Prevalence and risk factor assessment of Tropheryma whipplei in a rural community in Gabon: a community-based cross-sectional study M. Ramharter1,2,3, N. Harrison3, T. B€ uhler1,2, B. Herold3, H. Lagler3, F. L€ otsch1,3, G. Mombo-Ngoma1,2,4, C. M€ uller5, A. A. Adegnika1,2,6, P. G. Kremsner1,2 and A. Makristathis7 1) Centre de Recherches Medicales de Lambarene, H^opital Albert Schweitzer, Lambarene, Gabon, 2) Institut f€ur Tropenmedizin, Universit€at T€ubingen, T€ubingen, Germany, 3) Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria, 4) Departement de Parasitologie-Mycologie, Universite des Sciences de la Sante, Libreville, Gabon, 5) Division of Gastroenterology, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 6) Leiden University Medical Centre, Leiden, The Netherlands and 7) Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

Abstract Tropheryma whipplei is the causative agent of Whipple’s disease and has been detected in stools of asymptomatic carriers. Colonization has been associated with precarious hygienic conditions. There is a lack of knowledge about the epidemiology and transmission characteristics on a population level, so the aim of this study was to determine the overall and age-specific prevalence of T. whipplei and to identify risk factors for colonization. This molecular epidemiological survey was designed as a cross-sectional study in a rural community in Central African Gabon and inhabitants of the entire community were invited to participate. Overall prevalence assessed by real-time PCR and sequencing was 19.6% (95% CI 16–23.2%, n = 91) in 465 stool samples provided by the study participants. Younger age groups showed a significantly higher prevalence of T. whipplei colonization ranging from 40.0% (95% CI 27.8–52.2) among the 0–4 year olds to 36.4% (95% CI 26.1–46.6) among children aged 5–10 years. Prevalence decreased in older age groups (p 20 years (%) Sex, n (%) Female Male Nationality, n (%) Gabonese Others Not known Ethnicity, n (%) Bapunu Fang Nzebi Massango Others Not known Religion, n (%) Christian Muslim Traditional None Not known Tropheryma whipplei carriage, n (%) All age groups 0–4 years old 5–10 years old 11–20 years >20 years old a

24.7 25.8 23.4 65 88 95 217

(19.9)a (20.9)a (18.8)a (14) (18.9) (20.4) (46.7)

238 (51.2) 227 (48.8) 406 (87.3) 26 (5.6) 33 (7.1) 165 91 67 29 68 45

(35.5) (19.6) (14.4) (6.2) (14.6) (9.7)

336 10 18 46 55

(72.3) (2.1) (3.9) (9.9) (11.8)

91 26 32 12 21

(19.6) (40.0) (36.4) (12.6) (9.7)

Standard deviation.

A total of 117 households participated in this study with a mean of 4 (2.8) persons per household. No case of T. whipplei was recorded in 69 (59%) households and in 48 (41%) at least one case of T. whipplei was observed. Households with T. whipplei carriers were located randomly across the entire village. Household characteristics were analysed for risk factors associated with T. whipplei colonization. No association was found between households with or without T. whipplei carriers and factors including type of housing (wooden or concrete building) as well as the presence of a toilet, electricity, a refrigerator or the usage of different water sources (river, public well and rainwater; data not shown). Participants’ risk factors were assessed in univariate analysis indicating age, sex and number of people sharing a bed as significant risk factors for T. whipplei (Table 2). Multivariate logistic regression analysis demonstrated that increasing age was associated with reduced risk for T. whipplei with an odds ratio of 0.96/year (95% CI 0.94–0.97), while male sex had an odds ratio of 1.64 (95% CI 1.01–2.67) and was therefore associated with a higher risk of T. whipplei. The number of people sharing a bed was associated with infection by an odds ratio of 1.21 (95% CI 0.97–1.51) in multivariate analysis.

