Review Pan American Journal

of Public Health

A systematic literature review of leptospirosis

outbreaks worldwide, 1970–2012
Claudia Munoz-Zanzi,1 Emily Groene,1 Bozena M. Morawski,1 Kimberly Bonner,1 Federico Costa,2
Eric Bertherat,3 and Maria Cristina Schneider4

Suggested citation Munoz-Zanzi C, Groene E, Morawski BM, Bonner K, Costa F, Bertherat E, et al. A systematic literature review of leptospirosis
outbreaks worldwide, 1970–2012. Rev Panam Salud Publica. 2020;44:e78. https://doi.org/10.26633/RPSP.2020.78

ABSTRACT Objective. This review describes the geographic and temporal distribution of, detection methods for, and
other epidemiological features of published leptospirosis outbreaks, with the aim of informing efforts to stan-
dardize outbreak-reporting practices.
Methods. We conducted a systematic review of leptospirosis outbreaks reported in the scientific literature and
ProMED during 1970–2012. Predefined criteria were used to identify and classify outbreaks and a standard
form was used to extract information.
Results. During 1970–2012, we identified 318 outbreaks (average: 7 outbreaks/year; range: 1–19). Most out-
breaks were reported in the Latin America and the Caribbean region (36%), followed by Southern Asia (13%),
and North America (11%). Most outbreaks were located in tropical and subtropical ecoregions (55%). Quality
classification showed that there was clear description of laboratory-confirmed cases in 40% of outbreaks.
Among those, the average outbreak size was 82 cases overall (range: 2–2 259) but reached 253 cases in
tropical/subtropical ecoregions. Common risk factors included outdoor work activities (25%), exposure to
floodwaters (23%), and recreational exposure to water (22%). Epidemiologic investigation was conducted in
80% of outbreaks, mainly as case interviews. Case fatality was 5% overall (range: 0%–60%).
Conclusions. Outbreak reporting increased over the study period with outbreaks covering tropical and
non-tropical regions. Outbreaks varied by size, setting, and risk factors; however, data reviewed often had
limited information regarding diagnosis and epidemiology. Guidelines are recommended to develop standard-
ized procedures for diagnostic and epidemiological investigations during an outbreak and for reporting.

Keywords Leptospirosis; Leptospira; disease outbreaks; zoonoses; public health surveillance.

Leptospirosis is a zoonotic infection caused by the patho- in tropical climates due to favorable environmental condi-
genic species of the spirochete bacteria Leptospira. The infection tions for pathogen survival. Modeling of the global burden of
will remain subclinical in the majority of infected people. leptospirosis estimated an annual morbidity of 14.8 cases per
Infected people who are symptomatic often have non-specific 100 000 population, with 1.03 million cases and 58 900 deaths
symptoms, like those found in dengue, malaria, and influenza. due to leptospirosis each year (1). Prevalence is often endemic
However, leptospirosis can also be deadly in up to 10% of at varying levels, from very low levels in temperate regions (2)
patients (1). Human infection is mostly caused through contact to hyperendemic with strong seasonality in tropical regions (3).
with water or soil contaminated with urine from animals shed- The visibility of leptospirosis as an important public health
ding Leptospira, including rats, livestock, dogs, and wildlife. problem increases when there are recognized outbreaks,
Leptospira is distributed worldwide, but is especially prevalent which are often linked to floods, natural disasters (4, 5), and

1
University of Minnesota, Minneapolis MN, United States of America. 3
World Health Organization, Geneva, Switzerland.
* Claudia Munoz-Zanzi, [email protected] 4
Pan American Health Organization, Washington DC, United States of America.
2
Universidade Federal da Bahia, Salvador BA, Brazil.

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Review Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012

