Tropicalmed 07 00260

Tropical Medicine and
Infectious Disease
Review
Epidemiology of Leptospirosis: The First Literature Review of
the Neglected Disease in the Middle East
Elena Harran 1,2, * , Christo Hilan 2 , Zouheira Djelouadji 1 and Florence Ayral 1
1 Laboratoire des Leptospires et d’Analyses Vétérinaires, Université de Lyon, VetAgro Sup, USC 1233,
69280 Marcy l’Etoile, France
2 Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon
* Correspondence: elena.harran@etu.univ-lyon1.fr
Abstract: Leptospirosis is a major zoonotic disease that has emerged worldwide, and numerous
studies performed in affected countries have provided epidemiological knowledge of the disease.
However, currently, there is inadequate knowledge of leptospirosis in the Middle East. Therefore, we
grouped publications from various Middle Eastern countries to acquire a general knowledge of the
epidemiological situation of leptospirosis and provide an initial description of the leptospiral relative
risk and circulating serogroups. We conducted a detailed literature search of existing studies describ-
ing Leptospira prevalence and seroprevalence in Middle Eastern countries. The search was performed
using online PubMed and ScienceDirect databases. One hundred and one articles were included in
this review. Some countries, including Iran, Turkey, and Egypt, reported more publications compared
to others, such as Lebanon, Kuwait, and Saudi Arabia. Frequently, the seroprevalence of leptospirosis
varied considerably between and within countries. The prevalence of leptospirosis was comparable in
most Middle Eastern countries; however, it varied between some countries. The methods of detection
also varied among studies, with the microscopic agglutination test used most commonly. Some hosts
were more recurrent compared with others. This review summarizes the epidemiological situation of
Citation: Harran, E.; Hilan, C.;
Leptospira infection in the Middle East, reporting predominant serogroups—Sejroe, Grippotyphosa,
Djelouadji, Z.; Ayral, F. Epidemiology
Icterohaemorrhagiae, Autumnalis, and Pomona—that were identified in the most commonly tested
of Leptospirosis: The First Literature
Review of the Neglected Disease in
hosts. Our findings emphasize the need to develop a deeper understanding of the epidemiology
the Middle East. Trop. Med. Infect. of Leptospira spp. and prioritize the disease as a public health problem in this region. To achieve
Dis. 2022, 7, 260. https://doi.org/ this goal, increased awareness is critical, and more publications related to the topic and following a
10.3390/tropicalmed7100260 standardized approach are needed.
Academic Editors: Sérgio Santos de

Keywords: Leptospira; one health; diagnosis; epidemiology; middle eastern countries
Azevedo and Clebert José Alves
Received: 2 September 2022

Accepted: 20 September 2022
Published: 24 September 2022 1. Introduction
Publisher’s Note: MDPI stays neutral Leptospirosis is a zoonosis that is prevalent worldwide and has major impacts on both
with regard to jurisdictional claims in humans and animals [1,2]. The disease is caused by species of Leptospira, a spirochaete
published maps and institutional affil- bacterium with increasing genetic diversity [3,4]. To date, 38 species of pathogenic Lep-
iations. tospira have been described, and new species are continually being discovered [5]. The
morbidity and mortality rates of leptospirosis in humans are estimated at 1 million and
60,000 cases, respectively [6]. Of the reported cases, 2.90 million disability-adjusted life
years are estimated to be lost per annum [7]. Various human-acquired syndromes, ranging
Copyright: © 2022 by the authors.
from flu-like to life-threatening hepatorenal syndromes, have been described to be associ-
Licensee MDPI, Basel, Switzerland.
ated with leptospirosis in the literature [8–10]. In severe cases, mortality rates vary between
This article is an open access article
5% and 20% [6]. Humans, as well as wild and domestic animals, can be infected either
distributed under the terms and
directly following contact with the body fluid of Leptospira-infected animals or indirectly
conditions of the Creative Commons
Attribution (CC BY) license (https://
when exposed to environments contaminated by leptospirosis [11–14]. Animal Leptospira
creativecommons.org/licenses/by/
infection presents not only as acute clinical manifestations observed in humans but also as
4.0/).
a chronic infection that can lead to major economic depletion due to reproductive failure [2].
Trop. Med. Infect. Dis. 2022, 7, 260. https://doi.org/10.3390/tropicalmed7100260 https://www.mdpi.com/journal/tropicalmed

Trop. Med. Infect. Dis. 2022, 7, 260 2 of 21
Following several human leptospirosis outbreaks reported worldwide [15], this infectious
disease has been categorized as a (re-) emerging disease and is still qualified as such by the
World Health Organization (WHO) [16].
The limit of understanding of the natural history of Leptospira infection and the under-
recognition of its burden are due to insufficient diagnosis, largely as a result of the two
stages experienced by the host [17,18]. The first stage of leptospirosis is the septicemic
or acute stage, which occurs in the first week of infection, wherein the host generally
shows symptoms of Leptospira circulating in the bloodstream [1,2,17,19]. The second
stage of the disease is the immune stage, which generally occurs in the second week of
infection, wherein the host starts to acquire and show anti-Leptospira antibodies in the
serum [1,2,17,19]. Currently, the most accurate test to detect the acute phase of infection is
the polymerase chain reaction (PCR) [18]; this technique is highly sensitive and can rapidly
detect the Leptospira species [17,20]. Treatment following a positive PCR result at this stage
might be effective, unlike the culture and microscopic agglutination test (MAT), which
is less advantageous for early diagnosis. Culture is time-consuming and known for its
difficulty in isolating Leptospira, whereas the MAT only detects antibodies indicating a past
or current infection [8,21]. Nonetheless, MAT is considered the immunological reference
standard method for leptospirosis experimental diagnosis by the World Organization for
Animal Health (WOAH) [22] and the WHO [23]. Another supportive immunological
test for the detection of antibodies is enzyme-linked immunosorbent assay (ELISA) [24].
Although the diagnostic accuracy of ELISA has not been completely established [25], the
facilities of performing ELISA (manipulation with killed antigens) rather than MAT (live
antigens) shows a promising alternative to several laboratories in tropical countries which
reported its high sensitivity and specificity [26,27].
In recent years, cases of human and animal leptospirosis have been reported in nu-
merous countries in the Middle East through direct and/or indirect diagnostic techniques.
Human cases commonly involve farmers, rice field workers [28–36], travelers [37], and
plumbers [38]. Leptospirosis cases in children and/or adults in contact with infected live-
stock or contaminated water have also been reported [28,39–41]. However, cases without a
clear history of pathogenicity [42] and those without obvious occupational activities known
to be risk factors for leptospirosis transmission have also been noted in some Middle
Eastern countries and are qualified as “inner-city related”. Moreover, cases of co-infection
with both dengue fever and leptospirosis have been described in the Middle East [43].
Animal case reports normally include numerous species but mainly involve livestock.
Furthermore, the direct detection of leptospirosis in water resources has been reported [44].
Preventive measures to reduce health and economic consequences following Leptospira
infection in the community relies on a deep understanding of the epidemiology, public
awareness, and vaccination of domestic animals and populations at risk. The knowledge
of the predominant serogroup of a host is an important guide for an effective vaccination
since the latter strategy only bestows a protective immunity restricted to homologous or
closely associated serovars [45].
This review aimed to acquire general knowledge about the epidemiological situation of
leptospirosis in the Middle East and provide an initial description of the leptospiral relative
risk and circulating serogroups in this region to develop and adopt prophylactic strategies
if necessary. This study focused on collecting and revising the available data on the
prevalence of Leptospira in humans and animals in the Middle East. We expect to determine
the variability in Leptospira spp. prevalence and seroprevalence in different Middle Eastern
countries according to variations in related records/publications. Variability was expected
because leptospirosis outbreaks are related to local factors, such as environmental and
meteorological factors, and because it is commonly reported in reviews from different
geographical areas, such as Africa, the Pacific Islands, and China. For instance, Africa
reported a variability in the seroprevalence between 2.3% and 19.8% in hospital patients
having febrile illness [46]; in Pacific Islands (y = number of islands), the seroprevalence
varied between 19.6% and 45.0% in cattle (y = 4) and between 10% and 88% in humans
(y = 7) [47], and in China, human case studies reported a seroprevalence between 8.2%
and 56.7% [48]. In addition, we expected to find similar genetic profiles or circulating
serogroups in particular hosts, such as humans, cattle, and rodents of the Middle East, as
has been reported in other areas. For instance, we expect to find the predominance of the
serogroups Icterohaemorrhagiae (ICT) in humans and rodents [49,50] and Sejroe (SJ) in
cattle [51], as has been shown in previous literature. However, for some other hosts, no
specific serogroups were expected.
2. Materials and Methods

2.1. Literature Search
We conducted a detailed literature search of the existing studies describing the Lep-
tospira seroprevalence and prevalence in Middle Eastern countries. In our review, we
included the following countries; Bahrain, Cyprus, Egypt, Iran, Iraq, Jordan, Kuwait,
Lebanon, Oman, Palestine, Qatar, Saudi Arabia, the Syrian Arab Republic, Turkey, the
United Arab Emirates, and Yemen.
The search was conducted using PubMed and ScienceDirect online databases. Search
terms were used to manually find relevant articles and included “((Leptospira) OR (Lep-
tospirosis)) AND (Middle East) AND (Prevalence)”, “((Leptospira) OR (Leptospirosis))
AND (Middle East country name) AND (Prevalence)”, “((Leptospira) OR (Leptospiro-
sis)) AND (Middle East) AND (Seroprevalence)”, “((Leptospira) OR (Leptospirosis)) AND
(Middle East country name) AND (Seroprevalence)”, “((Leptospira) OR (Leptospirosis))
AND (Middle East) AND (Human)”, “((Leptospira) OR (Leptospirosis)) AND (Middle
East) AND (Animals)” without any stipulation or precondition on publication date. Similar
research terms were also used in Google Scholar to extract relevant articles.
2.2. Inclusion and Exclusion Criteria

Both fully accessible publications and abstracts describing the seroprevalence and
prevalence of leptospirosis in humans or animals were included in this review, regardless
of their publication date. Publications that did not describe this topic were excluded. In
addition, publications written in a language other than English were excluded; nevertheless,
if the latter publication contained an English abstract with relevant data for the review,
it was included.
2.3. Data Extraction

The data extracted from the retrieved publications, abstracts, or reviews included
the author, year of publication, and geographical location. Additional information on the
chosen hosts, their effectiveness, prevalence, seroprevalence, method of detection [culture,
PCR, MAT, ELISA, serology for serogroup identification (SSI), or direct method], reference
serovars, and identified serogroups were also extracted. Serogroups referring to any host
in the Middle East were reported, regardless of the titers obtained in the SSI. The latter
methods included the MAT, indirect immunofluorescent antibody test (IFAT), complement
fixation test, lysis-agglutination test (LAT), immunoglobulin test, silver staining (SS), latex
agglutination test, macroscopic plate agglutination test (MPAT), microtube agglutination
analysis, and agglutination test.
2.4. Distribution of Publications

