DISCUSSION
There have been a notable change in the epidemiology of rickettsial
spotted fever globally and these could be attributed to warmer
temperatures and increased relative humidity that have occurred in
recent times due to cycles of drought and rains. These cycles stimulates
increased physiological processes that in turn lead to rapid growth and
ultimately accelerated reproduction. Other factors that could be
responsible for the observed notable changes are;-i) infringement of
humans into ecological territories that are ticks reserves as a result
of increased human population, ii) increased human contact with ticks
which are reservoirs and transmitters of tick-borne SFGR pathogens due
to increased outdoor activities, iii) improved global trade and travels
that have facilitated the distribution of tick vectors and their
suitable animal hosts in a short space of time, iv) as well as migration
of animals including birds which have the capacity to introduce exotic
ticks and their pathogens into new territories.
Genetic materials of R. africae , R. parkeri and R.
tamurae were the three SFGR that were detected amongst the ticks genera
collected in this study. These three species are closely related and
they are the etiologic agents of African and American tick bite fever
that are very prevalent in the sub-Saharan African, United States of
America and Brazil and rickettsiosis in Japan respectively (Bogovic et
al., 2016). African tick bite fever is generally transmitted byAmblyomma ticks which servers as its host and wild rodents are it
reservoir from which it is transmitted to it humans through ticks bite
(Bogovic et al., 2016).
Even though rickettsial diseases are found globally, there is no one
single tick-borne rickettsial diseases that is found all over the world
rather they are restricted to a given geographical regions and are
transmitted by ticks inhabiting the given region. Majority of the
populace living in the sub-Saharan Africa might be seropositive toR. africae but hardly do they succumb to African tick bite fever
as it is with travelers to the endemic regions of Africa.
Sero-prevalence of R. africae in Cameroon is between 11.9% -
51.8% while in Senegal it ranges between 21.4% -51% (Ndip et al.,
2004; Mediannikov et al., 2010; Consigny et al., 2005). In a group of
940 travelers to South Africa, majority (27%) of them had flulike
symptoms as a result of contacting R. africae the etiologic agent
of African tick-bite fever upon returning from their travel (Prabhu et
al., 2011). Also Prabhu et al., (2011), reported a seroprevalence of
51.7% among inpatients identified with febrile fever who were tested
for acute SFGR and TGR in Moshi, Tanzania. May June
Thu1Unit of Risk Analysis and Management, Hokkaido
University Research Center for Zoonosis Control, N 20 W 10, Kita-ku,
Sapporo, 001-0020 Japan
2Laboratory of Parasitology, Faculty of Veterinary
Medicine, Graduate School of Infectious Diseases, Hokkaido University, N
18 W 9, Kita-ku, Sapporo, 060-0818 Japan
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May
June Thu
Yongjin Qiu
3Hokudai Center for Zoonosis Control in Zambia, School
of Veterinary Medicine, University of Zambia, P. O. Box 32379, Lusaka,
Zambia
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Yongjin
Qiu
Keita Matsuno
4Laboratory of Microbiology, Faculty of Veterinary
Medicine, Graduate School of Infectious Diseases, Hokkaido University, N
18 W 9, Kita-ku, Sapporo, 060-0818 Japan
5Global Station for Zoonosis Control, Global
Institution for Collaborative Research and Education (GI-CoRE), Hokkaido
University, N 18 W 9, Kita-ku, Sapporo, 060-0818 Japan
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Matsuno
Masahiro Kajihara
6Division of Global Epidemiology, Hokkaido University
Research Center for Zoonosis Control, N 20 W 10, Kita-ku, Sapporo,
001-0020 Japan
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Akina Mori-Kajihara
6Division of Global Epidemiology, Hokkaido University
Research Center for Zoonosis Control, N 20 W 10, Kita-ku, Sapporo,
001-0020 Japan
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Mori-Kajihara
Ryosuke Omori
7Division of Bioinformatics, Hokkaido University
Research Center for Zoonosis Control, N 20 W 10, Kita-ku, Sapporo,
001-0020 Japan
8Precursory Research for Embryonic Science and
Technology (PRESTO), Japan Science and Technology Agency, Saitama,
332-0012 Japan
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Omori
Naota Monma
9Department of Infection Control, Fukushima Medical
University, 1 Hikarigaoka, Fukushima, 960-1295 Japan
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Monma
Kazuki Chiba
10Fukushima Institute for Public Health, 16-6 Mitouchi
Houkida, Fukushima, 960-8560 Japan
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Chiba
Junji Seto
11Yamagata Prefectural Institute of Public Health,
1-6-6 Toka-machi, Yamagata, 990-0031 Japan
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Mutsuyo Gokuden
12Kagoshima Prefectural Institute for Environmental
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Masako Andoh
13Laboratory of Veterinary Public Health, Joint
Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto,
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Hideo Oosako
14Kumamoto Prefectural Institute of Public-Health and
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Ken Katakura
2Laboratory of Parasitology, Faculty of Veterinary
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5Global Station for Zoonosis Control, Global
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6Division of Global Epidemiology, Hokkaido University
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Chihiro Sugimoto
5Global Station for Zoonosis Control, Global
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15Division of Collaboration and Education, Hokkaido
University Research Center for Zoonosis Control, N 20 W 10, Kita-ku,
Sapporo, 001-0020 Japan
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Norikazu Isoda
1Unit of Risk Analysis and Management, Hokkaido
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The majority of data on ATBF cases that have been documented to date
have been obtained from tourists returning from countries to which it is
endemic, most from the Southern Africa countries like Botswana, South
Africa, and Zimbabwe (Nilssona et al., 2017; Prebhu et al., 2011;
Bogovic et al., 2016; Socolovschi et al., 2007). Bogovic et al. (2016)
reported a case of ATBF in a Slovenian traveler returning from Uganda.