water-sports events (6, 7). However, there are many gaps in the based on the following reporting quality criteria: i) description
understanding of risk factors for outbreaks, determinants of of laboratory diagnosis of cases using the World Health Organi-
their magnitude, and options for early detection and prediction zation (WHO) Leptospirosis Disease Burden study definitions
(8). Despite leptospirosis being reportable in many countries (1); ii) outbreak case ascertainment method (community or
(9), limitations of laboratory diagnosis and reporting affect sys- hospital/provider-based); and, iii) description of defined out-
tematic case data collection, outbreak detection, and complete break time. Based on these criteria, outbreaks were classified
characterization of outbreaks. The objective of this study was to into Option 1 (those with ≥1 confirmed or probable case with-
characterize the frequency, epidemiology, and clinical features out any other criteria), Option 2 (those with ≥1 confirmed case
of leptospirosis outbreaks, as well as reporting practices, by without any other criteria), Option 3 (those with ≥1 confirmed
conducting a systematic review of the scientific literature and case and defined time period), and Option 4 (those with ≥1 con-
ProMED, an Internet-based outbreak reporting system. firmed case, defined time period, and active case ascertainment)
(Table 1). We assessed outbreak classification quality control by
MATERIALS AND METHODS reclassifying a 15% random sample of all reports. Inter-rater
agreement was also assessed in a 10% random sample of out-
Potential articles for the systematic review were identified by break reports. In the case of uncertain classification, CMZ made
searching 38 electronic database sources (list available from corre- final inclusion decisions.
sponding author upon request) for articles published and indexed
from 1 January 1970 to 31 December 2012, which contained the Data analysis
terms “Leptospira,” “leptospirosis,” “Weil disease,” or “Weil’s
disease,” while excluding “Leptospirillum.” Search term strings Part 1 of the analysis described all outbreaks (regardless of
were customized to each electronic database’s individual sub- accuracy quality criteria) by location, year of occurrence, size,
ject headings and query structure. For regional and non-English and setting. In addition to country and WHO region, location
databases, relevant translations of leptospirosis were included in was classified by ecoregion based on the Terrestrial Ecore-
searches; e.g., “leptospirose” for African Index Medicus. Reports gions of the World (10). Ecoregions are defined as relatively
were stored and organized using RefWorks® bibliographic soft- large units of land or water containing a distinct assemblage
ware to initially detect duplicates. Reports from gray material of natural communities that share a large majority of species,
were collected from ProMED and entered manually. dynamics, and environmental conditions. There are 867 ter-
We reviewed article titles and abstracts to identify and exclude: restrial ecoregions, classified into 14 different biomes such as
i) reports with no data; i.e., literature reviews, letters, and other forests, grasslands, or deserts (10). Part 2 of the analysis char-
reports on human leptospirosis that did not contain data or that acterized outbreaks meeting Option 2 criteria; i.e., reporting ≥1
discussed leptospirosis generally; ii) reports with data collected laboratory-confirmed case, by case demography, risk factors,
before 1970 and after 2012; and, iii) reports with data unrelated to and clinical manifestations.
human cases; i.e., articles related to wildlife, laboratory, or animal
reservoirs. Articles were classified as describing human leptospi- RESULTS
rosis outbreaks if they described an event or events meeting the
following criteria: i) event classified by the author or reporting 1. Overall description of all outbreaks (N = 318)
entity as an “outbreak,” or “epidemic,” or “elevated” number of
human leptospirosis cases; or, ii) event included at least two sus- Search results. We reviewed a total of 19 454 search results
pected cases that were geographically and temporally related. across 38 databases for leptospirosis outbreaks (Figure 1).
Final articles were assessed for leptospirosis outbreak accuracy The review yielded 318 leptospirosis outbreaks (270 from

TABLE 1. Assessment checklist to evaluate the quality of evidence for leptospirosis outbreak from a systematic literature
review, 1970–2012

Quality criteria Leptospirosis outbreak definition Laboratory confirmation Case ascertainment whether Time period Number of outbreaks
with standard methods community or hospital/
and definitionsa provider-based
All By author or at least two … … … 318
epidemiologically related cases
Option 1 By author or at least two Outbreak with at least one … … 188
epidemiologically related cases confirmed case or with
probable cases only
Option 2 By author or at least two Outbreak with at least one … … 127
epidemiologically related cases confirmed case
Option 3 By author or at least two Outbreak with at least one … Defined duration 86
epidemiologically related cases confirmed case reported
Option 4 By author or at least two Outbreak with at least one Active ascertainment of Defined duration 54
epidemiologically related cases confirmed case cases whether community reported
or hospital/provider-based
a
Laboratory confirmed: four-fold increase in MAT titer between acute and convalescent samples, MAT titer ≥1:400 in single sample, positive for Leptospira by PCR, culture, or immunohistochemistry. Probable cases: positive for IgM, MAT
titer ≥1:100 and <1:400 in single acute sample.
MAT: microagglutination test. PCR: polymerase chain reaction.
Source: Prepared by authors from study-collected data.