Information regarding the methods of detection applied and the serogroups identified
were retrieved from both research papers and case studies because the objective was to
dispose of all the available information regarding the circulating Leptospira in the Middle
East. Nonetheless, information regarding the prevalence and seroprevalence of Leptospira
was only retrieved from research papers. However, the cartography demonstrating the
geographical distribution of the Middle East publications included all retrieved publications
(research papers, case studies, and reviews).
the geographical distribution of the Middle East publications included all retrieved pub-
Trop. Med. Infect. Dis. 2022, 7, 260 lications (research papers, case studies, and reviews). 4 of 21
3. Results
3. Results
3.1. Literature Search
3.1. A
Literature
databaseSearch
search using the previously cited queries retrieved 7169 articles (458 arti-
A database
cles from PubMed search
and using the previously
6711 from cited queries
Science Direct), retrieved
of which 7169 articles
7058 were (458The
excluded. articles
ex-
from PubMed and 6711 from Science Direct), of which 7058 were excluded.
clusion criteria were based on the absence of adequate information about leptospirosis in The exclu-
sion criteria
humans were based
or animals on that
or those the absence
were notofpublished
adequateininformation
English. The about leptospirosis
review yielded 111in
humans or animals or those that were not published in English. The
articles (104 research papers and case studies and 7 reviews), with publication dates review yielded
var-
111 articles
ying between(104
1947research papers
and 2021. and case
Seventeen studies
of the latterand 7 reviews),
articles with publication
were published dates
prior to 2000;
varying between
however, 1947 and
the remaining 2021. Seventeen
94 articles of theafter
were published latter articles wereincrease
a remarkable published prior to
in publica-
2000; however, the remaining
tion throughout the last decade. 94 articles were published after a remarkable increase in
publication throughout the last decade.
3.2. Distribution of Leptospira Seroprevalence and Prevalence in Middle Eastern Countries
3.2. Distribution of Leptospira Seroprevalence and Prevalence in Middle Eastern Countries
The reported publications comprised research papers, case studies, and review arti-
The reported publications comprised research papers, case studies, and review articles
cles that included 14 countries (Figure 1). Publications related to Oman were included but
that included 14 countries (Figure 1). Publications related to Oman were included but did
did not record any seroprevalence or prevalence, as they only involved case studies
not record any seroprevalence or prevalence, as they only involved case studies [37,40,43].
[37,40,43]. Detailed data on prevalence, seroprevalence, and serogroup/serovar infor-
Detailed data on prevalence, seroprevalence, and serogroup/serovar information related
mation related to each publication can be found in Table S1.
to each publication can be found in Table S1.
Figure 1. Geographical distribution of the Middle Eastern publications. Map created with DIVA-
Figure
GIS 1. Geographical
version distribution
7.5 and designed of the
with QGIS Middle
3.16.1 Eastern publications. Map created with DIVA-GIS
Hannover.
version 7.5 and designed with QGIS 3.16.1 Hannover.
Some countries tested a high number of hosts but recorded a low seroprevalence and
Some countries tested a high number of hosts but recorded a low seroprevalence and
contrariwise. For example, Palestine tested 2018 rodents and Cyprus tested 261 cattle, 195
contrariwise. For example, Palestine tested 2018 rodents and Cyprus tested 261 cattle,
goats, and 507 sheep, and both the countries reported a seroprevalence of 0% [52–54] by
195 goats, and 507 sheep, and both the countries reported a seroprevalence of 0% [52–54]
SSI. However, Egypt tested two cats and two weasels, and one of each host showed posi-
by SSI. However, Egypt tested two cats and two weasels, and one of each host showed
tive antibody titers [55].
positive antibody titers [55].
Studies from other countries have focused on determining the seroprevalence in par-
Studies from other countries have focused on determining the seroprevalence in
ticular hosts. For example, two studies from Jordan reported a seroprevalence of 49.7%
particular hosts. For example, two studies from Jordan reported a seroprevalence of 49.7%
and 92.3% in cattle only by SSI [56,57]. Among studies from the United Arab Emirates,
one showed a seroprevalence of 4.1% [58] in camels, and another showed a seroprevalence
of 1.7% in cattle [59]. In Yemen, a seroprevalence of 41.3% [60] and 42% [61] by ELISA
was reported in humans, and a seroprevalence of 6.7% by SSI was reported in camels in
Saudi Arabia [62].
The Syrian Arab Republic has one of the lowest rates of publications on this topic, with
only one publication in 1984. However, the seroprevalence by SSI was reported as 2.9%,
11.9%, and 33.9% in sheep, goats, and cattle, respectively [63]. In contrast, Iran, Turkey, and
Egypt were the most reported countries in the Middle East, with 50, 21, and 16 publications,
respectively, with both low and high seroprevalence reported. A seroprevalence of 1.1% [64]
and 0.05% [65] was reported by SSI in humans in Iran and Turkey, respectively. Again, using
SSI, a seroprevalence of 0% [44,55,66,67] was reported in camels, cattle, donkeys, dogs, horses,
rodents, and sheep in Egypt. A seroprevalence of 71% [68] in dogs, 82.1% [69] in humans, and
78.4% [70] in cattle were reported by SSI in Iran, Turkey, and Egypt, respectively.
Iran, Turkey, and Egypt also reported studies that estimated the prevalence of the
Leptospira infection in various hosts, although many of these reported prevalence values
were low. For example, a prevalence of 0% was reported in Iran [71] in goats, and a
prevalence of 0% was reported in Egypt [44,55,66] in humans, buffaloes, camels, cattle,
donkeys, horses, sheep, water buffaloes, and weasels by PCR and/or culture. Moreover, a
prevalence of 1.4% [72] in cattle has been reported in Turkey. Only one remarkably high
prevalence of 74.4% [69] was reported in humans in Turkey by dark field microscopy (DFM).
The highest prevalence in the Middle East was reported in Iraq (94.3%) by DFM and direct
microscopic examination (DFE) [73]. The detailed data on Leptospira seroprevalence and
prevalence in Middle Eastern countries are shown in Tables 1 and 2, respectively.
Table 1. Summary of Leptospira seroprevalence in the Middle East according to the test performed (SSI or ELISA) and the country from which the sampling originated.
Total Number of Seroprevalence Total Number of Seroprevalence

Country Number of Articles Publication Year Host References
Host Tested Range SSI Host Tested Range Elisa
Cattle 261 0% - - [54]
Cyprus 1 2000 Goats 195 0% - - [54]
Sheep 507 0% - - [54]
Human 4334 0.5–49.7% 1278 16% [44,66,67,74–78]
Buffaloes 409 15.4–30% 97 20% [44,55,75,79]
Cats 2 50% - - [55]
Camels 82 0–50% - - [44,75,79,80]
[44,55,66,67,70,75,
Cattle 1093 0–78.4% - -
79]
Donkeys 73 0–29% - - [44,55,67,75]
Egypt 14 1957–2018
Dogs 394 0–58.3% - - [44,55,66,67,81]
Goats 317 1.5–42.1% - - [66,67,75]
Horses 14 0% - - [44]
Pigs 158 14.3–43.8% - - [67,75]
Rodents 1087 0–75.9% - - [44,55,66,67]
Sheep 736 0–45.4% - - [44,66,67,75,79,82]
Water buffaloes 99 14.1% - - [66]
Weasels 2 50.00% - - [55]
Human 1782 1.1–61.6% 3983 10.4–64.7% [34,64,83–97]
Buffaloes 130 25.40% - - [98]
Caspian seal 164 5.3–25.8% - - [99,100]
Cats 213 4.9–27.03% - - [101,102]
Cattle 1178 17.4–37.8% - - [103–107]
Dogs 48 71% - - [68]
Iran 36 2003–2021
Donkeys 170 40–41.2% - - [108,109]
Goats 210 8.5–11.7% - - [110–112]
Horses 541 7.8–39.2% - - [108,109,113]
Mules 20 39.2% - - [109]
Rodents 187 21.2–33% - - [114,115]
Sheep 412 10.9–19.3% - - [105,110]
Cattle 334 57.3–85% 96 7.3% [73,116,117]
Dogs 218 17% - - [118]
Iraq 4 2010–2017
Goats 153 22.4–57.9% - - [116]
Sheep 199 24.6–42.9% - - [116]
Table 1. Cont.
Total Number of Seroprevalence Total Number of Seroprevalence

Host Tested Range SSI Host Tested Range Elisa
Jordan 2 1992–2019 Cattle 448 49.7% 240 92.3% [56,57]
Human 207 1.9% - - [52]
Palestine 2 1948 Cattle 1665 8.5–9.5% - - [52,53]
Rodents 2018 0% - - [52,53]
Saudi Arabia 1 2009 Camels 90 6.7% - - [62]
Syrian Arabic Human 407 0% - - [63]
1 1984
Republic Cattle 1894 33.9% - - [63]
Sheep 1735 2.9% - - [63]
Goats 1203 11.9% - - [63]
Horses 258 0% - - [63]
Human 1834 0.05–62.8% 192 42.8–82.1% [65,69,119–122]
Turkey 14 1999–2016 Rodents 59 8.5% - - [123]
Cattle 21722 3.4–45% 4560 14–38.6% [72,119,124–127]
Dogs 116 44% - - [128]
Sheep 200 8% - - [119]
Buffaloes 93 32.3% - - [129]
United Arab Camels 73 4.1% - - [58]
2 1994–2020
Emirates Cattle - - 350 1.7% [59]
Yemen 2 2015–2018 Human - - 467 41.3–42% [60,61]
Table 2. Summary of Leptospira prevalence in the Middle East according to the test performed (PCR or culture) and the country from which the sampling originated.
Total Number of Prevalence Range Total Number Of Prevalence Range

Host Tested PCR Host Tested Culture
Human 175 0% 175 0% [44]
Buffaloes 38 0% 38 0% [44,55]
Cats 2 50% 2 50% [55]
Camels 22 0% 22 0% [44]
Cattle 634 0–1.1% 634 0–1.1% [44,55]
Donkeys 30 0% 30 0% [44,55]
Egypt 5 1957–2015
Dogs 193 11.3–12% 261 0–11.3% [44,55,81]
Horses 14 0% 14 0% [44]
Rodents 370 24–26% 1461 0.37–7% [44,55,66]
Sheep 124 0% 189 0% [44,55,82]
Water buffaloes 12 0% 12 0% [66]
Weasels 2 0% 2 0% [55]
Human 119 50.4% - - [97]
Camels 130 14.6% - - [130]
Caspian Seals 128 18.7–20.3% - - [100]
Cats 132 21.2% - - [131]
Iran 9 2010–2018
Cattle 238 14.3–43% 98 1.0% [71,103,132]
Goats 26 0% - - [71]
Rodents 151 3.3–11.3% 151 0% [115]
Sheep 110 4.5% - - [71]
Iraq 1 2017 Dogs 37 13.5% - - [118]
Kuwait 1 1983 Rodents - - 49 16.3% [133]
Lebanon 1 1947 Rodents - - 70 5.70% [134]
Human - - 192 14–45.7% [69,120]
Turkey 6 2006–2015 Cattle 499 0–9.4% - - [72,135]
Rodents 102 16.9–46.5% - - [123,136]
Saudi Arabia 1 2009 Camels - - 36 0% [62]
3.3. Surveillance Methods Used in the Middle East

Various direct or indirect methods of detection (MOD) have been reported in 104 publica-
tions, as shown in Table 3. The indirect methods—MAT or ELISA—were most commonly used,
either solely (n = 52) with MAT in addition (n = 38), or in parallel with other methods (n = 40).
Culture or direct PCR MODs were also commonly used either solely (n = 8) or in parallel with
others (n = 26) but in fewer numbers of publications. Some of the reported MODs are LAT [66],
IFAT [97], and MPAT [116] for SSI and immunoperoxidase (IP) [137], DFM [73], DFI [134], and
DFE [120] for direct diagnosis. The PCR target genes varied according to each publication, and
the list of genes is shown in Table 4.
Table 3. Methods of detection performed in 104 publications (research articles and case studies) in
the Middle East.
Major Tests Performed Number of Articles Supplementary Information

MAT only 38
ELISA only 14
PCR only 7 mPCR, qPCR, nPCR
Culture only 2
MAT, ELISA * 8
MAT, culture * † 3
MAT, PCR * † 2
ELISA, PCR * † 1
PCR, culture † 1
ELISA, culture * † 4
MAT, ELISA, PCR * † 1
MAT and others * 3 DFE, IFAT, MPAT
Culture and others * † 3 DFE, CFT, LAT, DFI, IFT, IGT
PCR and others † 1 IFAT, S
Culture, PCR and others * † 1 IFAT
MAT, culture and PCR * † 2
MAT, culture, PCR and others * † 1 PGE
IFAT, DFM, SS, DFE, LAG,
MAT, culture and others * † 4
MPAT
Culture, ELISA, and others * † 1 DFM, DFE
MAT, ELISA, culture and others * † 1 MAA, DFM
Others * 5 AT, LAT, IFA
Others 1 IP
104
mPCR, multiplex PCR; qPCR: quantitative PCR; nPCR, nested PCR; DFE, dark field examination; IFAT, indirect
immunofluorescent antibody test; CFT, complement fixation test; LAT, lysis-agglutination test; DFI, dark field
illumination; IFT, Immunofluorescent technique; IGT, immunoglobulin test; S, sequencing; PGE, Pulsed-gel
electrophoresis; DFM, dark field microscopy; SS, silver staining; LAG, latex agglutination test; MPAT, macroscopic
plate agglutination test; MAA, Microtube agglutination analysis; AT, Agglutination Test; IP, immunoperoxidase;
*, MAT and ELISA in parallel with other techniques; †, PCR and culture in parallel with other technics.
Table 4. PCR target genes used by 15 studies.
PCR Target Genes Number of Articles

rrs (16s rRNA) 6
lipl32 1
rrs (16s rRNA) and lipl32 1
g1/g2 primers 2
lig1/lig2 primers 1
g1/g2 primers and lig1/lig2 primers 1
flaB 1
hap1 1
NM 1
15
NM, not mentioned.
3.4. Geographical Distribution of Serogroups in the Middle East

