Ege Üniversitesi Tıp Fakültesine başvuran tüberküloz olgularının moleküler epidemiyolojisi
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Tarih
2017
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: Tüberküloz (TB), insanlık tarihi kadar eski bir hastalık olarak bilinir. Klinik olarak süreğen, granülomatöz nekrozitan bir hastalıktır. Pulmoner tüberküloza bağlı ölümlerin ve bulaşın azaltılmasında, tüberkülozun toplum içerisindeki hızlı yayılımını, bulaşta rol oynayan dinamikleri ve reenfeksiyon ile reaktivasyon arasındaki farkı gösteren epidemiyolojik özelliklerinin bilinmesi önemli rol oynar. Moleküler tekniklerin gelişmesiyle, M. tuberculosis suşlarının tiplendirilmesi, toplum içindeki enfeksiyonun orijini, yayılması ve direnç kazanmış olan suşların erken saptanması gibi önemli epidemiyolojik soruların yanıtını verebilir. Bu nedenle; Ege Üniversitesi Tıp Fakültesi Mikrobiyoloji laboratuvarında akciğer ve akciğer dışı tüberküloz (AD-TB) tanısı konan hastaların materyallerinden moleküler teknik ile identifikasyonu, genotiplemesi ve antimikrobiyal ilaçlara direnç durumu da bakılmıştır. Aynı zamanda bu hastaların klinik, radyolojik ve biyokimyasal değerlendirmesi yapılarak aileler ile bu veriler arasında ilişki olup olmadığının bakılması amaçlanmıştır. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Mikrobiyoloji laboratuvarında 2009 - 2014 yılları arasında Akciğer TB ve ya AD-TB tanısı alan 402 hastanın laboratuvarda tanı için değerlendirmeleri yapılan örneklerden spoligotyping yöntemi ile moleküler tiplendirmeleri yapılmıştır. Bu hastaların retrospektif olarak dosya taramaları yapılmış ve demografik verileri, doğum yeri, bölgesi, tüberküloz izolasyon yılı, geçirilmiş tüberküloz öyküsü, eşlik eden hastalıklar, ilaç dirençleri, Tüberkülin Cilt Testi (TCT), temas öyküsü, İnterferon-gamma salınım testi sonucu (Quantiferon), klinik ve radyolojik bulguları, aldıkları tedavileri, biyokimyasal verileri, hastane yatışları ve mortalitesi taranmıştır. Bulgular: Toplam 402 (238 erkek, ortalama yaş 52 ± 18.4) TB hastası çalışmaya alınmıştır. Hastaların 248 (%61.7)'i akciğer TB, 135 (%33.6) 'i AD-TB, 19 (%4.7)'u hem Akciğer TB hem de AD-TB tanısı almıştır. Hastaların 203 (% 50.5)'ü Ege bölgesinden, 146( % 36.3)'sına ek hastalık eşlik etmekte ve 85 ( % 21.1)'inde immün yetmezlik durumu saptanmıştır. Laboratuvarda değerlendirilen örneklerde üretilen M.tuberculosis suşlarının moleküler tiplendirmeleri yapıldığında 52'sinin (%12.9) ailesi net belirlenemedi. Belirlenenlerin ise %40'ı T1, %8.2'si H3, %7'si LAM7-TUR, %5'i H1, % 4 'ü LAM3 - S (karma) ve % 4 U ailesinden oluşmaktaydı. Aileler arasında yaş dağılımı, radyolojik ve klinik bulgular, laboratuvar verileri bakımından anlamlı fark yoktu, gruplar benzer özellik göstermekteydi. Ancak; ilaç direnci açısından bakıldığında Beijing ailesinin % 55.6'sı rifampisin (R), izoniazid (H)(1 µg/ml) - H(0.2 µg/ml) ve streptomisin (S) dirençliydi ve bu oranlar diğer ailelerden anlamlı olarak daha yüksekti (p<0.001). Hastaların %71.6 'sı TB nedeni ile hastaneye yatmıştır ve 1 yıl içindeki mortalite oranı %17.9'dur. Aileler arasında hastane yatışı ve mortalite bakımından anlamlı fark bulunmamıştır. Sonuç: M.tuberculosis suşlarının tiplendirilmesi, toplum içindeki enfeksiyonun orijini, yayılması ve direnç kazanmış olan suşların erken saptanması gibi önemli cevapları bize verebilir. Bu çalışmada en sık T1 ailesinin bölgemizde saptandığı ve Beijing ailesinin farklı şekilde yüksek direnç suşu içerdiği gösterilmiştir. Ancak bu ailelerin özellikleri ve klinik yansımalarına yönelik başka bölgelerde de çalışmalara ihtiyaç duyulduğu belirlenmiştir.
