SciELO - Scientific Electronic Library Online

 
vol.54 número4Hyperparathyroid pathology treated in three Costa Rican hospitalsPrevalence of intestinal parasites in food handlers in a rural community in Cojedes, Venezuela índice de autoresíndice de assuntospesquisa de artigos
Home Pagelista alfabética de periódicos  

Serviços Personalizados

Journal

Artigo

Indicadores

Links relacionados

  • Não possue artigos similaresSimilares em SciELO

Compartilhar


Acta Médica Costarricense

versão On-line ISSN 0001-6002versão impressa ISSN 0001-6012

Acta méd. costarric vol.54 no.4 San José Out./Dez. 2012

 

Original

Epidemiological behavior of cases of suspected leptospirosis in five health  regions of Costa Rica

Jorge Sequeira-Soto1 y Juan José Romero-Zúñiga2

 

Authors’ Memberships: Leptospirosis National Reference Center (Centro Nacional de Referencia de Leptospirosis -CNRL). Costa Rican Institute of Research and Teaching of Nutrition and Health (Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud, INCIENSA).1 Regional Postgraduate in Veterinary Sciences. National University, Heredia, Costa Rica.2
Abbreviations: CNRL, Leptospirosis National
Reference Center
; FIC, Leptospirosis cases research
files; INCIENSA, Costa Rican Institute of Research and Teaching of Nutrition and Health; MAT, Microagglutination Technique; MS, Ministry of Health; PR, Prevalence Ratio Support Resources: This study usede funds provided by INCIENSA.

Correspondence: jsequeira@inciensa.sa.cr  


Abstract

Background and aim: The prevention and control of leptospirosis depends on the knowledge about the exposure of people to possible risk factors, which are reported in the national surveillance system for this event. This study describes the epidemiologic behavior of the cases of suspected leptospirosis, which were researched using the protocol in force in the country.

Methods: Across-sectional study that describes the epidemiologic behavior of the cases of suspected leptospirosis using the data of the case investigation forms of the surveillance system for this event. Laboratory data was obtained from the INCIENSA´s National Leptospirosis Reference Center. The period of study was between 2004 and 2008 in the Brunca, Central Este, Huetar Atlántica, Huetar Norte and Pacífico Central regions, according to the structural organization of the Costa Rican Ministry of Health.

Results: 498 case investigation forms were analyzed. The most frequent occupations are those described as “without risk” (37.3%), students (23.2%) and agricultural (22.1%). The exposure to domestic animals prevails (67.6%), of this 92% were dogs. The presence of rodents is reported in 52.6% of the cases. A 29.5% had contact with ponds or swimming pools and 28% with stagnant waters, both with a prevalence of 1, 88 and 1, 71(p<0,05).

Conclusion: The frequency of cases in groups “without occupational risk” indicates that the case investigation form must be redesigned to incorporate other variables that include recreational ones.

Keywords: Leptospirosis, epidemiological surveillance, risk factors


The taxonomy of this bacteria is more complex now than in the previous two species classification; recognizing a pathogenic specie known as Leptospira interrogans and a saprophytic non pathogenic, Leptospira biflexa. Since many years, the Subcommittee of Leptospiraceae’s Taxonomy has been dabbling in the modification of the old serologic taxonomy into new molecular methods to classify the zoonosis. Since 2007, 13 species have been accepted, and includes more than 260 pathogenic serovarieties. Also, 60 saprophytic serovarieties are now grouped in 6 species. The Leptospiraceae family includes two more genres, Turneria parva (T. parva) and Leptonema (L. illini).1-3

The clinical presentation of the disease in the human being starts with a feverish first stage, 2 to 20 days after infection. Once the immune system phase starts, a second stage occurs which coincides with the elimination of the leptospira organisms in urine, in the case of humans, the elimination is reduced because of the acid pH.4 The most common clinical presentation is an anicteric leptospirosis, as a subclinic form or of moderate severity in where the presence of a sudden onset fever is notable. 4,5 The icteric form is more uncommon (5-10% of all cases), but it is usually of much greater severity and mortality, associated with pulmonary hemorrhage involvement in some cases, presenting a high mortality.5.9 The clinical presentation of the disease, being so broad, results in its confusion with other similar diseases, complicating its diagnosis when this other diseases are endemic in regions where leptospirosis is common. This occurs in diseases like dengue, yellow fever, malaria, rickettsiosis, influenza and, when there are hemorrhagic manifestations, it can be confused with other hemorrhagic viral diseases such as hantavirus.5,10