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Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012 Review

FIGURE 1. Flow chart of a systematic literature review of This was followed by outbreaks in the temperate broadleaf
leptospirosis outbreaks reported in scientific literature from and mixed forest ecoregion (21.7%; 69/318) (Figure 2). Many
1970 to 2012 outbreaks in tropical and subtropical forest were in Eastern,
Southeast, and Southern Asia, with most of them in coastal cities
Master database and islands. All the outbreaks reported in Middle and Western
n = 19 454
Africa (n = 24) were in the tropical/subtropical moist broadleaf
forest. Outbreaks occurring in North, Central, and South Amer-
ica occurred in diverse ecoregions, e.g., tropical, subtropical,
Remove all entries classified as duplicate
Remove 13 545 temperate, and Mediterranean ecoregions; outbreaks occurring
citations, not related to leptospirosis,
and/or not related to humans
citations in Central America and the Caribbean tended to be near coastal
cities and islands. Among outbreaks occurring in Europe, the
most common ecoregion was temperate broadleaf and mixed
Initial outbreak database with
4 816 classified as
forest.
citations for classification
n = 5 909
non-outbreaks Temporal distribution. During 1970–2012, there was an aver-
age of seven outbreaks each year (range: 1–19) (Figure 3).
Reporting increased after 1993 and peaked during 1997–1999
Preliminary outbreak classification based on Reclassified 10%
(n = 44). Twelve outbreaks were extracted from reports pub-
title and abstract, including records unable to randomsample of lished in the study period that did not include information
be classified based on title and abstract non-outbreak
n = 1 093 articles
about when the outbreak occurred.
Outbreak setting. Outbreaks were reported to have occurred
in urban, rural, and mixed urban/rural settings in 16% (52/318),
82 not found 15% (47/318), and 9% (27/318) of reports, respectively. In 24%
Obtain all articles. All languages in
database included. Classification of articles 405 classified as (76/318) of outbreaks, information provided did not allow for
performed via article scans if unable to
6 unable to classify due determine from title/abstract
non-outbreaks setting classification. The lowest proportion of urban outbreaks
to language was reported during 1979–1984 (0%), increasing to 47% during
2000–2002. Eighty-three of the 318 (26%) outbreaks occurred in
an occupational setting, of which 66% (55/83), 7% (6/83), and
Final number of citations 110 classified as
241 unable to extract
n = 600 redundant
27% (22/83) were in a rural, urban, or undetermined occupa-
due to language
(521 publications + 79 ProMED posts) outbreak reports tional settings, respectively. Occupational setting-associated
(not duplicate
articles) outbreaks were most common during 1985–1987 (47.6%; 10/21),
1988–1990 (69.2%; 9/13), and 1991–1993 (53.3%; 8/15), with a
Final number of completed extractions
n = 249
decreasing trend after 1993. The overall number of outbreaks
(201 publications + 48 ProMED posts) in a recreational setting was small (10.4%; 33/318); however, it
represented 23.8% (5/21) of outbreaks in 1985–1987 and 17.6%
(6/34) of outbreaks in 2009–2012.
Data collected from 318 unique
outbreaks 2. Laboratory-confirmed outbreaks (N = 127)
Source: Prepared by authors from study-collected data.
At least one laboratory-confirmed leptospirosis case was
reported clearly in 39.9% (127/318) of all outbreaks, in addition
to probable and/or suspect cases. Sixty-one outbreaks reported
scientific literature and 48 from ProMED) from 64 different probable cases only, which were diagnosed serologically using
countries. Seventy percent (n = 222) were in English and the ELISA and/or microagglutination test (MAT). The proportion
rest were translated from Spanish (n = 62), Portuguese (n = 14), of outbreaks with laboratory-confirmed cases was greatest in
French (n = 7), Georgian (n = 6), Japanese (n = 3), Italian (n = 2), the earlier years of this review, with 60% (9/15) in 1970–1972
Russian (n = 1), and Bosnian (n = 1). and 73.3% (11/15) in 1973–1975 and a decreasing trend over
Regional distribution. The regions of the world reporting time. The proportion in the later years, 2009–2012, was 23.5%
the most outbreaks were Latin America and the Caribbean (8/34). Eighty-six outbreaks had ≥1 confirmed leptospirosis
with 35.8% (114/318), followed by Southern Asia with 12.9% case and stated a defined time for the outbreak duration (Option
(41/318), and North America with 10.7% (34/318) (Figure 2). 3); active case ascertainment was used in 54 of those outbreaks
Among outbreaks occurring in the Latin America and the Carib- (Option 4). Only the 127 outbreaks that reported ≥1 laboratory-​
bean region, 45.6% (52/114) were located in the Caribbean confirmed case (Option 2) were used for the purpose of this
(mostly Cuba with 42 outbreaks) and 45.6% (52/114) in South further epidemiological and clinical characterization (Table 1).
America (mostly Brazil with 28 outbreaks). At the country level, Outbreak epidemiological characteristics. Overall average
the highest numbers of leptospirosis outbreaks were reported outbreak size was 82 cases (range: 2–2 259). The ecoregion with
in Cuba (13.2%; 42/318), followed by India (11.9%; 38/318), and the largest average outbreak size was the tropical/subtropical
the United States of America (10.4%; 33/318). dry broadleaf forest ecoregion (253 cases, n = 17) followed by
Outbreaks by ecoregion. The largest proportions of the moist broadleaf forest (77 cases, n = 46), and temperate broad-
outbreaks were located in the tropical and subtropical moist leaf forest (14 cases, n = 35). Extraction of risk factor information
broadleaf forest ecoregion (32.1%; 102/318) and the tropical showed that 25% (32/127) of outbreaks were related to work
and subtropical dry broadleaf forest ecoregion (22.6%; 72/318). activities such as farming and agriculture, as well as other

