A tuberculosis (TB) paleopatológiája

Átírás

1 To be or not to be that is the question: from Shakespeare s Hamlet (written about 1600) TB or not TB? A tuberculosis (TB) paleopatológiája Pálfi György SZTE TTIK Embertani Tanszék

2 Kutatási előzmények

3 Konferenciák, kutatások, kiadványok: Tuberculosis : Past & Present

4 tbc white plague

5 Mycobacteriális fertőzések paleopatológiája TBC Mycobacterium tuberculosis complex csoport M. tuberculosis, M. bovis, M. africanum, M. microti LEPRA Mycobacterium leprae

6 Specifikus fertőzések paleopatológiája - tuberculosis Története Magyarországon a legkorábbi paleopatológiai lelet a római korból ismert de: valószínűsíthetők hazai neolit leletek is! Európában bizonyítottan a neolitikum óta ismert (pl. Heidelbergi lelet) Legrégebbi bizonyított eset (DNS is): Izrael, 9 ezer éves 500 ezer éves H. erectus leletnél is felvetették (bizonytalan) Evolúció-genetikai alapon feltételezik, hogy 2-3 millió éve kialakulhatott a Mycobacterium tuberculosis baktérium Leggyakoribb kórokozók Mycobacterium tuberculosis Mycobacterium bovis M. tuberculosis genetikailag ősibbnek tekinthető, mint a M. bovis ebből következően nem igazak azok az állítások, miszerint az emberi tbc a szarvasmarha-félék háziasítását követően alakult ki.

7 A tuberculosis paleopatológiai diagnosztikája Általános makroszkópos-morfológiai vizsgálatok: diagnosztika a csont-ízületi elváltozások típusa és megoszlása alapján Paleoradiológiai vizsgálatok: a makroszkópos-morfológiai vizsgálatokat kiegészítő eljárások, különböző orvosi képalkotó technikák (rtg, CT, stb) alkalmazásával Paleohisztológiai vizsgálatok: mikroszkópiai technikák alkalmazása a tbc-okozta elváltozások kórszövettani kimutatásához Molekuláris biológiai vizsgálatok: genetikai (DNS) és biokémiai (mikolsav és protein-markerek) módszerek alkalmazása a Mycobacterium-fertőzés igazolására

8 Humán csont-ízületi tuberkulózis Krónikus tuberkulózisban szenvedők mintegy 5%-nál figyelhető meg a csontváz érintettsége Fertőzés útja: -Vérárammal - Direkt fertőzés a környező szervekből Leggyakrabban érintett területek: - gerincoszlop - nagy megterhelésnek kitett ízületek Schematic drawing of TB involvement of a long bone (PANUEL et al., 1999)

9 Humán csont-ízületi tuberkulózis spondylitis tuberculosa Pott gibbus

10 Humán csont-ízületi tuberkulózis csípőízületi tuberculosis

11 Humán csont-ízületi tuberkulózis előrehaladott stádiumú tbc az avar korból

12 Vertebral tuberculosis Tuberculous spondylitis. French medieval case. (PALFI et al., 1992) Spinal TB, 2 foci of destruction. Modern case, Switzerland (ORTNER, 1999) Spinal TB with ankylosis. Hungarian medieval case (unpublished, photo G. Pálfi)

13 Calcifications of tuberculous origin - rare conditions in paleopathology - useful material for paleomicrobiological studies (e.g. DONOGHUE et al., 1998, HAAS et al., 1999, PALFI et al., 1999) Examples : 1-7-8th century 2-17th century 3-18th century mummy, X-ray 1 2 3

14 No. 65

15 Paleoepidemiology of TB Hungary th century mummy collection, Vác. Case 39 Partially mummified remains of an 18-yearold male. Ankylosis of several vertebrae and extreme degree angular kyphosis of spine (PAP et al., 2001, PALFI et al., 2001)

16 Paleoepidemiology of TB Hungary th century mummy collection, Vác. Case 39 Typical morphological changes of advanced-stage childhood Pott s disease from pre-antibiotic era Evidence of MTB DNA (paleomicrobiological study by DONOGHUE et al., 2000) (82) 123 bp

17 Mycobacterium tuberculosis in 18th Century Hungarians - distribution and molecular aspects Helen D. Donoghue Medical Microbiology Dept, Windeyer Institute, UCL European Society of Mycobacteriology 2002 Eurpean Meeting Dubrovnik, Croatia

18 MTB +ve bodies by age at death Age (Years) >80 TB +ves TB -ves Number of bodies examined Konklúzió: a 265, századi váci múmia-lelet mintegy 70%-a M. tuberculosis fertőzött volt. (A ténylegesen betegek aránya egyelőre nem tisztázott.) Helen D. Donoghue European Society of Mycobacteriology 2002 Eurpean Meeting Dubrovnik, Croatia

