Original Articles
 
Prevalence and mode of spread of hepatitis B and C in rural Sindh, Pakistan
 
Z Abbas, NL Jeswani, GN Kakepoto, M Islam, K Mehdi, W Jafri
Medicare Clinics, Departments of Paediatrics,
Pathology and Medicine,
The Aga Khan University Hospital
Karachi, Pakistan.


Corresponding Author
: Dr. Zaigham Abbas
Email: zaigham@akunet.org


Abstract

The aim of this study was to determine the prevalence and identify risk factors associated with the spread of hepatitis B and C in the rural areas of the upper Sindh Province, Pakistan. Included in this cross-sectional survey were 873 subjects belonging to 174 families residing in Jarwar, a small town of upper Sindh. A study using a systematic random sampling method was undertaken. One questionnaire per household was filled out and blood samples collected for hepatitis B surface antigen (HBsAg), hepatitis B core antibody total (HBcAb), and hepatitis C antibody (anti-HCV). HBsAg was reactive in 44 (5%), HBcAb in 494 (56.6%) and anti-HCV in 294 (33.7%). In the case control study, independent risk factors for exposure to hepatitis B were male sex, age greater than 16 years, absence of vaccination, previous history of jaundice, and family history of liver disease (adjusted odds ratios 1.4, 2.1, 1.7, 1.8 and 1.8, respectively). Independent risk factors for hepatitis C were age greater than 16 years, previous dental procedures, history of liver disease, lack of vaccination, and 10 or more injections in a year (adjusted odds ratios 3.7, 2.1, 2.4, 1.8 and 2.9, respectively). There was indication of intrafamilial and household clustering: for hepatitis C, parent to child p=0.001, sibling-tosibling p=0.046; for hepatitis B, spouse-to-spouse p=0.052 and parent to child p=0.001. In conclusion, there is high exposure to hepatitis B and C in upper Sindh. There is a need to educate people about hepatitis B vaccination and iatrogenic factors responsible for transmission. The study suggests the possibility of intrafamilial spread of these viruses.

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Pakistan is in a zone of intermediate endemicity for both hepatitis B and C with prevalence of 3-4% for hepatitis B and
4-6% for hepatitis C.[1,2,3] However in some areas of the country the prevalence is still very high. Hepatitis B virus (HBV) and C virus (HCV) infections may lead to cirrhosis and hepatocellular carcinoma and are major public health concerns in Pakistan. Hepatitis C has become a major health problem in developing countries, including Pakistan. The risk factors for the transmission of HCV infection may vary substantially between countries and within the same country.[4] The aim of this study was to determine the prevalence and identify the risk factors associated with the spread of hepatitis B and C in the rural areas of the upper Sindh Province, Pakistan.
 
Methods

Participants were inhabitants of Jarwar, a small agricultural town about 100 kilometers from Sukkur, a city in the upper part of the Sindh Province. Jarwar has a population of about 10,000 inhabitants, a mixed population of Sindhi-speaking Hindus and Muslims. People living in the town are affluent and more educated than in the neighboring villages. The town has one government hospital and many private clinics run by physicians, dispensers and quacks. The residents living in one sector of the town were invited to participate in this study.
 
