Meningitis tuberculosa: un desafío diagnóstico en pediatría

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.

Incidence and Predictors of Poor Outcome amongChildhood Tuberculosis in the North of Cameroon

Background. Childhood tuberculosis (TB) has been neglected by TB programs in Sub-Saharan Africa. The aim of this study was to determine the incidence and predictors of poor outcome in children with TB in the North region of Cameroon. Methods.It was a retrospective cohort study based on hospital TB registers and treatment TB forms, in all of the 18 functional diagnosis and therapeutic centers (DTC) in the North region. All children aged 0-15years, on anti-TB treatment between 2010-2016 were enrolled. Logistic regression was used to find independent factors associated to poor outcome. Results. Of the 668 children included [321 (48.1%) boys], the median (25th-75thpercentile) age was 11(6-14) years, with 75.9% children aged >5 years. Pulmonary TB was the most common (62.9%) with 34.3% smear-negative pulmonary TB. Extrapulmonary TB (62.1%) was mostly found in children aged 0-5years. HIV/TB coinfection was 10.3%. Incidence (95%CI) of poor outcome was 4.0 %( 2.5-5.5%). Predictors [OR (95%CI)] of poor outcome were: HIV positivechildren [3.995(1.131-14.112), p=0.031], management in peripheral DTC [32.451(4.211-250.099), p=0.001], and transferred in patients from a peripheral zone toward a 3rdor 4thDTC category [4.602(1.092-19.386), p=0.037]. Conclusion.Incidence of poor outcome of childhood TB was quite low in the North region of Cameroon. HIV, peripheral TDC and transferred in patients were predictors of poor outcome. A better management of HIV, retraining DTC personnel and early reference from peripheral DTC would reduce poor outcome among childhood TB.

Tuberculosis pediátrica intestinal. Un caballo de Troya / Pediatric Intestinal Tuberculosis. A Trojan Horse

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.

Diagnostic value of polymerase chain reaction targeting insertion sequence IS1081 for the diagnosis of pediatric tuberculosis

Background: Aim of this study was to evaluate the efficacy of PCR targeting IS1081in diagnosis of pediatric tuberculosis and compare the results with MGIT culture.Methods: This prospective study was conducted in the department of pediatrics, S.N. medical college, Agra. 100 subjects (28 pulmonary 72 extra pulmonary) were registered in study. The specimens obtained from these cases were subjected to Ziehl'Neelsen staining (ZN), MGIT 960 TB culture and PCR targeting insertion sequence IS1081. Sensitivity, specificity, PPV and NPV of PCR were calculated in pulmonary and extra pulmonary specimens. The results of PCR IS1081 were compared to MGIT culture.Results: Microscopy with ZN staining was positive in 12 (12%) samples. MGIT culture was positive in 44% samples with maximum positivity in sputum (70%). PCR IS1081 has shown 93.3% sensitivity in pulmonary tuberculosis, while PCR IS1081 has shown 93.1% sensitivity in extra pulmonary tuberculosis.' In diagnosis of childhood tuberculosis PCR IS1081 was found to be statistically significant (p value <0.05) as compared with MGIT culture. Result was statistically significant (p value <0.05) in CSF samples only.Conclusions: The study concluded that the PCR targeting sequence IS1081 technique is the most sensitive technique for a quick identification of MTB in pulmonary and extra pulmonary tuberculosis.

Application of T-SPOT.TB in pediatric tuberculosis and advances of T-SPOT.TB in other body fluids except blood / 国际儿科学杂志

As a new immunoassay,T-SPOT.TB has been widely used in the diagnosis of tuberculosis in children.A large number of clinical trials show that it has better sensitivity and specificity simultaneously,compared with other diagnostic methods for tuberculosis in children.This article focuses on the principle,influence factors and specific applieation,and reviews advances in other body fluids except blood of T-SPOT.TB.

Diagnosis and management of childhood tuberculosis in public health clinics in a rural area in the Philippines: Results from a community surveillance

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Childhood tuberculosis (TB) remains a significant health problem worldwide despite the increase in its emphasis on national health programs.</p><p style="text-align: justify;"><strong>OBJECTIVE:</strong> This study aimed to describe how TB in children is identified and managed in a routine TB program in a rural setting in a high-burden country.</p><p style="text-align: justify;"><strong>METHODS:</strong> This is a prospective, community-based surveillance study in public rural clinics in the Philippines. Observations on case finding and management of TB in children as well as contact tracing in an existing TB program are described.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Out of 266 children with presumptive TB, 41 (15.4%) were cases of TB, 15 (5.6%) had latent TB infection (LTBI), 81 (30.5%) had TB exposure, and 129 (48.5%) had no TB. There were 37 (90%) TB cases who were clinically diagnosed. Ninety-three percent (93%) of children with TB disease were cured or completed treatment. Among 25 children targeted for isoniazid preventive therapy (IPT) for LTBI and TB exposure, only 12 (52%) completed the recommended 6 months of IPT. Only 40 (43%) children aged 0 to 4 years exposed to smear-positive TB cases were screened.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Barriers in the diagnosis, low IPT completion, and problems in contact tracing may hinder the successful implementation of TB programs for children.</p>

Tuberculosis contact tracing among children and adolescent referred to children's hospital in Rio de Janeiro, Brazil

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. .

Functional polymorphisms in CYP2C19 & CYP3A5 genes associated with decreased susceptibility for paediatric tuberculosis.

