Pulmonary infections in the returned traveller
Trimble et al. Pneumonia
Pulmonary infections in the returned traveller
Ashleigh Trimble 0 1
V. Moffat 2
A. M. Collins 0 3
0 Respiratory Infection Group, Liverpool School of Tropical Medicine , Pembroke Place, Liverpool L3 5QA , UK
1 Crosshouse Hospital , Kilmarnock Road, Crosshouse KA2 0BE , UK
2 Aintree Hospital , Longmoor Lane, Liverpool L9 7AL , UK
3 Respiratory Research Group, Royal Liverpool and Broadgreen University Hospital Trust , Prescot Street, Liverpool L7 8XP , UK
Pulmonary infections in the returned traveller are a common presentation. A wide variety of infections may present with pulmonary symptoms. It is important for clinicians to differentiate the cause of these symptoms. The risk of contracting certain travel-related pulmonary diseases depends on travel destination, length of stay, activities undertaken and co-morbidities. Some pathogens are found worldwide, whilst others are related to specific locations. This review article will discuss the approach to diagnosing and treating pulmonary infections in the returned traveller.
Travel; Traveller; Pulmonary infections; Tropics; Respiratory infections
International travel has steadily increased over the last few
decades, and is no longer only for the wealthy and healthy.
The number of travellers reached more than one billion
for the first time in 2012 and continues to rise . There
are many risk factors that increase the likelihood of
developing a travel-related illness and this review will
focus on pulmonary-related infections (Table 1) [2–4].
Many illnesses are self-limiting and are a result of
common pulmonary viruses that are prevalent worldwide
[3, 5] but in certain circumstances travel-related
pulmonary infections are serious and have potentially fatal
implications, and can even cause epidemics.
Air travel has shown how efficiently pulmonary
infections can be transmitted. Data suggests the risk of
disease transmission to a symptom-free passenger within
the aircraft cabin is associated with sitting within 2
rows of a contagious passenger for a flight time of more
than 8 h. This association is mainly derived from
investigations of in-flight transmission of tuberculosis (TB)
. Aircraft cabin ventilation appears to be a key factor
enabling disease transmission. This was highlighted by
the spread of severe acute respiratory syndrome (SARS)
during a short-haul flight in 2002 . With sea travel
(especially cruising) becoming more popular, the ageing
population of travellers with multiple pre-existing
conditions is also a concern.
Clinicians should be aware of particular diseases that
may present in the returned traveller and rank their
diagnostic likelihood based on destination, length of stay
and symptom duration (Tables 2 and 3).
Pneumonia is a frequent cause of fever amongst
returned travellers . Awareness of travel locations may
be key to identifying the organism responsible, and
polymerase chain reaction (PCR) testing is very important to
look for atypical etiologies. Routinely, patients are started
on antibiotics based on local guidelines for
communityacquired pneumonia. It is unlikely these regimens will
contain appropriate first-line therapy or be of sufficient
duration to cover for pneumonias caused by Coxiella
burnettii (Q fever)  or Burkholderia pseudomallei
(melioidosis), which have been isolated in recent outbreaks
that have occurred in Europe and South East Asia .
Pulmonary infections are diagnosed in up to 24% of
returned travellers with fever, making it as common as
travellers’ diarrhea, with influenza being the most
common vaccine-preventable infection acquired (vaccine
protective against H1N1, H3N2 and two influenza B
virus strains) [10, 11]. Pre-travel advice should be that
travellers with co-morbidities should be vaccinated
against both seasonal influenza virus and
pneumococcus . It should be noted that the influenza vaccine
does not currently offer protection against the most
recent strains causing epidemics (H5N1, H7N9) and
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Table 1 Specific Risk factors
and Brugia malayi)
SARS severe acute respiratory syndrome, MERS Middle Eastern respiratory
syndrome, HIV human immunodeficiency virus
the risk of acquiring the illness depends on season of
travel and length of stay in affected areas .
In this review, we will discuss various pulmonary
infections that are more common in returned travellers. A clear
and thorough approach to a symptomatic returned
traveller is an essential skill for the acute/general physician and
general practitioner (Table 4). Particular attention should
be given to infections that may spread by
human-toTable 2 Incubation periods of pulmonary infections
Viral: influenza, SARS, MERS, Nipah
Bacterial: common organisms causing
pneumonia (Streptococcus pneumoniae,
Haemophilus influenzae), melioidosis,
Legionellosis, plague, pertussis, diphtheria
Medium (10–21 days) Viral: MERS, Nipah, hantavirus
Bacterial: pertussis, melioidosis
Fungal: histoplasmosis, coccidioidomycosis
Eosinophilic: ascariasis, hookworm, strongyloides,
SARS severe acute respiratory syndrome, MERS Middle Eastern respiratory
syndrome, TB tuberculosis
human transmission. Clinicians should be aware of where
to source information should they suspect a travel-related
infection or if they have concerns for public health.
Infections related to travel are constantly evolving and it is
important for clinicians to remain up to date with current
disease outbreaks and management recommendations.
Pulmonary infections caused by viruses and
Upper pulmonary infections are more common than
lower pulmonary infections. In general, the types of
pulmonary infections that affect travellers are similar to those
in non-travellers, and exotic causes are rare [2, 13, 14]. An
Australian study collected data over a 3-year period; it
showed around 28% of Australian travellers returning
from Asia developed an acute pulmonary infection within
72 h (defined as an illness episode involving the presence
of at least two upper pulmonary symptoms; e.g.,
sorethroat, coryza). This translates to an incidence of 106.4
per 10,000 traveller days. PCR testing on these travellers
was analyzed for influenza A and B virus, adenoviruses,
respiratory syncytial virus (RSV), picornaviruses and
parainfluenza viruses 1, 2, and 3. Only 1% of these travellers
acquired influenza A virus, with no data for the other
detectable viruses included .
There is evidence that contracting a common upper
pulmonary virus potentiates the risk of contracting a
tropical disease as well. A study in 2008  showed
that during an epidemic of chikungunya in India, 87% of
confirmed cases were also co-infected with RSV and
another upper respiratory virus, 41% were co-infected
with RSV alone and 9% were co-infected with influenza
virus and adenovirus. It is likely that a parallel outbreak
of pulmonary viral infections during this time resulted in
higher morbidity and mortality during this epidemic.
Bacterial pathogens are generally not related directly
to a particular travel destination. Streptococcus
pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae,
and Chlamydophila pneumoniae are the most common
organisms known to cause pneumonia throughout the
world and risk of infection is not directly related to
travel. More specific illnesses caused by C. burnettii (Q
fever), Legionella pneumophila (Legionella), Bordetella
Pertussis (pertussis), Corynebacterium diphtheriae
(diphtheria) and Leptospira (leptospirosis) are normally
a result of an epidemic within a country [2, 10, 14].
