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International Journal of Infectious Diseases (2008) 12, 351—357

http://intl.elsevierhealth.com/journals/ijid

REVIEW

The globalization of leptospirosis: worldwide


incidence trends
Georgios Pappas a,*, Photini Papadimitriou a, Vasiliki Siozopoulou a,
Leonidas Christou b, Nikolaos Akritidis c

a
Institute of Continuing Medical Education of Ioannina (ICMEI), Har. Trikoupi 10, Ioannina, 45333, Greece
b
1st Division of Internal Medicine of the Medical School at the University of Ioannina, Ioannina, Greece
c
Internal Medicine Department of the General Hospital ‘‘G. Hatzikosta’’ of Ioannina, Ioannina, Greece

Received 25 June 2007; accepted 18 September 2007


Corresponding Editor: William Cameron, Ottawa, Canada.

KEYWORDS Summary
Leptospirosis; Objectives: Leptospirosis continues to be a significant zoonosis of the developing world. Glo-
Epidemiology; balization, in the context of international travel, particularly for recreational activities and
Incidence military expeditions, has led to increased exposure of individuals from the developed world to the
disease, as recent outbreaks show.
Methods: We evaluated the trends in annual leptospirosis incidence for individual countries
worldwide through reports from national and international organizations, the published medical
literature on the subject, and web searches with the terms ‘leptospirosis’ and the individual
country names. Inter-country variations in leptospirosis incidence, when relevant official data
were available, were also analyzed.
Results: The Caribbean and Latin America, the Indian subcontinent, Southeast Asia, Oceania,
and to a lesser extent Eastern Europe, are the most significant foci of the disease, including areas
that are popular travel destinations.
Conclusions: Leptospirosis is a re-emerging zoonosis of global importance and unique environ-
mental and social correlations. Attempts at global co-ordination and recognition of the true
burden of an infectious disease with significant mortality should be encouraged.
# 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Introduction endemicity in animal vectors and human exposure, it is gen-


erally confined to the developing parts of the world, being
Leptospirosis remains one of the most common and most randomly reported from industrialized countries2 often as an
dreaded zoonotic infections worldwide.1 Traditionally related imported disease following international travel to exotic des-
to certain socioeconomic or climatic conditions that favor tinations.3 In recent years, a new trend in human leptospirosis
outbreaks has been observed related to recreational activities
among the wildlife (a form of tourism that is becoming increas-
* Corresponding author. Tel.: +30 26510 28289. ingly popular) and army expeditions, either for training or for
E-mail address: gpele@otenet.gr (G. Pappas). combat-related purposes in similar environments.4—7 Thus

1201-9712/$32.00 # 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijid.2007.09.011
352 G. Pappas et al.

leptospirosis has become an important infectious agent to take general search engines), using leptospira/leptospirosis and
into account when preparing for such expeditions, and this is individual country and region names as keywords. ProMED-
reflected in efforts to define and utilize successful preventive mail, an electronic system reporting infectious disease out-
antibiotic administration policies.8 breaks, developed by the International Society for Infectious
Eradication of the disease involves not only the duties of Diseases, was also used. When available, official national
the veterinarian but also adequate health and surveillance data were used, even if not in concordance with data from
networks in the developing world; awareness of the evolution international organizations. For countries without such offi-
of the global incidence of human disease is important for cial data, data from international organizations were used.
acknowledging the relative risks in international travel and in The medical literature was used only when including signifi-
highlighting world areas that should move at the epicenter of cant epidemiological information, or (in the case of seropre-
enhanced disease surveillance and attempts at control from valence studies) in the absence of any other data regarding
international health organizations. We sought to define the disease status in a country. Serial data on incidence were
areas of the world where leptospirosis is at present a public evaluated for the presence of epidemiologic trends for indi-
health problem and a potential risk for visitors, and to define vidual countries. In calculating the annual incidence, when
the patterns present in the changing (if changing) incidence this information was not provided in the source references,
of the disease over the last decade. population data derived from official publications such as the
CIA World Factbook9 were used.
Methods
Results
Data on the prevalence of human leptospirosis for each
country from 1996 onwards were sought from health minis- Table 1 lists the annual incidence of human leptospirosis for
tries or other official national organizations, public health certain countries, including the 28 countries with the highest
international organizations, and the medical literature. The incidence, and other important countries. As is shown clearly
medical literature was searched through MEDLINE (but also in Figure 1, the endemicity of the disease is mainly located in

