Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2826_Библиотеки_им_академика_М_И_Перельмана.pdf
Fever in the Returned Traveller 23
Rickettsiae inhabit the alimentary tract of these arthropods and infection is spread to humans by inoculation of their faeces through broken
human skin, generally produced by scratching. A variety of Rickettsial
species with wide geographical distribution can cause travel-related
infection, but most commonly Rickettsia africae (African tick-bite fever)
or Rickettsia conorii (Mediterranean spotted or tick bite fever) is identi-
fied. Incubation is 5–7 days. R. africae is endemic in cattle ticks and
infection is seen in those returning from game parks in southern Africa.
Fever, malaise, lymphadenitis, rash and particularly eschar all suggest
infection. Diagnosis is by serology. Treatment with doxycycline should not
be delayed in patients with a suggestive clinical picture and appropriate
travel history.
FEVER IN THE RETURNED TRAVELLER
Fever is the most common symptom in people returning from tropical travel.
Malaria is the most common cause of febrile illness in recent travellers and is
potentially fatal; therefore, prompt assessment of these patients is essential.
Most patients in this group present within 1 month of travel. Table2.3 lists the
causes of fever in travellers from the tropics; however, in some patients no
specific cause is found. The most common causes are discussed in greater
detail below.
Viral haemorrhagic fever (VHF)nd is a rare cause of fever in returning
travellers caused by a heterogeneous number of zoonotic viruses. The Ebola
outbreak in West Africa has brought them to global attention. Despite being
rare, due to the transmissibility and significant mortality associated with a
Table 2.3 Common causes of fever after travel to the tropics
Malaria
Enteric fever (typhoid and paratyphoid fevers)
Arbovirus infection (dengue/chikungunya)
Rickettsia
HIV seroconversion
Amoebic liver abscess
Acute schistosomiasis – Katayama fever
Viral hepatitis
Viral respiratory tract infection – influenza, avian
influenza, MERS-CoV, SARS
Gastroenteritis
Leptospirosis
Tuberculosis
Febrile illness unrelated to foreign travel –
includes respiratory and urinary tract infection
Consider early in
the assessment
24 Infectious diseases
Table 2.4 Typical incubation periods for tropical infections
Incubation period Infection
Short (<10 days)
Medium (10–21 days) Malaria, enteric fever, brucellosis, leptospirosis, African
Long (>21 days) Viral hepatitis (A–E), tuberculosis, HIV, schistosomiasis,
number of these viruses, potential cases require immediate strict isolation
and infection control practices. VHF should be considered when assessing
patients with fever who have returned from high-risk countries, particularly
countries in sub-Saharan or West Africa (Lassa, Marburg and Ebola
viruses). Crimean-Congo haemorrhagic fever is found in southern Africa
and parts of Asia. Suspected cases should be discussed immediately with
the local Infectious Diseases team and Health Protection unit as per local
policy.Within the UK, risk assessment information can be found on https://
www.gov.uk/topic/health-protection/infectious-diseases.
Arboviral infections, gastroenteritis, melioidosis,
meningitis, respiratory infection (bacterial and viral),
Rickettsial infection
trypanosomiasis, EBV, CMV, HIV, viral haemorrhagic
fevers
amoebic liver abscess, visceral leishmaniasis, filariasis,
brucellosis, tuberculosis, malaria
Approach to diagnosis
In addition to a full medical history, a detailed travel history and physical
examination will help to formulate an appropriate differential diagnosis:
• Dates of travel and illness onset: this will allow assessment of the
incubation period; Table 2.4
• Destination: all countries visited should be noted on a timeline, including
airport stopovers. Details of travel in rural and urban areas including
types of accommodation should also be recorded.
• Exposure: all possible exposure to vectors (mosquitoes, flies, ticks,
snails), animals, fresh water, healthcare facilities (needle and blood
exposure, surgery) and any sexual exposure should be recorded.
• Activities: such as working in hospitals or refugee camps, caving, visiting
game parks.