We relied on all SSI tests (such as MAT, LAT, IFAT, and MPAT) to demonstrate the
serovars/serogroups circulating in most Middle Eastern countries. Reference serovars were
also determined to evaluate the results in a dependent manner, as presented in Table 5.
A total of 51 reference serovars, each referring to a specific serogroup, were reported in
the Middle East. Twenty serogroups were identified, each with its own occurrence in
the Middle East; however, only those related to the predominant hosts in this region are
presented (Figure 2). The top five reported hosts in the Middle East were cattle, humans,
rodents, sheep, and goats, with a population density of 28,595, 8564, 3351, 3789, and 2078,
respectively. The predominant serogroups identified in the previously cited hosts were SJ
(n = 3200), Grippotyphosa (GRIP) (n = 938), ICT (n = 515), Autumnalis (AUT) (n = 404), and
Pomona (POM) (n = 102). Other serogroups such as Cynopteri (n = 12), Celledoni (n = 7),
and Mini (n = 5) were also identified but had low numbers. However, each host had a
predominant serogroup, including AUT for goats; SJ for cattle; and ICT for humans, sheep,
and rodents. All serogroups presented in Table 5, except for Andamana, were identified in
Egypt, Turkey, Iran, Iraq, Palestine, Jordan, and the Syrian Arab Republic. Other countries
also reported serogroup identification in other hosts; however, they were not presented
because the number of hosts was relatively low.
Table 5. Reference serogroups and serovars in the Middle East.
S* S S* S S* S S* S S* S
AND Andamana BAT Bataviae Icterohaemorrhagiae Pyrogenes Wolffi
Australis CAN Benjamin Mankarso Patoc TAR Hyos
SEM
AUS Bratislava Canicola Javanica Semaranga Tarassovi
Jalna CEL Celledoni JAV Poi Balcanica
Autumnalis CYN Cynopteri Sorexjalna Bovis*
Bulgarica DJA Djasiman Georgia Burgas
AUT
Butembo Sentot MINI Mini Hardjo
SJ
Rachmat GRI Grippotyphosa Swajizak Istrica
Arborea Borincana PAN Panama Polonica
HEB
BAL Ballum Hebdomadis * POM Pomona Saxkoebing
Castellonis ICT Copenhageni PYR Alexi Sejroe
AND, Andamana; AUS, Australis, AUT, Autumnalis, BAL, Ballum, BAT, Bataviae, CAN, Canicola, CEL, Celledoni,
CYN, Cynopteri, DJA, Djasiman; GRI, Grippotyphosa, HEB, Hebdomadis, ICT, Icterohaemorrhagiae, JAV, Javanica,
PAN, Panama; PYR, Pyrogenes, SEM, Semaranga, SJ, Sejroe, TAR, Tarassovi, S *, serogroup, S, Serovar, *: Bovine
strain of Leptospira.
Figure 2. Distribution of serogroups in the five major hosts in the Middle East. Plot created by
Figure 2. Distribution of serogroups in the five major hosts in the Middle East. Plot created by
RStudio (RStudio Team (2021), RStudio: Integrated Development Environment for R; RStudio, PBC,
RStudio (RStudio Team (2021), RStudio: Integrated Development Environment for R; RStudio, PBC,
Boston, MA, USA; URL http://www.rstudio.com/, accessed on 22 June 2022).
Boston, MA, USA; URL http://www.rstudio.com/, accessed on 22 June 2022).
4. Discussion
4. Discussion
To the best of our knowledge, this is the first review to summarize the prevalence and
To the bestofofleptospirosis
seroprevalence our knowledge, and this is the infection
Leptospira first review to summarize
in the Middle East. theThe
prevalence
disease,
and seroprevalence
which continues to inflictof leptospirosis
a high burden and Leptospirahas
worldwide, infection in the Middle
been neglected East. The
in this particular
disease, From
region. whicha continues to inflict aalmost
broad perspective, high burden worldwide,
all Middle Eastern has beenreported
regions neglected in this
informa-
particular region. From a broad perspective, almost all Middle
tion on the prevalence and/or seroprevalence of leptospirosis and Leptospira circulating Eastern regions reported
information However,
serogroups. on the prevalence
the prevalence and/or
valuesseroprevalence
and serogroupofdistribution
leptospirosis and according
differed Leptospira
circulating
to hosts andserogroups.
countries. However, the prevalence values and serogroup distribution
differed
The according
prevalencetoand hosts and countries.
seroprevalence of leptospirosis in humans appear important in the
Middle TheEast,
prevalence
especially andwhen
seroprevalence
compared with of leptospirosis
the prevalence in humans appear important
and seroprevalence in
in other
the Middle
regions East, especially
worldwide. when compared
Many leptospirosis with the
outbreaks have prevalence and seroprevalence
been described in tropical and in
other regions
subtropical worldwide.
regions, including Many
Latinleptospirosis
America, Northernoutbreaks have been
America, described
Southern in tropical
Asia, and Africa,
and subtropical
with some having regions, including
incidence Latin America,
rates reaching 100 per Northern America,per
100,000 habitants Southern Asia, and
year [46,138,139].
However,
Africa, with to the
somebesthaving
of our knowledge,
incidence rates a seroprevalence
reaching 100and perprevalence of >41% have
100,000 habitants not
per year
been reportedHowever,
[46,138,139]. in these regions,
to the bestdespite
of ourhaving an adequate
knowledge, climate to support
a seroprevalence Leptospira
and prevalence of
survival
>41% have andnotfavorable human exposure.
been reported Indeed, the
in these regions, highest
despite seroprevalence
having an adequate ratesclimate
reportedto
recently
support inLeptospira
Latin Americasurvival wereand40.2%, 23.6%, 8.8%,
favorable human andexposure.
7.2% in Brazil,
Indeed,Peru, theColombia,
highest
and Ecuador, respectively
seroprevalence rates reported [140].recently
In addition, the highest
in Latin Americaprevalence
were 40.2%, reported
23.6%,in8.8%,
Africa is
and
19.8% [46]. These results may be due to the sampling design
7.2% in Brazil, Peru, Colombia, and Ecuador, respectively [140]. In addition, the highestbeing subject to selection
bias by onlyreported
prevalence reportinginsevere/laboratory-confirmed
Africa is 19.8% [46]. These results cases and/or
may behospital
due to patients with
the sampling
acute
designfebrile
being illness.
subject to Such a research
selection bias by design cannot provide
only reporting an accurate presentation
severe/laboratory-confirmed of
cases
leptospirosis
and/or hospital cases because
patients with theacute
disease is only
febrile known
illness. Such to acause severe
research complications
design in 5%
cannot provide
to
an10% of cases
accurate [141]. Theof
presentation reported prevalence
leptospirosis casesand seroprevalence
because the diseaserates in the
is only known Middle East
to cause
are higher (>42%) when either applying the same or different
severe complications in 5% to 10% of cases [141]. The reported prevalence and selection bias. This region
not only reported
seroprevalence acute
rates in cases but also
the Middle Eastasymptomatic cases relevant
are higher (>42%) to the
when either controlled
applying thegroup
same
and recorded higher seroprevalence than the previously cited regions
or different selection bias. This region not only reported acute cases but also asymptomatic [84]. For instance,
Iran
casestested seroprevalence
relevant in both healthy
to the controlled group and and hospitalized
recorded higher patients and recorded values
seroprevalence than theof
48.5% and 64.7%,
previously respectively
cited regions [84,95].
[84]. For Therefore,
instance, the risk
Iran tested factors for acquiring
seroprevalence the disease
in both healthy and
in the Middle East may be more important than those in other
hospitalized patients and recorded values of 48.5% and 64.7%, respectively [84,95]. regions.
SSI combined with MAT was reported in our review as the indirect method of
serogroup identification. The tests related have the advantage of identifying a partic-
ular serogroup using available reference strains for manipulation. Therefore, the host
serum is exposed to a panel of serovars, and the results vary in a dependent manner.
Various serogroups have been reported in the Middle East; however, these serogroups
are unlikely to be exhaustive, given that they could have been expanded with the use of
additional reference serovars. In the top five hosts (humans, rodents, goats, sheep, and
cattle) of this region, the predominant serogroup was SJ in cattle; AUT in goats; and ICT in
humans, sheep, and rodents. The predominance of each serogroup in each of these hosts
has been commonly reported in the literature, except in the case of goats. Serogroup SJ has
been the most commonly reported serogroup in cattle in different countries worldwide,
including the United States of America, France, Ireland, the Netherlands, Belgium, and
others [51,142–145]. The serogroup ICT is commonly reported in rats worldwide [50,146]
and is known to be the major causative agent of leptospirosis in humans [147,148]. In sheep,
the predominance of the latter (ICT) serogroup supports previous observations in other
countries [149]. In the case of goats, the predominance of the serogroup AUT has not been
reported regularly in other countries worldwide [150–152] but has been commonly reported
in related publications in the Middle East. However, this result appears robust given that
the number of MAT positive cases associated with AUT (n = 191) in goats was considerably
higher than the expected serogroup SJ (n = 12), which is considered predominant in goats
in other countries [153,154]. Nonetheless, local variation may have led to such results and,
as this is the first epidemiological study in the Middle East, it may be an indication of the
most predominant serogroup in goats in this region. However, this assumption should be
consolidated or proven by further studies. Moreover, the preponderance of the serogroup
ICT in sheep in the Middle East can be explained by the high probability of their infection
by rodents (carrying ICT) or their capacity for selective carriage of some ICT strains, as
described for other hosts (pigs) in the literature [2]. The predominance of the serogroup
ICT in humans in the Middle East may be due to infection by cattle, sheep, and rodent
carriers of this serogroup, during their occupational work (farmers, rice farmers), travel, or
contact with contaminated water. It may also be due to the importance of pathogenicity
caused by the latter (ICT) serogroup leading to leptospirosis susceptibility and, therefore,
its diagnostic examination [1]. Despite the various biases within the collected data, data
regarding the serogroups in the Middle East remain informative because the objective
of this review was to describe the circulating serogroups regardless of their titers and
MODs used. In addition, no records of human or animal vaccination were mentioned in
the selected publications; therefore, the serogroups detected in the Middle East were not