This study is one of the first attempting a molecular epidemiological survey to investigate the prevalence of T. whipplei on a community level in Africa. The high prevalence of 19.6% T. whipplei carriers among the asymptomatic general population of a rural village in Gabon is in line with previous results where the prevalence was 31.2% in two villages in rural Senegal [18]. Age-specific analysis revealed a high prevalence of carriage in children between 0–4 years (40%) and 5–10 years of age (36.4%), but significantly lower carriage rates in older children and young adults between 11 and 20 years of age (12.6%). Our data show comparatively lower rates of T. whipplei carriage in Gabon compared with the Senegalese study reporting up to 75% prevalence in children below the age of 5 years. Interestingly, the prevalence in the adult population (9.7%) was comparable to data from high-income countries including France where the prevalence in case series was reported to be between 4% in the general adult population and 12% in the high-risk population of sewer workers [12]. Finally, the comparatively higher prevalence of T. whipplei among children indicates that colonization may not persist for life and that maintenance of colonization in adulthood potentially necessitates repeated re-infections. However, the alternative explanation of this finding may be the long-term carriage of T. whipplei in certain individuals. Future prospective studies are needed to address this epidemiological question. Whereas our data confirm a higher risk of colonization with T. whipplei in children, our data also show an association between male sex and colonization. Whether this may be a result of increased exposure or higher susceptibility in our study population remains to be further investigated. The absence of associations between household characteristics including sanitation and T. whipplei carriage is in contrast to previous reports [19]. Although intuitively convincing, we

TABLE 2. Univariate and multivariate risk factor analysis for Tropheryma whipplei carriage

Risk factor Age Age >10 years Sex (male) Persons sharing bed Persons sharing household House type Toilet Electricity Fridge

Univariate analysis

Multivariate analysis


95% CI


95% CI

0.96 0.19 1.62 1.33 1.09 1.05 1.04 1.60 1.36

0.94–0.97 0.12–0.31 1.02–2.59 1.07–1.65 1.02–1.17 0.64–1.74 0.58–1.85 0.73–3.51 0.85–2.20

0.96 * 1.64 1.21 * * * * *

0.94–0.97 * 1.01–2.67 0.97–1.51 * * * * *

*Not included in multivariate logistic regression model.

ª2014 The Authors Clinical Microbiology and Infection ª2014 European Society of Clinical Microbiology and Infectious Diseases, CMI, 20, 1189–1194


Ramharter et al.

speculate that socio-economic differences were only minor in our study population and potential differences were further diluted by close social contacts between families. However, our data are supportive of a proposed person-to-person transmission, presumably favoured under poor sanitary conditions, as indicated by an association between number of persons sharing a bed and presence of T. whipplei. As a higher number of persons per bed was most often the result of multiple children sleeping in the same bed and as children are the most important risk group, this finding is in line with the overall epidemiological understanding of T. whipplei infection. The hypothesis of human-to-human transmission, most likely through a faecal–oral or oral–oral route, has also been proposed by a study conducted in France, where family members of patients with Whipple’s disease and of asymptomatic carriers were screened for T. whipplei. The family members had a higher prevalence of T. whipplei than the general population and in some families the same genotype was circulating, supporting the theory of intra-familial transmission of T. whipplei [24]. In our study we did not use genotyping to further investigate the possibility of transmission between family members as we had no cultures of T. whipplei available to employ this method. Our study did not assess the impact of diarrhoea on T. whipplei carriage in stool samples as reported previously [15]. Persons with acute diarrhoea provided stool samples only after recovery and therefore our data do not add information about the potential of T. whipplei as a diarrhoeagenic pathogen. Hence, our data demonstrate a high prevalence of T. whipplei among an asymptomatic population in rural Gabon and we conclude that asymptomatic T. whipplei carriage is very common in this part of Central Africa. The high prevalence among children suggests an increased risk for transmission during childhood with male sex and bed sharing constituting further risk factors associated with T. whipplei carriage.

Acknowledgements We are grateful for the enthusiastic support by the Gabonese field workers and the support by the community health workers in Bindo. The participation by the community of Bindo is greatly appreciated.

Author Contributions MR and AM designed and conducted the study, analysed the data and drafted the manuscript; NH, TB, BH, HL, FL, GMN,

Tropheryma whipplei epidemiology


CM, AAA and PGK contributed to study design, data analysis and drafting of the manuscript.

Funding We acknowledge financial funding for this study provided by the Austrian National Bank Anniversary Fund (grant number 13685). The work had logistical support from the Global Infectious Disease Control Association.

Transparency Declaration The authors report no competing interests.

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Prevalence and risk factor assessment of Tropheryma whipplei in a rural community in Gabon: a community-based cross-sectional study.

Tropheryma whipplei is the causative agent of Whipple's disease and has been detected in stools of asymptomatic carriers. Colonization has been associ...
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