• Pre-travel vaccination and prophylaxis used: no vaccination is 100%
effective; however, some confer extremely effective protection, such
as vaccination against yellow fever and hepatitis A and B. Malaria
prophylaxis has to be appropriate for the area visited and taken reliably
without premature cessation. Appropriate prophylaxis with full adherence
does not exclude malaria within the differential.
Fever in the Returned Traveller 25
Investigations
The initial work-up of a febrile patient who has recently travelled is listed
below. Additional studies depend on exposure and other factors:
• FBC with differential WCC, U&Es, LFTs, blood glucose
• Malaria rapid antigen test followed by thick and thin blood malaria films;
repeat after 12–24 hours if initial films negative. At least three in total
should be taken
• Blood cultures
• Urine microscopy and culture and stool culture
• Chest X-ray ± liver and spleen ultrasound scan
• HIV test
• Serology for specific antibody detection as necessary
• Pregnancy test for women with childbearing potential.
nd
Malaria
Malaria is caused by a protozoan parasite widespread in the tropics and
subtropics (see www.malariaatlas.org for interactive map showing current
distribution of malaria.) Approximately half of the world’s population is at
risk of malaria; however, sub-Saharan Africa is disproportionally affected,
with the region seeing 92% of malaria cases globally in 2017. Increasing
prevention and control strategies have seen the global mortality rates for
malaria drop by 60% since 2000. In endemic areas, mortality is principally
in infants. With those who survive to adulthood acquiring significant immunity. In hyperendemic areas, an exaggerated immune response to repeated
malarial infections leads to massive splenomegaly, anaemia and elevated
IgM levels.
Aetiology
Malaria is transmitted by the bite of infected female Anopheles mosquitoes.
Occasionally it is transmitted in contaminated blood (transfusions, contaminated equipment, intravenous drug users sharing needles). Rarely the
parasite is transmitted by importation of infected mosquitoes by air (airport
malaria).
Five malaria parasites infect humans. Plasmodium falciparum is
responsible for most malaria-related deaths, and infection can rapidly
progress from an acute fever with rigors to severe multiorgan failure,
coma and death. Once successfully treated, this form does not relapse.
Of the other malaria parasites, P. vivax is the most dominant malaria
parasite outside sub-Saharan Africa. Along with P. ovale, P. malariae
and P. knowlesi, P. vivax cause a more benign illness. However, P. ovale
and P. vivax may relapse and P. malariae may run a chronic course over
months or years.
26 Infectious diseases
In the UK, between 1300 and 1800 cases of malaria are reported each
year. Most often this occurs in people of African or South Asian origin and
50% of cases occur in patients who have visited friends and family in
endemic areas.
Specific country information for malaria can be found at http://
travelhealthpro.org.uk.
Pathogenesis
The infective form of the parasite (sporozoites) passes through the skin and,
via the bloodstream, enters the liver. Here they multiply inside hepatocytes
as merozoites. After a few days the infected hepatocytes rupture, releasing
merozoites into the blood, where they are taken up by erythrocytes and pass
through further stages of development, before ultimately terminating with the
rupture of the red cell. Rupture of red blood cells contributes to anaemia and
releases pyrogens, causing fever. Red blood cells infected with P. falciparum
adhere to the endothelium of small vessels and the consequent vascular
occlusion causes severe organ damage, chiefly in the gut, kidney, liver and
brain. P. ovale and P. vivax remain latent in the liver as hypnozoites, and this
is responsible for the relapses that may occur.
Clinical features
The incubation period varies:
• 10–14 days in P. falciparum, P. vivax and P. ovale infection
• 18 days to 6 weeks in P. malariae infection.
The onset of symptoms may be delayed (up to 3 months, 1 year in vivax
malaria) in the partially immune or after prophylaxis. There is an abrupt onset
of fever, tachycardia and rigors, followed by profuse sweating. This may be
accompanied by anaemia and hepatosplenomegaly. Atypical presentations
without fever may occur.
P. falciparum infection is a medical emergency because patients
can deteriorate rapidly. These patients should be managed in a highdependency or intensive care setting under the guidance of specialists
in infectious diseases. P. falciparum infection can also be complicated by
Gram-negative septicaemia which would require the addition of empirical
antibiotic cover.
