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In endemic regions, tuberculosis in children constitutes a bigger fraction of total cases as compared to those in low endemic regions, regardless of the implications, this phenomenon has been historically neglected. Pediatric tuberculosis has an insidious onset and quickly develops into disseminated disease and the young are at a special risk for dissemination. Some studies suggest that measures to contain adult tuberculosis are not enough to manage tuberculosis in children, meaning that pediatric tuberculosis needs dedicated attention. Children are harder to diagnose than adults, because collecting samples is difficult, and their bacterial yield is low. In endemic countries, such as Mexico, where contact with Mycobacterium tuberculosis is common, immunological tests are inconsistent, especially in immunocompromised children. With the disruption of Mexican healthcare services by the COVID-19 pandemic, there is an uncertainty of how the situation has evolved, current data about tuberculosis indicates a drop in the national report of cases: 15.4 per 100,000 persons in 2021, compared with pre-COVID 2019 17.7 per 100,000 persons, a small increase in mortality: 1.7 per 100,000 in 2021 compared with 2019 1.6 per 100,000, a drop in treatment success: 80.4% in 2021 compared with 85.4% in 2019, and a decrease in national vaccination rates: an estimate of 86.6% children between 1 and 2 years-old were vaccinated in 2021 compared with 97.3% reported national rate in 2018-2019. There is a need for new research on regions with high tuberculosis incidence, to clarify the current situation of pediatric tuberculosis and improve epidemiological surveillance.

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Resumen La meningitis por Mycobacterium tuberculosis es infrecuente en pediatría y su diagnóstico definitivo representa un desafío clínico. Presentamos el caso de un lactante de dos años, que presentó un cuadro de meningitis crónica. Se logró el diagnóstico tras la sospecha imagenológica y la confirmación tras la búsqueda seriada del complejo M. tuberculosis por RPC en LCR y en biopsia de tejido cerebral. A pesar de sus complicaciones, el paciente respondió favorablemente al tratamiento antituberculoso. En Chile, la tuberculosis es infrecuente en niños y los síntomas son generalmente inespecíficos. Los hallazgos en RM cerebral asociados a alteraciones del LCR permiten sospechar el compromiso meníngeo precozmente. Se recomienda iniciar el tratamiento antituberculoso empírico ante la sospecha, ya que mejora el pronóstico. A pesar de los avances diagnósticos y terapéuticos, la meningitis tuberculosa sigue teniendo una alta tasa de complicaciones y un pronóstico ominoso.

Abstract Mycobacterium tuberculosis meningitis is rare in the pediatric population and its definitive diagnosis represents a clinical challenge. We present the case of a 2-year-old infant with chronic meningitis. Diagnosis was accomplished by suggestive radiological findings and serial search for M. tuberculosis complex by real-time polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF) and in brain tissue. Despite the complications, the patient evolved favorably with the tuberculosis treatment. In Chile, tuberculosis is a rare disease in children and symptoms are generally nonspecific. Brain MRI findings associated with CSF alterations allow early suspicion of MTBC. Start of empirical antituberculosis treatment upon suspicion is recommended given it is associated with better prognosis. Despite diagnostic and therapeutic advances, MTBC continues to have a high complication rate and an ominous prognosis.

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Resumen La tuberculosis (TB) intestinal y peritoneal es una enfermedad regional, crónica, específica, generalmente secundaria a TB pulmonar avanzada. Mayormente adopta la forma localizada en el tejido linfoide ileal. El diagnóstico puede sospecharse por los síntomas, los antecedentes del paciente y las pruebas de imagen, entre ellas radiografía de tórax, tomografía axial computarizada y ecografía. La confirmación precisa realizar una colonoscopia y toma de biopsia para demostración de granulomas caseificantes y del bacilo ácido-alcohol resistente. Presentamos un caso de un niño que consulto por absceso perianal y fístula, tratado como enfermedad intestinal inflamatoria y cuya radiografía de tórax motivó la sospecha y estudio de TB.

Abstract Intestinal and peritoneal tuberculosis (TB) is a regional, chronic, specific disease, generally secondary to advanced pulmonary TB. It is mostly localized at the ileal lymphoid tissue. The diagnosis may be suspected due to the symptoms, the patient's history, and imaging tests, such as chest x-ray, computerized axial tomography and echography. For confirmation, it is necessary to perform a colonoscopy and a biopsy sample to show caseating granulomas and the acid-alcohol resistant bacillus. We present the case of a child who consulted for a perianal abscess and fistula that were treated as inflammatory bowel disease, whose chest x-ray encouraged the suspicion and study of TB.

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We followed 35 children meeting a research definition for unconfirmed tuberculosis (TB) but in whom a pediatric pulmonologist did not diagnose or treat TB. After a median follow-up of 16.4 months, most children were not diagnosed with TB following a comprehensive evaluation. However, 2 were diagnosed with TB, demonstrating high TB risk (6%; exact 95% CI, 1%-19%). In some contexts, researchers may wish to supplement these research definitions with clinical decision data and longitudinal follow-up in order to improve specificity.

