| Sažetak | Uvod Multipla skleroza (MS), demijelinizacijska je bolest središnjega živčanog sustava, neidentificirana uzroka. Rasprostranjenost bolesti pokazuje da njena učestalost može varirati i unutar teritorijalno obližnjih područja.
Cilj istraživanja U Gorskome kotaru, Hrvatska, visokoga rizika za MS, odrediti
razlike u epidemiološkim, serološkim, imunološkim i genetskim posebnostima izmeđuMS bolesnika i kontrolnih ispitanika u Gradovima Čabru (visoki rizik za MS) i Vrbovskome (niski rizik za MS).
Metode i ispitanici Retrospektivno istraživanje vezano uz 19 bolesnika u Gradu Čabru i 9 u Gradu Vrbovskome, dokazanih slučajeva MS-a (Poserovi kriteriji), i dvostrukoga broja kontrolnih ispitanika, provedeno je u razdoblju od 2001. do 2004. Plan istraživanja uključivao je ispitivanje epidemioloških deskriptivnih pokazatelja i case-control istraživanja (anketa «od vrata do vrata») o demografskim podacima, profesiji, društveno-ekonomskome stanju, osobnim obilježjima, osobnoj i porodičnoj anamnezi, uvjetima stanovanja, obilježjima plodnoga razdoblja u žena, o dojenju i prehrani, kontaktu sa životinjama do 18.
godine. Uzorak krvi uzet je od svakog ispitanika za biokemijske, serološke, imunološke i genetske analize.
Glavni pokazatelj ishoda Analiza je provedena u svih MS bolesnika koji su na dan prevalencije, 31. ožujka 2001., boravili u Gradovima Čabru i Vrbovskome, da bi se najprije izračunale prevalencija, incidencija i smrtnost od MS-a, potom za svaki pokazatelj pojedinačno, kako bi se omjer odnosa (OR) i 95%-tni interval pouzdanosti (CI) za sve pokazatelje koji su bili u bolesnika negoli u kontrolnih ispitanika, i obrnuto.
Rezultati U Gradu Čabru sirova je prevalencija MS-a iznosila 160,3/100.000 stanovnika; prosječna incidencija (1948.·-2004.) bila je 5,52/100.000 stanovnika na godinu (95% CI, 3,27-8,72); prosječna smrtnost u godini dana (1946.-2004.) bila je 2,76/100.000 stanovnika (95% CI, 1,26-5,24); spolni indeks (Ž/M) iznosio je 1,11; početno doba bilo je u 28,53 (10,04) godini; prosječno trajanje bolesti do dana prevalencije iznosilo je 27,26 (11,11) godina; porodičnih bilo je 52,63%; prosječno dijagnostičko vrijeme bilo je 4,5
(6,58) godina. U Gradu Vrbovskome, sirova prevalencija MS-a iznosila je 66,14/100.000 stanovnika; prosječna incidencija (1948.-2004.) bila je 1,99/100.000 stanovnika na godinu (95% CI, 0,91-3,78), (P=0,009); prosječna smrtnost u godini dana (1946.-2004.) bila je 0,88/100.000 stanovnika (95% CI, 0,24-2,27), (P=0,06); spolni indeks (ŽIM) iznosio je 1,25; početno doba bilo je u 27,52 (8,58) godini (P=0,79); prosječno trajanje bolesti do dana prevalencije iznosilo je 19,34 (9,52) godine (P=0,264); porodičnih slučajeva bilo je 11,1 % (P=0,042); prosječno dijagnostičko vrijeme bilo je 5,27 (4,48) godina. U obama je Gradovima dobno specifična prevalencija u oba spola prevladavala u skupini 30. i 49. godine. U Gradu Čabru, MS bolesnici bili su redom Hrvati, potomci kroatiziranih Nijemaca i/ili Slovenaca (P=0,026); u Gradu Vrbovskome, bolesnici su bili većinom Srbi (P=0,026). Varijable povezane sa zamjetnim rizikom za MS u Gradu Čabru, obuhvaćale su: bavljenje
poljoprivredom, stočarstvom i šumarstvom (P=0,007), alergije u bolesnika (P=0,019) i članova porodice (P=0,0018), ozljede (P=0,002), soljenje nitritima (P=0,03), pijenje alkohola (P=0,0009), hranu bogatu masnoćama životinjskoga podrijetla (P=0,000001), potrošnju zobi i proizvoda od zobi (P=0,0057), svijetlu kosu i oči (P=0,05), otvorenu kanalizaciju (P=0,000013), trajno boravljenje u mjestu rođenja do 18. godine (P=0,017), te porodičnu MS (P=0,0046). Prezimena porodičnih slučajeva MS-a, bila su njemačkoga (30%), slovenskoga (40%) i slovensko-njemačkoga (20%) podrijetla. MS bolesnice u Gradu Čabru bile su u najvećem broju kućanice (P=0,029), s ranom menarhom (P=0,018), ranim začećem, trudnoćom i porođajem (n.s.). Nije ustanovljena povezanost sa saniranim zubalom (P=0,010), redovitom potrošnjom povrća i voća (P=0,009), ribe svježe (P=0,002) i smrznute (P=0,00007), mesa divljači (P=0,03), suhomesnatih proizvoda sušenih na vjetru (P=0,004), korištenjem vode iz vodovoda (P=0,011), zatvorenom kanalizacijom (P=0,000013), kontaktom s domaćim životinjama (P=0,01), te kućom zidanom od opeka (P=0,01).