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Review Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012

FIGURE 2. Global distribution of human leptospirosis outbreaks reported in the literature by ecoregion obtained from a systematic
literature review from 1970 to 2012

0 4,000 8,000 12,000 kilometers

outbreaks Mediterranean Forests. Woodlands and Scrub Tropical and Subtropical Coniferous Forests

Boreal Forests/Taiga Montane Grasslands and Shrublands Tropical and Subtropical Dry Broadleaf Forests

Deserts and Xeric Shrublands Rock and Ice Tropical and Subtropical Grasslands, Savannas and Shrublands

Flooded Grasslands and Savannas Temperate Broadleaf and Mixed Forests Tropical and Subtropical Moist Broadleaf Forests

Inland Water Temperate Conifer Forests Tundra N

Mangroves Temperate Grasslands. Savannas and Shrublands

Source: Prepared by authors from study-collected data.

outdoor jobs that exposed people to rodents and contaminated as the most common serovar. Reports from 8% of outbreaks
environment (e.g., landscaping, sewer management). Exposure (10/127) described an intervention that was implemented as a
to floodwaters due to increased rainfall, monsoon, or natural result of the investigation, including measures to stop exposure
disasters (e.g., typhoons) was identified in 23% of outbreaks (i.e., shutting down a fountain, pool closure, use of protective
(29/127). Twenty-two percent (28/127) of the outbreaks were clothing, euthanasia of infected dog), use of chemoprophylaxis,
linked to exposure to recreational swimming, water sports, or use of vaccination, and education programs.
domestic use, e.g., bathing. A few outbreaks (4%; 5/127) were Demographic and clinical presentation. Of the 127 outbreaks
linked to Leptospira exposure from dogs. Almost all outbreaks with ≥1 laboratory-confirmed case, 28% (36/127) included
linked to swimming (96%; 27/28) and dog exposure (80%; 4/5) adults only, 29% (37/127) included adults and children, 10%
were described as point source. Twenty-three outbreaks (18%) (13/127) involved children only, and 32% (41/127) did not pro-
did not have enough information to determine outbreak setting. vide age information. Based on 33 outbreaks with reliable sex
Outbreak investigation. Outbreak investigation was carried distribution data, the average proportion of male cases was 77%
out in 80% (101/127) of outbreaks. A formal outbreak investiga- (range: 40%–100%). Eighty-one percent (103/127) of outbreaks
tion using a case-control approach to identify potential exposure included clinical information about the patients (Table 2). Fever
sources was used in 26% of outbreaks (26/101). In a large majority was reported in almost all outbreaks, and jaundice and renal
(73%; 4/101) of outbreaks, information on exposure was based failure were common complications. More adults-only out-
on case interviews. Further investigation involving reservoir breaks reported renal symptoms, anorexia, and altered mental
laboratory testing was carried out in 32% (32/101) of outbreaks. state compared to outbreaks involving children. Conversely,
In three instances, the human outbreak investigation was initi- pulmonary symptoms, meningitis, hepatitis, pancreatitis, ocular
ated subsequent to an animal leptospirosis outbreak. Among 92 symptoms, and myalgia were more common among children-​
outbreaks with available data, most common MAT titers were only outbreaks. Case fatality (number of deaths/number of
to serogroup Icterohaemorrhagiae occurring in outbreaks with confirmed leptospirosis cases) was calculated for 83 outbreaks
swimming/water exposure, occupational, and flooding as risk reporting detailed case counts and vital status, resulting in
factors. Titers to serogroup Sejroe were the second most com- 5% (range: 0%–60%) overall fatality, 1% (range: 0%–6%) for 10
mon and present in occupational-related outbreaks. Further children-only outbreaks, 4% (range: 0%–60%) for 34 adults-only
etiologic investigation (n = 38) through isolation found L. inter- outbreaks, 7% (range: 0%–35%) for 24 generalized outbreaks,
rogans as the most common species and Icterohaemorrhagiae and 7% (range: 0%–51%) for 15 outbreaks of undetermined age.

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Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012 Review

FIGURE 3. Number of human leptospirosis outbreaks by setting obtained from a systematic review of literature between 1970 and
2012 (n = 306)a

45

40 Recreation/sports
Occupational
35 Rural
Urban
30 Undetermined
Number of outbreaks

25

20

15

10

0
2

2
97

97

97

98

98

98

99

99

99

99

00

00

00

01
-1

-1

-1

-1

-1

-1

-1

-1

-1

-1

-2

-2

-2

-2
70

73

76

79

82

85

88

91

94

97

00

03

06

09
19

19

19

19

19

19

19

19

19

19

20

20

20

20
Year of outbreak

a
12 additional outbreaks were reported in the reviewed time period but did not include a specific year.
Source: Prepared by authors from study-collected data.

TABLE 2. Number and proportion of leptospirosis outbreaks obtained from a systematic literature review from 1970 to 2012
reporting specific clinical manifestations

Outbreak age distributiona

Clinical presentation Children only Adults only Both Undetermined Total
(number of outbreaks) (n = 12) (n = 35) (n = 32) (n = 24) (n = 103)b
Fever 12 (100%) 31 (89%) 32 (100%) 20 (83%) 95 (92%)
Jaundice 7 (58%) 17 (49%) 19 (59%) 9 (38%) 52 (50%)
Renal injury 3 (25%) 17 (49%) 18 (56%) 8 (33%) 46 (45%)
Pulmonary injury 3 (25%) 3 (9%) 11 (34%) 9 (38%) 26 (25%)
Meningitis, neurological 5 (42%) 7 (20%) 8 (25%) 5 (21%) 25 (24%)
Stiff neck 1 (8%) 4 (11%) 5 (16%) 2 (8%) 12 (12%)
Uveitis, other eye symptoms 3 (25%) 3 (9%) 3 (9%) 2 (8%) 11 (11%)
Anorexia, weight loss … 7 (20%) … 2 (8%) 9 (9%)
Altered mental state … 2 (6%) 4 (13%) … 6 (6%)
Hepatitis, pancreatitis 2 (17%) … … 2 (8%) 4 (4%)
Myalgia, other pain 1 (8%) 1 (3%) 1 (3%) 1 (4%) 4 (4%)
a
For a given age group, percentage is the proportion of outbreaks reporting occurrence of the specific clinical presentation (≥1 patient).
b
n = 103, total outbreaks with ≥1 confirmed case and with clinical information in the report.
Source: Prepared by authors from study-collected data.

