A02v40n5 2 PDF
A02v40n5 2 PDF
A02v40n5 2 PDF
ABSTRACT
Leptospirosis is a zoonotic disease that has emerged to cause epidemics in urban communities in developing countries. However, little is known
about the infection in the general population. A seroprevalence survey was performed on a random sample of 1,390 subjects in Salvador, Brazil.
Data on environmental and socioeconomic factors were collected. The microagglutination test of serum samples was used to show any prior
Leptospira infection. The overall seroprevalence was 12.4%. Among the seropositive individuals, 111 (61%) had high titers for serovars of the
Icterohaemorrhagiae serogroup. Seroprevalence increased with age and was similar for males and females. A positive correlation between
Leptospira infection and low educational level was found. These findings indicate that a significant proportion of this urban population is
exposed to pathogenic Leptospira. Public health actions for leptospirosis control will need to target not only the traditional groups at risk of
infection with severe forms of this disease, but also the general population that is at risk.
Key-words: Leptospirosis. Seroprevalence. Epidemiology. Urban epidemics.
RESUMO
A leptospirose é uma zoonose que tem emergido causando epidemias em comunidades urbanas de países em desenvolvimento. Entretanto,
pouco é conhecido sobre infecção na população geral. Inquérito de soroprevalência foi realizado em amostra randômica de 1.390 indivíduos
de Salvador, Brasil. Dados sobre fatores ambientais e sócio-econômicos foram coletados. Teste de Microaglutinação de amostras de soro foi
utilizado para evidenciar infecção anterior por Leptospira. Soroprevalência global foi 12,4%. Entre os soropositivos, 111 (61%) tinham altos
títulos para os sorovares do serogrupo Icterohaemorrhagiae. A soroprevalência aumentou com a idade e foi similar entre homens e mulheres.
Encontrou-se correlação positiva entre infecção por Leptospira e baixo nível educacional. Os achados indicam que significativa proporção
dessa população urbana está exposta a Leptospira patogênica. Ações de saúde pública para controle desta doença necessitarão ter como alvo
não só os tradicionais grupos de risco associados às suas formas graves, como também a população geral sob risco.
Palavras-chaves: Leptospirose. Soroprevalência. Epidemiologia. Epidemias urbanas
Leptospirosis is a zoonotic disease of global importance4 16. In Transmission is closely related to environmental factors2 15 17 27,
many countries, the disease is restricted to specific occupational such that inadequate sanitary and rainwater sewage systems and
groups, such as sewage system workers, mine workers, wetland waste accumulation favor human contact with the excreta from
agriculturists, soldiers and abattoir workers dealing with bovine animal reservoirs17 20 27.
meat, among others1 8 25 However, in the large urban centers of In Brazil, annual epidemics occur in major urban centers such
tropical developing countries9 17 22 31, leptospirosis affects not as São Paulo, Rio de Janeiro, Salvador and Recife, during seasonal
only occupational risk groups but also the general population5. periods of flooding and heavy rainfall2 6 17 28. Nationwide, more
1. Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, BA. 2. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/Ministério da Saúde, Salvador, BA.
3. Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York, USA
Support: Secretaria de Desenvolvimento Urbano do Estado da Bahia, PRONEX/MCT-CNPq (Contract no. 661086/1998-4); CENEPI/FUNASA/MS and the National Institutes of
Health, USA (TW00919-07 and AI052473-01A1)
Address to: Dr. Juarez Pereira Dias. Instituto de Saúde Coletiva/UFBA. Basílio da Gama s/nº, Campus Universitário do Canela, 41110-040 Salvador, BA, Brasil.
Tel: 55 71 3383-7412; Fax: 55 71 3283-7460.
e-mail: [email protected]
Recebido para publicação em: 18/08/2006
Aceito em: 17/08/2007
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than 10,000 suspected cases are reported each year. Between network19. Despite 77% of the population having access to some
1987 and 1997, 32,436 of these reported cases were confirmed form of garbage collection, there was significant variation in the
by laboratory tests. On the basis of confirmed cases, the annual access to this service among different areas in the city. This study
incidence has been as high as 2.1 cases per million population. was performed as part of an evaluation to determine the impact of a
Population-based surveillance in the city of Salvador found that the large-scale project (Projeto Bahia Azul) to improve the sanitation
infection rate for severe leptospirosis was 12.5 cases per 100,000 infrastructure of Salvador 3. The evaluation studies were performed
inhabitants during a single epidemic season17. The mortality rate in 30 sentinel sites in ten selected sewage drainage basins
among cases identified during this epidemic was 15%. (Figure 1) that had been selected through a previous study by
However, information from hospital-based surveillance in Teixeira, 200229 30. The population-based sample included 1,390
Brazil 6 17 significantly underestimates the impact of urban subjects selected by simple random sampling, without reposition7,
leptospirosis. Severe leptospirosis is believed to account for from among the 68,749 residents in the ten sewage drainage
a fraction (5-15%) of all clinical infections13. Furthermore, basins. The study subjects were enrolled between May and July
serological surveys have been restricted to evaluating traditional risk 1998, in accordance with informed consent procedures. The study
groups 19 32. Hence, there is limited understanding of the protocol was approved by the Research Ethics Committee of the
seroprevalence of infection and circulation of pathogenic Leptospira Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, an
among the general urban population. Identification of factors that entity linked to the Brazilian Ministry of Health.
