In most cases the risk of infection can be quantified thanks to a family and
social anamnesis.
Tuberculosis is a disease caused by a bacillus called
Mycobacterium tuberculosis, or Koch's bacillus. The bacillus can affect any
organ in the body, but it usually affects the lungs, causing death by
asphyxiation. The transmission of this disease occurs generally by respiratory
tract through the contact of the droplets of saliva dispersed with the cough or
with the sneeze, but also more simply with the intimate contact, speaking,
singing, with kisses and so on.
In rare cases, mother-to-child transmission during pregnancy has also been
documented, and transmission can also rarely occur through the gastrointestinal
tract, skin or mucous membranes. People around the sufferer can inhale the
bacillus and become infected.
Tuberculosis can also be contracted through other routes, although less frequent:
- the enterogenic pathway, which occurred in the past by ingestion of milk
contaminated by Mycobacterium Bovis: today, however, it is an "exceptional"
event due to the pasteurisation processes of milk and derivatives
- the air-lympho-hematogenous pathway, which would originate from mycobacteria
that stop in the lymphatic tissue, in particular the tonsils, and from there
they would reach the lung through the blood
- congenital tubercular infection caused by passing through the placenta of
mycobacteria: in order to occur, tuberculous lesions of the placenta must be
present. This is a rather rare event
- the cutaneous route, due to a wound
- the ocular pathway that presupposes an injury to the conjunctiva and only in
exceptional cases
- the urogenital path, not contagious and currently very rare.
Based on the immune responses of the host affected by the tubercle bacillus, three forms of tuberculosis
are distinguished:
- primary
consequent to the first contact between tubercle bacillus and host organism.
It declines subtly with fever, sweats, organic decay, asthenia, persistent and
annoying dry cough).
Tuberculous infection begins when mycobacteria reach the pulmonary alveoli,
where they attack and replicate within alveolar macrophages.
The primary site of
infection in the lungs is called the Ghon outbreak. Bacteria are collected from
dendritic cells, which do not allow their replication but which can carry the
bacilli to the local mediastinal lymph nodes. Further diffusion through the
bloodstream goes to the more distant tissues and organs, where secondary TB
lesions can develop in the lung apices, peripheral lymph nodes, kidneys, brain
and bones.
Tuberculosis is classified as one of the granulomatous inflammatory conditions.
Macrophages, T lymphocytes, B lymphocytes and fibroblasts are the cultured cells
that form the granuloma, with the lymphocytes surrounding the infected
macrophages. Granuloma not only prevents the spread of mycobacteria, but
provides a local environment for cell communication of the immune system. Inside
the granuloma, the T lymphocytes (CD4 +) produce cytokines such as interferon
gamma, which causes an attempt of destruction by the phagocyte bacteria
macrophages, but without significant evidence, since the Mycobacterium
tuberculosis are Catalase positive bacteria (therefore resistant to killer
polymorphonuclear enzymes)
- post-primary
which occurs in subjects previously sensitized towards the tubercle bacillus
and in which mechanisms of immunity acquired by making them tuberculous positive
to the Tine test are operative (a rapid test, performed with an injection, to
verify a suspicion of tuberculosis).
The post-primary miliary or nodular outbreak, which arises in an individual
who has already had, in a near or distant epoch, a tubercular process, either by
the arrival of new germs or by aspiration through the bronchi of a caseous
material flowing from a cavern in formation or for the passage of the germs in
the circle and their secondary localization in a pulmonary zone, can heal
perfectly, can undergo fibrosis and subsequent calcification or it can give rise
to the formation of a cavern.
This last case manifests itself if the body's defenses tended to eliminate germs and to circumscribe the outbreak are not sufficient. In the formation of the cavern the caseous substance, formed by necrosis of the pulmonary tissue, is fluidized by proteolytic enzymes, coming from the white blood cells, flows into the bronchi through the destroyed wall of one of them and in the lung a loss of substance is realized: cave. Caves can rarely be formed in the primary period, but more frequently they are formed in the postprimary: they constitute the fondamental element of the t. chronic pulmonary.
Chest radiographs in two projections indicate the location, extent, and
characteristics of tuberculous lung lesions. By using a tomography or
high-definition CT scan, suspicious lesions can be explored with greater
accuracy.
In any case, the radiological diagnosis of tuberculosis is not simple, since in
the differential diagnosis we must consider different diseases that give similar
pictures:
• rounding thickening in the lung: it may be the radiological image of a tuberculoma or a malignant tumor;
• pulmonary infiltrate: more often it is a sign of bronchopneumonia or bronchial carcinoma but it can also appear in this way, also a tuberculous pneumonia;
• empty space in the pulmonary tissue: it is the classic image of the tuberculous caverns but it can also be the modality of presentation of cysts, abscesses or malignant tumors;
• pleural effusion: in the case of tuberculosis it is a sign of tuberculous pleurisy but it can also appear in many other diseases, for example in heart
failure, in pneumonia and in malignant pleural lesions;
• lymphadenomegaly: it is rather nonspecific and in addition to tuberculosis it may be present in sarcoidosis, malignant tumors, toxoplasmosis, actinomycosis and AIDS.