concluded according to antibodies developed by vaccination but by infection. Such results
help orient the type of vaccine that will be regarded as effective to each host. For instance,
protection against Leptospira serovar ICT and SJ through vaccination should reduce the
risk of leptospirosis in humans and cattle, respectively. Nonetheless, the adequacy of the
serogroup repartition in the Middle East may be questioned because of the possibility of
cross-reactions, which may lead to the consideration of serogroups that are not actually
present. However, the distribution of the serogroups was analyzed at the whole population
scale to minimize the effects of cross-reaction in our results, as has been performed in
previous studies [144,155].
As expected, the reported seroprevalence and prevalence differed according to studies,
likely due to variability in the MODs of Leptospira spp. Some diagnostic methods, such as
PCR or any other direct method, can only detect nucleic acids in the first week of the host
infection, known as the bacteremia phase of infection [1]. However, other MODs, such as
MAT, ELISA, or any other SSI, can detect antibodies days after the onset of the disease and
for a much longer duration [27]. The difference in the time margin between the persistence
of the bacteria and the antibodies in host tissues lessens the chances of prevalence reports,
in contrast to the chances of seroprevalence reports.
Several studies have reported null prevalence and seroprevalence. For some studies,
this can be due to the small sampling size (<30 samples), 26 goats [71], 22 camels and
14 horses [44], five sheep [67], two weasels [55], one cattle, and one dog [67], which may
not indicate the true distribution of the infection in the geographic location. Moreover,
the sampling size may not be sufficient to detect an infected or exposed host if present
in the population; indeed, a sampling size of 26 individuals allows the detection of a
minimum prevalence or seroprevalence of 11% [156]. In the case of Cyprus, the country
did not state human leptospirosis cases for several consecutive years [157], except for
the year 2003 when 0.3 cases of 100,000 habitants were infected [158]. However, the
case definition may not respond to sensitive detection of the Leptospira infection given
that many asymptomatic or moderate cases could be experienced by the host, including
humans. The European Center for Disease Prevention and Control reports were sent in
accordance with the case definitions established by the European Union that included
Cyprus. The general principles for the application of the case definitions are to only report
laboratory-confirmed symptomatic cases, while suspected cases were only regarded as
cases if they revealed a clear clinical picture with a judicious laboratory diagnosis [157,158].
In addition, the 2008 case definition was restricted to pathogenic Leptospira spp., namely
L. interrogans, whereas, starting in 2012, all pathogenic Leptospira spp. were considered in
the detection panel [157]. Such pathogenic Leptospira species restrictions may lead to an
underestimation of the incidence [158]. Moreover, a null seroprevalence was reported in
cattle, goats, and sheep in Cyprus, and, to the best of our knowledge, only a few imported
calves tested positive in 1983 [54]. However, one publication is insufficient to determine the
seroprevalence of ruminants in Cyprus but could explain the possibility of acquiring such
seroprevalence. Surprisingly, studies in Palestine reported a null seroprevalence in rodents,
even with a high sampling number. This may have been due to the antibody response
of the Leptospira-infected rodent, which is frequently found to be under the threshold of
positivity [159,160]. It may also be due to the remarkable variation in prevalence and/or
seroprevalence from one rat colony to another starting from 0%, as reported in previous
studies [161,162]. Thus, the apparent seroprevalence in Palestine could be underestimated
compared with the true seroprevalence of the tested rodents because the sampling concerns
a limited number of colonies (n = 2). Although the seroprevalence is null in rodents,
infections have been detected in Palestine in both humans (seroprevalence of 1.9%) [52] and
cattle (seroprevalence of 8.5% and 9.5%) [52,53]. The apparent seroprevalence in both hosts
was elucidated by co-authors, who suggested that numerous outbreaks of leptospirosis in
hundreds of cattle were the cause of human infection, such as those reported a few years
prior to sampling [163,164].
Some countries have reported a remarkable seroprevalence range in the human popula-
tion. The greater the number of studies combining various factors, such as the time interval
between the two studies, the spatial variation, and the design of the study adapted in
different publications related to the same country, the greater the seroprevalence variability.
An important time interval in the same country could lead to variations in disease
epidemiology. For example, in Egypt, a seroprevalence of 0.5% was reported in 1957 [63],
whereas a seroprevalence of 49.7% was reported in 2015 [44]. The risk factors for acquiring
the disease depend on the environmental features and animal carrier abundance, which
differ with the spatial variation, explaining such variability [165,166]. Therefore, spatial
variability in the same country with a large surface area and an important distribution of
studies throughout those areas, such as Iran, Turkey, and Egypt, could lead to seropreva-
lence variability. In addition, the lack of comparable design studies in the same host may
lead to variable seroprevalence. The design of the study is specific to each publication
because the sampling criteria were unique; some groups were chosen because of their ten-
dency to be infected due to their occupations or professional activities, some were chosen
randomly as controlled groups [65,66], and others were sampled for a differential diagnosis
(cases of hepatitis, acute febrile illness for humans, and brucellosis for cattle) [74,76,127].
However, when the same type of group was chosen, low seroprevalence variability was
observed. For instance, in the case of humans in Yemen, when only two publications
targeting similar types of groups (people at risk) were reported, the seroprevalence ranged
between 41.3% [60] and 42% [61]. The sampling period may also have had a major impact
on the incidence of leptospirosis throughout the year because of the seasonal pattern of
the disease and its recrudescence in specific seasons, in which the highest incidence occurs
mainly in summer or/and fall in temperate countries and in rainy seasons in warm-climate
regions [8]. Therefore, the seroprevalence can differ throughout the year in a particu-
lar country and within the same population. For instance, a study in the north of Iran
(temperate region) demonstrated a higher prevalence of leptospirosis in individuals in
autumn and summer compared with that in spring [83]. In summary, the greater the
number of studies combining the latter factors, the greater the seroprevalence variability.
Moreover, the more these factors vary between publications, the lower the comparability of
the prevalence or seroprevalence.
The epidemiological knowledge of leptospirosis is unclear for some countries in the
Middle East because of the type and content of publications. For instance, studies in Oman
only reported case studies [37,40,43]; therefore, the magnitude of leptospirosis in Oman
remains unknown. However, a high prevalence is expected due to the globalization of
travel and trade, occupational activities, and the temperate climate of the country [167].
Other countries, such as Saudi Arabia and the United Arab Emirates, only reported a
prevalence and/or a seroprevalence in a few hosts (camels and cattle) due to a greater
interest in describing the health status of the mammals that are largely present in these
countries. Epidemiological knowledge is also lacking in some countries in the Middle East
due to the absence of studies. For instance, in the twenty-first century, Lebanon, Kuwait,
and the Syrian Arab Republic did not renew their interest in studying Leptospira infection.
This suggests that leptospirosis is not within the public health policy priorities and/or
that its burden is underestimated; this is in contrast to that noted in other Middle Eastern
countries, such as Iran, which continuously show their interest in studying the disease by
attempting to revise and authenticate its detection methods [168,169].
The time interval between the reported publications, the difference in the spatial
environment, the particular design of the study adapted, and the number of publications
related to each country led to the cognizance of leptospirosis variable epidemiology in the
Middle East. Therefore, heterogeneous strategies applied in each country and between
different Middle Eastern countries should be limited as much as possible, and a harmonized
strategy should be adapted for better comparison of epidemiological studies relating to the
seroprevalence of leptospiral infection.
• For the detection methods, PCR and culture should be prioritized for direct detection
and MAT and ELISA for indirect detection. These methods can be applied in parallel
when sampling particular hosts, whereas their efficacy can be limited to others. For
instance, direct methods should be prioritized in the case of rodents because they have
a low antibody response to leptospiral infection [159].
• As MAT remains the reference detection method, a minimum and common panel of
serovars from selected serogroups should be included in all Middle Eastern countries
that require shared reference strains. The minimum number of serogroups that should
be tested are ICT, GRIP, SJ, CAN, AUT, and POM.
• A common human case definition should be a reference to all Middle Eastern countries
to report the maximum, confirmed, and suspected number of clinical cases of Leptospira.
Random sampling could be performed to describe the epidemiological situation in
humans more comprehensively, considering asymptomatic or moderate cases.
• For the surveillance of Leptospira infection in domestic animals, an analysis of data
on a continuous basis following diagnostic examinations in veterinary laboratories
should be considered to determine the distribution of Leptospira. Such data should be
communicated to the organizations and the public, indicating the applied diagnostic
method of examination. Moreover, the sampling modalities should be stated by the
community of veterinary practitioners in order for them to be interpreted at the Middle