U Gradu Vrbovskome, MS bolesnici su jeli hranu bogatu masnoćama
životinjskoga podrijetla (P=0,03), mahunarke (P=0,027), pili alkohol (P=0,006), stanovali u drvenim kućama (P=0,067), te rjeđe pili neprokuhanu vodu (P=0,05).
Početna simptomatologija MS-a {poglavito osjetno-motorna i vidna), klinički tijek i razvoj invalidnosti, bili su slični u objema skupinama bolesnika. Popratne bolesti ustanovljene su isključivou bolesnika u Gradu Čabru koji su imali i učestalije komplikacije tijekom raznih terapijskih postupaka.
Koncentracije serumskih protutijela bile su bitno povećane jedino u bolesnika u Gradu Čabru i to protiv citomegalovirusa (P=0,00025), Epstein-Barr virusa (P=0,006), parotitis virusa (P=0,037) i respiratomoga sincicijskoga virusa (P=0,008). Serologija inokulacije hepatitis B virusom bila je pozitivna u 10,5% bolesnika u Gradu Čabru (P=0,18), koji su pokazivali i četiri puta veću infestaciju Toxoplasmom gondii negoli kontrolni ispitanici. Protutijela IgG-a protiv Borrelie burgdorferi, nađena su u krvi 2% ispitanika.
Aleli -A3 (P=0,03) i -DR2 (P=0,004), nađeni su jedino u bolesnika u Gradu Čabru.
Zaključak Naše istraživanje potvrđuje da genetičke, društvene, jezične i
kulturološke raznolikosti susjednih područja u Gorskome kotaru, Hrvatska, uvjetuju neujednačenu rasprostranjenost MS-a. U Gradu Čabru, familijarni (pseudo)klaster MS-a, "utjecaj osnivača" i danas je u velikoj mjeri čimbenik za održavanje većeg rizika za MS. Alergijska dijateza, te među ekološkim čimbenicima u prvome redu masno-mesna prehrana, alkoholizam i higijensko-sanitarni standard, utječu na patogenezu MS-a u genetski sklonih
jedinki u obama Gradovima. |
| Sažetak (engleski) | Background Multiple sclerosis (MS) is a demyelinating disease of the central nervous
system of unknown aetiology. The geographical distribution of MS shows that her
frequency can also vary inside territorially closed areas.
Objective To determine the epidemiological, clinical, serologic, immunologic and genetic
differences between MS-patients and controls in the Municipalities of (high-risk
area) and Vrbovsko (low-risk area), which are situated in Gorski kotar, area of high-risk for
MS in Croatia.
Methods and subjects Retrospective study of 19 patients from Municipality of Čabar and
9 patients from Municipality of Vrbovsko, clinically definite cases of MS (Poser's criteria),
and double number of controls, has been carried out between 2001-2004. Plan of
investigation included evaluation of descriptive epidemiological rates and case-control
studies ("door to door" interview) about demographic data, profession, socio-economic
status, specificity of personalities, personal and family anamnesis, specificities of housing,
specificities of fertility period in women, breast feeding and nutrition, exposure to animal
contact before age of 18. Blood sample was taken from each individual for biochemical,
serologic, immunologic and genetic analysis.
Main Outcome Measures Analysis was carried out for all MS patients present in
Municipality of and Municipality of Vrbovsko on the prevalence day of March 31-
2001 in order to calculate the prevalence, incidence and mortality of MS, and then for each
indicator, in order to calculate the Odds Ratio (OR) and 95% Confidence Interval (CI) for
all indicators that were more frequent in patients then in controls, and vice versa.
