CONTENTS




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First of all...
Thank you for answering our poll. Now you may see the results and the false statement in each group.

We all know that scientific truth is often temporary, rejected when new data are available or replaced by more current evidence. After all this process is one of the attractive characteristics of medical science. In this context some visitors may have suggested different answers from ours, and possibly can support their answers, which may prove "more correct" in the future.

Question 19
Check the correct answer

1.BCG was developed in 1908 and first used in 1909 1
2.BCG was developed in 1908 and first used in 1921 5
3.BCG was developed in 1918 and first used in 1921 3
4.BCG contains live attenuated M.tuberculosis bacilli 6
5.BCG is considered an effective vaccine and the major concern regarding vaccination is the possibility of adverse reactions. 1


The false statement is 2

It took 13 years Léon Charles Albert Calmette and Camille Guérin to produce a live attenuated microorganism and perform vaccination on real people. The whole task started in 1908 at Lille, France, but the First World War broke up and made things difficult for the two researchers. They relocated to Paris in 1919. On July 18th, 1921 the pediatrician Benjamin Weil-Hallé vaccinated in the Charité Hospital of Paris a newborn whose mother died from tuberculosis a few hours after delivery.

Question 20
In which lesion acid-fast bacilli are not found?

1.TUberculous chancre 1
2.Lupus vulgaris 6
3.Erythema induratum of Bazin 3
4.Miliary tuberculosis 1
5.Tuberculosis verrucosa cutis 5


The false statement is 3

Erythema induratum of Bazin is a tuberculid; no living mycobacteria are found in these lesions.

Question 21
Check the correct answer

1.Usual findings after BCG administration are erythema, pain, local abscesses, ulceration, keloid formation and blistering. 6
2.BCG revaccination is followed by an unusually high incidence of skin adverse reactions and should be avoided 1
3.Keloid formation is reported to about 10% of children undergoing BCG vaccination 5
4.1-5 day after BCG vaccination a red papule appears in the site of administration 2
5.The BCG vaccine (strain Copenhagen-1331), currently used in Greece, comes only second in global BCG production numbers. 2


The false statement is 1

Keloid formation is reported as high as 5%. A red papule appears in the vaccination site after 3-4 weeks. Strain Copenhagen-1331 does not rank even third as far as annual production is concerned.

Question 16
(Diabetes). Check the false statement.

1.The risk of developing tuberculosis is increased fivefold in patients with diabetes. 4
2.Increased susceptibility of diabetic patients to M.tuberculosis is attributed to impaired pulmonary defence mechanisms and alveolar microangiopathy. 2
3.Pulmonary tuberculosis lesions in diabetic patients are more frequent in the lower than the upper lobe. 11
4.The result of the TST does not depend on how well blood glucose is controlled. 28
5.Diabetic patients run a higher risk of hepatotoxicity when given INH chemoprophylaxis. 3


The false statement is 4

Diabetics are at 2-5 times greater risk of developing tuberculosis. This may be due to altered PMN cell function, reduced activity of monocytes and macrofages (impaired phagocytosis of intracellular microorganisms) and altered lymphocyte function. Diabetic microangiopathy of alveolar septa interferes with local inflammation processes.
Perez and Guzman reported an increased incidence of lower lobes disease in diabetic patients. Other reports do not agree with overall increased incidence, but only to special diabetic groups, such as women or patients over 40 yrs old.
TST should be carefully assessed in diabetics because in case of poor diabetes control anergy may alter the response.
All diabetics taking isoniazid should get pyridoxin and be followed closely for peripheral neuropathy and hepatotoxicity.

Question 17
(Transplantation). Check the false statement.