East region level.
• Veterinary practitioners should be encouraged to provide all available information on
animals and herds to enable a good diagnosis and improve epidemiological analyses.
Information on the reason for examination, and the farms, herds (size and type),
and animals (age, sex, clinical status) at diagnostic testing will facilitate improved
epidemiological analysis and the ability to suggest risk factors to move toward more
efficient risk-based surveillance in the future.
5. Conclusions
This review summarizes the epidemiological situation of Leptospira infection in the
Middle East. Leptospirosis was found to be endemic in the countries of the Middle
East for which data were available, excluding Cyprus. Variability in the prevalence and
seroprevalence of Leptospira spp. has been reported in these countries. Furthermore,
several serogroups have been reported in hosts in the Middle East, including ICT, GRIP, SJ,
CAN, AUT, and POM. Some serogroups might be considered for certain hosts, whereas
others are commonly reported in hosts worldwide. Therefore, a deeper understanding
of the epidemiology of Leptospira spp. is required. In addition, leptospirosis should be
prioritized as a public health problem in this region, for which increased awareness is
critical. Therefore, more publications following a harmonized and appropriate study
design, while also prioritizing particular seasons leading to leptospirosis recrudescence,
and specific spatial environment or risk factors favorable for bacterial existence and survival
are needed to achieve this goal.
Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/tropicalmed7100260/s1, Table S1: Summary of Leptospira preva-
lence, seroprevalence and serovars distribution in the Middle East.
Author Contributions: Conceptualization, E.H. and F.A.; writing—original draft preparation, E.H.;
methodology, E.H.; formal analysis, E.H.; writing—review and editing, F.A.; validation, E.H., F.A.,
Z.D. and C.H.; supervision, F.A., Z.D. and C.H. All authors have read and agreed to the published
version of the manuscript.
Funding: This research was funded by VetAgro Sup, and E.H. PhD candidate grants from AUF,
USEK, and CNRS-L.
Data Availability Statement: The data presented in this study are available in Supplementary Materials.
Acknowledgments: We express our gratitude to VetAgro Sup for Angeli Kodjo as Director of the
Laboratoire des Leptospires et d’Analyses Vétérinaires, VetAgro Sup, France for financial support.
We also acknowledge Ikram Mehkfi’s help from the library of VetAgro Sup and the library employees
of USEK for their support with some research papers.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Haake, D.A.; Levett, P.N. Leptospirosis in Humans. In Leptospira and Leptospirosis; Adler, B., Ed.; Springer: Berlin/Heidelberg,
Germany, 2015; Volume 387, pp. 65–97. ISBN 978-3-662-45058-1.
2. Ellis, W.A. Animal Leptospirosis. In Leptospira and Leptospirosis; Adler, B., Ed.; Springer: Berlin/Heidelberg, Germany, 2015;
Volume 387, pp. 99–137. ISBN 978-3-662-45059-8.
3. Picardeau, M. Virulence of the Zoonotic Agent of Leptospirosis: Still Terra Incognita? Nat. Rev. Microbiol. 2017, 15,
297–307. [CrossRef] [PubMed]
4. Reller, M.E.; Wunder, E.A.; Miles, J.J.; Flom, J.E.; Mayorga, O.; Woods, C.W.; Ko, A.I.; Dumler, J.S.; Matute, A.J. Unsuspected
Leptospirosis Is a Cause of Acute Febrile Illness in Nicaragua. PLoS Negl. Trop. Dis. 2014, 8, e2941. [CrossRef] [PubMed]
5. Vincent, A.T.; Schiettekatte, O.; Goarant, C.; Neela, V.K.; Bernet, E.; Thibeaux, R.; Ismail, N.; Mohd Khalid, M.K.N.; Amran, F.;
Masuzawa, T.; et al. Revisiting the Taxonomy and Evolution of Pathogenicity of the Genus Leptospira through the Prism of
Genomics. PLoS Negl. Trop. Dis. 2019, 13, e0007270. [CrossRef]
6. Costa, F.; Hagan, J.E.; Calcagno, J.; Kane, M.; Torgerson, P.; Martinez-Silveira, M.S.; Stein, C.; Abela-Ridder, B.; Ko, A.I. Global
Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoS Negl. Trop. Dis. 2015, 9, e0003898. [CrossRef] [PubMed]
7. Torgerson, P.R.; Hagan, J.E.; Costa, F.; Calcagno, J.; Kane, M.; Martinez-Silveira, M.S.; Goris, M.G.A.; Stein, C.; Ko, A.I.; Abela-
Ridder, B. Global Burden of Leptospirosis: Estimated in Terms of Disability Adjusted Life Years. PLoS Negl. Trop. Dis. 2015, 9,
e0004122. [CrossRef] [PubMed]
8. Levett, P.N. Leptospirosis. Clin. Microbiol. Rev. 2001, 14, 296–326. [CrossRef] [PubMed]
9. Bharti, A.R.; Nally, J.E.; Ricaldi, J.N.; Matthias, M.A.; Diaz, M.M.; Lovett, M.A.; Levett, P.N.; Gilman, R.H.; Willig, M.R.; Gotuzzo,
E.; et al. Leptospirosis: A Zoonotic Disease of Global Importance. Lancet Infect. Dis. 2003, 3, 757–771. [CrossRef]
10. Zaki, S.R.; Shieh, W.-J.; Epidemic Working Group at Ministry of Health in Nicaragua; Pan American Health Organisation; US
Department of Agriculture; Centers for Disease Control and Prevention. Leptospirosis Associated with Outbreak of Acute Febrile
Illness and Pulmonary Haemorrhage, Nicaragua, 1995. Lancet 1996, 347, 535–536. [CrossRef]
11. Murray, G.L. The Molecular Basis of Leptospiral Pathogenesis. Curr. Top. Microbiol. Immunol. 2015, 387, 139–185. [CrossRef]
12. Garba, B.; Bahaman, A.R.; Bejo, S.K.; Zakaria, Z.; Mutalib, A.R.; Bande, F. Major Epidemiological Factors Associated with
Leptospirosis in Malaysia. Acta Trop. 2018, 178, 242–247. [CrossRef]
13. Brito Monteiro, M.; Egídio de Sousa, I.; Piteira, M.; Coelho, S.; Freitas, P. Leptospirosis, a Re-Emerging Threat. Cureus 2021, 13,
14. Cilia, G.; Bertelloni, F.; Fratini, F. Leptospira Infections in Domestic and Wild Animals. Pathogens 2020, 9, 573. [CrossRef]
[PubMed]
15. Hartskeerl, R.A.; Collares-Pereira, M.; Ellis, W.A. Emergence, Control and Re-Emerging Leptospirosis: Dynamics of Infection in
the Changing World. Clin. Microbiol. Infect. 2011, 17, 494–501. [CrossRef] [PubMed]
16. World Health Organization. A Brief Guide to Emerging Infectious Diseases and Zoonoses. WHO Regional Office for South-East
Asia, 2014. Available online: https://apps.who.int/iris/handle/10665/204722 (accessed on 12 September 2021).
17. Picardeau, M.; Bertherat, E.; Jancloes, M.; Skouloudis, A.N.; Durski, K.; Hartskeerl, R.A. Rapid Tests for Diagnosis of Leptospirosis:
Current Tools and Emerging Technologies. Diagn. Microbiol. Infect. Dis. 2014, 78, 1–8. [CrossRef]
18. Musso, D.; La Scola, B. Laboratory Diagnosis of Leptospirosis: A Challenge. J. Microbiol. Immunol. Infect. 2013, 46, 245–252.
[CrossRef] [PubMed]
19. Agampodi, S.B.; Matthias, M.A.; Moreno, A.C.; Vinetz, J.M. Utility of Quantitative Polymerase Chain Reaction in Leptospirosis
Diagnosis: Association of Level of Leptospiremia and Clinical Manifestations in Sri Lanka. Clin. Infect. Dis. 2012, 54, 1249–1255.
[CrossRef]
20. Picardeau, M. Diagnosis and Epidemiology of Leptospirosis. Med. Mal. Infect. 2013, 43, 1–9. [CrossRef]
21. Benacer, D.; Zain, S.N.M.; Amran, F.; Galloway, R.L.; Thong, K.L. Isolation and Molecular Characterization of Leptospira interrogans
and Leptospira borgpetersenii Isolates from the Urban Rat Populations of Kuala Lumpur, Malaysia. Am. J. Trop. Med. Hyg. 2013, 88,
704. [CrossRef]
22. World Health Organization. Chapter 3.1.12. Leptospirosis. In OIE Terrestrial Manual 2021; World Health Organization: Geneva,
Switzerland, 2021; Volume 3, ISBN 978-92-95108-18-9. Available online: https://www.woah.org/fileadmin/Home/fr/Health_
standards/tahm/3.01.12_LEPTO.pdf (accessed on 14 September 2021).
23. World Health Organization. Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control; World Health Organization:
Geneva, Switzerland, 2003; ISBN 92-4-154589-5. Available online: https://apps.who.int/iris/handle/10665/42667 (accessed on
14 September 2021).
24. Sethi, S.; Sharma, N.; Kakkar, N.; Taneja, J.; Chatterjee, S.S.; Banga, S.S.; Sharma, M. Increasing Trends of Leptospirosis in Northern
India: A Clinico-Epidemiological Study. PLoS Negl. Trop. Dis. 2010, 4, e579. [CrossRef]
25. Niloofa, R.; Fernando, N.; de Silva, N.L.; Karunanayake, L.; Wickramasinghe, H.; Dikmadugoda, N.; Premawansa, G.; Wickra-
masinghe, R.; de Silva, H.J.; Premawansa, S. Diagnosis of Leptospirosis: Comparison between Microscopic Agglutination Test,
IgM-ELISA and IgM Rapid Immunochromatography Test. PLoS ONE 2015, 10, e0129236. [CrossRef]
26. Bajani, M.D.; Ashford, D.A.; Bragg, S.L.; Woods, C.W.; Aye, T.; Spiegel, R.A.; Plikaytis, B.D.; Perkins, B.A.; Phelan, M.; Levett, P.N.;
et al. Evaluation of Four Commercially Available Rapid Serologic Tests for Diagnosis of Leptospirosis. J. Clin. Microbiol. 2003, 41,
27. Ooteman, M.C.; Vago, A.R.; Koury, M.C. Evaluation of MAT, IgM ELISA and PCR Methods for the Diagnosis of Human
Leptospirosis. J. Microbiol. Methods 2006, 65, 247–257. [CrossRef]
28. Sahneh, E.; Delpisheh, A.; Sayehmiri, K.; Khodabakhshi, B.; Moafi-Madani, M. Investigation of Risk Factors Associated with
Leptospirosis in the North of Iran (2011–2017). J. Res. Health Sci. 2019, 19, e00449.
29. Najafi, N.; Davoudi, A.R.; Alian, S.; Ahangarkani, F.; Asghari, E. Clinical and Laboratory Findings on Complication in Patients
with Leptospirosis in Mazandaran Province, Iran. Arch. Clin. Infect. Dis. 2015, 10, e24695. [CrossRef]
30. Babamahmoodi, F.; Babamhmoodi, A. Recovery from Intracranial Hemorrhage Due to Leptospirosis. Case Rep. Med. 2011, 2011,
504308. [CrossRef]
31. Erdinc, F.S.; Koruk, S.T.; Hatipoglu, C.A.; Kinikli, S.; Demiroz, A.P. Three Cases of Anicteric Leptospirosis from Turkey: Mild to
Severe Complications. J. Infect. 2006, 52, e45–e48. [CrossRef] [PubMed]
32. Alavi, L.; Alavi, S.M.; Khoshkho, M.M. Risk Factors of Leptospirosis in Khuzestan, South West of Iran, 2012. Int. J. Enteric Pathog.
2013, 1, 69–71. [CrossRef]
33. Khosravi, M.; Bastani, B. Acute Renal Failure Due to Leptospirosis in a Renal Transplant Recipient: A Brief Review of the