For a long time, leptospirosis has been considered a worldwide zoonotic disease, given its epidemiological characteristics. This spirochaete has been found in every mammal including aquatic mammals.2

However, from a anthropocentric point of view, the most important natural hosts are of domestic or wild character, that are related to household environment or peridomiciliary, such as dogs, cattle and rodents.5,11-14 When leptospira organisms colonize the proximal renal tubules, their elimination is possible during the lepstopiuric phase, altogether with their great ability of survival in wet environments,15 makes infection possible when entering through the mucosa and skin wounds.4,16 The human being gets infected directly through the urine of an infected host or indirectly through infected solutions, including puddles, rivers and lakes, that keeps the organism viable, penetrating through a lacerated skin, allowing the entrance of the organism into the blood circulation. Epidemiologically an occupational transmission has been reported; identified in the beginnings of the disease, especially in workers like veterinarians, ranchers, rice, corn and sugarcane farmers; and more recently a household and recreational transmission has become important.4,17,18 There is evidence that the behavior of the disease vary between ecological niches;19 thus it is necessary to characterized this behavior with the purpose of identifying the possible risks factors to intervened to control and prevent new cases.

The disease is distributed along all Costa Rica in a greater or lesser degree; however, traditionally, health regions of North Huetar, Central North, Central Pacific, Atlantic Huetar and Brunca report the higher number of cases, 74% of the nation’s total.

In this study, the epidemiological behavior of the suspected cases of leptospirosis in the five more prevalent health regions in Costa Rica is described, through an analysis of variables that compiled the investigation of leptospirosis suspected cases, of the Surveillance System of the disease between 2002 and 2008.

Materials and Methodology

Units of Analysis: The information in the leptospirosis cases research files (FIC) was used as an unit of analysis, that were detected by the Leptospirosis National Surveillance System in the regions of North Huetar, Central Pacific, East Central, Atlantic Huetar and Brunca between 2004 and 2008.

Case: For the purpose of this study, suspected cases were those found in the FIC.

Data and Analysis Detection: The information of the FIC was obtained from the Ministry of Health’s Heath Areas, between 2004 and 2008. The complementary information of the results of the sent samples for the diagnosis of leptospirosis was compiled in a database of the CNRL of INCIENSA in the same period of time. The database was made with the Epiinfo 3.5.1 program. The prevalence ratio and intervals of confidence were calculated at 95%, of the occupational, exposure and protective measures variables. The information analysis was made through Epiinfo 3.5.1, Epidat 3.1 and Win Episcope 2.0 programs. 21.22

Type of Study and Variables: Descriptive (Statistical) Study, through analysis of demographics, environmental, occupational and laboratory variables, contained in the FIC.24 Age variable was stratified in age groups with 20 years intervals. Occupational variable was stratified depending on the reported risks of acquiring the disease: students, housewives, agricultural and livestock activities, “other no-risk occupations” (office workers, operators, drivers, security guards, etc) and “other risk occupations” (slaughter line operators, tourist guides and topographers, etc). Table 1

Laboratory Diagnosis: Positive samples are those with a title of ≥1:320 in MAT analysis. Using Dri-Dot® (Biomerieux) technique, positive samples were classified, detecting total anti-Leptospira antibodies; or were positive samples in the culture. In the other hand, negative samples were those that resulted as negative by some or all diagnostic techniques mention above.

Results

The information was compiled from a total of 498 cases, distributed as follows: 80 from Brunca region (16.1%), 258 from East Central region (51.8%), 39 from Atlantic Huetar region (7.8%), 59 from North Huetar region (11.8%) and 62 from Central Pacific region (12.4%). According to data from health regions and the Ministry of Health, in the period of study, 1339 suspected cases were notified, and should be investigated and each FIC should go to its respective Ministry of Health area in its Health region. When asked, representatives of Health Surveillance Teams of the Ministry of Health, in relation to what was the cause of the lack of information available, the response was that the information

was lost because of flooding in the facilities, and lost of data caused by computer damaging without backups, and also problems to send the information compiled by the staff of the CCSS (Caja Costarricense de Seguro Social – Costa Rica’s Social Welfare) to the Ministry of Health in each respective Health Area.

24.9% of the compiled FIC, correspond to the latest approved and current edition by the Ministry of Health (2002).16 The rest 75.1% were researched through another type or version of the ballots, from the 1998’s epidemiological surveillance protocol (10.6%) and the 2000’s leptospirosis prevention and management protocol (58.2% and respective ballots from other events (i.e. Hantavirus) or another type of documentation like letters or non standardized administrative reports (6.2%).