Investigations
The conventional method for diagnosing malaria is examination of a thick
and thin blood film. Thick smears detect malaria parasites and thin smears
are used for parasite identification and for quantification of the percentage
of parasitized red cells (in P. falciparum infection). Rapid diagnostic tests
detect parasite antigens and are used in many UK laboratories in addition to
blood films and are useful as an immediate screen when the expertise for
reading blood films is not readily available. If clinical suspicion for malaria
is high but initial blood films are negative, these investigations should be
Fever in the Returned Traveller 27
Table 2.5 Major features of severe or complicated falciparum
malaria in adults
Impaired consciousness or seizures
Renal impairment
Oliguria
Haemoglobinuria
Acidosis
Hypoglycaemia
Pulmonary oedema or acute respiratory distress syndrome (ARDS)
Haemoglobin ≤80 g/L
Disseminated intervascular coagulation or spontaneous bleeding
Shock (blood pressure <90/60)
Parasitaemia >10%
repeated in 12 and 24 hours. Pregnancy testing should be undertaken in all
women of childbearing potential, as falciparum malaria in pregnancy is more
likely to be complicated, diagnosis can be difficult and treatment strategies
are different.
Assessment should include careful evaluation for the features of severe
malaria shown in Table 2.5 and would routinely include FBC, U&Es, LFTs and
blood glucose. Blood gases, serum lactate, clotting studies and blood cultures
should be taken in patients who are unwell. Thrombocytopenia is common
and in isolation does not reflect severe or complicated disease.
Management
Treatment of uncomplicated falciparum malaria
Patients should be admitted to hospital at least for the first 24 hours as
there can be rapid deterioration. Careful evaluation for the features of severe
disease must be made. Although a parasitaemia of >10% is considered to
represent severe disease, patients with a parasitaemia of >2% possess
an increased risk of developing severe disease, and these patients should
receive parenteral therapy – see below.
Chloroquine is still widely used to treat non-falciparum malaria.
However, there is increasing resistance to chloroquine in some strains of P.
vivax, and co-infection with P. falciparum is common in some parts of the
world. It is therefore sensible to use oral artemisinin combination therapy
(ACT), where available, for all cases of malaria. Following successful
treatment of P. vivax or P. ovale malaria, it is necessary to give a 2- to
3-week course of primaquine (0.25–0.5 mg daily) to eradicate the hepatic
hypnozoites and prevent relapse. This drug can precipitate haemolysis in
patients with glucose-6-phosphate dehydrogenase deficiency. Specific
28 Infectious diseases
treatment should be led by an infectious diseases specialist according to
the UK malaria treatment guidelines.
Severe falciparum malaria (indicated by the presence of any of the
features listed in Table 2.5) is a medical emergency, and patients should be
cared for in an appropriate high-dependency or intensive care environment.
Expert advice should be sought. Parenteral therapy should be given to
patients who have a >2% parasitaemia, are pregnant (following specialist
advice) or in which the oral route is unavailable. Intravenous artesunate
is the treatment of choice but if unavailable then intravenous quinine is a
suitable alternative.
Careful monitoring of blood sugar, renal function, fluid balance,
clotting studies and for respiratory distress is required so that supportive
measures can be instituted early. Development of shock may be
secondary to Gram-negative septicaemia and broad-spectrum antibiotics
should be considered.
Prevention and control
Effective prevention of malaria includes the following elements (ABC):
• Awareness of risk
• Bite avoidance – using mosquito repellents, covering up with permethrin-
impregnated clothing, sleeping under impregnated bednets
• Chemoprophylaxis.
As a result of changing patterns of resistance, advice about
chemoprophylaxis should be sought from an appropriate travel advice centre
before leaving for a malaria-endemic area. Prophylaxis does not afford full
protection.