Literature. Transpl. Proc. 2007, 39, 1263–1266. [CrossRef]
34. Alavi, S.M.; Khoshkho, M.M. Seroprevalence Study of Leptospirosis among Rice Farmers in Khuzestan Province, South West
Iran, 2012. Jundishapur. J. Microbiol. 2014, 7, e11536. [CrossRef]
35. Alian, S.; Davoudi, A.; Najafi, N.; Ghasemian, R.; Ahangarkani, F.; Hamdi, Z. Clinical and Laboratory Manifestation and Outcome
of Icterohemorrhagic Leptospirosis Patients in Northern Iran. Med. J. Islamic Repub. Iran 2015, 29, 308.
36. Nia, A.M.; Alimohammadi, A.; Habibi, R.; Shirzadi, M.R. Spatial and Statistical Analysis of Leptospirosis in Guilan Province,
Iran. Int. Arch. Photogramm. Remote Sens. Spat. Inf. Sci. 2015, 40, 497.
37. Al-Abri, S.S.; Abdel-Hady, D.M.; Al Mahrooqi, S.S.; Al-Kindi, H.S.; Al-Jardani, A.K.; Al-Abaidani, I.S. Epidemiol-
ogy of Travel-Associated Infections in Oman 1999–2013: A Retrospective Analysis. Travel Med. Infect. Dis. 2015, 13,
38. Bukhari, H. An Unusual Cause of Hemoptysis in a Young Male Patient. J. Taibah Univ. Med. Sci. 2007, 2, 50–55. [CrossRef]
39. Kurtoglu, M.G.; Tuncer, O.; Bozkurt, H.; Çaksen, H.; Berktas, M.; Ceylan, E.; Kirimi, E. Report of Three Children with Leptospirosis
in Rural Area of the East of Turkey. Tohoku J. Exp. Med. 2003, 201, 55–60. [CrossRef]
40. Idris Al Abaidani, S.A.K.; Ghugey, S.L.; Baqi, M.; Al-Mashikhi, K.; Al-Abri, S. Four Cases of Nontravel-Related Leptospirosis in
Oman: A Call for Action. J. Epidemiol. Glob. Health 2016, 6, 215. [CrossRef]
41. Mansour-Ghanaei, F.; Sarshad, A.; Fallah, M.; Pourhabibi, A.; Pourhabibi, K.; Yousefi-Mashhoor, M. Leptospirosis in Guilan, a
Northern Province of Iran: Assessment of the Clinical Presentation of 74 Cases. Med. Sci. Monit. 2005, 11, 219–223.
42. Jayakrishnan, B.; Ben Abid, F.; Balkhair, A.; Alkaabi, J.K.; Al-Rawas, O.A.; George, J.; Al-Zeedy, K. Severe Pulmonary Involvement
in Leptospirosis: Alternate Antibiotics and Systemic Steroids. Sultan Qaboos Univ. Med. J. 2013, 13, 318–322. [CrossRef]
43. Mohammad, E.; Mohsin, N.; Al-Abri, S.; Al-Abaidani, I.; Jha, A.; Budruddin, M.; Khalil, M.; Pakyarra, A.; Busaidy, S.A. Acute
Renal Failure in a Patient with Both Leptospirosis and Dengue Fever. Oman Med. J. 2008, 23, 3.
44. Samir, A.; Soliman, R.; El-Hariri, M.; Abdel-Moein, K.; Hatem, M.E. Leptospirosis in Animals and Human Contacts in Egypt:
Broad Range Surveillance. Rev. Soc. Bras. Med. Trop. 2015, 48, 272–277. [CrossRef]
45. Chapman, A.J.; Faine, S.; Adler, B. Antigens Recognized by the Human Immune Response to Vaccination with a Bivalent
Hardjo/Pomona Leptospiral Vaccine. FEMS Microbiol. Immunol. 1990, 2, 111–118. [CrossRef]
46. Allan, K.J.; Biggs, H.M.; Halliday, J.E.; Kazwala, R.R.; Maro, V.P.; Cleaveland, S.; Crump, J.A. Epidemiology of Leptospirosis in
Africa: A Systematic Review of a Neglected Zoonosis and a Paradigm for ‘One Health’in Africa. PLoS Negl. Trop. Dis. 2015, 9,
47. Guernier, V.; Goarant, C.; Benschop, J.; Lau, C.L. A Systematic Review of Human and Animal Leptospirosis in the Pacific Islands
Reveals Pathogen and Reservoir Diversity. PLoS Negl. Trop. Dis. 2018, 12, e0006503. [CrossRef] [PubMed]
48. Dhewantara, P.W.; Mamun, A.A.; Zhang, W.-Y.; Yin, W.-W.; Ding, F.; Guo, D.; Hu, W.; Costa, F.; Ko, A.I.; Magalhães, R.J.S.
Epidemiological Shift and Geographical Heterogeneity in the Burden of Leptospirosis in China. Infect. Dis. Poverty 2018, 7,
10–23. [CrossRef]
49. Tyring, S.K.; Lupi, O.; Hengge, U.R. (Eds.) Chapter 27—Other Spirochetoses. In Tropical Dermatology; Churchill Livingstone:
Edinburgh, UK, 2006; pp. 345–358. ISBN 978-0-443-06790-7.
50. Boey, K.; Shiokawa, K.; Rajeev, S. Leptospira Infection in Rats: A Literature Review of Global Prevalence and Distribution. PLoS
Negl. Trop. Dis. 2019, 13, e0007499. [CrossRef] [PubMed]
51. Wikse, S.E. Update on Leptospira Hardjo-Bovis Control in Beef Herds. In American Association of Bovine Practitioners Proceedings of
the Annual Conference; Texas A&M University: College Station, TX, USA, 2006; pp. 79–87. [CrossRef]
52. Bernkopf, H.; Stuczynski, L.A.; Gotlieb, T.; Halevy, C. Serological, Examination of Human and Cattle Sera from Palestine for the
Presence of Antibodies against a Bovine Strain of Leptospira. Trans. R. Soc. Trop. Med. Hyg. 1948, 42, 259–265. [CrossRef]
53. Bernkopf, H. Report on Bovine Leptospirosis in Palestine Submitted to the Agricultural Research Committee by the Board; North Holland
Publishing Co.: Amsterdam, The Netherlands, 1948.
54. Economides, P. Control of Zoonoses in Cyprus. Rev. Sci. Tech. (Int. Off. Epizoot.) 2000, 19, 725–734. [CrossRef] [PubMed]
55. Felt, S.A.; Wasfy, M.O.; El-Tras, W.F.; Samir, A.; Rahaman, B.A.; Boshra, M.; Parker, T.M.; Hatem, M.E.; El-Bassiouny, A.A.;
Murray, C.K.; et al. Cross-Species Surveillance of Leptospira in Domestic and Peri-Domestic Animals in Mahalla City, Gharbeya
Governorate, Egypt. Am. J. Trop. Med. Hyg. 2011, 84, 420–425. [CrossRef]
56. Ismail, Z.B.; Abutarbush, S.M.; Al-Majali, A.M.; Gharaibeh, M.H.; Al-Khateeb, B. Seroprevalence and Risk Factors of Lep-
tospira Serovar Pomona and Leptospira Serovar Hardjo Infection in Dairy Cows in Jordan. J. Infect. Dev. Ctries. 2019, 13,
473–479. [CrossRef]
57. El-Sukhon, S.N.; Abo-Shehada, M.N.; Abuharfiel, N.; Atmeh, R.F. Prevalence of Leptospiral Antibodies in Cattle in Northern
Jordan. Trop. Anim. Health Prod. 1992, 24, 127–128. [CrossRef]
58. Afzal, M.; Sakkir, M. Survey of Antibodies against Various Infectious Disease Agents in Racing Camels in Abu Dhabi, United
Arab Emirates. Rev. Sci. Tech. (Int. Off. Epizoot.) 1994, 13, 787–792. [CrossRef]
59. Barigye, R.; Hassan, N.A.; AlQubaisi, D.M.N.; Abdalla-Alfaki, I.M. Serological Evidence of Coxiella Burnetii, Leptospira
Interrogans Hardjo, Neospora Caninum and Bovine Pestivirus Infections in a Dairy Cattle Herd from the United Arab Emirates.
Vet. Ital. 2020, 56, 163–168. [PubMed]
60. Alastot, E.M.; Al-Shamahy, H.A. Prevalence of leptospirosis amongst slaughterhouse workers and butchers in sana’a city-yemen.
Univers. J. Pharm. Res. 2018, 3, 17–20. [CrossRef]
61. Al-Robasi, A.-B.A.; Rohaim, W.D.; Al-Danani, D.A. Seroprevalence of Leptospira Antibodies among Populations at Risk. J.
Microbiol. Infect. Dis. 2015, 5, 1–4. [CrossRef]
62. Hussein, M.F.; El-Nabi, A.G. Serological Evidence of Leptospirosis in Camels in Saudi Arabia. J. Anim. Vet. Adv. 2009, 8,
1010–1012.
63. Jeblawi, M. Investigation of the Spread of Leptospirosis in Humans and Domestic Animals in the Syrian Arab Republic. Veterinaria
1984, 33, 95–111.
64. Hashemi, S.-A.; Arzamani, K.; Abdollahpour, G.; Beheshti, N.; Alavinia, M.; Azimian, A.; Neela, V.K.; van Belkum, A.;
Ghasemzadeh-Moghaddam, H. Seroprevalence of Leptospira Infection in Occupational Risk Groups in North Khorasan Province,
Iran. Heliyon 2021, 7, e05983. [CrossRef] [PubMed]
65. Şencan, İ.; LeblebïCïOğlu, H.; Sünbül, M.; Esen, Ş.; Eroğlu, C.; Günaydin, M. The Prevalence of Leptospirosis in Human Beings
and Rats in Samsun. Flora Infeksiyon Hast. Klin. Mikrobiyoloji Derg. 1999, 6, 58–63.
66. McGuire, C.D.; Myers, D.M. Leptospirosis in Egypt. Am. J. Trop. Med. Hyg. 1957, 6, 532–539. [CrossRef]
67. Sebek, Z.; Sixl, W.; Valova, M.; Schaffler, R. Leptospirosis in Man, in Wild and in Domestic Animals at Waste Disposal Sites in
Cairo. Geogr. Med. Suppl. Geogr. Medica. Sonderband 1989, 3, 141–150.
68. Arzamani, K.; Abdollahpour, G.; Ghasemzadeh-Moghaddam, H.; Alavinia, M.; Neela, V.; Hashemi, S.-A. High Prevalence of
Leptospirosis among Stray Dogs of Bojnurd County, Northeast of Iran. Int. J. Infect. Dis. 2020, 101, 544. [CrossRef]
69. Yilmaz, H.; Turhan, V.; Yasar, K.K.; Hatipoglu, M.; Sunbul, M.; Leblebicioglu, H. Characteristics of Leptospirosis with Systemic
Inflammatory Response Syndrome: A Multicenter Study. Ann. Clin. Microbiol. Antimicrob. 2015, 14, 54. [CrossRef] [PubMed]
70. Mahmoud, H.E.; Hassan, E.-S.R.; Nagwa, A.S.; Eman, I.S. Leptospirosis in Bovine with Special Reference to Mastitis. Am.-Eurasian
J. Agric. Environ. Sci. 2008, 3, 205–210.
71. Moshkelani, S.; Javaheri-Koupaei, M.; Moazeni, M. Detection of Brucella spp. and Leptospira spp. by Multiplex Polymerase Chain
Reaction (PCR) from Aborted Bovine, Ovine and Caprine Fetuses in Iran. Afr. J. Microbiol. Res. 2011, 5, 4627–4630. [CrossRef]
72. Gumussoy, K.S.; Ozdemir, V.; Aydİn, F.; Aslan, O.; Atabek, E.; Ica, T.; Dogan, H.O.; Duman, Z.; Ozturk, A. Seroprevalence of
Bovine Leptospirosis in Kayseri, Turkey and Detection of Leptospires by Polymerase Chain Reaction. J. Anim. Vet. Adv. 2009, 8,
1222–1229.
73. Ajaj, E.A.; Farwachi, M.I.A. Detection of Bovine Leptospirosis Using Different Conventional Laboratory Tests in Nineveh Province,
Iraq. J. Anim. Health Prod. 2013, 1, 32–35.
74. Barsoum, I.S.; Moch, R.W.; Botros, B.A. Leptospiral Agglutinating Antibodies in Sera of Patents with Hepatitis in Cairo Hospitals
(Egypt). J. Egypt Public Health Assoc. 1972, 47, 114–120.
75. Maronpot, R.R.; Barsoum, I.S. Leptospiral Microscopic Agglutinating Antibodies in Sera of Man and Domestic Animals in Egypt.
Am. J. Trop. Med. Hyg. 1972, 21, 467–472. [CrossRef]
76. Ismail, T.F.; Wasfy, M.O.; Abdul-Rahman, B.; Murray, C.K.; Hospenthal, D.R.; Abdel-Fadeel, M.; Abdel-Maksoud, M.; Samir, A.;
Hatem, M.E.; Klena, J. Retrospective Serosurvey of Leptospirosis among Patients with Acute Febrile Illness and Hepatitis in
Egypt. Am. J. Trop. Med. Hyg. 2006, 75, 1085–1089. [CrossRef]
77. Elzahaby, A.A.; Zaky, S.; Hassanain, N.A.H.; Hassan, E.-S.R.; Hassanain, M.A.H.; Hegazy, M.; Maher, A.M. Seroprevalence of
Leptospirosis among People in Shabramant Village, Egypt. Al-Azhar Assiut Med. J. 2018, 16, 168.
78. Murray, C.K.; Gray, M.R.; Mende, K.; Parker, T.M.; Samir, A.; Rahman, B.A.; Habashy, E.E.; Hospenthal, D.R.; Pimentel, G. Use of