take part in the dynamics of the circulation of Leptospira among the Data collection. After enrollment, a questionnaire was
general population, such as environmental transmission factors, may administered at an interview to obtain demographic data (name,
contribute towards improving current knowledge of the epidemiology address, gender and age), socioeconomic data (income and
of urban leptospirosis and towards drawing up policies and schooling) and information on environmental characteristics
interventions aimed at controlling this emerging health problem. (garbage collection and storage, contact with rodents, flooding
A citywide survey in Salvador, Brazil, was performed in 1998 of household and surroundings and water supply frequency). In
to evaluate the health impact of a large-scale intervention aimed at addition, the environmental status in loco was surveyed as part of
improving the sanitary infrastructure of the city. Through retrospective the Projeto Bahia Azul evaluation, to obtain information on water
evaluation of the serum samples obtained during this survey, we had supply, sanitary sewage and rainwater drainage systems, flooding
the opportunity to determine the prevalence of Leptospira infection and garbage collection frequencies and disposal points.
in the population of Salvador and identify possible environmental, Serologic case confirmation. The microagglutination test
socioeconomic and biological factors associated with prior infection. (MAT) was used to detect anti-Leptospira antibodies in the subjects’
serum samples11. Six reference strains (Leptospira interrogans
serovar Copenhageni strain M20, serovar Icterohaemorrhagiae
MATERIAL AND METHODS
strain RGA, serovar Canicola strain Hond Utrecht IV and serovar
Autumnalis strain Autumnalis; Leptospira kirchneri serovar
Setting and population. This study was conducted in Cynopteri strain Cynopteri; and Leptospira biflexi serovar Patoc
Salvador, a city of 2.3 million inhabitants. Although the main water strain Patoc 1) and three clinical isolates (Leptospira interrogans
supply network served more than 90% of households at the time serovar Copenhageni strain Fiocruz L1-130, serovar Canicola
of the study, only 22% were connected to the main sanitary sewage strain Fiocruz L1-133 and serovar Hurstbridge strain L1-125)
SALVADOR
Bacia de Peripei
BRAZIL
BAHIA Bacia de Cobre
Bacia de Calafate
Bacia do Medio
Camaragibe 0 150 km
Bacia de Tripas
Bacia de Armacao
Bacia da Barra
Figure 1 - ����������������������
Geographical location of
��� the
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city of ������������
Salvador in ������������������
Brazil and the 10 sewage
����������������
drainage ��������������
basins within
Salvador which were used as sentinel sites for the study, 1998.
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Revista da Sociedade Brasileira de Medicina Tropical 40(5):499-504, set-out, 2007
obtained from patients during surveillance in Salvador17 were used. and surroundings and access to an enclosed piped water source
These represented a total of six serogroups (Autumnalis, Canicola, in the household. Crude prevalence and age-adjusted prevalences
Icterohaemorrhagiae, Cynopteri, Patoc and Hurstbridge). The were estimated for each sentinel area and each sewage drainage
cross-absorption agglutination test and monoclonal antibody basin21. An indirect approach was used for seroprevalence rate
methods were used beforehand to determine the serovar status standardization according to age, using the sample population
for the clinical isolates, at the WHO Collaborative Laboratory for rates as a basis. Prevalence ratios (PR) and Spearman’s rank
Leptospirosis (Royal Tropical Institute, Amsterdam, Holland) correlation coefficients (r) were calculated in order to test for
and Oswaldo Cruz Foundation (Salvador, Brazil). Prior isolation associations. The specific seroprevalence was calculated for
studies from clinical cases found that the serovar Copenhageni exposure to the serogroup Icterohaemorrhagiae, which was the
was the principal agent for outbreaks in Salvador17 27. The use of principle etiological agent for leptospirosis in Salvador17.
this reduced serovar battery accounted for 98% of the positive
agglutination reactions when an expanded 25-serovar battery was
RESULTS
used to evaluate samples from leptospirosis patients identified
during surveillance in Salvador17 27. MAT titers of > 1:50 in relation
to strains belonging to pathogenic serogroups were defined as Of the 1,390 subjects studied, 58.3% were female, 56.5% had
evidence for prior Leptospira infection. an educational level corresponding to incomplete basic schooling
Statistical analysis. The statistical analysis of individual-level (1st-8th grades), 26.3% reported a family income of less than
data included stratification of crude and age-adjusted prevalences US$45 per month and 74.7% were 15 years old and over (Table 1).
