2017 French health authority guidelines for neonates at risk of early-onset sepsis: Adherence and barriers in a tertiary hospital.

The objective of this study was to evaluate the adherence to the French Health Authority's 2017 guidelines concerning early-onset sepsis (EOS) in neonates. This 6-month prospective observational study was conducted in 2020 in a tertiary hospital maternity unit. Neonates were classified according to their risk of EOS and the level of appropriate surveillance was analyzed. The risk of EOS was determined for 69.9% of the 1024 included neonates. Of the 123 neonates with a moderate or high risk of EOS, the optimal clinical surveillance was 88%. Even in a tertiary hospital, with training of caregivers, adherence to guidelines was incomplete. Some corrective measures are suggested and should be applied to enhance the adherence.

Aminoglycoside prescription: compliance with national guidelines in a pediatric hospital.

OBJECTIVE: Our study aimed to describe the use of aminoglycosides (AGs) in the pediatric population in acute settings and to assess its compliance with the most recent national recommendations. METHODS: A single-center retrospective study conducted over a 5-month period. Pediatric patients who received at least one dose of AGs in emergency or intensive care unit were included. Compliance with the 2011 French recommendations was assessed. RESULTS: A total of 153 AG prescriptions (120 with gentamicin and 33 with amikacin) for 139 patients (median age of patients = 10 months [IQR: 3-36]) were analyzed. Most of the AG prescriptions were initiated in the emergency department (n = 117, 76%) and, overall, compliance with national guidelines was met in half (n = 77) of the prescriptions. In the emergency department, cases of misuse concerned the indication, mostly for patients with pyelonephritis. In the pediatric intensive care unit setting, the misuse concerned underdosing and a low rate of pharmacological monitoring. CONCLUSION: AGs are still misused in pediatric acute settings. In order to limit drug resistance and to be more efficacious, higher doses should be used and monitoring should be performed, in particular in pediatric intensive care units. In the emergency department, more objective criteria should be used to initiate AGs.

Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants - identification of 11 novel mutations in CYBB.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X-linked CGD (X91-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910 , X91- or X91+ ), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910 -CGD and two X91- -CGD). One X910 -CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91- -CGD were also novel; one deletion, c.-67delT, was localized in the promoter region of CYBB; the second c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91- -CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three-dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91- -CGD patients correlates with mild clinical forms of CGD, whereas X910 -CGD and X91+ -CGD cases remain the most clinically severe forms.

Endogenous endophthalmitis as a severe complication following a Streptococcus pyogenes infection.

The diagnosis of endogenous endophthalmitis is challenging. We report a pediatric case of endogenous endophthalmitis due to Streptococcus pyogenes angina. A previously healthy 33-month-old child presented to the emergency department with a history of fever and fatigue related to bacterial angina. On physical examination, an opalescent cornea was noticed and the diagnosis of endogenous endophthalmitis was confirmed by the pediatric ophthalmologist. Streptococcus pyogenes was found in blood culture and in the anterior chamber fluid. There was an adverse outcome with posterior vitrectomy and eye atrophy. Since endogenous endophthalmitis can lead to a poor visual outcome, urgent therapeutic management is necessary.

Splenic infarction associated with transient anti-prothrombin antibodies is a rare manifestation of acute Mycoplasma pneumoniae infection.

We report the first paediatric case of splenic infarction following acute Mycoplasma pneumoniae infection with induction of anti-prothrombin (aPT) antibodies. A 12-year-old boy was admitted to the paediatric emergency department for a left pleuropneumonia and a splenic infarction. aPT antibodies were transitorily detected. The patient recovered fully after antibiotic therapy and a 3-month course of anticoagulation treatment. Antiphospholipid (aPL) antibodies induced by acute infections have already been reported but cases of clinically relevant thrombosis remain rare. The pathogenicity of aPT antibodies is discussed here. We hypothesize that these antibodies were involved in this symptomatic hypercoagulable state.

Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular / Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma

La evaluación de la respuesta a los diferentes tratamientos aplicados es un factor decisivo en el manejo clínico de los pacientes con carcinoma hepatocelular. Con ella se logra determinar la eficacia del tratamiento y detectar de forma precoz la recidiva del tumor tratado o la aparición de nuevas lesiones que puedan ser candidatas a nuevos tratamientos. Cuando se aplican tratamientos locorregionales, que inducen necrosis, o terapias moleculares, que tienen efectos antiangiogénicos, las lesiones tratadas suelen presentar un cambio en su comportamiento por imagen. Cabe resaltar que no suelen presentar una disminución de su tamaño, al menos inicialmente, e incluso algunas lesiones pueden aparentemente aumentar de tamaño. Por ello es imprescindible conocer el mecanismo de acción de cada tratamiento utilizado y el espectro de imagen que pueden producir esos tratamientos en las distintas técnicas que se emplean en su valoración

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response

Neonatal fever: A puzzling case.

Toxoplasmosis is a potentially serious fetal infection associated with maternal seroconversion of toxoplasmosis during pregnancy. Follow-up and treatment vary between different countries. We present a case of congenital toxoplasmosis with unusual physiopathology and symptomatology. The mother was immunized before the beginning of pregnancy but immunosuppressive treatments for Crohn disease maintained during the pregnancy could explain toxoplasmosis reactivation in the mother and congenital toxoplasmosis. The baby presented reversible B lymphopenia and hypogammaglobulinemia.

Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma. / Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular.

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response.

[Acute epiglottitis due to Haemophilus influenzae b: A severe consequence of increased skepticism about vaccination]. / Épiglottite aiguë à Haemophilus influenzae b : conséquence grave du scepticisme vaccinal.

Acute epiglottis is a life-threatening disease in relation with the occurrence of an acute upper airway obstruction. Its incidence has fallen dramatically since the widespread introduction of Haemophilus influenzae type b (Hib) conjugate vaccine. We report the case of a 26-month-old child who was not fully immunized and presented acute upper airway respiratory distress with fever. The symptoms quickly evolved to a respiratory arrest condition with bradycardia, revealing epiglottitis due to Hib. Despite high immunization coverage with great efficacy and occurrence of herd immunity, this entity still exists because of the French population's skepticism of the routine vaccination schedule.

[Bacillus Calmette-Guérin osteomyelitis. A case report in a former preterm baby]. / Ostéomyélite secondaire à une vaccination par le bacille de Calmette et Guérin : à propos d'un cas chez un ancien prématuré.

Postvaccination osteo-articular mycobacterial infectious disease is a rare and potentially serious complication after Bacillus Calmette-Guérin (BCG) vaccine. We report on a case of a former preterm baby born at 30 weeks of gestation who was vaccinated with BCG Copenhagen strain at 2 months of age. He presented 6 months later with a painful limp, which was found to be a mono-articular osteitis of the right ankle. Histology of the biopsy showed signs of mycobacterial infection and molecular analysis confirmed a BCG infection. Blood tests did not reveal any immunodeficiency associated with the disease (IFN-gamma levels were normal). The course of the disease was favorable with 9 months of antibiotic therapy against mycobacteria. BCG complications should lead to screening for immunodeficiency. The prognosis of BCG osteitis is excellent if the disease is localized. No link between prematurity and BCG complications has been found to date. BCG vaccination of premature infant should be the same as for the general population.

Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Española para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Española de Trasplante Hepático, la Sociedad Española de Radiología Médica, la Sociedad Española de Radiología Vascular e Intervencionista y la Sociedad Española de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE.

Predicting the development of liver cirrhosis by simple modelling in patients with chronic hepatitis C.

