The Perils of Travel Jeffrey H. Phillips, M.D., F.A.C.P. Internal Medicine Clinical Update October...

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The Perils of The Perils of TravelTravel

Jeffrey H. Phillips, M.D., Jeffrey H. Phillips, M.D., F.A.C.P.F.A.C.P.

Internal Medicine Clinical Internal Medicine Clinical UpdateUpdate

October 26, 2005October 26, 2005

Case HistoryCase History

50 year old plaintiff attorney and his wife 50 year old plaintiff attorney and his wife vacationed in Costa Rica 6/12 – 6/20vacationed in Costa Rica 6/12 – 6/20

4 days after returning home, he 4 days after returning home, he developed chills, weakness, nausea, and developed chills, weakness, nausea, and fever to 104fever to 104oo..

Went to PHP ER 6/26 where WBC 5600, Went to PHP ER 6/26 where WBC 5600, Hct 40.7, platelets 185,000, normal urine Hct 40.7, platelets 185,000, normal urine and CMP, malaria smear negative, and and CMP, malaria smear negative, and CXR normalCXR normal

“…“…the sickest I have ever been.”the sickest I have ever been.”

Case history (continued)Case history (continued) Seen in office 6/29 with T 99.5Seen in office 6/29 with T 99.5oo; diffuse ; diffuse

erythematous maculopapular rash over erythematous maculopapular rash over extremities and thorax, no petechiae; extremities and thorax, no petechiae; exam of pharynx, chest, heart, and exam of pharynx, chest, heart, and abdomen normal; no adenopathyabdomen normal; no adenopathy

Lab: WBC 1800, Hct 47, and platelets Lab: WBC 1800, Hct 47, and platelets not counted “due to significant platelet not counted “due to significant platelet clumping”clumping”

Dengue fever antibodies drawn 6/29: Dengue fever antibodies drawn 6/29: IgM 43 (positive > 11); IgG 2 (positive > IgM 43 (positive > 11); IgG 2 (positive > 11)11)

What is dengue?What is dengue?

Disease caused by any one of four closely Disease caused by any one of four closely related viruses (DEN-1, DEN-2, DEN-3, or related viruses (DEN-1, DEN-2, DEN-3, or DEN-4)DEN-4)

Most common arboviral disease in the Most common arboviral disease in the world; more than 2/5 of world population world; more than 2/5 of world population at risk (2.5 billion people)at risk (2.5 billion people)

Estimated 50-100 million cases annuallyEstimated 50-100 million cases annually 250,000-500,000 with dengue hemorrhagic 250,000-500,000 with dengue hemorrhagic

feverfever 24,000 deaths24,000 deaths

HistoryHistory From African word that means “bone From African word that means “bone

breaking”breaking” First reports of dengue fever epidemics First reports of dengue fever epidemics

occurred simultaneously in 1779-80 in three occurred simultaneously in 1779-80 in three locations: Africa, Asia and North America locations: Africa, Asia and North America (Philadelphia). (Philadelphia).

After World War II, largely due to increased After World War II, largely due to increased international travel, dengue fever became international travel, dengue fever became established as a global pandemic. established as a global pandemic.

Today, dengue epidemic activity is found in Today, dengue epidemic activity is found in large portions of Central and South America, large portions of Central and South America, the Caribbean, Africa, Southeast Asia, and the Caribbean, Africa, Southeast Asia, and even parts of Australia and New Zealand. even parts of Australia and New Zealand.

Dengue VirusDengue Virus Belongs to the family Flaviviridae Belongs to the family Flaviviridae

(flavoviruses)(flavoviruses) Transmitted by the Transmitted by the Aedes aegyptiAedes aegypti and and A. A.

albopictusalbopictus mosquitoes mosquitoes Composed of single-stranded RNAComposed of single-stranded RNA Infection with one serotype is thought to Infection with one serotype is thought to

produce lifelong immunity to that serotype produce lifelong immunity to that serotype but only a few months immunity to the but only a few months immunity to the othersothers

Mosquito remains infected for life but only Mosquito remains infected for life but only causes illness in humanscauses illness in humans