This list may be very relevant to the treating clinician.
Travel to international mass gatherings is a proven risk
factor for the spread of pulmonary infection. For
example, during pilgrimage to Mecca, pneumonia caused
by S. pneumoniae is the leading cause of hospitalization
and intensive care unit admissions during the Hajj
(nearly 40% of patients). Out of 300 participants less
than 5% had been vaccinated despite 65% being eligible.
North Africa, Middle East
South and Central Asia
diphtheria, TB, avian flu
HIV-associated Katayama syndrome, tropical pulmonary eosinophilia
pulmonary infections, TB (Wuchereia bancrofti), Loeffler’s syndrome (hookworm,
Q fever, tropical pulmonary eosinophilia (Wuchereia
bancrofti) Loeffler’s syndrome (hookworm, ascariasis,
strongyloides) hydatidosis, toxocariasis
Melioidosis, Loeffler’s syndrome (hookworm, ascariasis,
Melioidosis, tropical pulmonary eosinophilia (Brugia
malayi), Loeffler’s syndrome (strongyloides, hookworm),
histoplasmosis, leptospirosis, diphtheria, tropical pulmonary
eosinophilia (Wuchereia bancrofti), Loeffler’s syndrome
(ascariasis, strongyloides), hydatidosis, toxocariasis
Table 3 Causes of pulmonary infections associated with specific geographical areas
SARS, hantavirus, Nipah virus,
dirofilariasis, Katayama syndrome,
Melioidosis, dirofilarisis, pertussis
HIV human immunodeficiency virus, SARS severe acute respiratory syndrome, MERS Middle Eastern respiratory syndrome, TB tuberculosis
Improved pre-travel vaccination advice could prevent
diseases for many travellers .
Particular attention should be paid to travellers returning
from influenza-endemic areas, taking into account newly
reported sub-types. The burden of influenza occurs in the
winter months in temperate regions, in the Northern
Hemisphere from November to April and the Southern
Hemisphere from April to October. In the tropics, the
virus circulates at a low level all year round . Influenza
is diagnosed from viral throat swabs using real time PCR
(rt-PCR) that can differentiate particular influenza
Avian influenza sub-type H5N1 virus has caused death
in humans since 1997, predominately in Asia and North
East Africa, with a current upsurge of cases in Egypt.
From 2003 to October 2015, there have been a total of
844 laboratory-confirmed cases with mortality rates of
Table 4 Checklist for taking a travel history
Treatment or procedures Hospital treatment in country, tattoos
Healthcare worker, business, visiting relatives,
farmer, cave explorer, water exposure
Immunizations, prophylaxis, insect repellents
Unprotected sex, paid sex, multiple partners
Birds, domestic animals, wildlife
more than 50% . H7N9 is the most recently
reported sub-type. It was first diagnosed in March 2013
in China and is characterized by rapidly progressive
pneumonia, pulmonary failure and acute pulmonary
distress syndrome (ARDS) . As of October 2015,
there have been 679 laboratory-confirmed cases, with
275 reported deaths .
Treatment of influenza remains a controversial topic
but generally supportive management is adopted. Current
recommendations are early administration of a
neuraminidase inhibitor (e.g., oseltamivir) to the affected individual
and their close contacts . A recent meta-analysis of
the H1N1 pandemic showed that hospitalized patients
treated with a neuraminidase inhibitor had a lower
mortality, and that this was further reduced by early
Prevention of avian influenza has proved difficult due
to the antigenic diversity of the circulating viruses,
which has hampered vaccine development .
Healthcare professionals should take post-exposure prophylaxis
(e.g., oseltamivir) after a patient has been diagnosed with
avian influenza and personal protective equipment is
Severe acute respiratory syndrome (SARS) and Middle
Eastern respiratory syndrome (MERS)
Like influenza, other viral epidemics are gathering
publicity, heightening awareness and recognition worldwide.
MERS and SARS are zoonotic coronavirus infections with
regular media coverage due to their symptom severity,
associated mortality rates and anxiety regarding potential
human-to-human transmission. Bats are thought to be the
main intermediate host for both viruses, while there is
compelling evidence that camels are also responsible for
transmission of the MERS coronavirus [22, 23].
SARS was first reported as an atypical pneumonia to
the World Health Organization (WHO) in November
2002 in China and subsequently spread worldwide. The
first reported epidemic occurred in a Hong Kong hotel
in February 2003. The virus was transmitted to 16 hotel
guests who were staying on the same floor as an infected
individual, and the virus spread through international air
travel thereafter. WHO identified the coronavirus
responsible through nasopharyngeal culture within 2 weeks
of this event. More than 30 countries reported affected
individuals, with more than 8,000 confirmed cases
worldwide and a 9.6% mortality rate .
The pulmonary symptoms associated with SARS
(typically, non-productive cough and subsequent dyspnea)
did not present until several days after initial exposure
to the virus. As SARS is caused by an airborne virus, the
risk of transmission was greatest amongst those involved
in the direct care of an infected individual. Since no
medications effectively treated SARS, interrupting
transmission was the key to controlling the outbreak. Simple
public health measures, such as wearing surgical masks,
offered the most effective protection against
transmission and there were no further confirmed cases as of
July 2003 .
The public health lessons learned during the SARS
epidemic have proved invaluable in limiting the spread
of MERS cases worldwide. MERS was first recognized in
September 2012 and, as of October 2015, 1,611 cases
have been reported with more than 570 related deaths
. To date, the largest cluster of cases to occur outside
of the Middle East was reported in South Korea in May
2015. The index case was a businessman who developed
pulmonary symptoms upon returning from a trip to the
Middle East. A total of 185 cases were identified, with
36 deaths (19.5% mortality rate) . This proved the
migrating capabilities of the virus and potential for
outbreaks worldwide. Any clinician who sees an individual
returning from the Middle East presenting with fever
and pulmonary symptoms within 14 days of travel
should consider MERS as a diagnosis and prompt
investigations (diagnosed by nasopharyngeal culture) and
public health control methods should be initiated. No
specific treatments or vaccine have been developed to
As with most infections, the groups with the poorest
outcomes related to MERS infection are the young
(<12 years), the elderly (>65 years), immunocompromised
patients and those with multiple co-morbidities .
Clinically, presentation is similar to SARS but MERS has a
longer incubation period and greater severity of
pulmonary symptoms and an even higher mortality risk. All cases
of MERS confirmed worldwide to date have had a direct
or indirect link with the Middle East—predominately
Saudi Arabia. It has proven to be less contagious than
SARS so far, although it is expected that a more virulent
virus will evolve.
Where SARS and MERS have attracted much media
coverage, it should not be forgotten that the plague
bacillus (Yersinia pestis) still affects a great number of
people each year . The pneumonic plague has seen
endemic outbreaks in certain parts of Africa, with sporadic
cases occurring worldwide.