BACKGROUND: Data are scarce on the natural history of chronic hepatitis C (CHC) in patients with mild hepatitis C who did not respond to anti-viral therapy. AIM: To predict the risk of progression to cirrhosis, identifying patients with the more urgent need for therapy with effective anti-virals. METHODS: A cohort of 1289 noncirrhotic CHC patients treated with interferon-based therapy between 1990 and 2004 in two referral hospitals were followed up for a median of 12 years. RESULTS: Overall, SVR was achieved in 46.6% of patients. Data from a randomly split sample (n = 832) was used to estimate a model to predict outcomes. Among nonresponders (n = 444), cirrhosis developed in 123 (28%) patients. In this group, the 3, 5 and 10-year cumulative probabilities of cirrhosis were 4%, 7% and 22%, respectively, compared to <1% in the SVR-group (P < 0.05). Baseline factors independently associated with progression to cirrhosis in nonresponders were: fibrosis ≥F2, age >40 years, AST >100 IU/L, GGT >40 IU/L. Three logistic regression models that combined these simple variables were highly accurate in predicting the individual risk of developing cirrhosis with areas under the receiving operating characteristic curves (AUC) at 5, 7 and 10 years of ~0.80. The reproducibility of the models in the validation cohort (n = 457, nonresponders = 244), was consistently high. CONCLUSIONS: Modelling based on simple laboratory and clinical data can accurately identify the individual risk of progression to cirrhosis in nonresponder patients with chronic hepatitis C, becoming a very helpful tool to prioritise the start of oral anti-viral therapy in clinical practice.

[Extensive swelling reaction after a pentavalent vaccination]. / Réaction locale étendue à un vaccin pentavalent.

Injection site reactions (ISRs) are quite common side effects defined by a local adverse drug reaction directly caused by a vaccine. Twenty-four hours after an intramuscular injection (in the deltoid muscle) of the diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, Haemophilus influenza type b (DTPCa-Hib) combined vaccine, a 3-year-old boy developed fever. A few hours later, local redness and swelling appeared at the injection site, with rapid extension to the entire limb, it was pain-free, and no other clinical anomalies were present. The patient received intravenous antibiotics for suspected cellulitis. The progression was favorable in 12h (apyrexia and decreased limb swelling), allowing the intravenous antibiotic treatment to be discontinued. Since the child was in excellent general health and recovery was fast, an ISR was diagnosed. Extensive limb swelling is frequent, mostly after the fourth dose of DTPCa-Hib. Deltoid muscle injection of DTP vaccine increases the risk of ISR compared to injection in the thigh, before the age of 3 years. The introduction of acellular pertussis vaccine decreased the risk of general side effects but may increase the risk of ISR. These reactions disappear with symptomatic treatment and do not contraindicate the product.

Assessment of the IgA immunosorbent agglutination assay for the diagnosis of congenital toxoplasmosis on a series of 145 toxoplasmic seroconversions.

A retrospective analysis of 145 medical records from our teaching hospital laboratory showed an overall specificity of greater than 97% for the IgA immunosorbent agglutination assay (ISAGA A) performed on the sera of babies to diagnose congenital toxoplasmosis (CT). These actualized data emphasize the ability of this test to confirm a diagnosis of congenital toxoplasmosis.

[YEL-AND meningoencephalitis in a 4-year-old boy consecutive to a yellow-fever vaccine]. / Méningo-encéphalite après vaccination anti-amarile : syndrome de YEL-AND.

Yellow fever is a vector-borne disease transmitted by an endemic mosquito in sub-Saharan Africa and tropical South America. It causes fever and possibly liver and renal failure with hemorrhagic signs, which may be fatal. The yellow-fever vaccine is an attenuated vaccine that is recommended for all travelers over the age of 9 months in high-risk areas. Adverse effects have been reported: minor symptoms (such as viral syndrome), hypersensitivity reactions, and major symptoms such as viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND). The yellow-fever vaccine-associated autoimmune disease with central nervous system involvement (such as acute disseminated encephalomyelitis) associates fever and headaches, neurologic dysfunction, seizures, cerebrospinal fluid (CSF) pleocytosis, and elevated protein, with neuroimaging consistent with multifocal areas of demyelization. The presence of antibodies or virus in CSF, within 1-30 days following vaccination, and the exclusion of other causes is necessary for diagnosis. We describe herein the case of a 4-year-old child who presented with severe encephalitis consecutive to a yellow-fever vaccine, with favorable progression. Diagnosis is based on the chronology of clinical and paraclinical signs and the presence of yellow-fever-specific antibodies in CSF. The treatment consists of symptomatic treatment and immunoglobulin injection.