Table 1 Annual incidence of leptospirosis worldwidea

Countries with the highest incidence Countries for which no Other countries
data are available,
Rank Country Annual incidence per Country Annual incidence per
probably endemic
million population million population
1 Seychelles 432.1 India Belarus 3.4
2 Trinidad and Tobago 120.4 Malaysia Bulgaria 3.7
3 Barbados 100.3 Bangladesh Chile 1.6
4 Jamaica 78 Vietnam Colombia 1.6
5 Costa Rica 67.2 Laos Czech Republic 1.8
6 Sri Lanka 54 Nepal France 3.9
7 Thailand 48.9 Cambodia Germany 0.7
8 El Salvador 35.8 Indonesia Greece 3
9 New Zealand 26 Myanmar Honduras 3.1
10 Uruguay 25 China Hungary 3.1
11 Cuba 24.7 Iran Ireland 2.2
12 Nicaragua 23.3 Suriname Italy 0.7
13 Croatia 17.3 Haiti Lithuania 2.2
14 Russia 17.2 Peru Mexico 1
15 Ukraine 15.3 Netherlands 1.9
16 Dominican Republic 13.8 Panama 1.3
17 Brazil 12.8 Paraguay 1.9
18 Ecuador 11.6 Serbia and Montenegro 1.5
19 Argentina 9.5 Singapore 2
20 Romania 9.4 South Korea 2.8
21 Australia 8.9 Spain 0.3
22 Portugal 6.8 UK 0.6
23 Denmark 6 USA 0.1
24 Latvia 5.6 Venezuela 3.8
25 Slovenia 5.4
26 Philippines 4.8
27 Slovakia 4.4
28 Taiwan 4.1
a
Data as indicated in the text.
The globalization of leptospirosis 353