The 29-year-old Slovenian man without underlying illnesses sought care
after returning from a two weeks visit to Uganda for fever, chills,
pains and complained of a tick bite a day prior to departing the
country. Lorusso et al. (2013) were the first people to report aboutR. africae in ticks in Uganda where R. conorii had
previously been reported by Socolovschi et al. (2007) as being
prevalent. Similarly, Angerami et al. (2018) reported ATBF on a
Brazilian who visited South Africa upon his return to Brazil. He had
eschar and symptoms characteristics of ATBF which was confirmed by both
immunological and molecular diagnostic methods to be infected byR. africae. African tick bite fever had also been reported for
the first time by Harrison et al. (2016) on an Austrian traveler to East
Africa who acquired the disease through tick bite during a visit to
Tanzania. ATBF is generally a mild disease and to date, there has not
been any reported deaths attributed to infection of R. africae.However, just like R. parkeri rickettsiosis, the disease caused
by R. africae is often associated with an inoculation eschar at
the spot of attachment of the tick vector. Usually, the symptoms
associated with ATBF normally appear many days after the development of
the eschar and they are usually that of fever, headache, myalgia,
regional lymphadenopathy and generalized rash in about 50% of the
cases.
Amblyomma variegatum tick has been reported to be the vector ofR. africae with a prevalence of 97.1% in Uganda (Nakao et al.,
2013). However, Waner et al. (2014), reported finding the DNA ofR. africae in Hyalomma detritum tick collected from a wild
boar in Israel indicating that the spotted fever group rickettsia is not
limited in distribution to the African continent nor to a given host
tick. Similarly, Yssouf et al. (2014) reported the detection of R.
africae in 90% of A. variegatum , 1% of R.
appendiculatus and 2.7% of Rhipicephalus (Boophilus) microplusin study ticks collected from locally domesticated animals in the Union
of the Comoros, as well as in 77.14% in A. variegatum ticks
obtained from cattle imported into the country. Also, Maina et al.
(2014) reported the detection of R. africae –genotype DNA in
92.6% of adult A. variegatum ticks collected from domestic
ruminants in Kenya even though they found no evidence of the pathogen in
blood specimens in the domestic animals sampled. R. africaegenetic materials have been detected by PCR from different species of
ticks belonging to Amblyomma, Rhipicephalus, Hyalomma genera in
several African countries such as Mali, Senegal, Guinea, Liberia, Sudan,
Democratic Republic of Congo, Cameroon, Nigeria, Niger, Kenya and
Burundi (Parola et al., 2013; Bogovic et al., 2016) and these reports
are in consonant with our finding as the DNA of R. africae was
detected in the different genera of ticks that we assessed.
R. parkeri a member of the spotted fever group rickettsia is the
etiologic agent of American tick bite fever that is prevalent in the
South and North America continents is transmitted by Amblyomma species.
The spotted fever disease associated with the organism is characterized
by eschar related ailments in humans which are similar to symptoms of
Rocky Mountain spotted fever. The index rickettsiosis spotted fever case
caused by R. parkeri was first recognized by
Paddock
et al., (2004) and ever since then; numerous cases have been identified
and reported in many southeastern states of the USA (Kimita et al.,
2016; Paddock et al., 2008). Cowdry, (1993), was the first to describe
the finding of the organism in the tissues and eggs of female A.
maculatum ticks that were collected in Jackson County, Missouri.
However, Parker et al. (1963), isolated the organism for the first time
from Gulf Coast ticks that were collected in South eastern Texas and
ever since then, R. parkeri a SFG rickettsiae have been
frequently detected in A. maculatum. However, R. parkerihas been detected in other tick species other than A. maculatumas Williamson et al., (2010), reported the detection of its DNA inD. variabilis in ticks removed from persons in Texas, USA.R. parkeri infections in dogs and cows have been described in
southeastern United States. Infection of humans by R. parkeri in
most cases is associated with a necrotic eschar at the point of
inoculation after several days of an infected tick bite and it is
usually with a low grade to moderate fever that is very similar to RMSF
though less in severity. Some of the symptoms associated with R.
parkeri rickettsioses are fever, inoculation eschar, macules or papules
rashes, vesicles or pustules, petechiae on palms or soles, headache,
myalgias, sore throat, lymphadenopathy, diarrhea, nausea or vomiting
(Paddock et al., 2008). No case of R.parkeri rickettsiosis have
however been reported in Central America though A. maculatum is
widely distributed throughout the region even though a mild
eschar-related rickettsiosis that is very akin to R. parkeririckettsiosis have been reported in a traveler who returned from
Honduras (Paddock et al., 2008). Since the first human disease case
caused by R. parkeri was reported by
Paddock
et al. (2004), numerous cases of rickettsioses caused by R.
parkeri have been reported among persons residing in the ecological
range of the vector tick A. maculatum in the USA. Infections and
eschar associated illness with R. parkeri have been frequently
reported in several Latin American countries such as Argentina, Brazil,
and Uruguay, and the organism has been detected in A. tristeticks (Romer et al., 2011). For the first time, here we report the
detection of genetic material of R. parkeri in the African
continent and the epidemiological implications are not well known.