Of 498 FIC, 386 (77.5%) had a first initial laboratory sample, in which 68 were positive (17.6%) and 318 were negative (82.4%). A total of 107 had a second sample (21.5%) in which 29 were positive (27.1%) and 78 were negative (72.9%). As shown in table 1, when analyzing the suspected cases in a global manner, with both samples and without taking into account if the time defined by protocol was fulfilled between both of them,24 a positivity of 20.7% was reported. In the analysis of sample-taking time, only 9.5% of all cases fulfilled the first sample-taking time (7-10 days of the onset of symptoms) and of the second sample (10-20 days of the first sample), without a significant difference between analyzed regions (p= 0.75). % of investigated cases

Epidemiological Behavior in Cases Investigated

A total of 498 FIC were compiled between 2004 and 2008, with age information in 469 cases. 29.4% of this cases belong to the age group between 0 and 19 years old, 41.2% belong to the ages between 20 and 39 years old, 23.7% between 40 and 59 years old and 5.8% were 60 years old or more. Nonetheless, a significant difference (p<0.05) was found on the distribution according to health regions, thus for example, in the Brunca and North Huetar, the age group of 0-19 years old contributed to a important percentage of cases (figure 1). In general, 83% of cases were man, without significant difference between regions (p=0.33).

Through time, date distribution of the onset of symptoms of suspected cases of leptospirosis, were similar in five regions, with the exception of East Central region, where the reported cases increased irregularly between 2005 and 2008

(figure 2).

Evaluation of Exposure and Protective Factors

When analyzing the behavior of exposure variables that were traditionally reported in the literature as risk factors for acquiring the disease, activities classified as low risk for acquiring the disease represent the highest percentage of the investigated group (table 2). However, when analyzing the prevalence ratio, this group presents the lowest probability of positivity on the laboratory (RP<1, IC95%: 0.49-1.24) altogether with housewives group (RP<1, IC95%: 0.141.66). The student group was placed second, followed by people related to agricultural activities. It’s noticeable, that less than 2% of the cases, performed livestock activities that were related traditionally to higher risk of acquiring the disease. When prevalence ratio of positive cases by laboratory were analyzed, in different occupational groups, agricultural and livestock activities and also other “risk” occupations, showed a slightly higher prevalence in comparison with other activities. However, none can be

interpreted as a possible significant association, because IC intervals include the unit (table 3).

As seen in table 4, more than 67% reported an exposure to domestic animals, of these less than 40% have nonspecific vaccination or vaccine specificity (valid FIC lack of reports of this information). The exposure to domestic animals represents more than 80% of the Brunca region. The main domestic animal reported were dogs, representing 95% of the cases of domestic animals. North Huetar showed an important percentage, on contacts with cattle, horses and pigs.

Almost 83% of cases presented an adequate management of solid waste, with significant difference between regions (p<0.05); however, more than half of this reports reported the presence of rodents, without a significant difference between regions (p>0.05).

A little less than 30% of cases, reported contact with stagnant water, recreational activities in wells and pools in the last 30 days, a significant difference between regions was found (p<0.05), with the exception of North Huetar, where almost 50% reported contact with wells and pools, 30 days prior to the onset of symptoms. These two variables

showed a significant association when analyzing the prevalence ratio (table 3). On the other hand, Central Pacific region, points a higher percentage of cases, related to flood  regions (31.4%), higher than the country’s average (10.3%).

The FIC compiled information about the use of three protective measures against leptospirosis: use of boots, long sleeve shirts and gloves during workday. More than half of the cases investigated (58.8%) used boots during workday, however; the use of gloves and long sleeves shirt were found only in 15.7% and 16.2% respectively; variables with significant difference in regional distribution (p<0.05) (figure 3). In those occupations related to agricultural or livestock activities, when analyzing the protective measures, 88.3% of cases used boots, 29.3% used long sleeves shirts and 20.5% used gloves.

Discussion

Epidemiological Behavior of Cases Investigated

The study findings about the epidemiological behavior of cases, according to age and genre, are congruent to previous reports of the Ministry of Health between 2002 and 2006.25 A big proportion of cases presented in individuals younger than 20 years old, predominantly in North Huetar region, and in less proportion in Brunca region. Bigger efforts should be performed to comprehend the causes of this disease in age groups, evaluating the possibility of its relation to recreational activities, not occupational.