Table 2 Selected regions, districts, and provinces with a


high human leptospirosis incidencea

Region/district/province Country Annual incidence


per million
population
Andaman Islands India 500
Loei Thailand 467.8
Guadeloupe France 311.9
Roi Et Thailand 299.3
North Queensland Australia 288
Khon Kaen Thailand 286.4
Kalasin Thailand 286
Figure 1 Global annual incidence of human leptospirosis. Lampang Thailand 269.3
Colors reflect incidence, in declining order: red, pink, green, Pollonaruwa Sri Lanka 247.2
yellow. Gold reflects areas with probable, but not estimated, Surin Thailand 240
high incidence. White reflects absence of data. Matale Sri Lanka 236
Kegalle Sri Lanka 228.2
Matara Sri Lanka 215
the Caribbean and Central and South America, as well as in Kalutara Sri Lanka 200
Southeast Asia and Oceania. Brunca Costa Rica 171
In developing this list, significant drawbacks became French Polynesia France 105.8
apparent. There were no data for many developing countries, Azores Portugal 83
and for certain developing countries the data may be con- New Caledonia France 59.3
sidered unreliable. In some countries, reported cases were a
Data as indicated in the text. Data for Andaman Islands are
found to range from significant numbers to zero within a year,
from an International Leptospirosis Society Survey, available at:
while the absence of reported cases for certain other coun- http://www.leptonet.net/html/ils_worldwide_survey.asp.
tries may not be as a result of absence of the disease when
neighboring countries appear to be hyperendemic. This latter
point seems to be the case for many Asian countries, includ- Nicaragua also come high on the list; in the latter, the
ing India, where the disease is known to be present, Malaysia, incidence is higher in the southern regions of Rio San Juan,
where an outbreak occurred during the Eco-Challenge that neighboring Costa Rica, and Carazo (annual incidence 50—60
took place in 2000, and the majority of Africa, where the per million), but also in the northern regions of Jinotega and
disease is known to cause random outbreaks, as occurred Nueva Segovia, neighboring Honduras, according to epide-
recently in Kenya. Another drawback was the low statistical miological reports from the Ministry of Health.13 This is in
significance of results from countries with small populations contrast to outbreaks in previous years, which, following
(for example, Vanuatu reported five cases in 2003, which Hurricane Mitch in 1998, were located in the regions of Esteli
equals an annual incidence of 24.3 per million population, and Chinandega. The significantly lower incidence of the
but reported no cases in 2004, incidence falling to zero). disease in Panama, Guatemala, and Honduras may represent
Inter-country variation was also significant, and for certain the actual situation or an artifact derived from inadequate
countries the burden of disease was high in some provinces surveillance systems. Cuba expresses significant scientific
while being non-existent in others. Table 2 summarizes such interest in the disease, having hosted three Leptospirosis
world areas and their annual leptospirosis incidence accord- International meetings in the last 5 years (Institute of Tro-
ing to official data. pical Medicine ‘‘Pedro Kouri’’). For the Dominican Republic, a
contrast between data available from the Office Interna-
The Americas tional des Epizooties (OIE),14 used in estimating the incidence
in Table 1, and reports from ProMED,15 which denote extre-
The disease is absent from Canada and has been removed mely few cases for 2005, is characteristic of the inconsistency
from the notifiable diseases list in the USA, where few annual of data in various world regions.
cases occur, randomly related to recreational activities in The disease is endemic in the Caribbean islands, according
fresh water.5 Hawaii is the exception, with an estimated to annual reports from the Caribbean Epidemiology Centre:
annual incidence of 12.9 per million population.10 in 2000, more than 500 cases were confirmed from Caribbean
In Mexico, a small increase in reported annual cases has islands, leading to a cumulative annual incidence of >100 per
been observed in recent years according to data from the million population.16 Barbados retains an increased inci-
General Directorate of Epidemiology,11 the majority of cases dence, despite the active government attempts at preven-
in recent years originating from the South Atlantic region of tion and education on the risks for the disease.17 On the other
Veracruz. In Costa Rica, the incidence is higher in the Cen- hand, although Jamaica figures high in the endemicity list,
tral-South Pacific region of Brunca, and in the Huetar Atlan- leptospirosis is not a notifiable disease in this country.
tica and Huetar Norte regions, while being very low in the According to the Caribbean Epidemiology Centre, Trinidad
densely populated central regions of the country, according and Tobago and Suriname are the countries requesting eva-
to data from the National Epidemiological Surveillance Sys- luation of most samples in the region. The former, data
tem.12 Other countries of the region, such as El Salvador and derived from the local press,18 ranks second in the list of
354 G. Pappas et al.

