified protein derivative (PPD-B) antigen and commercial polypeptide antigen, respectively. IFN-γ assays were performed on whole blood samples collected from positive SICTT reactors and showed that 103 (95.37%) animals were positive.Conclusion:M. tuberculosis complex may be isolated from raw milk and not all infected animals shed mycobacterial bacilli in their milk. The use of polypeptide antigen in ELISA provides better diagnostic efficacy than PPD-B antigen. The IFN-γ assay is more sensitive than both SICTT and ELISA. It should be used in parallel with SICTT to allow the detection of more positive animals before they become a source of infection to other animals and humans.

Influence of Ionizing Radiation on the Allergic Reactivity of Tuberculosis-Infected Laboratory Animals

Allergic examination using PPD-tuberculins is the main method of life-time tuberculosis diagnostics in farm animals and poultry. However, it is known about a decrease in the diagnostic value of allergic reactions after irradiation of animals, the occurrence of non-specific, pseudo-allergic reactions. One of the reasons for the manifestation of non-specific reactions may be autosensitisation (autoallergisation) of the body by the breakdown products of personal tissues, which is especially pronounced with radiation damage. Ionizing radiation affects the manifestation of tuberculin sensitivity, the course of tuberculosis and autoimmune processes in the body. Differential diagnostics of non-specific tuberculin reactions remains not yet a fully solved problem, although there are many tests for its implementation. After the accident at the Chernobyl nuclear power plant, a considerable number of animals remained in the adjacent territories contaminated with radioactive substances, including those infected with the causative agent of tuberculosis and atypical mycobacteria. It is known that irradiation leads to autosensitisation of the body by the breakdown products of its own tissues and the development of non-specific pseudoallergic reactions to heterologous allergens. Therefore, work was carried out to study the allergic reactivity of tuberculosis patients and laboratory animals sensitised with atypical mycobacteria irradiated with gamma radiation (200 guinea pigs). It was established that 14-60 days after infection with tuberculosis pathogens, 90-100% of cavies developed allergic reactions to PPD-tuberculin for mammals and poultry, mainly to a homologous allergen. Allergic reactivity persisted until 90 days of the study. After exposure to sublethal (non-lethal) doses of gamma rays, infected and intact cavies developed non-specific reactions to tuberculin and heterologous allergens: mallein and brucellin. In cavies uninfected with the causative agent of tuberculosis, 7 days after gamma radiation exposure, non-specific reactions to mycobacterial allergens were observed at a dose load of 200 R in 16.6%; 150 R – 5.3% in the group, and after 27 days in irradiated doses of 50 R and 100 R in 25% and 33% of the studied animals, respectively. Isolated reactions to brucellin and mallein occurred in animals infected with the causative agent of tuberculosis and intact animals 60 days after irradiation with doses of 50 R, 100 R and 150 R. The manifestation of non-specific allergies in irradiated animals depended on the radiation dose rate and radiosensitivity of the animals

Tuberculin conversion rate after BCG vaccination of apparently healthy infants in a resource-poor setting

Background: Although Bacillus Calmette Guerin (BCG) vaccine remains one of the most important public health preventive measures against tuberculosis (TB), the presence of a BCG scar may not imply an immune response. Tuberculin reactivity after BCG vaccination has been the most common measure of the effect of the BCG vaccine. Post-vaccination BCG-induced tuberculin reactivity ranges from no induration to an induration diameter of 15 mm. However, tuberculin conversion in infants is usually about 10 mm in more than 90% of infants tested at 12 weeks post-vaccination age. Objective: This study sought to assess the tuberculin conversion rate after BCG vaccination. Materials and Methods: It was a hospital-based cross-sectional study. Two hundred and eighty (280) infants aged 13 to 15 weeks who received BCG vaccination within one month of birth were enrolled. The BCG scar diameter was measured, and Mantoux test was done. Data were analyzed by using the Statistical Package for Social Sciences (SPSS), version 20 (Chicago Il). Results: Among the 280 BCG-vaccinated infants, tuberculin conversion rate was 64%, whereas scar failure rate was 28.9%. Overall, 75.9% of infants with a BCG scar had a positive Mantoux test. The BCG-vaccinated infants with a BCG scar were about six times more likely to have a tuberculin conversion than those without a BCG scar (OR =5.641, 95% C.I = 3.227 to 9.859). Conclusion: There was a 64% conversion rate among the BCG-vaccinated infants. The presence of the BCG scar correlated well with the tuberculin conversion rate.