The lack of the existence of standardization and systematicity in the process of investigation in suspected cases is noticeable, mostly because the majority of FICs are outdated. An important part of the problem resides in the differences between FICs versions of some variables. For example, the 2000’s version asks about the exposure 15 days prior to the onset of symptoms; meanwhile, the 2002’s version asks about the exposure 30 days prior. This inconvenient is worsen when using files from other events or not standardized documentation that does not compiled epidemiological variables of importance.

From the total of investigated cases, the laboratory was capable of identifying as less than 21% positive samples, through serology. This low percentage can be explained mainly because of the low capacity of the system to recover second samples (27.7%), and because of the limited percentage of samples taken in the time indicated by protocol. The non-compliance of these criteria causes an important subdiagnosis by the laboratory and therefore, the inability of the system to identify adequately the confirmed cases of leptospirosis.

Analyzing the pattern of occurrence of the disease in occupationalgroups,itisnoticeablethatthemostrepresentative group are those individuals that performed activities that epidemiologically (in other literature) has not been related with an increased risk for acquiring the disease occupationally, such as drivers, office workers and merchants, etc. The student group and individuals working in agricultural activities group came second. However, despite the higher frequency of this groups, the activities “without risk”, the students and housewives presents a prevalence ratio that could suggest a lowest risk in presenting a positive sample, since the IC 95% limits, are close to the statistical significance. So, there is a necessity of developing a different epidemiological approach from the traditional one, framed by a paradigm as seen the leptospirosis as a mainly occupational disease.

It draws attention, the low percentage of suspected cases investigated that performed livestock activities, while a prevalence ratio is slightly higher, such activities are strongly related to the disease, with the increased risk of acquiring the disease as described by many authors.4, 26, 27 This conditions is particularly important in areas, like North Huetar region, where the livestock activity is very important, and where a high percentage of cases, associated with cattle, horses and pigs are reported.

With the compiled information by the case investigation ballot, we can conclude that the most frequent exposure factor in suspected cases is the exposure to domestic animals, primarily dogs. The investigated cases, indicate that involved domestic animals where 35% vaccinated; however, the instrument at present is incapable to identify the type of vaccination or at least if they received a vaccine against leptospirosis and when did they received it, making this information useless when trying to direct the efforts to control and prevent the disease.

It is necessary, that efforts must delve in the identification of the behavior of this disease in peridomiciliary animal groups, and especially if associated with positive cases. This way, the intervention of organisms and institutions, such as the Ministry of Agriculture and Livestock (Ministerio de Agricultura y Ganadería – MAG) are essential, into identifying suspected cases or confirmed cases of leptospirosis, with the purpose of initial identification of sources of infection in animal groups of zoonotic importance, like canines, cattle, pigs, horses and old world rats and mice (Murinae). Precisely, the exposure to rodents, are the same in all regions equally. In a lower percentage the contact with stagnant water and recreational exposure to wells and pools, showed a higher probability of obtaining a positive sample in the laboratory in a significant manner.

The observations made, suggests that epidemiological behavior differ in some regions, for example, North Huetar region, presents a high incidence of cases, related to animals and recreational activities, Central Pacific region reports a higher number of cases related to floods, however, further studies should be made, that involves the analysis of the zoonotic epidemiological behavior and analytic studies of risk factors.

Utility of the Case Investigation Ballot

The investigation of suspected cases represents an important step in the epidemiological surveillance process. The system compiled the information needed to identify possible points of control and prevention of the disease. In accordance to the compiled information in this study, a higher frequency to identify the possible risk factors incorporated in FIC (identified now on the literature). It is necessary to identify other predisposing factors of the dissemination of rodents that were reported in half of the cases, even if 80% of these cases have an adequate solid waste management, resulting in a reduction of predisposing factors for the presence of rodents.

In the other hand, representation of the students and low risk of acquiring the disease occupations groups, suggest the possibility of a recreational relation for the transmission to humans, like rivers, lakes or any humid zone that allow the organism to survive. However, the only question asked in the FIC refers to a 30 days contact to pools or wells prior to the onset of symptoms, not taking into account other sources of infection such as fishing activities, canopy, climbing, or other sports as soccer without the use of footwear,3, 28-32 such data can be used with the purpose of identifying possible asymptomatic or mild symptomatic cases.

