Intralesional Measles, Mumps, Rubella Vaccine versus Tuberculin Purified Protein Derivative Injections in the Treatment of Palmoplantar and Periungual Warts: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Palmoplantar and periungual warts tend to be recalcitrant. Intralesional immunotherapy can provide high efficacy with additional benefit to distant warts. However, evidence on comparative effects between intralesional immunotherapy with measles, mumps, rubella vaccine (MMR) and tuberculin purified protein derivative (PPD) and roles of dermoscopy in predicting treatment outcomes in palmoplantar/periungual warts is limited. OBJECTIVES: The study aimed to compare efficacy and safety of intralesional MMR and PPD injections in treatment of palmoplantar/periungual warts and explore associations between dermoscopic findings and treatment outcomes. METHODS: We conducted a double-blind randomized controlled trial involving 40 patients with palmoplantar/periungual warts who were equally assigned to receive MMR or PPD. Intralesional injection was done every 2 weeks until clearance or maximum of 5 treatments. RESULTS: Complete resolution was higher in MMR than PPD group (90.0% vs. 80.0% in index lesion and 81.3% vs. 54.6% in distant lesions, respectively), although the differences were statistically nonsignificant. Dermoscopic findings were not significantly associated with complete resolution. Local swelling, i.e., the most common adverse event, occurred more frequently in PPD (40.0%) than MMR group (10.0%). CONCLUSION: This study suggests that intralesional immunotherapy with either MMR or PPD is efficacious in palmoplantar/periungual warts, with MMR showing a trend toward higher clearance and lower adverse events.

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain.

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. CONCLUSION: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. WHAT IS KNOWN: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. WHAT IS NEW: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

The use of natural killer cell activity and PPD test in the prediction of results in intravesical BCG treatment of patients with nonmuscle-invasive bladder cancer.

PURPOSE: To predict the efficacy of intravesical BCG therapy in patients with nonmuscle-invasive bladder tumors (NIBC) by using components of the cellular immune response such as the tuberculin skin test (PPD) and natural killer (NK) activity measurement. METHODS: Ninety-nine patients who were started on intravesical BCG therapy for NIBC were evaluated prospectively. Patients who were included in the intermediate, high, and very high-risk groups according to the EAU NMIBC Scoring System and who had never received intravesical BCG therapy previously were included. The clinical and demographic characteristics of the patients (age, gender, EAU NMBIC risk group, EORTC progression and recurrence scores, CUETO progression and recurrence scores, presence and types of comorbidity) were recorded. NK activity was measured and the PPD test was applied 3 days before the start of intravesical BCG therapy. The results of PPD were measured in millimeters 72 h after the test. RESULTS: PPD values measured before BCG treatment, as an independent variable, were found to be significantly lower in patients with recurrence. A significant correlation was detected between NK activity results obtained before BCG treatment and recurrence after treatment, when the cutoff was 200-500 pg/dl. There was no significant relationship between the time to recurrence and PPD and NKA measurements. CONCLUSION: We conclude that the results of PPD test and NK activity measurement performed before starting intravesical BCG therapy in NIBC may be a marker that can be used to predict the risk of recurrence under treatment.

Tuberculosis: Common Questions and Answers.

Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.

Bilateral Ocular Tuberculosis in a Child with Negative Tuberculin Skin Test (TST): A Diagnostic Dilemma.

PURPOSE: To report a case of bilateral ocular tuberculosis (OTB) in a child with negative Tuberculin skin test (TST). METHODS: Case report. OBSERVATIONS: A 12-year-old malnourished systemically asymptomatic boy presented with sudden profound loss of vision in both eyes. Dense vitritis precluded fundus visualization in right eye (RE). In left eye, fundus findings of extensive vasculitis associated with multifocal retinochoroiditis were suggestive of OTB. However, negative TST, normal chest X-ray, and gram negative bacteriuria led to confusion between endogenous endophthalmitis and OTB. Based on strong clinical suspicion and high-resolution chest tomography (HRCT) of thorax which was suggestive of TB-pneumonitis, a diagnosis of presumed OTB was made. A good response to anti-tubercular-treatment and corticosteroids, with resolution of retinochoroiditis lesions, vasculitis, and vitritis, further supported our diagnosis. CONCLUSIONS: This case highlights the importance of keeping a high index of suspicion for TB-associated uveitis in children, based on clinical findings.

