Download Zoonotic aspects of vector-borne infections

Rev. Sci. Tech. Off. Int. Epiz., 2015, 34 (1), 175-183
Zoonotic aspects of vector-borne infections
A.-B. Failloux (1)* & S. Moutailler (2)
(1) Research and Expertise Unit for Arboviruses and Insect Vectors, Virology Department, Institut Pasteur,
Paris, 25-28 rue du docteur Roux, 75724 Paris Cedex 15, France
(2) Joint Research Unit for Molecular Biology and Parasitic/Fungal Immunology (BIPAR), French Agency for
Food, Environmental and Occupational Health and Safety (ANSES), French National Institute for Agricultural
Research (INRA), Alfort Veterinary School (ENVA), Animal Health Laboratory, 14 rue Pierre et Marie Curie,
94701 Maisons-Alfort, France
*Corresponding author: [email protected]
Summary
Vector-borne diseases are principally zoonotic diseases transmitted to humans
by animals. Pathogens such as bacteria, parasites and viruses are primarily
maintained within an enzootic cycle between populations of non-human
primates or other mammals and largely non-anthropophilic vectors. This ‘wild’
cycle sometimes spills over in the form of occasional infections of humans and
domestic animals. Lifestyle changes, incursions by humans into natural habitats
and changes in agropastoral practices create opportunities that make the borders
between wildlife and humans more permeable. Some vector-borne diseases have
dispensed with the need for amplification in wild or domestic animals and they can
now be directly transmitted to humans. This applies to some viruses (dengue and
chikungunya) that have caused major epidemics. Bacteria of the genus Bartonella
have reduced their transmission cycle to the minimum, with humans acting as
reservoir, amplifier and disseminator. The design of control strategies for vectorborne diseases should be guided by research into emergence mechanisms in
order to understand how a wild cycle can produce a pathogen that goes on to
cause devastating urban epidemics.
Keywords
Arthropod – Emergence – Epidemic – Vector – Zoonosis.
Introduction: from enzootic
cycle to epidemic cycle, from
epidemic cycle to urban cycle
Vector-borne diseases are responsible for 22.8% of emerging
infectious diseases and 28.8% of those that have emerged
over the past decade (1). This resurgence has coincided
with climate change, which supports the hypothesis that
the climate is influencing the emergence of vector-borne
diseases, as vectors are sensitive to environmental conditions
(rainfall, temperature, etc.). These diseases are among the
leading causes of morbidity and mortality in both humans
and animals. For example, dengue fever infects between
50 and 100 million people each year, with a mortality
rate of up to 2.5% (2). Rift Valley fever was responsible
for massive epizootic outbreaks among domestic animals,
killing 3,500 lambs and 1,200 ewes in Kenya in 1930 (3).
West Nile fever decimated part of the bird population on
the North American continent and infected 40,000 people,
with nearly 1,700 deaths between 1999 and 2013. The
tick-borne encephalitis virus is responsible for the most
important neuroinvasive disease transmitted by ticks in
Europe and Asia, with several thousand human cases a
year and mortality of up to 35% depending on the subtype concerned (4). Their common feature is that they
have an etiological agent of viral origin. There are more
than 500 arthropod-borne viruses, one-quarter of which
cause human diseases, such as haemorrhagic fever and
meningoencephalitis, which can result in death (5).
Mosquitoes are the leading vector for human infectious
agents, followed by ticks (6). Globally, ticks are the vectors
that transmit the greatest variety of infectious agents
(bacteria, parasites and viruses) to both humans and
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animals. It is important to note that no ticks are specific
to humans, who always become infected accidentally. As
they transmit an enormous number of bacteria, parasites
and viruses, ticks are the main vectors for the majority of
zoonoses worldwide. For example, Lyme disease, which is
associated with bacteria of the tick-borne genus Borrelia,
has become widespread in temperate regions, especially in
the United States, with nearly 300,000 new cases each year,
compared with only 60,000 in Europe.
