تفشي ڤيروس التهاب الكبد الوبائي سي

تفشي ڤيروس التهاب الكبد الوبائي سي
Hepatitis C virus
HCV EM picture 2.png
Electron micrograph of hepatitis C virus purified from cell culture. Scale: black bar = 50 nanometres
تصنيف الفيروسات
Group:
Group IV ((+)ssRNA)
Family:
Genus:
Species:

ڤيروس التهاب الكبد الوبائي سي Hepatitis C virus (HCV)، هو ڤيروس صغير (55-65 ن.م) مغلف، حساس-موجب، ذو رنا فردي من فصيلة الڤيروسات المصفرة. ڤيروس التهاب الكبد لوبائي سي يسبب التهاب الكبد الڤيروسي سي في البشر. ويقدر أن هذا الڤيروس يتسبب في 25% من حالات التليف الكبدي و25% من حالات سرطان الخلايا الكبدية في العالم. في اليابان أكثر من 70% من الحالات المصابة بالتليف الكبدي وكثر من 80% من الحالات المصابة بسرطان الكبد تظهر فيها عدوى ڤيروس التهاب الكبد الوبائي سي.

تقترح دراسات التاريخ لطبيعي من البيانات أن الإصابة بالتليف الكبدي أبطأ لدى الأشخاص المصابون بالعدوى مثل الأطفال والبالغون الصغر، حيث تكون أبطاً بنسبة 5% في المصابين بالتليف الكبدي في العشرين سنة الأولى من عمرهم، عن الأشخاص المصابون بالعدوى في البالغين الأكبر سناً، حيث تتسبب العدوى في خدوث تليف الكبد ل10-20% من المصابين في العشرين سنة الأولى من حياتهم.


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الانتشار

انتشار ڤيروس التهاب الكبد الوبائي سي في العالم، 1999

تقدر منظمة الصحة العالمية المصابون بهذا الڤيروس بأكثر من 170 مليون شخص.[1]

معدلات الانتشار واسعة جداً، أمريكا الشمالية، اوروبا، أستراليا، والشرق الأقصى (أكثر من 2.5%)؛ بعض بلدان البحر المتوسط، أمريكا الجنوبية، أفريقيا والشرق الأوسط (2.5% إلى 10%)؛ بوليڤيا، بوروندي، الكاميرون، مصر، الگابون، غينيا، منغوليا ورواندا (أقل من 10%).

في الولايات المتحدة يقدر أن هناك 2.7 مليون شخص مصابون بعدوى مزمنة.[2] في الولايات المتحدة يتسبب هذا الڤيروس في وفاة 8000 إلى 13.000 شخص سنوياً ومعظمهم من قاموا بعمليات زراعة كبد في الولايات المتحدة مصابون بعدوى مزمنة من هذا الڤيروس. في أمريكا الجنوبية معدل الإصابة أكبر من 60%.[3]

في اوروپا أكثر من 1% من السكان لديهم أجسام مناعية من هذا الڤيروس.[4] يقدر أن هناك 2.5 مليون مصاب بالڤيروس في اوروپا. في إيطاليا أكبر معدلات انتشار للفيروس على مستوى اوروپا، حيث تصل إلى 3.5-4.5%.[5] وترتفع المعدلات إلى أكثر من 20% في جنوب البلاد.[6]في المملكة المتحدة يوجد 200.000 شخص بالغ يحملون الڤيروس.[7]

في إيطاليا يوجد أكثر من 1.6 مليون شخص مصاب بعدوى هذا الڤيروس. في پاكستان تبلغ معدلات حاملوا الأجسام المناعية أكثر من 5%.


الإصابة

من الصعب تقدير العدوى بهذا الڤيروس بأنها <25% من الحالات المصابة بالتهاب الكبد الوبائي سي الحاد. 20% منها أظهرت إختبارات طبيعية لوظائف الكبد بالرغم من العدوى.

في الولايات المتحدة وصلة ذروة العدوى في 1989 حيث كان عدد الحالات أكثر من 240.000 شخص. وحاليا تظهر 20-30.000 حالات جديدة سنوياً.

في كندا تصل معدلات العدوى إلى 20 لكل مليون شخص (2004)، 16 لكل مليون شخص (2006) و22 لكل مليون في 2008.[8]

الانتقال

تم تحديد عدة طرق لانتقال العدوى. وتشمل تعاطي المخدرات عن طريق الحقن، نقل الدم ومنتجاته، النشاط الجنسي، غسيل الكلى، والانتقال للأجنة عن طريق الأم، وزراعة الأعضاء. ومع ذلك في أكثر من 30% من الحالات لا يوجد أي من الطرق المعروفة السابقة لنقل العدوى. يزداد انتشار الأجسام المضادة بتقدم العمر.