global incidence. A recent outbreak following a flood was Russia is unknown: outbreaks related either to floods35 or
reported from Guyana, with a characteristically high death to recreational activities like swimming in rivers,36 and a
toll and a large campaign of prophylactic administration of trend for disease urbanization37 and the increased role of
doxycycline to more than 120 000 people implemented by the canine leptospirosis38 are the main recent epidemiologic
Panamerican Health Organization.19 The disease is also pre- characteristics.
sent in Haiti, although official data for the last decade are
lacking; in 1995 the annual incidence per million was eight, Asia
and an increasing trend was observed in 1996.20 The hyper-
endemic French territory of Guadeloupe is also located in this Underreporting is a major problem in evaluating the presence
region. and the actual incidence of leptospirosis in many Asian
Although the disease is present in South America, it is not countries. In India, leptospirosis is a major health problem
notifiable in the majority of countries, and data on annual obviously related both to the monsoons and poor sanitary
cases are derived mostly by the OIE. Official data from the conditions, with multiple epidemics reported in recent
Department of Epidemiology of Uruguay denote that the years.39—43 The Andaman and Nicobar Islands top the list
disease is particularly endemic in the southeastern provinces of the most endemic areas of the world, shown in Table 2, yet
of Florida and Rocha (annual incidence 132 and 100 per no official incidence data on most provinces of India
million population, respectively).21 There are no official data exist. Similar environmental and sanitary conditions, with
available for Peru for recent years, although localized epi- the added burden of overcrowding, apply to neighboring
demiological studies in the Amazon Forest region have Bangladesh and Nepal, where the disease was recently recog-
stressed the endemicity of the disease.22,23 Data for Brazil nized as an important alternative diagnosis in patients with
may represent in general the overall endemicity, as studies in suspected dengue and febrile diseases in general, respec-
the Sao Paulo region have shown;24 studies in other regions tively.44,45 In Sri Lanka the disease is hyperendemic, espe-
though, as in Santa Maria have shown a hundred-fold actual cially in the south and north-central provinces, and in the
incidence.25 The absence of continuous surveillance data southern province of Sabaragamuwa, the annual incidence is
precludes drawing any conclusions, since the latter study >140 per million population, according to data from the
may have actually witnessed an outbreak. Urbanization of the Ministry of Health.46 The Seychelles islands possess the high-
disease has consistently been demonstrated in Brazil.26,27 In est incidence worldwide, with annually reported cases and
Argentina the majority of cases are reported from Buenos Aires incidence remaining more or less constant from 1988 onwards
and the northern region of Santa Fe, according to the Direc- according to Ministry of Health and Social Services reports.47
torate of Epidemiology of the Ministry of Health.28 According The incidence may actually be slightly higher, since tentative
to the OIE, most cases in Venezuela (and the highest incidence, surveillance yielded an annual incidence above 1000 per
almost double that of the country’s) present in the northern, million population in the 1995—1996 period.48 In this study,
Caribbean districts of District Capital, Aragua, Anzoategui, serogroups Icterohaemorrhagiae and Hurstbridge, the latter
and Carabobo. OIE numbers for Ecuador, and the estimated related to adverse outcome, were found to be the most
incidence, may actually be higher if ProMED reports on an prevalent.
outbreak in the Pacific province of Manabi29 are taken into There are no data on the presence of leptospirosis in
account, with an estimated incidence for 2002 for this province countries plagued by war such as Afghanistan and Iraq. There
near 100 per million population. are also no data for Pakistan and the countries of the
Middle East. The disease is present in Iran, although data
Europe are limited: a recent study identified 74 patients during a
period of three months in a northern region,49 while another
Most of the factors related to leptospirosis endemicity (tro- study yielded high seroprevalence, especially for serovar
pical climate, stagnant waters, poor levels of sanitation, Hardjo, in a tribal population of West-Central Iran.50 A recent
flooding) are generally absent from Europe, and the overall outbreak of leptospirosis in Tajikistan51 and a 1998 outbreak
situation has not changed significantly over the past decade. in Kazakhstan raise worries about the emergence of the
Local climate and environmental factors have sometimes disease in the former Soviet Republics of Central Asia.
been implicated in fluctuations of annual reported cases, The burden of human leptospirosis in Southeast Asia is
as in France30 and the Czech Republic;31 in the latter country huge. Thailand has been the source of a protracted major
an increase in annual cases was observed following floods outbreak in the 21st century, subsequent to flooding, and
both in 1997 and 2002. An extended review of epidemiology localized mainly in the northeast region of the country.52
patterns of the disease in the last 40 years in Germany32 Data from the Ministry of Health underline the dramatic,
outlined a partial incidence increase since 1998 attributed to sustained incidence in certain regions53 (see also Table 2).
rat population expansion and the re-emergence of canine Fears of the emergence of leptospirosis outbreaks following
leptospirosis. Data from the Italian Ministry of Health33 show the 2004 tsunami disaster did not materialize though, pos-
a steady predominance of cases in the northern wealthy sibly due to the beneficial effect of salt water mixing with
provinces of Lombardia and Veneto. Data from the Portu- fresh waters.3 A recent study from the Thailand—Myanmar
guese Ministry of Health for the period 2001—200534 show an border confirmed leptospirosis as the second, post-malaria,
increasing incidence in the Azores islands, which account most frequent cause of fever in this region.54 There are no
now for more than 50% of the annual cases. official data for Vietnam, Lao People’s Democratic Republic,
Central and Eastern European countries demonstrate the Cambodia, and Indonesia, but studies on the incidence of
highest incidence as shown in Table 1, data derived from the the disease in certain patient populations (jaundiced,55,56
OIE. The actual extent and distribution of the disease in non-malaria febrile patients55) and seroprevalence55 have
The globalization of leptospirosis 355

