EM guidemap - Fever in the returned traveler

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Introduction

General principles and problem-solving ideas

• common causes of fever after tropical travel
• selected tropical diseases causing fever in the returned traveler

Clinical history

• infections by interval between exposure and onset of fever
• incubation period for selected tropical diseases
• checklist of important travel historical facts
• infections associated with specific exposures
• common symptom/disease associations

Examination

• physical signs/disease associations

Diagnostic testing

• hematological abnormalities

Appendix

Common tropical diseases with wide distribution

• malaria
• dengue fever
• typhoid fever
• leptospirosis

Less common tropical diseases with wide distribution

• brucellosis

Less common tropical diseases with limited distribution

• scrub typhus
• plague
• visceral leishmaniasis
• relapsing fever

Hemorrhagic viruses and their known distribution
 

Introduction

- this guidemap offers an emergency physician basic guidance on how to problem-solve the problem of fever in the returned traveler, and it is mainly written for emergency physicians in the USA, who have little experience with tropical diseases that could cause a fever in the returned traveler eg. malaria, dengue fever, or typhoid fever

- the guidemap offers a basic outline on how to take a targeted history and perform a targeted examination => mainly by using clinical clue tables to narrow the likely differential diagnoses

- this guidemap does not provide extensive textbook details on all the different tropical diseases, and it only provides brief capsules of information on some of the more important tropical diseases that cause a fever in the returned traveler => see the appendix section for further details
 

General principles and problem-solving ideas

- fever in the returned traveler may not be due to a tropical disease acquired as a result of exposure in a tropical country, and the fever is often due to common infectious diseases that could be acquired in any worldwide urban area eg. upper respiratory infections, urinary tract infections or pneumonia (accounts for > 50% of cases)

- the most common tropical disease causing a fever in a returned traveler is malaria (30 - 40 % of cases), which should be the primary diagnosis-of-exclusion even if the traveler is afebrile at the time of clinical examination

- the exact frequency of different infections varies widely with the place of study (travel clinic or general hospital practice), and the host country of the returned travellers
 

Common causes of fever after tropical travel (rough order of likelihood)

Malaria  Respiratory infections (including pneumonia)  Diarrheal illness - salmonellosis, shigellosis  Hepatitis  Urinary tract infection  Dengue fever  Typhoid (enteric) fever  Rickettsial infection  Infectious mononucleosis  Pharyngitis

- if malaria is a diagnostic possibility, then diagnostic studies (thick and thin blood smears) should be performed repeatedly (q 8 - 12 hourly for the first 24 - 48 hours) because the degree of parasitemia may be low in the early stages of the disease => initial false-negative diagnostic test

- dengue fever is probably the second most frequent tropical disease causing fever in a returned traveler - especially in travelers to central and south America, or south-east Asia

- other important tropical infections to always consider, in addition to malaria and dengue fever, are typhoid fever (enteric fever), viral hepatitis and leptospirosis

Fever in a returned traveler from a malarious area should be regarded as malaria until proved otherwise; typhoid fever should also seriously be considered; malaria and typhoid fever may co-exist in the same patient

- the risk of acquiring a tropical infection depends on the exposure risk => short-term travel limited to urban areas puts the traveler at little risk of acquiring a tropical disease, while prolonged travel in rural areas (especially if the traveler lived in primitive conditions off the beaten track) increases the risk of acquiring a tropical infection

- the type of tropical disease exposure depends on the area of the world visited eg. prolonged primitive travel in rural Indo-china puts the traveler at increased risk of acquiring malaria, dengue fever, leptospirosis, scrub typhus and Japanese encephalitis; while a similar style of travel in central Africa increases the risk of acquiring malaria, African trypanosomiasis, schistosomiasis or visceral leischmaniasis

- an emergency physician should keep in mind the possibility of rare "cannot miss" diseases (eg. rabies, plague, anthrax, Lassa fever) that may represent a public health concern
 

Selected tropical diseases causing fever in the returned traveler

Common with wide distribution arbovirus and dengue fever viral hepatitis enteric fever malaria tuberculosis (not a short-term risk)  Less common with wide distribution poliomyelitis acute HIV infection brucellosis amebic liver abscess toxoplasmosis filariasis  Less common with limited distribution yellow fever scrub typhus leptospirosis plague leishmaniasis schistosomiasis viral hemorrhagic fever louseborne/tickborne typhus relapsing fever  melioidosis trypanosomiasis

Problem-solving ideas

- first approach the problem of fever in the returned traveler with the idea that one always needs to exclude malaria, and obtain a detailed trip itinerary history to determine whether the patient visited any malarious areas +/- whether he was exposed to mosquito bites +/- whether he took antimalarial prophylaxis medication

- concurrently, check for the possibility of exposure to other common tropical diseases like typhoid fever and dengue fever, and the likelihood of the patient having a cosmopolitan, non-tropical infectious disease (eg. influenza, pneumonia, UTI, pharyngitis) based on the individual patient's specific symptomatology

- more thorough problem-solving history-taking will need to be focused on establishing whether there are certain combinations of exposure-risk (eg. water, soil, contaminated food, insect or animal bites, caving, sexual encounters) + compatible incubation period of the disease + specific combinations of symptomatology/physical signs to suggest a particular disease

- examples of specific clues that may help focus attention on a particular tropical disease include:-