Certain genotypes have been associated with certain transmission routes: subtypes 1a and 3a are associated with intravenous drug use; subtype 1b mainly spread via blood transfusion and various other nosocomial modes of transmission. It should be noted that this association is not absolute.

تعاطي المخدرات عن طريق الحقن

The prevalence of Hepatitis C among intravenous drug users is ~80%.[4] The rate differs somewhat between countries with Australia reporting a 75% rate[9] and 90% in Pakistan[10]

In the United States ~60% of all hepatitis C is due to intravenous drug use.

A prospective study in the United Kingdom estimated the rate of acquisition of the virus to be 0.4% per year of drug use.[11] A study in Ireland estimated the rate to be 0.66% per year.[12]

نقل الدم

Before the introduction of routine hepatitis C screening of blood the incidence of post transfusion hepatitis in the US was about 5% per patient (1 per 200 units).[13] This risk has now dropped to ~1/30 million units. In haemophiliacs the prevalence of hepatitis c is >90%.

النشاط الجنسي

ينتقل ڤيروس التهاب الكبد الوبائي سي جنسياً لكنه أظهر معدل انتقال منخفض.[14][15]

المعدل بين الرجال ممن يقيمون علاقات جنسية مع رجال أكثر ارتفاعاً (4-8%) عن عموم السكان.

غسيل الكلى

معدلات الانتشار بين مرضى غسيل الكلى أعلى من 50%.[16] تقلل التحاليل والعلاجات الخاصة بإلتهاب الكبد الوبائي سي من إنتشار الڤيروس. لا تزال معدلات الخطورة أعلى من 1.38-1.9%/سنوياً.[17] Transmission within dialysis units has been reported.[18]

الولادة

ينتقل الڤيروس في فترة الولادة. لا تقلل الولادة القيصرية من إحتمال إنتقال الڤيروس.

زراعة الأعضاء

ترتبط زراعة الكلى في إيطاليا بإنتشر 33% من الحالات.[19] وهناك عامل خلط حيث كان جميع زارعي الكلى يقومون بغسيل الكلى وقد يكون إنتقال الڤيروس قد حدث قبل الزرع.

العدوى العرضية

تصل معدلات الإصابة العرضية بين 0.2 و10%.[20]

التراكيب الوراثية

Based on genetic differences between HCV isolates, the hepatitis C virus species is classified into seven genotypes (1-7) with several subtypes within each genotype (represented by lower-cased letters).[21][22] Subtypes are further broken down into quasispecies based on their genetic diversity. Genotypes differ by 30-35% of the nucleotide sites over the complete genome.[23] The difference in genomic composition of subtypes of a genotype is usually ~20-25%. Currently there are over 80 subtypes recognised. Subtypes 1a and 1b are found worldwide and cause 60% of all cases.

While there were initially multiple proposed typing schemes a consensus was reached in 1994 at the 2nd International Conference of HCV and Related Viruses [24]

Over 85% of the world's nearly 170 million hepatitis C virus case live in African, Southeast Asian and Middle Eastern countries where genotypes 4-6 are common. Genotype 4 is highly prevalent in Egypt with more than 19% of the population infected and chronic HCV representing one of the top five leading causes of death. This is due in part to ineffective response to interferon alpha treatment against this genotype.[25]

التوزيع الوراثي

The preponderance and distribution of the various HCV genotypes varies considerably between countries and regions. Additionally it tends to differ by route of transmission: genotypes 1a and 3a are closely associated with intravenous drug use and genotype 1b is seen more often in patients who acquire HCV through blood transfusion.[26] Recombinant strains have also been reported.

التركيب الوراثي 1

13 subtypes have been identified: these have been termed 1a to 1m.

In North America, genotype 1a predominates followed by 1b, 2a, 2b, and 3a.[27] In Europe, genotype 1b is predominant followed by 2a, 2b, 2c, and 3a.

