Risk factors for Buruli ulcer, Benin.We identified risk factors for Buruli ulcer The Buruli ulcer (also known as the Bairnsdale ulcer) is an infectious disease caused by Mycobacterium ulcerans, from the same family of bacteria which causes tuberculosis and leprosy. (BU) in Benin in an unmatched case-control study case-control study,
n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. at the Centre Sanitaire et Nutritionnel Gbemoten in southern Benin. A total of 2,399 persons admitted from 1997 through 2003 and 1,444 unmatched patients with other conditions in 2002 were recruited. Adjusted odds ratios were determined for age, sex, place of residence, Mycobacterium bovis Mycobacterium bovis A mycobacterium that causes a TB-like infection in cows; before pasteurization was common, M bovis spread to humans via contaminated milk BCG BCG bacille Calmette-Guérin.
1. bacillus Calmette-Guérin
n.pr See bacille Calmette-Guórin. vaccination vaccination, means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms. at birth, type of water for domestic use, and occupation. Children <15 years of age and adults >49 years of age had a higher risk for BU. Use of unprotected water from swamps was associated with increased risk for BU; this association was strongest in adults >49 years of age. Sex was not a risk factor for BU. Our data showed that BU was mainly associated with age, place of residence, and water sources in all age groups. Risk for BU was higher in BCG-vaccinated patients [greater than or equal to] 5 years of age.
The World Health Organization (WHO) defines Buruli ulcer (BU) as "an infectious disease Infectious disease
A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. involving the skin, caused by Mycobacterium ulcerans Mycobacterium ulcerans (M. Ulcerans) is a slow-growing mycobacterium that classically infects the skin and subcutaneous tissues, giving rise to indolent nonulcerated (nodules, plaques) and ulcerated lesions. , characterized by a painless pain·less
Free from complication or pain: a painless operation.
painless·ly adv. nodule nodule: see concretion.
In geology, a rounded mineral concretion that is distinct from, and may be separated from, the formation in which it occurs. , papule papule /pap·ule/ (pap´ul) a small, circumscribed, solid, elevated lesion of the skin.pap´ular
n. pl. , plaque or edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. , evolving into a painless ulcer with undermined edges, often leading to invalidating in·val·i·date
tr.v. in·val·i·dat·ed, in·val·i·dat·ing, in·val·i·dates
To make invalid; nullify.
in·val sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention . Sometimes bones are destroyed." (1). After tuberculosis and leprosy leprosy or Hansen's disease (hăn`sənz), chronic, mildly infectious malady capable of producing, when untreated, various deformities and disfigurements. , BU is the third most common mycobacterial mycobacterial
emanating from or pertaining to mycobacterium.
may be caused by Mycobacterium tuberculosis (see cutaneous tuberculosis), M. disease (1). Incidences have increased recently, especially in West Africa West Africa
A region of western Africa between the Sahara Desert and the Gulf of Guinea. It was largely controlled by colonial powers until the 20th century.
West African adj. & n. (2-6). In 1997, WHO recognized BU as an emerging public health problem.
Classically, BU is a disease of rural areas and associated with wetlands. Endemic foci exist in tropical Africa Tropical African rain forests are tropical moist forests of semi-deciduous varieties distributed across nine West African countries -- Benin, Ghana, Guinea Bissau, Guinea, Ivory Coast, Liberia, Nigeria, Sierra Leone and Togo. , the Americas, Australia, and Asia (1,7,8). Epidemiologic observations concentrate on descriptive information or identification of new foci; however, few case-control studies have been published (2,3,9). Our objective was to assess sociodemographic variables and selected environmental factors associated with BU in Benin.
Patients and Methods
Benin is a West African West Africa
A region of western Africa between the Sahara Desert and the Gulf of Guinea. It was largely controlled by colonial powers until the 20th century.
West African adj. & n. country with 6,752,569 inhabitants
The game is based loosely on the concepts from SameGame. : 51% are female (Third General Census, 2002. unpub. data). The population is young: 48% are <15 years old. Benin was formerly divided into 6 regions (Atlantique, Mono, Borgou, Zou, Oueme, and Atacora); however, each region is now divided into 2 regions (Atlantique/Littoral, Mono/Couffo, Borgou/Alibori, Zou/Colline, Oueme/Plateau, and Atacora/Donga).
The Centre Sanitaire et Nutritionnel Gbemoten (CSNG) in Zou, Benin, is the regional referral center for BU treatment. From 1989 through 2003, CSNG treated >4,000 BU patients. This study included the period 1997-2003. The population of Zou in 2001 was 1,112,943.
Endemic foci of BU are associated with stagnant bodies of water (ponds, backwaters, and swamps). Data from the Benin Demographic and Health Survey (DHS DHS Department of Homeland Security (USA)
DHS Department of Human Services
DHS Department of Health Services
DHS Demographic and Health Surveys
DHS Dirhams (Morocco national currency) ) 2001 show that 34.5% of the Zou community drink unprotected water (rain water, unprotected well, surface water) (10). The sample size calculated with EpiInfo (Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. , Atlanta, GA, USA) was 147 cases and 147 hospital controls (control-case ratio 1, odds ratio [OR] [greater than or equal to] 2, proportion of exposition to unprotected water in controls 34.5%, power 80% [1 - [beta]], and 95% confidence level [alpha] = 0.05).
Since we had a large amount of data at our disposal, we analyzed the entire group of case-patients and all controls recruited during 6 months in 2002. The duration of enrollment of controls was limited to 6 months because of problems of availability of the healthcare staff.
All patients with suspected BU were examined by a physician (C.Z.) and the nurse (J.A.) in charge of the CNSG CNSG Commander, Naval Security Group (Command) . Historic and clinical data were recorded on standard forms. One or more of the following features suggested by WHO were used to diagnose BU (1): typical nodular nodular
marked with, or resembling, nodules.
see nodular fasciitis (below).
a firm painless nodular swelling, 0. , indurated in·du·rat·ed
Hardened, as a soft tissue that becomes extremely firm.
hardened; abnormally hard. plaque or edematous e·dem·a·tous
Marked by edema. lesion; [greater than or equal to] 1 painless chronic ulcers chronic ulcer
A long-standing ulcer with fibrous scar tissue at its base. with undermined edges or a depressed scar; swelling over a painful joint, suggesting bone involvement; slowly developing lesion (weeks or months); no fever or regional lymphadenopathy lymphadenopathy /lym·phad·e·nop·a·thy/ (-op´ah-the) disease of the lymph nodes.
angioimmunoblastic lymphadenopathy , angioimmunoblastic lymphadenopathy with dysproteinemia ; and residence or travel in a zone endemic for BU.
CSNG admitted 2,468 suspected BU patients from 1997 through 2003. Sixty-nine patients were excluded: 56 with recurrent cases and 13 with another definitive diagnosis; 2,399 patients with BU were enrolled in the study.
Hospital Control Recruitment
In 2002, controls were recruited among patients seen at CSNG for conditions other than BU: 21% had malaria, 6.0% had bronchitis bronchitis (brŏnkī`tĭs), inflammation of the mucous membrane of the bronchial tubes. It can be caused by viral or bacterial infections or by allergic reactions to irritants such as tobacco smoke. , 5.6% had rheumatism rheumatism (r`mətĭzəm), general term for a number of disorders that cause inflammation and pain in muscles, bones, joints, or nerves. , and 5.5% had parasitosis par·a·si·to·sis
n. pl. par·a·si·to·ses
Infestation with parasites.
a disease caused by a parasitic infestation. See also helminthiasis. . The frequency of all other conditions was <5%.
CSNG had 2 types of clinics: 1 for persons <5 years old and 1 for all others. Both clinics interviewed and examined people 3 times a week. For those [greater than or equal to] 5 years old (group 1), the head nurse interviewed all patients with a disease other than BU. For those <5 years old (group 2), the parents or a guardian of 5 subjects were interviewed from each clinic. This method generated an unmatched control group of 1,444 persons.
The Ethical Committee of Benin approved this study. All persons or their mothers or guardians received information about the disease and its treatment. All BU cases and controls received treatment. Verbal consent was obtained from participants or their parents or guardians.
Data were available from case files; information on the same variables was collected from controls. Data were then analyzed to identify potential risk factors for BU. All data on age, sex, region of residence, occupational activity, Mycobacterium mycobacterium
Any of the rod-shaped bacteria that make up the genus Mycobacterium. The two most important species cause tuberculosis and leprosy in humans; another species causes tuberculosis in both cattle and humans. boris BCG scar status, and type of domestic water used were recorded during the clinical examination.
Water sources were categorized cat·e·go·rize
tr.v. cat·e·go·rized, cat·e·go·riz·ing, cat·e·go·riz·es
To put into a category or categories; classify.
cat into 4 groups: pumped water, river, mixed sources (pumped and river), and swamps. The 4 groups were classified into 2 groups: protected water (pumped) and unprotected water (all other sources). Residences were categorized as Zou, Oueme, and other.
A total of 525 children were in group 1:339 BU cases and 186 controls. Complete data, except water sources, were available for 339 persons (case-patients and controls). These persons were analyzed by logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. . When water source was entered into the model, this number decreased to 246. Age was divided into 3 groups: <1 year, 1-2 years, and 3-4 years. Occupation was not introduced into the model for children <5 years of age.
Group 2 had 3,252 persons: 2,032 BU patients and 1,220 controls. Because data were missing for 930 persons (775 BU patients and 155 controls), 2,322 persons were analyzed by logistic regression. This number was reduced to 1,775 and 1,332 persons, respectively, when water sources and water sources or activities were introduced into the model. Age was divided into 4 groups based on the ORs shown in Table 1: 5-14 years, 15-29 years, 30-49 years, and [greater than or equal to] 50 years. Occupation was grouped as follows: attending or not attending school (for school-age persons), farmer, housewife, and other (e.g., salesperson, tailor, hairdresser, or teacher).
Data were analyzed with SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. version 9.05 (SPSS Inc., Chicago, IL, USA) and EpiInfo version 6.02. Because of the selection method of controls in the clinic for children, control children <5 years old were underrepresented un·der·rep·re·sent·ed
Insufficiently or inadequately represented: the underrepresented minority groups, ignored by the government. , and analysis was performed separately for these children. Crude ORs and 95% confidence intervals confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. (CIs) were calculated to evaluate the association between BU and various factors. Contingency tables contingency table
A statistical table that shows the observed frequencies of data elements classified according to two variables, with the rows indicating one variable and the columns indicating the other variable. were analyzed with the Pearson [chi square chi square (kī),
n a nonparametric statistic used with discrete data in the form of frequency count (nominal data) or percentages or proportions that can be reduced to frequencies. ] test.
A backward elimination procedure, based on likelihood ratio, was used to select variables to include in logistic regression models. Because age and occupation were correlated (Spearman spear·man
A man, especially a soldier, armed with a spear. [rho] = 0.626), we introduced either age or occupation into the logistic models logistic models,
n.pl statistical models that describe the relationship between a qualitative dependent variable (that is, one that can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. . Some interactions were tested in the logistic model including age with the likelihood ratio test. Interaction between age and water source appeared significant; thus, separate logistic models were established for each age category. Because sex and occupation were virtually redundant (e.g., female and housewife), models including occupation were established separately for each sex. Adjusted ORs and 95% CIs were derived from the final logistic models. For these models, goodness of fit Goodness of fit means how well a statistical model fits a set of observations. Measures of goodness of fit typically summarize the discrepancy between observed values and the values expected under the model in question. Such measures can be used in statistical hypothesis testing, e. was assessed with the Hosmer and Lemeshow test.
Table 2 shows results of univariate analysis for group 1 (crude ORs and 95% CIs). Age, place of residence, and water sources were associated with BU. Sex was not associated with BU. The risk for BU was [approximately equal to] 3x higher in children without a BCG scar. BU was associated with having a BCG scar (p = 0.047). Risk for BU was particularly high when the water source was a swamp compared with pumped water (OR 47.59, 95% CI 13.76-164.61).
Table 3 shows results of multivariate analysis multivariate analysis,
n a statistical approach used to evaluate multiple variables.
n a set of techniques used when variation in several variables has to be studied simultaneously. for group 1. In this model, age, place of residence, and water sources were associated with BU. The risk for BU was high in children 3-4 years old (OR 6.74, 95% CI 2.67-17.03), those living in Oueme (OR 2.78, 95% CI 1.35-5.70) or other places (OR 9.74, 95% CI 2.27-41.76), and those using unprotected water (OR 2.27, 95% CI 1.22-4.22). Sex and a BCG scar were not associated with BU.
Table 1 shows distribution of case-patients and controls by age group. The age groups used (5-14, 15-29, 30-49, and [greater than or equal to] 50 years) were based on the crude ORs found. The 30- to 49-year age group had the lowest risk for BU.
Table 4 shows results of univariate analyses for persons [greater than or equal to] 5 years old. All variables were associated with BU infection. Risk for BU was highest in persons using mixed sources of water (OR 16.72, 95% CI 10.63-26.31). The risk for BU in those using river water was similar to that of those using swamp water. When water sources were classified as protected and unprotected water, the OR was 5.15 (95% CI 4.22-6.28) for those using unprotected water.
In the 5-14-year age group, no difference concerning schooling was observed between case-patients and controls. In those >14 years old, more controls were housewives than were case-patients (28.5% vs. 2.6%), and more case-patients were farmers than were controls (49.4% vs. 29.0%).
Univariate analyses by sex and occupation showed that in males, being school age and being a farmer produced the higher risk for BU (data not shown). Young boys (independent of school attendance) had the greatest risk. In females, school-age girls and farmers had similar risks for BU, but housewives had the lowest risk (data not shown).
Table 5 shows results of logistic regression analyses of risk factors for BU in persons [greater than or equal to] 5 years old. Occupation was excluded because it correlated with age. The model included age, BCG scar, place of residence, and water sources but excluded sex (not significant). When adjusted for other variables, children 5-14 years old had a higher risk for BU (OR 11.64, 95% CI 8.01-16.91). The OR (95% CI 3.04-6.27) for BU was 4.36 in those [greater than or equal to] 50 years old. Risk for BU was associated with exposure to unprotected water sources (OR 4.62, 95% CI 3.61-5.90). Absence of a BCG scar decreased the risk for BU (OR 0.40, 95% CI 0.31-0.52). Living a greater distance from CSNG was strongly associated with an increased risk for BU (OR 13.02, 95% CI 8.03-21.11).
Logistic regression showed a strong interaction between age and water source. Thus, a logistic model was produced for each age group. Adjusted ORs and 95% CIs derived from models in the different age groups showed that absence of a BCG scar decreased the risk for BU in all age groups (data not shown). Risk for BU associated with residence of patients was reduced in those [greater than or equal to] 50 years old. BU patients were 1.94 x more likely than controls to use unprotected water (OR 1.94, 95% CI 1.20-3.12), and ORs were at least twice those in other age groups (data not shown).
Final results of multivariate The use of multiple variables in a forecasting model. analyses by sex and occupation in patients [greater than or equal to] 5 years old showed that the risk for BU was similar in both sexes for the following factors: BCG scar, place of residence, and water sources (data not shown). Risk for BU in boys was strongly associated with school age (OR 4.63, 95% CI 2.63-8.15). This risk was lower in girls (OR 2.75, 95% CI 1.59-4.76). Risk in female farmers was strongly increased (OR 3.51, 95% CI 1.97-6.26). Housewives showed a strong decreased risk for BU (OR 0.06, 95% CI 0.03-0.13).
This is the first large case-control study to describe sociodemographic and environmental factors associated with BU. Our data show that BU was associated with age, place of residence, and water sources for all persons, and that BU was associated with a BCG scar in persons [greater than or equal to] 5 years old.
In accordance with previous studies (1-3,11), the risk for BU was higher in children <15 years old. Children 3-4 years old had an increased risk for BU if they used unprotected water and lived in areas endemic for BU. That clothing provides protection against BU has already been reported in Cote d'Ivoire (3). In Africa, infants [less than or equal to] 1 year of age are often protected by clothes, bonnets, and booties. At [approximately equal to] 1-2 years of age, children begin to walk and play in dirt near their home, and those 3-4 years of age are more independent and roam freely in the environment, usually scantily scant·y
adj. scant·i·er, scant·i·est
1. Barely sufficient or adequate.
2. Insufficient, as in extent or degree.
scant clothed clothe
tr.v. clothed or clad , cloth·ing, clothes
1. To put clothes on; dress.
2. To provide clothes for.
3. To cover as if with clothing. , which increases exposure to a contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. environment. Use of unprotected water increases BU risk (OR >40), especially in children <5 years old. These associations have been previously reported (9,12,13). Molecular studies showed M. ulcerans in water, mud, fish, aquatic insects Aquatic insects live some portion of their life cycle in the water. They feed in the same ways as other insects. Some diving insects, such as predatory diving beetles, can hunt for food underwater where land-living insects cannot compete. , and snails from swamps in regions endemic for BU (14-18). Material from swamps, ponds, or river regions may contaminate con·tam·i·nate
1. To make impure or unclean by contact or mixture.
2. To expose to or permeate with radioactivity.
con·tam·i·nant n. skin surfaces with M. ulcerans, which can result in introduction of the causative caus·a·tive
1. Functioning as an agent or cause.
2. Expressing causation. Used of a verb or verbal affix.
caus agent into skin when it is broken by trauma or insect bites (15,19).
Children 5-14 years old and persons >49 years old were at higher risk for BU. Their attire and contact with environmental sources of M. ulcerans may be a relevant factor. Elderly persons through repeated episodes of exposure to M. ulcerans may acquire latent infections that are reactivated by age-related immunosuppression immunosuppression
Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects. . Results from the logistic model in the [greater than or equal to] 50-year age group support this concept. In this age group, risk for BU showed a lower correlation with unprotected water than in other age groups.
Although adults 15-49 years old are frequently exposed to wetlands, their risk for BU was lower, which suggests acquired resistance to the disease. We speculate that this resistance may be related to acquired specific immunity specific immunity
Immunity against a specific antigen or disease. or to cross-immunity from other mycobacterioses (20).
We previously reported that men >59 years old in Zou had a higher risk for BU than women, but men and women in the <59-year-old group were equally at risk (11). Our present study did not confirm sex differences in either those >50 or [less than or equal to] 50 years of age. These 2 studies differ in design: the earlier study (11) of the general population of Zou showed that 43% were boys and men. In this study, the percentage of male control subjects was slightly higher (47%) and may suggest that no differences in risk exist. The percentages of school-age and nonschool-age male BU patients increased relative to controls, while the percentages of female farmers and school-age and nonschoolage girls were nearly equal. Although we did not evaluate specific work or duties, girls often carry water and perform other tasks, but young boys usually play and frequent contaminated environments. Reduced risk for BU in housewives may be related to their reduced contact with contaminated environments. Differences between age and occupation may reflect differences in age-specific frequency and intensity of exposure to M. ulcerans.
From 1997 to 2001, CSNG received patients mainly from the Zou Region (6). Few patients come to CSNG from remote areas for treatment of diseases other than BU. The total number of BU patients is likely underestimated because of complex socioeconomic factors involved in care seeking and treatment of chronic diseases such as BU (21).
Studies that evaluated the presence or absence of BCG scars to determine vaccination status reported that scars develop in most vaccinated persons (22,23). No association was found between BU and BCG status in children <5 years old after adjustment for age. In persons [greater than or equal to] 5 years old, a BCG scar resulted in a risk factor of 2.5 for BU compared with those without a BCG scar (Table 5). Our results differ from those of 2 prospective studies that reported that BCG vaccination partially protects against BU (24,25). However, this protection seemingly decreased after 6 months (24).
In children in Benin [greater than or equal to] 5 years old, a BCG scar may represent a risk factor for BU. Vaccination may rarely introduce M. ulcerans intradermally in·tra·der·mal
Within or between the layers of the skin: an intradermal injection.
in from contaminated skin (26). At CSNG, BU developed in several patients at the site of BCG vaccination (J. Aguiar, C. Steunou, C. Zinsou, unpub, data).