Aedes aegyptiAedes aegypti Mosquito Mosquito

EpidemiologyEpidemiology Aedes Aedes mosquitos found worldwide mosquitos found worldwide

between latitudes 35between latitudes 35oo N and 35 N and 35oo S S AedesAedes mosquitos are efficient vectors: mosquitos are efficient vectors:

Highly susceptible to dengue virusHighly susceptible to dengue virus Feeds preferentially on human bloodFeeds preferentially on human blood Daytime feeder with imperceptible biteDaytime feeder with imperceptible bite Restless; several people may be bitten in Restless; several people may be bitten in

a short period for one blood meala short period for one blood meal Incidence in travelers returning from Incidence in travelers returning from

tropicstropics 2 % in early 1990s to 16 % in early 2000s2 % in early 1990s to 16 % in early 2000s

Reinfestation by Aedes aegypti in the Americas 1970 2002

Worldwide increase of Worldwide increase of DHFDHF

South East Asia:South East Asia: 1960s: <10,000 cases1960s: <10,000 cases 1990s: > 200,000 cases1990s: > 200,000 cases

Americas:Americas: 1980s: 15,000 cases1980s: 15,000 cases 1990s: 56,000 cases1990s: 56,000 cases 2001 alone: 15,000 cases2001 alone: 15,000 cases

Dengue in the U.S.A.Dengue in the U.S.A. Dengue epidemics occurred in the USA in the 1800s and Dengue epidemics occurred in the USA in the 1800s and

the first half of the 1900sthe first half of the 1900s Recent indigenous transmission (Texas)Recent indigenous transmission (Texas)

1980: 23 cases, first locally acquired since 19451980: 23 cases, first locally acquired since 1945 1986: 9 cases1986: 9 cases 1995: 7 cases1995: 7 cases 1997: 3 cases1997: 3 cases 1998: 1 case1998: 1 case 1999: 18 cases1999: 18 cases

2001 (Hawaii); 2001 (Hawaii); Aedes albopictusAedes albopictus implicated in implicated in 122 122 dengue infectionsdengue infections

Replication and Replication and TransmissionTransmission

of Dengue Virus (Part 1)of Dengue Virus (Part 1)1. Virus transmitted to human in mosquito saliva

2. Virus replicates in regional nodes

3. Virus infects white blood cells and lymphatic tissues

4. Virus released and circulates in blood

Replication and Replication and TransmissionTransmission

of Dengue Virus (Part 2)of Dengue Virus (Part 2)5. Second mosquito ingests virus with blood

6. Virus replicates in mosquito midgut and other organs, infects salivary glands

7. Virus replicates in salivary glands

Dengue Clinical Dengue Clinical SyndromesSyndromes

Undifferentiated febrile illnessUndifferentiated febrile illness Classic dengue feverClassic dengue fever Dengue hemorrhagic feverDengue hemorrhagic fever Dengue shock syndromeDengue shock syndrome Other unusual syndromesOther unusual syndromes

Undifferentiated FeverUndifferentiated Fever

May be the most common May be the most common manifestation of denguemanifestation of dengue

Most infections in children under 15 Most infections in children under 15 years are asymptomatic or minimally years are asymptomatic or minimally symptomaticsymptomatic

Often accompanied by Often accompanied by maculopapular rash and URIs, maculopapular rash and URIs, especially pharyngitisespecially pharyngitis

Classic Dengue FeverClassic Dengue Fever Older children, adolescents, and adultsOlder children, adolescents, and adults Incubation period 3 to 14 days (usual 4 to 7) after Incubation period 3 to 14 days (usual 4 to 7) after

bitebite Sudden onset of fever in all patients; lasts 5 to 7 Sudden onset of fever in all patients; lasts 5 to 7

daysdays Frontal headache and retro-orbital painFrontal headache and retro-orbital pain Severe myalgias and arthralgias (“break bone Severe myalgias and arthralgias (“break bone

fever”)fever”) Maculopapular rash in about 50 %Maculopapular rash in about 50 % Nausea/vomiting; taste aberrationsNausea/vomiting; taste aberrations Leukopenia, thrombocytopenia, elevated LFTs, Leukopenia, thrombocytopenia, elevated LFTs,

and hyponatremiaand hyponatremia

Hemorrhagic Hemorrhagic manifestations of denguemanifestations of dengue

Skin hemorrhages: petechiae, purpura, Skin hemorrhages: petechiae, purpura, ecchymosesecchymoses