Potencialidad de la región costera de Córdoba -Colombia- para el cultivo de tilapia nilótica / Potential of the Cordoba coastal region Colombia for the culture of Nile tilapia

Objetivo. Identificar las áreas con alta potencialidad para el cultivo de tilapia nilótica en la región costera de Córdoba, Colombia. Materiales y métodos. Cinco capas de información fueron incorporadas en un sistema de información geográfica: ubicación potencial de estanques, calidad del suelo, calidad del agua, infraestructura vial, población, limitantes y restricciones. Se recopiló información cartográfica, se revisaron los planes de ordenamiento territorial (POT) de los municipios costeros, se obtuvieron imágenes de satélite de la zona y se tomaron muestras de agua y suelo; esta información fue evaluada, organizada e introducida en la base de datos de sistemas de información geográfica (SIG). Se aplicaron herramientas de análisis espacial y se establecieron modelos de análisis que permitieron la generación e integración de los diferentes temas y la construcción final del mapa de aptitud para el cultivo de tilapia. Resultados. El 2% del área de estudio resultó apta para el cultivo de tilapia nilótica. El alto índice de necesidades básicas insatisfechas (NBI) y las deficiencias en la infraestructura vial tuvieron efecto negativo sobre la potencialidad para la tilapicultura. Altas concentraciones de hierro y ligera acidez en algunas áreas posibilitan la presencia de suelos sulfatados ácidos. La alta turbidez y sólidos suspendidos afectaron la calidad del agua, además de la reducida capacidad de drenaje que en algunas áreas evidencian los riesgos de inundación. Conclusiones. El municipio de San Antero presentó la mejor aptitud para el cultivo de tilapia; sin embargo el área deltaico-estuarina, los ambientes lacustres y sus alrededores en la cuenca baja del Sinú, no resultaron aptos.

Objective. To identify areas with high potential for Nile tilapia farming in the coastal region of Córdoba (Colombia). Materials and methods. Five information layers were incorporated into a geographical information system, including potential location of ponds, soil quality, water quality, road infrastructure and population, and limitations and constraints. Mapping information was collected, and land use plans (POT) of the coastal municipalities were reviewed; satellite images of the area were obtained and water and soil samples were collected. This information was evaluated, organized, and entered into the Geographical Information System (GIS) database. Spatial analysis tools were applied, and models of analysis that allowed the generation and integration of different subjects and the final construction of the suitability map for growing tilapia were established. Results. 2% of the study area was suitable for growing Nile tilapia. The high rate of unsatisfied basic needs (NBI) and deficiencies in road infrastructure had a negative effect on the potential for tilapia farming. High concentrations of iron and slight acidity in some areas suggest the presence of acid sulphate soils. High turbidity and suspended solids affected water quality, in addition to the small drainage capacity in some areas, which shows flood risk. Conclusions. The town of San Antero was the best fit for tilapia culture, but the delta-estuarine area, the lakes and surrounding environments in the lower basin of the Sinu River were not eligible.