Enteric fever
Enteric fever is an acute systemic illness characterized by fever, headache
and abdominal discomfort. Typhoid, the typical form of enteric fever, is
caused by Salmonella typhi. A similar but generally less severe illness known
as paratyphoid is due to infection with S. paratyphi A, B or C. Humans are the
only reservoir of infection and spread is faecal–oral. The incubation period is
10–14 days. Typhoid fever is most prevalent in overcrowded areas with poor
sanitation, with around 150 000 deaths per year mainly in India and Africa.
nd
Clinical features
There is an insidious onset of intermittent fever, headache and dry cough
and relative bradycardia. During the second week of illness, an erythematous maculopapular rash (‘rose spots’) develops on the upper abdomen and
thorax, with cervical lymphadenopathy, splenomegaly and hepatomegaly.
Diarrhoea may develop. Complications, usually occurring in the third week,
include pneumonia, meningitis, acute cholecystitis, osteomyelitis, intestinal
perforation and haemorrhage.
Fever in the Returned Traveller 29
Investigations
Diagnosis requires the culture of S. typhi or S. paratyphi. Organisms can be
cultured from the blood, faeces and urine, depending on the stage in the illness that individuals present. Where the diagnosis is in doubt, bone marrow
cultures may be positive even after starting antibiotics. A blood count shows
non-specific leukopenia. The Widal test has limited clinical use and can be
misinterpreted, so should not be used.
Management and prevention
Increasing antibiotic resistance is seen in isolates of S. typhi, especially in the
Indian subcontinent. Chloramphenicol, co-trimoxazole and amoxicillin may
still be effective in some cases, but resistance to all of these drugs (known
as multidrug-resistant (MDR) typhoid) is spreading rapidly. In most areas
the treatment of choice is a quinolone (e.g. ciprofloxacin), but resistance
is starting to appear to this as well, and treatment should ideally be based
on known local resistance patterns. To reduce relapse rates and persistent
carriage, treatment should be continued for 14 days. Some patients become
chronic carriers, with the focus of infection in the gall bladder, and prolonged
antibiotic treatment is indicated. Vaccination with injectable inactivated or
oral live attenuated vaccines gives partial protection.
Enterocolitis
Other Salmonella species (S. choleraesuis and S. enteritidis) cause a selflimiting infection presenting with diarrhoea and vomiting (Table 2.6) and are
a cause of travellers’ diarrhoea – see below and Table 2.7.
Dengue fever
Dengue viruses (a member of the Flaviviridae family) are transmitted to humans
through bites of infected female Aedes aegypti mosquitoes. These are found
mainly in Asia, Africa, and Central and South America, where they are a common
cause of fever that may be fatal. After an incubation period of 4–7 days, there is
an abrupt onset of fever, headache, retro-orbital pain and severe myalgia, often
with a skin rash. Dengue haemorrhagic fever (DHF) is a severe form with thrombocytopenia, increased vascular permeability (indicated by a rising haematocrit),
ongoing fever and spontaneous bleeding. Additional signs of circulatory failure
indicate dengue shock syndrome. Initial diagnosis is mainly clinical and it should
be considered in all travellers returning from endemic regions. Laboratory diagnosis usually relies on serology, which should be taken 5 days after the onset of
illness. PCR detection of the virus or its components (non-structural protein, NS1)
in the blood is also available for earlier confirmation. Treatment is supportive as
no specific therapy is available. Early recognition of deterioration to DHF should
identify patients who require more aggressive supportive approaches.
30 Infectious diseases
Table 2.6 Pathogenic mechanisms of bacterial gastroenteritis
where established
Pathogenesis Mode of action Clinical
Mucosal
adherence
Mucosal
invasion
Toxin
production
Enterotoxin
Cytotoxin
Effacement
of intestinal
mucosa
Penetration +
destruction of
mucosa
Fluid secretion
without mucosal
damage
Damage to
mucosa
presentation
Moderate
watery diarrhoea
Bloody diarrhoea
Profuse watery
diarrhoea
Bloody diarrhoea
Examples
Enteropathogenic
E.coli (EPEC)
Enteroaggregative
E.coli (EAggEC)
Diffusely adhering
E.coli (DAEC)
Shigella spp.
Campylobacter spp.