19 Korai tbc-s csontelváltozások - atypical / early-stage skeletal TB alterations Costal periostitis. French medieval cases (PALFI et al., 2000) Endocranial granular impressions. Medieval case, Switzerland (SCHULTZ, 1999) Circumferential pitting on vertebrae (Egypt, 2nd-1st millenium BC, BAKER, 1999)

20 Korai tbc-s csontelváltozások - atypical skeletal TB changes in a Hungarian series Identification of Mycobacterium tuberculosis complex DNA in ancient, atypical TB cases Example : series of Bácsalmás (Hungary, 17th c.), graves no. 39, 85, 118 lane 2 : Bácsalmás 39 lane 6 : Bácsalmás 85 lane 8 : Bácsalmás 118 (HAAS et al., 1999)

21 Korai tbc-s csontelváltozások - association of early-stage skeletal TB alterations Terry Anatomical Collection, Smithsonian Institution, Washington D.C., beginning of the 20 th century 1 3 Example : Case No rib periostitis 2 - vertebral hypervascularisation 3, 4 - endocranial changes 4 (PALFI et al., 2000) 2

22 Paleoepidemiology of TB Relatively high frequency of TB meningitis in medieval Europe (SCHULTZ, 1999) High infant mortality and high prevalence (43/105) of TB-like infections in the medieval (6-10th and 12-13th centuries) series of La Celle, Southern France (MACZEL et al., 2000, PALFI et al., 2000) - 17 possible cases of TB meningitis /39 new-born and children remains Cases of probable TB meningitis from La Celle (MACZEL, PALFI, 2000)

23 Paleoepidemiology of TB a trilateral research project ( ) France - La Celle medieval series: paleomicrobiological study of probable TB meningitis cases (preliminary results by A. ZINK) Lane 4: grave year-old child Lane 5: grave 36A 0-1 year-old child 123 bp Grave 21C (~4 year-old child): the nucleotid sequence of the 123 bp PCR product fits exactly the expected sequence of the IS6110 of the MTB DNA

24 PALEOPATHOLOGICAL RESULTS* Classical TB changes LaC-6 (6-10th c.): Mat., M Ba-61 (16-17th c.): Juv., M Cso-205 (7-8th c.): Ad., F PhD Thesis of Marta MACZEL (Szeged - Marseille, 2003 Ba-85 (16-17th c.): Mat., M

25 MOLAT - Minor Osseous Lesions Attributable to Tuberculosis (PhD Thesis of M. MACZEL, 2003) Hau-208 (11-14th c.): adult Cso-189 (7-8th Cso-221 (7-8th c.): Inf. II. c.): Juv., F? Ba-115 (16-17th c.): Juv., M Ba-78 (16-17th c.): Inf.I. LaC-21C (13th c.): Inf.I. Hau-909 (11-14th c.): Juv., M

26 2010-es kutatások Smithsonian Institution, Terry Collection, Washington DC, USA

27 Smithsonian Institution National Museum of Natural History

28

29

30

31

32 Reflections on three 17 to 19-year-oldjuvenile individuals as victims of tuberculosis, from the Terry Anatomical Collections György PÁLFI 1, Donald J. ORTNER 2, Olivier DUTOUR 3 1 Department of Biological Anthropology, University of Szeged, Szeged, Hungary; 2 Department of Anthropology, National Museum of Natural History, Smithsonian Institution, Washington DC, USA; 3 University of Aix-Marseille, Faculty of Medicine, Marseille, France & Department of Anthropology, University of Toronto, Canada

33 In the framework of an international research program about the variability of skeletal bone lesions due to tubercular infection, 1728 skeletons were studied from the Terry Anatomical Collection (NMNH, Smithsonian Institution, Washington DC). The collection dates from the first half of the 20 th century, a period marked by a high prevalence of tuberculosis (causing the death of at least 15% of the individuals whose bone remains make up the collection) before the introduction of antituberculars.

34 The evaluation of the entire set of data is still in progress. Our present study is limited to the discussion of the pathological lesions of three individuals, who had died of TB at a young age (most of the collection is made up of adult samples and shows a scarcity of juvenile cases).

35 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB As our first case (N o 129), we examined the remains of a male Afro- American individual who had died of tuberculous spondylitis at the age of 19, according to the death certificate of the morgue. The skeleton shows a remarkable collection of lesions, most of being destructive and concerning mainly the spine and the ribs. A thorough study concluded a multifocal cystic spondylitis. The costal lesions present two characteristic features: periosteal appositions relating to a pneumo-pleural infection, and lesions caused by osteitic erosive TB. Some signs of tuberculous meningitis and traces of an initial stage sacro-ileitis were also detected.