1.Transplant recipients present more frequently extrapulmonary or disseminated tuberculosis. 2
2.A TST reaction equal or greater than 5 mm is considered positive in patients who underwent transplantation. 7
3.BCG may be administered to patients who underwent transplantation. 31
4.Transplant recipients require chemoprophylaxis if they come in contact with a contagious tuberculosis patient. 4
5.Tuberculosis infection in such patients is usually the result of reactivation of latent tuberculosis infection. 4


The false statement is 3

Transplanted patients have a greater incidence of extrapulmonary or disseminated tuberculosis. This is especially prominent in high immunosuppression groups, such as bone marrow and heart transplantation. Organs and systems involved include the gastrointestinal tract, the liver, the musculosceletal and genitourinary systems, skin, CNS, larynx, tonsils and eyes.
A TST reaction of 5mm or greater is considered positive. Such patients should be checked for tuberculosis and if disease is not confirmed, they should be given chemoprophylaxis with isoniazid. Chemoprophylaxis is also indicated in immunocompromised patients in close contact with an active tuberculosis case.
BCG vaccination of immunocompromised patients may lead to severe, or even fatal, disease.
Tuberculosis in transplantation patients are due to reactivation, secontarily to primary infection and rarely to transmission of tuberculosis through the graft.

Question 18
(Other). Check the false statement.

1.Hematological malignancies have a higher incidence of tuberculosis than solid organ cancers. 1
2.Patients with leukemia have a higher risk of developing disseminated or extrapulmonary disease. 3
3.Screening using the Mantoux technique must be done in patients who are going to receive aggressive chemotherapy that may induce severe immunosuppression. 5
4.In drug abusers, besides the hypergammaglobulinemia, studies have shown impaired T lymphocyte function. This leads to diminished delayed hypersensitivity skin test reactions. 8
5.The high compliance of drug abusers concerning antituberculosis treatment is an unexplained paradox. 31


The false statement is 5

Intravenous drug users frequently have elevated IgM and IgG levels, as well as circulating autoantibodies. Hypergammaglobulinemia may be due to the continuous injection of antigens in blood circulation. Delayed hypersensitivity skin reaction is damped if not absent. Other investigators report altered T-cell function in vitro and increased or decreased T-cell numbers in vivo.
Obviously drug users compliance is a major problem. In some cases law dictates their arrest to ensure proper treatment and protect the community.

Question 13
Check the false statement.

1.Tuberculin is a labile biological product and may lose part of its antigenicity if exposed to light for a prolonged time period 3
2.When using a tuberculin vial for administering multiple PPD test, the main risk is contaminating the solution and producing false positive results 5
3.Tuberculin RT23 contains the Tween 80 stabilizing ingredient. 2
4.The antigenicity of a tuberculin vial containing 5 IU / 0.1 ml PPD is the same irrespective of the geographic area of the world used 36
5.Tuberculing should never rest more than 45 minutes in a plastic syringe before use 8


The false statement is 4

Several studies show that a tuberculin's antigenicity varies when used in different geographic areas and populations. This is attributed to variations in the prevalence of environmental mycobacteria, the population nutritional status, infectious diseases, parasitic infections and genetic factors. For these reasons, each country should have its own cut-off points when using a specific tuberculin. The tuberculin should be chosen and used for a long time period so that health service employees can get well acquainted with the specific product. Frequent changes of the tuberculin used would lead to confusion regarding interpretation of results.

Question 14
Check the false statement.

1.To detect a patient with tuberculosis infection you have to use a solution containing 5 IU/ 0.1 ml PPD. 4
2.The size of TST reaction is not linearly related to the severity of tuberculosis infection 0
3.When a TST reaction is borderline at 48 hours after administration it should be reassessed at 72 hours 4
4.The TST reaction induration remains the same for almost a week 14
5.Booster effect has the same charecteristics in children as in adults 32


The false statement is 5

Booster effect is caused by frequent TSTs and is less prominent in children, diminishing with younger age of the child. To avoid this confusing effect, if we have to perform a second Mantoux, this should be done within 10 days from the first one, or after 360 days.
Frequent TSTs, e.g. every 1-2 years, after BCG administration, lead to a positive reaction for many years after vaccination and complicates the diagnosis of infection.

Question 15
Check the false statement.