• freshwater exposure in Africa => schistosomiasis
• freshwater exposure when rafting or swimming in Central and South America => leptospirosis
• speliologists on a caving trip => histoplasmosis or rabies
• zoologists on a field trip => anthrax, brucellosis, plague, tularemia, Q fever, leptospirosis, viral hemorrhagic fever
• health-care worker in a refugee camp => louse-borne typhus, typhoid fever, hepatitis, meningococcus, HIV, relapsing fever, tuberculosis
• military personnel stationed in the Pacific + history of skin eschar + febrile illness with generalized lymphadenopathy/splenomegaly => scrub typhus
• food-borne diseases => typhoid fever and other enteric fevers, traveler's diarrhea, shigellosis, salmonellosis, amebiasis, hepatitis A, trichinosis, fascioliasis, and brucellosis
• eating unpasteurized milk products => brucellosis
• promiscuous sexual activities with prostitutes => common sexually transmitted diseases, hepatitis B and C, or acute HIV
• close contact with rodents => plague, leptospirosis, Hantavirus, relapsing fever
• hiking in tick-infested bush in Africa => tick typhus
• camping + tick bite => Rocky Mountain spotted fever, ehrlichiosis, babesiosis, relapsing fever

Clinical history

- the major focus of the clinical history is to determine the likelihood of the patient  acquiring a tropical infection based on the time and place of exposure => the clinician should determine the time range between possible exposure and the onset of symptoms using the shortest and longest possible incubation periods, while assuming variable potential exposure at all points during travel

- the number of differential diagnoses can be narrowed by knowing the incubation period of the various tropical diseases +/- the major symptom complex
 

Infections by interval between exposure and onset of fever

Short incubation periods (7 - 10 days) arborviruses anthrax babesiosis brucellosis dengue fever diphtheria ehrlichiosis hemorrhagic fevers with renal syndrome (hantavirus) influenza Japanese encephalitis Lassa fever Legionnaire's disease leptospirosis Loeffler's syndrome Lyme disease malaria measles meningococcal infection plague poliomyelitis psittacosis Q fever rabies relapsing fever rickettsial infection toxocariasis toxoplasmosis trichinosis tularemia typhoid fever viral hemorrhagic fever yellow fever yersinia  Intermediate incubation period (14 - 30 days) amebic liver abscess babesiosis clonochiasis CMV virus fascioliasis hepatitis A, C and E HIV leptospirosis Loeffler's syndrome measles melioidosis poliomyelitis psittacosis Q fever rabies rubella schistosomiasis toxocariasis toxoplasmosis trypanosomiasis viral hemorrhagic fever (few - Crimean-Congo, Lassa, Marburg-Ebola)  Long incubation period (months) amebic liver abscess bartonellosis brucellosis clonorchiasis CMV fascioliasis filariasis hepatitis B, C histoplasmosis HIV leishmaniasis Lyme disease malaria (pl. vivax and pl. malariae) melioidosis rabies syphilis trypanosomiasis tuberculosis

-  when fever starts > 14 days after potential exposure => dengue fever and many arbovirus infections are unlikely causes

- by contrast, Katayama fever (acute schistosomiasis) occurs 2 - 6 weeks after exposure as the worms migrate through the body (patient may present with fever, rigors, headache, myalgia, dry cough, urticaria, hepatosplenomegaly, eosinophilia)
 

Incubation period for selected tropical diseases

Malaria - 7 days (minimum) to 12 weeks (maximum)  Dengue fever - 3 to 14 days  Typhoid fever - 3 days to 3 months; usually 1 - 3 weeks  Hepatitis A - 15 to 50 days  Hepatitis B - 45 to 180 days  Viral hemorrhagic fevers - 2 to 21 days

- additional historical facts of importance include type of residence, nature of participatory activities (eg. recreational hiking, rafting in freshwater, swimming or wading), exposure to animal or insect bites, contact with native soil, and any sexual encounters
 

Checklist of important travel historical facts

time of travel - season/month/year of travel duration of stay areas visited: countries, rural or urban, savannah or forest living conditions eg. modern hotel or primitive rural residence use of protective clothing and/or bed-netting and/or insect repellents animal or insect bite exposure  (rabid animals, bats, rodents, mosquitos, fleas, lice, tsetse flies) food and drink exposure (raw vegetables or fruit, unpasteurized milk products, raw or undercooked meat or fish) sexual activities and/or body piercing/tatoo activities recreational or occupational exposures to freshwater (rafting, swimming, wading) or caves (rabies, histoplasmosis) or fresh soil (strongyloides) pre-travel vaccinations (yellow fever, hepatitis A and B, typhoid fever, meningococcus, poliomyelitis), antimalarial prophylaxis therapy, and/or traveller's diarrhea antibiotic prophylaxis previous surgery (gastrectomy, splenectomy) general state of health and the degree of any state of immunosuppression pattern of fever any anti-microbials, anti-inflammatory agents, or antipyretic agents taken

- pre-travel vaccination has variable effectiveness, especially if the timing of vaccination was not optimal eg. hepatitis A and yellow fever immunization are usually very effective, while vaccination against typhoid fever is only 60 - 70% effective if given at the appropriate pre-travel time

- childhood vaccinations against poliomyelitis, diphtheria and measles may not provide full-proof immunity without a pre-travel booster

- antimalarial chemoprophylaxis does not guarantee protection against malaria - especially if the incorrect anti-malarial drugs were taken, if antimalarial drug doses were skipped or prematurely discontinued, or if exposure to drug-resistant malaria occurred
 

Infections associated with specific exposures

Freshwater leptospirosis schistosomiasis  Mosquitos arbovirus dengue filariasis malaria yellow fever  Fleas tick-borne typhus plague  Lice relapsing fever epidemic typhus trench fever  Sandflies leishmaniasis sandfly fever  Tsetse flies african trypanosomiasis  Ticks babesiosis Crimean-congo hemorrhagic fever ehrlichiosis Lyme disease scrub typhus Rickettsial spotted fevers tick-borne encephalitis tularemia  Rodents hantaviruses murine endemic typhus Lassa fever leptospirosis plague  Soil (including barefoot exposure) amebiasis coccidiomycosis histoplasmosis melioidosis strongyloidiasis  Animal bites or animal tissue exposure anthrax brucellosis plague psittacosis Q fever rabies toxoplasmosis tularemia  Ingestions unpasteurized milk (brucellosis, salmonellosis, tuberculosis) raw fish (clonorchiasis, paragonomiasis, vibrio bacteria, hepatitis A) raw or undercooked animal flesh (trichinosis, salmonella, typhoid fever)  Injections, tatoos and transfusions hepatitis B and C HIV malaria toxoplasmosis american trypanosomiasis  Infected persons viral hemorrhagic fever (eg. Ebola, Lassa, Marburg) typhoid fever meningococcus tuberculosis

