Non-tuberculous mycobacteria

Danas je poznato oko 150 vrsta netuberkuloznih mikobakterija. Ovi okolišni patogeni, premda niskog patogenog potencijala, mogu u čovjeka uzrokovati niz bolesti. Općenito uzrokuju četiri klinička entiteta: plućnu bolest, limfadenitis, kožne promjene te diseminiranu bolest, najčešće kod imunokompromitiranih osoba. Postavljanje dijagnoze mikobakterioze nije nimalo jednostavno te su u tu svrhu razrađeni kriteriji koji uključuju kliničku prezentaciju, mikrobiološke nalaze te radiološke promjene. Samo liječenje ovih bolesti dugotrajno je i komplicirano. Preporučuje se primjena kombinacije lijekova, ovisno o vrsti mikobakterije, te trajanje liječenja najmanje 12 mjeseci od negativizacije kulture. U Hrvatskoj se danas godišnje otkriva između 150–450 izolata te oko dvadesetak bolesnika s mikobakteriozom. Od ukupnog broja izolata prevladava M. gordonae, saprofitna mikobakterija koja samo iznimno dovodi do razvoja bolesti. Od patogenih mikobakterija, uzročnika mikobakterioze, u Hrvatskoj su najznačajnije M. avium, M. intracellulare, M. xenopi, M. kansasii, M. chelonae i M. abscessus.Currently, there are approximately 150 Mycobacterium species identified. Despite their low pathogenic potential, these organisms are able to cause a variety of diseases in humans including lung disease, lymphadenitis, cutaneous infections and disseminated disease, most commonly in immunocompromised persons. The diagnosis of mycobacteriosis is challenging and includes criteria that combine clinical presentation of disease, microbiological findings and radiographic appearance. The treatment of non-tuberculous mycobacteria infections is also troublesome and long lasting. Current guidelines propose the specific drug regimens depending on the species isolated and duration of therapy for at least 12 months after culture conversion. In Croatia, about 150–450 isolates of non-tuberculous mycobacteria are detected per year, but the number of patients is significantly lower, around 20 per year. The most frequently isolated species is M. gordonae, a saprophytic organism that rarely causes disease. In Croatia, the most significant non-tuberculous mycobacteria causing disease are M. avium, M. intracellulare, M. xenopi, M. kansasii, M. chelonae and M. abscessus

Plućna infekcija izazvana organizmom Nocardia asteroides: prikaz slučaja

Presentation is made of a 53-year-old woman with pulmonary infection caused by Nocardia asteroides. Tracheal aspirate was obtained and examined microbiologically. Direct smear of the tracheal aspirate stained with Gram stain revealed gram-positive branched filamentous hyphae and numerous leukocytes. Pure culture of colonies of a chalky white appearance grew on the blood agar after prolonged incubation. The Gram stained direct slide prepared from the culture showed gram-positive branching filaments. The microorganism was identified as Nocardia asteroides by standard methods.Prikazana je 53-godišnja bolesnica s plućnom infekcijom uzrokovanom mikroorganizmom Nocardia asteroides. Uzet joj je trahealni aspirat i pretražen je mikrobiološki. U direktnom mikroskopskom preparatu iz aspirata traheje bojenom po Gramu vidljive su gram pozitivne razgranate filamentne hife uz puno leukocita. Na krvnom agaru nakon duže inkubacije porasla je čista kultura kolonija bijelog, kredastog izgleda. Preparat iz kulture bojen po Gramu pokazao je gram pozitivne razgranate filamente. Primjenom standardnih metoda mikroorganizam je identificiran kao Nocardia asteroides

DETERMINATION OF THE RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS AGAINST ISONIAZID BY MULTIPLEX PCR METHOD

SAŽETAK Cilj: Ispitati mutacije u katG i inhA genima kliničkih izolata vrste Mycobacterium tuberculosis (M. tuberculosis), otpornih na izoniazid (INH). Metode: Za to su ispitivanje izdvojena ukupno 103 klinička izolata vrste M. tuberculosis, prikupljena u razdoblju od 1999. do 2006. na području Hrvatske, kojima je fenotipskom metodom proporcije prema Canettiju, na Löwenstein-Jensen podlozi, utvrđena otpornost na INH. Ispitivanje mutacija u katG i inhA genima, provedeno je multipleks PCR metodom. Ta se metoda zasniva na otkrivanju mutacije AGC→ACC u katG genu, te inhAC-15T mutacije u regulatornoj regiji mabA-inhA operona. Rezultati: Za 76 sojeva (75%) od ukupno 103 ispitivana soja vrste M. tuberculosis, utvrđena je genetska osnova otpornosti na INH. Ustanovljena je povezanost između mutacije u kodonu 315 katG gena, te razvoja otpornosti na druge antituberkulotike. Zaključak: Potrebno je ispitati genetske osnove otpornosti na INH, jer se katG mutacija pokazuje kao pretkazivač mogućega razvoja otpornosti na druge antituberkulotike.ABSTRACT Aim: To detect mutations in katG and inhA genes in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates resistant to isoniazid (INH). Methods: A total of 103 isolates collected from 1999 to 2006 in Croatia and identified as INH-resistant M. tuberculosis strains by standard susceptibility testing proportion method according to Canetti were investigated. Multiplex PCR method was used to detect an AGC to ACC mutation in the katG gene and an inhAC-15T mutation in the regulatory region of the mabA-inhA operon. Results: Genetic basis of INH resistance was found for 76 (75%) of total 103 M. tuberculosis strains investigated. There was a correlation between mutation in 315 codon of katG gene and acquisition of resistance to other antituberculous drugs. Conclusions: Mutation in katG gene in INH resistant M.tuberculosis strains is highly predictive for acquisition of resistance to other antituberculous drugs