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

OBJECTIVES: Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. METHODS: To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). RESULTS: Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/µl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/µl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/µl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/µl (50/100 person-years, 95% CI 32, 73). CONCLUSIONS: TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/µl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

Immunotherapy in cutaneous warts: comparative clinical Study between MMR vaccine, tuberculin, and BCG Vaccine.

BACKGROUND: Warts are common viral infection of the skin. Treating warts are still an ongoing challenge and no general agreement is reached, on the best treatment, despite different therapeutic approaches. Intralesional (IL) immunotherapy has recently been shown to be effective in treating various wart forms. AIMS: To assess the efficacy and safety of IL tuberculin, IL MMR vaccine, and intradermal (ID) BCG vaccination in treating viral warts. PATIENTS AND METHODS: Sixty patients with single or multiple warts were divided equally into three groups. Group A received IL MMR vaccine, and group B received IL tuberculin every 3 weeks (maximum 3 times). Group C received ID BCG vaccination in the arm with one month interval (maximum 3 times). Recurrence was followed up for 6 months. RESULTS: In group A, complete response occurred in 30%, partial response in 5%, and no response in 65%. In group B, complete response occurred in 45%, partial response in 20%, minimal response in 10% and no response in 25%. In group C, complete response occurred in 70%, partial response in 5%, minimal response in 5%, and no response in 20%. No recurrence was observed in group A and B but occurred in one patient in group C with the same lesion. CONCLUSIONS: Immunotherapy by IL tuberculin and ID BCG vaccination are safe, effective, and inexpensive techniques in treating all types of warts even if recalcitrant or multiple but immunotherapy by IL MMR vaccine has shown less effectiveness and less safety technique.

Efficacy and safety of intralesional injection of vitamin D3 versus tuberculin PPD in the treatment of plantar warts: A comparative controlled study.

BACKGROUND: Several destructive and immunotherapeutic methods are used in treatment of plantar warts, but an effective method with no or reduced recurrence has not been found till now. OBJECTIVES: To evaluate the efficacy and safety of intralesional (IL) vitamin D3 (Vit.D3 ) injection vs IL tuberculin purified protein derivative (PPD) injection in the treatment of plantar warts. METHODS: Sixty patients with plantar warts were randomized into 3 equal groups: group I treated using IL tuberculin PPD every 2 weeks, group II treated using IL Vit.D3 every 4 weeks, and group III treated with IL saline every 2 weeks till complete clearance or for a maximum of 3 sessions. The follow-up period was 6 months. RESULTS: There was a statistically significant improvement in therapeutic groups than control with more significant improvement in group II than I. Regarding number of sessions required for complete response, there was a positive significant correlation in both groups, but more significant in group I. There was a negative correlation between the number of lesions and the response to treatment in both groups. Group II showed significantly better response to treatment in male patients. Both modalities were well tolerated, with no remarkable side effects and no recurrence in cured patients of both groups. CONCLUSIONS: Both IL PPD and Vit.D3 injection are safe and effective for treatment of plantar warts even recalcitrant or multiple, with no postprocedural downtime, better results, and patient satisfaction. IL Vit.D3 injection has a superior advantage than PPD.

A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts.

BACKGROUND: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. METHODS: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. RESULTS: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. LIMITATION: Unicentric trial. CONCLUSION: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

Role Of Tuberculin Test As A Diagnostic Tool For Tuberculosis.