Assuming that the prevalence of HBV and HCV in 15 % of the population Jawar (at 95% confidence level) with a bound error of estimation 5%, design effect of 1.5% and assuming 10% refusal we aimed to approach 755 individuals. Sampling was done by a systematic sampling method to include every 6th house. The first house was chosen based on simple random sampling. Where we were refused, the next household in the same direction was chosen instead. The sampling unit was all families (households) living together in a house. Trained social workers visited the homes to explain the purpose of the study and to invite the inhabitants and informed consent was obtained. For children less than 18 years of age, the head of the household gave the consent. An interviewer belonging to the same sex as the study subject administered a questionnaire on sociodemographic characteristics, and risk factors for hepatitis B and C infections. Parents, usually mothers, supplied information for children too young to reply themselves. The questionnaire explored the possible demographic, social and medical risk factors associated with hepatitis B and C. Demographic data included age, marital status, education status, monthly family income, household information, type of work, and duration of job. Social risk factors included sharing of toothbrush or razor at home, shave from barber-shop, tattooing, cautery, and ear piercing. History of injections included types of syringes, number of injections in the last year, whether a new syringe and needle were opened in front of the patient, condition of the dressing room, treatment by intravenous infusions and the responsible healthcare provider. Detailed medical history was taken and included history of hospitalisation, transfusion, previous surgery, and dental procedures. Finally, all the women were asked about their obstetric history including modes of delivery, abortion, healthcare provider, and obstetric procedures. We excluded infants of less than one year of age from the study as positive anti-HCV in infancy is a reflection of circulating maternal antibodies rather than true exposure.
 
5 mL of venous blood was drawn. The samples were centrifuged and stored at -20°C and transported on wet ice to the Abbott Laboratories in Karachi where sera were tested for HBsAg, hepatitis B core antibody total (anti-HBc) and anti-HCV using 3rd generation ELISA (Abbott). The subjects who were positive only for one viral antibody (anti-HCV or anti-HBc) were then compared with subjects negative for both, who were taken as controls. The serological results were provided to the subjects at completion and were kept strictly confidential.
 
Statistical analysis was done using SPSS package (Chicago, IL) version 11. Double data entry was done to ensure quality control. Mean and standard deviation (SD) were calculated for quantitative variables, and proportions for categorical variables. We used Yates corrected chi square test for dichotomous variables. Student’s t test was used to test the difference in the means of continuous variables when the distribution had homologous variance by the Bartlett’s test.
 
We compared patients who were HCV antibody positive but not anti-HBc antibody positive, with subjects negative for both antibodies. Similarly anti-HBc positive patients without anti-HCV positivity were compared with subjects negative for both antibodies to identify the risk factors. Simple logistic regression analysis was performed to measure association of outcome with each independent variable; odds ratios (OR) and 95% confidence intervals (CI) were calculated for each risk factor. Significant risk factors at the 25% level were entered in the multivariate logistic regression analysis to identify the independent risk factors for outcome. p value < 0.05 was considered statistical significant, all p values were two-sided.
 
Results
 
The sampling frame comprised 873 subjects belonging to 174 familial clusters, 471 (54%) male, age range 2-80 years, median age 25 years. There were 207 (23.7%) children up to 15 years of age. All patients belonged to the Sindhi ethnic group. The average monthly household income was 87 USD. Sixty-five percent were illiterate, 383 (44%) had received the hepatitis B vaccine. HBsAg was reactive in 44 (5%), and anti- HBc in 494 (56.6%). Anti-HCV antibody was positive in 294 (33.7%). Both anti-HCV and anti-HBc were positive in 214 (24.5%), either of two positive in 574 (65.8%) and both negative in 299 (34.2%). There were 80 (9.2%) subjects who were HCV antibody positive but not anti-HBc antibody positive, and 280 (32.1%) anti-HBc positive patients who were anti-HCV negative.
 
As seen in Figure 1, the prevalence of HCV antibodies increased with age to reach a peak in the age group of 31-50 years. Only one child of age less than 5 years had positive anti-HCV antibody (1/41=2.4%) while 7 children of this age group had anti-HBc (17.1%). Prevalence of these antibodies in children of age group 6-15 years was 11.5% (19/165) and 42.5% (70/165), respectively. In young adults between the ages of 16 and 30 years, the prevalence of hepatitis C and B antibodies further increased to 31.5% (119/378) and 55.8% (211/378), respectively. This upward trend continued in the age group of 31-50 years to 53.4% (124/232) and 55.8% (211/378), respectively. In subjects greater than 50 years the prevalence was 50.9% (27/53) and 81.1% (43/53). (Figures 1 and 2) Forty-four percent of the total population had received hepatitis B vaccination. This rate was 68.3% (28/41) for age up to 5 years.