Historically, there have been 3 pandemics involving the
bubonic (swollen, painful lymph nodes) and pneumonic
plague in the 6th century, the 14th century and the 19th
century; however, it also re-emerged in the 1990s with a
more limited distribution .
The pneumonic plague occurs as a complication of the
bubonic plague and is the only form capable of
transmission from human-to-human via pulmonary droplets.
Clinical sequelae are a dry cough within 24 h of first
exposure, which becomes productive before hemoptysis
occurs with the sputum becoming increasingly more
bloodied within the next 24–48 h—this is a sign of
certain mortality. The major clinical clues in diagnosing
the pneumonic plague are travel history, rapid onset of
symptoms (sometimes hours from being asymptomatic to
fever and cough/hemoptysis) and bilateral pneumonia
[27, 28]. The patient is most contagious when hemoptysis
develops; simple protective measures, such as wearing
masks, help prevent transmission .
The last reported outbreak of the pneumonic plague
was in Madagascar in September 2014. There were 263
reported cases, with a 26.9% mortality rate. The plague
has been endemic on the island for the past 30 years—it
is the most severely affected country in the world .
While developing countries are at most risk of
outbreaks of the disease, sporadic cases can occur elsewhere.
Four patients were diagnosed in July 2014 with
pneumonic plague in Colorado, United States of America
(USA). The index patient contracted the disease from his
pet dog. No deaths occurred and all patients rapidly
responded to antibiotic treatment; streptomycin,
tetracyclines and sulphonamides are used as the standard
antibiotics, with gentamicin and fluoroquinolones as
alternatives . All close contacts should be given
prophylactic antibiotics and monitored for symptoms.
The plague bacillus has previously been used in
biological warfare during the 20th century. Yersinia Pestis is
an attractive agent due to easy accessibility, simple culture
needs and transmission via aerosol . It is important
point to note that a plague outbreak can be easily
controlled with simple public health measures and readily
available antibiotics; however, if inappropriately managed
the pneumonic plague is almost certainly fatal.
Hantaan and Nipah viruses
Two viral infections noted to be causing outbreaks
throughout the world are the Hantaan (causing
hantavirus cardiopulmonary syndrome [HPS]) and Nipah
viruses. Both diseases were microscopically discovered in
the 1990s and are zoonotic; they are transmitted to
humans via rodents and via bats and pigs, respectively.
Both have a range of clinical symptoms and may present
with flu-like symptoms continuing onto encephalitis
with Nipah virus or pulmonary failure and cardiogenic
shock in Hantavirus-related infections [32, 33].
The first Nipah outbreak was in Malaysia in 1999; a
total of 276 cases were diagnosed with a 38.4% mortality
rate . The outbreak spread into Singapore and it was
discovered that the virus was transmitted to humans
from pigs; this resulted in a cull of more than 1 million
pigs to control the outbreak. Since then, outbreaks have
occurred in Bangladesh and India with a mortality rate
of around 75% . Most cases presented with
pulmonary symptoms (cough, dyspnea and bilateral opacities
covering the majority of the lung fields on chest
radiograph) and there was a higher human-to-human
transmission rate in comparison to the Malaysian outbreak
. The Nipah virus was readily identified in the saliva
of infected patients, allowing easy disease transmission.
There have only been outbreaks of the Nipah virus in
South East Asia to date, but there is potential for this
disease to occur in other countries. The intermediate host
(fruit bats from the Pteropodidae family) has an extensive
habitat distribution and is native to parts of Africa and
northern Australia . The treatment is limited to
supportive care—control methods to prevent
human-tohuman transmission are very important to stop rapid
spread. Studies have shown the antiviral drug ribavirin
may reduce mortality from the infection .
At present, more than 21 Hantaviruses from the
Bunyaviridae family have been identified as causing
illness in humans. Signs of infection range from
proteinuria to pulmonary edema and frank hemorrhagic illnesses
. HPS is most likely to occur in the Americas although
there are sporadic case reports from Europe . The
disease is most likely to be transmitted in areas where
sanitation is poor or in rural farming areas. Rodents shed the
virus in their urine, droppings and saliva, and the virus is
transmitted between humans via pulmonary droplets .
The first reported outbreak occurred in 1993 in the
USA, although retrospectively it seems the Hantaviruses
have been causing fatal pulmonary illnesses since the
1950s . The cluster of around 30 cases in 1993
occurred in an area of southwest USA known as the ‘Four
Corners’. Clinicians identified a series of cases of a severe
and acute pulmonary illness affecting young healthy adults
where non-cardiogenic pulmonary edema developed
rapidly. To date, more than 600 cases of HPS have been
reported in the USA . In 2012, the virus was discovered
at Yosemite National Park where potentially hundreds of
travellers were exposed to the infection. Ten cases of HPS
were confirmed, 3 of which were fatal .
Treatment for Hantavirus remains supportive.
Intravenous fluids should be used with caution, as aggressive
fluid resuscitation is likely to accelerate the progression
to pulmonary edema and failure due to capillary leakage
. Extracorporeal membrane oxygenation (ECMO)
treatment has dramatically reduced mortality rates .
The benefits of ribavirin therapy remain undetermined
due to small trial numbers . To date, only one
Hantavirus has evolved to transmit via
human-tohuman contact (the Andes virus, named after its
geographical discovery location in 1996).
Accurate diagnosis requires a high degree of suspicion
and should be considered in an individual presenting
from a recent stay in North or South America with
rapidly progressing pulmonary symptoms and/or signs .
The risk to a traveller in contracting any of the above
outbreak diseases remains small given their limited
geographical distribution at present. The risk of exposure
may be increased by several factors (Table 1) such as
activities undertaken, close contact with an infected
individual, and not seeking appropriate pre-travel
information or recommendations. As a clinician it is important
to have up-to-date knowledge on current outbreaks
occurring worldwide and their relevant geography as prompt
recognition and diagnosis may prevent an epidemic.
Q fever, caused by C. burnettii, is a worldwide zoonotic
disease. Outbreaks in humans have been linked to
abattoirs and carriage of C. burnettii by wind from farms of
affected animals. Ticks can also act as a reservoir. It is
not strictly a travel-related illness but it is most likely
found in areas where contamination with animal waste
is common. It presents as an acute febrile illness with
non-specific signs such as atypical pneumonia . Rural
travelling is the greatest risk factor for acquiring the
disease. Most recently, Q fever outbreaks have occurred
in Hungary, where 70 cases were confirmed by
microimmunofluorescence testing and treated with 3 weeks of
a tetracycline. No deaths occurred. Efforts to reduce the
spread of Q fever after an outbreak include elimination
of manure and disinfection of affected farms .
Legionella (L. pneumophila) is a bacterium that can
cause anything from a mild febrile illness to the
potentially fatal form of pneumonia known as Legionnaires’
disease. The bacterium is ubiquitous in the environment,
and the same agent causes sporadic cases and outbreaks.
Outbreaks are typically linked to contaminated water
systems where conditions are ideal for rapid growth of
the organism . In 2014, the WHO confirmed 302
cases of Legionellosis in Lisbon, Portugal, that were
related to a contaminated industrial cooling tower, with
5 deaths as a result of the disease . Most cases are
reported after travel to developed countries in Europe or
North America. At risk individuals are those with
comorbidities, the elderly, smokers and the
immunosuppressed. It is caused by inhalation of aerosols containing
the bacterium and accounts for 2–15% of hospital
admissions for community-acquired pneumonia, with a summer
or autumn peak . Identification of affected individuals
is by urinary PCR and treatment is with a macrolide
Pertussis and diphtheria
Pertussis and diphtheria are vaccine-preventable
pulmonary infections; poor vaccine uptake has led to a recent
increase in cases in developed countries. It is important,
therefore, to take a full vaccination history in returned
travellers who present with pulmonary symptoms .
Pertussis is a worldwide endemic-epidemic disease
with outbreaks most likely during summer/autumn time.
Pertussis is thought to still cause around 63,000 deaths
per year in children under 5 years of age, although there
is uncertainty over these estimates in view of the paucity
of reliable surveillance data .
Recently, there has been an increase in the number of
adolescent and young adults being diagnosed in some
high-income countries, likely due to decreased
vaccination uptake rates and a change in the vaccine itself. It
is thought that the acellular vaccine currently used
appears to have a short-lived immunity leading to
increased infection rates . Macrolide antibiotics are
given to affected individuals to prevent further spread
of pertussis .
Diphtheria presents as an acute infectious disease
affecting the upper pulmonary tract caused by toxins
produced by the bacterium. Characteristic features are
membranous pharyngitis with fever, enlarged anterior
cervical lymph nodes and edema of the soft tissues of
the neck . This manifestation may lead to airway
obstruction. The bacterium has a short incubation period
but untreated individuals may remain infectious for up
to 4 weeks. Both pertussis and diphtheria are potentially
fatal but easily preventable.
Leptospirosis is contracted either through direct contact
with infected animal urine, or urine-contaminated water
. It can be found worldwide, but is predominantly
found in tropical and subtropical countries (during rainy
season). Those taking part in water sports are most at
risk (an outbreak was reported among canyoning
participants in Martinique, France) . Increased cases are
also found in rural parts of a country where drinking
water can be easily contaminated with the bacteria; for
example, where wells have been poorly constructed .
Lately, there has been an increase in the number of
cases noted in Europe, with 97 cases identified in the
Netherlands in 2014 (4.6-fold increase in comparison to
previous years). Dutch tourists reported 33 cases of
leptospirosis, and most of these tourists acquired the
disease in Thailand .
The clinical course of leptospirosis is variable, with
symptoms from myalgia to fever with cough and shortness
of breath. Weil’s disease is its severest form and may
develop in 1–5% of cases. Patients progress from mild
flulike symptoms to signs of organ failure (jaundice and
spontaneous bleeding) .
Where there is a high degree of clinical suspicion for
leptospirosis, treatment should be instigated. Diagnosis
is serological (via microscopic agglutination test [MAT]
for antibodies or PCR urine antigen test) but it may take
around 10 days after the onset of symptoms for these
tests to become positive . In early mild disease,
penicillin and tetracycline antibiotics are effective .
Where the clinically more severe Weil’s disease is
manifest, patients may require organ support, and there is
little evidence that antibiotic use is of any benefit at this
stage . In 2014, there were a total of 76 confirmed
cases of leptospirosis in England and Wales, of which 22
were acquired overseas; the majority of these were related
to recreational water exposure .
Recreational activities such as camping and visiting rural
and agricultural areas lead to increased risk to exposure to
the bacterium that causes tularemia . Typically found
in the Northern Hemisphere, the number of infected cases
are underestimated and underreported . Outbreaks
have been reported on Martha’s Vineyard (Massachusetts,
USA), Sweden and Finland in the last 15 years .
Francisella tularensis is the bacterium responsible for
what is a potentially fatal multi-systemic disease.
Reservoirs of transmission are via ticks, biting flies, aerosol,
water exposure and food . There are 4 identified
subtypes and clinical presentation depends on biotype,
method of transmission and port of entry. There are 6
major clinical presentations: ulceroglandular, glandular,
oculoglandular, oropharyngeal, pneumonic and typhoidal
. Pulmonary features may consist of lobar
pneumonia, pulmonary effusions, infiltrates and hilar
lymphadenopathy. Mortality in untreated pneumonic tularemia
can be up to 60% .
Early diagnosis and treatment is key to prognosis, but
isolation of the bacterium is hazardous and time
consuming and most laboratories do not accept samples for
culture . Agglutination and enzyme-linked
immunosorbent assay (ELISA) tests are the diagnostic tests of
choice . Aminoglycosides are bactericidal against F.
tularensis and WHO recommend a 10-day course .
As an aside, F. tularensis subspecies tularensis (Type A)
is one of the most infectious pathogens known to man,
and these properties have led to tularemia being identified
as a potential weapon of bioterrorism .
In South East Asia and northern Australia, a particular
Gram-negative organism called B. pseudomallei is
responsible for an endemic of melioidosis disease .
Most commonly, the initial presentation is with
lowgrade fever and atypical pneumonia, rapidly progressing
to multi-organ dysfunction. The mortality rate is very
high, ranging from 14 to 40% in general and up to 80%
with inappropriate antimicrobial therapy . Difficulties
in culturing the bacterium responsible mean that
underreporting is likely. The bacterium resides in soil and
water with transmission occurring mainly from
percutaneous inoculation and inhalation. Exposure is most
likely to occur during the wet seasons in affected areas
or after natural catastrophes such as tsunamis.
Sporadic cases of the infection are now being reported
worldwide and manifestations of latent forms of the
disease are appearing some tens of years after initial
exposure . As the number of international travellers
continues to rise, particularly to more rural parts of
South East Asia and northern Australia, this could lead
to an increase in the number of travel-related
melioidosis cases in the future.
Early recognition of melioidosis is essential as the
bacterium is resistant to nearly all drugs given for
community-acquired pneumonia . Current treatment
recommendations are ceftazidime or a carbapenem,
followed by eradication therapy with trimethoprim and
sulfamethoxazole for at least 3 months. There has been
recent interest in vaccine development due to both public
health and bioweapon concerns . Mouse model
vaccination has proved successful but to date there has been
no testing on humans .