Background & objectives: Tuberculosis (TB) bacilli ingested by macrophages evade host immune responses by multiple mechanisms including the inhibition of apoptosis. As the cytochrome-P-450 system (CYP) contributes to apoptosis it has been suggested that genetic variation in CYP may be associated with susceptibility to TB infection. This study was carried out to evaluate cytochrome P-450 polymorphisms in Chinese Han children and to investigate the effect of these polymorphisms in paediatric TB. Methods: Frequencies for the CYP2C19, CYP3A4, CYP3A5 and CYP2E1 mutated alleles and genotypes were compared between 142 Chinese paediatric TB patients and 150 non-infected controls by real time PCR genotyping on peripheral leukocyte DNA. Results: CYP2C19 (636 G>A, rs4986893) A allele and AG genotype were associated with decreased susceptibility to TB (P = 0.006, OR= 0.33, 95% CI: 0.15-0.76; and P = 0.005, OR =0.31, 95% CI: 0.14-0.72 respectively), as were the CYP3A5 (6986A>G, rs776746) G allele and particularly homozygous GG (recessive mode) genotype (P = 0.004, OR=0.61, 95% CI: 0.43-0.85; and P=0.002, OR=0.47, 95% CI: 0.29-0.76). Interpretation & conclusions: The data suggested that CYP2C19 and CYP3A5 polymorphisms affect susceptibility to paediatric TB. Further studies are indicated to confirm and elucidate these observations.

Determinants of childhood tuberculosis - A case control study among children registered under Revised National Tuberculosis Control Programme in a district of South India.

Aim: To study the determinants of Tuberculosis (TB) in children between the age group of 0-14 years receiving treatment under Revised National TB Control Programme (RNTCP) . Methods: A case (registered under RNTCP) control study was undertaken with 41 cases and 82 controls. Results: Factors found to have significance according to binary logistic regression were low-birth weight (LBW) [Odd’s ratio=3.56],Malnutrition [Odd’s ratio=3.96], Passive smoking [Odd’s ratio=6.28] and exposure to fire-wood smoke [Odd’s ratio=6.91]. Conclusion: LBW, malnutrition, passive smoking and fire-wood smoke are the risk factors to be addressed to prevent pediatric TB.

Clinical profile and treatment outcome of Tuberculous Lymphadenitis in children using DOTS strategy.

Background: Extra pulmonary TB (EPTB) including tuberculous lymphadenitis is becoming more common probably due to human immuno deficiency virus (HIV) co-infection. While children do experience a high TB related morbidity and mortality, management of TB in children is challenging. The present study was designed to study the treatment outcome of DOTS strategy for pediatric tuberculous lymphadenitis. Objective: To study the efficacy of DOTS strategy for pediatric lymphhnode tuberculosis. Methods: Retrospective analysis of 669 children of lymphnode tuberculosis treated with DOTS strategy over 9½ years. Results: Mean age was 9.8 years with significantly more girls (61.3%) than boys (38.7%) {c2=34.08, P< 0.001 (S)}. Most of the patients were in the age group of 11-14 years (48.0%) followed by 6-10 years(34.5%) and 0-5 years(17.5%) respectively. Cervical tuberculous lymphadenitis (88.2%) was the commonest form for all ages followed by axillary lymphadenitis in 3.3%. TB of other sites was seen in only 57 (8.5%) cases. Out of total 622 (93%) cases of lymphnode TB where fine needle aspiration and/ or excisional biopsy was done, it was positive (84.2%) and negative (15.6%) respectively for AFB/ cytology, while it could not be done in 47 patients due to inaccessible sites. Category I, II and III was started on 15.4%, 7.5% and 77.1% patients respectively. Overall, treatment completion rate was 94.9% and the default rate was 2.2% with a failure rate of 2.5%. Death rate was 0.3%. Conclusion: The study confirms the efficacy of DOTS strategy for pediatric TB lymphadenitis

Clinical profile and treatment outcome of Tubercular Pleurisy in pediatric age group using DOTS strategy.

A significant proportion of global tuberculosis (TB) caseload is contributed by children. Management of pediatric TB especially EPTB is challenging. The present study was designed to study demographic, clinical profile and treatment outcome of DOTS strategy for pediatric tubercular pleurisy. Aim: To study the efficacy of DOTS strategy. Methods: Retrospective analysis of 106 TB pleurisy children treated with DOTS Results: Mean age was 10.8 years (median age 12.2 years) with more females (51.9%) than males (48.1%)c1 2=0.15; P= 0.698 (NS). In the age group of 0-5, 6-10 and 11-14 years, there were 15.1%, 30.2% and 54.7% patients respectively. Fever was the commonest symptom (98.1%) followed by cough (77.4%) and chest pain (55.7%). History of contact could be elicited only in 2/3rd of cases unilateral effusion (61.3%) was commonest, followed by empyema (22.6%), massive effusion and broncho-pleural fistula each in 13.2% cases respectively. Bilateral effusion was seen in 3.8% cases only. Conventional methods (mantoux, radiograph, ultrasound, pleural aspiration) and minimal invasive surgical techniques, percutaneous pleural biopsy were done to arrive at the diagnosis. Diagnosis was made by X-ray Chest in 92.5%, exudative pleural fluid (100%) predominantly lymphocytic in 85.8%, positive AFB smear and culture in 4.7 and 5.7% cases respectively. Category I, II and III was started on 35.9%, 2.8% and 61.3% patients respectively. Overall treatment completion rate was 94.3%, 4.7% default rate, 0.9% failure rate and no deaths. Conclusion: The study confirms early detection by simple tests and ensuring complete treatment using DOTS strategy.

Tuberculosis infantil en Valdivia: Experiencia clínica en 16 años / Tuberculosis in infancy: sixteen year experience

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.