Tuberculosis congénita - el desafío parte con la madre / Congenital tuberculosis - the challenge starts with the mother

La tuberculosis es la enfermedad infecciosa por un solo agente que provoca más muertes en el mundo. A la fecha, no hay un registro de casos de embarazadas con tuberculosis en el mundo ni en Chile, y menos de los casos de tuberculosis congénita. El diagnóstico en ambas situaciones suele ser tardío y con malos resultados clínicos. Se presenta una revisión de la literatura con relación a tuberculosis perinatal y dos casos clínicos de los binomios madre e hijo afectados.

Tuberculosis is the single agent infectious disease that causes the most deaths in the world. To date, there is no record of pregnant women with tuberculosis in the world or in Chile, even less of congenital tuberculosis. Diagnosis in both situations is usually late and with poor clinical results. A literature review is presented in relation to perinatal tuberculosis and two clinical cases of affected mother and child binomials.

Preterm Twins Born to a Mother with Miliary Tuberculosis: Importance of Early Recognition and Prompt Response in Infection Control to Manage Congenital Tuberculosis Exposure in a Neonatal Intensive Care Unit.

Delayed diagnosis of congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) is a serious problem in terms of infection control. Here, we report our preemptive infection control activities implemented after the diagnosis of miliary TB in a mother of preterm twins (index twins, NB1 and NB2) in the NICU. In addition, we reviewed previous case reports of congenital TB exposure in the NICU setting. Immediately after diagnosing miliary TB in the mother, the index twins were isolated before their TB diagnosis and received preemptive anti-TB medication; contact investigations were also conducted. Eventually, NB1 was diagnosed with congenital TB at 29 days of age, and NB2 showed no definite evidence of TB. Through contact investigation, 11 of the 16 exposed infants received isoniazid prophylaxis and no positive tuberculin skin test results were obtained after 3 months. One of the 31 exposed healthcare workers showed new interferon-gamma release assay conversion. Moreover, our case showed a much shorter contagious period compared to that in previous reports (8 versus 17-102 days). This suggests that a high index of suspicion and prompt measures can help prevent congenital TB outbreaks and reduce the burden of infection control activities in the NICU.

TB or not TB? Challenges in diagnosing and treating maternal and neonatal tuberculosis.

We present the case of a pregnant woman who died from disseminated tuberculosis (TB), and the difficulties encountered in diagnosing TB disease in her newborn. We discuss the burden of maternal and neonatal TB and the need for a different approach, one that is not solely based on bacteriologic evidence which, in most cases, tends to be inconclusive. We also explore the difficulties physicians and national TB programs face in managing and developing effective policies for these two highly vulnerable and neglected populations. There is an urgent need for a more realistic approach to neonatal and infant TB diagnosis.

Congenital tuberculosis after in vitro fertilization: suggestion for tuberculosis tests in infertile women in developing countries.

Congenital tuberculosis (CTB) after in vitro fertilization (IVF) is a major new problem in developing countries. Only 16 cases of CTB after IVF have been reported, and no tuberculosis (TB) tests were performed before IVF in these cases. However, on the basis of data in the literature and from the World Health Organization, the incidence of CTB has been substantially underestimated. We describe two cases of CTB after IVF in detail in our center and provide new insight into the important issue of controlling TB vertical transmission in developing countries. Performing an early diagnosis of CTB, mostly based on evidence of maternal infection and a high index of clinical suspicion, is a challenge. However, most mothers have no symptoms of TB infection during prepartum, and infertility may be the only symptom. Infertility caused by genital TB is common in countries with a high TB burden, and IVF is considered to be an effective treatment to improve their fertility. Therefore, this may lead to more CTB cases without thorough TB tests before IVF. We suggest that thorough TB tests should be conducted in infertile women before IVF to prevent CTB.

Congenital Tuberculosis: A New Concern in the Neonatal Intensive Care Unit.