DISCUSSION particular increase after the mid-1990s. Results also revealed

substantial differences in outbreak detection, diagnosis,
The number of reported leptospirosis outbreaks increased methods of source identification, and response. Furthermore,
during the time period investigated in this review, with a this review revealed gaps in the quality and completeness

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Review Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012

TABLE 3. Recommendation for leptospirosis outbreak reporting based on findings from a systematic literature review, 1970–2012

Recommendations for reporting Highlights from literature review

Surveillance • Describe surveillance type (passive, active) 89% had as outbreak definition “increase in number of cases”
• Describe case ascertainment method (hospital-based, community-based) 56% had specific dates
• State outbreak definition including population, location, and duration 42% did not state case finding process
Diagnostics • State suspect, probable, and confirmed case definitions and case counts 52% applied recognized case definitions
• State laboratory diagnostic effort with respect to number of cases 40% stated at least one laboratory-confirmed case
Increase in use of rapid tests without confirmation
Outbreak characteristics • Describe setting (urban, rural) and source Location often identified as city instead of population affected
• Describe epidemic curve and outbreak type (point source, continuous 30% with undetermined source, no or broad risk factors
common source) 15% with breakdown of cases by age, sex
• Describe case demographic features
• Describe number of deaths, fatality ratio
• Describe clinical features of cases and deaths
Outbreak response • Describe type of outbreak investigation 54% with outbreak investigation
• Describe identification of causal agent 10% with outbreak response
• Describe outbreak response and timeline 32% reported causative agent
Source: Prepared by authors from study-collected data.

of reporting. Systematic detection and standardized report- to specialized laboratories for MAT and/or PCR, the confirma-
ing of outbreaks are necessary to understand determinants, tory tests, is a significant barrier to achieve confirmation and, in
mechanisms, and trends across different geographic regions. the face of an outbreak, antibiotic treatment without waiting for
Leptospirosis continues to cause outbreaks resulting in laboratory diagnostic results is recommended clinical practice
excess illness, deaths, and health care costs (11–15). As with (22). As the availability of various commercial rapid tests con-
many other infectious diseases (16), attention to leptospiro- tinues to increase (23), research is needed to identify their role
sis increases after recognized outbreaks, but dissipates after in leptospirosis surveillance and accurate outbreak detection
the emergency has subsided, resulting in the slow pace of and response.
outbreak research. Significant improvements in outbreak Temporal and geographic distribution of outbreaks showed
detection, investigation, and reporting quality are needed to an increase over time and widespread occurrence in various
better predict, prepare for, and reduce the health impact of lep- ecoregions globally (Figure 2) that are consistent with the
tospirosis outbreaks. known epidemiology of high incidence in tropical and subtrop-
Table 3 contains a checklist of items involved in the process ical ecoregions (1), although outbreaks occurred in non-tropical
of outbreak detection, diagnosis, epidemiological investiga- ecoregions as well. There was a noticeable gap in reports from
tion, and response with corresponding recommendations for countries in the African region, even in ecoregions generally
developing reporting standards; it also highlights key barriers suitable for leptospirosis transmission. Knowledge on lepto-
and limitations revealed in the data review. Although efforts spirosis in Africa is limited; however, more leptospirosis and
to develop standards for diagnosis and clinical management febrile illness research is being done in various countries,
of leptospirosis clinical cases are increasing (17–19), there are including Tanzania (24, 25), the Central African Republic (26),
inadequate efforts to develop improved methods for out- and Burkina Faso (27). These studies have begun to reveal lep-
break research focused on leptospirosis. Furthermore, a lack tospirosis as a recurrent cause of febrile illness in the African
of baseline surveillance information can lead to difficulties in region. More research will provide better information on risk
accurately differentiating epidemic from background endemic areas and infection dynamics.
disease transmission (20), resulting in unrecognized outbreaks, We observed an increase in the number of outbreak reports
delayed responses, and missed opportunities to collect critical linked to floods, particularly during the later years included in
outbreak data. the review (1994–2012). This association has long been recog-
Outbreaks were classified by criteria evaluating certainty nized and believed to be the result of multiple factors. Increases
of a leptospirosis outbreak (Table 1), based on description of in rainfall and floods of different magnitudes can alter the local
laboratory-confirmed cases, that cases occurred within a ecology of leptospirosis as well as the animal reservoir and
defined time period, and that a reliable number of cases were human population’s conditions and behaviors. Heavy rain or
obtained from active case ascertainment. These quality crite- excess water can facilitate dispersion of leptospires from the
ria were selected because leptospirosis can be misdiagnosed soil, where they can survive for long periods of time, to surface
as other diseases (e.g., dengue, chikungunya, influenza, other water (28). Lastly, displacement, interruption of rodent control
acute viral or bacterial illnesses) (18, 21) and due to the need to activities, and reduced access to safe water can result in out-
recognize outbreaks as an increase in cases from baseline within breaks, while disruptions of health care services can limit access
a particular timeframe. In most outbreak reports, laboratory to prompt care (20). Data review showed that while outbreaks
diagnosis for leptospirosis was attempted; however, only 40% after swimming or other recreational exposure to contaminated
clearly described identification of laboratory-confirmed cases water were almost exclusively point source outbreaks, expo-
(Table 1). Furthermore, 61 outbreaks reported only probable sure sources in flood-related outbreaks are difficult to ascertain.
cases, which is consistent with an increase in the use of rapid The associations between rainfall, environmental exposure, and
tests based on detection of IgM antibodies. The need for access leptospirosis risk are being investigated with epidemiological