1.History of BCG administration or infection with environmental mycobacteria render TST difficult to assess 3
2.Chronic administration of cimetidine or indomethacin may produce a false negative TST 4
3.Frequent TST administration after BCG vaccination may extend the time period of positive TST reaction 10
4.Children receiving BCG immediately after birth have a comparable TST reaction size with children vaccinated at an older age 34
5.TST reaction size assessment should not be assigned to the child parents 3


The false statement is 4

The closer to the neonatal period the BCG administration, the less intence the delayed hypersensitivity reaction resulting from it.
All recomendations regarding the interpretation of the TST result after BCG vaccination refer to vaccination at the neonatal period.
Age is not the only but remains the most important factor. The BCG strain and the specific tuberculin product are other determining factors.

Question 10
Check the false statement.

1.Tuberculosis in West Europe, USA, Canada, Australia and Japan is a health problem concerning selected groups and not the general population. 1
2.Since 1980 the incidence of tuberculosis worldwide is about 60 cases per 100,000 of population, presenting only small fluctuations. 0
3.95% of tuberculosis cases worldwide are noted in developing countries. 6
4.Tuberculosis indices have remarkably improved in countries of the former Union of Socialists Soviet Republics 23
5.The 18 of the 20 countries with the greater incidence of tuberculosis (80% of the world caseload) are in Africa and Asia. 0


The false statement is 4

Tuberculosis incidence and drug-resistance have both increased in ex-USSR territories. This observation may be partly attributed to a more systematic recording of tuberculosis patients in these countries.

Question 11
Check the false statement.

1.The combination of tuberculosis and AIDS is the main factor increasing mortality in this patient group. 0
2.Other factors increasing morbidity or mortality are inappropriate treatment choices, poor patient compliance, diagnosis delays and multiresistant M.tuberculosis. 0
3.10-12% of tuberculosis mortality is reported in developed countries. 17
4.Patients with AIDS and tuberculosis are less contagious than tuberculosis patients not suffering from AIDS. 13
5.The greater incidence of HIV positive tuberculosis patients is reported in the geographic area located south of Sahara desert, followed by South-east Asia. 0


The false statement is 3

The percentage of total tuberculosis mortality occuring in developed countries is less than 5%. Statement number 4 is true. HIV positive patients may die from tuberculosis, may host more frequently secondarily drug-resistant mycobacteria but are nevertheless less contagious than HIV-negative patients because they do not develop communicating cavitary lesions where mycobacteria multiply avidly. This is due to deficient or absent late hypersensitivity reaction mechanisms in HIV-positive patients.

Question 12
Which one is false? All children with LTBI should be treated because

1.Drugs against tuberculosis are safer in children. 1
2.In this age group M.tuberculosis infection is de facto recent. 1
3.Children run a greater risk of active disease in a short time period after infection. 1
4.Children have a longer life expectation than adults and this fact increases the probability of reactivation of latent M.tuberculosis. 0
5.Children host a greater number of mycobacteria (mycobacterial load) than adults. 27


The false statement is 5

Children have a much smaller mycobacterial load (10-100 thousand vs 100 mil -1 bil.)

Question 7
Check the false statement.

1.The intensity of exposure will depend on various factors, including population density, family size, climate and age of the source of infection. 0
2.The younger the source patient, the greater the number of children infected. 12
3.The probability of infection depends on the number of infectious droplet nuclei that remain suspended in the air and the duration of exposure of a susceptible child. 2
4.The risk of infection increases as the droplet diameter increases above 5 μm. 29
5.Coughing is the main mechanism of air droplet generation. Other mechanisms are sneezing, singing and talking. 1


The false statement is 4

The opposite statement is true; The smaller the particles, the more possible the infection because (1) small particles stay in the air for longer periods and (2) they are able to reach the host bronchioles.

Question 8
Check the false statement.

1.The number of bacilli present in the source case is estimated to be between 100 -10000 when nodular lesions are present and between 10 million -1 billion when cavitary lesions are present. 3
2.Smear positive tuberculosis cases constitute by far, the most important source of infection 3
3.It is estimated that an annual risk of infection of 1%, corresponds roughly to an incidence of new smear-positive tuberculosis cases of 50 per 100.000 population. 10
4.In areas with high incidence of HIV infection the annual risk of tuberculosis infection is not reliable 7
5.Μ.africanum is the most common cause of tuberculosis in Africa. 21


The false statement is 5

M.africanum is part of the M.tuberculosis complex but is a rare cause of tuberculosis even in Africa where it was first isolated.