This pattern is also found in South Korea (48% cases) [28][29] Mongolia,[30] and Morocco[31]

In Uzbekistan type 1 is predominant followed in frequency by type 3.[32] This pattern is also found in Belarus, Moldova and Russia,[33] China,[34] Indonesia,[35] Iran,[36] and Taiwan.[37] In Germany 70% of cases are due to type 1 (20% 1a and 80% 1b) and 25% to type 3.[26] This pattern is also found in Brazil[38] and Western Siberia.[39]

Genotypes 1 and 2 are both common in West Africa and have considerable genomic variability.[40]

In the الولايات المتحدة genotype 1 is responsible for ~75% of cases.

In Ireland the genotype associated with an outbreak due to the use of contaminated anti-D immunoglobulin was 1b.[41] In Romania ~90% of cases are due to type 1b[42] This appears to have been the use of blood transfusions in pregnancy and surgery.

In Greece genotype 1 accounts for ~40% cases.[43] In Poland 55% of cases are due to type 1.[44]

Genotype 1 accounts for ~60% of all cases in Italy[45] and 1b is the most common subtype.[6] The prevalence of this genotype there is thought to be due to the use of improperly sterilised reusable syringes in the past.

In هولندا this genotype accounts for ~50% of cases.[46] In Croatia this genotype accounts for ~60% of cases.[47]

In Tunisia 90% of cases are due to type 1b.[48]

95% of isolates in تركيا are type 1.[49] The most common subtype is 1b.[50] The strains in Turkey are most closely related to those in Japan, Europe and the USA.

In Japan, subtype 1b is responsible for up to 73% of cases.[51]

In Syria 19% of cases were genotype 1a and 27% were genotype 1b.[52]

In Jordan 40% of cases were type 1a, 33% were type 1b and 26.7% were type 4.[53]

In Lebanon this genotype is the second most common (after genotype 4) in non drug users: genotype 1a accounts for 12.5%-43.3% of cases and 1b for 8.0-34.4%.[54]

Genotype 1a and 1b have been reported from Bahrain but their prevalence is not known.[55]

This is the second most common type in Thailand (after genotype 3).[56] Subtype 1a accounted for 21% of all cases and 1b for 13.8%.


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التركيب الوراثي 2

Eighteen subtypes are known (2a-2r). This genotype accounts for 8% of cases in Europe.[57] In Greece genotype 2 accounts for ~7% cases.[43] In Belgium type 2 infection (6% of cases) has been associated with invasive medical examinations.[58] In the Netherlands this type accounts for ~10% of cases.[46] In Italy this type accounts for 25% of cases.[45]

Subtypes 2a and 2b are relatively common in North America, Europe and Japan. Subtype 2c is common in northern Italy.

Subtype 2k/1b was originally isolated from St Petersburg, Russia but has also been identified in Cyprus.[59] It is associated with intravenous drug use.

The genotype 2 strains from Africa can be divided into four clades that correlate with their country of origin: (1) Cameroon and Central African Republic; (2) Benin, Burkina Faso and Ghana';(3) the Gambia, Guinea, Guinea-Bissau and Senegal;(4) Madagascar.[60]

In Guinea-Bissau type 2 accounts for the vast bulk of the isolates.[61] In Ghana 85% of the isolates are type 2.[62]

In South Korea type 2 accounts for almost 50% of cases.[29]

Although type 4 is predominant in Egypt, type 2 also occurs there.[63]

التركيب الوراثي 3

Eleven subtypes are known (3a-3j). This genotype is the predominant type in India[64] and Pakistan[65] followed by type 1. In Pakistan type 3 accounts for 55-85% cases and type 1 10%.[66][67] It has been suggested that the pattern in Pakistan is due to the reuse of medical equipment without adequate sterilization.[65] Type 3 accounts for 60% of isolates in India.[68] This pattern is also found in north east Brazil where type 3 is the most common isolate (50% cases) followed by type 1 (40% cases).[69]

Subtype 3a is particularly prevalent in intravenous drug abusers in Europe and the United States.[70]

In Greece and Poland genotype 3 accounts for ~30% cases.[43][44] The proportion of type 3 infections in Greece may be higher than this with other studies reporting rates of 40%.[71] In the Netherlands this type accounts for ~30% cases.[46] In Croatia this genotype accounts for ~35% of cases.[47] In Italy this genotype accounts for ~5% of cases.[45]

In Iran genotype 3a accounts for 58% of cases.[72]

Genotype 3 is the predominate isolate among drug users in Lebanon where is responsible for 57.1% of cases.[73] Among non drug users genotype 4 is the most common (34.2-53.3% of cases) followed by type 1 (genotype 1a: 12.5-43.3%; genotype 1b: 8.0-34.4%).[54]

Although genotype 4 is predominant in Egypt, type 3 also occurs[63]

This is the most common type in Thailand accounting for almost 40% of cases[56] All the type 3 strains analysed in this study were of the 3a subtype.