The efficacy of BCG in preventing dissemination dissemination Medtalk The spread of a pernicious process–eg, CA, acute infection Oncology Metastasis, see there of tuberculosis in children is well known (27). BCG vaccination at birth also provides protection against the development of M. ulcerans osteomyelitis osteomyelitis (ŏs'tēōmī'əlī`tĭs), infection of the bone and bone marrow. Direct infection of bone usually occurs through open fractures, penetrating wounds, or surgical operations. (28,29). The disparity in the results of our case-control study may reflect known variations of efficacy of BCG (30). Factors related to host and the causative agent may explain varying protection of BCG against BU (31). An alternative explanation is variation of BCG coverage for controls (general population or hospital controls) compared with BU patients (32). From 1993 to 1999, BCG vaccination coverage in Zou was stable ([approximately equal to] 90%-100%). A matched case-control study in Benin of neighborhood controls and BU cases to assess the efficacy of BCG vaccination at birth is in progress. This ongoing study will evaluate the validity of our findings (33).
Cases and controls are likely to have similar equal exposures to environmental transmission factors for BU. Results of our study are consistent when comparing data from other regions in Benin or only from Zou.
This case-control study confirms findings of previous studies, which indicated that children < 15 years of age are at highest risk for acquiring BU (1,6), and that in areas endemic for BU, exposure to unprotected water is a risk factor for the disease. (1,14). Our study demonstrates that the association between BU and exposure to unprotected water is not as strong in patients [greater than or equal to] 50 years of age than in other age groups. This suggests that BU in older people may be related to reactivation reactivation
to become active after a period of quiescence or, as in bacterial and viral infections, latency.
cross reactivation of latent infections by M. ulcerans. This study also demonstrates differences between sexes, which may be associated with age-influenced domestic, agricultural, and recreational activities. BCG vaccination is a risk factor for BU in persons [greater than or equal to] 5 years old. Because of the diversity of conditions encountered among controls, we do not believe that these conditions have influenced our results.
Programs for provision of protected water for drinking and domestic use would have the greatest effect on control of BU in Benin. This effect could be accomplished by drilling wells and supplying pumps. Appropriate educational programs that promote behavioral changes should also reduce the frequency of BU.
We thank all personnel at the Centre Sanitaire et Nutritionnel for their contributions to the study.
This work was partly supported by the Damien Foundation (Brussels, Belgium), the General Directorate for the International Cooperation (Brussels, Belgium. Project: Buruli Ulcer in Benin) and the American Registry of Pathology (Washington DC, USA).
(1.) World Health Organization. Buruli ulcer-Mycobacterium ulcerans infection. In: Asiedu K, Scherpbier R, Raviglione M, editors. WHO/CDS/CPE/GBUI/2000.1. Geneva Geneva, canton and city, Switzerland
Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : The Organization; 2000. p.9-14.
(2.) Amofah GK, Sagoe-Moses C, Frimpong EH. Epidemiology of Buruli ulcer in Amansie, West District, Ghana. Trans R Soe Trop Med Hyg. 1993;87:644-5.
(3.) Marston BJ, Diallo MO, Horsburgh R, Ostroff SM, Good RC. Emergence of Buruli ulcer disease in the Daloa region of Cote d'Ivoire. Am J Trop Med Hyg. 1995;52:219-24.
(4.) Josse R, Guedenon A, Darie H, Anagonou S, Portaels F, Meyers WM. Les infections cutanees a Mycobacterium ulcerans: ulceres de Buruli. Med Trop (Mars). 1995;55:363-73.
(5.) Aguiar J, Domingo MC, Guedenon A, Meyers WM, Steunou C, Portaels F. L'ulcere de Buruli, une maladie mycobacterienne importante et en recrudescence recrudescence /re·cru·des·cence/ (re?kroo-des´ens) recurrence of symptoms after temporary abatement.recrudes´cent
n. au Benin. Bull Seances Acad R Sci Outre ou·tré
Highly unconventional; eccentric or bizarre: "outré and affected stage antics" Michael Heaton. Mer. 1997;3:325-56.
(6.) Debacker M, Aguiar J, Steunou C, Zinsou C, Meyers WM, Guedenon A, et al. Mycobacterium ulcerans disease (Buruli ulcer) in a rural hospital, southern Benin, 1997-2001. Emerg Infect infect /in·fect/ (in-fekt´)
1. to invade and produce infection in.
2. to transmit a pathogen or disease to.
1. Dis. 2004;10:1391-8.
(7.) Tsukamura M, Mikoshiba H. A new Mycobacterium which caused skin infection. Microbiol Immunol. 1982;26:951-5.
(8.) Faber WR, Peirera Arias-Bouda LM, Zeegelaar JE, Kolk AHJ AHJ Authority Having Jurisdiction
AHJ American Heart Journal
AHJ Authority Housing Jurisdiction
AHJ Alternative Health Journal , Fonteyne P-A, Toonstra J, et al. First reported case of Mycobacterium ulcerans infection in a patient from China. Trans R Soc Trop Med Hyg. 2000;94:277-9.
(9.) Aiga H, Amano T, Cairncross S Cairncross can refer to the following people, and is a not uncommon name of Scottish origin:
American composer and theatrical producer whose best known Broadway productions include Sweet Charity (1966) and The Will Rogers Follies (1991). . Assessing water-related risk factors for Buruli ulcer: a case-control study in Ghana. Am J Trop Med Hyg. 2004;71:387-92.