Mycobacterium marinum infection of the hand in an immunocompromised aquarium hobbyist

M. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely distributed in the aquatic environment. In the previous century, epidemics took place due to inadequately chlorinated swimming pool water. Nowadays the majority of infections are acquired through contact of previously damaged skin with contaminated fish tank water. We present a case of M. marinum infection of the hand in an aquarium hobbyist which stayed unrecognized for 2 years. After confirming the correct diagnosis, the patient was successfully treated with a regiment containing clarithromycin and rifampicin. The aim of this paper is to raise the awareness of the possibility of M. marinum infection when encountered with non-healing nodular/verrucous/ulcerative lesions of the extremities. ly: MyriadPro-Bold;color:black;mso-ansi-language:EN-US;mso-fareast-language:HR; mso-bidi-language:TA\u27&gt;   </p

CHILDHOOD TUBERCULOSIS: AN ANCIENT DISEASE IN THE YOUNGEST GENERATION IN THE 21ST CENTURY FROM EPIDEMIOLOGICAL POINT OF VIEW

Tuberkuloza u djece je po svojim epidemiološkim i kliničkim osobitostima posebna bolest. Kako najveći dio djece ima mikroskopski negativne iskašljaje, smatralo se da oboljela djeca malo doprinose prijenosu bolesti. Stoga se tuberkulozi u djece pridavalo manje javnozdravstveno značenje te je uglavnom bila zanemarena u nacionalnim programima borbe protiv tuberkuloze. Kako tuberkuloza u djece obično nastane nakon brze progresije svježe infekcije, reflektira prijenos uzročnika i cirkulirajućih sojeva u populaciji pa je dobar indikator učinkovitosti nacionalnih programa. Neliječena je latentna infekcija među djecom izvor širenja bolesti u sljedećim generacijama. Prognoza rano otkrivene i pravilno liječene tuberkuloze je odlična pa se razvoj novih dijagnostičkih metoda i lijekova za tuberkulozu dječje dobi nameće kao nužnost. Pitanje učinkovitijeg cjepiva, koje bi se moglo koristiti i za zaštitu djece inficirane HIV-om, ostaje potrebom za kvalitetniju prevenciju na globalnoj razini. Što bolje implementiranje nove Stop TB Strategije, u čijoj se osnovi nalazi i strategija Directly Observed Treatment Short-Course (DOTS) značajno doprinosi smanjivanju globalne pojavnosti tuberkuloze u odraslih, a time štiti i djecu od infekcije i bolesti. Takve mjere trebaju biti praćene i poboljšavanjem općih uvjeta (prehrane, socioekonomskih uvjeta i nadzora nad čimbenicima okoliša) za bolji utjecaj na smanjivanje morbiditeta i mortaliteta od tuberkuloze u dječjoj dobi.Childhood tuberculosis (TB) has distinct epidemiological and clinical features. TB burden in children worldwide and in Croatia, the risk of infection and disease, as well as disease characteristics, sources of infection in children, diagnostic difficulties, impact of HIV on pediatric tuberculosis, limits of BCG- vaccine and program implications are discussed in this paper. Children younger than 15 years account for 15%-20% of global TB burden, which is often associated with severe TB-related morbidity and mortality. Childhood TB is rarely sputum-smear positive on microscopy. That is probably the reason for the lower priority traditionally given to children by TB control programs compared to that of adult disease. Young children are at a high risk of rapid progression from infection to disease, reflecting recent transmission rather than secondary reactivation. Therefore, the pediatric burden potentially provides a useful measure of current transmission within a community and it is a good indicator of the efficacy of TB control achieved in a particular community. Strict contact tracing and use of preventive chemotherapy is important to reduce TB-related suffering of children. Untreated latent TB infection in children provides the seed of the epidemic for the next generation. Evidence of an adult TB index case is a clue for diagnosis of childhood TB in low-endemic countries. Prognosis of early detected and properly treated TB is excellent. Consequently, new diagnostic methods and treatment options are an imperative. Among HIVcoinfected children, the optimal timing for highly active antiretroviral therapy initiation and drug combinations that have minimal interactions with anti-TB drugs need to be further explored. The most effective vaccine, suitable even for HIV-infected children, remains the need for successful prevention at the global level. The Stop TB Strategy, which builds on the previous Directly Observed Treatment Short-Course Strategy (DOTS) developed by the World Health Organization, has a critical role in reducing the worldwide burden of the disease and thus in protecting children from infection and disease. The management of children with TB should be in line with the Stop TB Strategy, taking into consideration the particular epidemiology and clinical presentation of TB in children. In addition to reducing the burden of adult TB, attention to childhood nutrition and improvement of socioeconomic conditions of communities is likely to have an impact on TB transmission to children