التركيب الوراثي 4

Worldwide genotype 4 accounts for ~20% of all chronic infections.[74] Eighteen subtypes are known (4a - 4r).

الشرق الأوسط

Curiously genotype 4 is the most common genotype in the Arab countries of the Middle East while rare in the non Arab countries.[54][75] In Egypt (where the prevalence rate is ~13% of the population)[76] the distribution of this genotype (specifically subtype 4a) is thought to be due to the mass treatment programmes for schistosomiasis in that country from the 1930s until the 1980s when oral treatment became available.[77][78] In Egypt genotype 4 is responsible for >90% of cases.

It is the most common genotype in Saudi Arabia (62% of all cases).[79] In the United Arab Emirates this genotype accounted for 46% of isolated from females.[80] Curiously in the same study genotype 3a was the most common type in the males. This genotype has been identified in Yemen but its overall prevalence has not yet been reported.[81] In Syria this genotype accounts for 30% of cases.[52] In Jordan this genotype accounts for 26.7% of cases.[53] In Lebanon this genotype is the most common in non drug users (34.2-53.3% of cases)[54] In Kuwait this genotype may account for 64% of cases.[82] It is the most common genotype in Qatar.[83] It has been reported from Bahrain but its prevalence is not known.[55]

أفريقيا

Within Africa both types 1 and 4 are common in Cameroon[84] and Kenya.[85] Type 4 is also found in the Central African Republic,[86] Gabon,[87] Nigeria[88] the Republic of the Congo,[89] South Africa,[90] Sudan[91] Tanzania[92] and Uganda.[93] The majority of isolates from the Central African Republic (82%) are of this genotype.[94] This is similar to that found in south Cameroon where 75% of isolates are type 4.[95]

35% of cases in Libya are of genotype 4.[96]

اوروپا

Outside of Africa and the Middle East this genotype has been isolated in several European countries including Austria,[97] Belarus,[98] Belgium,[99] Croatia,[47] Cyprus,[100] Denmark,[101] France,[102] Greece[103] Italy[104][105] Portugal,[106] the Netherlands,[107] Romania,[42] Sicily,[108] Spain[109] and تركيا.[49]

Within Europe the prevalence of type 4 varies between countries from 7% in northern Europe to 24% in southern Europe.[110] In Greece genotype 4 accounts for ~15% cases.[43] A similar proportion has been reported in Poland.[111] In the Netherlands this type accounts for ~10% of cases.[46] In Croatia this genotype accounts for ~3% of cases.[47] In Spain this genotype has been reported to be responsible for ~20% of cases.[112] In Italy this type accounts for ~5% of cases.[45]

الأمريكتين

In the Americas it has been isolated in Brazil,[38] Canada,[113] Martinique,[114] the United States[115] and Venezuela.[116]

آسيا

It has also been isolated in Asia: India,[68] Iran[117] and South Korea.[29]

التركيب الوراثي 5

No subtypes have yet been identified for this genotype. It is found mainly in South Africa[118] (40% of cases) but it is also found in Austria,[97] Belgium,[119] Canada,[113] Cyprus,[100] Ethiopia,[120] France,[121] Germany,[122] Martinique,[114] Namibia,[123] Pakistan,[124] Saudi Arabia[125] Spain[126] and Syria.[127]

An unusually large number of cases of type 5a have been reported from Rhodes.[43]

التركيب الوراثي 6

21 subtypes of genotype 6 have been recognised. It is most common genotype in Asia and represents perhaps 1/3 of all cases.[128] It is found in Cambodia,[129] China (20% cases),[130] Hong Kong, India,[68] Indonesia,[131]Laos,[132] Myanmar (48% of cases),[133] Pakistan,[124] تايلند[134] and Vietnam (52% of cases).[135] It is also found in Americans and Australians[136] of Asian origin. It has occasionally been isolated in Canada[113] and Martinique.[114] It is a diverse genotype and now contains genotypes that were originally classified as genotypes 7, 8, 9 and 11.[131] It has been reported in Germany.[122] It has also been isolated in Turkey.[137]

In Thailand this type accounts for 20% of cases.[56]

التركيب الوراثي 7

هو من أحدث التركيبات الوراثية المعرفة والتركيب الوراثي المفرد الوحيد الموصوف حتى الآن.

المصادر

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