 

Common symptom/disease associations

Sore throat bacterial or viral pharyngitis diphtheria HIV seroconversion Lyme disease poliomyelitis psittacosis tularemia viral hemorrhagic fever  Cough amebiasis (hepatic) anthrax filarial fever histoplasmosis legionnaire's disease Loeffler's syndrome malaria measles melioidosis plague Q fever relapsing fever schistosomiasis trichinosis tuberculosis typhoid fever typhus viral hemorrhagic fever

Abdominal pain amebiasis anthrax arboviruses brucellosis campylobacter fascioliasis legionnaire's disease relapsing fever salmonellosis schistosomiasis shigellosis trichinosis tuberculosis tularemia typhoid fever viral hemorrhagic fever yersinia  Diarrhea amebiasis anthrax campylobacter clostridium difficile legionnaire's disease malaria melioidosis plague  relapsing fever salmonellosis shigellosis typhoid fever (children) viral hemorrhagic fever yersinia

 

Examination

- particular attention should be paid to the presence of anemia, jaundice, generalized lymphadenopathy, hepatomegaly, splenomegaly and skin rashes/ulcers

- the presence of petechiae and/or mucosal bleeding suggests a viral hemorrhagic fever or other hemorrhagic infectious diseases such as meningococcus, Rocky Mountain spotted fever, typhus, plague, vibrio vulnificus or leptospirosis

- most viral hemorrhagic fevers are due to mosquito or tick transmission, or contact with an infected rodent or an infected person (person-to-person spread)

(* see the appendix for further details on the different types and distribution of viral hemorrhagic fevers)

- the presence of generalized lymphadenopathy suggests a disease other than malaria
 

Physical signs/disease associations

Generalized maculopapular rash arbovirus CMV dengue fever drug reaction ebola fever echovirus hepatitis B herpes hominis V6 HIV seroconversion infectious mononucleosis leptospirosis measles mycoplasma parvovirus B19 psittacosis rat-bite fever relapsing fever rubella scarlet fever secondary stphilis trichinosis typhus  Petechial rash arbovirus dengue fever infectious mononucleosis leptospirosis meningococcemia plague rat-bite fever relapsing fever Rocky Mountain spotted fever trichinosis tularemia typhus vibrio vulnificus hemorrhagic virus (see the appendix for a more complete list) yellow fever  Ulcerations or chancre or buboes anthrax histoplasmosis plague tularemia trypanosomiasis typhus  Jaundice CMV fascioliasis hepatitis, viral leptospirosis malaria relapsing fever toxoplasmosis trypanosomiasis typhoid fever typhus yellow fever  Generalized lymphadenopathy arbovirus bartonellosis brucellosis CMV dengue fever diphtheria filarial fever histoplasmosis HIV seroconversion infectious mononucleosis leishmaniasis Lyme disease plague psittacosis schistosomiasis secondary syphilis toxplasmosis trypanosomiasis tuberculosis tularemia typhus  Hepatomegaly amebiasis babesiosis bartonellosis CMV dengue fever fascioliasis hepatitis, viral histoplasmosis leishmaniasis malaria Q fever relapsing fever schistosomiasis trypanosomiasis tuberculosis typhus  Splenomegaly babesiosis bartonellosis brucellosis CMV endocarditis filarial fever histoplasmosis infectious mononucleosis leishmaniasis leptospirosis malaria melioidosis psittacosis Q fever relapsing fever schistosomiasis toxoplasmosis trichinosis trypanosomiasis tuberculosis tularemia typhoid fever typhus  Meningitis/encephalitis anthrax arboviruses bacterial meningitis histoplasmosis Legionnaire's disease leptospirosis Lyme disease malaria rabies relapsing fever trypanosomiasis tuberculosis typhoid fever

- the pattern of fever is of little diagnostic use because the fever-patterns are not consistent, and because patients are rarely monitored in hospital for prolonged periods in order to study their fever patterns

- some distinctive fever-patterns include:-

• double quotidian fever (two fever spikes per 24 hour period) - mixed malaria infections, visceral leischmanisis, disseminated gonococcal infection
• dromedary or camel back fever curve (3 - 4 day afebrile period flanked by two periods of elevated temperature) - dengue fever, relapsing fever, quartan malaria
• continuous fever - typhoid fever, typhus
• remittent fever (daily fluctuations of > 2°C with the daily lower point not reaching normal) - bacterial septicemias, pulmonary tuberculosis, african trypanosomiasis, early typhoid fever
• intermittent fever (daily low drops below normal with large variation between the peak and the nadir) - malaria, pyogenic abscesses, miliary tuberculosis, typhoid fever

Diagnostic testing

- baseline diagnostic tests include:-

• CBC and differential
• thick and thin blood smears for malaria
• urinalysis
• blood culture
• renal and hepatic biochemistry
• stool and urine cultures prn
• stored sera samples for later "paired sera" testing
• chest X-ray if clinically indicated
• LP for altered LOC or clinical signs of meningitis