36 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB multifocal cystic spondylitis

37 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB

43 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Traces of cold abscess

44 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Traces of cold abscess

45 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Rib lesions: periosteal appositions relating to a pneumo-pleural infection, and lesions caused by osteitic erosive TB

46 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Rib lesions: periosteal appositions relating to a pneumo-pleural infection, and lesions caused by osteitic erosive TB

47 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Early signs of tuberculous meningitis

48 No. 129, Black Male, 19 Years, Cause of Death: vertebral TB No. 129, Black Male, 19 Years, Cause of Death: vertebral TB Early signs of tuberculous meningitis

49 No. 306, White Female, 17 Years, Cause of Death: lung TB The second case (N o 306) was a Euro-American female individual who had died of pulmonary TB at the age of 17. Remarkable endocranial lesions can be noticed at the frontal and parietal levels suggesting a very probable case of TB meningitis. These lesions include a remodelling of several vertebrae with abnormal hypervascularization at the thoracic level and rather superficial alterations at the lumbar level. This individual also shows signs of very fine periosteal appositions on several long bones and on the visceral face of several ribs. This suggests the association of four types of earlystage (or minor ) skeletal lesions, which are likely to be attributed to tuberculosis.

50 No. 306, White Female, 17 Years, lung TB endocranial lesions - very probable TB meningitis

51 No. 306, White Female, 17 Years, lung TB No. 306, White Female, 17 Years, lung TB endocranial lesions - very probable TB meningitis

52 No. 306, White Female, 17 Years, lung TB endocranial lesions - very probable TB meningitis

53 No. 306, White Female, 17 Years, lung TB fine periosteal appositions on a long bone

54 No. 306, White Female, 17 Years, lung TB remodelling of vertebrae: superficial alterations at the lumbar level

55 No. 306, White Female, 17 Years, lung TB remodelling of vertebrae: abnormal hyper-vascularization at the thoracic level

56 No. 306, White Female, 17 Years, lung TB remodelling of vertebrae: abnormal hyper-vascularization at the thoracic level

57 No. 306, White Female, 17 Years, lung TB fine periosteal appositions on several ribs

58 No. 306, White Female, 17 Years, lung TB fine periosteal appositions on a rib (viceral face)

59 No. 329, Black Male, 17 Years, Cause of Death: TB, cranial lesions, syphilis? The last case we studied (N o 329) was an Afro-American male individual who had died at the age of 17. The skeleton presents manifold localizations of constructive and destructive lesions, the latter being largely predominant. According to the death certificate of the morgue, this teenager had died of tuberculosis, syphilis and cranial lesions. The cranial lesions are reflected in the form of lytic lesions with perforations on the skull vault. The morphology of these lesions suggests very clearly a case of cranial TB differing from a syphilitic process. We note the coexistence of the signs of cranial tuberculous osteitis and those of endocranial lesions suggesting TB meningitis.

60 No. 329, Black Male, 17 Years, Cause of Death: TB, cranial lesions, syphilis? At the postcranial level of the skeleton we can observe the traces of mainly osteolytic lesions relating to probable tuberculous osteitis (pelvis, ribs). We are to mention as well the osseous consequences of an advanced-stage TB arthritis on the right ankle. Periosteal appositions can only be seen in association with lytic lesions. A spina ventosa of the left ulna can be noted, which is a scarce form, although typical for osseous tuberculosis. In addition to the lesions mentioned above, the spine shows signs of a very destructive, multifocal TB osteitis. The pathological alterations of this skeleton can be explained by an extremely aggressive tuberculous osteitis. No skeletal signs suggesting syphilis can be found on the rest of this sample.

61 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? lytic lesions with perforations on the skull vault

62 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? lytic lesions with perforations on the skull vault

63 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? signs of cranial tuberculous osteitis and those of endocranial lesions suggesting TB meningitis

64 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? signs of cranial tuberculous osteitis and those of endocranial lesions suggesting TB meningitis

65 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? spina ventosa

66 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? osteolytic lesions relating to tuberculous osteitis

67 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? osteolytic lesions relating to tuberculous osteitis

68 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? destructive, multifocal TB spondylitis

72 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? tuberculous osteitis of a rib

73 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? tuberculous osteitis of a rib

74 No. 329, Black Male, 17 Years, TB, cranial lesions, syphilis? TB arthritis on the right ankle

75 Reflections on three 17 to 19-year-oldjuvenile individuals as victims of tuberculosis, from the Terry Anatomical Collections The study of these three individuals has brought about new data on the least known skeletal modes of expression of oteo-articular tuberculosis, and has the aim of contributing to a better paleopathological definition of this infection. No. 129 No. 306 No. 329