Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Prevalence and clinical characteristics of pulmonary TB among pregnant and post-partum women.

SETTING: Antenatal care (ANC) and postpartum care (PPC) clinic in Manhiça District, Mozambique.OBJECTIVE: To estimate the prevalence of TB among pregnant and post-partum women and describe the clinical characteristics of the disease in a rural area of Southern Mozambique.METHODS: We conducted a cross-sectional TB prevalence study among pregnant and post-partum women recruited from September 2016 to March 2018 at the Manhiça Health Care Center (MHC). We recruited two independent cohorts of women consecutively presenting for routine pregnancy or post-partum follow-up visits.RESULTS: A total of 1,980 women from the ANC clinic and 1,010 from the PPC clinic were enrolled. We found a TB prevalence of 505/100,000 (95% CI: 242-926) among pregnant women and 297/100,000 (95% CI: 61-865) among post-partum women. Among HIV-positive pregnant women, TB prevalence was 1,626/100,000 (95% CI: 782-2,970) and among postpartum HIV-positive women, TB prevalence was 984/100,000 (95% CI: 203-2,848).CONCLUSIONS: The burden of TB was not higher in postpartum women than in pregnant women. Most TB cases were detected in HIV-positive women. TB screening and diagnostic testing among pregnant and postpartum women attending ANC and PPC clinics in Manhiça District is acceptable and feasible.

Thoracic ultrasound for TB diagnosis in adults and children.

Thoracic ultrasound is an appealing alternative to chest radiography for the diagnosis of TB. Based on research experience conducting thoracic ultrasound for adults and children in South Africa, three key considerations for potential scale-up were identified. First, thoracic ultrasound requires a comprehensive training programme for novice users; artificial intelligence may be used to simplify training and interpretation. Second, a robust ultrasound device is needed with good subpleural resolution and a probe suitable for children. Third, comprehensive scanning of the lungs is time-intensive, and shorter scanning protocols may be more feasible in clinical practice.

L'échographie thoracique est une alternative attrayante à la radiographie pulmonaire pour le diagnostic de la TB. En prenant appui sur l'expérience acquise lors d'études ayant utilisé l'échographie thoracique chez l'adulte et l'enfant en Afrique du Sud, trois considérations clés pour une éventuelle utilisation accrue de cet outil ont été identifiées. Premièrement, tout nouvel utilisateur d'un échographe thoracique doit suivre un programme de formation exhaustif. L'intelligence artificielle pourrait être utilisée pour simplifier la formation et l'interprétation des résultats. Deuxièmement, un échographe de qualité est nécessaire, avec une bonne résolution sous-pleurale et une sonde adaptée à l'enfant. Troisièmement, une scannographie exhaustive des poumons est chronophage ; des protocoles de scannographie plus courts pourraient être plus faciles en pratique clinique.

Treatment outcomes and safety in children with rifampicin-resistant TB.

BACKGROUND: The treatment of rifampicin-resistant TB (RR-TB) in children is evolving rapidly. As newer regimens are introduced into routine care, it is vital to compare their outcome and safety with well-characterised clinical cohorts treated with historical regimens.METHODS: Study sample comprised a prospective observational cohort of children on routine RR-TB treatment, enrolled from 2011 to 2015 in Cape Town, South Africa. Children were followed for safety, treatment response and outcome.RESULTS: Of 136 children included, 27 (19.9%) were living with HIV and 48 (37.8%) had severe TB. The median time-to-culture conversion in children with bacteriological confirmation (n = 44) was 28.5 days (IQR 14.5-45). Overall, 118/129 (91.5%) had favourable TB treatment outcomes. Of 106 (77.9%) children who received an injectable drug, 9 (8.5%) developed hearing loss and 7/136 (5.1%) developed other Grade 3 or higher adverse events likely related to treatment.CONCLUSIONS: In this cohort with a substantial proportion of children with severe manifestations of TB and with HIV, TB treatment outcomes were excellent. Apart from hearing loss, few children developed severe adverse events related to treatment. This study provides robust reference data for future evaluation of shorter, injectable-sparing regimens.

Integration of TB into child health policies in Africa's high-burden countries: a normative analysis.

Integration of paediatric TB care into decentralised child health services has the potential to reduce the large proportion of childhood TB that remains undiagnosed. We performed a review of national guidelines and policies for TB and child health to evaluate the normative integration of paediatric TB into existing child health programmes in 15 high TB burden countries in Africa. While integration is addressed in 80% of the national strategic plans for TB, the child health strategies insufficiently address TB in their plans to reduce child mortality. Emphasis needs to be put on multi-sectoral collaboration among national health programmes.