- certain hematological abnormalities may suggest a particular disease
 

Hematological abnormalities

Anemia amebiasis babesia bartonellosis brucellosis leishmaniasis malaria trypanosomiasis  Neutrophilia amebiasis babesia campylobacter diphtheria legionnaire's disease leptospirosis meningococcal meningitis plague relapsing fever salmonellosis shigellosis trypanosomiasis tularemia yersinia  Neutropenia arboviruses brucellosis dengue fever leishmaniasis measles typhoid fever viral hemorrhagic fevers  Lymphocytosis CMV infectious mononucleosis malaria toxoplasmosis trypanosomiasis  Eosinophilia drug reaction fascioliasis filarial fever Loeffler's syndrome schistosomiasis toxocariasis trichinosis  Thrombocytopenia brucellosis dengue fever HIV seroconversion leishmaniasis leptospirosis malaria relapsing fever trypanosomiasis typhoid fever viral hemorrhagic fevers yellow fever

 

Appendix

I have included brief clinical decriptions of a select number of tropical diseases -- the list is not meant to be complete, and it reflects my arbitrary decision to provide useful problem-solving information on some selected tropical diseases -- consult the emedicine.com textbook, if necessary, for more comprehensive information on a greater variety of tropical diseases

- the number of tropical diseases that can cause a fever in the returned traveler is large, and the following list includes the more common tropical diseases that should be considered (in rough order of importance and clinical likelihood)
 

Common tropical diseases with wide distribution

Malaria

any patient who has been potentially exposed to malaria, and who presents with a fever or unexplained systemic illness, should be assumed to have life-threatening malaria until proved otherwise malaria is due to four different species of the plasmodium parasite, and the incubation period is about 8 - 30 days (shortest for pl.falciparum) after a bite from an infected Anopheles mosquito, which bites from dusk to dawn pl. falciparum predominates in tropical Africa, Eastern Asia, Oceania, Haiti, Dominican Republic and the Amazon basin of South America; pl. vivax predominates in Central America, the Middle East, India and Southeast Asia most severe complications (cerebral malaria, hemolytic anemia, renal failure, severe hypoglycemia, non-cardiogenic pulmonary edema, shock) are due to the pl. falciparum parasite misdiagnosis of malaria is frequent because it often presents with non-specific symptoms and signs - vomiting, anorexia, diarrhea, diffuse abdominal pain (mimicing gastro-enteritis) and fever, chills, headache, and myalgias (mimicing flu); and because the degree of parasitemia may be low during the first few days resulting in false-negative blood smears for malaria untreated falciparum malaria evolves into cerebral malaria (altered LOC suggesting a toxic encephalopthy, seizures or coma) which is the most common cause of death from malaria hepatic dysfunction is usually mild and any jaundice is usually secondary to the hemolytic anemia hepatosplenomegaly is variable in degree, and may be delayed and not present at the time of initial presentation; prominent hepatosplenomegaly is more common in chronic malaria thrombocytopenia is common and may be due to splenic sequestration the characteristic fever patterns suggestive of malaria may be delayed, and may not always develop eg. quotidian (daily) and tertian (every 48 hours) fever spikes; erratic and hectic fever patterns may predominate; a measurable fever may not be present at the time of initial clinical presentation the proto-typical "malaria paroxysm" is uncommon because patients are usually treated before the parasite's asexual cycle becomes synchronous partial host immunity and/or prophylactic consumption of antimalarial drugs may delay the presentation and temporarily ameliorate the severity of symptoms malaria cannot be accuratedly diagnosed by history and clinical exam, and the only consistent sign is fever - so malaria should be the primary diagnosis in any febrile patient returning from a visit to a malarious locale patients should be interrogated about blood transfusions, needle sharing, tatooing, or residence near an airport (airport or runway malaria) or migrant labor camp if there is no history of exposure to mosquitos in malaria-endemic rural areas  laboratory abnormalities are common - increased LDH (80%), thrombocytopenia (60%), leukopenia (50%), anemia (30%), mildly increased liver enzymes (25%) and elevated serum creatinine (15%); atypical lymphocytosis may be found, but leucocytosis > 15,000/cu.mm is rare the microscope is the key to diagnosis - thick and thin blood smears should routinely be ordered q 8 - 12 hourly for the first two days (thick smears are 20 - 40x more sensitive than thin smears and > 200 HP fields should be examined before a thick smear slide is declared negative) microscopic clues suggesting falciparum malaria in a giemsa-stained blood smear include:- small tight rings, only ring forms seen, high-grade parasitemia (>3%), multiple parasitized erythrocytes, banana-shaped gametocytes severe malaria is defined as infection with falciparum malaria and the presence of any of the following markers:- cerebral malaria, hypoglycemia, respiratory distress due to severe metabolic acidosis, temperature > 104°F unresponsive to acetaminophen, hypotension, oliguria/anuria, hematocrit < 20% or falling rapidly, serum creatinine > 1.5mg/dl, parasitemia > 5%, hemoglobinuria (blackwater fever), spontaneous bleeding or jaundice appropriate consulation with an infectious disease specialist should always be sought if the diagnosis of malaria is possible in a returned traveler => a decision may be made to empirically treat the patient even if the blood smears are negative for malaria  chloroquine is used for malaria acquired in an area where the malaria is known to be chloroquine-sensitive; mefloquine, or quinine + doxycycline, or quinine alone is used for suspected chloroquine-resistant infection; quinine + doxycycline is used for malaria suspected to be resistant to chloroquine and mefloquine; alternative regimens for multi-drug resistant malaria include artesunate + mefloquine, halofantrine, and quinine + fansidar (sulfadoxine/pyrimethamine) chloroquine, quinine or artesunate is given by IV infusion for severe malaria; the mortality rate of properly-treated severe malaria is about 20% blood transfusions are often recommended for severe anemia (hematocrit < 20%) and exchange tranfusions may be warranted for severe falciparum malaria; aggressive over-hydration may induce ARDS and should be avoided