Gingival and nasal bleedingGingival and nasal bleeding GI bleeding: hematemesis, melena, GI bleeding: hematemesis, melena,

hematocheziahematochezia HematuriaHematuria Gum bleeding, epistaxis; menorrhagia Gum bleeding, epistaxis; menorrhagia

less commonless common Positive tourniquet test for capillary Positive tourniquet test for capillary

fragilityfragility

Tourniquet testTourniquet test Inflate blood pressure Inflate blood pressure

cuff to a point cuff to a point midway between midway between systolic and diastolic systolic and diastolic for 5 minutesfor 5 minutes

Positive test: 20 or Positive test: 20 or more petechiae in a more petechiae in a 1-in square patch on 1-in square patch on the forearmthe forearm

Dengue hemorrhagic Dengue hemorrhagic feverfever

Primarily a disease of children < 15Primarily a disease of children < 15 Begins as fever subsides; patients get Begins as fever subsides; patients get

restless or lethargic, exhibit bleeding restless or lethargic, exhibit bleeding manifestations, and have abdominal pain manifestations, and have abdominal pain and vomitingand vomiting

Hallmark of DHF is really capillary Hallmark of DHF is really capillary leakage, not hemorrhageleakage, not hemorrhage

Autopsies show serous effusions of Autopsies show serous effusions of pericardial, peritoneal, and fluid spaces pericardial, peritoneal, and fluid spaces as well as petechial hemorrhages over as well as petechial hemorrhages over most organsmost organs

PEI = A/B x 100

Pleural effusionPleural effusion

Clinical Case Definition Clinical Case Definition forfor

Dengue Hemorrhagic Dengue Hemorrhagic FeverFever

Fever, or recent history of acute feverFever, or recent history of acute fever Hemorrhagic manifestationsHemorrhagic manifestations Low platelet count (100,000/mmLow platelet count (100,000/mm33 or or

less)less) Objective evidence of “leaky Objective evidence of “leaky

capillaries:”capillaries:” elevated hematocrit (20% or more over elevated hematocrit (20% or more over

baseline)baseline) low albuminlow albumin pleural, peritoneal, or pericardial effusionspleural, peritoneal, or pericardial effusions

4 Necessary Criteria:4 Necessary Criteria:

Signs and Symptoms Signs and Symptoms in 57 Hospitalized in 57 Hospitalized

Cases of DHF, Puerto Cases of DHF, Puerto Rico, 1990 - 1991Rico, 1990 - 1991

SIGNS AND SYMPTOMS FREQUENCY PERCENT

Fever 57 100 %Rash 27 47.4%Hepatomegaly 6 10.5%Effusions 3 5.3%Frank shock 3 5.3%Coma 2 3.5%Any hemorrhage 57 100 %

Hemorrhagic Signs Hemorrhagic Signs and Symptoms in 57 and Symptoms in 57 Hospitalized Cases of Hospitalized Cases of

DHF, Puerto Rico, DHF, Puerto Rico, 1990 - 19911990 - 1991

SIGNS & SYMPTOMS FREQUENCY PERCENT

Microscopic hematuria 28 51.9%Petechiae 26 45.6%Epistaxis 13 22.8%Gingival hemorrhage 8 14.0%Blood in stools 8 14.0%Positive tourniquet test 5 31.3%

Hemorrhagic Signs Hemorrhagic Signs and Symptoms in 57 and Symptoms in 57 Hospitalized Cases of Hospitalized Cases of

DHF, Puerto Rico, DHF, Puerto Rico, 1990 - 19911990 - 1991

SIGNS & SYMPTOMS FREQUENCY PERCENT

Blood in vomitus 4 7.0%Bleeding venipuncture 4 7.0%Hemoptysis 3 5.3%Vaginal hemorrhage 2 3.5%Gross hematuria 2 3.5%Other hemorrhage 2 3.5%

Warning signs in DHF Warning signs in DHF that shock is impendingthat shock is impending

Abdominal pain - intense and Abdominal pain - intense and sustainedsustained

Persistent vomitingPersistent vomiting Abrupt change from fever to Abrupt change from fever to

hypothermia, with sweating and hypothermia, with sweating and prostrationprostration