of prior Leptospira sp. infection according to biological, social, Among these subjects, 172 presented evidence for prior Leptospira
economic, social and environmental characteristics of subjects infection according to the microagglutination test. The overall
and calculation of their respective prevalence ratios (PR) and 95% seroprevalence was 12.4% (95% CI: 10.7-14.2). There was no
confidence intervals (CI). The chi-squared test was used to evaluate statistically significant difference between the proportions of prior
trends relating to prior Leptospira infection among different strata Leptospira infection in male and female subjects (14.0 vs 11.2%;
of environmental conditions. Linear regression analysis was used to p = 0.127). The prevalence of prior infection was associated with
assess the relationship between Leptospira seroprevalence and age. increasing age among the subjects (β = 0.024, p = 0.00) (Figure
The association between reported sightings of rats in the household 2). The group aged 15 years old and over had a risk of infection that
environment and seropositivity was evaluated using logistic regression, was 2.2 times greater (95% CI: 1.44-3.35) than the risk among those
which allowed socioeconomic and environmental variables to be under 15 years old (Table 1). However, it is worth noting that the
treated as potential confounders and effect modifiers. group under 15 years of age had a prevalence of infection of 6.5%
Ecological-level analysis was performed using the sewage (95% CI: 4.27-9.78) (Table 1). The seroprevalence was inversely
drainage basins as the analysis unit. The seroprevalence of associated with increased schooling (χ2 trend = 6.93; p = 0.039)
Leptospira sp was correlated with variables that included the and income levels (χ2 trend = 6.93; p = 0.008). Leptospira infection
proportions of male subjects, subjects aged 15 years and over, was not significantly associated with access to piped water, reported
subjects with less than 8 years of schooling (among those aged sightings of rats, presence of uncollected garbage or flooding around
15 years and over), households with incomes of less than two the household (Table 1).
minimum monthly salaries and subjects who reported the The seroprevalence rates did not differ significantly among
presence of rodents, garbage collection, flooding of household subjects living in the 10 sewage drainage basins within Salvador
30
27
25
23,8
22,7
Seroprevalence (%)
20 18.7
19.1 19.2
16.5 17.3 17.3
15.3 15.7
15 14.2 14.2 14.7
12.4 11.9
11.5
10.5 10.4
10 8.8 9.1 9.5 10
8.4
7.2 6.6 6.4
5.7 4.9
5 4.4
0
1 2 3 4 5 6 7 8 9 10
Sewage drainage basins
Figure 2 - Adjusted seroprevalence of Leptospira infection and 95% confidence intervals according to sewage
drainage basins in Salvador, Brazil, 1998.
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Dias JP cols
responses no % 25
Gender
% 20
male 580 81 14.0 1.24 0.94 - 1.64
female 810 91 11.2 - 1.0 15
Age (years) 10
> 15 1,038 149 14.3 2.20 1.44 - 3.35
< 15 352 23 6.5 - 1.0 5
Education level 0
university 47 4 8.5 - 1.0 0-4 5-9 10-19 20-29 30-39 40-49 50-59 60-69 70 and +
high school (9th-11th grades) 291 30 10.3 1.19 0.44 - 3.24 Male Female
basic schooling (1st-8th grades) 861 119 13.8 1.55 0.60 - 4.03
Figure 3 - Prevalence (%) of prior Leptospira infection according to sex
no schooling 54 13 24.1 2.47 0.86 - 7.14
and age group. Salvador, Brazil, 1998.
Household income
> 8 mms 135 12 8.9 - 1.0 of the 172 seropositive subjects. The other 61 (35.5%) subjects
< 8 and > 5 mms 133 9 6.8 0.78 0.34 - 1.79 subjects had highest MAT titles against the other five pathogenic
< 5 and > 2 mms 695 81 11.7 1.28 0.72 - 2.28 serovars. The prevalence of seropositive subjects whose highest
< 2 mms 427 70 16.4 1.73 0.96 - 3.09 agglutination titers were against the Icterohaemorrhagiae
Reported flooding in the household Table 2 - Correlation coefficients for the association between age-
yes 527 69 13.1 1.10 0.82 - 1.46 adjusted seroprevalence of Leptospira sp infection and selected variables.
