Neonatal Tuberculosis Research Articles

Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended.

How to manage neonatal tuberculosis.

This article reports the recommendations for managing neonatal tuberculosis (TB) drawn up by a group of Italian scientific societies. The Consensus Conference method was used, and relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Group experts concluded that if suspicion is aroused, it is necessary to undertake promptly all of the investigations useful for identifying the disease not only in the newborn, but also in the mother and family contacts because a diagnosis of TB in the family nucleus can guide its diagnosis and treatment in the newborn. If the suspicion is confirmed, empirical treatment should be started. Breast-fed newborns being treated with isoniazid should be given pyridoxine supplementation at a dose of 1 mg kg(-1) day(-1). Mothers with active-phase TB can breast-feed once they have become smear negative after having received appropriate treatment.

Risk Factors and Complications Associated with Tuberculosis in Pregnancy and Neonates in Limpopo Province, South Africa

Basic Antenatal Care (BANC) was introduced in Primary Health Care (PHC) facilities in order to reduce the burden of consistently high maternal and neonatal mortality rate. The study identified risk...

Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (I): epidemiología y diagnóstico. Tuberculosis congénita

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.

Perspectives on tuberculosis in pregnancy

Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations.

Neonatal tuberculosis: an experience that teaches

Objective: This study reports on an experience following contact by a large number of newborn babies with a nurse infected by active tuberculosis (TB). Methods: A large number of newborn babies were checked for possible contact with Mycobacterium tuberculosis (MTB) using interferon-gamma tests (IGTs) to determine specific treatment. Results: One hundred and seven infants showed a positive IGT positive and were not affected by active TB. All were treated with anti-tubercular drugs and were followed-up for 1 year. None of the infants developed active TB and all infants showed normal tuberculin skin tests and chest-x-rays, as well as IGT results at the end of treatment. Conclusions: Our experience suggests that newborns are at low risk of infection after contact with a nurse with active TB. IGTs can be used to assess possible contact with MTB and to determine a reduced number of infants to treat.

High tuberculosis exposure among neonates in a high tuberculosis and human immunodeficiency virus burden setting

Maternal and neonatal tuberculosis (TB) are under-recognised, particularly in settings with a high burden of human immunodeficiency virus (HIV) infection. Retrospective audit of neonates routinely screened for TB in a South African hospital during 2009. Surveillance sources reviewed included routine clinical, laboratory and pharmacy records. Among 70 neonates (60% HIV-exposed) screened for TB, the median gestational age was 35.5 weeks (IQR 33-38), and the median birth weight was 2000 g (IQR 1530-2484). The neonates were grouped according to a history of documented TB exposure: maternal TB in 41/70 (59%), suspected maternal TB in 9/70 (13%), other documented household TB exposure in 5/70 (7%), and no known TB exposure 15/70 (21%). Of the 50 neonates exposed to confirmed or suspected maternal TB, 36 (72%) were initiated on TB chemoprophylaxis, 5 (10%) received TB treatment and 9 (18%) received no intervention. Eight (8/50, 16%) were diagnosed with TB, all of whom were born to mothers with suspected or proven TB. Maternal TB, primarily among HIV-infected women, was the main indication for TB screening of neonates. Routine TB screening of pregnant women and TB care in mothers and infants should be improved in settings with a high burden of TB and HIV.

Perinatal Tuberculosis associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis [HLH] is a reactive disorder characterized by generalised non-malignant histiocytic proliferation with prominent hemophagocytosis. It may be either primary [familial (FLH)] or secondary [infection or malignancy associated]. Organisms incriminated for infection associated hemophagocytic syndrome (IAHS) include viruses, bacteria, spirochetes, fungi and parasites. Reports of IAHS associated with tuberculosis in neonates are rare. The authors report a case of perinatal tuberculosis presenting as hemophagocytic lymphohistiocytosis.

Neonatal Tuberculosis

According to the World Health Organization, more than 2 billion people, equal to one third of the world's population, are infected with Mycobacterium tuberculosis (TB) bacilli, the microbes that cause TB. In addition, over the past decade, the incidence of postnatal TB in infants has shown an escalating trend in response to the global increase in TB. In providing the best possible care for infants in newborn nurseries and NICU, providers must recognize the trends of TB and multidrug resistant TB in infants globally and consider the possible effects on health care in the United States. The potential risk factors, clinical manifestations, diagnostic strategies, and management plans, specific to the care of infants in the neonatal intensive care unit, is vastly important in maintaining a high index of suspicion for neonatal TB.

HIV/TB Co-infection in Nigerian children

Tuberculosis (TB) is an important cause of childhood morbidity and mortality. The burden of childhood disease is not as well documented as that of adult disease, partly because of the difficulty of confirming the diagnosis. In Africa children have been estimated to account for 20-40% of TB case load. Children infected with M. tuberculosis have a high risk of progression to disease, the younger children being at highest risk. Infected children represent a reservoir of future adult disease. The incidence of childhood TB has increased in developing countries. This resurgence is partly attributed to the coexisting burden of human immunodeficiency virus (HIV) disease, which is most pronounced in Sub-Saharan Africa, Nigeria ranking third highest prevalence. The pattern of childhood HIV and TB infection mirror these epidemics in the adult population. The number of children co-infected with HIV and TB is rising, and so is the incidence of congenital and neonatal TB. In addition the emergence of multi-drug resistance TB and extensively drug-resistant TB has occurred within the context of a high prevalence of HIV and TB. The diagnosis of TB has always been difficult in children and is compounded by HIV co-infection. The clinical symptoms in both diseases are similar, and the radiological changes may be non-specific. Treatment of both conditions in children is a challenge due to drug interactions and problems with adherence. There are few stable syrup formulations of antituberculous and antiretroviral drugs in children, and hence division of tablets gives rise to unpredictable dosing and emergence of resistance. To reduce the morbidity and mortality of TB and HIV, existing childhood TB programs must be strengthened, and antiretroviral drug therapy and prevention of mother-to-child transmission programs scaled up. HIV prevalence in the adult population must also be reduced. An increased emphasis on childhood TB, with early diagnosis and treatment, must be a priority.

Tuberculosis and tuberculosis/HIV co-infection in pregnancy

Both tuberculosis (TB) and human immunodeficiency virus (HIV) affect women aged 15-29 years. This is the prime childbearing age group with an increasing mortality due to HIV. The key to the prevention of neonatal TB among these women is early recognition of TB, based primarily on maternal history and relevant investigations of the mother and newborn. There are World Health Organization (WHO) guidelines for maternal prophylaxis and therapy and prophylaxis to the newborn on the stage of the maternal disease. In HIV-infected women, CD4 counts should be monitored urgently as a guide to antiretroviral (ARV) prophylaxis. When the CD4 count is <200 cells/mm(3), WHO recommends that the mother should be treated with combination antiretroviral therapy (cART). In resource-rich settings most guidelines recommend treatment with cART when the CD4 count is <350 cells/mm(3). The combination of ARVs and anti-TB therapy poses difficulties which can be resolved by combination of different drugs. In both conditions, evidence suggests that in resource-limited settings exclusive breastfeeding is recommended, with the addition of flash heating of the mothers' milk for HIV-infected women.

Pregnancy and tuberculosis: to assess tuberculosis cases in pregnancy in a developing region retrospectively and two case reports

PREGNANCY AND TUBERCULOSIS (TB): To assess TB cases during pregnancy in a developing region retrospectively and to present two case reports. Since TB cases activated by HIV infection during pregnancy are well reported in the literature, we aimed to investigate the aggressiveness of pulmonary TB among pregnant women and to assess the effects of TB on the fetus in Kutahya, an area where HIV positive cases are not seen. The medical records between 2000 and 2005 of the Provincial Health Directorate and Dispensary Against Tuberculosis in Kutahya were reviewed and analyzed retrospectively. Between 2000 and 2005, 667 pulmonary TB cases were examined in the Kutahya region. Of these, 106 occurred in women at reproductive ages between 20 and 44. All were HIV negative cases. In this area, five TB cases were found during pregnancy. There were three cases seen in the first trimester, but pregnancy was ended by curettage. Two women had pulmonary TB and gave birth. Five cases were evaluated as class 1 TB. During and after pregnancy, isoniazid, rifampin, ethambutol, and pyrazinamide (INH + RFP + ETB + PRZ) were used for the treatment. Resistance to anti-TB drugs was not seen during the treatment. Neither congenial nor neonatal TB was seen. Generally, TB is expected to be more aggressive during pregnancy. Since our cases were HIV negative, it can be thought that TB did not progress aggressively. Less aggressiveness and non-resistance to TB treatment in HIV-negative pregnant women compared with HIV-positive women were observed. Therefore, HIV infection results in greater mortality than the triple combination of human immunodeficiency virus, mycobacterium TB, and pregnancy. Besides, the advance of TB in pregnant women was not different from that in non-pregnant women in Kutahya. The fetus and the newborn were not affected. INH, RFP, ETB, and PRZ were used for therapy.

Tuberculosis congénita: Presentación infrecuente de una enfermedad habitual

Congenital tuberculosis is a severe rapidly progressive disease which differs from neonatal tuberculosis because patients present tuberculous lesions during their first weeks of life, primary hepatic complex or hepatic caseous granulomas, confirmation of tuberculosis in placenta or in maternal genital tract (uterus or adnexa), and exclusion of birth channel or postnatal exposure. We report a case of a 20 days newborn baby admitted to the neonatal unit with fever, hepatoesplenomegaly, abdominal distension and respiratory symptoms. Abdominal echography showed ascitis, diffuse hepatomegaly and splenomegaly, focal hipoecoical spleen images and portal lymphadenopathy. Thorax X-ray with micronodular infiltrates. Maternal pneumonia with pleural effusion was reported during pregnancy. Empirical treatment was initiated with 4 antituberculous drugs: isoniazid, rifampicin, pyrazinamide and ethambutol suspecting tuberculosis. She died the next day. M. tuberculosis was obtained in a gastric lavage culture, blood cultures and post mortem spleen puncture.

Tuberculosis and human immunodeficiency virus co-infection in children: management challenges

The pattern of childhood human immunodeficiency virus (HIV) and tuberculosis (TB) infection mirror these epidemics in the adult population. The number of children co-infected with HIV and TB is rising, and the incidence of congenital and neonatal TB is similarly increasing. In addition, the emergence of multidrug resistant TB and extensively drug-resistant TB has occurred within the context of a high prevalence of HIV and TB. The diagnosis of TB has always been difficult in children and is compounded by HIV co-infection. The clinical symptoms in both diseases are similar, and the radiological changes may be non-specific. Treatment of both conditions in children is a challenge due to drug interactions and problems with adherence. In most developing countries, there are few medicines specifically tested and manufactured for children, with few stable syrup formulations. Thus antituberculosis and antiretroviral tablets have to be divided, giving rise to unpredictable dosing and the possible emergence of resistance. To reduce the morbidity and mortality of TB and HIV, existing childhood TB programmes must be strengthened, and antiretroviral drug therapy and mother-to-child transmission programmes scaled up. An increased emphasis on childhood TB, with early diagnosis and treatment, must be a priority. The provision of isoniazid prophylaxis to HIV-infected children exposed to an adult case of TB or, in areas with a high prevalence of TB, to HIV-infected children (irrespective of a TB contact) may be effective in reducing the morbidity and mortality from childhood TB.

Tuberculosis in Neonates and Infants

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed. Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-gamma assay. Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved. According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6-9 months. All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4-10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1-2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months. Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-gamma, and tumor necrosis factor antagonists have been tested with promising results.

Tuberculose du nouveau-né dans une unité de néonatologie tropicale

We report three cases of tuberculosis observed in a neonatal unit in a country characterized with a high endemia of tuberculosis. Case reports. – Case 1. A term infant presented at the age of 35 days, with cough since day 18, respiratory distress and bronchopneumonia. Her mother had unrecognised tuberculosis since pregnancy. Post mortem biopsies of the infant confirmed the diagnosis of tuberculosis and social survey found out pulmonary tuberculosis in the newborn’s aunt. Case 2. A term infant presented at the age of 30 days with cough since day 13, respiratory distress, nodular pulmonary lesions and right pleural effusion. Her mother had cough and stomatitis since the eighth month of pregnancy and nodular pulmonary lesions. Tuberculosis and HIV were confirmed in the mother and the infant. Social survey found tuberculosis in the newborn’s paternal uncle. Case 3. A term but hypotrophic infant presented on the first day of life, with haemorrhagic troubles and respiratory distress. Tuberculosis and HIV were confirmed in the mother and the infant. Social survey found tuberculosis in the father, in a friend of her and in her three-month-old child. Conclusion. – Congenital or neonatal tuberculosis is an under-estimated emergent disease, with a need for early diagnostic methods and consensual therapeutic protocols to improve its management.

An infant with progressive pneumonia: case of neonatal tuberculosis with review

An infant with progressive pneumonia: case of neonatal tuberculosis with review

An infant with progressive pneumonia: case of neonatal tuberculosis with review

An infant with progressive pneumonia: case of neonatal tuberculosis with review

Prevention of neonatal tuberculosis

Prevention of neonatal tuberculosis

Neonatal tuberculosis with pulmonary cavitation

Summary A case is reported of tuberculosis in a 5-week-old infant who presented with cervical lymphadenopathy. A pulmonary cavity was shown on the chest X-ray. Bilateral tuberculosis otitis developed as well.