BACKGROUND: Childhood Tuberculosis remains one of the major public health concerns in developing countries like Pakistan and is responsible for high rates of morbidity and mortality in children. Although tuberculin skin test is very commonly used by physicians all over the world, its interpretation always remains difficult and challenging. The objective of this study was to determine the frequency of positive tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis. METHODS: This Cross-sectional study was conducted in the department of Paediatric Ayub Teaching Hospital, Abbottabad from 1st February 2015 to 30th April 2016. A total of 150 patients were observed in this study. Children of either gender who were aged 1-15 years admitted in ward with tuberculosis were included in the study by using nonprobability convenient sampling technique. We injected 0.1 ml (10 units) of tuberculin purified protein derivative (PPD) into the anterior surface of the forearm and induration was read at 72 hours after administration. Data was entered and analysed using SPSS version 10. RESULTS: Out of 150 children, 84 (56%) were males and 66 (44%) were females. The mean age was 7.8±3.84 years. Of these 75 (50%) were vaccinated and 75 (50%) were unvaccinated. In vaccinated Group 5.3% children had positive tuberculin skin test while in unvaccinated Group 2.7% children had positive tuberculin skin test and this difference was found statistically insignificant (pvalue= 0.40). Pulmonary TB was the diagnosis in 67 (44.7%), TBM in 65 (43.3%), abdominal TB in 7 (4.7%), disseminated TB in 4 (2.7%) and military TB in 7 (4.7%) patients. CONCLUSIONS: The positivity of tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis was found to be insignificant in our study. We conclude that Tuberculin Skin Test should not be used as a sole diagnostic tool for diagnosing the disease in children of our region..

[The study of ocular tuberculosis during the 19th and early 20th century].

During the 19th and early 20th century the achievements in the study of ocular tuberculosis were of great significance. The development of pathological anatomy in those years helped physicians to understand the histological image and the pathophysiology of the disease and allowed the scientists to detect the specific anatomical structures of the eye, where the disease could be present. The physicians of those years tried to describe the clinical image of the disease and to give value information, in order to facilitate the diagnosis. Despite major efforts made in the field of clinical approach to ocular tuberculosis, the treatment of the disease in those years was not very effective. Nevertheless, the physicians of the time used every new pharmacological or not pharmacological treatment to fight the disease.

Estudio comparativo de concordancia y costes entre la prueba de la tuberculina y QuantiFERON ®-TB Gold In-Tube en el diagnóstico de la infección latente tuberculosa en contactos de pacientes con tuberculosis pulmonar / Comparative study of concordance and costs between tuberculin skin test and QuantiFERON ®-TB Gold In-Tube in the diagnosis of latent tuberculosis infection among contacts of patients with pulmonary tuberculosis

Introducción: El diagnóstico de la infección latente tuberculosa (ILT) es posible realizarlo mediante la prueba de la tuberculina (PT) o bien a través de las denominadas técnicas de interferon-γ release assays (IGRAS, «análisis de liberación del interferón-γ»), siendo QuantiFERON®-TB Gold In-Tube (QF-G-IT) la más usada. Los IGRAS permiten evitar algunos inconvenientes de la PT, especialmente la reacción cruzada con la vacuna con bacilo de Calmette-Guérin (BCG). No obstante, también presentan algunos problemas, como son los derivados del coste de la técnica, así como el ser un método de laboratorio que precisa una infraestructura y experiencia adecuadas. No existe un claro consenso sobre cuál de las técnicas debería utilizarse de forma prioritaria para el diagnóstico de la ILT. Método: Se trata de un estudio comparativo entre la PT y la QF-G-IT en nuestra cohorte de contactos de pacientes con tuberculosis pulmonar durante el período de estudio (n = 101). Se realizó un análisis de la concordancia global y por grupos según los contactos estuvieran vacunados con BCG o no. Se realizó, además, un estudio de costes de ambas técnicas y de las estrategias diagnósticas basadas en ellas. Resultados: La concordancia entre la PT y la QF-G-IT fue aceptable en el global de la muestra, pero muy buena en el grupo de no vacunados. Se registraron muy pocos casos de valores indeterminados. El estudio de costes mostró que la PT era más económica que la QF-G-IT; sin embargo, al analizar el coste de las estrategias según cada técnica, la PT mostró un mayor coste-beneficio. Conclusión: Aconsejamos considerar QF-G-IT como la única y preferente técnica para el diagnóstico de la ILT en contactos convivientes, basados en una buena concordancia general entre ambas técnicas (más aún si eliminamos el efecto de la vacuna) y un estudio de costes favorable a QF-G-IT (AU)

