Intrafamilial Transmission of HCV in Egypt: Causes and Implications

INTRAFAMILIAL TRANSMISSION OF HCV

By

Dr: Mahmoud El-Bendary Assistant Prof. of Tropical Medicine Mansoura Faculty of Medicine Mansoura University- EGYPT

Liver disease is a leading cause of morbidity and mortality among Egyptians. More than 900,000 patients are suffering from chronic liver disease. The major cause is infection with hepatitis C virus (HCV), with 70-140 thousand newly reported cases, annually. Furthermore, it is also prospected that the rate will reach its peak 2012

HCV is most efficiently transmitted primarily by parenteral routes: Blood transfusion. Transfusion of blood products. Shared needles. Hemodialysis. Tattooing. Needle sticks. Sharp instrument injuries.

Comparisons with other countries Global estimates of HCV ~ 200,000,000 persons. Under 2% total. Percent Prevalence USA ~ 1.8% Germany ~ 0 6%, Canada ~ 0 8% France ~ 1 1% Australia ~ 1 1% Japan ~ 1 5 2 3% -community micro epidemics Italy ~ 2 2% Egypt blood donors 10.8%

In patients with chronic HBV the virus can be transmitted both by vertical from mothers positive (HBsAg) and (HBeAg) and by horizontal (sexual and non-sexual) routes. Spouses and siblings of HBsAg-positive subjects are frequently found to have a high prevalence of serological markers of current or past HBV infection.

But the epidemiological relevance of intrafamilial transmission of HCV has not been clearly established. HCV has also been detected in persons in whom no clear risk factor has been defined, and these cases constitute about 40%-45% of HCV infections

These findings are probably related to the nature of HCV infection. In contrast to HBV, the titer of viral HCV in serum is low and detectable only after amplification by PCR . Moreover, HCV RNA titers in body fluids that might be vehicles for transmission, such as saliva, semen, vaginal fluids and urine, are very low, and may fluctuate (down to zero) during the course of HCV infection

However, a large proportion of patients who had not been exposed to any obvious risk factor were found to be infected with HCV . In these patients, intrafamilial and/or sexual transmission of the virus was suspected The occurrence of such transmission has been debated

In recent studies, strong correlations reported in Egyptian populations with HCV seroprevalence between first degree relatives. These correlations could be accounted for by a combination of specific modes of intrafamilial viral transmission and genetic predisposition to HCV infection

HOUSE HOLD SEXUAL VERTICAL

HOUSEHOLD CONTACTS

The environment can serve as a reservoir for infectious virus. HCV transmission by unapparent percutaneous exposures has been caused by cross-contamination from - reused needles and syringes. -multiple-use medication vials. - infusion bags, and injecting-drug instrument -Sharing razors and nail scissors between family members and patients An experimental study demonstrated that the infectivity of HCV in blood after exposure to drying and storage at room temperature (Kamili et al.,2007).

With the use of RT-PCR or bDNA techniques, HCVRNA has been detected in many systemic fluids other than in blood, including : Pritoneal effusion Seminal Vaginal secretion Urine & feces Typhoid secretion

Despite primary hepatotropism, HCV can affect tissues and organs such other than the liver as Kidneys, Thyroid, Salivary glands, Eyes, or The hematopoietic and lymphatic systems .

HCV genotyping between the index cases and infected family contacts can clarify whether the infection is acquired in or out of the family setting.

Intrafamilial HCV transmission is associated with the : Severity of liver disease in the index patients, The number of family members infected with HCV, The duration of exposure. Sexual contact with the index patient.

prevalence of HCV among relatives of asymptomatic index cases with that of relatives of index cases with CLD, underlined that: none of the family members of asymptomatic HCV positive patients was infected, while 9.4% of the relatives of subjects affected by CLD were HCV-positive.

SEXUAL TRANSMISSION

Transmission through sexual contacts has been implicated, although this may be a rather inefficient mode of transmission

The prevalence of positive anti- HCV in spouses is different.It was found that : -spouses of anti-HCV +ve patients were more likely to be infected with HCV than other family members -The infection rate increased with duration of marriage (more than 15 years ). -multiple sexual partners were a risk factor -Transmission rates ranging from 0.5 to 2% per year of relationship (Alter et al.,1989).

ON THE OTHER HAND long term monogamous relationships with a partner with chronic HCV have found little evidence for sexual transmission of HCV. (Terrault et al.,2002).

The CDC states that "data indicate overall that sexual transmission of HCV appears to occur, but that the virus is inefficiently spread through this manner. They do, however, call for further research into this controversial area(CDC1998).

VERTICAL TRANSMISSION

average rate of vertical HCV transmission appears to be approximately 5%. -Rates of vertical transmission are dependent upon five factors: -presence or absence of HCV RNA in the mother; -high or low HCV viral load; -HIV status of the mother; -Vaginal vs. caesarean delivery; -Breast vs. bottle feeding

In fact, the CDC and the American Academy of Pediatrics do not feel that there is a risk from either breast feeding or vaginal delivery and have chosen not to recommend caesarean section or bottle feeding to HCV-infected mothers without HIV (CDC 1998 )

STDF (according to the Presidential decree number (218-2007): is responsible for funding Scientific Research and Technological development, in a manner that supports the complete Cycle of innovation

HCV control research program-1 TC/2/Health/2009/hep

Multicenteric Study of Epidemiological Aspect in Intrafamilial Spread of HCV Infection and Genetic Susceptibility in Egyptian Population

In recent studies, strong correlations reported in Egyptian populations with HCV seroprevalence between first degree relatives. These correlations could be accounted for by a combination of specific modes of intrafamilial viral transmission and genetic predisposition to HCV infection

To identify the possible risk factors of transmission of HCV among Egyptian families investigate the transmission of HCV by genotyping and sub-genotyping of HCV RNA sequences and finally to investigate the role of genetic factors in HCV susceptibility.

A multicenter study involving 3 research centers (Upper & Lower Egypt) where : one Thousand HCV index cases and their families will be recruited from multicentric areas & will be subjected to HCV RNA quantification, genotyping, sequencing, and phylogenetic analysis. HLA genotyping for host DNA to ascertain genetic susceptibility.

The average size of Egyptian families around 4.5 0.5. ( ! 5000 cases) Positive cases of HCV antibodies and or HCV RNA will be served as cases group. All household member who are negative for either HCV antibodies and RNA by PCR will be served as ve control for comparative analysis.

Two questionnaires will be designed to be used in the structured interviews with the target participants at the virology unites to collect the actual data. The questionnaires will be tested through pilot survey with a group of similar participants.

Clinical include:- 1.Complete history taking and clinical examination 2.Routine blood Biochemical liver profile, Blood sugar and creatinine) 3.Viral markers for HBV HCV 4.Abdominal US 5.PCR testing 6.Genetic analysis and investigation sheet test (CBC,