Tuberculin skin tests following Bacille Calmette Guerin vaccination in Africa: a protocol for systematic review and meta-analysis.

Tuberculin reactivity following tuberculin skin test which is the most common measure of the effect of the Bacille Calmette Guerin (BCG) vaccination has remained complex. This protocol is aimed to assess the effect of BCG vaccine on tuberculin skin test in Africa as a guide to better understanding or resolving this complexity. A search strategy is developed using MeSH, key words, text words, and entry terms. Five databases will be searched, including PubMed, African Journals Online (AJOL), Google Scholar, Research Gate, and Cochrane Library. Only observational studies conducted in Sub-Saharan Africa and retrievable in English language will be included. The primary measurable outcome of this study is pooled prevalence of positive tuberculin skin tests. Secondary outcomes are factors that influence Tuberculin Skin Test (TST) positivity such as BCG type, the dose of BCG, age at BCG vaccinates, time/interval between BCG vaccination and TST, and type of tuberculin unit used for TST. Identified studies will be screened and selected based on inclusion criteria. Data will be extracted into Zotero, Microsoft Excel and CMA software. Both quality scores and the risk of bias for individual studies will be reported. Studies will be assessed for methodological, clinical, and statistical heterogeneity. Funnel Plots will be used for assessing publication bias. The results will be presented in tabular format in addition to a narrative synthesis. The pooled prevalence of effect of BCG vaccine on TST in Africa will be examined in relation to factors that influence TST positivity.

Primitive Cavum Tuberculosis: An Unusual Location of Mycobacteria

<i>Objective:</i> This is a 17-year-old patient with no known history who had consulted the ENT department of the CHU-Gabriel Touré for persistent obstruction of the right nose. Its clinical history dates back to approximately 03 years, marked by a unilateral right nasal obstruction of progressive installation and permanent evolution associated with purulent posterior rhinorrhea, anosmia, right hypoacusis, headaches in helmet and an alteration of the state. general. There was no notion of cough, evening fever or epistaxis. These symptoms motivated several unspecified treatments without improvement. Before the onset of ptosis and ipsilateral blindness, he consulted us for support. We noted on otoscopy a dull right eardrum with a hearing loss of 25 decibels (db). Ophthalmological examination showed ptosis, ophthalmoplegia and blindness on the right side. Nasofibroscopy revealed a budding lesion taking up the entire right half of the roof of the nasopharynx filling the Rosenmüller fossa. There was no palpable cervical adenopathy. HIV serology was negative. Maxillofacial computed tomography revealed a rectilinear nasal sinus osteolytic expansive tumoral process extending to the optic nerve as well as to the oculomotor muscles with grade II proptosis (figure 1). Two repeated biopsies of the lesion found tuberculosis in front of a gigantocellular epithelioid granuloma with caseous necrosis. Intradermal tuberculin reaction and AFB sputum became negative. The chest X-ray was normal. We carried out the surgical excision of the lesion and the diagnosis of tuberculosis was confirmed by the anatomopathological examination. The patient was placed under anti-tuberculosis verification according to the 2RHZE / 4RH Protocol. The evolution was favorable after two months with normalization of the signs on nasofibroscopy.

SARS-COV-2 Infection and Anti-Tuberculosis Immunity: Temporal Association or Real Protective Role?

Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies; it would have large positive repercussions for developing countries.