Introduction: Recently diagnosis of latent tuberculosis infection (LTBI) can be made using the tuberculin skin test (TST) or by techniques known as interferon-γ release assays (IGRAS), being QuantiFERON®-TB Gold In-Tube (QF-G-IT) the most used. The IGRAS avoid some drawbacks of the TST, especially cross-reaction with bacillus Calmette-Guérin (BCG) vaccine, but also present some problems such as those arising from cost and the need of having an adequate infrastructure and experience. There is no clear consensus on which technique should be preferentially used for the diagnosis of LTBI. Methods: This is a comparative study between the TST and QT-G-IT in a cohort of contacts of patients with pulmonary tuberculosis during the study period. An analysis of global agreement and groups was performed according to whether the contacts were vaccinated with BCG or not. A study of costs of both techniques and diagnostic strategies based on these techniques was performed. Results: The agreement between TST and QF-G-IT was acceptable in the whole sample yet it was very good in the unvaccinated group. Few cases of indeterminate values were recorded. The cost study showed that TST was cheaper than QF-G-IT; however when we analyzed the cost of the strategies according to each technique, the QF-G-IT showed a better cost-benefit. Conclusion: We suggest considering QF-G-IT as the only preferred technique for the diagnosis of LTBI in household contacts, based on good overall agreement between the 2 techniques (even if we eliminate the effect of the vaccine) and a cost analysis favorable to QF-G-IT (AU)

A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma.

BACKGROUND: Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of 'in situ' tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC. METHODS: Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety. RESULTS: Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year. CONCLUSIONS: Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted.

Immune approaches in tuberculosis therapy: a brief overview.

TB is typically caused by Mycobacterium tuberculosis, a symbiotic bacterium present in one-third of the world's population. There any many factors triggering overt clinical disease in a small proportion of humans. In our view the major role in the process is played by the host's immune response, especially self-directed, destructive inflammation. Conventional chemotherapy produces bactericidal or bacteriostatic effects, but immunopathological changes can only be corrected by immunotherapy. Various attempts have been made to identify the optimal immune intervention. Some have shown promising effects, but many have failed. It is commonly believed that the field started in 1890: the year Robert Koch announced his tuberculin therapy. In the Pên Ts'ao Kang Mu, classical Chinese materia medica, published during Ming dynasty, Li Shi Chen (1518-1593) recommended, as a remedy for hemoptysis, to collect from the sputum "…blood lumps, roast them till they are black, and take then them as a powder". In retrospect, this is perhaps the earliest recorded reference relating to immunotherapy of TB with heat-killed mycobacteria. Modern science is obviously geared toward more palatable approach, but without hindsight from often disdained empirical evidence no progress can be made. The clinical experience from various trial and error processes is briefly discussed in this review.

Intradermal injection of PPD as a novel approach of immunotherapy in anogenital warts in pregnant women.

Immunotherapy for treatment of recalcitrant warts was used through different modalities including intralesional injection of purified protein derivative (PPD), which is an extract of Mycobacterium tuberculosis, used for testing exposure to tuberculin protein, either from a previous vaccination or from the environment. This method is used to evaluate the efficacy of a new approach of intradermal injection of PPD in the treatment of anogenital warts in pregnant women. A total of 40 pregnant women, aged 20-35 years, and presented with anogenital warts were enrolled in this study. Human papillomavirus (HPV) typing was done using the GP5+/GP6+ PCR assay. The patients were treated with weekly injections of PPD given intradermally in the forearms, and evaluated for the response regularly. HPV type-6 was the predominant genotype (67.5%). Overall, the improvement in this study was 85% and was related to the extent of tuberculin reactivity. Nineteen (47.5%) patients demonstrated complete clearance, 15 (37.5%) had partial response, and three (7.5%) had minimal response. Three (7.5%) cases did not respond to treatment. Side effects were minimal and insignificant. Treatment of anogenital warts in pregnant women with intradermal injection of PPD was found to be a unique, safe, and effective modality of immunotherapy.