BACKGROUND: Congenital tuberculosis (TB) is rare in the United States. Recent immigration patterns to the United States have made the diagnosis of congenital TB an important public health issue. PURPOSE: To explore the epidemiology, pathophysiology, diagnostic evaluation, treatment, and prognosis for congenital TB. The implications for exposed healthcare professionals in the neonatal intensive care unit (NICU) setting are also explored. METHODS/SEARCH STRATEGY: Relevant articles were accessed via PubMed, CINAHL, and Google Scholar. FINDINGS/RESULTS: Until 1994, fewer than 400 cases of confirmed congenital TB had been reported in the literature worldwide. An additional 18 cases were reported from 2001 to 2005. Neonatal providers need to be aware of the potential for congenital TB infection as the immigrant population in the United States continues to increase, many of whom originate from TB endemic countries. IMPLICATIONS FOR PRACTICE: The interpretation of TB-specific tests is problematic in newborns due to decreased sensitivity and specificity. Congenital TB should be ruled out in infants with signs and symptoms of sepsis or pneumonia and in whom broad-spectrum antibiotic therapy does not improve their clinical status. IMPLICATIONS FOR RESEARCH: The interpretation of TB-specific tests is problematic in newborns due to decreased sensitivity and specificity; more research is needed regarding best practice in diagnosis. Established protocols are needed to address the healthcare of TB-exposed providers in the NICU.

Congenital tuberculosis presenting as otorrhoea in a preterm infant.

A premature infant of 25 weeks' gestational age presented at 8 weeks after birth with otorrhoea from the left ear. Following a course of topical and systemic antibiotics, the patient deteriorated developing facial nerve paralysis and cervical lymphadenitis. Contrast-enhanced CT and MRI of the head showed a destructive process of the left temporal bone. These findings prompted the clinicians to send swabs from the purulent discharge from the ear for acid-fast bacilli stain. Furthermore, surgical exploration and debridement were undertaken. Cultures from ear discharge and biopsy-taken during surgical procedure-revealed the presence of Mycobacterium tuberculosis complex. The patient developed necrotizing otitis media, left temporal bone osteomyelitis and cervical lymphadenitis. The infant's mother was found to have an endometrial biopsy positive for M. tuberculosis suggesting the diagnosis of congenital tuberculosis.

Congenital tuberculosis: case report and review of the literature.

Congenital tuberculosis is rare, even where tuberculosis (TB) is endemic. A 14-day-old girl presented with a 3-day history of fever and respiratory distress. Her mother was diagnosed with a disseminated TB infection immediately after the delivery which was confirmed by a positive TB-polymerase chain reaction (TB-PCR) and subsequent culture from ascites and sputum. The infant was separated from her mother at birth. Her chest radiograph showed bilateral miliary nodules. Congenital TB was strongly suspected because of the symptoms, signs and maternal TB history, and was confirmed by TB-PCR and culture from the gastric lavage. Timely administration of standard anti-TB therapy resulted in a good outcome. The case highlights the importance of maternal TB history and typical miliary pattern on chest radiography for early diagnosis of congenital or neonatal TB which in turn facilitates prompt treatment and the prognosis.

A pre-term infant of 32 weeks gestation with congenital tuberculosis treated successfully with antituberculosis chemotherapy.

An infant of 32 weeks gestation was separated from her mother at birth for treatment of hyaline membrane disease and, on recovery, was cared for by adoptive parents. At 25 days, she was treated for pneumonia with immunoglobulins and multiple antibiotics and appeared to respond. Her symptoms recurred at 8 weeks and tuberculosis was confirmed by detection in an acid-fast bacilli smear of gastric aspirate. Her mother presented with disseminated tuberculosis with meningitis 1 month after delivery. Criteria for the diagnosis of congenital tuberculosis in the infant were confirmed.

