Reviewer's report 
 Hepatitis B virus infection in male volunteer blood donors in Karachi, Pakistan Title: 
 1  18 February 2005 Version: Date: 
 Keith Sabin Reviewer: 
Reviewer's report: 
General 
The manuscript presents the analysis of data collected in a case-control study of HBV infection from 
blood donors in Karachi, Pakistan. This is a useful area of inquiry for directing appropriate 
prevention activities. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached): 
There are several serious problems with this manuscript that I hope could be overcome but that is 
dependent on what data were collected and are available to the authors. 
Throughout the paper, the authors refer to HBV seroprevalence or HBV infection, and this is 
misleading. It only becomes clear what they are actually measuring, chronic HB infection, in the Methods section where they state that only HBsAg results are used. This is an important condition to 
understand because it represents the pool of infectious people in the community. However, at not 
point is this mentioned. Further, there is an assumption made in the prevalence rates that all people 
who do not test HBsAg+ are not infected and indeed susceptible to infection. What you report is the 
prevalence of chronic infection, but the denominator contains more than just susceptible people. It is 
important that, at a minimum, test results for total anti-HBc be included in these analyses. This would 
represent all people who were ever infected with HBV, of whom the HBsAg+ folks are likely a small 
subset. The people with anti-HBc+ results have resolved infections and are not susceptible to future infection and should be reported separately if the real interest is in seroprevalence. Further, chronic 
HBV infection is generally, more commonly the result of infection in early childhood. From birth to 
age 10, the risk of developing a chronic HB infection reduces geometrically. Chronic infection resulting from acute infection in adulthood is known but not common, relative to childhood infection. It would not be surprising that the risks that led to chronic infection occurred during childhood, either 
at birth or during the first 10 years of life. Therefore, measures of association for exposures in the 
recent past have little meaning. Also, case-control studies typically are statistically founded on incident cases. Since these are clearly prevalent cases, the measures of association should be adjusted to become prevalence ratios, not odds ratios. On the whole, while the significant findings 
are completely plausible, they could represent behaviors associated with SES or some other factor 
that remains similar from early childhood, e.g., a child who received a lot of injections is still receiving 
many injections as an adult. I suggest that the analyses be revisited and reconsidered given that this 
report is focused on chronic infection. The findings that chronically HB infected patients are 
receiving large numbers of injections suggests that they could be a potential source of infection for 
new, acute cases of HBV infection. 
Other issues: 
Is citation 3 actually Gaza, Germany or is it Gaza, Palestinian Authority? The latter, I think. 
Many of the citations seem inaccurate and need to be verified more closely. #8 discusses 
transmission modes in Pakistan but is cited as a global source, even though, vertical transmission is 
omitted from the list. 
Cite Lemon et al. (c. 1990, Lancet, I think) for horizontal transmission. 
On page 4, many of the citations on HBV are actually articles on HCV. Further, the final statement of 
the first paragraph is incorrect. High prevalence of history of HBV among HCC patients is expected 
anywhere in the world and is not suggestive of high prevalence in a country. High prevalence of 
HCC in a country would be suggestive of high prevalence of HBV/HCV in said country. 
Page 5, Methods: need to explain "exchange basis" because many readers will not know what this 
means. 
Page 8: Death of a family member due to liver disease is highly suggestive of transmission mode, if 
you know the family member (siblings = horizontal or vertical; spouse = sexual; parent = vertical, etc.) 
Page 12: Saliva is not a route of transmission for HBV 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Reviewer's report 
 Hepatitis B virus infection in male volunteer blood donors in Karachi, Pakistan Title: 
 1  18 February 2005 Version: Date: 
 Keith Sabin Reviewer: 
Reviewer's report: 
General 
The manuscript presents the analysis of data collected in a case-control study of HBV infection from 
blood donors in Karachi, Pakistan. This is a useful area of inquiry for directing appropriate 
prevention activities. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached): 
There are several serious problems with this manuscript that I hope could be overcome but that is 
dependent on what data were collected and are available to the authors. 
Throughout the paper, the authors refer to HBV seroprevalence or HBV infection, and this is 
misleading. It only becomes clear what they are actually measuring, chronic HB infection, in the Methods section where they state that only HBsAg results are used. This is an important condition to 
understand because it represents the pool of infectious people in the community. However, at not 
point is this mentioned. Further, there is an assumption made in the prevalence rates that all people 
who do not test HBsAg+ are not infected and indeed susceptible to infection. What you report is the 
prevalence of chronic infection, but the denominator contains more than just susceptible people. It is 
important that, at a minimum, test results for total anti-HBc be included in these analyses. This would 
represent all people who were ever infected with HBV, of whom the HBsAg+ folks are likely a small 
subset. The people with anti-HBc+ results have resolved infections and are not susceptible to future infection and should be reported separately if the real interest is in seroprevalence. Further, chronic 
HBV infection is generally, more commonly the result of infection in early childhood. From birth to 
age 10, the risk of developing a chronic HB infection reduces geometrically. Chronic infection resulting from acute infection in adulthood is known but not common, relative to childhood infection. It would not be surprising that the risks that led to chronic infection occurred during childhood, either 
at birth or during the first 10 years of life. Therefore, measures of association for exposures in the 
recent past have little meaning. Also, case-control studies typically are statistically founded on incident cases. Since these are clearly prevalent cases, the measures of association should be adjusted to become prevalence ratios, not odds ratios. On the whole, while the significant findings 
are completely plausible, they could represent behaviors associated with SES or some other factor 
that remains similar from early childhood, e.g., a child who received a lot of injections is still receiving 
many injections as an adult. I suggest that the analyses be revisited and reconsidered given that this 
report is focused on chronic infection. The findings that chronically HB infected patients are 
receiving large numbers of injections suggests that they could be a potential source of infection for 
new, acute cases of HBV infection. 