TB is a commonly found disease in certain parts of the
world. The risk of TB as a travel-related disease has not
been well established. A study from Italy in 2005
concluded that over half of returned travellers with
pneumonia or TB presented with a febrile illness but no
pulmonary symptoms . TB can be transmitted on
airplanes; a flight from Baltimore to Honolulu showed 4
of 15 passengers had a positive tuberculin skin test after
sitting in close proximity to a passenger with
pulmonary TB . An overall probability of infection is 1 in
1,000 when a symptomatic source is present in close
Risk is linked to longer-term travel to areas of higher
prevalence and proximity to affected individuals. Those
most at risk would be healthcare workers or individuals
visiting relatives . TB risk in long-term travellers (of
greater than 3 months) is the same as the local
population in high endemic areas. A Dutch study showed there
was substantial risk to long-term travellers with an
overall incidence rate of 3.5 per 1,000 person-months
travelled; however, no-one in this study had received a
Bacillus Calmette–Guérin (BCG) vaccine prior to
travelling, therefore incidence amongst those who have been
vaccinated is likely to be lower .
In recent years, multidrug-resistant TB (MDR-TB) and
extensively drug-resistant TB (XDR-TB) have become
increasingly important public health problems in many
countries (Eastern Europe, parts of Asia and Southern
Africa) . The potential risk of transmission of
particularly dangerous forms of TB requires renewed
vigilance. Since 2006, WHO have been informed of several
incidences of patients travelling (short-haul) by air with
MDR-TB and XDR-TB. In these cases, only close family
members have been later diagnosed with the disease, but
a potential risk to other travellers is possible given the
infectious nature of these strains of TB . WHO have
since published guidelines for TB and air travel to
prevent the spread of the disease .
The main advice to clinicians is that the number of TB
infections is increasing, as are MDR-TB and XDR-TB
disease. The risks to most travellers in contracting TB
are small but increase depending on vaccination status,
length of travel, mode of travel and travel destination. If
pulmonary symptoms persist, despite negative standard
microscopy, culture and sensitivity testing, TB should be
added to the differential diagnosis list and should be
Pulmonary infections caused by fungi
Fungal infections in the absence of immunosuppression
generally occur in the Americas, where the exact
destination of the traveller plays an important role in
distinguishing the fungus responsible.
Histoplasmosis and coccidioidomycosis
Histoplasmosis should be considered in travellers
returning from the Midwest and central states of North
America, throughout Latin America and Central and
Western Africa [68–70]. In 2013, approximately 300 cases
were reported in the South West region of China, the first
to be reported in Asia .
Coccidioidomycosis (Valley fever) has long been
recognized as a travel-related mycosis. Endemic areas are in
Southern California, Arizona and Central and South
America . In returned travellers when common
causes for flu-like illness, non-productive cough and
pleuritic chest pain have been ruled out but symptoms
continue to persist, an underlying fungal infection
should be considered as a differential diagnosis.
Histoplasma capsulatum is endemic in North and
Latin America, while H. dubiosii is mainly found in
Central and Western Africa . The organism grows
in soils enriched with bat and bird droppings, and
human infection generally occurs after dust inhalation of
disturbed soil. The incubation period is relatively short,
and symptoms develop within 2 weeks of exposure
. Reticulonodular shadowing on chest radiograph is
common, often with mediastinal lymphadenopathy.
Detection of the histoplasma antibody in urine or
serum is the most sensitive and widely used diagnostic
method . Detection of coccidioidomycosis (Coccidioides
immitis) is similar but radiologically a cavitating pneumonia
may be seen .
In healthy individuals, fungal infections are generally
self-limiting. In those who are immunocompromised,
and/or go on to develop severe infection with systemic
complications, antifungals have been proven to be
effective . In contrast to histoplasmosis, coccidioidomycosis
infection generally leads to acquired immunity therefore
recurrence is unlikely .
Pulmonary infections caused by helminths
Pulmonary symptoms such as wheeze, breathlessness and
hemoptysis and an eosinophilia in a returned traveller
should prompt investigations for helminths. These
infections may present as Loeffler’s syndrome (a result of larval
migration through the lungs) or tropical pulmonary
eosinophilia (hypersensitivity to lymphatic filarial worms).
Specific to schistosomiasis infections, Katayama syndrome
should be suspected in travellers returning from Africa or
South East Asia with fresh water exposure presenting with
fever, eosinophilia, dry cough and urticarial rash. Other
rare pulmonary presentation of helminths infections (such
as paragonimus, toxocariasis and dirofilariasis) should be
considered depending on travel destination and
incubation period . Treatment of these infections is generally
straightforward once the causative helminths have been
In 20% of hydatidosis (echinococcosis tapeworm) there
are pulmonary infiltrations. The majority of cases are
asymptomatic but following a leaking hydatid cyst in the
liver, patients may present with pleuritic chest pain,
breathlessness and cough; a ‘water lily’ sign may be seen
on chest radiograph . Surgery (aspiration) and
antiparasitic drugs are required to fully treat the infection.
The clinical spectrum of pulmonary infections in the
returned traveller is vast. History taking is paramount
(exact dates, contacts, length of stay, place of travel and
timings of onset of symptoms) and a high degree of
suspicion early on in the patient’s management is vital.
Most cases of pulmonary infections in travellers are
mild and self-limiting but travel-specific pulmonary
infections have high mortality rates if interventions are
The main modes of transmission for pulmonary
infections are by droplets or direct contact, hence the
importance of implementing protective barriers and
involving public health colleagues early to prevent
further transmission. Advice is always available from
online resources and specialist centers—as a clinician it is
important to familiarize yourself with guidelines and
protocols on travel-related infections. The WHO and
Centers for Disease Control and Prevention (CDC) are
continually updating guidelines on travel-related
We identified references for this review by searches in
different databases (PubMed, Ovid MEDLINE, Embase
and Cochrane) and references from relevant articles.
The following MeSH headings were used: “pulmonary”,
“respiratory”, “tropical disease” ‘travellers”, “travel”,
The references were all further assessed by reading
the title and abstract. Only articles published in English
were included. We further assessed the references of all
selected publications. The final reference list was
generated on the basis of relevance to the topics covered in
All authors met ICMJE authorship criteria. AT, AC conceived and designed
the research plan. AT, VM contributed to the acquisition, analysis and
interpretation of the data. AT, VM, AC contributed equally to the writing of
the first draft of the manuscript and writing of the manuscript. AT, VM, AC
critically reviewed the manuscript for important intellectual content and
agreed with the manuscript results and conclusions. All authors read and
approved the final manuscript.
Where to look for help
British Infection Association (BIA), for United Kingdom recommendations
and guidelines: www.britishinfection.org/
Centers for Disease Control and Prevention (CDC): www.cdc.gov/
National Travel Health Network and Centre: www.nathnac.org/
ProMED-mail (electronic reporting system for infectious diseases
World Health Organization outbreak data: www.who.int/csr/don/en/
1. UNWTO. Annual Report 2013 . UNWTO; 2013 . Available from: http://www2. unwto. org/publication/unwto-annual-report-2013 . Accessed 1 Nov 2015 .