Patient-Specific Leptospira Isolates in the Diagnosis of Leptospirosis Employing Microscopic Agglutination Testing (MAT). Trans.
R. Soc. Trop. Med. Hyg. 2011, 105, 209–213. [CrossRef]
79. Horton, K.C.; Wasfy, M.; Samaha, H.; Abdel-Rahman, B.; Safwat, S.; Abdel Fadeel, M.; Mohareb, E.; Dueger, E. Serosur-
vey for Zoonotic Viral and Bacterial Pathogens among Slaughtered Livestock in Egypt. Vector-Borne Zoonotic Dis. 2014, 14,
80. Hatem, M.E. Studies on Leptospira Groups of Microorganisms with Special Reference to Purification and Cultivation. M.V. Sc.
Thesis, Faculty of Veterinary Medecine, Cairo University, Giza, Egypt, 1976.
81. Maronpot, R.R.; Barsoum, I.S.; Ezzat, E. Canine Leptospirosis in Cairo. J. Infect. Dis. 1971, 123, 548–550. [CrossRef] [PubMed]
82. Hatem, M.E.; Samir, A. The First Recorded Epidemic of Leptospirosis in Sheep in Egypt. Rev. Sci. Tech. Off. Int. Epiz. 2014, 33,
83. Araghian, A.; Elmi, A.; Farahbakhsh, M.; Hosseini, S.; Faezi, S. Seroepidemiology of Leptospirosis in Guilan Province, Northern
Iran: Comparison between MAT and IgM-ELISA Techniques. J. Infect. Dev. Ctries. 2018, 12, 109–114. [CrossRef] [PubMed]
84. Ebrahimi, A.; Alijani, L.; Abdollahpour, G.R. Serological Survey of Human Leptospirosis in Tribal Areas of West Centarl Iran.
Iran. J. Med. Sci. 2003, 28, 93–95.
85. Esen, S.; Sunbul, M.; Leblebicioglu, H.; Eroglu, C.; Turan, D. Impact of Clinical and Laboratory Findings on Prognosis in
Leptospirosis. Swiss Med. Wkly. 2004, 134, 347–352.
86. Sakhaee, E. Detection of Leptospiral Antibodies by Microscopic Agglutination Test in North–East of Iran. Asian Pac. J. Trop.
Biomed. 2011, 1, 227–229. [CrossRef]
87. Esmaeili, S.; Naddaf, S.R.; Pourhossein, B.; Hashemi Shahraki, A.; Bagheri Amiri, F.; Gouya, M.M.; Mostafavi, E. Seroprevalence
of Brucellosis, Leptospirosis, and Q Fever among Butchers and Slaughterhouse Workers in South-Eastern Iran. PLoS ONE 2016,
11, e0144953. [CrossRef]
88. Alikhani, A.; Babamahmoodi, F.; Alian, S.; Zameni, F.; Ghorbani, A.; Shojaeefar, A. Sero-Epidemiological Study of Leptospirosis
in Healthy People in Qaemshahr, Iran, 2015. J. Maz. Univ. Med. Sci. 2016, 26, 78–84.
89. Khalili, M.; Askari, N.; Sakhaei, E.; Ghezeljeh, A.; Abdollahpour, G. Serological Survey of Human Leptospirosis in Southeast Iran.
Online J. Vet. Res. 2014, 18, 29–34.
90. Javid, N.; Dadgar, T.; Khodabakhshi, B.; Bazour, M.; Sedaghat, M.; Bakhshandeh-nosrat, S.; Rahimi, S.; Ghaemi, E.A. Seroepidemi-
ology of Anti-Leptospira Antibody in Golestan Province, North of Iran. Int. J. Mol. Clin. Microbiol. 2012, 2, 124–127.
91. Mobarez, A.M.; Amiri, F.B.; Esmaeili, S. Seroprevalence of Q Fever among Human and Animal in Iran; A Systematic Review and
Meta-Analysis. PLoS Negl. Trop. Dis. 2017, 11, e0005521. [CrossRef] [PubMed]
92. Noorimanesh, S.; Shafighi, T.; Abdollahpour, G. A Survey on Leptospirosis in Persons Referred to Shahid Beheshti Hospital in
Astara. SSU J. 2016, 24, 366–374.
93. Babamahmoodi, F.; Salmani Mojaveri, M.; Babamahmoodi, A.R. Seroepidemiology of Leptospirosis in Workers of High Risk
Occupation in Mazandaran Province–Iran 2007–2008. J. Maz. Univ. Med. Sci. 2009, 19, 10–15.
94. Imandar, M.; Hassanpour, A.; Asgarlou, S.; Abdollahpour, G.R.; Sadeghi, Z.M.; Khakpoor, M. Seroprevalence of Leptospirosis in
Industrial Livestock Slaughterhouse Workers in Khoy City. Sci. J. Kurd. Univ. Med. Sci. 2011, 16, 77–85.
95. Honarmand, H.; Eshraghi, S.; Khoramizadeh, M.R.; Hartskeerl, R.; Mansour, G.F.; Abdolahpour, G.; Eshraghian, M. Distribution
of Human Leptospirosis in Guilan Province, Northern Iran. Iran. J. Public Health 2007, 36, 68–72.
96. Honarmand, H.R.; Mansour, G.F.; Eshraghi, S.; Khoramizadeh, M.R.; Abd Elahpour, G.R. The Epidemiology of Leptospirosis in
Guilan Provice-2003. J. Gorgan Univ. Med. Sci. 2005, 7, 52–56.
97. Zakeri, S.; Sepahian, N.; Afsharpad, M.; Esfandiari, B.; Ziapour, P.; Djadid, N.D. Molecular Epidemiology of Leptospirosis in
Northern Iran by Nested Polymerase Chain Reaction/Restriction Fragment Length Polymorphism and Sequencing Methods. Am.
J. Trop. Med. Hyg. 2010, 82, 899–903. [CrossRef]
98. Abdollah, G.; Ramin, A.; Sanajoo, D. Seroinvestigation of Buffaloes Leptospirosis in Urmia District. J. Anim. Sci. Res. 2016, 26,
59–68.
99. Namroodi, S.; Shirazi, A.S.; Khaleghi, S.R.; Mills, J.N.; Kheirabady, V. Frequency of Exposure of Endangered Caspian Seals to
Canine Distemper Virus, Leptospira Interrogans, and Toxoplasma Gondii. PLoS ONE 2018, 13, e0196070. [CrossRef]
100. Garshasbi, V.; Naddaf, S.R.; Aghighi, Z.; Hassan, N.; Pooya, M.; Mostafavi, E. Leptospirosis in Caspian Sea Littoral, Gilan
Province, Iran. Acta Trop. 2018, 181, 11–15. [CrossRef] [PubMed]
101. Jamshidi, S.; Akhavizadegan, M.; Bokaei, S.; Maazi, N.; Ghorbanali, A. Serologic Study of Feline Leptospirosis in Tehran, Iran.
Iran. J. Microbiol. 2009, 1, 32–36.
102. Mosallanejad, B.; Ghorbanpoor Najaf Abadi, M.; Avizeh, R.; Abdollahpoor, G.; Abadi, K. A Serological Survey of Leptospiral
Infection of Cats in Ahvaz, South-Western of Iran. Iran. J. Vet. Med. 2011, 5, 49–52.
103. Shafighi, T.; Abdollahpour, G.; Salehi, T.Z.; Tadjbakhsh, H. Serological and Bacteriological Study of Leptospirosis in Slaughtered
Cattle in North of Iran (Rasht). Afr. J. Microbiol. Res. 2010, 4, 2118–2121.
104. Khalili, M.; Sakhaee, E.; Aflatoonian, M.R.; Abdollahpour, G.; Tabrizi, S.S.; Damaneh, E.M.; Hossini-Nasab, S. Seroprevalence of
Bovine Leptospiral Antibodies by Microscopic Agglutination Test in Southeast of Iran. Asian Pac. J. Trop. Biomed. 2014, 4, 354–357.
[CrossRef]
105. Ramin, A.G.; Azizzadeh, F. Seroepidemiological Detection of Antibodies against Leptospira spp. Using Microscopic Agglutination
Test in Urmia Cows and Sheep. Acta Vet. 2013, 63, 53–61. [CrossRef]
106. Abdollahpour, G.; Shafighi, S.T.; Sattari TAbrizi, S. Serodiagnosis of Leptospirosis in Cattle in North of Iran, Gilan. Iranian J. Vet.
Med. 2009, 3, 7–10.
107. Poorghafoor Langroodi, P. Sero-Epidemiological Survey of Leptospirosis in Cattle Golestan Province. J. Anim. Environ. 2019, 11,
47–52.
108. Hajikolaei, M.R.H.; Haidari, M.; Abdollapour, G. Comparison of Leptospiral Infection in the Horse and Donkey. Bull. Vet. Inst.
Pulawy 2005, 49, 175–178.
109. Ali, H.; Saeid, S. Seroprevalence of Leptospiral Infection in Horses, Donkeys and Mules in East Azerbaijan Province. Afr. J.
Microbiol. Res. 2012, 6, 4384–4387.
110. Haji Hajikolaei, M.; Rezaei, S.; Ghadrdan Mashhadi, A.; Ghorbanpour, M.; Abdollahpour, G. Comparison of Leptospira
Interrogans Infection in the Goats and Sheep. Iran. J. Vet. Med. 2016, 10, 113–119.
111. Maleki, S. Serologic Study on Leptospiral Infection in Goats in Khorramabad, West Iran. Bull. Georgian Nat. Acad. Sci. 2014, 8,
553–558.
112. Haji, K.M.; Ghorbanpour, M.; Keshavarzi, Y.M.; Abd Elahpour, G.R. Seroprevalence of Leptospiral Infection in Goats of Ahvaz.
Iran. J. Vet. Med. 2007, 62, 93–96.
113. Khousheh, Y.; Hassanpour, A.; Abdollahpour, G.; Mogaddam, S. Seroprevalence of Leptospira Infection in Horses in Ardabil-Iran.
Glob. Vet. 2012, 9, 586–589.
114. Darvish, J.; Arzamani, K.; Abdolahpoor, G.; Shirzadi, M.R. Rodent Leptospirosis in North Khorasan Province, Northeast of Iran.
Int. J. Infect. Dis. 2016, 45, 465. [CrossRef]
115. Esfandiari, B.; Pourshafie, M.R.; Gouya, M.M.; Khaki, P.; Mostafavi, E.; Darvish, J.; Bidhendi, S.M.; Hanifi, H.; Nahrevanian, H.
An Epidemiological Comparative Study on Diagnosis of Rodent Leptospirosis in Mazandaran Province, Northern Iran. Epidemiol.
Health 2015, 37, e2015012. [CrossRef]
116. Al-Badrawi, T.Y.G.; Habasha, F.G.; Sultan, S.H. Serological Study of Leptospirosis in Cattle, Sheep and Goats in Baghdad Province.
Al-Anbar J. Vet. Sci. 2010, 3, 78–82.
117. Ajaj, E.A.B.; Al-FARWACHİ, M.I. Serosurvey of Leptospira Interrogans Serovars Hardjo and Pomona in Cattle in Nineveh
Province, Iraq. Anim. Health Prod. Hyg. 2013, 2, 156–158.
118. Alfattli, H.H.H.H.; Al-Mohamed, S.A.A. First Serological and Molecular Detection of Leptospira Interrogans Serovar Canicola
Bacteria in Dogs in Some Iraqi Governorates. J. Educ. Coll. Wasit Univ. 2017, 1, 621–636. [CrossRef]
119. Ozdemir, V.; Erol, E. Leptospirosis in Turkey. Vet. Rec. 2002, 150, 248–249. [CrossRef]
120. Turhan, V.; Polat, E.; Murat Atasoyu, E.; Ozmen, N.; Kucukardali, Y.; Cavuslu, S. Leptospirosis in Istanbul, Turkey: A Wide
Spectrum in Clinical Course and Complications. Scand. J. Infect. Dis. 2006, 38, 845–852. [CrossRef] [PubMed]
121. Bilir, O. An Old Zoonosis Coming from Afar: Leptospirosis. Platelets 2016, 7150, 67734.43.
122. Babür, C.; Ozdemir, V.; Kiliç, S.; Erol, E.; Esen, B. Anti-Leptospira Antibodies in Slaughterhouse Workers in Ankara. Mikrobiyoloji
Bul. 2003, 37, 143–150.
123. Sunbul, M.; Esen, S.; Leblebicioglu, H.; Hokelek, M.; Pekbay, A.; Eroglu, C. Rattus Norvegicus Acting as Reservoir of Leptospira
Interrogans in the Middle Black Sea Region of Turkey, as Evidenced by PCR and Presence of Serum Antibodies to Leptospira
Strain. Scand. J. Infect. Dis. 2001, 33, 896–898. [PubMed]
124. Şahin, M.; Aydin, F.; Özdemir, V.; Genç, O.; Güler, M.A. Serological Survey of Bovine Leptospirosis in Kars and Ardahan Provinces.
Turk. J. Vet. Anim. Sci. 2002, 26, 17–25.
125. Kocabiyik, A.L.; Cetin, C. Bovine Leptospirosis in South Marmara Region of Turkey: A Serological Survey. Rev. Méd. Vét. 2004,
155, 606–608.
126. Aslantaş, Ö.; Özdemir, V. Determination of the Seroprevalence of Leptospirosis in Cattle by MAT and ELISA in Hatay, Turkey.
127. Genç, O.; Otlu, S.; ŞAHİN, M.; Aydin, F.; Gökce, H.I. Seroprevalence of Brucellosis and Leptospirosis in Aborted Dairy Cows.
128. Aslantaş, Ö.; Özdemir, V.; Kiliç, S.; Babür, C. Seroepidemiology of Leptospirosis, Toxoplasmosis, and Leishmaniosis among Dogs
in Ankara, Turkey. Vet. Parasitol. 2005, 129, 187–191. [CrossRef]