[A child with sepsis-associated encephalopathy]. / Encéphalopathie associée au sepsis (EAS), un cas pédiatrique.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction due to a systemic response to infection. We report the case of a 4-year-old girl with fever and vomiting for 48h, brought to the university hospital of Grenoble because of vigilance disorders, loss of verbal fluency, and a cerebellar syndrome. She had a biological infectious syndrome. Infectious encephalitis was suggested first, but the cerebral scan and the lumbar punction were normal. Magnetic resonance imaging (MRI) showed a diffuse brain edema with extended involvement of cortical and basal ganglia. The electroencephalogram was globally slow. The infectious syndrome was explained by perforated appendicitis with peritonitis, treated by surgery and antibiotic therapy. Other infectious explorations were negative. No metabolic or autoimmune diseases were found. Hence, our final diagnosis was sepsis-associated encephalopathy. After 1 year of follow-up care, her clinical exam, MRI, and EEG were normal. Sepsis-associated encephalopathy has been increasingly described in the adult population, but until today only three pediatric cases have been published. It is diagnosed when the patient has a severe infectious syndrome associated with neurologic symptoms, mostly vigilance or consciousness disorders, no signs of shock, and only when other potential reasons have been ruled out. The MRI shows non-specific diffuse lesions with vasogenic edema on the subcortical substance or on the basal ganglia and the thalami. The electroencephalogram is slowed down on the whole. The main differential diagnoses are infectious encephalitis, acute disseminated encephalomyelitis, and cerebral vasculitis. Posterior reversible encephalopathy syndrome is an MRI diagnosis that presents characteristics similar to SAE. In the future, it could be discovered that it is the same physiopathology. At the moment, we only treat the symptoms and the causative infection. Most of the time, patients have neurologic sequelae that affect their verbal fluency. It can persist from a few months up to 6yrs. Although quite slow, the neurologic progression is good. The mechanisms are studied and there are hopes for specific treatments. The main explanation seems to be immune with alterations of the blood-brain barrier. Cytokines and activated leukocytes may attack the cerebral substance.

[Unusual presentation of a severe Mycoplasma pneumoniae infection: report of 2 cases]. / Présentation inhabituelle d'une infection grave à Mycoplasma pneumoniae, à propos de 2 observations.

Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary symptoms are most common in children. We describe herein two unusual severe forms of M. pneumoniae infection without initial pulmonary symptoms. The first case is an 8-month-old boy who was hospitalized in the pediatric intensive care unit with severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical infection. Initial blood tests and x-ray did not aid the diagnosis. The blood tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared 24h later, and there was a pneumonia outbreak on the chest radiograph. The boy was given josamycin and improved quickly. The second case concerns an 8-year-old child who was hospitalized in the pediatric intensive care unit with toxic shock. No clinical infectious origin was found. A broad-spectrum antibiotic therapy was started with ceftriaxone and josamycin. The M. pneumoniae blood test came back positive, which confirmed the diagnosis of septic shock in M. pneumoniae, requiring adjustment of the antibiotic therapy. Current guidelines for the choice of probabilistic antibiotic therapy in case of severe sepsis do not include the case of M. pneumoniae. The early initiation of antibiotic therapy plays a major role in the prognosis of these patients. It seems useful to search for M. pneumoniae in cases of severe atypical infections, particularly in the absence of pulmonary symptoms.

Mammary herpes: a little known mode of neonatal herpes contamination.

Neonatal herpes is a severe disease. We report a case with a fatal outcome, whose transmission was linked to mammary herpes. The lack of early diagnosis delayed appropriate therapeutic management. The purpose of this report is to alert clinicians to this potential mode of transmission.

[Mendelian susceptibility to mycobacterial disease: a case report of disseminated infection due to Mycobacterium avium]. / Syndrome de susceptibilité mendélienne aux infections mycobactériennes : à propos d'un cas d'infection disséminée à Mycobacterium avium.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic syndrome that predisposes patients to infections caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guérin (BCG) vaccines and nontuberculous environmental mycobacteria in children free of classical immunodeficiencies. This syndrome consists of impaired antimycobacterial immunity (axis IL12/INF-γ) constituting a new immune deficiency and outlining its major role in mycobacterial immunity. We report a new case of MSMD through the observation of a young girl with a disseminated infection due to Mycobacterium avium. The molecular defect was 2 autosomal recessive mutations of the IL12Rß1 gene (gene encoding for the ß1 chain of the IL12 receptor) leading to the absence of the IL12 receptor on the activated T lymphocytes' surface. IL-12RB1 deficiency is the most common genetic etiology of MSMD. Today, there are 6 MSMD-causing genes, leading to 13 distinct genetic disorders. The clinical phenotype differs between patients. The description of the molecular and immunological basis of this syndrome has allowed us to explain the pathophysiology of antimycobacterial immunity and is essential to understanding and managing these diseases.