Author s response to reviews Title: Prevalence of chronic hepatitis B virus infection and infrastructure for its diagnosis in Madagascar: implication for the WHO's elimination strategy Authors: Soa Fy ANDRIAMANDIMBY (soafy@pasteur.mg) Marie-Marie Olive (marie-marie.olive@cirad.fr) Yusuke Shimakawa (yusuke.shimakawa@gmail.com) Fanjasoa Rakotomanana (fanja@pasteur.mg) Iony Razanajatovo (ionyr@pasteur.mg) Tsarasoa Andrianinarivomanana (tsarasoa@pasteur.mg) Jea-Pierre Ravalohery (jpierre@pasteur.mg) Seta Andriamamonjy (seta@pasteur.mg) Christophe Rogier (christophe.rogier@gmail.com) Jean-Michel Heraud (jmheraud@pasteur.mg) Version: 3 Date: 19 Jul 2017 Author s response to reviews: Antananarivo, July 19th, 2017 Resubmission letter Dear Editor in Chief of BMC Public Health, Thank you very much for evaluation our manuscript entitled Prevalence of chronic hepatitis B virus infection and infrastructure for its diagnosis in Madagascar: implication for the WHO s elimination strategy (PUBH-D-16-02727R2). To our knowledge, this is the first report showing seroprevalence of chronical hepatitis B virus infection including representative samples collected from multiple areas spread out through the
country. Previous studies were controversial as these surveys were limited from one or two locations in the country or limited on at risk population. We discuss about epidemiological risk factor linked to seropositivity and provide proxies to define high risk area. Our result can be used for public health decision to achieve program elimination of hepatitis B. We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission to BMC Public Health. Yours Sincerely, Responses to reviewer s comments Brian T Montague, DO MS MPH (Reviewer 1): Thank you for the opportunity to review again your interesting work. Overall, the revisions made strengthen the manuscript significantly. There are still a few issues of concern in the current version, correction of which would strengthen the manuscript. 1) Reviewer reports: If the authors wish to present boh the infrastructure and serosurveys together in one manuscript, then the infrastructure survey needs to have a section in the methods and the results of that survey should be separated from the methods and included in the results portion. As it stands, the authors have combined the two in one paragraph with only single sentence description of the methods "We obtained the list of facilities with a capacity for HBV testing from the Ministry of Health in April 2016, and contacted someone who was responsible at each facility to provide the collected information." Appropriate to the methods discussion would be a description of how the assessment was made (informal interview vs survey or standardized questionnaire, if an interview was a guide used, if no guide how did they assure that the same information was collected for each site, etc.) The remainder of that paragraph which describes the results of the survey is appropriate to the results section
Author s response: Thank you for the useful comments. Now this has been clarified in the sub-section Infrastructure for HBV testing/treatment in Madagascar in the methods section as below: In April 2016, we first requested the Ministry of Health to generate a list of facilities including information on each of these items. Subsequently we verified the list by contacting a person responsible at each facility using a standardised questionnaire. (P 7, Line 145 and 146) 2) Reviewer reports: With regard to the WHO recommendations, I do not think that the authors summary statement fully captures the content of the guidelines. Statement: "Subsequently, the World Health Organization (WHO) has developed a strategy to eliminate HBV as a public health threat by 2030, aiming to reduce the incidence of new chronic infections by 90% and HBV-related mortality by 65%. Increasing the coverage of HBV testing and antiviral treatment became an important target [4], and the feasibility of "screen and treat" HBV program in resource-limited settings was recently demonstrated by the PROLIFICA project in West Africa." In the cite guideline treatment is presented as the last component of a multipronged strategy for hepatitis B control including 1) vaccines 2) PMTCT 3) blood safety 4) harm reduction 5) treatment. They summarize this approach for high burden settings as follows "For example, for hepatitis B virus epidemics, in certain countries with high prevalence of this virus, the most significant public health benefits are likely to be achieved by focusing efforts on reducing deaths by the prevention of early-life infection through birth-dose and childhood vaccination, and the treatment of people with chronic hepatitis infection." While the guidelines cite the Prolifica study, they do not offer that as the primary model for hepatitis B control. In review of the Prolifica study, it is important to note that it is not screen and treat all positives as the name would imply but rather linkage to assessment with treatment as indicated by the 2012 EASL guidelines.
It is true that adding the goal of treating those with chronic active hepatitis B is new, relatively, in resource limited settings where access has been a concern. The authors could capture this point but keep the bigger picture of hepatitis B control if the gave the overall recommended framework for hepatitis B control as above and then indicated the new addition of the goal of treatment of those with chronic active hepatitis to reduce hepatitis B morbidity and mortality. Author s response: We appreciate this comment. Now the statement related with WHO guidelines has been modified as below: Subsequently, the World Health Organization (WHO) has developed a strategy to eliminate HBV as a public health threat by 2030, aiming to reduce the incidence of new chronic infections by 90% and HBV-related mortality by 65%. Increasing the coverage of HBV testing and antiviral treatment became one of the important targets, and the feasibility of a community-based HBV screening and linkage to care with antiviral therapy in resource-limited settings was recently demonstrated by the PROLIFICA project in West Africa 3) Reviewer reports: the authors have retained the framing of the significance of this work soley in the context of Madagascar and it is interesting and clearly of local relevance. There is potential as mentioned in my prior comments to examine the larger relevance of what was found in Madagascar to similar resource limited, intermediate-high prevalence settings. Developing that aspect would make the manuscript of broader interest. Author s response: Indeed, it is very important to discuss the relevance of the work done in Madagascar to other context. We have modified conclusion as below: Our study demonstrated a higher seroprevalence of HBsAg in rural areas where the access to HBV testing is limited, and in people with a low SES who may be unable to pay for HBV testing and treatment. This clearly requires the need to decentralize the management of chronic HBV carriers in Madagascar by using simple and low-cost diagnostic tools. A similar exercise
deserves to be carried out in other low- and middle-income countries as this may help in designing an evidence-based national hepatitis plan.