(10.) Benin Demographic and Health Survey. 2003. [cited 29 Jun 2006]. Available from http://www.measuredhs.com/pubs /pdftoc.cfm?ID=366&PgName=country.cfm0ctry_id=52
(11.) Debacker M, Aguiar J, Steunou C, Zinsou C, Meyers WM, Scott JT, et al. Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Trop Med Int Health. 2004;9:1297-304.
(12.) Lunn HF, Connor DH, Wilks NE, Barnley GR, Kamunvi F, Clancey JK, et al. Buruli (mycobacterial) ulceration ulceration /ul·cer·a·tion/ (ul?ser-a´shun)
1. the formation or development of an ulcer.
2. an ulcer.
1. Development of an ulcer.
2. in Uganda (a new focus of Buruli ulcer in Madi District, Uganda). East Afr Med J. 1965;42:275-88.
(13.) Uganda Buruli Group. Epidemiology of Mycobacterium ulcerans infection (Buruli ulcer) at Kinyara, Uganda. Trans R Soc Trop Med Hyg. 1971;65:763-75.
(14.) Johnson RC, Makoutode M, Sopoh GE, Elsen P, Gbovi J, Pouteau LH, et al. Buruli ulcer distribution in Benin. Emerg Infect Dis. 2005;11:500-1.
(15.) Portaels F, Elsen P, Guimaraes-Peres A, Fonteyne P-A, Meyers WM. Insects in the transmission of Mycobacterium ulcerans infection. Lancet lancet /lan·cet/ (lan´set) a small, pointed, two-edged surgical knife.
n. . 1999;353:986.
(16.) Portaels F, Chemlal K, Elsen P, Johnson PD, Hayman JA, Kirkwood R, et al. Mycobacterium ulcerans in wild animals WILD ANIMALS. Animals in a state of nature; animals ferae naturae. Vide Animals; Ferae naturae. . In: Collins MT, Manning B, editors. Mycobacterial infections in domestic and wild animals. Vol. 20. Paris: Office International de Epizooties. Scientific and Technical Review; 2001. p. 252-64.
(17.) Eddyani M, Ofori-Adjei D, Teugels G, de Weirdt D, Boakye D, Meyers WM, et al. Potential role for fish in transmission of Mycobacterium ulcerans disease (Buruli ulcer): an environmental study. Appl Environ Microbiol. 2004;70:5679-81.
(18.) Marsollier L, Severin T, Aubry J, Merritt RW, Saint Andre JP, Legras P, et al. Aquatic snails, passive hosts of Mycobacterium ulcerans. Appl Environ Microbiol. 2004;70:6296-8.
(19.) Meyers WM, Shelly WM, Connor DH, Meyers EK. Human Mycobacterium ulcerans infections developing at sites of trauma to skin. Am J Trop Med Hyg. 1974;23:919-23.
(20.) Smith JH. Epidemiologic observations on cases of Buruli ulcer seen in a hospital in the lower Congo. Am J Trop Med Hyg. 1970;19:657-43.
(21.) Amofah G, Bonsu F, Tetteh C, Okrah J, Asamoa K, Asiedu K, et al. Buruli ulcer in Ghana: results of a national case search. Emerg Infect Dis. 2002;8:167-70.
(22.) Floyd S Floyd is a variant spelling of the Welsh name Lloyd, which means grey, and may refer to: Places
(23.) Fine PE, Ponnighaus JM, Maine N. The distribution and implications of BCG scars in northern Malawi. Bull World Health Organ. 1989;67:35-42.
(24.) Uganda Buruli Group. BCG vaccination against Mycobacterium ulcerans infection (Buruli ulcer). Lancet. 1969;1:111-5.
(25.) Smith PG, Revill WD, Lukawgo E, Rykushin YP. The protective effect of BCG against Mycobacterium ulcerans disease: a controlled trial controlled trial Clinical research A clinical study in which one group of participants receives an experimental drug while the other receives either a placebo or an approved–'gold standard' therapy. See Blinding, Double-blinded. in an endemic area Endemic area
A geographical region where a particular disease is prevalent.
Mentioned in: Leprosy, Scrub Typhus of Uganda. Trans R Soc Trop Med Hyg. 1977;70:449-57.
(26.) Debacker M, Zinsou C, Aguiar J, Meyers WM, Portaels F. First case of Mycobacterium ulcerans disease (Burnli ulcer) following a human bite. Clin Infect Dis. 2003;36:e67-8.
(27.) World Health Organization. Issues related to the use of BCG in immunization immunization: see immunity; vaccination. programmes: a discussion document. Publication no. WHO/V + 13/99.23. Geneva: The Organization.
(28.) Portaels F, Aguiar J, Debacker M, Steunou C, Zinsou C, Guedenon A, et al. Prophylactic prophylactic /pro·phy·lac·tic/ (pro?-fi-lak´tik)
1. tending to ward off disease; pertaining to prophylaxis.
2. an agent that tends to ward off disease.
n. effect of Mycobacterium bovis BCG vaccination against osteomyelitis in children with Mycobacterium ulcerans disease (Buruli ulcer). Clin Diagn Lab Immunol. 2002;9:1389-41.