More on search for causes of sensitization to tuberculin PPD for mammals in cattle

Despite the large number of papers dealing with the description of proposed methods for bovine tuberculosis diagnosis and mechanisms of non-specific reaction development in diseased and healthy animals, various aspects require further study. Many specialists are still of the view, formulated when studying causes of pseudoallergic reactions, that the agents of actinomycosis, trematode infections etc. can cause sensitization of the animal body to tuberculin PPD for mammals. The possibility of sensitization of cattle body to Аctinomyces bovis tuberculin was studied in 240 animals identified as actinomycosis diseased among 3,473 tested animals. Only 11 (4.6%) of the total number of diseased animals were reactors to tuberculin PPD for mammals. During bacteriological tests of material from animals euthanized for diagnostic purposes (tuberculin reactors and nonreactors with a confirmed postmortem diagnosis of actinomycosis), acid-tolerant nontuberculous mycobacterium (NTM) cultures were isolated. The results of the experiment conducted in 628 cows of a dairy holding confirmed that Actinomyces bovis lacks tuberculin-associated allergenicity: actinomycosis was detected only in one of 96 (15.2%) tuberculin reactors. The conducted clinical tests with high significance level (Р &lt; 0.005) showed that there is no association between allergic reaction to tuberculin PPD for mammals and actinomycosis infection. The obtained results are indicative of imperfections in differential diagnosis, and further studies in this field should significantly contribute to gaining a better insight into non-specific sensitization of cattle body to tuberculin.

BCG re-vaccination in Malawi: 30-year follow-up of a large, randomised, double-blind, placebo-controlled trial

SummaryBackgroundA large, double-blind, randomised, placebo-controlled trial of repeat BCG found 49% efficacy against leprosy but no protection against tuberculosis after 6–9 years’ follow-up in 1995. We report here additional follow-up, which resulted in greatly increased tuberculosis case numbers, and allowed subgroup analysis.MethodsNearly 47 000 individuals of all ages living in northern Malawi with a BCG vaccine scar were randomly assigned (1:1) between 1986 and 1989 to receive a second BCG or placebo. The investigators and project staff remained masked to all interventions. Enhanced passive surveillance ensured ascertainment of tuberculosis and leprosy to the end of 2018. Tuberculosis case definitions included rigorous microbiological or histological confirmation. Prespecified subgroup analyses were by tuberculosis type, age at vaccination, time since vaccination, previous tuberculin reactivity, HIV status and Mycobacterium tuberculosis lineage. The original trial is registered with ISRCTN registry, ISRCTN11311670.FindingsIn follow-up until Dec 31, 2018, 824 participants had developed tuberculosis, including 786 with pulmonary disease, of whom 383 (63%) of 607 with known HIV status were HIV positive. There was no effect of a second BCG overall (odds ratio [OR] 0·92; 95% CI 0·80–1·05), or for pulmonary (0·93; 0·81–1·07), or lymph node tuberculosis (0·60; 0·31–1·17). The OR was lower for those with known HIV-negative tuberculosis (0·77; 0·59–1·00), for those vaccinated as children (aged <5 years, 0·74; 0·41–1·35; aged 5–14 years, 0·77; 0·60–0·99), and for cases arising at least 20 years after vaccination (0·79; 0·63–1·01). There were no differences by tuberculin status at vaccination, or lineage. There was no evidence of protection against leprosy beyond 10 years after vaccination (although there have been only nine diagnostically certain cases since 1995).InterpretationThere was no evidence that repeat BCG vaccination provides appreciable protection against overall tuberculosis in this rural African population with a high prevalence of HIV. Subgroup effects should not be overinterpreted given the multiple analyses done. However, the evidence for modest protection against HIV-negative tuberculosis, and for a delayed benefit in those vaccinated as children, is consistent with other observations in the literature.FundingLEPRA, Wellcome Trust, Bill & Melinda Gates Foundation.

Tuberculosis prevalence in animals and humans in the Republic of Kazakhstan.

Background and Aim:Tuberculosis is an infectious disease that affects humans and animals. This study aimed to review the influence of economic and organizational, veterinary, and sanitary measures on the epizootic situation of animal tuberculosis and the epidemiological situation of human tuberculosis in the Republic of Kazakhstan.Materials and Methods:The epizootic situation of cattle tuberculosis in Kazakhstan was studied based on the annual statistics of allergy testing of animals with tuberculosis by the Committee for Veterinary Control and Supervision of the Ministry of Agriculture of the Republic of Kazakhstan, according to the results of allergic, clinical, and pathological studies, including laboratory studies of biomaterials from animals that reacted to tuberculin. Tuberculinization of cattle in the country is performed twice in the spring and autumn using tuberculin purified protein derivative for mammals. In addition, mass diagnosis of human tuberculosis is conducted by radiology.Results:The authors assessed the epizootic situation of tuberculosis in cattle in Kazakhstan from 1991 to 2019. The analysis results showed that at the beginning, the epizootic situation in cattle tuberculosis was challenging. However, since 2001, there has been a noticeable decrease in tuberculosis in animals in Kazakhstan, which has had a favorable effect on the epidemic situation of human tuberculosis.Conclusion:According to the analysis results, the measures used in the Republic of Kazakhstan to prevent tuberculosis improved the well-being of livestock farms. The proper conduct by qualified veterinary specialists on allergy testing of animals and differential diagnosis of nonspecific tuberculin reactions allows establishing an accurate epizootic picture of tuberculosis. Furthermore, strict adherence to instructions on the diagnosis and prevention of tuberculosis, implementation of developed veterinary, sanitary, and organization, and economic measures can improve the epizootic picture of tuberculosis, reducing the risk of human tuberculosis.

Renal involvement in sarcoidosis

Sarcoidosis is a systemic granulomatosis that affects the lungs and mediastinum. Renal involvement is rare in this disease. It's most commonly granulomatous interstitial nephritis. The most common form of presentation is naked renal failure. This is a retrospective study that collected 12 cases of sarcoidosis complicated by acute renal failure. The study consisted of identifying the epidemiological, clinical, biological and histologic data that confirmed the diagnosis from January 1994 to January 2016. A search for extra-renal placement of sarcoidosis concerned all cases. Then, a study of the therapeutic and evolutionary profile was carried out in all cases. Twelve patients (8 males and 4 females) with a mean age of 43 years. The intradermal tuberculin reaction sit negative in 6 cases. Biological analysis showed acute renal failure with a median creatinine of 54.32 mg/L, biological inflammatory syndrome in all cases, normal blood calcium in 9 cases, hypercalcaemia in 6 cases, hypercalciuria in 4 cases, hypergammaglobulinemia of polyclonal appearance in 3 cases and elevated proteinuria in 2 cases. Renal ultrasound was normal in all patients. The renal biopsy performed in all cases showed tubulointerstitial nephropathy. The extra-renal signs found were pulmonary interstitial syndrome in 4 cases, dry syndrome in 4 cases, mediastinal lymphadenopathy in 4 cases, one patient presented a unilateral uveitis. Two patients underwent extra-renal treatment. All patients were on corticosteroids with a clear improvement in creatinine and normalisation of renal function in all patients. The average follow-up time was 18 months. Renal involvement during sarcoidosis is rare (10%) but may progress to renal failure (3% of cases). The renal biopsy is of great interest to maintain the diagnosis of sarcoidosis, especially in the absence of other extra-renal signs. Renal involvement during sarcoidosis is rarely revealing and may delay diagnosis, leading to chronic and even end-stage renal disease.

The distribution of tuberculin reaction among children at school entry in Madaba, Jordan

The present study reports the results of a tuberculin test survey of a representative sample of BCG unvaccinated children at school entry age in the Madaba district in Jordan in 1991-92. Preschool household contacts of positive schoolchildren and a 5% random sample of negative schoolchildren were also screened by the same test. Three out of the 746 children screened by the initial school survey were found to be positive giving a prevalence rate of 0.4%. The overall prevalence rate of infection among preschool contacts was found to be 10.1% [28.6% among the contacts of the positive schoolchildren compared to 8.1% among contacts of the negative children]