Intégrer la prise en charge antituberculeuse de l'enfant aux services de soins pédiatriques décentralisés pourrait permettre de réduire la proportion élevée de cas de TB pédiatriques qui restent non diagnostiqués. Nous avons examiné les politiques et recommandations nationales en matière de TB et de soins pédiatriques afin d'évaluer l'intégration normative de la TB pédiatrique aux programmes de prise en charge pédiatrique existant dans 15 pays africains à forte prévalence de TB. Cette intégration est abordée dans 80% des plans stratégiques nationaux pour la TB, mais les stratégies relatives aux soins pédiatriques ne tiennent pas suffisamment compte de la TB dans leurs plans visant à réduire la mortalité infantile. Il convient de mettre l'accent sur la collaboration multisectorielle entre les programmes de santé nationaux.

Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems.

Cholecystokinin (CCK) is a neuropeptide that modulates processes such as digestion, satiety, and anxiety. CCK-type peptides have been characterized in jawed vertebrates and invertebrates, but little is known about CCK-type signalling in the most ancient group of vertebrates, the agnathans. Here, we have cloned and sequenced a cDNA encoding a sea lamprey (Petromyzon marinus L.) CCK-type precursor (PmCCK), which contains a CCK-type octapeptide sequence (PmCCK-8) that is highly similar to gnathostome CCKs. Using mRNA in situ hybridization, the distribution of PmCCK-expressing neurons was mapped in the CNS of P. marinus. This revealed PmCCK-expressing neurons in the hypothalamus, posterior tubercle, prethalamus, nucleus of the medial longitudinal fasciculus, midbrain tegmentum, isthmus, rhombencephalic reticular formation, and the putative nucleus of the solitary tract. Some PmCCK-expressing neuronal populations were only observed in adults, revealing important differences with larvae. We generated an antiserum to PmCCK-8 to enable immunohistochemical analysis of CCK expression, which revealed that GABA or glutamate, but not serotonin, tyrosine hydroxylase or neuropeptide Y, is co-expressed in some PmCCK-8-immunoreactive (ir) neurons. Importantly, this is the first demonstration of co-localization of GABA and CCK in neurons of a non-mammalian vertebrate. We also characterized extensive cholecystokinergic fibre systems of the CNS, including innervation of habenular subnuclei. A conspicuous PmCCK-8-ir tract ascending in the lateral rhombencephalon selectively innervates a glutamatergic population in the dorsal isthmic grey. Interestingly, this tract is reminiscent of the secondary gustatory/visceral tract of teleosts. In conclusion, this study provides important new information on the evolution of the cholecystokinergic system in vertebrates.

Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça.

SETTING: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. OBJECTIVE: To determine the drug resistance patterns of laboratory-confirmed TB cases. DESIGN: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. RESULTS: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). CONCLUSION: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.

Carga viral indetectable tras la adición de raltegravir al tratamiento de una adolescente con virus de la inmunodeficiencia humana embarazada de 36 semanas y en fracaso virológico / Undetectable viral load after the addition of raltegravir in a 36 week pregnant adolescent with high-level HIV viraemia

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Meningitis pediátrica. ¿Cuándo podemos estar tranquilos? / Pediatric meningitis. When can we be calm?

Introducción: Desde que en 1980 se publicó la Escala de Boyer, se han propuesto muchas herramientas clínicas para distinguir entre meningitis viral (MV) y meningitis bacteriana(MB). En los últimos años se ha validado el Bacterial Meningitis Score (BMS), instrumento que identifica a los niños con muy bajo riesgo de padecer MB. Nuestro objetivo es determinarla eficacia de la Escala de Boyer modificada con la proteína C reactiva (PCR), y validar en nuestra población pediátrica el BMS. Métodos: Se realizó un análisis retrospectivo de los niños de3 meses a 15 años de edad hospitalizados con el diagnóstico de meningitis entre 1994 y 2007. Se aplicó la Escala de Boyer, añadiéndose una puntuación correspondiente a la PCR. La sensibilidad y la especificidad se calcularon en los puntos de corte determinantes para la toma de decisiones (puntuaciones 3 y 5). En el caso del BMS, se valoró su sensibilidad y especificidad a partir del cumplimiento de los criterios de inclusión propuestos por sus autores. Resultados: En total se incluyeron 145 casos, de los cuales46 fueron MB y 99 MV. Se determinó la PCR en 73 de ellos. La modificación de la Escala de Boyer con la PCR aumentó la sensibilidad en el punto de corte 5 de un 83 a un 100%, permaneciendo la sensibilidad en el 100% en ambos casos. En el caso del BMS, el cumplimiento de al menos uno de los cinco criterios de riesgo identificó los casos de MB con una sensibilidad del 100% y una especificidad del 61,22%. Conclusión: Una puntuación de más de 5 en la Escala de Boyer modificada con la PCR identifica de forma precisa los casos de meningitis de etiología bacteriana en nuestro medio. El BMS es muy eficaz para determinar los casos de muy bajo riesgo de MB. La combinación de ambas herramientas resulta muy útil en el manejo de los pacientes con sospecha de meningitis (AU)