2. Korzeniewski K , Nitsch-Osuch A , Lass A , Guzek A. Respiratory infections in travelers returning from the tropics . Adv Exp Med Biol . 2015 ; 849 : 75 - 82 . PMID: 25381557 , http://dx.doi.org/10.1007/5584_2014_ 89 .
3. Hearn P , Johnston V. Assessment of returning travellers with fever . Medicine . 2014 ; 42 : 66 - 72 . doi:10.1016/j.mpmed. 2013 .11.009.
4. Gherardin A , Sisson J. Assessing fever in the returned traveller . Australian Prescriber An independent review . 2012 ; 35 ( 1 ): 10 .
5. Jennings LC , Priest PC , Psutka RA , Duncan AR , Anderson T , Mahagamasekera P , et al. Respiratory viruses in airline travellers with influenza symptoms: results of an airport screening study . J Clin Virol . 2015 ; 67 : 8 - 13 . PMID: 25959149 , http://dx.doi.org/10.1016/j.jcv. 2015 .03.011.
6. Mangili A , Gendreau MA . Transmission of infectious diseases during commercial air travel . Lancet . 2005 ; 365 : 989 - 96 . PMID: 15767002 , doi:10.1016/ S0140-6736(05)71089- 8 .
7. Ansart S , Pajot O , Grivois JP , Zeller V , Klement E , Perez L , et al. Pneumonia among travelers returning from abroad . J Travel Med . 2004 ; 11 : 87 - 91 . PMID: 15109472 , http://dx.doi.org/10.2310/7060.2004.17055.
8. Gyuranecz M , Sulyok K , Balla E , Mag T , Balazs A , Simor Z , et al. Q fever epidemic in Hungary, april to july 2013 . Euro Surveill . 2014 ;19. PMID: 25108535 , http://dx.doi.org/10.2807/ 1560 - 7917 .ES2014.19.30.20863.
9. Saïdani N , Griffiths K , Million M , Gautret P , Dubourg G , Parola P , et al. Melioidosis as a travel-associated infection: case report and review of the literature . Travel Med Infect Dis . 2015 ; 13 : 367 - 81 . PMID: 26385170 , http://dx. doi.org/10.1016/j.tmaid. 2015 .08.007.
10. Johnston V , Stockley JM , Dockrell D , Warrell D , Bailey R , Pasvol G , British Infection Society and the Hospital for Tropical Diseases , et al. Fever in returned travellers presenting in the United Kingdom: recommendations for investigation and initial management . J Infect . 2009 ; 59 : 1 - 18 . PMID: 19595360 , http://dx.doi.org/10.1016/j.jinf. 2009 .05.005.
11. Cadorna-Carlos JB , Nolan T , Borja-Tabora CF , Santos J , Montalban MC , de Looze FJ , et al. Safety , immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: a randomized, controlled, phase III trial . Vaccine . 2015 ; 33 : 2485 - 92 . PMID: 25843270 , http://dx.doi.org/10.1016/j.vaccine. 2015 .03.065.
12. Sridhar S , Belhouchat K , Drali T , Benkouiten S , Parola P , Brouqui P , et al. French Hajj pilgrims' experience with pneumococcal infection and vaccination: a knowledge, attitudes and practice (KAP) evaluation . Travel Med Infect Dis . 2015 ; 13 : 251 - 5 . PMID: 25725996 , http://dx.doi.org/10.1016/j. tmaid. 2015 .02.002.
13. Leder K , Sundararajan V , Weld L , Pandey P , Brown G , Torresi J , Groupa GSS . Respiratory tract infections in travelers: a review of the GeoSentinel surveillance network . Clin Infect Dis . 2003 ; 36 : 399 - 406 . PMID: 12567296 , http://dx.doi.org/10.1086/346155.
14. O'Brien DP , Leder K , Matchett E , Brown GV , Torresi J. Illness in returned travelers and immigrants/refugees: the 6-year experience of two Australian infectious diseases units . J Travel Med . 2006 ; 13 : 145 - 52 . PMID: 16706945 , http://dx.doi.org/10.1111/j.1708- 8305 . 2006 .00033.x.
15. Ratnam I , Black J , Leder K , Biggs BA , Gordon I , Matchett E , et al. Incidence and risk factors for acute respiratory illnesses and influenza virus infections in Australian travellers to Asia . J Clin Virol . 2013 ; 57 : 54 - 8 . PMID: 23380660 , http://dx.doi.org/10.1016/j.jcv. 2013 .01.008.
16. Sankari T , Hoti SL , Govindaraj V , Das PK . Chikungunya and respiratory viral infections . Lancet Infect Dis . 2008 ; 8 : 3 - 4 . PMID: 18156080 , doi:10.1016/S1473- 3099(07)70295- 5 .
17. Harper SA , Fukuda K , Uyeki TM , Cox NJ , Bridges CB , Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR Recomm Rep . 2004 ; 53 (RR-6): 1 - 40 . PMID: 15163927 .
18. Li Q , Zhou L , Zhou M , Chen Z , Li F , Wu H , et al. Epidemiology of human infections with avian influenza A(H7N9) virus in China . N Engl J Med . 2014 ; 370 : 520 - 32 . PMID: 23614499 , http://dx.doi.org/10.1056/NEJMoa1304617.
19. Influenza at the human-animal interface: World Health Organization . Available from: http://www.who. int/influenza/human_animal_interface/ about/en/. Accessed 10 May 2016 .
20. Muthuri SG , Venkatesan S , Myles PR , Leonardi-Bee J , Al Khuwaitir TS , Al Mamun A , PRIDE Consortium Investigators , et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data . Lancet Respir Med . 2014 ; 2 : 395 - 404 . PMID: 24815805 , doi:10.1016/S2213-2600(14)70041- 4 .
21. Hala IA , Nagwa FE . Human pandemic threat by H5N1 (avian influenza) . Afr J Microbiol Res . 2014 ; 8 : 406 - 10 . http://dx.doi.org/10.5897/AJMR10.303.
22. Al-Tawfiq JA , Zumla A , Memish ZA . Travel implications of emerging coronaviruses: SARS and MERS-CoV . Travel Med Infect Dis . 2014 ; 12 : 422 - 8 . PMID: 25047726 , http://dx.doi.org/10.1016/j.tmaid. 2014 .06.007.
23. Hui DS , Memish ZA , Zumla A. Severe acute respiratory syndrome vs. the Middle East respiratory syndrome . Curr Opin Pulm Med . 2014 ; 20 : 233 - 41 . PMID: 24626235 , http://dx.doi.org/10.1097/MCP.0000000000000046.
24. Parashar UD , Anderson LJ . Severe acute respiratory syndrome: review and lessons of the 2003 outbreak . Int J Epidemiol . 2004 ; 33 : 628 - 34 . PMID: 15155694 , http://dx.doi.org/10.1093/ije/dyh198.
25. WHO. Middle East respiratory syndrome coronavirus (MERS-CoV): World Health Organization ; 2015 . [ Updated 2015 - 12 - 05 00:11:04]. Available from: http://www.who.int/emergencies/mers-cov/en/. Accessed 1 Nov 2015 .
26. WPRO. Middle East respiratory syndrome coronavirus (MERS-CoV): WPRO | WHO Western Pacific Region; 2015 [updated 2015-09-13 08:54:51 . Available from: http://www.wpro.who.int/outbreaks_emergencies/wpro_ coronavirus/en/. Accessed 1 Nov 2015 .
27. Stenseth NC , Atshabar BB , Begon M , Belmain SR , Bertherat E , Carniel E , et al. Plague: past , present, and future. PLoS Med . 2008 ; 5 , e3. PMID: 18198939 , http://dx.doi. org/10.1371/journal.pmed.0050003.
28. Kool JL . Risk of person-to-person transmission of pneumonic plague . Clin Infect Dis . 2005 ; 40 : 1166 - 72 . PMID: 15791518 , http://dx.doi.org/10. 1086/428617.
29. WHO. Plague in Madagascar: World Health Organization ; 2015 . [ updated 2015 - 06 - 21 07:05:15.] Available from: http://www.who.int/csr/disease/ plague/madagascar-outbreak/en/. Accessed 10 Nov 2015 .
30. Runfola JK , House J , Miller L , Colton L , Hite D , Hawley A , Centers for Disease Control and Prevention (CDC) , et al. Outbreak of human pneumonic plague with dog-to-human and possible human-to-human transmission-Colorado, june-july 2014 . MMWR Morb Mortal Wkly Rep . 2015 ; 64 : 429 - 34 . PMID: 25928467 .
31. Prentice MB , Rahalison L. Plague . Lancet. 2007 ; 369 : 1196 - 207 . PMID: 17416264 , doi:10.1016/S0140-6736(07)60566- 2 .
32. Jonsson CB , Figueiredo LT , Vapalahti O. A global perspective on hantavirus ecology , epidemiology, and disease. Clin Microbiol Rev . 2010 ; 23 : 412 - 41 . PMID: 20375360 , http://dx.doi.org/10.1128/CMR.00062- 09 .
33. Chong HT , Kamarulzaman A , Tan CT , Goh KJ , Thayaparan T , Kunjapan SR , et al. Treatment of acute Nipah encephalitis with ribavirin . Ann Neurol . 2001 ; 49 : 810 - 3 . PMID: 11409437 , http://dx.doi.org/10.1002/ana.1062.
34. Chua KB , Lam SK , Goh KJ , Hooi PS , Ksiazek TG , Kamarulzaman A , et al. The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia . J Infect . 2001 ; 42 : 40 - 3 . PMID: 11243752 , http://dx.doi.org/10.1053/jinf.2000.0782.
35. SEARO. Nipah virus outbreaks in the WHO South-East Asia Region: SEARO | WHO South-East Asia Region ; 2013 . [updated 2013-02-11 12:10:49] . Available from: http://www.searo. who.int/entity/emerging_diseases/links/nipah_virus_ outbreaks_sear/en/. Accessed 20 Nov 2015 .
36. Luby SP , Gurley ES , Hossain MJ . Transmission of human infection with Nipah virus . Clin Infect Dis . 2009 ; 49 : 1743 - 8 . PMID: 19886791 , http://dx.doi.org/10. 1086/647951.
37. Global_ NiphaandHendraRisk_20090510.png (2027Ã-1358): World Health Organization ; 2015 . Available from: http://www.searo. who.int/entity/emerging_ diseases/links/information_regarding_nipah_virus/en/. Accessed 20 Nov 2015 .
38. Gizzi M , Delaere B , Weynand B , Clement J , Maes P , Vergote V , et al. Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages . Eur J Clin Microbiol Infect Dis . 2013 ; 32 : 1341 - 5 . PMID: 23670277 , http://dx.doi.org/10.1007/s10096- 013 - 1885 -x.
39. Zaki SR , Khan AS , Goodman RA , Armstrong LR , Greer PW , Coffield LM , et al. Retrospective diagnosis of hantavirus pulmonary syndrome , 1978 - 1993 : implications for emerging infectious diseases . Arch Pathol Lab Med . 1996 ; 120 : 134 - 9 . PMID:8712893.
40. CDC - Reported Cases of HPS - Hantavirus: centre for disease control . 2015 . Available from: http://www.cdc.gov/hantavirus/surveillance/index.html. Accessed 20 Nov 2015 .
41. Hartline J , Mierek C , Knutson T , Kang C. Hantavirus infection in North America: a clinical review . Am J Emerg Med . 2013 ; 31 : 978 - 82 . PMID: 23680331 , http://dx.doi.org/10.1016/j.ajem. 2013 .02.001.
42. Crowley MR , Katz RW , Kessler R , Simpson SQ , Levy H , Hallin GW , et al. Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation . Crit Care Med . 1998 ; 26 : 409 - 14 . PMID: 9468181 , http://dx.doi.org/10.1097/ 00003246 - 199802000 - 00047 .
43. Mertz GJ , Miedzinski L , Goade D , Pavia AT , Hjelle B , Hansbarger CO , Collaborative Antiviral Study Group, et al. Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America . Clin Infect Dis . 2004 ; 39 : 1307 - 13 . PMID: 15494907 , http://dx.doi.org/10.1086/425007.
44. Falkinham 3rd JO , Hilborn ED , Arduino MJ , Pruden A , Edwards MA . Epidemiology and ecology of opportunistic premise plumbing pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa . Environ Health Perspect . 2015 ; 123 : 749 - 58 . PMID: 25793551 .
45. Sakamoto R. Legionnaire 's disease, weather and climate . Bull World Health Organ . 2015 ; 93 : 435 - 6 . PMID: 26240466 , http://dx.doi.org/10.2471/BLT.14.142299.
46. Managing legionella in hot and cold water systems: health and safety executive . 2015 . Available from: http://www.hse.gov.uk/healthservices/ legionella.htm. Accessed 22 Nov 2015 .
47. Larson HJ , Cooper LZ , Eskola J , Katz SL , Ratzan S. Addressing the vaccine confidence gap . Lancet . 2011 ; 378 : 526 - 35 . PMID: 21664679 , doi:10.1016/ S0140-6736(11)60678- 8 .
48. WHO. Pertussis vaccines: WHO position paper - september 2015 . Wkly Epidemiol Rec . 2015 ; 90 : 433 - 58 . PMID: 26320265 .
49. Carbonetti NH . Bordetella pertussis: new concepts in pathogenesis and treatment . Curr Opin Infect Dis . 2016 ; 29 : 287 - 94 . PMID: 26906206 , doi:10. 1097/QCO.0000000000000264.
50. Burkovski A. Diphtheria and its etiological agents . In: Burkovski A, editor. Corynebacterium diphtheriae and related toxigenic species . Erlangen: Springer Netherlands ; 2014 . p. 1 - 14 . doi:10.1007/ 978 - 94 - 077 - 7624 -1_ 1 .
51. Hochedez P , Escher M , Decoussy H , Pasgrimaud L , Martinez R , Rosine J , et al. utbreak of leptospirosis among canyoning participants, Martinique , 2011 . Euro Surveill . 2013 ; 18 :20472. PMID:23725775.
52. Wynwood SJ , Graham GC , Weier SL , Collet TA , McKay DB , Craig SB . Leptospirosis from water sources . Pathog Glob Health . 2014 ; 108 : 334 - 8 . PMID: 25348115 , doi:10.1179/2047773214Y.0000000156.
53. Pijnacker R , Goris MG , Te Wierik MJ , Broens EM , van der Giessen JW , de Rosa M , et al. Marked increase in leptospirosis infections in humans and dogs in the Netherlands , 2014 . Euro Surveill . 2016 ;21. PMID: 27168584 , http://dx.doi. org/10.2807/ 1560 - 7917 .ES. 2016 .21.17.30211.
54. Health Care Workers | Leptospirosis | CDC: Centre for Disease Control . 2015 . Available from: http://www.cdc. gov/leptospirosis/health_care_workers/ index .html. Accessed 22 Nov 2015 .
55. Katz AR , Ansdell VE , Effler PV , Middleton CR , Sasaki DM . Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii , 1974 - 1998 . Clin Infect Dis . 2001 ; 33 : 1834 - 41 . PMID: 11692294 , http://dx.doi.org/10.1086/324084.
56. Brett-Major DM , Coldren R. Antibiotics for leptospirosis . Cochrane Database Syst Rev . 2012 ; 2 , CD008264 . PMID:22336839.
57. Common animal associated infections quarterly report (England and Walesfourth quarter 2014): Public Health England ; 2015 . Available from: https:// www.gov. uk/government/publications/common-animalassociatedinfections-quarterly-reports-2015 . Accessed 22 Nov 2015 .
58. Ulu-Kilic A , Doganay M. An overview: tularemia and travel medicine . Travel Med Infect Dis . 2014 ; 12 (6 Pt A ): 609 - 16 . PMID: 25457302 , http://dx.doi.org/10. 1016/j.tmaid. 2014 .10.007.
59. Cowley SC . Editorial: proinflammatory cytokines in pneumonic tularemia: too much too late ? J Leukoc Biol . 2009 ; 86 : 469 - 70 . PMID: 19720615 , http://dx.doi.org/10.1189/jlb.0309119.
60. Tärnvik A , Chu MC . New approaches to diagnosis and therapy of tularemia . Ann N Y Acad Sci . 2007 ; 1105 : 378 - 404 . PMID: 17468229 , http://dx.doi.org/10. 1196/annals.1409.017.
61. Clinicians | Tularemia | CDC: Centre for Disease Control . 2015 . Available from: http://www.cdc.gov/tularemia/clinicians/index.html. Accessed 10 Nov 2015 .
62. Hoffmaster AR , Aucoin D , Baccam P , Baggett HC , Baird R , Bhengsri S , et al. Melioidosis diagnostic workshop , 2013 . Emerg Infect Dis . 2015 ;21. PMID: 25626057.
63. Fisher DA , Harris PN . Melioidosis: refining management of a tropical time bomb . Lancet . 2014 ; 383 : 762 - 4 . PMID: 24284288 , doi:10.1016/S0140- 6736(13)62143- 1 .
64. Limmathurotsakul D , Funnell SG , Torres AG , Morici LA , Brett PJ , Dunachie S et al. Steering group on melioidosis vaccine development. Consensus on the development of vaccines against naturally acquired melioidosis . Emerg Infect Dis . 2015 ;21. PMID: 25992835 , http://dx.doi.org/10.3201/eid2106.141480.
65. Matteelli A , Beltrame A , Saleri N , Bisoffi Z , Allegri R , Volonterio A , SIRL Study Group , et al. Respiratory syndrome and respiratory tract infections in foreign-born and national travelers hospitalized with fever in Italy . J Travel Med . 2005 ; 12 : 190 - 6 . PMID: 16086893 , http://dx.doi.org/10.2310/ 7060.2005.12404.
66. Cobelens FG , van Deutekom H , Draayer-Jansen IW , Schepp-Beelen AC , van Gerven PJ , van Kessel RP , et al. Risk of infection with Mycobacterium tuberculosis in travellers to areas of high tuberculosis endemicity . Lancet . 2000 ; 356 : 461 - 5 . PMID: 10981889 , doi:10.1016/S0140-6736(00) 02554 - X .
67. Martinez L , Blanc L , Nunn P , Raviglione M. Tuberculosis and air travel: WHO guidance in the era of drug-resistant TB . Travel Med Infect Dis . 2008 ; 6 : 177 - 81 . PMID: 18571104 , http://dx.doi.org/10.1016/j.tmaid. 2007 .10.004.
68. Pan B , Chen M , Pan W , Liao W. Histoplasmosis : a new endemic fungal infection in China? Review and analysis of cases . Mycoses . 2013 ; 56 : 212 - 21 . PMID: 23216676 , http://dx.doi.org/10.1111/myc.12029.
69. Panackal AA , Hajjeh RA , Cetron MS , Warnock DW . Fungal infections among returning travelers . Clin Infect Dis . 2002 ; 35 : 1088 - 95 . PMID: 12384843 , http:// dx.doi.org/10.1086/344061.
70. Information for Health Professionals about Histoplasmosis | Types of Diseases | Histoplasmosis | Fungal Disease | CDC: Centre for Disease Control . 2015 . Available from: http://www.cdc.gov/fungal/diseases/histoplasmosis/ health-professionals.html. Accessed 10 Nov 2015 .
71. Checkley AM , Chiodini PL , Dockrell DH , Bates I , Thwaites GE , Booth HL , British Infection Society and Hospital for Tropical Diseases , et al. Eosinophilia in returning travellers and migrants from the tropics: UK recommendations for investigation and initial management . J Infect . 2010 ; 60 : 1 - 20 . PMID: 19931558 , http://dx.doi.org/10.1016/j.jinf. 2009 .11.003.
72. Kunst H , Mack D , Kon OM , Banerjee AK , Chiodini P , Grant A. Parasitic infections of the lung: a guide for the respiratory physician . Thorax . 2011 ; 66 : 528 - 36 . PMID: 20880867 , http://dx.doi.org/10.1136/thx.2009.132217.