Question 9
Check the false statement.

1.Tuberculosis in adults develops as a result of progression of primary tuberculosis, exogenous reinfection or endogenous reactivation. 1
2.The highest risk of disease in adults is 3 to 4 years after infection. 25
3.Children are in greater risk of developing tuberculosis the first 12 months after infection. 6
4.The lifetime risk of progression from infection to disease is estimated to be about 10% if the infection has been acquired during childhood, without chemoprophylaxis 4
5.The risk of tuberculosis in people co-infected with M. tuberculosis and HIV has been shown to range from 5-15% per year. 8


The false statement is 2

The risk of active disease is greater during the first two years and then declines until the 5th (or the 7th) year after infection. After this time period the host has a latent infection and an annual risk of reactivation about 5-7%.

Question 4
Check the false statement.

1. The number of primary tuberculous lesions in children is between one and three. 3
2.Mycobacteria leave the lymph nodes and reach the circulation, either directly or indirectly (through the lymphatic system), leading to a subclinical bacteremia. 2
3.Delayed hypersensitivity towards M.tuberculosis is expressed on the 3rd-8th week and terminates the dissemination of mycobacteria. 1
4.Children with AIDS experience bacteremia at the same extent and total duration as healthy children. 20
5.Tuberculous pleuritis appears 4-8 months after primary infection and is more frequent in children more than 5 yrs old. 1


The false statement is 4

Children with AIDS show increased susceptibility to tuberculosis and environmental mycobacteria. Disseminated disease in these children is common. This is why extrapulmonary disease is much more frequent in this group when compared with immunoefficient children.

Question 5
Check the false statement.

1.The probability of adolescents and adults developing cavities increases when delayed hypersensitivity is compromised. 22
2.Tuberculous pleuritis and nodular erythema are manifestations of a delayed hypersensitivity reaction. 1
3.The host defence against M.tuberculosis is not proportional to the size of Mantoux. 4
4.The probability of developing tuberculous meningitis or miliary tuberculosis is greater the first 3-12 months after infection. 0
5.As a general rule we can say that calcification of the lesions reduces the probability of active tuberculosis. 0


The false statement is 1

It is not true that in adolescents and adults the tendency to develop cavitation increases when the delayed hypersensitivity reaction to mycobacterial products is attenuated. On the contrary, when the delayed hypersensitivity reaction is intense, more cytokines and a greater enzymatic activity is observed in tuberculous lesions, leading to liquefaction and cavitation.

Question 6
Check the false statement.

1.Hilar lymph node involvement, with or without a primary parenchymal lesion, is the classic radiologic finding of tuberculosis. 0
2.A primary lesion in the right lung (excluding the apex) leads to a right hilar adenitis. 0
3.A primary lesion in the left lower lobe, often leads to hilar adenitis of both lungs. 3
4.Among infected children with normal chest x-ray, 30-60% have a positive CT for lymph node involvement. 4
5.Paratracheal adenitis is more common in children older than 5 yrs old and has a much better prognosis. 20


The false statement is 5

Paratracheal adenitis is observed more commonly in infants and young children, and is due to a more extensive disease and a greater bacterial burden. Most children with miliary tuberculosis present a right paratracheal lymphadenitis.

Question 1
Check the false statement.

1.Infected children less than 6 yrs of age, are at a greater risk of developing tuberculosis. 8
2.Tuberculous meningitis and miliary tuberculosis are more common in children less than 3yrs old. 2
3.Differential diagnosis between overt and latent (subclinical) tuberculosis is more straightforward in children 38
4.Children are mainly infected from other family members. 1
5.Antituberculous drugs are better tolerated by children than by adult patients 1


The false statement is 3

Differentiating between a child with tuberculous infection and a child with tuberculous disease is often an intimidating process. The doctor's task is hard because we cannot easily isolate the tuberculosis bacilli in every patient. M.tuberculosis isolation is the definitive diagnosis. There is a 30-50% probability of isolating M.tuberculosis in three morning gastric aspirates taken from a child with pulmonary tuberculosis. Isolation rates depend on the quality of samples, the laboratory's ability to isolate and identify the mycobacteria and the bacterial load accumulated overnight in the patient's stomach.