Results In the Municipality of the crude prevalence of MS was 160.3 per 100.000
inhabitants; annual mean incidence (1984-2001) was 5.52 per 100.000 inhabitants per year
(95% CI, 3.27-8.72); annual mortality rate (1946-2001) was 2.76 per 100.000 inhabitants
(95% CI, 1.26-5.24); sex ratio (F/M) was 1.11; mean age of onset was 28.53 (10.04) years;
mean duration of disease to prevalence day was 27.26 (11.11) years; an affected family
member was identified in 52.63% of the autochthonous population; mean diagnostic time
was 4.5 (6.58) years.
In the Municipality of Vrbovsko crude prevalence of MS was 66.14 per 100.000
inhabitants; annual mean incidence (1948-2001) was 1.99 per 100.000 inhabitants per year
(95% CI, 0.91-3.78), (P=0.009); annual mortality rate (1946-2001) was 0.88 per 100.000
inhabitants (95% CI, 0.24-2.27), (P=0.06); sex ratio (F/M) was 1.25; mean age of onset was
27.52 (8.58) years (P=0.79); mean duration of disease to prevalence day was 19.34 (9.52)
years (P=0.264 ); an affected family members was identified in 11.1 % of the autochthonous population (P=0.042); mean diagnostic time was 5.27 (4.48) years. In both municipalities,
the age-specific prevalence within both genders prevailed in the 30-49 age group.
In the Municipality of MS patients were all Croats, descendants of croatized
Germans and/or Slovenians (P=0.026). In the Municipality of Vrbovsko MS patients were
mostly Serbs (P=0.026). Variables connected to significant risk of MS in the Municipality
of included professions in agriculture, farming and forestry professions (P=0.007),
allergies in patients (P=0.019) and family members (P=0.0018), injuries (P=0.002), usage
of salt with nitrites (P=0.03), alcohol consumption (P=0.0009), food rich in animal fats
(P=0.000001); consumption of oat and it's products (P=0.0057), light colors of hair and
eyes (P=0.05), open type of sewage system (P=0.000013), constant area of residence until
age of 18 (P=0.017) and family history of MS (P=0.0046). Sumames of familiar MS
patients were all of German (30%), Slovenian (40%) and Slovenian-German (20%) origin.
Female MS patients from Municipality of were mostly housewives (P=0.029) with
early menarche (P=0.018), early conception, pregnancy and birth (n.s.). No connection was
found with dental fillings and structures (P=0.010), regular consumption of fruits and
vegetables (P=0.009), fresh fish (P=0.002), frozen fish (P=0.00007), meat of wild animals
(P=0.03), meat products dried on the air (P=0.004), usage of water from the pipe (P=0.011),
closed sewage system (P=0.000013), contact with domestic animals (P=0.01) and with the
house made of bricks (P=0.01).
In the Municipality of Vrbovsko MS patients were eating more food rich in animal fats
(P=0,03), beans (P=0,027), consumption of alcohol (P=0,006), living in wooden houses
(P=0,067) and were rarely drinking unboiled water (P=0,05).
Initial symptomatology of MS (mainly motor and visual symptoms), clinical course and
development of disability were similar in both groups of patients. Associated diseases were
present within the MS patients from Municipality of and they had more frequent
complications during various therapeutic procedures.
Concentration of serum antibodies was significantly increased only within group of MS
patients from Municipality of Čabar as follows: against cytomegalovirus (P=0.00025),
Epstein-Barr virus (P=0.006), parotitis virus (P=0.037) and respiratory syncytial virus
(P=0.008). Serologic tests for Hepatitis B virus was positive in 10.5% MS patients from
Municipality of Čabar (P=0.18) and they shown four times higher infestation with
Toxoplasma gondii then controls. IgG antibodies to Borrelia burgdorferi were present in the
blood of 2% of patients. Alleles -A3 (P=0.03) and -DR2 (P=0.004) were present only in
the MS patients from Municipality of Čabar.
Conclusion Our investigation confirms that genetic, ethnic, sociological, linguistic and
cultural differences of neighboring zones in Gorski kotar, Croatia are responsible for
heterogenic distribution of MS in this area. In the Municipality of familiar
(pseudo)cluster of MS, «founder effect» is present maintaining the greater risk for MS.
Allergy diathesis and mainly fat/meat dietary regime, alcoholism and low hygiene-sanitary
standard amongst ecologic factors, play a role in the etiopathogenesis od MS in genetically
disposed individuals in both Municipalities. |