confirmed the endemicity of the disease. Hurstbridge was the Conclusions


most common serovar identified in this study, while a ser-
oprevalence study in the Mekong Delta of Vietnam showed In a rapidly changing world, where borders are continuously
evidence of recent infection in 41/1400 tested individuals, a crossed due to international tourism trends, tropical infec-
seroprevalence of 18.8%, and Bataviae the most common tions including leptospirosis have emerged as significant
serogroup identified.57 A recent seroprevalence study in causes of imported morbidity, and in the case of leptospiro-
children in South Vietnam yielded a seroprevalence rate of sis, mortality. For a disease for which a lot is still to be
11%.58 There are also no data for Malaysia, host of the most learned on its pathogenesis and treatment principles,2
significant recreational event-related outbreak;4 further- awareness of disease epidemiology and patterns of global
more the disease has been incriminated in 12.6% of febrile incidence may allow for enhanced practices of prevention.
patients in a large study.59 Data from the OIE for Philippines This is especially important since in recent years leptospirosis
are in concordance with a significant, climate-related (mon- outbreaks have characteristically been present in young
soons, floods) burden, while microbiological studies from this healthy populations, including athletes and military recruits,
region have shown a predominance of serogroup Javanica, while urbanization of the disease is of increasing concern.
serovar Poi.60 As expected, global coordination, either under the aus-
There are no official data for China; the disease though is pices of international humanitarian organizations or through
certainly endemic, and the cause of periodic outbreaks in specialized societies such as the International Leptospirosis
certain provinces.61 Taiwan exhibits a significant steady Society (ILS), is the warranted first step towards disease
burden of disease; according to OIE data, the disease is control. The World Health Organization and ILS have recently
believed to have only emerged in the last 30 years.62 A steady initiated the development of a global database called Lep-
number of annual cases are reported annually to the OIE from toNet (accessed at http://www.leptonet.net).
South Korea. For Japan, only the South Pacific island of Obviously adequate disease notification is a futile target,
Okinawa presents a significant disease burden.63 since many endemic countries exhibit inadequate health and
surveillance networks. In the era of molecular medicine,
Oceania notification on Leptospira species and serovars prevailing
in different regions (a subject only briefly touched on in
In continuity with the hyperendemic Southeast Asia zone, the present study as being of specialized interest — relevant
Oceania also exhibits a significant burden of leptospirosis. information can be found in an ILS report)70 may allow
In Australia, according to data from the Department of for better recognition of trends and risks and better imple-
Health and Ageing,64 most cases are derived from Queens- mentation of other preventive measures.
land, where the annual incidence is 28 cases per million Conflict of interest: No conflict of interest to declare.
population, the remaining cases emerging from New South
Wales. North Queensland is one of the world areas with the
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