(29.) Portaels F, Aguiar J, Debacker M, Guedenon A, Steunou C, Zinsou C, et al. Mycobacterium bovis BCG vaccination as prophylaxis prophylaxis (prō'fĭlăk`sĭs), measures designed to prevent the occurrence of disease or its dissemination. Some examples of prophylaxis are immunization against serious diseases such as smallpox or diphtheria; quarantine to confine against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease. Infect Immun. 2004;72:62-5.
(30.) Fine PE. BCG: the challenge continues. Scand J Infect Dis. 2001;33:243-5.
(31.) Fenner F. Homologous homologous /ho·mol·o·gous/ (ho-mol´ah-gus)
1. corresponding in structure, position, origin, etc.
1. and heterologous heterologous /het·er·ol·o·gous/ (het?er-ol´ah-gus)
1. made up of tissue not normal to the part.
1. immunity in infections of mice with Mycobacterium ulcerans and Mycobacterium balnei Mycobacterium bal·ne·i
Mycobacterium marinum. . Am Rev Tuberc. 1957;76:76-89.
(32.) Wunsch-Filho V, Moncau JE, Nakao N. Methodological considerations in case-control studies to evaluate BCG vaccine BCG vaccine
A vaccine containing attenuated human tubercle bacilli that is used for immunization against tuberculosis. Also called tuberculosis vaccine. effectiveness. Int J Epidemiol. 1993;22:149-55.
(33.) Nackers F, Dramaix M, Johnson RC, Zinsou C, Robert A, et al. Mycobacterium BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin. Am J Trop Med Hyg. 2006: in press.
Martine Debacker, * Francoise Portaels, * Julia Aguiar, ([dagger]) Christian Steunou, ([dagger]) Claude Zinsou, ([dagger]) Wayne Meyers, ([double dagger double dagger
A reference mark () used in printing and writing. Also called diesis.
Noun 1. ]) and Michele Dramaix ([section])
* Institute of Tropical Medicine tropical medicine, study, diagnosis, treatment, and prevention of certain diseases prevalent in the tropics. The warmth and humidity of the tropics and the often unsanitary conditions under which so many people in those areas live contribute to the development and , Antwerp, Belgium; ([dagger]) Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin; ([double dagger]) Armed Forces Institute of Pathology Armed Forces Institute of Pathology A section of the US military which provides consultations, reference atlases and educational programs for pathologists , Washington, DC, USA; and ([section]) Universite Libre de Bruxelles, Brussels, Belgium
Dr Debacker is a researcher at the Institute of Tropical Medicine in Antwerp. Her research interests include epidemiologic, clinical, and microbiologic aspects of BU and multidrug-resistant tuberculosis.
Address for correspondence: Michele Dramaix, Ecole de Sante Publique, Universite Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium; email: email@example.com
Table 1. Distribution of cases of Buruli ulcer and controls by age, Centre Sanitaire et Nutritionnel Gbemoten, Zou, Benin * Age group, y Cases (%) Controls (%) Total 5-9 432 (21.3) 38 (3.1) 470 10-14 405 (19.9) 59 (4.8) 464 15-19 223 (11.0) 117 (9.6) 340 20-24 163 (8.0) 140 (11.5) 303 25-29 149 (7.3) 157 (12.9) 306 30-34 84 (4.1) 140 (11.5) 224 35-39 72 (3.5) 136 (11.1) 208 40-44 44 (2.2) 98 (8.0) 142 45-49 53 (2.6) 81 (6.6) 134 50-54 68 (3.3) 60 (4.9) 128 55-59 66 (3.2) 45 (3.7) 111 60-64 105 (5.2) 52 (4.3) 157 65-69 65 (3.2) 38 (3.1) 103 70-74 50 (2.5) 32 (2.6) 82 75-79 36 (1.8) 17 (1.4) 53 [greater than 17 (0.8) 10 (0.8) 27 or equal to] 80 Subtotal 2,032 1,220 3,252 Missing 367 224 591 Total 2,399 1,444 3,843 Age group, y Crude OR (95% CI) p value 5-9 6.69 (2.86-16.62) <0.001 10-14 4.4 (1.77-9.24) 0.002 15-19 1.12 (0.5-2.53) NS 20-24 0.68 (0.3-1.54) NS 25-29 0.56 (0.25-1.26) NS 30-34 0.35 (0.15-0.81) 0.010 35-39 0.31 (0.14-0.72) 0.0046 40-44 0.26 (0.11-0.62) 0.002 45-49 0.38 (0.16-0.9) 0.025 50-54 0.67 (0.28-1.57) NS 55-59 0.86 (0.36-2.06) NS 60-64 1.19 (0.51-2.78) NS 65-69 1.01 (0.42-2.42) NS 70-74 0.92 (0.37-2.26) NS 75-79 1.25 (0.47-3.29) NS [greater