Dengue fever

the dengue flavivirus may produce a non-specific fever, or a hemorrhagic syndrome (dengue hemorrhagic fever - DHF) or shock (dengue shock syndrome - DSS) dengue is spread by a mosquito bite (mainly Aedes aegypti, which likes to lay its eggs in artificial containers found in and around homes in the tropics eg. discarded automobile tires), and is much more common in Southeast Asia and Central or South America compared to Africa the mosquito bites during the day and it may bite a number of people in one feeding because the mosquitos are nervous feeders and feeding is easily disrupted by the slightest movements  => multiple people from one household can develop dengue simultaneously  the incubation period is 3-14 days, and a 5-7 day febrile illness follows dengue fever is very unlikely if fever develops two weeks after a traveler returns home, or if the fever lasts longer than two weeks DHF or DSS may rarely develop later in the illness towards the time of defervescence (3rd - 7th day of illness), and DHF mainly occurs in children < 15 years of age and in patients who have previously had a dengue infection (immune enhancement may be the underlying pathological mechanism) dengue is usually a self-limited illness and recovery from dengue fever is usually complete dengue is usually asymptomatic in children younger than 15 years fever is the predominant sign; the fever is usually persistent and lasts 5-7 days; occasionally the fever may disappear for 12-24 hours after a few febrile days and then return (saddleback fever) headache, retro-orbital pain, backache, malaise, myalgia, abdominal pain, nausea/vomiting, mild sore throat, and altered taste frequently accompany the fever severe bone pain ("breakbone" fever) may occasionally occur in the legs and lumbar spine and be associated with profound malaise conjunctival injection, skin flushing and skin blotching are common in the early stages a truncal scarlatiniform or maculopapular rash occasionally occurs - either early or during defervescence of the illness; the rash characteristically starts on the back of the hands and feet and spreads to the arms and legs, and the face is rarely involved; characteristic sparing of islands of normal skin may occur in the diffuse erythematous skin rash ("white islands in a sea of red" resembling the appearance of pityriasis versicolor - except that the background is erythematous and not pigmented) generalized lymphadenopathy and pharyngeal injection are common; mild hepatomegaly occurs laboratory diagnosis criteria include:- isolation of the dengue virus from the blood, and demonstration of a 4x increase in serum antibody titres against the dengue virus (the turn-around time of the test is so long that some physicians don't bother to order the test when the disease is suspected) a chest X-ray often shows bilateral pleural effusions (right > left) leukopenia and thrombocytopenia and mildly elevated liver enzymes are common DHF is diagnosed by a positive tourniquet test (> 20 petechia per square inch below an inflated blood pressure cuff that is inflated to just below the systolic blood pressure for 5 minutes), presence of petechiae, purpura, or mucosal bleeding, GIT bleeding or thrombocytopenia < 100,000/cu.mm +/- laboratory evidence of DIC, and evidence of plasma leakage eg. ascites or pleural effusions or fluctuating hematocrit levels > 20% during the course of the illness DSS is diagnosed by the presence of all those criteria + evidence of circulatory shock; a rise in hematocrit of >20% may herald shock; the duration of shock is usually short and death follows within 8 - 12 hours treatment of DSS is supportive and the rapid clinical response to aggressive fluid therapy may be very dramatic; the mortality of untreated DSS may be 50% and it can be reduced to 5% with aggressive fluid therapy in an ICU see a clinical review in the bmj for further details

Typhoid fever

the classic syndrome of enteric fever due to Salmonella typhi is typified by an acute illness that initially consists of fever, headache, abdominal pain, relative bradycardia, splenomegaly and leukopenia; the illness gradually evolves through a few stages over a period of 4 weeks (although antibiotic use may markedly alter the classic pattern) occurs mainly in young adult travelers (< 30 years, males>females) to India or Mexico, or Central or South America, or other underdeveloped countries with poor sanitation conditions; the consumption of feces-contaminated food or beverages is the usual source of infection; the incubation period is usually 1 - 3 weeks (range of 3 days to 3 months) the fever may initially be remittent, and it then rises step-wise over a few days days to become sustained; the systemic illness may also progessively evolve step-wise over 1 - 2 weeks towards a point of eventual prostration  fever, headache, abdominal pain, +/- nausea, vomiting and constipation (or diarrhea, which is more common in children) predominates in the early stages, although mild extra-intestinal symptoms occur eg. slight non-productive cough, conjunctivitis, and infrequent pharyngitis rose spots (1-5mm blanching pale macules) occur in less than 50% of patients as faint macules over the mid-trunk during the early-mid-stages of the illness (rarely seen in dark-skinned patients) abdominal tenderness may be localized (eg. RLQ) or diffuse; mild or severe mild splenomegaly is more common than hepatomegaly during the second week; isolated generalized lymphadenopathy suggests other pathology altered behaviour or frank delirium may be prominent and out of proportion to the severity of the systemic illness during the second week and the patient may appear disproportionately apathetic and withdrawn; the "typhoidal state" may occur during the third week and it mainly consists of disordered mentation +/- extreme "toxemia"  abdominal distension, pea-soup diarrhea, intestinal hemorrhage or intestinal perforation may occur during the second-third week of illness other mid-late complications include acute cholecystitis, pneumonia, myocarditis or pyelonephritis untreated typhoid fever usually resolves after 4 weeks and the fever, altered mental state and abdominal distension slowly improve; however, spontaneous recurrence can occur after the patient has "ridden through the storm"  the diagnosis is made by culturing the bacteria from blood or bone marrow (90% positive) or stool (20 - 40% positive); bone marrow cultures may offer the highest yield if the patient has recently been taking antibiotics the Widal test is also positive in other salmonella diseases and it has limited use in the acute phase because it is only positive in 40 - 60% of cases; a >4x rise in antibodies against S typhi from paired sera taken 2 - 3 weeks apart is diagnostic a mild elevation of the serum bilirubin and liver enzymes is common; leukopenia is seen in 15 - 50% of cases and eosinopenia is common many conditions may mimic enteric fever - plague (rodent contact, flea bite exposure, sudden onset and rapid progression, severe prostration, buboes); intestinal anthrax (severe prostration, eating undercooked meat in endemic locales); melioidosis (severe prostration, pustular skin lesions, pulmonary nodular densities, travel to South-east Asia); bartonellosis (fever, headache, abdominal pain, severe prostration, hemolysis, renal failure, travel to Andean valleys of Peru or Ecuador or Colombia with history of sandfly bites within past one month); leptospirosis (relative bradycardia, conjunctival suffusion, myalgia and muscle tenderness, biphasic illness, azotemia, CSF pleocytosis, swimming or rafting in fresh water, animal contact with cattle or dogs); relapsing fever (recurrent fever pattern, conjunctival suffusion, skin rash,  splenomegaly, travel to Southeast Asia, Far East or Ethiopia, tick or louse vector); dengue fever; malaria; epidemic typhus; Yersinia enterocolitica (age > 40 years, history of significant underlying liver disease, non-sustained fever, erythema nodosum, polyarthritis, hepatic or splenic abscesses, travel to Scandinavia), Campylobacter fetus (associated thrombophlebitis); typhoidal tularemia (rabbit or tick exposure); brucellosis (myalgias, splenomegaly); and many other infectious diseases (legionella, rat bite spirillum, babesiosis, amebiasis, ehrlichiosis, Rocky Mountain spotted fever, trichinosis, visceral larva migrans, acute schistosomiasis) "common things occur commonly" => typhoid fever should be the presumed etiology of an enteric fever in the returned traveler unless there is a strong reason to suspect another cause

Leptospirosis

leptospires are endemic in many temperate and tropical countries, and ubiquitous in many wild and domestic animals and reptiles leptospiral spirochetes excreted in animal urine can become established in soil and water travelers may become infected when wading or swimming or rafting or windsurfing in contaminated waters travelers may also become infected by direct contact with infected animal tissues eg. hunters, farmers, sewerage workers, military personnel undergoing jungle-training leptospirosis is more common during the rainy season, and epidemics may occur with flooding following large hurricane storms in the Caribbean, Central and South America leptospires enter the body through cuts, abrasions, softened or waterlogged skin leptospires are widely distributed and can cause a systemic vasculitis clinical illness varies widely from a mild self-limited systemic illness (90%) to a severe, potentially fatal illness characterized by renal failure, liver failure and a hemorrhagic pneumonitis the incubation period is usually 5 - 14 days, and may be longer (> 30 days) the acute anicteric illness begins abruptly with a high remittent fever, headache, retro-orbital pain, photophobia, chills, rigors, conjunctival suffusion, abdominal pain and tenderness, anorexia, nausea, vomiting, diarrhea, cough, pharyngitis and a pretibial maculopapular rash (Fort Bragg fever) => the temperature subsides within 4 - 7 days and recovery is usually complete within 3 - 4 weeks conjunctival suffusion, photophobia, eye pain and excruciating calf, thigh and back muscle tenderness are common findings (leptospirosis should be suspected if a patient with a flu-like illness has signs of an aseptic meningitis and/or a severe myalgic syndrome) other findings include lymphadenopathy, hepatomegaly (common) and splenomegaly (rare) exanthematous rashes occasionally develop in the first week - often morbilliform, macular or urticarial aseptic meningitis occurs later in the immune phase of the illness (second week - when spirochetes can no longer be cultured from the blood or CSF) producing a bifrontal headache, meningism +/- an altered LOC: the CSF may initially be clear and CSF lymphocytosis is a delayed finding  Weill's disease (hepatic and renal and CNS involvement, and hemorrhagic diathesis) may occur after a 1 - 3 day improvement in the fever and other symptoms and present as a biphasic illness with the sudden onset of a high fever (saddleback fever) => it may progress rapidly to liver and renal failure, severe hemorrhagic pneumonitis, and circulatory collapse; however, the illness may not always be biphasic and Weill's disease can progress rapidly from the initial onset of the illness  acute renal failure occurs due to interstitial nephritis, or glomerulonephritis and ATN, during the second week of the illness hemorrhagic pneumonitis is associated with "snowflake" patchy alveolar infiltrates on chest X-ray; ARDS may develop in severe cases liver failure is associated with severe jaundice and moderatedly elevated liver enzymes cardiac arrhythmias secondary to myocarditis are common, but frank CHF is rare fatal disease is associated with widespread skin and mucosal and serosal hemorrhages anterior uveitis is a rare early-or-late complication routine blood tests are non-specific; anemia, leucocytosis, and proteinuria/hematuria with casts are common findings severe leucocytosis (20,000 - 40,000/cu.mm) is not uncommon and helps to distinguish leptospirosis from other causes of hepatitis liver enzymes and serum bilirubin are variably elevated and the CK is often disproportionately elevated (relative to liver enzymes) due to the myositis +/- myocarditis (helps to distinguish leptospirosis from other causes of hepatitis) thrombocytopenia, abnormal coagulation and bleeding times may occur in the absence of DIC DIC is defined by the presence of thrombocytopenia, low factor V and VIIIc levels, prolonged prothrombin, thrombin and aPTT times, normal or reduced serum fibrinogen, increased serum FDPs and increased anti-thrombin III levels a hemolytic uremic syndrome may rarely develop (renal failure + DIC + hemolytic anemia) leptospires can be recovered from the blood and CSF during the acute phase of the illness (first 7 - 10 days) and from the urine during the second week of the illness; however, laboratory identification of the cultures may take a few weeks a 4x rise in specific antibodies from paired sera collected 1 - 2 weeks and 3 - 4 weeks after illness onset is diagnostic PCR methods can detect leptospiral antigens in the first 7 - 10 days of the illness in the CSF and other body fluids antibiotic therapy usually involves a penicillin or tetracycline antibiotic excellent emedicine.com chapter on leptospirosis with much greater detail

 

Less common tropical diseases with wide distribution

Brucellosis

brucellosis is a worldwide zoonosis that is particularly common in the Mediterranean basin, the Arabian peninsula, the Indian subcontinent and parts of Mexico and Central and South America cattle, sheep, goats, camels are mainly affected; the infection is lifelong and people get exposed from direct contact with animals or their secretions, from inhaling infected aerosols, or drinking unpasteurized milk; veterinarians, farmers and slaughterhouse workers are at greatest risk the onset of illness can be acute and explosive, or insidious over weeks - after an incubation period of 2 - 4 weeks (rarely months) the initial symptoms are protean and non-specific with no specific focality - symptoms include fever, sweats, malaise, anorexia, headache, back pain, peculiar taste, malodorous sweat alimentary symptoms are common and include abdominal pain, nausea, vomiting, diarrhea or constipation, and weight loss the liver is commonly involved (painless hepatomegaly or mild hepatitis, rarely hepatic abscesses), but liver function tests are only slightly elevated; pancreatitis, acute cholecystitis and spontaneous bacterial peritonitis are rare complications osteo-articular complications are common and include arthritis (major joints), spondylitis, osteomyelitis, tenosynovitis and bursitis; sacroileitis is most common and is often unilateral or asymmetric CNS involvement is rare (<5%) - acute or chronic meningitis, encephalitis, myelitis, radiculoneuritis, and demyelinating syndromes generalized lymphadenopathy and splenomegaly are not common (10 - 15%) endocarditis (mainly the aortic valve) is rare (2%) airborne transmission can result in bronchitis, bronchopneumonia, lung abscesses, nodules or miliary disease, hilar lymphadenopathy or pleural effusions subacute orchi-epididymitis and testicular abscesses may occur hematological involvement causes anemia, leukopenia and thrombocytopenia transient rashes are rare (<5%) and include papules, ulcers and erythema nodosum anterior uveitis is a rare complication inadequately treated brucellosis may result in relapses (10%) and chronic infection bone marrow cultures have a higher yield than blood cultures (10 - 70%) - identification by culturing may take weeks, but rapid techniques allow for earlier identification; a Brucella serum antibody titre >1:160 or a 4x titre increase is diagnostic tetracyclines, rifampin and streptomycin are common antibiotic choices

 

Less common tropical diseases with limited distribution

Scrub typhus

the rickettsial organism (Orientia tsutsugamushi) occurs in a wide area of Eastern Asia, Northern Australia and the Western Pacific (mainly the islands of the western Pacific) found in scrub conditions that is transitional between forest and clearings, but also found in sandy beaches and more arid conditions; military personnel and field workers clearing fields are at greatest risk of exposure transmitted by the bite of chigger mites; wild rodents are disease reservoirs a local papule develops at the bite site, ulcerates and forms an eschar => regional lymphadenopathy => generalized lymphadenopathy in 4 days symptoms begin 6 - 18 days after the chigger bite (as the eschar matures) => sudden fever, headache, myalgia +/- ocular pain, conjunctival injection, non-productive cough, relative bradycardia => faint macular rash in 5 days => generalized lymphadenopathy and splenomegaly after the first week of illness (a common misdiagnosis is infectious mononucleosis)  nervousness, delirium, slurred speech, deafness, or nuchal rigidity infrequently develops in the second week of the illness; severe meningoencephalitis may occur fever and symptoms resolve in two weeks in untreated patients; the mortality rate of untreated patients is 0 - 30%; treatment rapidly shortens the illness and prevents mortality routine laboratory tests are of no diagnostic value the Weil-Felix test is not very sensitive or specific (also positive in leptospirosis); the specific PCR test is most diagnostic tetracycline antibiotics are frequently used to treat the disease

Plague

due to the yersinia pestis bacterium, which occurs worldwide, with most cases reported in Africa and Asia and the south-western USA a zoonotic infection in urban and sylvatic rodents and spread by fleas three forms of the disease - bubonic plague, septicemic plague and pneumonic plague the most common presentation is bubonic plague, which occurs 2 - 8 days after a bite from an infected flea => sudden onset of fever, chills, weakness and headache an intensely painful bubo develops in the regional lymph nodes; the bubo is 1 - 10 cm in size and consists of a smooth, egg-shaped lymph node or multiple, matted nodes; the overlying skin is warm and red; most bubos occur in the femoral or axillary region; there is sometimes no visible flea bite and visible signs of an ascending lymphangitis are usually absent; papules, pustules, or eschars may sometimes be seen at the site of a presumed flea bite the septic patients are febrile, lethargic and often prostrate; frank delirium may occur (patients with cat scratch fever or tularemia may have regional lymphadenopathy, but they are not as toxic-appearing, and hemoptysis secondary to hemorrhagic pneumonia does not usually occur) hepatosplenomegaly may occur purpura is common and acral gangrene can develop secondary to the extensive hemorrhagic necrosis plague pharyngitis and meningitis rarely occur shock is common and death occurs within a few days septicemia may sometimes occur without any bubo formation - called septicemic plague secondary pneumonic plague occurs due to hematogenous spread and presents with patchy bronchopneumonia or dense consolidation; pneumonic plague is highly contagious and person-to-person spread occurs via aerolized droplets; primary pneumonic plague could occur secondary to aerolization exposure from a biological weapon leucocytosis is common and myeloid reactions with very high WBC of 100,000/cu.mm can occur; cytoplasmic vacuolation, toxic granulations and Dohle bodies are common the platelet count is normal or low; DIC is a common complication diagnosis can readily be made by needle aspiration of the bubo => gram stain of the aspirate shows gram negative coccobacilli with bipolar staining (safety pin appearance) bubo aspirate and blood can be also cultured a 4x increase in serum titre (or titre > 1:160) against the YP F1 antigen is diagnostic antibiotic treatment includes streptomycin or tetracycline or ciprofloxacin for 10 days; chloramphenicol is used for plague meningitis plague is a reportable disease; patients with plague pneumonia should be treated in isolation units and close contacts should receive prophylactic antibiotics