Salvador, Bahia, Brazil, 1998*.
no 863 103 11.9 - 1.0
Access to piped water Variable Correlation p
regular 718 89 12.4 1.0 0.76 - 1.33 coefficients (r)
irregular 672 83 12.3 - 1.0 Male (%) 0.036 0.920
Reported presence in home environment or home surrounds of: Mean age -0.176 0.627
rats Schooling (%)1 0.782 0.008
yes 241 28 11.6 0.93 0.63 - 1.36 Family (%)2 -0.480 0.160
no 1,149 144 12.5 - 1.0 Reported rats (%)3 0.146 0.688
solid garbage Reported garbage (%)4 -0297 0.405
yes 848 111 13.1 1.16 0.87 - 1.56 Reported flooding (%)5 0.298 0.403
no 542 61 11.3 - 1.0 * The analysis unit was 10 sewage drainage basins
PR: prevalence rates mms: minimum monthly salary = US 45 1. Percentage of population with < 8 years of schooling among subjects aged 15
years and over.
95% CI: 95% confidence intervals
2. Percentage of family income < 2 minimum monthly salaries.
(Figures 1 and 3). The sewage drainage basins with the lowest 3. Percentage of interviewed population who reported presence of rats in the
environment surrounding the home.
and highest proportions of seropositive subjects (basins 5 and 9;
4. Percentage of interviewed population who reported presence of accumulated garbage
adjusted proportions of 8.4% and 18.7% respectively) were the in the environment surrounding the home.
regions with poorest socioeconomic conditions. Sewage drainage 5. Percentage of interviewed population who reported flooding in the home and its
basin 8, the area with the highest socioeconomic level, had an surroundings.
adjusted seroprevalence of 9.5%.
serogroup did not differ significantly between sewage drainage
Ecological analyses found that age-adjusted seroprevalence
basins and was not associated with poor environmental
was associated with the proportion of adults with less than 8 years
characteristics (data not shown).
of schooling (r = 0.782; p = 0.008) (Table 2). The environmental
characteristics relating to previously reported risk factors for
urban leptospirosis, such as flooding and reporting of rats, DISCUSSION
were also significantly associated with increased age-adjusted
seroprevalence rates. The Leptospira seroprevalence observed in Salvador indicates
Among the 172 subjects with anti-Leptospira antibodies that this agent has wide circulation in this city, regardless of
(MAT titer >1:50), 111 (64.5%) presented their highest sanitation conditions or socioeconomic situation. However,
agglutination titers against reference serovars belonging to the individual and ecological analysis showed that Leptospira sp was
Icterohaemorrhagiae serogroup. The highest MAT titers were inversely associated with education level. The seroprevalence
against reference serovars belonging to the Canicola serogroup, (12.4%) observed in Salvador was lower than what has been
which is associated with Leptospira carried in dogs, in six (3.5%) reported from other regions of Brazil24 and other developing
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Revista da Sociedade Brasileira de Medicina Tropical 40(5):499-504, set-out, 2007
countries19, where it ranged from 25.0 to 54.2%. It should be a risk factor for infection in this study. However, it must be noted
noted, however, that the highest levels have been reported among that, in agreement with the findings in the literature10, the present
selected populations living in high-risk areas where leptospirosis study found that men of productive age (21-50 years) had greater
is hyperendemic or where there is a high degree of exposure. seroprevalence than women did, although this difference was not
The relatively low seroprevalence rate observed in Salvador, statistically significant.
a city where the incidence of clinical severe leptospirosis is While no significant associations between environmental
high (10 per 100,000 population), may reflect the association of factors and Leptospira seroprevalence were found in the present
severe disease with Icterohaemorrhagiae serogroup infection12. study, the results allow the inference that the current sanitation
In Salvador, nearly two thirds of the Leptospira infections were infrastructure in Salvador has not been sufficient to prevent
due to the Icterohaemorrhagiae serogroup, and the frequency widespread environmental contamination with pathogenic
was slightly higher in poor areas. leptospires, since high seroprevalence was observed even in
It can therefore be inferred that in this city there was frequent areas considered to have adequate sanitation. The findings from
and widespread exposure to Rattus norvegicus, which is the this study provide support for the need for focused environmental
primary reservoir for leptospirosis in the urban environment12. sanitation programs using strategies for controlling urban rodent
This finding is further supported by the large (65%) proportion populations and their habitats, which in turn could reduce the
of seropositive individuals who had their highest MAT titers against contact between pathogenic Leptospira and humans.
strains belonging to Icterohaemorrhagiae, which is the serogroup
most associated with the domestic rat reservoir. ACKNOWLEDGEMENT
Despite the absence of significant differences between areas
with regard to overall seroprevalence, higher proportions of MAT
The authors acknowledge the laboratory assistance provided
seroreactivity to the pathogenic serogroup Icterohaemorrhagiae
by Patrícia Guimarães.
were found among subjects living in the sewage drainage basins
with the poorest socioeconomic conditions. This may partially explain
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