Introduction: Since Boyer's Score was published in 1980; many clinical tools have been proposed to distinguish between viral meningitis (VM) and bacterial meningitis (BM). Recently, it has been validated the Bacterial Meningitis Score (BMS), an instrument that identifies children at very low risk of BM. Our objective is to determine the accuracy of Boyer's Score modified with C-reactive protein (CRP) and to validate the BMS in our pediatric population. Methods: A retrospective study analysis of children (aged from 3 months to 15 years) hospitalized with a meningitis diagnosis in our pediatric center between 1994 and 2007. We calculated Boyer's Score and added a punctuation corresponding to CRP. The sensitivity and specificity were estimated in the scores cut off point that determine the taking of decisions (punctuations 3 and 5). We applied the BMS to all children using the inclusion criteria proposed by the authors, and calculated the sensitivity and specificity. Results: Among the 145 cases included, 46 had BM and 99 had VM. CRP was determined in 73 of them. The modification of Boyer's Score with CRP increased the sensibility of punctuation 5 from 83% to 100%; the specificity of this punctuation remained in 100% even if CRP was included or not. In the case of BMS, the fact of presenting at least one of the 5 criteria identified the cases of BM with a sensibility of 100% and a specificity of 61.22%. Conclusion: A punctuation of more than 5 in Boyer's Score modified with CRP identifies with high efficacy the cases of bacterial etiology. The BMS is very accurate for the identification of very low risk cases of BM. The combination of both scales is very useful in the management of patients with suspicion of meningitis ( AU)

Extent of extracranial disease is a powerful predictor of survival in patients with brain metastases from gynecological cancer.

Central nervous system metastasis from gynecological malignancy is a rare phenomenon that has been described in the past 30 years. The objective of this study is to analyze the treatment modalities and prognostic factors for brain metastases from gynecological tumors that predict prolonged survival. A retrospective chart and pathology review of 47 patients diagnosed with a gynecological tumor with brain metastasis in 1994-2004 was performed. Thirty patients had undergone initial diagnosis and treatment at our institution, and 17 patients were referred following primary treatment at an outside institution. Adjusted Chi-square, Kaplan-Meier survival estimates, log-rank tests, and Cox regression analysis were utilized for statistical analysis of the total cohort. Of the 3146 patients with newly diagnosed gynecological cancer in this 10-year period, 30 developed brain metastasis demonstrating an incidence of 0.95%. Overall median survival from the time of diagnosis of brain metastasis was 7.5 months (95% CI 4-15, range 9 days-64 months) and 40% survival at 1 year. Multivariate analysis revealed evidence of extracranial disease at time of metastasis diagnosis predicted decreased survival (hazard ratio 6.207), while papillary serous histology (hazard ratio 0.42), and use of any chemotherapy (hazard ratio 0.24) predicted longer survival. No other patient or tumor characteristics were found to be independent prognostic indicators affecting survival. Despite the ominous prognosis associated with the development of brain metastasis, these retrospective data suggest that multimodal therapy with whole brain radiation therapy, chemotherapy, and surgical resection of metastases in selected patients without evidence of extracranial and with solitary or multiple lesions can prolong survival.

Primary treatment of Bartholin's gland carcinoma with radiation and chemoradiation: a report on ten consecutive cases.

We reviewed our experience with primary radiation therapy for Bartholin's gland carcinoma (BGC) as an alternative to traditional surgical treatment. A retrospective study reviewed records from the Cancer Data Registry and Research Patient Data Registry from 1986 to 2002. Charts of ten women identified with BGC were reviewed for demographic information, presenting symptoms, tumor characteristics, treatment modalities, and complications, as well as for recurrence and survival. The incidence of BGC was 2.13% of all invasive vulvar cancer cases at the Massachusetts General Hospital (MGH). Four patients presented with clinical stage I disease, one with stage II, three with stage III, and two with stage IV. The median age at diagnosis was 63.5 years. There were five squamous cell carcinomas, two adenoid cystic carcinomas, two mucinous adenocarcinomas, and one small-cell carcinoma. After a change in treatment policy in 1986 from primary surgery that had often required postoperative radiation therapy, ten consecutive patients were treated with primary radiotherapy or chemoradiation therapy. Treatment included teletherapy combined with a boost to the primary site, regional nodes and/or interstitial brachytherapy. Short-term complications were mild and well tolerated; one patient developed late radiation-associated pelvic fractures. Four tumors recurred with a mean time to recurrence of 31.2 months. The median follow-up was 87.2 months (45-142). Three- and 5-year survivals were 71.5% and 66%, comparable to outcomes after surgery and postoperative radiation therapy. We conclude that primary radiation or chemoradiation therapy offers an effective alternative to surgery in the treatment of BGC with preservation of genital function and low morbidity.