Visceral leishmaniasis

known as kala-azar; found in eastern Africa, China and the Indian-Pakistan-Bangladesh subcontinent an important opportunistic infection in HIV positive patients in Spain, southern France and Italy rodents, dogs and other canines are the reservoirs spread by the bites of sandflies, that live in and around mud-hut walls the incubation period is many months the majority of infections are asymptomatic and resolve spontaneously usually produces a chronic illness with low-grade fever, hepatomegaly, massive soft splenomegaly, cachexia, weight loss, malaise, and anorexia +/- generalized lymphadenopathy (Sudan form) the skin eventually becomes dry, thin, scaly and greyish and secondary bacterial infections of the skin, middle ear and respiratory tract are common epistaxis, gingival bleeding and petechia are late signs anemia, leukopenia and hypergammaglobulinemia are very common untreated chronic infection leads to progressive cachexia and death from secondary infections rarely presents acutely with a high fever and chills mimicing malaria, typhoid fever or typhus subacute or chronic leishmaniasis may be confused with brucellosis, histoplasmosis, infectious mononucleosis, lymphoma, leukemia or hepatosplenic schistosomiasis diagnosed by bone marrow culture; spleen or lymh node aspirates may also show the organism also diagnosed by antileishmaniasal antibody testing, which may be falsely negative in HIV patients therapeutic drugs include liposomal amphotericin B, and pentavalent antimony compounds

Relapsing fever

due to the Borrelia spirochete occurs worldwide and spread by tick bites or lice louse-borne relapsing fever is found in the refugee camps of Ethopia, Eritrea and the Sudan the animal reservoir of tick-borne relapsing fever are small rodents campers or hunters sleeping in the wild are at risk - most common in hunting cabins of the western USA, southern British Columbia, the plateau regions of Mexico and in Central and South America; the soft tick feeds for 15 - 30 minutes, and the tick bite is painless and unnoticed by the sleeping victim the incubation period is 4 - 18 days the fever begins abruptly with chills, headache, malaise, arthalgias, myalgias, nausea and vomiting conjunctival suffusion and diffuse abdominal tenderness are common (30-50%); hepatomegaly, splenomegaly and jaundice may rarely develop (<5%) minor hemorrhage is common - petechia, epistaxis, hemoptysis or hematuria neurological involvement is far less common (<2%) - altered LOC, nuchal rigidity, cranial nerve palsies, seizures, coma a macular or petechial skin rash may develop for 1 - 2 days at the end of the primary febrile period  the fever usually lasts about 3 days and then disappears and the patient is asymptomatic for about 7 days => relapse of fever occurs; the cycle may repeat itself 3-5x and each relapse is less severe death may rarely occur from myocarditis or cerebral hemorrhage; death is not common in tick-borne relapsing fever diagnosis is by a routine examination of a blood smear using Wright or Giemsa stain during the febrile period => the organism lies between blood cells the syphilis and Lyme test may be falsely-positive initially confused with diseases causing a biphasic or relapsing fever pattern - malaria, typhus, dengue, yellow fever, Colorado tick fever and leptospirosis => a history of possible tick exposure and recurrent fever suggests the diagnosis of relapsing fever  effectively treated with tetracycline or erythromicin, penicillin or chlorphenicol; antibiotic therapy is often associated with a Jarisch-Herxheimer reaction

 

Hemorrhagic fever viruses and their known distributions

Americas Argentine (Junin) hemorrhagic fever - rodent, person-to-person transmission Bolivian hemorrhagic fever (Machupo virus) - rodent, person-to-person transmission Dengue fever - mosquito transmission Hemorrhagic fever with renal syndrome - rodent transmission Hantavirus pulmonary infection - rodent transmission Sabia virus infection - rodent transmission Venezualian hemorrhagic fever (Guanarito virus) - rodent transmission Yellow fever - mosquito transmission  Africa Chikungunya - mosquito transmission Crimean-Congo fever hemorrhagic fever - tick and person-to-person transmission Dengue fever - mosquito transmission Ebola - ? source, person-to-person transmission Lassa fever - rodent and person-to-person transmission Marburg - ? source, person-to-person transmission Rift Valley fever - mosquito transmission Yellow fever - mosquito transmission  Asia Chikungunya - mosquito transmission Crimean-Congo fever hemorrhagic fever - tick and person-to-person transmission Dengue fever - mosquito transmission Hemorrhagic fever with renal syndrome - rodent transmission Kyanasur Forest disease - tick transmission  Europe Crimean-Congo fever hemorrhagic fever - tick and person-to-person transmission Hemorrhagic fever with renal syndrome - rodent transmission Omsk hemorrhagic fever - tick transmission  Oceania and Australia Dengue fever - mosquito transmission

Disclaimer: My EM guidemaps reflect my personal approach to problem-solving/managing clinical cases in an ED setting and they should not be regarded as the standard of care. They merely represent the personal opinions of the author and they should only be used in clinical practice if the reader-user has substantial reason to believe that the clinical advice contained in the guidemaps is valid and accurate. The guidemaps are not meant to be "authoritative" and the reader-user should consult standard medical textbooks and expert opinion articles/guidelines for more authoritative advice. The reader-user should particularly confirm all drug doses, their indications and contra-indications, prior to their use.