Tuberculin immunotherapy: its history and lessons to be learned.

The use of tuberculin for the therapy of tuberculosis was attempted more than 100 years ago and abandoned because of its adverse reactions. In this historical review we point out that some of the intensive efforts to avoid the reactions were based on the best scientific rationale available at that time. Balancing the dosage and intervals of tuberculin delivery with clinical and laboratory monitoring of patients achieved a limited success, with implications, toward current research in the field. The role of economical and social aspects at that time is also a lesson to be learned toward current approaches to tuberculosis control.

Hughlings Jackson's suggestion for the treatment of epilepsy.

John Hughlings Jackson articulated a neurologic method of systematically evaluating the anatomy, physiology, and pathology of every patient with neurologic disease. He used this mode of analysis to develop a theory of the physiology of epilepsy. We examined an example of his method in a newly discovered, unpublished manuscript containing his suggestions for the treatment of epilepsy based on his physiologic ideas. He had his private papers destroyed at the time of his death, but the Rockefeller Library of the University College London Institute of Neurology, Queen Square, contains a collection of his papers probably saved from destruction by his collaborator James Taylor. Among these articles is an 1899 memorandum, labeled "For Private Circulation" and entitled "A Suggestion for the Treatment of Epilepsy." In it, Hughlings Jackson claimed that focal discharging lesions cause both focal and generalized epilepsy, and that the cells in the lesion discharge their energy more easily than normal tissue. Citing microscopic evidence that such lesions are congested and inflamed, and that tuberculin destroys such tissue in the lung, he reasoned that destroying these unstable neurons with tuberculin would improve epilepsy. In this private manuscript, Hughlings Jackson uses an unusually detailed analysis of the pathology, anatomy, and physiology of epilepsy to predict a scientific approach to its treatment.

Infecciones del sistema nervioso central en urgencias / Infections of the central nervous system in emergency department

Las infecciones del sistema nervioso central son enfermedades frecuentes en la atención urgente, pudiendo ser de origen bacteriano, parasitario o vírico. Los síntomas iniciales pueden ser inespecíficos, lo que puede dificultar y retrasar su diagnóstico, por lo que es de suma importancia toda la información que pueda obtenerse a través de la anamnesis y exploración física y con frecuencia exploraciones complementarias. En los últimos cien años, con la introducción de fármacos antibióticos ha disminuido de forma importante la mortalidad secundaria a meningoencefalitis, pero a pesar de ello siguen provocando alta morbi-mortalidad. Otros fenómenos, como las campañas de vacunación, movimientos migratorios, infección por el virus de la inmunodeficiencia humana y otros estados de inmunosupresión, han dado lugar a importantes cambios epidemiológicos como son la práctica desaparición de algunas infecciones o la aparición de otras previamente casi inexistentes. La lista de infecciones potenciales de sistema nervioso central es extensa por lo que en este artículo de revisión expondremos desde el punto de vista clínico, diagnóstico y terapéutico las más frecuentes en nuestro medio y algunas que, aunque poco frecuentes, pueden requerir atención urgente por su gravedad (AU)

Infections of the central nervous system are frequent diseases in emergency care. They can have a bacterial, parasitic or viral origin. Initial symptoms can be non-specific, which can complicate and delay diagnosis, hence the extreme importance of all the information that can be obtained through anamnesis and physical exploration, with frequent complementary explorations. In the last hundred years, with the introduction of antibiotic drugs, there has been a significant fall in mortality secondary to meningoencephalitis, but in spite of that they continue to provoke high morbidity and mortality. Other phenomena, such as vaccination campaigns, migratory movements, infection by HIV and other states of immunosuppression, have given rise to important epidemiological changes such as the virtual disappearance of some infections or the appearance of others that rarely existed previously. The list of potential infections of the central nervous system is extensive, which is why in this review we set out, from the clinical, diagnostic and therapeutic point of view, those that are most frequent in our environment and some that, although very infrequent, might require emergency attention due to their severity (AU)