Change in level of consciousness Change in level of consciousness (restlessness or somnolence)(restlessness or somnolence)

Sudden decrease in platelet countSudden decrease in platelet count

Clinical Case Definition Clinical Case Definition for Dengue Shock for Dengue Shock

SyndromeSyndrome 4 criteria for DHF plus…4 criteria for DHF plus… Evidence of circulatory failure Evidence of circulatory failure

manifested indirectly by all of the manifested indirectly by all of the following:following: Rapid and weak pulseRapid and weak pulse Narrow pulse pressure (Narrow pulse pressure ( 20 mm Hg) 20 mm Hg) OR OR

hypotension for agehypotension for age Cold, clammy skin, altered mental statusCold, clammy skin, altered mental status

Frank shock is direct evidence of Frank shock is direct evidence of circulatory failurecirculatory failure

Who is at risk for DHF Who is at risk for DHF and DSS?and DSS?

Major factor is pre-existing anti-dengue Major factor is pre-existing anti-dengue antibodyantibody previous infectionprevious infection maternal antibodies in infantsmaternal antibodies in infants

Virus strain and serotype (DEN-2>3>4>1)Virus strain and serotype (DEN-2>3>4>1) Age (youngest and oldest more likely)Age (youngest and oldest more likely) Host genetics (HLA determined Host genetics (HLA determined

susceptibility)susceptibility) Hypothesis of Hypothesis of antibody-dependent antibody-dependent

enhancementenhancement

Neutralizing antibody to Dengue 1 virus

Dengue 1 virus 1

Homologous Homologous Antibodies Form Antibodies Form Non-infectious Non-infectious

ComplexesComplexes

Non-neutralizing antibody

1 Complex formed by neutralizing antibody and virus

Non-neutralizing antibody to Dengue 1 virus

Dengue 2 virus

Heterologous Heterologous Antibodies Form Antibodies Form

Infectious Infectious ComplexesComplexes

Complex formed by non-neutralizing antibody and virus

Heterologous Complexes Heterologous Complexes Enter More Monocytes, Enter More Monocytes, Where Virus ReplicatesWhere Virus Replicates

Non-neutralizing antibody

Dengue 2 virus 2

Complex formed by non-neutralizing antibody and Dengue 2 virus

……infected monocytes release infected monocytes release vasoactive substancesvasoactive substances

……results in an amplified cascade of results in an amplified cascade of cytokines and complement activationcytokines and complement activation

……causing endothelial dysfunction, causing endothelial dysfunction, platelet destruction, and platelet destruction, and consumption of coagulation factorsconsumption of coagulation factors

……leading to plasma leakage and leading to plasma leakage and hemorrhagic manifestationshemorrhagic manifestations

Cases/hospitalizations – Cases/hospitalizations – Brazil Brazil

(Siquiera, et al; Emerging Infectious Diseases; Vol. 11, (Siquiera, et al; Emerging Infectious Diseases; Vol. 11, No. 1, p 50)No. 1, p 50)

Other unusual Other unusual syndromessyndromes

EncephalopthyEncephalopthy Mono- and polyneuropathiesMono- and polyneuropathies Transverse myelitis Transverse myelitis MyocarditisMyocarditis ParotitisParotitis Hepatic damage and jaundiceHepatic damage and jaundice Severe GI hemorrhageSevere GI hemorrhage

Making the Making the diagnosisdiagnosis

Travel HistoryTravel History Important for assessment of symptomatic Important for assessment of symptomatic

patients in non-endemic areaspatients in non-endemic areas Determine whether the patient traveled to Determine whether the patient traveled to

a dengue-endemic areaa dengue-endemic area Determine when the travel occurredDetermine when the travel occurred

If the patient developed fever more If the patient developed fever more than 2 weeks after travel, eliminate than 2 weeks after travel, eliminate dengue from the differential dengue from the differential diagnosisdiagnosis

Other Flavivirus infections Other Flavivirus infections in travelersin travelers

Yellow fever Yellow fever (Sub-Saharan Africa; (Sub-Saharan Africa; South South America)America)