On univariate analysis, of all risk factors, age = 16 years, previous history of hepatitis or jaundice, previous dental treatment, treatment by intravenous drips, more than 10 injections in one year (p=<0.001) and shave from barbers were associated with the risk of hepatitis C infection. (Table 3) Independent risk factors for hepatitis C were age = 16 years, previous dental procedure, and re-use of syringes as evident from the syringe jacket not being opened in front of the patient (adjusted odd ratios 6.1, 2.2, and 2.0, respectively). (Table 4) Table 5 and 6 depict the risk factors associated with coprevalence of anti-HCV and anti-HBc There was evidence of intrafamilial and household clustering: for hepatitis C, parentto-child p = 0.001, sibling-to-sibling p = 0.046; for hepatitis B, spouse-to-spouse p = 0.052 and parent-to-child p = 0.001. (Table 7)


















Discussion
Hepatitis B and C are two of the most prevalent public health problems worldwide and in Pakistan. A very high rate of exposure to HBV and HCV was found in this rural area of the upper Sindh province of Pakistan. This study explores the risk factors and routes of transmission accounting for this high prevalence. The prevalence of hepatitis B in Pakistan has dropped over the years from 10% to 4%.[1] This may be because of an increasing awareness about the vaccination and screening of blood for hepatitis B by blood banks. However the prevalence of hepatitis C has risen due to improper screening donors (due to the high cost of assay) and other modes of transmission. It is currently the major cause of liver disease-related mortality and morbidity in Pakistan with a large impact on healthcare.
 
As HBV and HCV have the same routes of transmission, dual infection may occur. Some of the significant risk factors identified by univariate analysis in this study, like dental treatment, intravenous infusion, and shave from barbers were common to both hepatitis B and C. Patients exposed to hepatitis B had not received the hepatitis B vaccine. The World Health Organisation has reported a worldwide prevalence of HCV positivity >10% in HBV-infected individuals.[5] Patients coinfected with both HBV and HCV may have more severe liver disease and higher mortality rates.[6,7] In our study one-fourth of the subjects showed evidence of exposure to both hepatitis B and C but most of them were HBsAg negative.
 
Local studies suggest that risk factors for HBV and HCV infections in this part of the world differ from those in the West. High poverty with low education level, unnecessary use of injections and re-use of syringes, and lack of knowledge of the modes of transmission of hepatitis are strong risk factors for these infections here. However, in most hepatitis patients, more than one risk factor is usually identified. In one study from upper Sindh, HCV was a leading cause of CLD.[8] The leading risk factor identified was the use of contaminated syringes. High prevalence of anti-HCV antibodies has been reported before from Hafizabad.[9] Re-used syringes and frequent therapeutic injections have been identified as major risk factors for hepatitis B and C in Pakistan.[9,10]
 
Re-use of disposable syringes and needles after soaking in the boiler or bowl with tepid water is common. In Pakistan, the proportion of injections per prescription is very high when compared to some other countries.[11,12,13] Giving intravenous drips, vitamin injections and antibiotics is common in the countryside. Lack of awareness of risks associated with injections and strong belief in the fast and powerful action of injections are driving injection overuse.[14] Parenteral drug administration is a good monetary incentive for practitioners as well. The number of injections given in the last few years is important.[15,16] In our study, subjects who received ten or more injections during the previous year had increased risk for HCV infection (adjusted OR = 2.9 95% CI: 1.6, 5.2).
 