Vector-borne pathogens (bacteria, parasites and viruses)
are transmitted between vertebrate hosts by an arthropod
vector that ensures biological transmission. These pathogens
include arboviruses, which are responsible for zoonoses that
originally existed solely in highly complex forest and rural
ecosystems. These zoonoses involve many vector species
(mainly zoophilic) that infect a wide variety of non-human
hosts. Viral emergence coincides with the uptake of a wild
virus by an anthropozoophilic arthropod (which bites both
humans and animals), thereby initiating a human-to-human
transmission cycle in which humans become the main
amplifier host. Anthropozoonoses mainly occur in an urban
environment where a single vector species and a single
(human) vertebrate host ensure transmission. Arboviroses
such as dengue fever or chikungunya have now dispensed
with the need for a sylvatic cycle to produce epidemics.
They have succeeded in exploiting the human environment
by taking advantage of the strong anthropophilic tendency
of vectors that feed on human blood and by expanding into
breeding sites created by humans. Tick-borne pathogens
include many bacteria, parasites and viruses that circulate
mainly in forest areas as part of a cycle involving ticks
and wild animals (rodents, rabbits, ungulates and birds).
Humans are only infected accidentally when they enter
forest habitats. Some bacteria or parasites circulate mainly
in domestic animals and, in this case too, humans are only
infected occasionally. Just as arboviruses infect mainly
humans, certain bacteria carried by fleas or sandflies are
transmitted from human to human without the need for a
mammal as an amplifier host.
Enzootic cycle with accidental
infection of humans
Arboviruses circulate primarily in a forest cycle in which
the virus is transmitted between populations of vertebrates
(such as monkeys and rodents), with zoophilic arthropods
acting as vectors. Humans are only infected accidentally.
Rift Valley fever, transmitted by mosquitoes, is a zoonotic
disease that primarily occurs in epizootic outbreaks when
environmental conditions exacerbate the proliferation
of vectors. Similarly, Venezuelan equine encephalitis,
transmitted by mosquitoes and endemic in the Americas,
caused the death of hundreds of thousands of horses in the
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1960s, with many human cases. Finally, Crimean-Congo
haemorrhagic fever, transmitted by ticks, causes outbreaks of
viral haemorrhagic fever with extremely rapid multiplication
of the virus in animals (cattle, sheep and goats, but with no
clinical signs), resulting in human infection with a very high
mortality rate. Tick-borne pathogens include many viruses,
bacteria and parasites that circulate mainly in forest zones
where ticks live alongside wild animals (rodents, rabbits,
ungulates and birds). Humans are only infected accidentally
when they enter forest environments. This applies to the
bacteria that cause Lyme disease, with thousands of new
cases reported each year in Europe and the United States.
Similarly, the tick-borne encephalitis virus is responsible
for the most important neuroinvasive disease transmitted
by ticks in Europe and Asia, with several thousand human
cases a year.
Examples of viruses transmitted
by mosquitoes/ticks
Rift Valley fever virus
The Rift Valley fever virus, described for the first time
in 1931 in Kenya’s Rift Valley (3), belongs to the family
Bunyaviridae and the genus Phlebovirus. It is responsible for
epizootic outbreaks affecting mainly domestic ruminants
(cattle, sheep, goats, buffalo), causing abortions and high
mortality rates in young animals. Before 1977, Rift Valley
fever was confined to sub-Saharan Africa, where it mainly
caused epizootic outbreaks; human cases were rare and
not serious. In 1977, there were widespread epizootic
outbreaks in the Nile delta where many human fatalities
were reported (7). The virus also struck the island of
Madagascar in 1990/1991 (8). In 2000, it occurred outside
the African continent, simultaneously in Yemen and Saudi
Arabia (9). Human infection usually presents as flu-like
symptoms with possible complications, such as encephalitis
and hepatitis, accompanied by haemorrhagic fever, often
leading to death. Unlike with other arboviruses, contact
with the tissue of infected animals or the inhalation of
aerosols can lead to infection. A live attenuated Smithburn
vaccine is available, which is administered mainly to cattle.