Pleural lesions or lesions close to the pleura can be diagnosed by ultrasound.
Tuberculin is a mixture of different proteins and polysaccharides obtained from
sterilized cultures of tuberculous microorganisms. Since the proteins extracted
from the various mycobacteria have a certain similarity between them, cross
reactions often occur with the so-called atypical mycobacteria, some of which
are pathogenic to humans. The test reproduces the body's immunological reaction
to mycobacterium. It can be performed both as a tampon test and as an
intracutaneous Mendel-Mantoux test. In the latter case, the procedure is as
follows:
• four distinct solutions are taken (with 1, 10, 100 and 1,000 units of
tuberculin). In case of suspicion of active tuberculosis start with the
concentration of 1, otherwise with that of 10;
• 0.1 ml of this solution is injected strictly intracutaneously. To do so, at
the time of injection the syringe needle must be kept up;
• if the injection is performed well, a flat area with a diameter of 2-3 mm is formed;
• the reaction must not be read before 72 hours: a hard area of at least 5 mm
is considered positive. It must be visible and palpable. The erythema
surrounding it is irrelevant to the assessment (B, Q;
• if the test is negative, after seven days it can be repeated with a higher
concentration. If the test is negative with a concentration of 100, tuberculosis
is very unlikely.
The test of the pad (or test of the tips) is performed with a standard dose of 5
or 10 Ul of tuberco lina and even if it is less precise, technically it is
simpler. It consists in the application of a pad with multiple tiny tips, on the
skin of the inner face of the arm for two seconds, turning slightly so that the
impression of the tampon remains on the skin. The reading must be done no sooner
than 72 hours: it is considered positive when at least three papules or
hardenings of more than 2 mm in diameter appear. This test gives false negative
results up to 10% of cases and rarely gives non-specific reactions if positive.
Regardless of the type of test, the tuberculin reaction may be missing for:
• immunodeficiency syndrome;
• immunosuppressive therapy;
• diseases of the lymphatic system.
Currently the latent infection is diagnosed in a non-immunized person with the
skin test, which causes a delayed hypersensitive reaction to an extract of M.
tuberculosis or with the blood tests "Elispot TBC" and "Quantiferon TBC Gold".
The two tests serve to identify T cells that produce IFN-γ in response to an
antigenic stimulus:
- An ELISA for measuring the concentration of IFN-γ in the supernatant (QuantiFERON TB-2G)
- An immuno-enzymatic test, used to demonstrate T cells that produce IFN-γ (T SPOT-TB)
The US Food and Drug Administration approved the QuantiFERON TB (QFT-TB) test
and is evaluating the T SPOT-TB test, which has already been approved in Europe.
These tests give positive results in most people who have a tuberculous
infection and give negative results in subjects vaccinated with BCG with little
chance of having tuberculosis.
Immunizations to TB or those with a previously terminated infection will respond
to the skin test with a delayed hypersensitivity identical to those who
currently have active infection, so the test should be used with caution,
especially on people from countries where immunization at TBC it is widespread.
The identification of mycobacteria can be performed on sputum, bronchial
secretions or directly on the injected tissue. The following methods can be used:
• Sputum analysis: microscopy can be observed under the microscope directly on
the sputum (acidophilus bacilli stained with the Ziehl-Neelsen method). Usually
one analysis is not enough, so the research must be carried out in the sputum
collected on three consecutive days. A sample is cultured for two weeks. If the
culture test is positive, an antibiogram must be performed. The final result is
obtained one to four weeks from the sample collection;
• bronchoscopy: bronchial secretions obtained with bronchoscopy are examined
using the same methods as sputum. It is possible to identify the DNA of
mycobacteria with a polymerase chain reaction (PCR);
• transbronchial biopsy, thoracoscopy: in the infected tissue (lung, bronchial
mucosa or lymph nodes) tuberculosis can be searched through histological examination.
One of the most common tests, considering the primary localization of the
lesions, is the chest radiograph, as it is able to highlight the presence of
small white spots in the pulmonary regions in which the immune system has
confined pathogens (inactive form).
Radiographic examination can also show larger gaps, a sign of the marked
bacterial activity and the consequent open cavities. In place of the traditional
X-ray, computerized tomography (CT) can be used, which provides particularly
sharp images making it easier to recognize the smallest lesions. In any case,
diagnostic confirmation is obtained only by demonstrating the presence of the
pathogen in the sputum; in some situations a bronchoscopy may also be necessary
to take a sample of bacteriological or histological material on which to perform
various analyzes.
Therefore, an examination of the sputum allows to confirm or not the presence of
the unwanted bacteria; further investigations include sending the sample to
special laboratories, where the bacilli are grown in a specific culture medium
and subjected to the antibiogram, a test to evaluate their sensitivity to
various antibiotics. This very important test allows to choose the most
appropriate and effective pharmacological therapy; unfortunately this operation
takes four to eight weeks, since the growth rate of microorganisms is
particularly slow.