Dental and medical procedures may carry a significant risk of hepatitis C and B infection.[17] The high prevalence of seropositivity for anti-HCV and anti-HBc in our study subjects with history of previous dental treatment stresses the importance of effective infection control methods to be practiced by dentists. Dental practice by unregistered practitioners is common in developing countries. These nonmedical personnel, and even some qualified dentists do not properly sterilise their equipment and thereby transmit bloodborne infections to their patients.[18,19] Improvement in basic hygiene and strict adherence to universal precautions is essential to prevent iatrogenic transmission of the infection. In Turkey, the most common risk factor for the transmission of HCV infection is surgery.[20]
 
There are significant nosocomial risk factors for hepatitis C transmission associated with clinical situations where patients receive blood.[21] In one study, anti-HCV frequency after one unit blood transfusion was almost the same (13.2%) as after multiple transfusions (15.4%).[22] A more sensitive immunoassay is required for blood donor screening for anti-HCV rather than the cheaper ICT tests used by many blood banks, particularly in rural areas. Equally important is the need for clear indications for single unit blood transfusion.
 
In our study getting a barber to shave you was identified as a risk factor for the transmission of hepatitis B and C similar to some other studies.[15,18,23,24] Barbers in rural areas use the same blade on different customers. They are mostly unaware that transmission of blood-borne pathogens like HBV, HCV and HIV can occur through shaving tools possibly through multiple small skin piercing injuries.[25] Both the customer and the barber himself are at risk of getting infected. In a study from Italy, tattooing, ear-piercing and barber shop shaving were associated with both types of parenterally transmitted hepatitides.[23] In another study conducted among barbers in China, the prevalence of HBsAg, anti-HBs and anti-HBc was 16.8%, 67.1% and 39.2%, respectively which was higher than that found in subjects with other professions such as employees of the departmental stores.[26] Therefore, health education programmes focusing on the barbers’ community may contribute to a reduction in the transmission of hepatitis.
 
In a local study done on 245 pregnant women, eight (3.3%) were tested positive for HBsAg.[27] All babies born to them were negative for hepatitis B. The authors concluded that vertical transmission in the early perinatal period is the least. In our study 7 children of age less than 5 years had anti-HBc (7/41=17.1%) while only one child had positive anti-HCV antibody (2.4%). Prevalence of these antibodies in children of age group 6-15 years was 42.5% (70/165) and 11.5% (19/165), respectively. It points to horizontal transmission during childhood rather than vertical transmission for these infections. The worldwide prevalence of HCV infection is relatively low in children, with an anti-HCV prevalence rate of 0.2%-0.4% in the Western world.[28] Blood transfusion is the principal route of transmission of HCV in children.[29] In our study, a child positive for HBcAb or anti-HCV was more likely to have an infected parent compared to an uninfected child, as also seen in some other studies.[16,30,31] This underscores the need to include vaccination against hepatitis B as part of the routine immunisation schedule for all age groups in this population. In our study, the probability of spouse-to-spouse transmission for HBV was higher when compared to HCV.
 
To conclude, there is high exposure to hepatitis B and C in almost epidemic proportions in the upper Sindh region, Pakistan. Independent risk factors for the transmission of these infections are family history, previous history of hepatitis, re-use of syringes, dental treatment, and shave from barbers. Intrafamilial clustering of cases may be due to inadvertent intrafamilial spread of these viruses or directly from the community. Due to the high cost of treatment of hepatitis B and C and the absence of a vaccine against the latter, the main focus should be on prevention.
 
There is a need to educate people about the iatrogenic factors responsible for the transmission of these infections and the importance of universal hepatitis B vaccination. Efforts should be made to discourage the unnecessary use of therapeutic injections and intravenous drips when alternate options are available; the re-use of unsterilised syringes, needles, blades and razors must be stopped. Surgical equipment needs to be sterile and proper screening of donated blood must be carried out. The HBV vaccination programme for neonates should be strictly implemented. High-risk groups should get tested for hepatitis B and C. It is very important, especially for health providers and policy makers, to recognise the risk factors involved in HCV and HBV infection and its co-infection with HDV in this area and design effective preventive programmes.
 
Acknowledgements
 
The study was funded by a grant from Getz Pharma. The sponsors did not have any role in the study process. There are no competing interests to declare.
 
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