Tuberculosis en lactantes menores de 3 meses / Tuberculosis in infants less than 3 months of age

Revisión de los lactantes menores de 3 meses con tuberculosis durante el periodo 1978-2014. Se diagnosticaron 8 casos (1,4% de las tuberculosis pediátricas): 3 tuberculosis congénitas, 3 sugestivas (biopsia endometrial no realizada) y 2 posnatales. La prueba de tuberculina fue negativa en 2 casos. La rentabilidad diagnóstica del cultivo (7/7, 100%) o PCR (3/3, 100%) de aspirado gástrico fue superior a la de la baciloscopia (5/8, 62%) y el test IGRA (1/3, 33%). Tres pacientes presentaron diseminación miliar y uno falleció. En conclusión, la tuberculosis en este grupo de edad es infrecuente, grave y de difícil diagnóstico. En ausencia de contactos posnatales conocidos, se recomienda descartar tuberculosis genital materna mediante biopsia endometrial

A review was conducted on infants less than 3 months of age diagnosed with tuberculosis between 1978 and 2014. Eight patients were diagnosed (1.4% of paediatric tuberculosis cases): 3 confirmed congenital tuberculosis, 3 suspected (endometrial biopsy was not performed), and 2 postnatal tuberculosis. Tuberculin skin test was negative in two patients. Diagnostic performance of culture (7/7, 100%) and PCR (3/3, 100%) of gastric aspirates was higher than that of acid-fast bacilli smears (5/8, 62%) and IGRA test (1/3, 33%). Three patients developed miliary disease, and one died. In conclusion, tuberculosis in this age group is rare, severe, and difficult to diagnose. In cases lacking known postnatal contacts, maternal genital tuberculosis should be ruled out by endometrial biopsy

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

BACKGROUND: Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. CASE PRESENTATION: We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. CONCLUSION: Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

Cerebral microcalcifications in a newborn with congenital tuberculosis.

Tuberculosis is a serious public health problem worldwide. In 2012, the World Health Organization estimated 8.6 million new cases and 1.3 million deaths due to the disease. In 2011, the incidence in Colombia was 24 cases per 100,000 inhabitants. There is little information about tuberculosis in pregnant women, and congenital infection is considered a rare disease that is difficult to diagnose, leads to high mortality, and may be confused with tuberculosis acquired after birth. In addition, it has been associated with HIV infection in mothers and infants. Moreover, there is increasing incidence of congenital syphilis in the world. In Colombia, the prevalence is 2.5 cases per 1,000 births and its frequency in the Instituto Materno Infantil-Hospital La Victoria is one case per 57 births. We report the case of a newborn under treatment for congenital syphilis and in whom microcalcifications were found in a transfontanelar ultrasound. This finding warned about the existence of another infectious agent. PCR was negative for cytomegalovirus, and IgM titers for toxoplasma, rubella and herpes I and II were also negative. After learning about a history of incomplete treatment for tuberculosis in the mother, we suspected the presence of an infection by the tubercle bacillus in the newborn. No acid-fast bacilli were demonstrated in three gastric juice samples. The IS6110 PCR assay was found positive in cerebrospinal fluid and urine, but not in blood. The newborn was treated with crystalline penicillin for 10 days along with isoniazid, rifampicin, pyrazinamide and streptomycin. The patient is currently under clinical monitoring.

Tuberculosis congénita, tras un enemigo oculto / Congenital tuberculosis, following a hidden enemy

La tuberculosis congénita es una enfermedad de baja ocurrencia, pero con alta morbimortalidad debido a que suele presentar signos inespecíficos, catalogándose a menudo solo como una sepsis neonatal. El diagnóstico correcto suele hacerse por los antecedentes maternos de síntomas graves en la gestación o de formas paucibacilares que se hacen reconocibles en el puerperio, incluyendo la ocurrencia de endometritis y síntomas pulmonares; también se identifica por las pruebas microbiológicas (baciloscopia, cultivos, pruebas genéticas). Radiográficamente el patrón más común es el miliar. En los laboratorios de sangre suele haber biomarcadores inflamatorios elevados, trombocitopenia y pruebas hepáticas anormales. El tratamiento farmacológico suele ser exitoso. Se presenta un caso de una recién nacida, hija de una madre paucibacilar, que fue tratada inicialmente como sepsis neonatal y mejoró luego de la terapia antituberculosa.