COMPARISON OF NEW AND OLD TESTS FOR THE DIAGNOSIS OF LATENT TUBERCULOSIS INFECTION (QuantiFERON and TST)

Tuberkuloza (TBC) druga je najčešća zarazna bolest na svijetu, uzrokovana bacilom Mycobacterium tuberculosis. Uz rijetku laringalnu, plućna tuberkuloza jedini je zarazni oblik bolesti, iako može zahvatiti bilo koji organ ljudskog tijela. Tuberkuloza je ponovni izazov liječnicima, jer se javlja uz brojne kronične bolesti i imunokompromitirana stanja, u starijoj životnoj dobi i jer neprikladno liječenje može dovesti do pojave rezistentnih oblika tuberkuloze. Stoga je dobra rana dijagnostika bolesti ključna za sve programe sprječavanja i suzbijanja tuberkuloze. Prije nego što je QuantiFERON odobren 2001. godine, tuberkulinski kožni test (PPD) bio je jedini test za otkrivanje latentne tuberkuloze. Za razliku od PPD-a, koji je test in vivo, postoje novi krvni testoviin vitro, tzv. IGRA-testovi (QuantiFERON i EliSPOT.TB). U radu su prezentirane prednosti i nedostaci obiju metoda, a pokazalo se da IGRA-testovi u odnosu prema PPD-u imaju višu specifičnost i osjetljivost.Tuberculosis (TB) is the second most common contagious disease, caused by Mycobacterium tuberculosis (M. tuberculosis). Besides a rare laryngeal tuberculosis, pulmonary tuberculosis is the only one contagious form of the disease, although it can affect any organ of the human body. TB represents a new challenge to the doctors because it appears with numerous chronic diseases, affects immunocompromised hosts, elderly people and because nonadequate therapy could create drug resistant tuberculosis. Early diagnosis of TB is fundamental for every tuberculosis control program. Before 2001 when QuantiFERON test was approved, tuberculin skin test (TST) was the only diagnostic test for detection of latent M. tuberculosis infection. In contrast of TST, which is in vivo test, the novel whole blood tests in vitro, so-called IGRA tests (QuantiFERON, Elispot.T-SPOT.TB) now exist. This paper presents advantages and disadvantages of both methods. IGRA tests are considered to have higher specifity and sensitivity than TST

Pulmonary tuberculosis

Tuberkuloza (TBC) je zarazna bolest koja može zahvatiti bilo koji organ ljudskog tijela, ali u 80–90 % slučajeva zahvaća pluća i pridružene respiratorne strukture. Zbog kapljičnog načina širenja, ovaj oblik bolesti je zarazan za okolinu pa stoga još uvijek predstavlja globalni javno zdravstveni problem. U 20. stoljeću mijenjala se klinička slika plućne tuberkuloze, ali i rizičnih grupa. Pojava zaraze HIV-om, produženje života bolesnika s kroničnim bolestima, ali i sve agresivniji medicinski postupci, pogodovali su nastanku novih skupina bolesnika koji značajno češće obolijevaju od TBC. Današnja strategija izravno nadziranog liječenja kratkog trajanja (DOTS, od engl. Directly Observed Therapy Short course) temelji se na kombinaciji više lijekova (da se spriječi razvoj rezistentnih sojeva) i na dovoljno dugom liječenju (da se osigura djelovanje na bakterije u različitim fazama metabolizma). Neadekvatna primjena antituberkulotika i nepridržavanje DOTS strategije dovodi do razvoja rezistentnih sojeva i multirezistente plućne tuberkuloze (MDR-TBC) koja predstavlja globalnu javno zdravstvenu opasnost.Tuberculosis (TB) is an infectious disease that can affect any organ of the human body. However, in 80–90 % of cases it affects the respiratory system. Pulmonary TB is highly contagious due to its way of spreading by aerosol and therefore still represents a global public health problem. In the 20th century pulmonary TB has changed its clinical presentation and also target groups of patients. The emergence of HIV-infection, prolonged life expectancy of patients with chronic diseases, and more aggressive medical procedures have favoured the emergence of new groups of patients at increased risk of contracting TB. The current control strategy of Directly Observed Therapy, Short Course (DOTS) is based on the combination of more drugs (to avoid the development of resistant strains) and long enough treatment (to ensure that bacteria in different phases of metabolism will be eradicated). Inadequate use of antituberculotic drugs and failure to follow the DOTS strategy leads to the development of resistant strains and multidrug-resistant pulmonary tuberculosis (MDR-TB), which represents a global public health problem