Beyond the variables mention above, other possible risk factors to be intervened by healthcare services were unable to identify. The actual FIC present a clear slant, in search of identifying mainly occupational exposures, for example, the protective measure variables. The improvement of this instrument through the incorporation of other epidemiological variables is necessary. The current case investigation ballot does not contemplate the presence of wounds in skin, or its number and location, this data has been demonstrated useful in identifying the risk of infection and install direct protective measures.33

The ballot, also collects information about the contact with floods and stagnant water zones, but does not identify the sources of these or the geographical region in which they are located, data that can be useful to install protective measures and alert the community.

It is also advisable that the file include variables related to water sources, open water drains, allowing dissemination of rodents; observation of the home environment, peridomiciliar and occupational has evidence suggesting the presence of rodents (nests, gnawed food, feces presence, etc). Also, it is advisable the zoning of suspected cases, since there are important differences in risk factors between rural and urban zones.3, 4

It is important to emphasize to the healthcare personnel, that recollection of data of suspected cases is needed, not only through interview, but also the observation of the household, peridomiciliar and occupational environments should be performed.

We concluded that the instrument used in the recollection of data in suspected cases should be restructure, making it more flexible to new patterns of occurrence of the disease in the Costa Rican population; incorporating findings of new research studies about risk factors in the country. The data obtained showed that while many cases are occurring in young people with activities related to the agricultural sector, a significant majority are activities and risk factors related to students or individuals with an occupation that are not traditionally related to a high exposure for leptospirosis. Unfortunately, the current instrument is incapable to identify these risk factors, as it focuses primarily in identifying leptospirosis as an occupational disease, so a new perspective should be reconsidered by all healthcare authorities.

Competing Interest: The authors have no conflict of interest to declare.

Acknowledgements: The results presented in this study would not have been possible without the support and cooperation of the staff of Health Areas of Brunca, East Central, Atlantic Huetar, North Huetar and Central Pacific, and the Ministry of Health’s Directorate of Health Surveillance, Costa Rica. We thank all of them.


References

1.Adler B, Peña A de la. Leptospira and leptospirosis. Vet Microbiol 2010; 140:287-96.         [ Links ]

2.Levett PN, Smy the L. Minutes International Committee on Systematics of Prokaryotes, Subcommittee on the taxonomy of Leptospiraceae, Quito, Ecuador: 2008. Int J Syst Evol Microbiol 2008; 58:1049-50.         [ Links ]

3.Faine S, Adlen B, Bolin B, Perolat P. Leptospira and Leptospirosis. Seg. ed. Editorial Medi Sci, 1999.         [ Links ]

4.Levett PN. Leptospirosis. Clin Microbiol Rev 2001; 14:296-326.         [ Links ]

5.Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, et al. Leptospirosis: a zoonotic disease of global importance. The Lancet 2003; 3:757-771.         [ Links ]

6.Doudier B, Garcia S, Quennee V, Jarno P, Brouqui P. Prognostic factors associated with severe leptospirosis. Clin Microbiol Infect 2006; 12:299-300.         [ Links ]

7.Dupont H, Dupont-Perdrizet D, Perie JL, Zehner-Hansen S, Jarrige B, Daijardin JB. Leptospirosis: prognostic factors associated with mortality. Clin Infect Dis 1997; 25:720-4.         [ Links ]

8.Segura ER, Ganoza CA, Campos K, Ricaldi JN, Torres S, Silva H, et al. Clinical Spectrum of Pulmonary Involvement in Leptospirosis in a Region of Endemicity, with Quantification of Leptospiral Burden. Clin Infect Dis 2005; 40:343-51.         [ Links ]

9.Trevejo RT, Ashford DA, Rigau-Pérez JG, McClure EM, Jarquín-González C, Amador JJ, et al. Epidemic leptospirosis associated with pulmonary hemorrhage-Nicaragua, 1995. J Infect Dis 1998; 178:1457-63.         [ Links ]

10.La Rocque R, Breiman R, Ari M, Morey R, Ara F, Hayes J, et al. Leptospirosis during Dengue Outbreak, Bangladesh. Emerg Infect Dis 2005; 11:11-14.         [ Links ]

11.André-Fontaine G. Canine leptospirosis-do we have a problem? Vet Microbiol 2006; 117:19-24.         [ Links ]

12.Ward MP. Seasonality of canine leptospirosis in the United States and Canada and its association with rainfall. Prev Vet Med 2002; 56:203-213.         [ Links ]

13.Sepúlveda A, Dimas J, Preciado F. La rata y el perro, importantes vectores de la leptospirosis en explotaciones pecuarias de Cd. Guzmán, Jalisco. Rev Cubana Med Trop 2002; 54:21-23.         [ Links ]