In Africa, nearly 30 species of mosquito belonging to the
genera Aedes, Culex, Anopheles, Eretmapodites and Mansonia
have been found naturally infected by Rift Valley fever
virus. It has also been isolated in other insects such as biting
midges, black flies and ticks. Rift Valley fever virus also has
an extremely wide range of vertebrate hosts. Factors known
to have increased the epidemic risk in the past include the
heavy rainfall that accompanied El Niño in East Africa in
1997 and 1998, the construction of the Aswan and Diama
dams in Egypt in 1977 and water impoundment along the
Senegal River in 1987. Rift Valley fever virus has very high
epidemic potential; the arrival of an infected human or
animal in the viraemic phase would probably be sufficient
to trigger vector-borne transmission because of the wide
range of hosts that the virus is capable of infecting.
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Venezuelan equine encephalitis virus
The Venezuelan equine encephalitis virus, which
is an alphavirus of the family Togaviridae, is endemic
in the New World. It was isolated for the first time in
1938 (10). The zoonotic cycle in tropical forest involves
rodents as reservoir hosts and mosquitoes of the
sub-genus Culex (Melanoconion) as vectors. The virus is
transmitted to humans and horses by mosquitoes of the
genera Psorophora (P. confinnis, P. columbiae) and Ochlerotatus
(O. taeniorhynchus, O. sollicitans). The substitution of
certain amino acids in the virus envelope (E2) of certain
enzootic strains would seem to have intensified viraemia
in horses, allowing infection of mosquitoes. Humans are
only accidentally infected and develop a highly debilitating
dengue-like fever that can sometimes degenerate into fatal
encephalitis.
Crimean-Congo haemorrhagic fever virus
Crimean-Congo haemorrhagic fever (CCHF) is caused
by a nairovirus of the family Bunyaviridae, causing severe
haemorrhagic fever in humans, with a mortality rate of
10–40%. The virus was isolated for the first time in the
Democratic Republic of Congo in 1944 (11) and is found
in Africa, Europe, the Middle East and Asia. The virus is
transmitted mainly by ticks of the genera Hyalomma (H.
marginatum or H. anatolicum), Rhipicephalus, Ornithodoros,
Boophilus, Dermatocentor and Ixodes. The vertebrate hosts
are wild mammals (including buffalo, wild boar and
mountain sheep) or domestic mammals (cattle, goats,
sheep, horses, camels); these animals become infected
with no apparent clinical signs (12). Only humans appear
to show pathological signs when infected by the virus,
which means that circulation of the virus can be detected
only from human cases among livestock or crop farmers
or veterinarians. Humans become infected by tick bites or
by direct contact with infected tissue or blood (13). There
is no vaccine for either humans or animals. Environmental
changes associated with human activities (war, new
agropastoral practices, etc.) appear to be the major factors
disrupting the zoonotic cycle and creating conditions
conducive to the emergence of epidemics. Of all the tickborne viruses infecting humans, CCHF is the one with the
widest geographic distribution, raising fears of an upsurge
of the disease in temperate regions, especially Western
Europe.
Tick-borne encephalitis virus
The tick-borne encephalitis virus belongs to the family
Flaviviridae and the genus Flavivirus. It was described for
the first time in 1931 in Austria, but the virus was not
isolated until 1937 in Russia (18). In countries where the
virus is present, reports of indigenous human cases and/or
its detection in ticks collected in the field show that the virus
foci are fairly stable. The wild cycle involves mainly tick
populations that remain infected throughout their lifetime
(19) (Ixodes ricinus in Western Europe and I. persulcatus in
Eastern Europe and Asia) and wild small mammals (field
mice, voles), which act as reservoirs (20). Several other wild
and domestic species, as well as humans, are believed to be
accidental hosts that develop little or no viraemia, rendering
them unable to transmit the virus via the vector (21). They
may nevertheless be used as sentinels for monitoring the
risk of zoonosis (22).
Human infection is seasonal, peaking in the spring
and summer, linked with the activity of the vector
ticks. The human endemic area covers most of Eastern
Europe, as well as Siberia and the Far East. These three
areas correspond to the three different sub-types of
the virus, with the geographic distribution of each virus
more or less correlating with the geographic distribution
of its vector. Human infection generally presents as flulike symptoms with possible complications, such as
meningoencephalitis of varying severity. Mortality is
between 0.5% and 3% for the European and Siberian subtypes, but can be as high as 35% for the Far Eastern subtype. Neurological sequelae occur in 10% of cases for the
European sub-type but are higher for the other sub-types
(23). Humans can also become infected by eating raw dairy
products (cheese, milk) (24). An inactivated vaccine is
available.
Examples of bacteria transmitted by ticks
Borrelia burgdorferi, sensu lato
Lyme disease is caused by spirochete bacteria
belonging to the species Borrelia burgdorferi sensu lato.
The natural cycle involves ticks of the genus Ixodes and
a wide range of animal species that can act as reservoirs
(rodents, rabbits, birds, lizards, etc.) (14, 15). The disease
has a very wide range, which coincides with that of its
various vectors, mainly in the northern hemisphere:
I. scapularis and I. pacificus in North America (east
and west coast respectively); I. ricinus in Western
Europe; and I. persulcatus in Eastern Europe and Asia.
The disease nevertheless appears to extend to the
southern hemisphere, with human cases reported in
Australia and South America. Animals and humans
are both infected by the bites of infected ticks. Of the
19 species of Borrelia identified to date, just one –
B. burgdorferi sensu stricto – is recognised as pathogenic for
humans in North America, compared with five species in
Europe: B. burgdorferi s.s., B. garinii, B. afzelii, B. spielmanii
and B. bavariensis. Three other species are potentially
pathogenic: B. bissetii, B. lusitaniae and B. valaisiana. In
humans, the most common clinical sign is inflammation
of the skin or erythema migrans. We also see arthritis,
neuroborreliosis or even delayed cutaneous manifestations,
depending on the Borrelia species involved (16, 17).
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Epidemic cycle,
from animals to humans
The emergence of a pathogen from a forest cycle involves
the enzootic cycle coming into contact with humans and
domestic animals. The trophic preferences of vectors
therefore play a fundamental role in transmitting pathogens
from animals to humans. Yellow fever, which originally
operated in a forest cycle in which the virus moved
between populations of monkeys and zoophilic mosquitoes
in the forest canopy, underwent a process of urbanisation,
mainly in Africa, where the virus is transmitted by a highly
anthropophilic domestic mosquito, Aedes aegypti. Similarly,
the West Nile virus formerly affected mainly migratory
birds that acted as animal reservoirs. It has now become
the second most widespread arbovirus in the world, after
the dengue virus. It infects humans, who were previously
only an accidental host, and over the past decade numerous
fatalities have been reported in Europe (Greece) and the
United States. Finally, Japanese encephalitis is one of the
major viral diseases in rural areas of the Asian continent,
where it once affected only wild birds and bats. This
epidemiological profile was completely overturned with
the introduction of intensive pig farming (pigs are the most
effective amplifier host), facilitating transfer of the virus to
humans living nearby. Certain tick-transmitted bacteria and
parasites are capable of infecting many wild animals, as well
as domestic animals, in which they cause serious disease.
This is true of the bacterium Anaplasma phagocytophilum,
which causes granulocytic anaplasmosis in animals and
humans, as well as of parasites of the genus Babesia. Close
contact with infected domestic animals is a source of human
infection as it increases the chance of encounters between
ticks and humans.
Examples of viruses transmitted by mosquitoes
Yellow fever virus
The yellow fever virus belongs to the genus Flavivirus of
the family Flaviviridae. It was isolated in West Africa in
1927. To date, seven genotypes have been identified: five in
Africa and two in the Americas (25). In Africa, the virus is
transmitted in a forest cycle between non-human primates
and zoophilic mosquitoes such as Aedes africanus. The virus
was able to leave the forest with the help of mosquitoes
capable of biting humans (Ae. luteocephalus, Ae. furcifer,
Ae. metallicus, Ae. opok, Ae. taylori, Ae. vittatus and members
of the simpsoni complex). Urban yellow fever is found
only in Africa, where human-to-human transmission is via
the anthropophilic mosquito Ae. aegypti. The situation is
completely different in the Americas, as only a forest cycle
remains, in which the virus circulates between monkeys
and sylvatic vectors of the genus Haemagogus. However, the
steady spread of the vectors Ae. aegypti and Ae. albopictus
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is raising concern over the return of urban yellow fever
epidemics in South America, as in the past. Although there
is a safe and effective vaccine, vaccine 17D, it is not used
extensively in the yellow fever-endemic region in Africa,
which covers 34 countries with 500 million inhabitants.
West Nile virus
The West Nile virus provides an impressive example
of the speed with which an arbovirosis can invade five
continents. This Flavivirus of the family Flaviviridae,
isolated in Uganda in 1937, is maintained in nature in
an enzootic cycle between Culex mosquitoes and several
bird species. There are seven West Nile virus strains, with
lineage 1 the most widely distributed in Africa, Europe and
the Americas. In 1994, the West Nile virus became more
active again in the Old World, with greater pathogenicity
for humans and/or horses. In 1996, there was an epidemic
in Bucharest (Romania) with more than 500 cases of
encephalitis. In 1999, 40 deaths were reported in Russia
and in 2000 eight deaths were reported in Israel. In 1999,
the West Nile virus (genotype NY99) was introduced to
New York, probably by an infected bird from the Middle
East, and spread throughout the Americas. By 2002, a new
genotype (WN02) had displaced it. WN02 has an amino
acid substitution (V159A) in the envelope protein, which
facilitated adaptation of the virus to mosquitoes of the genus
Culex (26). This illustrates the plasticity of the viral genome,
which can facilitate adaptation to other vectors, including
anthropophilic vectors that play a key role in the emergence
of epidemics. The West Nile virus has been isolated in more
than 70 species of mosquito, mainly of the genus Culex,
and in particular Culex pipiens, a sub-species of which
(C. p. molestus) has a preference for biting mammals.
Japanese encephalitis virus
The Japanese encephalitis virus belongs to the family
Flaviviridae and the genus Flavivirus and was first described
in 1871 in Japan during an encephalitis epidemic in horses
and humans. It is endemic in Asia, from the People’s Republic
of China to Indonesia and from India to the Philippines.
This virus has five strains: lineages 1, 2 and 3 are found
in subtropical and temperate regions, and lineages 4 and 5
are confined to the Indonesian archipelago (27). More than
3 billion people worldwide live in areas at risk, with an
estimated 30,000 to 50,000 cases each year. The geographic
area where Japanese encephalitis is endemic has expanded
over the past 70 years, with the virus spreading westwards.
The Japanese encephalitis virus is transmitted in a zoonotic
cycle between species of Culex (Culex tritaeniorhynchus) and
pigs or birds. Humans are only accidentally infected and are
considered a dead-end host for the parasite because of their
low level of viraemia. Nevertheless, this is beginning to
change owing to the growth in rice cultivation areas (where
vectors proliferate) close to pig farms, where pigs amplify
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the virus. For this reason, Japanese encephalitis should not
be considered an exclusively rural disease, as it is starting to
reach the outskirts of villages and even towns.
Examples of bacteria
and parasites transmitted by ticks
Anaplasma phagocytophilum
Human or animal granulocytic anaplasmosis is caused by
a small obligate intracellular gram-negative bacterium,
Anaplasma phagocytophilum, of the family Anaplasmataceae
(order Rickettsiales). Many tick species act as vectors for
this bacterium: I. ricinus in Europe, I. persulcatus in Russia
and Asia and I. scapularis, I. pacificus and I. spinipalpis in
the United States (28). This disease, described for the first
time in sheep in Scotland in 1932, has been reported in
both animals and humans in Europe, Asia, the United States
and Australia. Many wild mammals are naturally infected
with this bacterium, including rodents, insectivores and
wild ruminants such as roe deer (Capreolus capreolus) and
red deer (Cervus elaphus). In the United States, it appears
that domestic ruminants are not affected a great deal, but
in Europe, ruminant livestock (cattle, sheep, goats), along
with horses, are the animals most affected by this bacterium
(29). The first human cases of granulocytic anaplasmosis
were reported in the United States in the 1990s, and the
number of cases has continued to grow since. Its current
incidence is estimated at 6.1 cases per million inhabitants
(30). In Europe, cases were first described in Slovenia in
1997, followed by many other countries, including Sweden,
Greece, Spain, Russia and France. The real frequency of
human infection is probably underestimated because of the
high levels of seroprevalence detected, both in the United
States (11–15%) (31) and in Europe (2–28%) (32). The
clinical signs in domestic ruminants range from a high
fever to a reduction in milk yield; in other mammals, the
clinical signs can be very diverse, but the infection is often
asymptomatic. In humans, the disease causes a high fever
with chills, but, in general, anaplasmosis is not particularly
serious. A small number of fatalities have been reported in
both animals (domestic ruminants and wild animals) and
humans (less than 1% of cases) (29).
Babesia divergens, B. venatorum and B. microti
Babesiosis is caused by obligate parasites (intraerythrocytic
protozoa) that are transmitted by hard ticks and are capable
of multiplying in many wild and domestic animals. However,
only three species of Babesia are transmissible to humans:
B. divergens, B. venatorum (EU1) and B. microti. Fifty or
so human cases have been reported in Europe but this is
probably an underestimate, because babesiosis takes many
asymptomatic forms. Babesia divergens is a cattle parasite
that can be transmitted to humans by the bite of the tick
I. ricinus. This parasite is responsible for most of the human
babesiosis cases in Europe (33); it is most widespread in
temperate zones and its range continues to grow. This same
parasite is also capable of infecting wild animals, including
ungulates and some rodents (34, 35). Babesia venatorum,
a species phylogenetically related to B. divergens, is also
transmitted by the tick I. ricinus, and squirrels are strongly
suspected of acting as reservoirs. It is increasingly being
found in humans (36) and in ticks and wild ruminants in
peri-urban forest areas (35). Babesia microti is a parasite of
rodents transmitted by ticks of the genus Ixodes, including
I. ricinus in Europe. Although it is responsible for several
hundred human cases each year in the United States (37),
only one human case has been reported in Europe to
date (36).
Urban cycle: the unique role of
humans
Some pathogens have dispensed with the need for
amplification in wild or domestic animals and can now
be transmitted directly to humans. The dengue and
chikungunya viruses are prime examples of this: human
hosts act simultaneously as the reservoir, amplifier
and disseminator and the major vector is the strictly
anthropophilic Ae. aegypti, which is found in urban areas
that provide conditions conducive to their proliferation.
Dengue is the leading arbovirosis in terms of human
morbidity and mortality; this has been exacerbated in
recent decades by the co-circulation of four dengue
serotypes throughout virtually the entire inter-tropical
convergence zone. Chikungunya tends to invade tropical
regions, with incursions into temperate regions following
the modification of an amino acid in the viral envelope that
facilitates transmission by a vector which previously had
only rarely been involved in transmission, Ae. albopictus. The
bacteria Bartonella bacilliformis, transmitted by sandflies,
and Bartonella quintana, transmitted by body lice, illustrate
how bacteria are also able to dispense with an intermediate
animal amplifier host; humans are considered to be the
reservoir of both these pathogens.
Examples of viruses transmitted by mosquitoes
Dengue virus
The dengue virus, which is of the family Flaviviridae and
the genus Flavivirus, is responsible for the most important
arboviroses in terms of public health (38). There are four
serotypes (DENV-1 to DENV-4), each of which is subdivided
into five genotypes. Acquired immunity following infection
by one of the serotypes confers protective immunity against
the infecting serotype but not against the others. Ancestral
forms of dengue virus formerly circulated in sylvatic cycles
between populations of non-human primates and forest
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canopy mosquitoes, which are relatively non-anthropophilic.
These cycles have been described in Asia and Africa. Each
of the dengue serotypes responsible for recent epidemics
has evolved independently of the others from a sylvatic
strain of the same serotype. Nowadays, human infections
are caused by dengue virus strains which amplify only in
humans, who become reservoir, amplifier and disseminator
host. The clinical picture ranges from asymptomatic to
classic dengue fever to dengue haemorrhagic fever, which
can be fatal. Every year around 50–100 million people
are infected, with a mortality rate of up to 2.5%. While
classic dengue fever occurs practically everywhere in the
range of the urban vector, Ae. aegypti, dengue haemorrhagic
fever is more widespread in South-East Asia and tropical
America. The dengue fever situation there is worsening,
with a noticeable rise in the mortality rate. This appears to
have coincided with degradation of the urban environment
(rapid, uncontrolled urbanisation in developing towns and
cities), increasing the number of potential breeding sites
and promoting the proliferation of vectors. South-East
Asia has become the major focus of dengue virus, with the
co-circulation of four serotypes, resulting in a situation
of hyperendemicity. Dengue haemorrhagic fever was first
described in the Philippines in 1953–1954. In the absence
of specific symptomatic treatments, Sanofi Pasteur is
developing a tetravalent vaccine (phase III) against all four
serotypes (39).
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in waves is linked to the vector species Ae. albopictus. It
has been demonstrated that a single change in the amino
acids of the viral envelope glycoprotein E1 is responsible
for this adaptation (41). Under experimental conditions,
Ae. albopictus showed greater vector competence for the
new chikungunya virus variant (42, 43). In October 2013,
the first indigenous cases of chikungunya were reported in
the Caribbean, where Ae. aegypti is the only vector present
that is able to transmit the Asian-genotype chikungunya
virus. Since then, this epidemic wave has affected around
40 countries in the Americas, including the United States
and Brazil, causing over one million cases. Whether
transmitted by Ae. aegypti or Ae. albopictus, both of which
are highly anthropophilic, the Asian-genotype chikungunya
virus will continue to spread. It is now rife in the South
Pacific region (New Caledonia, Samoa, Tokelau, French
Polynesia). Candidate vaccines are currently being studied:
chimeric vaccines containing chikungunya virus structural
proteins connected to the overall structure of another
alphavirus; consensus-based envelope DNA vaccines; viruslike particles (i.e. viral particles with no genome) capable
of triggering the production of neutralising antibodies; or
a recombinant live attenuated measles vaccine expressing
chikungunya virus-like particles.
Examples of bacteria transmitted by lice, fleas
and sandflies
Chikungunya virus
Bartonella bacilliformis and B. quintana
The chikungunya virus, which was first isolated in Tanzania
in 1952, belongs to the family Togaviridae and the genus
Alphavirus. The name chikungunya derives from the
Makonde word meaning ‘that which bends’, referring to
the clinical signs of infected patients. Three genotypes
have been described: East/Central/South African (ECSA),
West African, and Asian. This virus, originally from Africa,
is maintained within a forest cycle involving non-human
primates and sylvatic mosquitoes of the genus Aedes, such
as Ae. furcifer, Ae. taylori, Ae. luteocephalus, Ae. dalzieli,
Ae. vittatus and Ae. africanus (40). Unlike in Africa, in Asia
the chikungunya virus circulates in urban areas, where
it is transmitted by house mosquitoes of the genus Aedes
(Ae. aegypti and Ae. albopictus), with humans acting as
the main amplifier host. Chikungunya symptoms include
high fever, joint pain, headache, muscular pain and a rash.
In 2004, the ECSA genotype of the chikungunya virus
re-emerged in Kenya, from where it spread for the first
time to the Indian Ocean region, causing unprecedented
epidemics. In 2006, epidemics were reported in India
and Africa (Cameroon, Gabon, Democratic Republic
of Congo). Since 2008, strains of the ECSA genotype
have circulated in South-East Asia (Malaysia, Singapore,
Thailand, Indonesia, Myanmar and Cambodia). The first
(exceptional) indigenous cases in Europe were reported
in Italy in 2007 and in France in 2010. This re-emergence
Bartonella bacilliformis causes Carrion’s disease (also known
as Oroya fever or Peruvian wart) and Bartonella quintana
causes trench fever. These gram-negative intracellular
bacteria belong to sub-group α2 of the class Proteobacteria
and the genus Bartonella. More than 30 species of Bartonella
have been isolated to date in humans and in domestic
and wild animals worldwide. A wide range of mammals
act as reservoirs for the different species of Bartonella, but
humans are the only known reservoir of B. bacilliformis
and B. quintana. These two bacteria were discovered in
1909 and 1914 respectively (44). While trench fever is
found throughout the world, the geographic distribution
of Carrion’s disease is confined to its vector range, namely
arid areas at altitudes of 500–3,000 metres in the Andes
mountains (Peru, Ecuador, Colombia), as well as in Bolivia,
Chile and Guatemala. Bartonella bacilliformis are transmitted
to humans by sandflies of the species Lutzomyia verrucarum,
and B. quintana are transmitted by body lice of the species
Pediculus humanis corporis. In most cases the first infection
is asymptomatic, but some patients develop Oroya fever or
trench fever when the bacteria enter the erythrocytes. In
some cases the bacteria can colonise secondary foci, such
as the liver; the spleen; vascularised tissues of the heart,
leading to endocarditis (B. quintana); or the endothelial cells
of the skin, causing rashes (Peruvian wart in the chronic
phase of B. bacilliformis) (45). Left untreated, infections
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with B. bacilliformis can lead to death in about 40% of cases.
Bartonella quintana was responsible for millions of human
cases among soldiers and is now considered to be a reemerging disease among the world’s homeless, with a high
seroprevalence, and in its chronic forms it does not respond
well to treatment with antibiotics (44).
Conclusions
Vector transmission owes its effectiveness to each component
in the vector-borne system – pathogen, vector insect and
vertebrate host (reservoir, amplifier and disseminator
hosts). But it also depends on the interactions of these
components within their environment, the characteristics
of which can affect the different actors directly or indirectly.
The genotypes of the pathogen, vector insect and vertebrate
hosts (broadly defined as vertebrates receptive to infection)
are known to influence successful transmission. Not just
any pathogen can be transmitted by any vector and be
hosted by any animal or human host. The relationship
between pathogen and vector can be measured in terms of
vector competence (46). Nevertheless, vector competence
does not stem solely from the cumulative effects of the
genotypes of the vector and the pathogen – it also depends
on the interactions between the two genotypes (47).
Similarly, vertebrate populations are not all equal in the face
of infection, because susceptibility varies depending on the
species and geographic population. Environmental factors
can affect transmission by aggravating or constraining it
(e.g. developing weather conditions can be conducive or
non-conducive to the proliferation of vectors or animals).
The vector system is complex and the same goes for control
strategies.
The greatest risk to human health comes from vector-borne
diseases that are largely maintained within an urban cycle
where high-density human populations create conditions
conducive to the proliferation of mainly anthropophilic
vectors. Recent epidemics of dengue fever or chikungunya
remind us that it should be a priority to develop a vaccine.
However, if we focus too heavily on humans and domestic
animals, the sylvatic cycle continues unabated while
remaining a source of infection for other cycles. Moreover,
some pathogens are quick to adapt to anthropophilic
vector-borne transmission; for example, a single change
in the amino acids of a viral envelope protein can lead to
devastating epidemics. In addition to studying the emergence
mechanisms, combining field work with basic research, we
need to: improve surveillance techniques by developing
tools for rapid pathogen detection; find alternative means
of prevention by testing vaccines against arthropod bites;
and propose new control strategies, without neglecting to
improve existing anti-vector control techniques.
Acknowledgements
The authors wish to thank all members of the Research
and Expertise Unit ‘Arboviruses and Insect Vectors’ and
the members of the Vectotiq team. Particular thanks go to
Dr Sarah Bonnet and Dr Muriel Vayssier for their advice
and helpful discussions. This article would never have seen
the light of day without the financial support of the Institut
Pasteur and the French Agency for Food, Environmental
and Occupational Health and Safety (ANSES), through
a cross-disciplinary research project (PTR-ChipArbo).
They would also like to thank the European Network
for Neglected Vectors and Vector-Borne Infections
(COST Action TD1303), as well as the Ticks and TickBorne Diseases Working Group of the Réseau Ecologie des
Interactions Durables at the French National Institute for
Agricultural Research (INRA).
182
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