Japanese encephalitis Japanese encephalitis (Asia)(Asia) Tick-borne encephalitis Tick-borne encephalitis (Europe)(Europe) West Nile fever West Nile fever (Africa; Middle East; (Africa; Middle East;

Europe; Europe; North America)North America) Dengue fever Dengue fever (Asia; Central, South, (Asia; Central, South,

and North and North Americas; Pacific; Africa)Americas; Pacific; Africa)

Differential diagnosis of Differential diagnosis of denguedengue

Arboviruses Arboviruses Chikungunya (often mistaken for dengue in SE Chikungunya (often mistaken for dengue in SE

Asia)Asia) Viral diseasesViral diseases

Hantavirus; measles; rubella; enteroviruses; Hantavirus; measles; rubella; enteroviruses; influenzainfluenza

Bacterial diseasesBacterial diseases Meningococcemia; scarlet fever; typhoidMeningococcemia; scarlet fever; typhoid

Parasitic diseasesParasitic diseases Leptospirosis; rickettsial diseases; malariaLeptospirosis; rickettsial diseases; malaria

Clinical EvaluationClinical Evaluation

Blood pressureBlood pressure Evidence of bleeding in skin or Evidence of bleeding in skin or

other sitesother sites Hydration statusHydration status Evidence of increased vascular Evidence of increased vascular

permeability-- pleural effusions, permeability-- pleural effusions, ascitesascites

Tourniquet testTourniquet test

Tourniquet testTourniquet test Inflate blood Inflate blood

pressure cuff to a pressure cuff to a point midway point midway between systolic and between systolic and diastolic for 5 diastolic for 5 minutesminutes

Positive test: 20 or Positive test: 20 or more petechiae in a more petechiae in a 1-in square patch on 1-in square patch on the forearmthe forearm

Laboratory TestsLaboratory Testsin Dengue Feverin Dengue Fever

Clinical laboratory testsClinical laboratory tests CBC--WBC, platelets, hematocritCBC--WBC, platelets, hematocrit AlbuminAlbumin Liver function testsLiver function tests Urine--check for microscopic hematuriaUrine--check for microscopic hematuria

Dengue-specific testsDengue-specific tests Virus isolationVirus isolation SerologySerology

Temperature, Virus Temperature, Virus Positivity and Anti-Positivity and Anti-

Dengue IgM , by Dengue IgM , by Fever DayFever Day

Dengue IgMMean Max. Temperature Virus

Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.

Fever Day

-4 -3 -2 -1 0 1 2 3 4 5 6

TreatmentTreatment

Mild and classic dengueMild and classic dengue

Outpatient treatmentOutpatient treatment Acetaminophen (not aspirin or Acetaminophen (not aspirin or

NSAIDs)NSAIDs) Fluid replacementFluid replacement BedrestBedrest Avoid injectionsAvoid injections Recheck platelets and Hct every 24 Recheck platelets and Hct every 24

hourshours

DHF and DSSDHF and DSS If platelets < 100,000/mmIf platelets < 100,000/mm3 3 or hemorrhagic or hemorrhagic

manifestations, admit to hospitalmanifestations, admit to hospital Typically occurs on day of defervescence (4 Typically occurs on day of defervescence (4

to 7 days after onset of illness); decrease in to 7 days after onset of illness); decrease in platelets precedes rise in Hct (diagnostic of platelets precedes rise in Hct (diagnostic of dengue)dengue)

Rise in Hct of 20% indicates considerable Rise in Hct of 20% indicates considerable plasma loss and requires ICU care and IVFsplasma loss and requires ICU care and IVFs

Worsening shock requires colloid or Worsening shock requires colloid or crystalloidcrystalloid

Monitor Hct and reduce IVFs when Hct < 40Monitor Hct and reduce IVFs when Hct < 40

Rehydrating Patients Rehydrating Patients > 40 kg> 40 kg

Volume required for rehydration is Volume required for rehydration is twicetwice the recommended maintenance the recommended maintenance requirementrequirement

Formula for calculating maintenance Formula for calculating maintenance volume: volume: 1500 + 20 x (weight in kg - 20)1500 + 20 x (weight in kg - 20)

For example, maintenance volume for 80 For example, maintenance volume for 80 kg patient is: 1500 + 20 x (80-20) = kg patient is: 1500 + 20 x (80-20) = 2700 ml2700 ml