Congenital tuberculosis is a disease of low occurrence, but with high morbidity and mortality due to the nonspecific signs usually present but that are often classified only as a neonatal sepsis. A correct diagnosis is made by maternal history of severe symptoms during pregnancy or paucibacillary forms that become recognizable in the postpartum period, including the occurrence of endometritis and pulmonary symptoms. It is also identified by microbiological tests (baciloscopy, cultures, genetic assays). Radiographically, the most common pattern is of miliary lesions. In blood tests, elevated inflammatory biomarkers, thrombocytopenia and abnormal liver tests are found. Drug treatment is usually successful. We present a case of a female baby born from a paucibacillary mother, it was handled first as neonatal sepsis, and her improvement after antituberculous therapy.

Microcalcificaciones cerebrales en un recién nacido con tuberculosis congénita / Cerebral microcalcifications in a newborn with congenital tuberculosis

La tuberculosis es un problema grave de salud pública a nivel mundial. La Organización Mundial de la Salud estimaba que en el 2012 se habían presentado 8,6 millones de casos nuevos y 1,3 millones de muertes a causa de la enfermedad. En Colombia, la incidencia en 2011 fue de 24 casos por 100.000 habitantes. No hay información sobre la tuberculosis en las mujeres gestantes y la infección congénita se considera una enfermedad rara, de difícil diagnóstico, que genera alta mortalidad y puede confundirse con la adquirida después del nacimiento. La tuberculosis se ha relacionado con la infección por el virus de la inmunodeficiencia humana en madres y neonatos. Por otra parte, los casos de sífilis congénita han aumentado en el mundo y, en Colombia, la prevalencia es de 2,5 casos por 1.000 nacimientos, en tanto que, en el Instituto Materno Infantil-Hospital La Victoria, la frecuencia es de un caso por 57 nacimientos. Se presenta el caso de un recién nacido en tratamiento para sífilis congénita que presentó microcalcificaciones detectadas en una ecografía transfontanelar, lo que alertó sobre la existencia de otro agente infeccioso. La prueba de PCR fue negativa para citomegalovirus, así como los títulos de IgM para toxoplasma, rubéola y herpes I y II. Dado el antecedente de un tratamiento incompleto para tuberculosis en la mujer gestante, se sospechó la presencia de infección por el bacilo de la tuberculosis. No se encontraron bacilos ácido-alcohol resistentes en tres muestras de jugo gástrico, y la prueba de PCR-IS 6110 fue positiva en líquido cefalorraquídeo y en orina, pero no en sangre. El recién nacido recibió tratamiento con penicilina cristalina durante 10 días, así como con isoniacida, rifampicina, pirazinamida y estreptomicina. Actualmente se le hace seguimiento clínico.

Tuberculosis is a serious public health problem worldwide. In 2012, the World Health Organization estimated 8.6 million new cases and 1.3 million deaths due to the disease. In 2011, the incidence in Colombia was 24 cases per 100,000 inhabitants. There is little information about tuberculosis in pregnant women, and congenital infection is considered a rare disease that is difficult to diagnose, leads to high mortality, and may be confused with tuberculosis acquired after birth. In addition, it has been associated with HIV infection in mothers and infants. Moreover, there is increasing incidence of congenital syphilis in the world. In Colombia, the prevalence is 2.5 cases per 1,000 births and its frequency in the Instituto Materno Infantil-Hospital La Victoria is one case per 57 births. We report the case of a newborn under treatment for congenital syphilis and in whom microcalcifications were found in a transfontanelar ultrasound. This finding warned about the existence of another infectious agent. PCR was negative for cytomegalovirus, and IgM titers for toxoplasma, rubella and herpes I and II were also negative. After learning about a history of incomplete treatment for tuberculosis in the mother, we suspected the presence of an infection by the tubercle bacillus in the newborn. No acid-fast bacilli were demonstrated in three gastric juice samples. The IS 6110 PCR assay was found positive in cerebrospinal fluid and urine, but not in blood. The newborn was treated with crystalline penicillin for 10 days along with isoniazid, rifampicin, pyrazinamide and streptomycin. The patient is currently under clinical monitoring.

Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (I): epidemiología y diagnóstico. Tuberculosis congénita / Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis

El cribado de tuberculosis (TB) gestacional mediante la realización de la prueba de tuberculina (PT) se recomienda a las embarazadas con síntomas compatibles, contacto íntimo con TB bacilífera o riesgo de progresión a formas activas. Las nuevas técnicas de diagnóstico interferon gamma release assay (IGRA) están indicadas en gestantes sin factores de riesgo, con PT positiva y antecedente de vacunación BCG, y en inmunodeprimidas con sospecha clínica y PT negativa. El diagnóstico de enfermedad es difícil, ya que los síntomas pueden ser inespecíficos y hay más formas extrapulmonares, por el retraso en las exploraciones radiológicas y por la mayor tasa de anergia a la tuberculina. La TB neonatal puede adquirirse de forma intrauterina (TB congénita) o por vía respiratoria tras el parto (TB posnatal). La TB congénita es excepcional, no produce malformaciones fetales y, aunque puede estar presente en el nacimiento, suele iniciarse a partir de la segunda semana de vida. En ausencia de antecedentes familiares, la TB neonatal debe sospecharse en caso de neumonía con patrón miliar, hepatoesplenomegalia con lesiones focales o meningitis linfocitaria con hipoglucorraquia, especialmente si la madre procede de áreas de alta endemia de TB. La PT es habitualmente negativa y la sensibilidad de los IGRA es inferior a la de niños de más edad. Sin embargo, la baciloscopia y el cultivo de jugo gástrico tienen una rentabilidad superior, especialmente en la TB congénita. Las técnicas de diagnóstico molecular permiten un diagnóstico precoz y la detección de mutaciones de resistencia farmacológica. El riesgo de formas diseminadas y la mortalidad son elevados

Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death

Diferencias en los hallazgos clínicos en dos grupos de población inmigrante afecta de tuberculosis / Differences in clinical features of two immigrant populations with tuberculosis

Se realizó un estudio descriptivo para identificar posibles diferencias en la presentación clínica de la tuberculosis entre 2 grupos de población inmigrante. Se incluyeron 94 pacientes visitados en urgencias y que fueron diagnosticados de tuberculosis activa en el periodo 2006-12. Cuarenta y nueve pacientes era originarios de Asia Central (A) y 45 de Latinoamérica (LA). La edad media (años [DE]) fue de 35,3 (13) años en los procedentes de A por 33,9 (10) en los de LA. Existía un predominio de varones en asiáticos (40/49 vs. 25/45; p = 0,006). Los pacientes procedentes de LA tenían mayor porcentaje de tuberculosis pulmonar. Los pacientes de A vivían en condiciones de hacinamiento con mayor frecuencia. Los pacientes de LA tenían más antecedentes de seropositividad para el VIH. La mayoría recibió tratamiento cuádruple. Dos pacientes latinoamericanos eran resistentes a isoniazida

A study was performed to assess differences in the clinical presentation of tuberculosis between two groups of immigrants. Ninety-four patients seen in the emergency room for newly diagnosed tuberculosis between 2006 and 2012 were included. Forty-nine patients were from Asian countries and 45 from Latin America. Mean age [years (SD)] was 35.3 (13) in Asian patients and 33.9 (10) in Latin American patients. Asian subjects were predominantly male (40/49 vs 25/45; P=0.006). Patients from Latin American countries had a higher rate of pulmonary tuberculosis. A higher percentage of Asian patients lived in overcrowded conditions, whereas HIV infection was more frequent among Latin Americans. Most patients were treated with a quadruple regimen. Resistance to isoniazid was documented in two patients from Latin America