than 1 or equal to] 80 Subtotal Missing Total * OR, odds ratio; CI, confidence interval; NS, not significant. Table 2. Univariate analysis of risk factors for Buruli ulcer in children <5 years of age, Centre Sanitaire et Nutritionnel Gbemoten, Zou, Benin * Variable Cases (%) Controls (%) (n = 339) (n = 186) Age, y < 1 31 (9.1) 44 (23.7) 1-2 154 (45.4) 103 (55.4) 3-4 154 (45.4) 39 (21.0) Sex Female 169 (50.6) 85 (46.4) Male 165 (49.4) 98 (53.6) Mycobacterium bovis BCG scar Present 158 (92.4) 170 (97.1) Absent 13 (7.6) 5 (2.9) Region Zou 238 (70.2) 152 (81.7) Oueme 60 (17.7) 29 (15.6) Other 41 (12.1) 5 (2.7) Water sources Protected (pump) 29 (30.2) 92 (54.8) Unprotected (combined types) 67 (69.8) 76 (45.2) River 7 (7.3) 44 (26.2) Unprotected (mixed) 15 (15.6) 29 (17.3) Swamp 45 (46.9) 3 (1.8) Variable Crude OR 95% CI p value Age, y <0.001 < 1 1 1-2 2.12 1.26-3.58 3-4 5.60 3.14-10.00 Sex NS Female 1 Male 0.85 0.59-1.22 Mycobacterium bovis BCG scar 0.047 Present 1 Absent 2.80 0.98-8.03 Region 0.001 Zou 1 Oueme 1.32 0.81-2.15 Other 5.24 2.02-13.55 Water sources <0.001 Protected (pump) 1 Unprotected (combined types) 2.80 1.59-4.93 River 0.50 0.21-1.24 Unprotected (mixed) 1.64 0.77-3.47 Swamp 47.59 13.76-164.61 * OR, odds ratio; CI, confidence interval; NS, not significant. Table 3. Multivariate analysis of risk factors for Buruli ulcer in 246 children (87 case-patients and 159 controls) <5 years of age, Centre Sanitaire et Nutritionnel Gbemoten, Zou, Benin * Adjusted OR Variable ([dagger]) 95% CI p value Age, y <0.001 <1 1 1-2 1.58 0.62-3.97 3-4 6.74 2.67-17.03 Region <0.001 Zou 1 Oueme 2.78 1.35-5.70 Other 9.74 2.27-41.76 Water sources 0.010 Protected 1 Unprotected 2.27 1.22-4.22 * OR, odds ratio; CI, confidence interval. ([dagger]) Adjusted for effects of all variables included in the model. Nonsignificant variables were sex and Mycobacterium bovis BCG scar. Table 4. Univariate analysis of risk factors for Buruli ulcer in persons [greater than or equal to] 5 years of age, Centre Sanitaire et Nutritionnel Gbemoten, Zou, Benin * Cases (%) Controls (%) Crude Variable (n = 2,032) (n = 1,220) OR Age, y 5-14 837 (41.2) 97 (8.0) 15.52 15-29 535 (26.3) 414 (33.9) 2.32 30-49 253 (12.5) 455 (37.3) 1 [greater than or equal to] 50 407 (20.0) 254 (20.8) 2.88 Sex Female 986 (49.2) 675 (57.0) 1 Male 1,017 (50.8) 510 (43.0) 1.36 Mycobacterium bovis BCG scar Present 969 (75.6) 610 (55.7) 1 Absent 313 (24.4) 486 (44.3) 0.41 Region Zou 1,110 (54.6) 883 (72.4) 1 Oueme 575 (28.3) 298 (24.4) 1.53 Other 347 (17.1) 39 (3,2) 7.08 Water sources Protected (pump) 296 (36.2) 887 (74.5) 1 Unprotected (combined types) 522 (83.8) 297 (25.5) 5.15 River 75 (9.2) 47 (4.1) 4.67 Unprotected (mixed) 137 (16.7) 24 (2.1) 16.72 Swamp 310 (37.9) 226 (19.4) 4.02 Variable 95% CI p value Age, y <0.001 5-14 11.96-20.13 15-29 1.90-2.84 30-49 [greater than or equal to] 50 2.31-3.59 Sex <0.001 Female Male 1.18-1.57 Mycobacterium bovis BCG scar <0.001 Present Absent 0.34-0.48 Region <0.001 Zou Oueme 1.30-1.81 Other 5.02-9.97 Water sources <0.001 Protected (pump) Unprotected (combined types) 4.22-6.28 River 3.17-6.89 Unprotected (mixed) 10.63-26.31 Swamp 3.24-4.99 * OR, odds ratio; CI, confidence interval. Table 5. Logistic regression analysis of risk factors for Buruli ulcer in 1,775 persons (754 case-patients and 1,021 controls) [greater than or equal to] 5 years of age, Centre Sanitaire et Nutritionnel Gbemoten, Zou, Benin * Adjusted OR Variable ([dagger]) 95% CI p value Age, y <0.001 5-14 11.64 8.01-16.91 15-29 2.21 1.60-3.05 30-49 1 [greater than or equal to] 50 4.36 3.04-6.27 Mycobacterium <0.001 bovis BCG scar Present 1 Absent 0.40 0.31-0.52 Region <0.001 Zou 1 Oueme 4.02 3.09-5.24 Other 13.02 8.03-21.11 Water sources <0.001 Protected 1 Unprotected 4.62 3.61-5.90 * OR, odds ratio; CI, confidence interval. ([dagger]) Adjusted for effects of all variables included in the model. The nonsignificant variable was sex.