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Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012 Review

(29–33) and laboratory methods (34, 35) to understand drivers needed before leptospirosis outbreak patterns can be fully char-
and mechanisms. However, further research is needed in the acterized. This is particularly important for areas expected to
area of outbreak prediction after heavy rains and related natu- be suitable for leptospirosis transmission but currently silent.
ral disasters, including the role of the environment as habitat of Among the reviewed sources, the completeness of report-
pathogenic Leptospira. Guidelines and recommendations exist ing varied across the categories summarized in Table 3. Most
for chemoprophylaxis for travel medicine or certain risk groups reports indicated an outbreak definition, but other elements,
(i.e., military, rice farmers) expecting exposure to a potentially particularly details in diagnostics and epidemiological descrip-
contaminated environment (36) but these need to be paired tion, were missing in a high number of outbreaks. Obtaining
with improved surveillance information on local individual relevant surveillance information, in particular when facing
and outbreak risk factors to avoid unnecessary medication. large public health emergencies, is frequently challenging, but
Similarly, guidelines for chemoprophylaxis for longer-term it is fundamental to understand outbreak impact, determinants,
occupational exposure to contaminated fields or floods need to and contributing risk factors (20). Efforts should be made for a
be developed with an improved understanding of underlying multisectoral and global effort to develop and use standardized
outbreak risk (37). outbreak data collection forms and user-friendly platforms for
Reliable and detailed data on sex and age distribution of cases reporting.
were limited; nevertheless, outbreak demographics revealed a
larger proportion of male than female cases, which is consis- Conclusions
tent with the known epidemiology of leptospirosis describing
higher incidences in men due to higher exposure risk (1). Most Leptospirosis outbreaks had a widespread distribution
outbreaks were in adult populations and there were a few and increased over the study period, in particular in tropical
children-only outbreaks (Table 2) with sources linked to special ecoregions. The impact can be significant due to the occur-
circumstances such as school or recreational activities. Lim- rence of large outbreaks and high fatality. However, outbreak
ited clinical data in the outbreak reports suggested that fever reporting practices were variable and with often limited infor-
was the most common manifestation overall and while more mation regarding diagnosis and epidemiology. More research
children-only outbreaks reported jaundice, pulmonary injury, is needed to understand leptospirosis outbreak predictors and
and meningitis, more adults-only outbreaks reported renal risk factors; however, lack of standardized diagnostic and epi-
injury. Comparative case studies have reported more jaundice demiological practices is a significant impediment. A concerted
and icteric forms of leptospirosis in adults than in children and global effort is needed to produce, and subsequently adopt,
(38, 39). Similar to our findings, studies have reported more guidelines for detection, investigation, and reporting of lepto-
frequent acute renal injury (40) and higher fatality rate in adults spirosis outbreaks.
than in children (38, 40). Pediatric leptospirosis is relatively less
described in the literature and mild illness is common (41, 42). Author contributions. CMZ, MCS, EB, and FC contributed to
More research is needed to fully understand distinct clinical developing the original concept. CMZ and BMM designed the
patterns that can help with early detection of outbreaks in review and collected the data. CMZ, EG, and KB performed
children and diagnosis and treatment. data analysis. CMZ and MCS wrote the paper. All authors con-
There are many elements influencing how these outbreaks tributed to interpretation of results and reviewed and approved
were identified in our review, including existing surveillance the final version.
systems to monitor trends and to identify outbreaks and labora-
tory capacity for diagnosis. Furthermore, this review was based Acknowledgments. We thank Christopher Campbell (Uni-
on outbreaks reported in the scientific literature, which relies versity of Minnesota) for assistance with data extraction and
on investigators’ interest and ability to publish. We included data management and the following individuals for their
ProMED in an attempt to cover non-scientific reporting; contribution with data extraction of non-English reports:
however, information provided was generally minimal. Con- Brooke Higgins (University of Minnesota), Mageen Caines
sequently, this review would underestimate the real impact of (University of Minnesota), Stefan Gherghelegiu (University
leptospirosis outbreaks. Authors’ indication of a leptospirosis of Minnesota), Tat’Yana Kenigsberg (University of Minne-
outbreak and its descriptive data may be subject to inaccuracy sota), Cynthia Yoon (University of Minnesota), Basant Motawi
due to lack of baseline data, case misclassification, and different (WHO), Chisato Ito (Simon Fraser University), Malin Finkerna-
approaches to ascertain information. Additionally, the ability to gel (Paul-Ehrlich-Institut), Giorgia Sulis (Università degli Studi
assess temporal trends is limited due to changes in laboratory di Brescia), and Carmen Morawski (Boise State University). We
capacity and surveillance systems over time, and some of the acknowledge the Global Leptospirosis Environmental Action
increase in reported leptospirosis outbreaks may be attributed Network (GLEAN) as contributors to initial discussions on
to expansion of laboratory access and/or changes in mandatory the scope of this review (CMZ, MCS, FC, and EB are GLEAN
reporting regulations. members).
For many infectious diseases, current surveillance programs
are not equipped with the necessary tools for early detec- Conflicts of interest. The authors declare no conflict of
tion, prevention, and follow-up strategies (43). The need to interest.
strengthen surveillance systems is particularly pressing at the
human–animal–environment interface, as spillover events, Disclaimer. Authors hold sole responsibility for the views
together with environmental drivers, can be a significant expressed in the manuscript, which may not necessarily reflect
contributor to leptospirosis outbreaks. The coverage of lepto- the opinion or policy of the RPSP/PAJPH and/or the Pan Amer-
spirosis surveillance is limited (9, 43) and further expansion is ican Health Organization.