Other issues: 
Is citation 3 actually Gaza, Germany or is it Gaza, Palestinian Authority? The latter, I think. 
Many of the citations seem inaccurate and need to be verified more closely. #8 discusses 
transmission modes in Pakistan but is cited as a global source, even though, vertical transmission is 
omitted from the list. 
Cite Lemon et al. (c. 1990, Lancet, I think) for horizontal transmission. 
On page 4, many of the citations on HBV are actually articles on HCV. Further, the final statement of 
the first paragraph is incorrect. High prevalence of history of HBV among HCC patients is expected 
anywhere in the world and is not suggestive of high prevalence in a country. High prevalence of 
HCC in a country would be suggestive of high prevalence of HBV/HCV in said country. 
Page 5, Methods: need to explain "exchange basis" because many readers will not know what this 
means. 
Page 8: Death of a family member due to liver disease is highly suggestive of transmission mode, if 
you know the family member (siblings = horizontal or vertical; spouse = sexual; parent = vertical, etc.) 
Page 12: Saliva is not a route of transmission for HBV 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Please review this paper.
user
Reviewer's report 
 Hepatitis B virus infection in male volunteer blood donors in Karachi, Pakistan Title: 
 1  18 February 2005 Version: Date: 
 Keith Sabin Reviewer: 
Reviewer's report: 
General 
The manuscript presents the analysis of data collected in a case-control study of HBV infection from 
blood donors in Karachi, Pakistan. This is a useful area of inquiry for directing appropriate 
prevention activities. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached): 
There are several serious problems with this manuscript that I hope could be overcome but that is 
dependent on what data were collected and are available to the authors. 
Throughout the paper, the authors refer to HBV seroprevalence or HBV infection, and this is 
misleading. It only becomes clear what they are actually measuring, chronic HB infection, in the Methods section where they state that only HBsAg results are used. This is an important condition to 
understand because it represents the pool of infectious people in the community. However, at not 
point is this mentioned. Further, there is an assumption made in the prevalence rates that all people 
who do not test HBsAg+ are not infected and indeed susceptible to infection. What you report is the 
prevalence of chronic infection, but the denominator contains more than just susceptible people. It is 
important that, at a minimum, test results for total anti-HBc be included in these analyses. This would 
represent all people who were ever infected with HBV, of whom the HBsAg+ folks are likely a small 
subset. The people with anti-HBc+ results have resolved infections and are not susceptible to future infection and should be reported separately if the real interest is in seroprevalence. Further, chronic 
HBV infection is generally, more commonly the result of infection in early childhood. From birth to 
age 10, the risk of developing a chronic HB infection reduces geometrically. Chronic infection resulting from acute infection in adulthood is known but not common, relative to childhood infection. It would not be surprising that the risks that led to chronic infection occurred during childhood, either 
at birth or during the first 10 years of life. Therefore, measures of association for exposures in the 
recent past have little meaning. Also, case-control studies typically are statistically founded on incident cases. Since these are clearly prevalent cases, the measures of association should be adjusted to become prevalence ratios, not odds ratios. On the whole, while the significant findings 
are completely plausible, they could represent behaviors associated with SES or some other factor 
that remains similar from early childhood, e.g., a child who received a lot of injections is still receiving 
many injections as an adult. I suggest that the analyses be revisited and reconsidered given that this 
report is focused on chronic infection. The findings that chronically HB infected patients are 
receiving large numbers of injections suggests that they could be a potential source of infection for 
new, acute cases of HBV infection. 
Other issues: 
Is citation 3 actually Gaza, Germany or is it Gaza, Palestinian Authority? The latter, I think. 
Many of the citations seem inaccurate and need to be verified more closely. #8 discusses 
transmission modes in Pakistan but is cited as a global source, even though, vertical transmission is 
omitted from the list. 
Cite Lemon et al. (c. 1990, Lancet, I think) for horizontal transmission. 
On page 4, many of the citations on HBV are actually articles on HCV. Further, the final statement of 
the first paragraph is incorrect. High prevalence of history of HBV among HCC patients is expected 
anywhere in the world and is not suggestive of high prevalence in a country. High prevalence of 
HCC in a country would be suggestive of high prevalence of HBV/HCV in said country. 
Page 5, Methods: need to explain "exchange basis" because many readers will not know what this 
means. 
Page 8: Death of a family member due to liver disease is highly suggestive of transmission mode, if 
you know the family member (siblings = horizontal or vertical; spouse = sexual; parent = vertical, etc.) 
Page 12: Saliva is not a route of transmission for HBV 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant