Defining and targeting high-risk populations in Buruli ulcer–Authors' reply
Authors: Quentin B Vincent, Marie-Françoise Ardant, Laurent Marsollier, Annick Chauty, Alexandre Alcaïs
Journal: The Lancet Global Health (2014)

We thank Jordi Landier and colleagues for their comments about our recent Article in The Lancet Global Health.1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar In their work, Landier and coworkers generalise some of our observations on Buruli ulcer in Benin to those for Cameroon, the country that has the fifth highest prevalence of Buruli ulcer worldwide. Briefly, they make use of age and sex distribution from the Cameroon national census to show that patients aged 5–14 years were twice as likely to be affected by Buruli ulcer as older individuals; and that boys were over-represented in individuals younger than 15 years, women were over-represented in patients aged 15–50 years, and that men and women were equally represented in patients older than 50 years. They advocate the use of national census references to produce incidence rates and incidence rate ratios (IRRs), which they believe to be the proper way to draw valid conclusions.We agree that this method is an appropriate way to assess whether Buruli ulcer is over-represented in children, but this issue was not central to our study. We also felt that the introduction of external data, the quality of which we cannot assess and which might not be relevant to areas where Buruli ulcer is endemic—ie, remote rural areas of tropical countries—could lead to bias. Nevertheless, our Article reports that the median age of the population in Benin in 2010 is significantly higher than the median age of our cohort,1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar leading to the same conclusion as the IRRs. Landier and colleagues also define elderly people as a high incidence group. We would be cautious about this conclusion because their report and others do not provide the number of patients in each age group to assess the uncertainty of their measure.2Debacker M Aguiar J Steunou C et al.Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.Trop Med Int Health. 2004; 9: 1297-1304Crossref PubMed Scopus (72) Google Scholar As an example, consideration of the low number of patients older than 60 years in our study (one of the largest worldwide) enticed us not to draw conclusions in that age category. With respect to the variation of the sex ratio with age, we are mindful that the national census correction is correct but negligible, because the general population sex ratio does not differ from 1 in Benin, whatever the age group considered.3UN Department of Economic and Social AffairsPopulation divisionWorld population prospects: The 2012 revision; highlights and advance tables.http://esa.un.org/unpd/wpp/index.htmDate: 2013Google Scholar Therefore, Landier and colleagues reach the same overall conclusions as us, an extremely valuable confirmation.Landier and colleagues note, as we did, that unbalanced age-gender distribution among patients with Buruli ulcer had previously been reported. However, the reference they quote is misleading, because it does not identify differential incidence by sex before the age of 60 years.2Debacker M Aguiar J Steunou C et al.Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.Trop Med Int Health. 2004; 9: 1297-1304Crossref PubMed Scopus (72) Google Scholar The research group stated in a later 2009 review that “there are no sex differences in disease instance among children and adults”,4Portaels F Silva MT Meyers WM Buruli ulcer.Clin Dermatol. 2009; 27: 291-305Summary Full Text Full Text PDF PubMed Scopus (132) Google Scholar as did another independent review cited by Landier and colleagues.5Jacobsen KH Padgett JJ Risk factors for Mycobacterium ulcerans infection.Int J Infect Dis. 2010; 14: e677-e681Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar This is regrettable because this important issue of the variation of the sex ratio with age, although repeatedly reported in research articles on Buruli ulcer, has been disregarded or even denied by most authors of review papers4Portaels F Silva MT Meyers WM Buruli ulcer.Clin Dermatol. 2009; 27: 291-305Summary Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 5Jacobsen KH Padgett JJ Risk factors for Mycobacterium ulcerans infection.Int J Infect Dis. 2010; 14: e677-e681Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar (see discussion in our Article1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar for details). This denial has far too long hampered the research on the causes of this age-dependent variation of the sex-ratio in Buruli ulcer, understanding of which will be of great physiopathological, clinical, and, as pointed out by Landier and colleagues, public health relevance.We declare no competing interests. We thank staff at the Centre de Dépistage et de Traitement de l'Ulcère de Buruli, Pobè, Benin; staff of the Laboratoire de Bactériologie, CHU, Angers, France; and staff from the Institut National de la Santé et de la Recherche Médicale (INSERM) U1163 for helpful discussions; and acknowledge support from la Fondation Raoul Follereau. QBV acknowledges support from the Fondation Imagine. LM and AA acknowledge support from the Agence Nationale de la Recherche. AA acknowledges support from the Fondation pour la Recherche Médicale (grant number DMI20091117308) . AA and LM acknowledge support from INSERM. We thank Jordi Landier and colleagues for their comments about our recent Article in The Lancet Global Health.1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar In their work, Landier and coworkers generalise some of our observations on Buruli ulcer in Benin to those for Cameroon, the country that has the fifth highest prevalence of Buruli ulcer worldwide. Briefly, they make use of age and sex distribution from the Cameroon national census to show that patients aged 5–14 years were twice as likely to be affected by Buruli ulcer as older individuals; and that boys were over-represented in individuals younger than 15 years, women were over-represented in patients aged 15–50 years, and that men and women were equally represented in patients older than 50 years. They advocate the use of national census references to produce incidence rates and incidence rate ratios (IRRs), which they believe to be the proper way to draw valid conclusions. We agree that this method is an appropriate way to assess whether Buruli ulcer is over-represented in children, but this issue was not central to our study. We also felt that the introduction of external data, the quality of which we cannot assess and which might not be relevant to areas where Buruli ulcer is endemic—ie, remote rural areas of tropical countries—could lead to bias. Nevertheless, our Article reports that the median age of the population in Benin in 2010 is significantly higher than the median age of our cohort,1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar leading to the same conclusion as the IRRs. Landier and colleagues also define elderly people as a high incidence group. We would be cautious about this conclusion because their report and others do not provide the number of patients in each age group to assess the uncertainty of their measure.2Debacker M Aguiar J Steunou C et al.Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.Trop Med Int Health. 2004; 9: 1297-1304Crossref PubMed Scopus (72) Google Scholar As an example, consideration of the low number of patients older than 60 years in our study (one of the largest worldwide) enticed us not to draw conclusions in that age category. With respect to the variation of the sex ratio with age, we are mindful that the national census correction is correct but negligible, because the general population sex ratio does not differ from 1 in Benin, whatever the age group considered.3UN Department of Economic and Social AffairsPopulation divisionWorld population prospects: The 2012 revision; highlights and advance tables.http://esa.un.org/unpd/wpp/index.htmDate: 2013Google Scholar Therefore, Landier and colleagues reach the same overall conclusions as us, an extremely valuable confirmation. Landier and colleagues note, as we did, that unbalanced age-gender distribution among patients with Buruli ulcer had previously been reported. However, the reference they quote is misleading, because it does not identify differential incidence by sex before the age of 60 years.2Debacker M Aguiar J Steunou C et al.Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.Trop Med Int Health. 2004; 9: 1297-1304Crossref PubMed Scopus (72) Google Scholar The research group stated in a later 2009 review that “there are no sex differences in disease instance among children and adults”,4Portaels F Silva MT Meyers WM Buruli ulcer.Clin Dermatol. 2009; 27: 291-305Summary Full Text Full Text PDF PubMed Scopus (132) Google Scholar as did another independent review cited by Landier and colleagues.5Jacobsen KH Padgett JJ Risk factors for Mycobacterium ulcerans infection.Int J Infect Dis. 2010; 14: e677-e681Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar This is regrettable because this important issue of the variation of the sex ratio with age, although repeatedly reported in research articles on Buruli ulcer, has been disregarded or even denied by most authors of review papers4Portaels F Silva MT Meyers WM Buruli ulcer.Clin Dermatol. 2009; 27: 291-305Summary Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 5Jacobsen KH Padgett JJ Risk factors for Mycobacterium ulcerans infection.Int J Infect Dis. 2010; 14: e677-e681Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar (see discussion in our Article1Vincent QB Ardant MF Adeye A et al.Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study.Lancet Glob Health. 2014; 2: e422-e430Summary Full Text Full Text PDF Scopus (72) Google Scholar for details). This denial has far too long hampered the research on the causes of this age-dependent variation of the sex-ratio in Buruli ulcer, understanding of which will be of great physiopathological, clinical, and, as pointed out by Landier and colleagues, public health relevance. We declare no competing interests. We thank staff at the Centre de Dépistage et de Traitement de l'Ulcère de Buruli, Pobè, Benin; staff of the Laboratoire de Bactériologie, CHU, Angers, France; and staff from the Institut National de la Santé et de la Recherche Médicale (INSERM) U1163 for helpful discussions; and acknowledge support from la Fondation Raoul Follereau. QBV acknowledges support from the Fondation Imagine. LM and AA acknowledge support from the Agence Nationale de la Recherche. AA acknowledges support from the Fondation pour la Recherche Médicale (grant number DMI20091117308) . AA and LM acknowledge support from INSERM. Supplementary Material Download .pdf (.11 MB) Help with pdf files Supplementary appendix Download .pdf (.11 MB) Help with pdf files Supplementary appendix Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort studyOur findings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specific aspect in areas endemic for Buruli ulcer; and specific disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our findings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer. Full-Text PDF Open AccessDefining and targeting high-risk populations in Buruli ulcerIn their article in The Lancet Global Health, Quentin Vincent and colleagues (July issue)1 analysed 1227 laboratory-confirmed cases of Buruli ulcer and provided clinically relevant results such as an operational classification of lesions. They reported unbalanced age and sex groups, as previously noted,2 and an over-representation of Buruli ulcer cases in children. Quantification of this over-representation is challenging—proper comparisons between age groups need estimation of age-specific incidence rates, which are rarely reported. Full-Text PDF Open Access