JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2002; 43: 71-74
REVIEW Tuberculosis in children R. GIACCHINO, G. LOSURDO Infectious Diseases Unit. Giannina Gaslini Childrens Hospital. Genoa, Italy Key words tubercolosis children Introduction From the second half of the 80s, the cases of tuberculo- sis (TBC) in Italy have been constantly increasing, with an incidence of 15-25:100,000 people. TBC infection, expressed as positivity to tuberculin test in index popu- lations as students and soldiers, increased from 5% in 1987 to 13% in 1995 1 . This increase in TBC cases in de- veloped countries is related to different factors, inclu- ding HIVepidemic and increased number of immigrants from countries with high TBC incidence and important socio-economic problems. These observations were confirmed by an epidemiologic study carried out from December 2000 to November 2001 in the Infectious Diseases Department of Gaslini In- stitute of Genoa, Italy 2 , in order to evaluate the impact of TBC infection in immigrant children. Mantoux test (5 IU) was performed in 60 of 114 immigrant children hospitali- zed or followed at Gaslini Institute. They included 40 ma- les and 20 females, mean age 4 years (range 1 month to 15 years). Thirty-four (57%) patients came from South America, especially from Ecuador (88%), 11 from Ea- stern Europe (18%), 9 from Middle East and North Afri- ca (15%), 4 from equatorial Africa (7%), 2 from Far East (3%). In 50 (83%) out of 60 children was Mantoux test negative, while in 10 cases (17%) it was positive. Among these latter, 5 had tuberculous disease with pulmonary lo- calization and one of them associated with cervical ade- nopathy, whereas another 5 were infected. In the study period, among children admitted to our Department, the prevalence of tuberculous disease was 4.3% in immigrant children compared 0.4% in native children. Methods The following international classification (3, 4, 5) was used to evaluate TBC even in the pediatric patient: TBC exposure: significant contact with a suspected or confirmed case of contagious pulmonary TBC. At this stage, skin test, chest X-ray, and clinical picture are negative or normal; TBC infection: positive reaction to tuberculin skin test (Mantoux), with no radiographic evidence of TBC, and/or negative bacteriologic studies; TBC disease: clinical and/or radiographic evidence of TBC disease or presence of positive culture for M. tuberculosis. Mantoux skin test (5 IU) remains the standard method to identify M. tuberculosis infection even in children, whe- reas tine test is not sensitive enough for evaluation of in- fection in pediatric patients. The interpretation of Man- toux test misuring diameter of the induration, depends on the different clinical and epidemiologic conditions. In particular, a reaction > 5 mm is classified as positive for the following groups: contact with suspected or known TBC patients; children with suspected TBC disease: chest X-ray compatible with TBC; clinical signs of TBC; immunocompromised children for therapy or disease (HIV infection, diabetes, cancer, chronic renal failure, malnutrition, etc.); Areaction of 10 mm is classified as positive in all the other children. increased risk of environmental exposure to TBC: children born in (or with parents coming from) highly endemic regions; frequent exposure to adults with HIV infection, home- less, intravenous drug addicts, nursing home residents, prisoners or institute residents, seasonal farm labourers; traveling and/or exposure in world areas with high prevalence. In case of contact with contagious or suspected subjects, the diagnostic and therapeutic procedures to perform are reported in Table I. Summary The increase in TBC casesi n developed countries is related to different factors, including HIV epidemic and increased num- ber of immigrants from countries with high TBC incidence and important socio-economic problems. An epidemiologic study was carried out from December 2000 to November 2001 in the infectious diseases department of Gaslini Childrens Hospital. Mantoux test was performed in 60 of 114 immigrant children hos- pitalized or followed at Gaslini Institute. The prevalence of tuberculosis disease was 4.3% in immigrant children compared to 0.4 in native children. R. GIACCHINO, ET