Tuberculosis therapy can usually be performed as an outpatient procedure. In
some cases hospitalization is necessary, at least for a certain period, for
example in the case of:
• extensive and advanced bilateral pulmonary tuberculosis in the presence of
some concomitant disease such as diabetes mellitus, alcoholism, kidney or liver disease;
• reactivation of tuberculosis and known resistance to antibiotic therapy;
• suspected incorrect treatment of the patient.
To avoid the selection of resistant micro-organisms a combination therapy with
different antibiotics is necessary. A good compliment of the patient is also
necessary, since antibiotic therapy must be continued for at least 6-9 months,
and secondary or secondary symptoms such as nausea and vomiting may occur. In
addition, during treatment with rifampicin and isoniazid, for their
hepatotoxicity, the patient must completely abstain from alcohol. In about 5-10%
of cases, side effects necessitate a change of therapy. The antibiotics that
must be considered (including tuberculostatic ones) are:
• rifampicin: can not be used in case of severe hepatopathies and can cause
nausea and vomiting. Rifampicin is hepatotoxic and may cause thrombocytopenia;
• isoniazid: severe hepatopathies and psychotic forms that are a
contraindication. In addition to nausea and vomiting, it can give hepatitis,
polyneuropathy and epileptic seizures;
• pyrazinamide: can not be administered in cases of renal insufficiency or gout
and causes hyperuricemia, arthralgia, nausea, rash and photosensitivity;
• streptomycin: contraindications are renal failure and vestibular nerve
injuries; can cause haemopathies and allergic reactions;
• ethambutol: it is contraindicated in optic nerve neuritis and renal failure;
it can cause nausea and reduction of visual acuity as well as of color
perception.
The standard tuberculosis therapy is based on the use, in an initial period of
2-3 months, of a combination of isoniazid, rifampicin, pyrazinamide and
streptomycin, followed by a stabilization phase of 6-7 months with isoniazid and rifampicin.
News update 2018 TBC care
The "Global tuberculosis report 2017" estimates that in 2016 there were 600
thousand new cases of rifampinin-resistant TB (RR-Tb), 490 thousand of which represented by cases of multiresistant TB (Mdr-Tb).
More than half of new cases (47%) occurred in 3 countries (India, China and Russian Federation). 6.2% of the cases of Mdr-Tb are represented by cases of
extremely resistant Tb (Xdr-Tb).
Globally, 4.1% of new cases and 19% of previously treated cases showed resistance to rifampicin.
In 2016, only 129,689 (22%) of the estimated 600,000 total cases eligible for
treatment for Mdr-Tb started therapy. The ten countries where the gap between
reported cases and estimated cases of MDR-TB is greatest are: India, Indonesia,
Nigeria, Philippines, South Africa, Pakistan, Bangladesh, Democratic Republic of
Congo, China, United Republic of Tanzania. The gap between the estimated number
of cases of MDR / RR-TB and the number of patients who started therapy for
MDR-TB, however, is higher in the following countries (in order of magnitude of
the gap): India, China, Russian Federation, Indonesia, the Philippines,
Pakistan, Nigeria, Myanmar and Uzbekistan.
In 2016, the WHO published new recommendations for resistant forms of MDR-TB
which provides a shorter-term regimen (9-12 months vs. about 2 years) and less
expensive in the event of sensitivity to second-line treatments and a rapid
diagnostic test to identify this subgroup of patients. These indications have
been received by more than 35 countries in Africa and Asia.
Patients with Xdr-Tb are not candidates for this treatment, but a regimen with
one of the two new drugs (bedaquiline and delamanid). In June 2017, 89 countries
had introduced bedaquiline and delamanid).
Bedaquiline is a diarylquinoline that targets the proton pump of adenosine triphosphate (ATP) synthase, a key enzyme that M. tubercolosis uses to derive energy. The drug therefore belongs to a new class of drugs that widen the therapeutic choices for patients with multi-resistant tuberculosis or with extended resistance for which, at present, there are no treatments able to control the infection. This molecule is potentially able to remain active against TB, which often becomes resistant to the older bacteriostatic drugs
The drug was approved in the United States in 2012 and in Europe in 2014 for the
treatment of MDR-TB
Delamanid, sold under the Deltyba brand, is a drug used to treat tuberculosis.
In particular, it is used, together with other anti-tuberculosis drugs, for
active tuberculosis resistant to multiresistant drugs. It is taken orally.
Common side effects include headache, dizziness and nausea. Other side effects
include prolongation of the QT interval. It has not been studied in pregnancy
since 2016. [4] Delamanid acts by blocking the production of mycolic acids
thereby destabilizing the bacterial cell wall. It is in the class of drugs based
on nitroimidazole.
Overall, the prognosis is good. With medical therapy the percentage of healing
is 100% and relapses occur in 1%. The prognosis is worse in case of debilitating
diseases.
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