14.Botazzo Á, Freitas JC de, Bracarense AP, Eckehardt E, Oliveira R de. Leptospirosis in slaughtered sows: serological and histopathological investigation. Braz J Microbiol 2002; 33:174-177.         [ Links ]

15.Trueba G, Zapata S, Madrid K, Cullen P, Haake DA. Cell aggregation: a mechanism of pathogenic Leptospira to survive in fresh water. Int Microbiol 2004; 7:35-40.         [ Links ]

16.Vinetz JM. Leptospirosis. Curr Opin Infect Dis 2001; 14:527-538.         [ Links ]

17.Keenan J, Ervin G, Aung M, McGwin G, Jolly P. Risk factors for clinical leptospirosis from Western Jamaica. Am J Trop Med Hyg 2010; 83:633-636.         [ Links ]

18.Belmaker I, Alkan M, Barnea A, Dukhan L, Yitzhaki S, Gross E. Risk of Transmission of Leptospirosis from Infected Cattle to Diary Workers in Southern Israel. Isr J Med Assoc J 2004; 6:24-27.         [ Links ]

19.Sarkar U, Nascimento SF, Barbosa R, Martins R, Nuevo H, Kalafanos I, et al. Population-based case-control investigation of risk factors for leptospirosis during an urban epidemic. Am J Trop Med Hyg 2002; 66:605-610.         [ Links ]

20.Costa Rica, Ministerio de Salud. Memoria Institucional 2004. San José: Ministerio de Salud; 2005.         [ Links ]

21.Dean AG, Arner TG, Sunki GG, Friedman R, Lantinga M, Sangam S, et al. Epi Info™, a database and statistics program for public health professionals. Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 2007.         [ Links ]

22.Hervada X, Santiago M, Vázquez E, Castillo C, Loyola E, Silva L. Epid at 3.1, Programa para análisis epidemiológico de datos tabulados. Xunta de Galicia, Organización Panamericana de Salud, Coruña, España, 2005.         [ Links ]

23.De Blas I, Ortega C, Frankena K, Noordhuizen JP, Thrusfield M. Win Episcope 2.0, improved epidemiological software for veterinary medicine. Zaragoza, España, 2001.         [ Links ]

24.Costa Rica, Ministerio de Salud. Protocolo para la Prevención y Control de la Leptospirosis. Ter. ed. San José, Costa Rica: 2002.         [ Links ]

25.Costa Rica, Ministerio de Salud. Memoria Institucional 2002-2006. San José: Ministerio de Salud; 2006.         [ Links ]

26.Valverde M, Ramírez J, Montes de Oca L, Goris M, Ahmed N, Hartskeerl R. Arenal, a new Leptospira serovar of serogroup Javanica, isolated from a patient in Costa Rica. Infect Genet Evol 2008; 8:529-33.         [ Links ]

27.Giraldo G, Orrego A, Santacruz M, Yepes E. Leptospirosis. Las aguas de la explotación porcina como vehículo de la Leptospira, en la zona central cafetera de Colombia. Arch Med Ve 2002; 34:69-78.         [ Links ]

28.Sánchez RM, Sierra AP, Suárez MB, Álvarez ÁM, Hernández JM, González MD, et al. Evaluación de la efectividad de una nueva vacuna contra la leptospirosis humana en grupos en riesgo. Rev Panam Salud Pública 2000; 8:385-92.         [ Links ]

29.Solano A, Boza R, Sáenz E. Leptospirosis en Humanos. Rev Costarric Cienc Med 1996; 17:41-60.         [ Links ]

30.Michel V, Branger C, Andre-Fontaine G. Epidemiology of leptospirosis. Rev Cubana Med Trop 2002; 54:7-10.         [ Links ]

31.Centers of Diseases Control and Prevention. Outbreak of leptospirosis among white-water rafters—Costa Rica, 1996. MMWR Morb Mortal Wkly Rep 1997; 46:577-579.         [ Links ]

32.Vinetz JM, Glass GE, Flexner CE, Mueller P, Kaslow DC. Sporadic Urban Leptospirosis. Ann Intern Med 1996; 125:794-798.         [ Links ]

33.Phraisuwan P, Whitney E a S, Tharmaphornpilas P, Guharat S, Thongkamsamut S, Aresagig S, et al. Leptospirosis: skin wounds and control strategies, Thailand, 1999. Emerg Infect Dis 2002; 8:1455-9.         [ Links ]


Received Date: January 4th, 2012 Accepted Date: August 7th, 2012

Creative Commons License Todo o conteúdo deste periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons