Infections in the returned traveller

1
 Infections in the returned traveller

• Following the completion of this lecture the

student should be able to:
– describe the infections seen in patient who have recently
travelled abroad
– describe the presentation of the unwell returned traveller
– formulate an approach to the diagnosis and management
of diarrhoea in the returned traveller
– formulate an approach to the diagnosis and management
of fever in the returned traveller
– understand the clinical importance of traveller’s diarrhoea
and malaria
2
Imported and travel-related infections

• Increase in international travel.

• Corresponding increase in travel-related infections,
particularly with travels to tropical countries.

3
 Travel-related infections
(according to aetiological / epidemiological groups)

Common world-wide
• Influenza
• Community-acquired pneumonia
• Meningococcal diseases
• Sexually transmitted infections

Climate
• Dermatophyte infections
• Folliculitis

5
 Controllable by public health measures
• Hepatitis A and E
• Viral gastroenteritis
• Traveller’s diarrhoea
• Bacterial food poisoning
• Bacillary dysentery
• Enteric fevers
• Cholera
• Giardiasis, Amoebiasis, Cryptosporidiosis
• Poliomyelitis
• Diphtheria
• HIV infection
6
 Contact with mud and water

• Leptospirosis
• Hookworms
• Strongyloidiasis
• Guinea worms
• Schistosomiasis
• Liver flukes

7
 Arthropod vectors
• Arboviral infections (mosquitoes, ticks, sandflies)
• Rickettsial diseases (mites, louse, ticks)
• Plague (rat flea)
• Malaria, Leishmaniasis (sandflies), Trypanosomiasis (tsetse fly, Triatoma )
• Filariasis (mosquitoes), Onchocerciasis (blackfly)

Zoonoses
• Brucellosis, rabies, anthrax

8
9
 Viral Haemorrhagic Fevers

• Yellow fever
• Dengue haemorrhagic fever
• Crimean-Congo haemorrhagic fever
• Hantavirus infections
• Lassa fever
• Marburg fever
• Ebola fever

10
11
12
Transmission of Ebola virus disease (EVD)

• It is thought that fruit bats are the natural hosts.

• Introduced into human population through close
contact with blood, secretions, organs or other bodily
fluids of infected animals such as fruit bats,
chimpanzees, gorillas, monkeys, forest antelope or
porcupines found ill or dead or in the rainforest.

13
Transmission of Ebola virus disease (EVD)

• Ebola then spreads through human-to-human

transmission via direct contact (through broken skin
or mucous membranes) with:
– Blood or body fluids of a person who is sick with
or has died from Ebola
– Objects that have been contaminated with body
fluids (like blood, faeces, vomit) from a person sick
with Ebola or body of a person who died from Ebola

14
15
• 15% to greater than 50% of travellers develop some
illness during or after travel.
• Most common are gastro-intestinal infections
– respiratory, cutaneous and sexually transmitted infections
also common
• Less common but importance disproportionate to
their incidence because
i. of importance of early intervention
e.g. amoebic liver abscess, melioidosis
ii. of transmissibility
e.g. viral haemorrhagic fever

16
Estimates of illness incidence of Europeans /
North American travellers to tropics (per 100,000)

Any health problems 45,000

Travellers diarrhoea 35,000
Malaria (no prophylaxis) 2000
Acute febrile RTI 1400
Giardiasis 700
Hepatitis (all types) 450
Amoebiasis 400

17
Estimates of illness incidence of Europeans /
North American travellers to tropics (per 100,000)

Gonorrhoea 300
Malaria <100
Syphilis 40
Shigellosis 20
Typhoid 3.5
Cholera 0.15

18
 Importance of travel-related
infections

• Unfamiliar to local medical services.

• Diagnostic difficulties.
• Unsuspected complications.
• Public health problem.

19
 Presentation of infections in the
unwell returned traveller

• Diarrhoea.
• Fever.
• Respiratory symptoms.
• Skin and soft tissue infections.
• Jaundice.
• Eosinophilia.

20
 Dengue Seabather’s
eruption

Bed bug

Swimmer’s itch

Common dermatologic lesions

in
travellers returning
Cutaneous
leishmaniasis
from
developing countries.

Ecthyma

Cutaneous larva
migrans

Eschar Phytophotodermatitis
21
 Diarrhoea

• Most common illness among travellers.

• 20-50% of travellers in first 2 weeks abroad.
• 12% first developed symptoms after returning home.
• 3% have persistent diarrhoea (lasts for > 14 days).

22
 Traveller’s diarrhoea

• Aztec two-step
• backdoor sprint
• Basra belly
• Coeliac flux
• Canary disease
• la turista
• Delhi belly
• GIs
• Greek gallop
• Gyppy tummy
• Poona poohs
• summer complaint
• Rome runs
• tourist trots
• San Franciscitis
• Turkey trots

23
 Traveller’s diarrhoea

“Occurrence of 3 or more loose or watery stools in any

24 hour period, with abdominal pain/cramp, in a
traveller from highly industrialized region to a
developing tropical region.”

• Travellers at high / intermediate / low risk

– overall risk from low-risk to high-risk area ~40%
– overall risk from low-risk to intermediate-risk area ~10%

24
Risk areas for traveller’s diarrhoea

25
 Traveller’s diarrhoea - causes
BACTERIA
VIRUS
– ETEC
Rota
– EAEC
Noro
– Campylobacter jejuni
– Shigella
– Salmonella
PROTOZOA
– Aeromonas
Giardia lamblia
– Plesiomonas shigelloides
Cryptosporidium
– Noncholera Vibrio spp.
– EIEC

26
27
Regional distribution of the most common pathogens
that cause traveller’s diarrhoea

28
 Traveller’s diarrhoea - clinical

• Symptoms start soon after arrival (2 to 15 days).

• Majority self-limiting (3 to 5 days).
• 10-15% have symptoms lasting more than 1 week.
• < 1% requires hospital admission.

29
 Traveller’s diarrhoea - severity

• Mild
– 1-2 stools olerable, is not distressing and
does not interfere with planned activities.
• Moderate previously

– 3-5 stools is distressing or interferes with planned

activities.
• Severe
– >6 stools is incapacitating or completely prevents
planned activities l dysentery is considered
severe 30
 Traveller’s diarrhoea - severity
• Mild
– diarrhoea that is tolerable, is not distressing
and does not interfere with planned activities.
• Moderate
– diarrhoea that is distressing or interferes with
planned activities.
• Severe
– diarrhoea that is incapacitating or completely
prevents planned activities
– all dysentery is considered severe
31
Traveller’s diarrhoea - chemoprophylaxis

• Significant morbidity
– considerable inconvenience, embarrassment,
disruption of travel and business arrangements
• Bacterial causes accounts for ~85%
– if sensitive decreases attack rate from 40% to ~4%
• Fluoroquinolone or rifaximin effective
– resistance to tetracycline and co-trimoxazole high

32
Timeline of prophylactic antibiotic use
against TD in chronological order

33
Traveller’s diarrhoea - chemoprophylaxis

Disadvantages
– usually mild and easily treated
– occurs in less than 50% of susceptible
– side-effects of antibiotics
– development of resistance
– false sense of security resulting in decreased compliance
with food and water precautions

34
 Chemoprophylaxis - indications

1. Unusually susceptible patients.

2. Infection unusually deleterious.

– use of proton pump inhibitors

– insulin dependent diabetes mellitus
– active inflammatory bowel disease
– steroids
– heart disease

35
 Traveller’s diarrhoea - treatment

• Oral rehydration.
• Anti-motility agents (loperamide) if mild.
• Antibiotics + anti-motility agents if moderate or severe
– Azithromycin - single dose preferred
– Fluoroquinolone - single dose alternative
– Extend daily dose up to 3 days if illness worsens
after 24 hours or fails to improve after 72 hours

36
Traveller’s diarrhoea management

37
 Traveller’s diarrhoea - prevention

• Develop diarrhoea from ingestion of contaminated

food or water.
• Little control over how food/water contaminated but
can control items to be ingested.

38
High-risk foods or beverages to avoid

1. Cooked items served at room temperature.

2. Sauces, dressings, other items in a common open
setting eg. a buffet.
3. Unpeeled and/or uncooked fruits and vegetables.
4. Tap water or ice.
5. Locally prepared milk.

39
 Low-risk foods or beverages

1. Cooked food served ‘steaming hot’ (59°C).

2. Fruits and vegetables properly washed and prepared
by traveller.
3. Dry food eg bread and crackers.
4. Items with high sugar content eg. syrups.
5. Bottled carbonated beverages
– beware ‘bottled’ water filled from tap

40
 Persistent diarrhoea

• Protozoal infection more likely

– Giardia lamblia, Cryptosporidium parvum, Cyclospora
cayetanensis
• Bacterial causes includes Shigella, Campylobacter.
• Helminths including Strongyloides stercoralis.
• Non-infectious causes includes lactose intolerance,
irritable bowel syndrome, inflammatory bowel disease.

41
42
 Persistent diarrhoea in returned
traveller - approach
• Travel history.
• Onset, duration and character of diarrhoea
– inflammatory diarrhoea (fever, blood or mucoid stools)
suggest invasive pathogens
• Associated symptoms.
• Investigations
– Multiplex PCR
– 3 stool samples for ova and parasites
– stool culture
43
 Persistent diarrhoea in returned
traveller - approach

• If positive results commence appropriate treatment.

