Microbiology JC090: Fever After Travelling Flashcards
Causes of death among tourists
- Cardiovascular (majority)
- Injury (majority)
- Infection (only small amount)
Health risks during travel
- Environmental risks
- accidents
- motion sickness
- travel by air
- altitude sickness
- heat and humidity
- UV radiation from sun
- foodborne / waterborne health risks
- exposure to cold
- animals / insects - Infections
- foodborne / waterborne diseases
- vectorborne diseases
- zoonoses
- STD
- bloodborne diseases
- airborne diseases
- diseases transmitted from soil and water
Risks to travellers
Depends on:
1. **Destination
2. **Season of travel
3. Duration of visit
4. ***Purpose / Nature of visit
5. Standards of accommodation and food hygiene
6. Behaviour of the traveller
7. Pre-existing health of traveller
- children / infants
- elderly
- pregnant women
- disabled people
- chronic medical illness
8. Pre-travel preparations
Travel health
- Medical counselling before travel
- assessment of health risks associated with travel
- **vaccinations, **antimicrobial prophylaxis, ***usual medications
- preferably 4-6 weeks before journey, particularly if vaccination may be required
- usually vaccine take 2-3 weeks before effective
- anti-malarials: 1-2 day/week - Remind patients of **Precautions / Risks during travel
- foodborne, waterborne, vectorborne transmissions
- **medical kit (esp. in patients with chronic disease)
- ***certification letter from doctor to prove medication required by patients - Follow up after travel
- indicated if:
—> suffer from chronic disease / disease during the travel
—> experience illness during the weeks following return
—> consider that they have been exposed to a serious infectious disease while travelling
—> spent >=3 months in a developing country
Fever in the traveller
2-10% international travellers will experience a febrile illness either during travel / within 2 weeks of returning
- 39% fever abroad only
- 37% fever abroad + at home
- 24% fever at home only
Problems:
- Detailed travel history required
- Knowledge in exotic diseases
***History taking in Travel medicine
- Detailed history of present illness
- Onset —> **Incubation period
- Duration
- **Symptomatology
—> Local: abdominal pain, diarrhoea, CNS S/S
—> Systemic signs: fever, relative bradycardia, rash, joint pain
- Fever pattern (periodic fever in malaria) - ***Complete travel history
- exact dates and places
- intermediate stops, mode of travel
- duration of stay (SpC Medicine)
- type of accommodation
- activities - ***Sexual exposure
- ***Needle / Blood exposure
- drug abuse, tattoo, body piercing, injection, medical procedures - ***Animal / Arthropod contacts
- any type of animals, bites, scratches, licks, spelunking
—> zoonotic infections - ***Exposure to water / soil (SpC Medicine)
- swimming, walking, rafting - ***Food / Drink exposure
- Prophylactic measures
- antibiotics, insect repellents
***Exposure history and related infections
- Sex, blood, body fluids, surgical operations, IV drug use:
- Hep B, Hep C, HIV, Syphilis - Tattoos, body piercing, other body modification procedures:
- Hep B, Hep C, HIV, Syphilis, ***NTM infections - ***Hospitalisation
- Antibiotic-resistant bacteria (colonisation / infection)
- Other nosocomial pathogens - Ingestion of raw / undercooked food
- various foodborne infections e.g. bacterial / viral GE, **salmonellosis, **traveller’s diarrhoea, **EHEC infection, **campylobacteriosis, protozoal, helminth infections, brucellosis, listeriosis, toxoplasmosis, Hep A, Hep E - Soil
- histoplasmosis, coccidioidomycoses, other endemic mycoses, cutaneous larva migrans, strongyloidiasis - Freshwater
- **schistosomiasis (Katayama fever), **leptospirosis - Arthropod bites
- arthropod-borne infections: **dengue, chikungunya, **Zika, rickettsioses, relapsing fever, ***malaria, babesiosis, leishmaniasis, trypanosomiasis, dirofilariasis - Dog, bat, other animal bites
- **rabies, bat rabies, herpes B virus infection, **bite wound infections - Animals, animal products
- Rodents: hantavirus e.g. Lassa fever, Crimean-Congo haemorrhagic fever, plague, rat-bite fever, **leptospirosis
- **avian influenza, MERS, ***Q fever, brucellosis, tularaemia, anthrax, psittacosis
Physical examination
- General
- Pallor
- Jaundice
- ***Skin lesions (rash, eschar, bite marks, needle marks)
- Bleeding tendencies (ecchymosis, gum bleeding) —> usually serious due to thrombocytopenia, clotting impairment - Systemic
- **Lymphadenopathy
- **Organomegaly (e.g. Hepatosplenomegaly)
- Localising sign (e.g. Meningism)
Investigations
- Haematological
- cell counts and differentials
- coagulation studies - Biochemistry
- LRFT
- creatinine kinase - Radiological imaging
- X-ray
- CT, MRI (as indicated) - Microbiological
- Microscopy: **blood film (parasites in malaria), **stool (parasites)
- Culture: blood, stool, urine, tissue, sputum
- Serology - Tissue biopsy
- Microbiology
- Histopathology
Presumptive (Differential) diagnoses
- What diagnoses are possible based on ***geographical areas visited?
- Eastern Africa: Malaria - What diagnoses are possible based on ***time of travel (incubation periods)?
- What diagnoses are possible based on ***activities, exposures, host factors, clinical and laboratory findings?
- Fever + Rash
- Fever + Joint symptoms
- Fever + CNS symptoms - Among possible diagnoses, what are **treatable, **transmissible?
- Isolation requirement
Common considerations of DDx
- Systemic infections
- vectorborne diseases e.g. **malaria, rickettsioses, **dengue (common in HK), chikungunya, Zika virus infection
- foodborne / waterborne diseases e.g. **enteric fever
- zoonoses e.g. **brucellosis, **Q fever
- leptospirosis
- **hep A, B, C, E - Respiratory tract infections
- **influenza, viral infections, **pneumonia, legionellosis - Enteric infections (Mostly)
- **traveller’s diarrhoea, **enteric fever including typhoid fever, dysentery (bacillary + amoebic dysentery), GE, cholera, giardiasis, amoebiasis, Norovirus / other enteric virus infections - STD, Bloodborne viruses
- HIV, HBV, HCV, other STD
Other recent considerations
- Epidemic / Pandemic prone infections
- SARS
- pandemic influenza
- **MERS-CoV (Middle East with contact history with camels)
- **avian / animal influenza virus
- viral haemorrhagic fevers
- ***Zika virus infection - Potential for local transmission
- **malaria
- **dengue
- chikungunya
- viral haemorrhagic fevers
- Zika virus infection - ***Antibiotic-resistant bacteria
- ESBL
- Carbapenemase-producing Enterobacteriaceae
- MRSA
- VRE
- MDRAB
- MDRPA
- highest risks in Indian subcontinent, SE Asia, Africa - Multi-resistant Candida auris
- Re-emerging infectious diseases e.g. measles in adults
First principle of management: Recognise infectious disease emergencies
- Haemorrhagic signs
- **meningococcaemia (petechiae rash)
- **gram -ve bacterial sepsis
- ***viral haemorrhagic fever - ***Malaria
- must exclude first
Malaria
5 Plasmodium species
1. **P. vivax (commonest)
2. **P. falciparum (commonest, causes most fulminant form of disease)
- ***Medical emergency (can die within a day)
- accounts for most mortality due to malaria
- prompt initiation of treatment +/- ICU monitoring)
3. P. malariae
4. P. ovale
5. P. knowlesi (only some countries in SE Asia)
- Blood protozoa
- transmission from person-to-person via bites of female ***Anopheles mosquitoes (瘧蚊) / occasionally blood transfusion
- **MUST be considered in all cases of **unexplained fever that start after ***7th day of stay in endemic area
- ***Medico-legal (SpC Medicine)
Classical symptoms:
1. **Periodic (Intermittent) fever with **48-72 hour cycle (not commonly seen in early stage)
2. Protean manifestations (mimic other diseases)
Life cycle of Plasmodium (from IASM L48)
- Infection: Sporozoites (from mosquito) enter hepatocytes
- Pre-erythrocytic/exoerythrocytic cycle: Merozoites replicate within hepatocytes and rupture into blood)
- Erythrocytic cycle: invasion into RBC
- Schizogony: Merozoites in RBC
- Gametogony: male/female Gametocytes (ingested by Anopheles mosquito) - Secondary schizogony: Hypnozoites in hepatocytes (P. vivax and P. ovale)
- Within mosquito
—> Zygote
—> Ookinete (penetrate stomach wall of mosquito)
—> Oocyst
—> Sporogony: formation of Sporozoitesu
Pathophysiology of Malaria (SpC Teaching Clinic + IASM L48)
- ***Hypoglycemia
- Derive energy by glycolysis of glucose to lactic acid - ***Haemolysis
- Decreased deformability
- Infection by parasites
- Clearance in splenomegaly
—> Jaundice, Iron depletion, Anaemia, Haemoglobinuria - ***Cytokine storm: TNF-A
- Thrombocytopenia
- ***Microvascular obstruction
- Adhesion of infected RBC to vessel by P. falciparum —> may obstruct brain vessels: dangerous)
- Multi-organ failure - ***Nephrotic syndrome
- Immune complex deposition in chronic infection by P. malariae) - Genetic diversity
NB:
- Host genetics: Absence of Duffy antigen protective against P. vivax
- Sickle cell: lower parasite density
Clinical features of Malaria (SpC Teaching Clinic)
- Asymptomatic for 1 week after bitten
- Incubation 2 weeks to 1 year
- ***Fever, chills, headache, abdominal pain, diarrhoea and cough
- ***Febrile paroxysms coordinated with rupture of RBC
- 24 hours for PF, PV and PO
- 3 days for PM - ***Hepatomegaly
- ***Splenomegaly
- Enlarge 3-4 days after onset
- Greater likelihood to relapse if splenomegaly fails to regress
- Hypersplenism: Pancytopenia - ***Jaundice
- ***Thrombocytopenia
When to suspect malaria?
- After ***7 days of stay in an endemic area (shortest incubation period for malaria)
- must be suspected if febrile patient who could have been exposed to malaria - Fever pattern
- usually not helpful - Malaria symptoms are **non-specific!!!
- **no pathognomonic S/S - Usually exclude malaria by investigations
- Severe malaria
- parasitaemia >5%
- impaired consciousness
- **acidosis
- hypoglycaemia
- **severe malarial anaemia
- **renal impairment
- **jaundice
- pulmonary edema
- **significant bleeding
- **shock
- hyperparasitaemia (P. falciparum >10%)
Diagnosis of malaria
- Demonstration of Plasmodium parasites
- **Blood smear (peripheral blood / marrow blood) —> most useful one
- thick and thin films
- tissue samples / post-mortem examination
- parasitaemia level
- 1 set of negative blood film does NOT exclude malaria (esp. if patient received prophylaxis / partial treatment)
- If first blood smear is negative and suspicion is still high:
—> **repeat 3 smear over 48 hours / alternative tests (Antigen / PCR) - Antigen detection
- not as sensitive as blood film - ***PCR
- most sensitive
Problematic areas for malaria
- Hyperendemicity
- ***Subsaharan Africa - Multidrug-resistant falciparum malaria
- SE Asia around ***Thailand
Treatment and Prevention of malaria
Treatment:
1. Severe / Falciparum malaria
- Artemisinin-based therapy (e.g. **IV Artesunate)
—> Artesunate 2.4 mg/kg IV BD on first day, then 2.4 mg/kg IV OD till oral therapy (total 9.6mg/kg in 3 days)
+
—> Doxycycline 100mg BD for 1 week
- **Quinine
- Other options
- Atovaquone-proguanil (Malarone)
- **Quinine + Doxycycline
- (*Mefloquine)
Prevention
1. Exposure
- long-sleeve shirts
- insect repellents (DEET, IR3535, Picaridin, BioUD, PMD)
- bednets
- avoidance of exposure
- Chemoprophylaxis
- choice of drugs depend on destination
- Doxycycline, Atovaquone-proguanil (Malarone), (***Mefloquine)
- start 1 day - 3 weeks before —> continue throughout —> 7 days - 4 weeks after travel
Case 1: Undifferentiated fever workup
- 44yo M
- HT, gout, OSA
- Diamond trader
- Africa 3 years, South Africa —> Central African Republic twice in recent years
- Visited Bangui and diamond mines
- 21/7 - 12/8
- Yellow fever, typhoid, cholera vaccine in May
- No anti-malarial prophylaxis
- 12/8: Fever, chills —> seen by GP, given Cefuroxime + Doxycycline
- 14/8: Admitted with 40.7 oC
- Must exclude malaria if travel to endemic areas
- Exclude other causes of undifferentiated fever
Case 2: Fever + Rash workup
- Countless mosquito bites —> malaria likely
- Rash
—> Not common in malaria (might be something else)
—> Rash of meningococcaemia (haemorrhagic, petechiae in nature)?
—> Serology +/- RT-PCR —> Dengue IgM positive
—> RT-PCR —> Dengue type 2
Dengue
- Asymptomatic / Subclinical infection
- Incubation period: ***4-7 days
- ***Rash: Generalised erythema rash
Vectors:
- ***Aedes aegypti (白紋伊蚊) / other Aedes species e.g. Aedes albopictus
Clinical course (**記住: Biphasic):
Phase 1:
- **sudden high fever (>=39oC), chilliness, prostration
- **frontal / retroorbital headache, backache, muscle, joint pain (“breakbone fever”)
- **facial flushing, eyelid puffiness, conjunctival congestion, **pain on moving eye balls
- transient **generalised macular rash in first 24 hour
- from day 2-4 of fever: cutaneous hyperasthesia / hyperalgesia, lymphadenopathy, anorexia, vomiting
Phase 2:
- fever subside within 3-4 days —> **generalised morbilliform rash **sparing palms / soles lasting for 1-5 days, associated with some scaling
- fever often reappears 1-2 days after lysis of temperature leading to ***biphasic temperature curve
Laboratory diagnosis:
1. Virus detection (first 5 days)
- Serum for **RT-PCR
- Serum for virus isolation (not performed)
2. **Ab detection (IgM)
3. **Ag detection (NS1 (nonstructural protein 1)) in blood
4. Common laboratory finding: **Lymphopenia, **Thrombocytopenia, **Deranged liver functions
Complications:
- Severe dengue (previously **dengue haemorrhagic fever + **dengue shock syndrome)
—> mainly in those who develop 2nd / 3rd episode of dengue infection due to different serotypes of virus
—> **epitaxis, **petechiae, oozing at IV drip sites, purpura, GI bleeding, ***internal bleeding in any organ / shock (usually in Phase 2)
Management:
- ***Supportive: symptomatic, transfusion if necessary
- Prevention: avoidance of mosquito bites, dengue vaccine available
Don’t forget other arboviruses: **chikungunya virus, **Zika virus (similar clinical features, distinguish by geographical location)