AL. 72 Clinical aspects Pediatric TBC presents some peculiar microbiologic and clinical features. TBC presents a lower contagiou- sness in pediatric age: children are less likely to cough and produce sputum and cavity in lung is unusual. Evolution of TBC infection towards disease is more fre- quent and clinical course is more rapid, especially in children aged less than 5 years. There is a higher incidence of severe extrapulmonary forms, whereas the radiological picture of lung disease often does not show the specific features of adult pa- tients. The majority of infected children with positive reaction to tuberculin are asymptomatic. The most frequent manifestations differ according to age (Table II). Children aged less than 1 year, often presenting negati- ve Mantoux test (60% of cases), are at higher risk of de- veloping severe and extrapulmonary forms. In particular, different clinical pictures can be observed at that age: miliary: cough, fever, malaise, weight loss, hepato- splenomegaly, lymphadenopathy, respiratory di- stress with typical chest X-ray picture (miliary 90%); meningitis: fever, headache, irritability, vomiting, lethargy, nucal rigidity, seizures, meningeal irrita- tion with typical results of cerebrospinal fluid (CSF) analysis: clear CSF, leukocyte count: 50- 500/mmc, increased proteins, low glucose (19-35% of cases); encephalitis: rare but severe (exitus 15-30% of ca- ses); lymphadenitis: superficial associated with paratra- cheal and supraclavicular lymphadenitis. The lymph nodes not painful, unilateral progressively increase in size and evolve to colliquation and fi- stulization. In the older child lung TBC infections are most fre- quent. The most common radiologic aspects are the fol- lowing: Hilar adenopathy, Obstructive emphysema, Pe- rifocal infiltrate, Focal bronchial pneumonia, Bronchial obstruction, Adenobronchial fistula, Atelectasis, Pleuri- tis, Lobar pneumonia, Acute pulmonary miliary. Other less frequent localizations, that can appear even 12 months or more after initial infection, include midd- le ears, mastoids, bones, and joints. Renal tuberculosis and post-primary pulmonary tuberculosis are rare in children, but can appear in adolescents 6 . Diagnostic aspects Diagnosis of TBC disease is based on different parame- ters, namely: family history (contact with suspected or known TBC cases); compatible clinical picture; Tab. I. Management of tuberculosis in pediatric age Mantoux test 5 IU positivity with reaction > 5 mm YES NO Chest X-ray Chest X-ray Negative Positive Negative Preventive chemotherapy Diagnosis and treatment for 6 months Preventive chemotherapy Mantoux test 5 IU After 3 months POSITIVE NEGATIVE Chest X-ray Negative Positive Suspension of therapy Preventive chemotherapy Diagnosis and for overall 6-9 months treatment Vaccine when necessary Tab. II. Tubercolosis in children: age and disease localization SITE CASES (%) MEAN AGE (YRS) Pulmonary 77.5 6 Lymphatic 13.3 5 Pleural 3.1 16 Meningeal 1.9 2 Bone/Joint 1.2 8 Other 1.0 12 Miliary 0.9 1 Genitourinary 0.8 16 Peritoneal 0.3 13 Modified by Starke JR. J Pediatr, 1989 73 TUBERCULOSIS AND HIV INFECTION imaging diagnosis (chest X-ray, chest CT, broncho- scopy); skin tuberculin reaction; identification of Mycobacterium tuberculosis by mi- croscopic examination (Ziehl-Neelsen method), cul- ture test or DNA probes. In the young child and in the frequent case of absent or non productive cough, the sample of choice for culture is gastric aspirate obtained early in the morning for th- ree consecutive days. Aspirates should be obtained th- rough nasogastric tube on child awakening, before get- ting up and having breakfast, in order to use bronchial secretions swallowed during the night. Bronchial secretions can also be sampled by bronchoal- veolar lavage 6 . Therapeutic aspects Therapy is correlated with different clinical and epide- miological situations: exposed children, especially when aged less than 5 years, should immediately undergo prophylaxis, sin- ce TBC incubation period during preschool age can be very short (6-8 weeks). In our country, characteri- zed by low resistance levels, Isoniazid remains the drug of choice. Duration of prophylaxis should be 3 months from the last contact with the index case. If Mantoux test remains negative after this period, prophylaxis should be suspended. Conversely, in ca- se of positivity, the child should be reevaluated and treated as an infected patient; Tab. III. Therapy of pediatric tuberculosis DISEASE REGIMENTS Pulmonary 6 months Extrapulmonary (except for miliary, meningeal and Osteoarticular 2 months: Isoniazid + Rifampin + Pyrazinamide 4 months: Isoniazid + Rifampin Meningeal 9-12 months Miliary 2-3 months: Isoniazid + Rifampin + Pyrazinamide + Streptomycin Osteoarticular 7-10 months: Isoniazid + Rifampin Suspected drug resistence: add Etambutol and/or Streptomycin Further treatment period according to clinical, radiologic and laboratory data Tab. IV. Pediatric doses of antituberculosis drugs DRUG DOSAGE (mg/kg/die) MAX DOSE SIDE EFFECTS Isoniazid 5-10 300 mg Liver Toxicity Peripheral neuropathy Hypersensitivity Seizures, psychosi Rifampin 15-20 600 mg Liver Toxicity Thrombocytopenia Drugs interaction Pyrazinamide 15-30 2 g Liver Toxicity Hyperuricemia Streptomycin 20-25 1 g Ototoxicity Nephrotoxicity Ethambutol 15-25 2.5 g Optic neuritis Red/green discrimination Gastrointestinal disorders Hypersensitivity R. GIACCHINO, ET AL. 74 infected children, following the classification men- tioned above, should undergo preventive chemothe- rapy. In fact the child infections are supposed to be recent and adequate treatment can reduce the risk of TBC disease evolution in 90% of cases. To this pro- posal Isoniazid therapy should be administered for 6- 9 months. In case of documented or suspected resi- stance, Rifampin or Rifampin plus Isoniazid should be administered for 6 months; children with TBC disease should follow the treat- ment program classically validated in the general ex- perience and in the literature (Table III). Dosage should be scrupulously followed and side effects should be evaluated (Table IV). Accurate epidemiologic monitoring, further clinical stu- dies aimed at highlighting TBC peculiar aspects in chil- dren, and adequate therapy can lead to TBC control in the child 3 5 7-9 . References 1 Linee Guida della Regione Liguria per la sorveglianza e il con- trollo della malattia Tubercolare. Regione Liguria. Dipartimento Sanit e Servizi Sociali. Servizio Igiene Pubblica e Veterinaria. Deliberazione n. 294 del 01/03/2000. 2 Losurdo G, Timitilli A, Castagnola E, Cristina E, Gigliotti AR, Cappelli B, Giacchino R. Studio epidemiologico sulla prevalenza della tubercolosi nel bambino immigrato. Congresso Nazionale di Antibioticoterapia in et pediatrica Milano, 22-23 Novembre 2001. Abstract page 218. 3 Tuberculosis at a Glance. A Reference Guide for Practitioners Co- vering the Basic Elements of Tuberculosis Care. New York City Department of Health. 1995. 4 Starke JR, Correa AG. Management of mycobacterial infection and disease in children. Ped Infect Dis J 1995;14:455-70. 5 Johns Hopkins Center for Tuberculosis Research. www.hopkins- tb.org 6 American Thoracic Society. Diagnostic Standards and classifica- tion of tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161:1376-95. 7 Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis, and Pulmonary Infections. Treatment of Tuberculo- sis and Tuberculosis Infection in Adults and Children. Clin Infect Dis 1995;21:9-27. 8 Acocella G. Il razionale della terapia medica. In: G. Di Pisa Tu- berculosis: 207-15 Ed Systems, 1993. 9 The New York City Department of Health. Tuberculosis Treat- ment. 3 rd Edition. City Health Information 1999;18(2) www.nyc. gov/html/doh/html/tb/tb.html. I Correspondence: Dr. Raffaella Giacchino, MD, Infectious Disea- ses Unit, G. Gaslini Childrens Hospital, Largo G. Gaslini 5, 16147 Genoa (Italy) - Tel. +39 010 5636220 - Fax +39 010 3776590 - E-mail: raffaellagiacchino@ospedale-gaslini.ge.it
Raising Mentally Strong Kids: How to Combine the Power of Neuroscience with Love and Logic to Grow Confident, Kind, Responsible, and Resilient Children and Young Adults
Dark Psychology & Manipulation: Discover How To Analyze People and Master Human Behaviour Using Emotional Influence Techniques, Body Language Secrets, Covert NLP, Speed Reading, and Hypnosis.
Dark Psychology: Learn To Influence Anyone Using Mind Control, Manipulation And Deception With Secret Techniques Of Dark Persuasion, Undetected Mind Control, Mind Games, Hypnotism And Brainwashing