129. Kenar, B.; Ozdemir, V. The Seroprevalence of Leptospirosis in Anatolian Buffaloes in Turkey. Rev. Med. Vet. 2013, 164, 331–335.
130. Doosti, A.; Ahmadi, R.; Arshi, A. PCR Detection of Leptospirosis in Iranian Camels. Bulg. J. Vet. Med. 2012, 15, 178–183.
131. Azizi, S.; Momtaz, H.; Goodarzi, A.M.; Tajbakhsh, E. Pcr Detection of Leptospira in Stray Cats, Probable Reservoir. Bull. L’académie
Vét. Fr. 2013, 166, 67–70. [CrossRef]
132. Shafighi, T.; Salehi, T.Z.; Abdollahpour, G.; Asadpour, L.; Akbarein, H.; Salehzadeh, A. Molecular Detection of Leptospira spp. in
the Urine of Cattle in Northern Iran. Iran. J. Vet. Res. 2014, 15, 402.
133. Bezjak, V.; Thorburn, H. Survey of Rats (Rattus norvegicus) in Kuwait for the Presence of Leptospira. Trop. Geogr. Med. 1983, 35,
33–36. [PubMed]
134. Kalfayan, B.H. Leptospira icterohaemorrhagiae in Rats of Beirut. Trans. R. Soc. Trop. Med. Hyg. 1947, 40, 895–900. [CrossRef]
135. Yesılmen, S.; Arserım, N.B.; Isık, N.; Icen, H. Determination of Prevalence of Pathogenic Leptospira spp. by Real-Time PCR in
Cattle in Diyarbakır. Yüzüncü Yıl Üniversitesi Vet. Fakültesi Derg. 2012, 23, 137–139.
136. Azkur, A.K.; Kaygusuz, S.; Aslan, M.E.; Gazyağci, S.; Gözütok, S.; Toyran, K. A Survey Study on Hantavirus, Cowpox Virus,
and Leptospira Infections in Microtus Hartingi in Kırşehir Province, Central Anatolia, Turkey. Turk. J. Vet. Anim. Sci. 2013, 37,
434–442. [CrossRef]
137. Saglam, Y.S.; Yener, Z.; Temur, A.; Yalcin, E. Immunohistochemical Detection of Leptospiral Antigens in Cases of Naturally
Occurring Abortions in Sheep. Small Rumin. Res. 2008, 74, 119–122. [CrossRef]
138. Munoz-Zanzi, C.; Groene, E.; Morawski, B.M.; Bonner, K.; Costa, F.; Bertherat, E.; Schneider, M.C. A Systematic Literature Review
of Leptospirosis Outbreaks Worldwide, 1970–2012. Rev. Panam. Salud Pública 2020, 44, e78. [CrossRef]
139. De Vries, S.G.; Visser, B.J.; Nagel, I.M.; Goris, M.G.; Hartskeerl, R.A.; Grobusch, M.P. Leptospirosis in Sub-Saharan Africa: A
Systematic Review. Int. J. Infect. Dis. 2014, 28, 47–64. [CrossRef]
140. Schneider, M.C.; Leonel, D.G.; Hamrick, P.N.; de Caldas, E.P.; Velásquez, R.T.; Paez, F.A.M.; Arrebato, J.C.G.; Gerger, A.; Pereira,
M.M.; Aldighieri, S. Leptospirosis in Latin America: Exploring the First Set of Regional Data. Rev. Panam. Salud Pública 2017, 41,
141. Doudier, B.; Garcia, S.; Quennee, V.; Jarno, P.; Brouqui, P. Prognostic Factors Associated with Severe Leptospirosis. CMI 2006, 12,
142. Ryan, E.G.; Leonard, N.; O’Grady, L.; Doherty, M.L.; More, S.J. Herd-Level Risk Factors Associated with Leptospira Hardjo
Seroprevalence in Beef/Suckler Herds in the Republic of Ireland. Ir. Vet. J. 2012, 65, 6. [CrossRef]
143. Hartman, E.; Franken, P.; Bokhout, B.; Peterse, D. Leptospirosis in Cattle; Milker’s Fever in Cattle Farmers. Tijdschr. Voor
Diergeneeskd. 1989, 114, 131–135.
144. Ayral, F.C.; Bicout, D.J.; Pereira, H.; Artois, M.; Kodjo, A. Distribution of Leptospira Serogroups in Cattle Herds and Dogs in
France. Am. J. Trop. Med. Hyg. 2014, 91, 756–759. [CrossRef]
145. Delooz, L.; Czaplicki, G.; Gregoire, F.; Dal Pozzo, F.; Pez, F.; Kodjo, A.; Saegerman, C. Serogroups and Genotypes of Leptospira spp.
Strains from Bovine Aborted Foetuses. Transbound. Emerg. Dis. 2018, 65, 158–165. [CrossRef] [PubMed]
146. Main, J. Chapter 39—Hepatobiliary and Splenic Infection. In Infectious Diseases, 3rd ed.; Cohen, J., Opal, S.M., Powderly, W.G.,
Eds.; Mosby: London, UK, 2010; pp. 423–429. ISBN 978-0-323-04579-7.
147. Farris, A.B.; Nielsen, G.P. 16—Genitourinary Infectious Disease Pathology. In Diagnostic Pathology of Infectious Disease, 2nd ed.;
Kradin, R.L., Ed.; Elsevier: Amsterdam, The Netherlands, 2018; pp. 429–467. ISBN 978-0-323-44585-6.
148. Scully, C. 9—Hepatology. In Scully’s Medical Problems in Dentistry, 7th ed.; Scully, C., Ed.; Churchill Livingstone: Oxford, UK, 2014;
pp. 276–293. ISBN 978-0-7020-5401-3.
149. da Silva, A.S.; Souza, C.F.; Baldissera, M.D.; Von Laer, A.E.; Lovato, L.T.; Sarturi, J.A.; Herrmann, G.P.; de Moura, A.B.; Favaretto,
J.A.; Frias-De-Diego, A. Relation of Reproductive Disturbance in Sheep and Leptospira interrogans Serovar Icterohaemorrhagiae
Infection: Impacts on Cellular Oxidation Status. Microb. Pathog. 2019, 130, 65–70. [CrossRef] [PubMed]
150. Lilenbaum, W.; Morais, Z.M.; Gonçales, A.P.; de Souza, G.O.; Richtzenhain, L.; Vasconcellos, S.A. First Isolation of Leptospires
from Dairy Goats in Brazil. Braz. J. Microbiol. 2007, 38, 507–510. [CrossRef]
151. Topazio, J.; Tonin, A.A.; Machado, G.; Noll, J.C.; Ribeiro, A.; Moura, A.B.; Carmo, G.M.; Grosskopf, H.M.; Martins, J.L.; Badke,
M.R. Antibodies to Leptospira interrogans in Goats and Risk Factors of the Disease in Santa Catarina (West Side), Brazil. Res. Vet.
Sci. 2015, 99, 53–57. [CrossRef]
152. Dhivahar, M.; Ambily, R.; Joseph, S.; Shyma, V.; Reshma, P.; Mini, M. Seroprevalence of Leptospirosis among Aborted Goats in
Kerala. Int. J. Curr. Microbiol. App. Sci 2019, 8, 1403–1407. [CrossRef]
153. Assenga, J.A.; Matemba, L.E.; Muller, S.K.; Mhamphi, G.G.; Kazwala, R.R. Predominant Leptospiral Serogroups Circulating
among Humans, Livestock and Wildlife in Katavi-Rukwa Ecosystem, Tanzania. PLoS Negl. Trop. Dis. 2015, 9, e0003607. [CrossRef]
[PubMed]
154. Lilenbaum, W.; Varges, R.; Ristow, P.; Cortez, A.; Souza, S.; Richtzenhain, L.; Vasconcellos, S. Identification of Leptospira spp.
Carriers among Seroreactive Goats and Sheep by Polymerase Chain Reaction. Res. Vet. Sci. 2009, 87, 16–19. [CrossRef] [PubMed]
155. Miller, M.; Annis, K.; Lappin, M.; Lunn, K. Variability in Results of the Microscopic Agglutination Test in Dogs with Clinical
Leptospirosis and Dogs Vaccinated against Leptospirosis. J. Vet. Intern. Med. 2011, 25, 426–432. [CrossRef] [PubMed]
156. Pfeiffer, D. Veterinary Epidemiology: An Introduction; John Wiley & Sons: Hoboken, NJ, USA, 2010; ISBN 1-4051-7694-6.
157. Leptospirosis—Annual Epidemiological Report 2016 [2014 Data]. Available online: https://www.ecdc.europa.eu/en/
publications-data/leptospirosis-annual-epidemiological-report-2016 (accessed on 3 March 2022).
158. Dupouey, J.; Faucher, B.; Edouard, S.; Richet, H.; Kodjo, A.; Drancourt, M.; Davoust, B. Human Leptospirosis: An Emerging Risk
in Europe? Comp. Immunol. Microbiol. Infect. Dis. 2014, 37, 77–83. [CrossRef]
159. Langoni, H.; de Souza, L.C.; Da Silva, A.V.; Cunha, E.L.P.; da Silva, R.C. Epidemiological Aspects in Leptospirosis. Research of
Anti-Leptospira spp. Antibodies, Isolation and Biomolecular Research in Bovines, Rodents and Workers in Rural Properties from
Botucatu, SP, Brazil. Braz. J. Vet. Res. Anim. Sci. 2008, 45, 190–199. [CrossRef]
160. Scialfa, E.; Bolpe, J.; Bardón, J.; Ridao, G.; Gentile, J.; Gallicchio, O. Isolation of Leptospira interrogans from Suburban Rats in Tandil,
Buenos Aires, Argentina. Rev. Argent. Microbiol. 2010, 42, 126–128.
161. Ayral, F.; Artois, J.; Zilber, A.-L.; Widén, F.; Pounder, K.C.; Aubert, D.; Bicout, D.J.; Artois, M. The Relationship between
Socioeconomic Indices and Potentially Zoonotic Pathogens Carried by Wild Norway Rats: A Survey in Rhône, France (2010–2012).
Epidemiol. Infect. 2015, 143, 586–599. [CrossRef]
162. Pratt, N.; Rajeev, S. Leptospira Seroprevalence in Animals in the Caribbean Region: A Systematic Review. Acta Trop. 2018, 182,
34–42. [CrossRef]
163. Freund, S. Leptospirosis in Cattle in Palestine. J. Comp. Pathol. Ther. 1947, 57, 62–66. [CrossRef]
164. Btesh, S. Infection of Man with Leptospira Bovis in Palestine. Trans. R. Soc. Trop. Med. Hyg. 1947, 41, 419–426.
165. Dhewantara, P.W.; Lau, C.L.; Allan, K.J.; Hu, W.; Zhang, W.; Mamun, A.A.; Soares Magalhaes, R.J. Spatial Epidemiological
Approaches to Inform Leptospirosis Surveillance and Control: A Systematic Review and Critical Appraisal of Methods. Zoonoses
Public Health 2019, 66, 185–206. [CrossRef] [PubMed]
166. Perez, J.; Brescia, F.; Becam, J.; Mauron, C.; Goarant, C. Rodent Abundance Dynamics and Leptospirosis Carriage in an Area of
Hyper-Endemicity in New Caledonia. PLoS Negl. Trop. Dis. 2011, 5, e1361. [CrossRef] [PubMed]
167. Awaidy, S.A.; Al Hashami, H. Zoonotic Diseases in Oman: Successes, Challenges, and Future Directions. Vector-Borne Zoonotic
Dis. 2020, 20, 1–9. [CrossRef]
168. Rostampour Yasouri, S.; Ghane, M.; Doudi, M.; Rezaee, A.; Naghavi, N.S. A Study of Leptospirosis Epidemiology in Iran and
Diagnostic Techniques for Human, Livestock and Environment Samples. Med. Lab. J. 2020, 14, 1–9. [CrossRef]
169. Aghaiypour, K.; Safavieh, S. Molecular Detection of Pathogenic Leptospira in Iran. Arch. Razi Inst. 2007, 62, 191–197.

Tropicalmed 07 00260

Uploaded by

Copyright:

Available Formats

Tropicalmed 07 00260

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Tropicalmed 07 00260

Uploaded by

Copyright:

Available Formats

Tropical Medicine and

Academic Editors: Sérgio Santos de

Received: 2 September 2022

Trop. Med. Infect. Dis. 2022, 7, 260. https://doi.org/10.3390/tropicalmed7100260 https://www.mdpi.com/journal/tropicalmed

2. Materials and Methods

2.2. Inclusion and Exclusion Criteria

2.3. Data Extraction

2.4. Distribution of Publications

Total Number of Seroprevalence Total Number of Seroprevalence

Total Number of Seroprevalence Total Number of Seroprevalence

Total Number of Prevalence Range Total Number Of Prevalence Range

3.3. Surveillance Methods Used in the Middle East

Major Tests Performed Number of Articles Supplementary Information

Table 4. PCR target genes used by 15 studies.

PCR Target Genes Number of Articles

3.4. Geographical Distribution of Serogroups in the Middle East

Table 5. Reference serogroups and serovars in the Middle East.

community of veterinary practitioners in order for them to be interpreted at the Middle

You might also like