However, because it has been documented as a human pathogen, its
involvement in human cases in the study sites may not be unlikely as it
may probably have gone undetected. We observed discordant phylogenetic
assignments of the omp A and omp B genes of sample 188 as
they were found to cluster with Candidatus_Rickettsia EU27216.1
and R. parkeri KY113110 respectively in Figs 4 and 5 and this was
shown to be so with nucleotide and amino acid alignments as shown in
Figures 2A to D.
Rickettsia sp. strain Ga-Seema is an incompletely described
rickettsial that was detected from three fed adult maleRhipicephalus simus ticks collected from two donkeys in 2014 in
Hlahlagane, Limpopo Province, South Africa by Halajian et al. (2018)
which has not been reported previously and its pathogenic potential is
currently unknown.
R. tamurae infection according to Imaokaa et al. (2013) is
associated with symptoms such as mild local inflammatory signs like
swellings, erythema, redness heat and pain. Symptoms of R.
tamurae infection mimics cellulitis with increased serum titers of
antibody against the organism (Halajian et al., 2018). Unlike most SFGR,
infection with R.tamurae is not associated with high fever,
generalized rash, lymphadenopathy as it is often seen in other spotted
fever rickettsioses. R.tamurae was first isolated from A.
testudinarium ticks in Japan and has the wild boar and domestic pigs as
it primary host although it can also infest deer, cattle, other
ungulates and domestic livestock as well as humans (Halajian et al.,
2018; Imaokaa et al., 2011; Motoi et al., 2013). R. tamurae has
been isolated from the skin biopsy specimen from wild boars and also in
ticks (Halajian et al., 2018). It was previously thought to be
non-pathogenic to humans until it was reported in human cases in Japan
(Halajian et al., 2018) as well as in Laos where its involvement in
spotted fever case was documented after a patient tested seropositive
for the organism (Gaowa et al., 2013). Phylogenetic analyses of theomp A and omp B sequences of sample 209 assigned them asR. africae and R. tamurae respectively and homology search
confirmed that omp A sequence is R. africae while theomp B sequence had 100% similarity with R. tamurae . We
performed nucleotide and amino acid sequences alignments with the two
sequences as shown in Figures 3A-D, the omp B showed complete
homology with R. tamurae indicating that sample B209 is most
highly R. tamurae in the omp B gene region while theomp A was closely related with R. africae . We are not sure
if recombination did occur in the two genes in question. Further study
like full genome sequencing is needed to elucidate this observation.R. tamurae has been associated with different Amblyommaspp. as reported by Blanco (Blanco et al.,2017) who detected the
pathogen in screened nymphs of A. ovale tick collected from small
mammals such as wild rodents and marsupials in Brazil while a recent
report stated its detection in a Haemaphysalis megaspinosa tick
(Blanco et al., 2017). However, this is the first report of R.
tamurae- like pathogen, the agent of SFG rickettsiosis in Japan and some
Far East Asian countries in A. variegatum tick collected from
cattle in the African continent.
Ticks as well as the diseases they transmit have an ecological range
constrained by animal host diversity, movement and climatic factors. The
current rapid expansion of ticks and the diseases they transmit into new
ecological niches can be attributed to increased mobility of pets and
animal migration over long distances. Due to climate change, new and
favorable niches are being created thus making the spread of ticks very
rapid over a wide range of ecological zones (Nooroong et al., 2018).
These might be possible factors why there is an increasing spread of
ticks and tick-borne diseases globally. For example, in Germany,Dermacentor reticulatus has spread to over a large part of the
country along with babesiosis that they transmit (Phongmany et al.,
2006) just as the ecological range of Ixodes ricinus the agent
that transmit anaplasmosis and Lyme borreliosis has extended greatly in
Sweden of recent (Gaowa et al., 2013). Similarly, D. veriabilisthe host and vector of RMSF has spread to the North-East of United
States of America (Berglund et al., 1995). The current climate change
has been reported to be the reason for these observable spread of ticks
and their vectored pathogens. With the change in global climate,
increased interaction of humans with ticks and expansive global trade in
animals as well as the migratory nature of animals (Heile et al., 2006;
Berglund et al., 1995; CDC, 2019; Palomar et al., 2012; Sparagano et
al., 2015), it is not unlikely that ticks-borne pathogens could be
easily introduced into new ecological niches thus fueling the global
spread of tick-borne diseases.