İntroduction and Purpose: Tuberculosis (TB) is known as an old disease with a history going back even to the origin of humanity. The clinical aspect is a chronic granulamatous disease. The epidemiological aspect of the disease plays a critical role in understanding the control of mortality and contamination, spread of the disease in community, dynamics of contamination and difference between re-infection and re-activation. Advance in the molecular diagnostic tools allows better typing of the TB, thus leads to discover origin of infection in community and early detection of resistant TB. In this study, we investigated with molecular techniques the identification, genotyping and drug resistance of TB bacilli in materials obtained from patients with pulmonary and extra-pulmonary TB in Ege University Hospital. The data were analyzed for correlation with biochemistry and clinical, radiological aspect of the disease. Material - Method: The molecular typing was made with spoligotyping method from bacilli obtained from 402 patients with a diagnosis of pulmonary and extra-pulmonary TB in Ege University Hospital between 2009 and 2014. The demographic data was extracted retrospectively from files of the patients including clinical and radiological findings, origin of case, date of diagnosis, co-morbidity, treatment, drug-resistance pattern, biochemistry, tuberculin skin test, Interferon-gamma release test, length of hospital stay and mortality. Results: The study was conducted on 402 patients (238 male, mean age 52 ± 18.4 years) with TB. Diagnosis of pulmonary Tb was present in 248 (%61.7), extra-pulmonray TB in 135 (%12.9) and 19 (%4.7) pulmonary and extra-pulmonary TB. The origin of the patients was Aegean area in 203 (%50.5) and co-morbidity was present in 146 (%36.3) and 85 (%21.1) with immunosuppression state. In the molecular typing of Tuberculosis of 52 (%12.9) samples the family of bacilli was not identified. The most identified family was found as T1 in %40 followed by H3 in %8.2, LAM7-TUR in %7, H1 in %5, LAM3-S (complex) in %4 and U family in %4. No correlation was found between families in terms of age, radiological and clinical data and laboratory findings. Drug resistance pattern is also investigated in families and drug resistance for Rifampicin (R), Isoniazid (H) (1 mg/ml) – H (0.2 mg/ml) and Streptomycin (S) resistance was found in %55.6 of Beijing family and was significantly higher when compared with other families (p<0.001). Hospitalization was present in %71.6 of patients and one year mortality was found as %17.6. No difference was found between families in terms of hospitalization and mortality rates. Conclusion: Molecular typing of TB bacilli allows to better understanding of the origin, spread of infection in community and early detection of resistant bacilli. In this study, we found that in our community dominant bacilli was T1 family and resistant bacilli was found in higher percentage in Beijing family. More studies on clinical aspect of this families and families from other areas are needed to better understand the behavior of TB in our community.
İntroduction and Purpose: Tuberculosis (TB) is known as an old disease with a history going back even to the origin of humanity. The clinical aspect is a chronic granulamatous disease. The epidemiological aspect of the disease plays a critical role in understanding the control of mortality and contamination, spread of the disease in community, dynamics of contamination and difference between re-infection and re-activation. Advance in the molecular diagnostic tools allows better typing of the TB, thus leads to discover origin of infection in community and early detection of resistant TB. In this study, we investigated with molecular techniques the identification, genotyping and drug resistance of TB bacilli in materials obtained from patients with pulmonary and extra-pulmonary TB in Ege University Hospital. The data were analyzed for correlation with biochemistry and clinical, radiological aspect of the disease. Material - Method: The molecular typing was made with spoligotyping method from bacilli obtained from 402 patients with a diagnosis of pulmonary and extra-pulmonary TB in Ege University Hospital between 2009 and 2014. The demographic data was extracted retrospectively from files of the patients including clinical and radiological findings, origin of case, date of diagnosis, co-morbidity, treatment, drug-resistance pattern, biochemistry, tuberculin skin test, Interferon-gamma release test, length of hospital stay and mortality. Results: The study was conducted on 402 patients (238 male, mean age 52 ± 18.4 years) with TB. Diagnosis of pulmonary Tb was present in 248 (%61.7), extra-pulmonray TB in 135 (%12.9) and 19 (%4.7) pulmonary and extra-pulmonary TB. The origin of the patients was Aegean area in 203 (%50.5) and co-morbidity was present in 146 (%36.3) and 85 (%21.1) with immunosuppression state. In the molecular typing of Tuberculosis of 52 (%12.9) samples the family of bacilli was not identified. The most identified family was found as T1 in %40 followed by H3 in %8.2, LAM7-TUR in %7, H1 in %5, LAM3-S (complex) in %4 and U family in %4. No correlation was found between families in terms of age, radiological and clinical data and laboratory findings. Drug resistance pattern is also investigated in families and drug resistance for Rifampicin (R), Isoniazid (H) (1 mg/ml) – H (0.2 mg/ml) and Streptomycin (S) resistance was found in %55.6 of Beijing family and was significantly higher when compared with other families (p<0.001). Hospitalization was present in %71.6 of patients and one year mortality was found as %17.6. No difference was found between families in terms of hospitalization and mortality rates. Conclusion: Molecular typing of TB bacilli allows to better understanding of the origin, spread of infection in community and early detection of resistant bacilli. In this study, we found that in our community dominant bacilli was T1 family and resistant bacilli was found in higher percentage in Beijing family. More studies on clinical aspect of this families and families from other areas are needed to better understand the behavior of TB in our community.
Açıklama
Anahtar Kelimeler
Tüberküloz, Moleküler Epidemiyoloji, M.tuberculosis Klinik İzolatları, Tuberculosis, Molecular Epidemiology, Clinical Isolates of M.tuberculosis