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Review Munoz-Zanzi et al. • Leptospirosis outbreaks worldwide, 1970–2012

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Revisión sistemática de los brotes de leptospirosis en el mundo, 1970-2012

RESUMEN Objetivo. Describir la distribución geográfica y temporal, los métodos de detección y otras características
epidemiológicas de los brotes de leptospirosis publicados con el fin de fundamentar los esfuerzos tendientes
a estandarizar las prácticas empleadas en la notificación de brotes.
Métodos. Se llevó a cabo una revisión sistemática de los brotes de leptospirosis notificados en la bibliografía
científica y en ProMED entre 1970 y 2012. Se utilizaron criterios predefinidos para identificar y clasificar los
brotes y se empleó un formulario estándar para extraer la información.
Resultados. Entre 1970 y 2012 se identificaron 318 brotes (promedio: 7 brotes/año; rango: 1-19), la mayoría
de ellos en América Latina y el Caribe (36%), región seguida por Asia meridional (13%) y América del Norte
(11%). La mayoría de los brotes se localizaron en ecorregiones tropicales y subtropicales (55%). La clasifi-
cación cualitativa reveló que en el 40% de los brotes había una clara descripción de los casos confirmados
por laboratorio. Entre ellos, el tamaño promedio del brote fue de 82 casos (rango: 2-2259 casos) pero alcanzó
los 253 casos en ecorregiones tropicales o subtropicales. Entre los factores de riesgo frecuentes figuraban
las actividades laborales al aire libre (25%), la exposición a agua proveniente de inundaciones (23%) y la
exposición a agua con fines recreativos (22%). En el 80% de los brotes se realizaron investigaciones epide-
miológicas, principalmente entrevistas de casos. La mortalidad específica de los casos fue del 5% (rango:
0%-60%).
Conclusiones. La notificación de brotes aumentó durante el período de estudio, y los brotes abarcaron
regiones tropicales y no tropicales. Los brotes fueron diferentes en cuanto a su tamaño, el entorno y los facto-
res de riesgo; sin embargo, los datos examinados con frecuencia incluían una información limitada respecto
del diagnóstico y la epidemiología. Se recomiendan directrices para elaborar procedimientos estandarizados
para las investigaciones diagnósticas y epidemiológicas durante un brote y para su notificación.

Palabras clave Leptospirosis; Leptospira; brotes de enfermedades; zoonosis; vigilancia en salud pública.

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