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OBJECTIVE: To compare the socio-demographic, clinical, and diagnostic characteristics and treatment outcomes between extrapulmonary tuberculosis (EPTB) and pulmonary tuberculosis (PTB) in children and adolescents in Rio de Janeiro, a high TB-burdened Brazilian city. METHODS: This retrospective study used data from patients with EPTB and PTB aged 0 - 18 years, notified on two national databases from 2014 to 2016. RESULTS: Among the 1008 patients, 144 (14.2%) had EPTB. Patients with EPTB showed higher odds of hospital-based diagnosis (odds ratio (OR): 6.76 [95% confidence interval (95% CI): 4.62-9.90]; p < 0.001), no laboratory confirmation (OR: 4.9 2.14 [95% CI: 3.07 - 7.85]; p < 0.001), and being <14 years old (OR: 3.13 [95% CI: 2.18-4.49]) than those with PTB. A diagnosis without laboratory investigation was observed among 301/864 (34.8%) patients with PTB, 48/144 (33.3%) with EPTB, and among those aged under five years with EPTB (15/27 [55.6%]). TB deaths were more frequent in patients with EPTB (5/144 [3.5%]) than in those with PTB (4/864[0.5%]) (p = 0.001); 4/5 (80%) TB deaths were due to TB meningitis; 50% died within 14 days of diagnosis. CONCLUSIONS: EPTB remains a clinical diagnostic challenge that needs to be addressed to fully benefit from the higher sensitivity laboratory investigations.

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Objective: To describe the investigation of latent tuberculosis infection and indication for isoniazid preventive therapy in children and adolescents evaluated at the children's hospital. Methods: This retrospective study examines all latent tuberculosis infection subjects with indication for isoniazid preventive therapy attended during 2002-2009 at the pulmonology outpatient clinic from children's hospital in Rio de Janeiro, Brazil. The subjects were classified into three groups by origin: (G1) primary and secondary health units; (G2) children's hospital-pulmonology outpatient clinic; and (G3) children's hospital-specialty outpatient clinics. The association between the variables examined and G1 was analyzed using uni- variate analysis. Results: Of the 286 latent tuberculosis infection cases included 169 (59.1%) were from G1, 56 (19.6%) from G2, and 61 (21.3%) from G3. Latent tuberculosis infection diagnosis without isoniazid preventive therapy prescription was present in 142 (49.6%) cases before arrival at the pulmonology outpatient clinic: 135 (95.1%) from G1, three (2.1%) from G2, and four (2.8%) from G3. Variables associated with G1 were presence of isoniazid preventive therapy criteria before attending the pulmonology outpatient clinic (OR: 62.3; 26.6-146.2), negative HIV infection status (OR: 9.44; 1.16-76.3); contact with pulmonary tuberculosis (OR: 5.57; 1.99-15.5), and residing in Rio de Janeiro city (OR: 1.89; 1.04-3.44). Conclusion: Strategies that increase latent tuberculosis infection identification and isoniazid preventive therapy prescription in primary and secondary health units are urgently needed. .

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OBJECTIVE: To describe the investigation of latent tuberculosis infection and indication for isoniazid preventive therapy in children and adolescents evaluated at the children's hospital. METHODS: This retrospective study examines all latent tuberculosis infection subjects with indication for isoniazid preventive therapy attended during 2002-2009 at the pulmonology outpatient clinic from children's hospital in Rio de Janeiro, Brazil. The subjects were classified into three groups by origin: (G1) primary and secondary health units; (G2) children's hospital-pulmonology outpatient clinic; and (G3) children's hospital-specialty outpatient clinics. The association between the variables examined and G1 was analyzed using univariate analysis. RESULTS: Of the 286 latent tuberculosis infection cases included 169 (59.1%) were from G1, 56 (19.6%) from G2, and 61 (21.3%) from G3. Latent tuberculosis infection diagnosis without isoniazid preventive therapy prescription was present in 142 (49.6%) cases before arrival at the pulmonology outpatient clinic: 135 (95.1%) from G1, three (2.1%) from G2, and four (2.8%) from G3. Variables associated with G1 were presence of isoniazid preventive therapy criteria before attending the pulmonology outpatient clinic (OR: 62.3; 26.6-146.2), negative HIV infection status (OR: 9.44; 1.16-76.3); contact with pulmonary tuberculosis (OR: 5.57; 1.99-15.5), and residing in Rio de Janeiro city (OR: 1.89; 1.04-3.44). CONCLUSION: Strategies that increase latent tuberculosis infection identification and isoniazid preventive therapy prescription in primary and secondary health units are urgently needed.

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BACKGROUND: Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss. AIM: We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(ε-caprolactone)-b-PEG-b-poly(ε-caprolactone) 'flower-like' polymeric micelles. MATERIALS & METHODS: The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia. RESULTS: Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH. CONCLUSION: Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration.

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A clinical experience of tuberculosis (TB) in 104 pediatric patients observed at the Hospital Regional de Valdivia (southern Chile), along a sixteen year period (1986 - 2001) is presented. Pulmonary TB was diagnosed in 88 cases, extrapulmonary TB in 19 cases and both localizations in three cases. Pulmonary TB was bacteriologically confirmed in 62.5% of cases, through either gastric aspirate or sputum samples. Gastric aspirate yielded 42.8% of positive cultures; two infants who presented central nervous system involvement, died. A case of congenital TB was observed in a 30 day old infant. There were no cases of AIDS in this experience. Pediatric TB has progressively decreased its incidence in our region, particularly the extrapulmonary localization, but still represents a challenging disease to clinicians.

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