The rehydration volume would be 2 x The rehydration volume would be 2 x 2700, or 2700, or 5400 ml (225ml/hr)5400 ml (225ml/hr)

Mosquito avoidanceMosquito avoidance

Only needed until fever subsides, to Only needed until fever subsides, to prevent prevent Aedes aegyptiAedes aegypti mosquitoes mosquitoes from biting patients, acquiring the from biting patients, acquiring the virus, and biting othersvirus, and biting others

Keep patient indoors or in a Keep patient indoors or in a screened sickroomscreened sickroom

Remember that virus positivity Remember that virus positivity follows the feverfollows the fever

Temperature, Virus Temperature, Virus Positivity and Anti-Positivity and Anti-

Dengue IgM , by Fever Dengue IgM , by Fever DayDay

Dengue IgMMean Max. Temperature Virus

Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.

Fever Day

-4 -3 -2 -1 0 1 2 3 4 5 6

PrognosisPrognosis

Classic dengueClassic dengue full recovery; convalescence may take weeks full recovery; convalescence may take weeks

because of asthenia and depressionbecause of asthenia and depression Dengue hemorrhagic feverDengue hemorrhagic fever

10-20% mortality without aggressive fluid 10-20% mortality without aggressive fluid replacementreplacement

0.2% with treatment0.2% with treatment Dengue shock syndromeDengue shock syndrome

> 40% mortality without aggressive fluid > 40% mortality without aggressive fluid replacementreplacement

< 1% mortality with treatment< 1% mortality with treatment

PreventionPrevention

Personal measuresPersonal measures Mosquito repellants with 20% to 30% Mosquito repellants with 20% to 30%

DEET DEET Protective clothing that is permethrin-Protective clothing that is permethrin-

impregnatedimpregnated Insecticides should be applied in dark Insecticides should be applied in dark

areas indoorsareas indoors Avoid repeated travel to countries where Avoid repeated travel to countries where

dengue is endemic (to avoid exposure to dengue is endemic (to avoid exposure to another serotype)another serotype)

Eliminate containers that could contain Eliminate containers that could contain waterwater

Reasons for Dengue Reasons for Dengue Expansion in the Expansion in the

AmericasAmericas Extensive vector infestation, with Extensive vector infestation, with

declining vector controldeclining vector control Unreliable water supply systemsUnreliable water supply systems Increasing non-biodegradable Increasing non-biodegradable

containers and poor solid waste containers and poor solid waste disposaldisposal

Increased air travelIncreased air travel Increasing population density in Increasing population density in

urban areasurban areas

Historical anecdoteHistorical anecdote 1950’s and 60’s - the Pan American Health 1950’s and 60’s - the Pan American Health

Organization tried to eradicate the Organization tried to eradicate the Aedes Aedes aegypti aegypti in in Central and South America. Central and South America.

This isolated dengue fever outbreaks to parts This isolated dengue fever outbreaks to parts of the Caribbean that had no eradication of the Caribbean that had no eradication programsprograms

1970’s - the program was discontinued due to 1970’s - the program was discontinued due to incompetent funds and lack of priority in the incompetent funds and lack of priority in the political agenda political agenda

The mosquito soon started to re-infest regions The mosquito soon started to re-infest regions in which it had been nearly eradicated. in which it had been nearly eradicated.

Today - the Today - the Aedes aegypti Aedes aegypti mosquito inhabits a mosquito inhabits a broader geographical region than before broader geographical region than before eradicationeradication

Reinfestation by Reinfestation by Aedes Aedes aegyptiaegypti

1930s 1970 1998

Vector Control Methods:Vector Control Methods:Chemical ControlChemical Control

Larvicides may be used to kill Larvicides may be used to kill immature aquatic stagesimmature aquatic stages

Ultra-low volume fumigation Ultra-low volume fumigation ineffective against adult mosquitoesineffective against adult mosquitoes

Mosquitoes may have resistance to Mosquitoes may have resistance to commercial aerosol sprayscommercial aerosol sprays

Vector Control Vector Control Methods:Methods:

Biological and Biological and Environmental ControlEnvironmental Control Biological controlBiological control

Largely experimentalLargely experimental Option: place fish in containers Option: place fish in containers

to eat larvae to eat larvae Environmental controlEnvironmental control

Elimination of larval habitatsElimination of larval habitats Most likely method to be Most likely method to be

effective in the long termeffective in the long term

Community ApproachesCommunity Approaches

Define communities at riskDefine communities at risk Involvement at all levels of age, Involvement at all levels of age,

educationeducation Advantages: built-in manpower, help Advantages: built-in manpower, help

develop resources and empower develop resources and empower community organizationscommunity organizations

Disadvantages: more difficult to Disadvantages: more difficult to organize, take longer to get off the organize, take longer to get off the groundground

Example of Community Example of Community Programs: Puerto RicoPrograms: Puerto Rico

Elementary school and Head Elementary school and Head Start programs to teach Start programs to teach children about dengue controlchildren about dengue control

Public service announcementsPublic service announcements Interactive exhibit at the Interactive exhibit at the

Children’s MuseumChildren’s Museum Boy Scout merit badge Boy Scout merit badge

programprogram

Dengue Vaccine?Dengue Vaccine?

No licensed vaccine at presentNo licensed vaccine at present Effective vaccine must be tetravalent Effective vaccine must be tetravalent

(4 serotypes)(4 serotypes) Field testing of an attenuated Field testing of an attenuated

tetravalent vaccine currently tetravalent vaccine currently underwayunderway

Effective, safe and affordable vaccine Effective, safe and affordable vaccine will not be available in the immediate will not be available in the immediate futurefuture

Trouble AheadTrouble Ahead

2.5 billion people at risk world-wide2.5 billion people at risk world-wide Widespread abundance of Widespread abundance of Aedes Aedes

aegyptiaegypti in at-risk areas in at-risk areas Increasing number of DHF cases due Increasing number of DHF cases due

to reinfection to reinfection in the Americas, 50-fold increase in in the Americas, 50-fold increase in

reported cases of DHF during 1989-reported cases of DHF during 1989-1993 compared to 1984-19881993 compared to 1984-1988

SummarySummary

Dengue is the most common cause of Dengue is the most common cause of arboviral disease worldwidearboviral disease worldwide

The disease is more prevalent now The disease is more prevalent now that at any other time, and its that at any other time, and its prevalence is expected to increaseprevalence is expected to increase

A severe manifestation of dengue is A severe manifestation of dengue is dengue hemorrhagic fever, which is dengue hemorrhagic fever, which is more common after a secondary more common after a secondary infectioninfection

A cost effective vaccine is neededA cost effective vaccine is needed

Case report - finaleCase report - finale

50 year old attorney became ill 50 year old attorney became ill 6/24, 4 days after returning from 6/24, 4 days after returning from Costa RicaCosta Rica

One week later, repeat WBC One week later, repeat WBC 5800, platelets 385,0005800, platelets 385,000

Convalescent titers: IgG rose > 4 Convalescent titers: IgG rose > 4 x baseline levelx baseline level

Out of work 2 weeks; full Out of work 2 weeks; full recovery over 4 weeksrecovery over 4 weeks

CDCCDC Outbreak NoticeOutbreak Notice Released: July 19, 2005Released: July 19, 2005

““Dengue in Travelers, Costa Rica and Dengue in Travelers, Costa Rica and Other Other Tropical and Subtropical Tropical and Subtropical Regions”Regions” Florida State Health Dept. reported 4 ill Florida State Health Dept. reported 4 ill

travelers who visited Costa Rica between travelers who visited Costa Rica between June 18 and June 26June 18 and June 26

All complained of fever and headache, 3 All complained of fever and headache, 3 required hospitalizationrequired hospitalization

In response, Ministry of Health in Costa Rica In response, Ministry of Health in Costa Rica enhanced surveillance and mosquito control enhanced surveillance and mosquito control measuresmeasures

Big question…Big question…

Why did this particular attorney not Why did this particular attorney not suffer the more severe forms of suffer the more severe forms of dengue from the bite of that dengue from the bite of that annoying, bloodsucking pestannoying, bloodsucking pest??

Professional courtesyProfessional courtesy

The Perils of Travel Jeffrey H. Phillips, M.D., F.A.C.P. Internal Medicine Clinical Update October...

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