Enteroinvasive
E. coli (EIEC)
Vibrio cholerae
Salmonella spp.
Campylobacter spp.
Enterotoxigenic
E. coli (ETEC)
Bacillus cereus
Staph. aureus
producing
enterotoxin B
Clostridium
perfringens type A
Salmonella spp.
Campylobacter spp.
Enterohaemorrhagic
E. coli (EHEC)
Schistosomiasis
Schistosomiasis is a parasitic infection caused by five schistosome
species. These parasites live in freshwater snails and the infectious
forms of the parasite – cercariae – penetrate skin when it comes in
contact with contaminated water. Prevalence is highest in sub-Saharan
Africa, but schistosomiasis is also found in other areas of Africa, South
Fever in the Returned Traveller 31
Table 2.7 Causes of travellers’ diarrhoea
Bacteria: 70%–90% of cases E. coli (enterotoxigenic)
E. coli (enteroaggregative)
Shigella spp.
Salmonella spp.
Campylobacter jejuni
Aeromonas and Plesiomonas spp.
Vibrio cholerae
Viruses: 10% Rotavirus
Noroviruses*
Protozoa: <5% Giardia intestinalis
Entamoeba histolytica
Cryptosporidium parvum
Cyclospora cayetanensis
Note: Co-infection with multiple pathogens occurs in approximately 10% of cases.
*Often associated with outbreaks of diarrhoea on cruise ships and in holiday resorts.
America, South East Asia, China and the Middle East. Acute symptoms
are more common in non-immune individuals such as travellers. Parasite
penetration through the skin may cause a localized pruritic papular rash
(‘swimmer’s itch’). A symptom free period then ensues over the next 3–4
weeks as the parasite migrates through the lungs and hepatic circulation
before systemic allergic features such as fever, rash, myalgia and pneumonitis (Katayama fever) develop. These allergic phenomena are common
in non-immune travellers but are rarely seen in local populations, who are
usually exposed to infection from early childhood onwards. Chronic complications of Schistosoma infection usually occur only in endemic areas
where there is a high parasite load; there may be intestinal, hepatosplenic,
pulmonary, genitourinary or neurological manifestations, but it is often
asymptomatic (Table 2.8).
Diagnostic approaches differ between returning travellers and those in
endemic settings. In returning travellers, serology taken at least 6 weeks
after exposure is the most useful diagnostic tool, as parasite load is usually
low and ova may not be detected in stool or urine by microscopy.
Swimmer’s itch is treated symptomatically. Acute schistosomiasis
syndrome is initially treated with corticosteroids to reduce the hypersensitivity
reaction to schistosome antigens and then praziquantel is administered after
acute symptoms have resolved and at least 4–6 weeks following exposure.
Chronic infection is treated with praziquantel.
Table 2.8 Summary of intestinal diseases caused by helminths (parasitic worms)
Helminth Clinical manifestations Diagnosis Treatment of choice
Nematodes (roundworms)
Small intestine
Strongyloides
stercoralis
Hookworm:
Ancylostoma
duodenale, Necator
americanus
Roundworm:
Ascaris lumbricoides
Trichinella spiralis Abdominal pain and diarrhoea. Larvae penetrate the
Toxocara canis Penetration of small intestine to lungs
Local dermatitis at site of skin penetration,
diarrhoea, malabsorption, disseminated disease.
Symptoms may continue for years as a result of
autoinfection
Local dermatitis at the site of skin penetration,
nausea, epigastric pain, iron deficiency anaemia
Often asymptomatic. Vomiting, abdominal
discomfort, anorexia, intestinal obstruction.
Pulmonary eosinophilia after migration to the lungs
bowel wall and invade striated muscle causing pain.
Periorbital oedema may be present
(bronchospasm), liver (hepatomegaly), heart,
brainand eye
Larvae in fresh stool,
serology
Detection of eggs
infaeces
Detection of eggs
infaeces
Serology, muscle
biopsy
Serology
Ivermectin/ Tiabendazole
Albendazole/mebendazole
Albendazole/mebendazole
Albendazole/mebendazole
Albendazole
32 Infectious diseases