• If negative results, consider empirical therapy.
• If no response to empirical therapy and symptoms
persist, refer for gastrointestinal assessment to
exclude non-infective causes.

44
 Fever in the returned traveller

• May represent a tropical infection or illnesses common

to non-travellers eg. upper RTI, pneumonia, urinary
tract infection.
• Should always raise suspicion for a severe or
potentially life-threatening tropical infection
– failure to diagnose and specifically treat may
have disastrous consequences

45
 Fever in the returned traveller

• Most important cause is falciparum malaria.

• Fever in a returned traveller should be regarded
as due to malaria until proved otherwise
– particularly applies to traveller in a malarious
area in preceding 3 months
• Other important causes are typhoid fever, dengue
fever, viral hepatitis and rickettsial infections.

46
Frequency of fever and diagnosis in four published series of returned travellers

47
Fever in the returned traveller - approach

• A stepwise and rational approach.

• First determine if the patient has a tropical disease
or an illness found in non-travellers.
• If a tropical infection is suspected, consider which
illnesses are potentially fatal, which are treatable
and which pose a public health risk.

48
 Approach to diagnosis

A working differential diagnosis formulated from:

• A complete history
• Physical examination
• Knowledge of the most common infections affecting
travellers and incubation periods of these diseases
• Appropriate laboratory investigations

49
 Approach to diagnosis - history
• Medical history
– overview of symptoms and their course
– symptoms while travelling that “resolved”
• Travel history
– arrival and departure dates
– all countries or regions visited
– purpose
– mode of travel
• Activities.
• Types of accommodation and living conditions.
50
 Approach to diagnosis - history

• Pre-travel vaccinations and chemoprophylaxis.

• Specific exposure history
– food and water
– insect bites or animal bites/exposure
– human (sexual contacts, medical procedures)
• dates of sexual activity, partner(s), precautions taken
• Fellow travellers with similar complaints

51
 Specific exposures and tropical infections
Exposure Infection or disease

Raw, undercooked Enteric infections, hepatitis, trichinosis

or exotic foods

Drinking untreated Salmonellosis, shigellosis, hepatitis, brucellosis

water; milk, cheese

Fresh water,
Schistosomiasis, leptospirosis
swimming

Sexual contact Syphilis, gonorrhoea, hepatitis, HIV

Malaria, dengue fever (mosquitoes); typhus, Crimean-Congo haemorrhagic fever,

Insect bites borreliosis, tularaemia (ticks); Chagas' disease (reduviid bugs); African
trypanosomiasis (tse tse flies)

Animal Rabies, Q fever, tularaemia, borreliosis, viral haemorrhagic fevers, plague 52

exposure/bites
 Approach to diagnosis - history

• Incubation period for a patient’s illness may be

estimated based on sequence of symptoms and
travel history
– eliminate potential infections and narrow
differential diagnosis
– e.g. dengue fever unlikely if returned more
than 10 days previously

53
 Physical examination

• Perform a thorough physical examination

– emphasis on skin, gastrointestinal, respiratory
and lymphoreticular system
• Look for skin lesions (maculo-papular rash, petechial
rash, ulcers), jaundice, anaemia, lymphadenopathy,
hepatomegaly, splenomegaly.

54
 Laboratory investigation

• Initial investigations include:

– Complete blood count with differential
– Thick and thin blood films
– Serum electrolytes and liver function tests
– Blood cultures
– Urinalysis
– Serological tests for arboviral infections

55
 Management

• Blood films for malaria parasites

– treat if malaria parasites identified
– if malaria suspected but patient ill and no
parasites identified, treat as for complicated
falciparum malaria

56
 Management

• Clinical diagnosis made but unconfirmed by tests

– perform appropriate investigations first and commence empiric
treatment
• increasingly prevalent multiple drug resistance
• modify empirical therapy in light of results

• No clinical diagnosis and patient not seriously ill

– avoid empiric treatment and perform appropriate investigations

57
Evaluation and initial management of fever in a returned traveller*

*Evaluation should also include the differential diagnoses that would be considered in a non-traveller with fever.
† Travel to high-risk area, rural or prolonged travel, non-compliance with prophylaxis. 58
 Malaria
In 2017
• ~3.4 billion people in 92 countries at risk of infection.
• 219 million cases worldwide (217 million in 2016).
– 200 million cases (92%) in Africa; 5% in South-East Asia
and 2% in Eastern Mediterranean.
– incidence rate declined globally between 2010 and 2017,
from 72 to 59 cases per 1000 population.
• 435000 malaria deaths
– 93% of all deaths in Africa.
– 61% of all deaths in children <5 years.
59
60
 Malaria

• Genus Plasmodium.
• 4 species considered true parasites of humans
– P. falciparum (malignant tertian)
– P. vivax (benign tertian)
– P. ovale (ovale tertian)
– P. malariae (quartan) P. knowlesi* – zoonotic malaria

• Anopheles mosquito
• 380 species
• 60 transmit malaria
61
62
 Malaria

• P. falciparum and P. vivax account for 95% of all cases.

• P. falciparum predominantly in tropics.
• P. vivax has widest distribution
– tropics, subtropics and some temperate regions
• P. malariae limited to subtropics.
• P. ovale confined to West Africa.

63
 Malaria – life cycle

• Sexual reproduction (sporogony) in the anopheline

mosquito.
• Asexual reproduction (schizogony) in liver cells and
red blood cells in humans.

64
 Life cycle - in the mosquito

• Male and female gametocytes from infected human

ingested when mosquito feeds.
• Gametocytes form oocyst containing sporozoites.
• Oocyst penetrates gut wall and rupture with release
of sporozoites.
• Some sporozoites enter salivary gland.
• Sporozoites infect human when mosquito next feeds.

65
 Life cycle - in humans

• Sporozoites enter blood and infect liver cells.

• Asexual reproduction forms schizonts in which
thousands of merozoites develop.
(preerythrocytic schizogony)
• Merozoites rupture from liver schizonts and enter red
blood cell.
• Ring-form trophozoites and schizont with merozoites
develop.

66
 Life cycle - in humans

• Merozoites rupture from red blood cells to invade other

red blood cells.
• Some merozoites form gametocytes that infect mosquito
at next feed and continue life cycle.
• In P. ovale and P. vivax infection, some sporozoites
remain dormant as hypnozoites in liver cells.

67
68
 Malaria - Clinical features

P. vivax infection (incubation period: 13 to 17days)

• Cold stage
– abrupt onset with chills or frank rigors
• Fever stage
– high fever (41°C), headaches, malaise, vomiting, thirst
• Sweating stage
– marked sweating, temperature normalise, exhaustion

*paroxyms every 48 hours (tertian)

69
 P. falciparum malaria

• Incubation period: 12 days (9 to 14).

• Onset often insidious.
• “flu-like” illness /non-specific symptoms
– headache, malaise, aches and pain
• Shaking chills or high fever often absent.
• Fever often low grade, continuous and irregular.

70
 P. falciparum malaria

• Cough
• Vomiting
• Diarrhoea
• Jaundice

Differential diagnosis:
– influenza, meningitis, bronchitis, hepatitis, gastroenteritis

71
 P. falciparum malaria - Pathology

• Knobs appear on parasitised red blood cells.

• Adhere to endothelial cells in capillaries and
post-capillary venules in brain, kidney and other organs.
• Plugging /obstruction of vessels.
• Tissue hypoxia and hypoglycaemia.
• Organ dysfunction.

72
73
 Why does P. falciparum
cause severe disease?

• High parasitaemia.
• Maturation of parasites almost exclusively in
vascular beds of internal organs.

74
P. falciparum malaria - Complications

• Cerebral malaria
– accounts for 80% of deaths
– majority < 5years old
– increasing headaches, restlessness, behavioural
change, confusion
– coma

75
P. falciparum malaria - Complications

• Severe anaemia.
• Acute renal failure.
• Algid malaria
– acute shock syndrome with circulatory collapse
– severe hypotension, rapid thready pulse and cold clammy skin
• Blackwater fever
– intravascular haemolysis
– haemoglobinuria with acute renal failure

76
P. falciparum malaria - Complications

• Hypoglycaemia.
• Disseminated intravascular coagulopathy.
• Acute respiratory distress syndrome.
• Pulmonary oedema.

77
 Malaria - Diagnosis

• Confirmation depend on finding parasites in stained

blood films.
• Thick blood films : establishes presence of parasites
• Thin blood films : species differentiation
• Single negative films do not rule out malaria
– repeat 12 hourly for 48 hours if malaria suspected
• If species uncertain, treat as P. falciparum.

78
Differential diagnosis of Plasmodium infection
on peripheral blood smears

79
Plasmodium falciparum

80
Plasmodium falciparum

81
Plasmodium vivax

Schuffners dots

82
 Malaria - Treatment

• Refer to lecture on Anti-malarial agents for details.

83
 Malaria - Prevention

Four principles
1. Be aware of risk.
2. Avoid being bitten by mosquitoes
– screened rooms, mosquito nets impregnated with insecticides,
long sleeved clothing and trousers, repellents
3. Take appropriate chemoprophylaxis.
4. Seek early diagnosis and treatment
– any febrile or flu-like illness within a year of returning

84
 Chemoprophylaxis

Start 1 to 2 days before and continue for 1 week after

leaving endemic area (malarone) or start 1 to 2 weeks
before and continue for 4 weeks after leaving endemic
area (mefloquine).
Chloroquine-resistant P. falciparum
– mefloquine
– doxycycline
– malarone

85