Tuberculous infection in children follows a different course compared with the course in an adult. During the first two years the term "subclinical tuberculosis" is much more appropriate than the term "tuberculous infection".

Our clinic has helped during the last 15 years 1450 children with "tuberculous infection", which were detected by the routine tuberculin reaction test and had a normal chest x-ray.

Two months after starting them on prevention regimen, among children <5 yrs old, 11.4% presented a positive x-ray, whereas this percentage was 5.7% in children 6-10 yrs old and 6.4% in children 11-14 yrs old. Of course the treatment regimen changed in all these cases.

Whereas extrapulmonary tuberculosis presents with specific symptoms, pulmonary tuberculosis diagnosis is based on epidemiological data (contact with a contagious adult), non-specific symptoms, non-specific x-ray findings (similar findings may be due to a variety of clinical entities) and positive tuberculin skin reaction, with a false negative rate higher than 15% in developing countries.

In conclusion, in children, subclinical disease, tuberculous disease and latent tuberculosis (dormant mycobacteria) are not completely different entities and the question "tb or not tb" is a constant dilemma even to specialised departments.

Question 2
Check the false statement.

1.Children have a mycobacterial load of 10,000 - 100,000, while adults have a load of 100,000,000 - 1,000,000,000. 8
2.Prevention treatment with isoniazid alone, often leads to mycobacterial secondary drug resistance 25
3.Prevention treatment regimens include: INH 9 mos, INH 6 mos, INH+RIF 3 mos, RIF 4 mos, RIF+PZM 2 mos. 8
4.Adults with positive direct smear examination are 5 times more infectious than patients with negative smear examination and positive sputum culture. 8
5.Asia, Africa and East Europe are the geographical areas presenting the higher prevalence of tuberculosis worldwide. 1


The false statement is 2

As far as common bacteria are concerned, a long period of exposure to a drug leads to a greater risk to develop resistance. This doesn't seem to hold for mycobacteria, with the exception of infection by a mono- or multi-resistant M.tuberculosis strain (primary resistance). Drug resistance develops through mutations. It has been found that at INH concentration of 0.2 μg/ml the rate of resistance mutations is 1.84 per 100 million mycobacteria, and at INH concentration of 1 μg/ml the rate is 1.7 per 100 million. That means that INH cannot influence the mutation rate and these mutations are completely random. We should also note that the intrabacterial INH concentration is 10-15 times that of plasma.

Although M.tuberculosis dies within 60 min after coming in contact with INH, prevention treatment lasts 6-9 months. We have to treat patients that long because INH acts on actively multiplicating mycobacteria which are scarce in patients with latent tuberculosis (dormant mycobacteria).

INH acts by inhibiting production of mycolic acid, a basic component of the cell membrane. Other mechanisms of action have been described.

In conclusion: development of drug resistance is rare and is due to a new random mutation (secondary resistance). This is due to the small number of mycobacteria found in the human host (child or adult) and the small rate of resistance mutations.

Question 3
Check the false statement.

1.Mycobacterial drug resistance is due to genetic mutation. 6
2.The rate of positive gastric aspirate culture (3 samples) is 30-35% in children with pulmonary tuberculosis 7
3.Rifampicin promotes catabolism of corticosteroids. 4
4.Inhaled corticosteroids may be responsible for a false negative tuberculin test. 30
5.All antituberculous drugs are administered once daily. 3


The false statement is 4

Systemic corticosteroids may render the tuberculin reaction test falsely negative after administering them for 3-4 weeks. Inhaled corticosteroids do not influence the course of tuberculosis or the delayed hypersensitivity reaction towards mycobacterial products. There has been one study in adults that showed that chronic treatment with inhaled corticosteroids may influence the host response, but it hasn't been confirmed neither in adults nor in children. Administration of inhaled budenoside in children for 9-12 consecutive months (mean dose 222 mg), didn't have any effect on the delayed hypersensitivity reaction or the host defence against tuberculosis. This is due to the small rate of drug absorption from the respiratory and intestinal mucosa.

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