OUR PATIENT

PBL SEMINAR FEVER IN A RETURNED TRAVELLER

OUR PATIENT CASEOur patient is Jenny Randall, a 23 y.o. female student who presents to her local doctor with cough and fever having recently returned from a 3 week holiday

IMPORTANT

Whats common is commonThe diagnosis is MALARIA MALARIA MALARIA until proven otherwise. 3Explanation for points:Just because she recently travelled doesnt mean that her fever is due to an exceedingly rare fungaemia picked up from an unusual breed of lizard. It is important to take a focused travel history as well as a normal history as though she never travelled at all. It s one of the few infections that can kill young healthy people within hours.

How to take a History from a Returned TravellerFeverWWQQAAB

5Chronic > 2 weeks duration

Quality: Pattern: Constant, every 48 hours, biphasic, intermittent

Quantity:High vs lowHave they taken their temperature?

Quality (pattern), Quantity (Height) etc are not that good signs and are often not used as they are often altered by drugs, and often vary between people for the same diseases

Aggravating allieviating factors: Drugs? (panadol etc)

Associated symptoms:Rash, generalized or multiple adenopathy, splenomegaly, anaemia, jaundice, polyarthritis etc can all indicate which infection it isSystemic symptoms: fevers, chills, night sweats, rigors, muscle aches, loss of weight (how much over what period of time). Can all be important clues as to how severe the infection is etc.

Travel History: CHOCOLATESCountry of birthHousingOccupationContactsOther drugsLeisure timeAnimalsTravel Eating and Drinking Sexual history

6Country of birthHousingDetails of living conditions en route and during the stay (fly screens, near water etc)OccupationContactsClose contact with others such as crowded living and sleeping arrangementsContact with other sick peopleOther drugsSelf-treatment with antibioticsIn particular, malaria may be suppressed by azithromycin, doxycycline, quinolones or clindamycinAsk have you ever injected drugs? as people can take things on holidays they often wouldntLeisure timeExposure to fresh water or surface water in recreational or other settings (schistosomiasis or leptospirosis)Water (swimming, wading, rafting, bathing in streams etc)Exploration of cavesDigging or soil contactAnimalsBites or licks to broken skin, direct contact, proximity to birds/rodentsTravel - Day by day travel itineraryFind out every locale and country visited as well as exact dates spent in each (Determine first possible and last possible dates of exposure. This gives you the shortest and longest incubation periods and therefore can help eliminate many diagnoses.When: season/month/yearAreas visited: urban or rural; altitudeDid they have a pre-travel assessment? Anti-malarial intakePill by pill history name, dose of all drugs.Immunization historyBoth of the last two do not exclude the possibility of the patient having it. Efficacy of the vaccine in the individual, compliance, and local drug resistance all need to be considered.The doctor can check the CDC website which provides country specific up to date information about outbreaksEating and Drinking Detailed dietary history (budget travel high risk eating habits can indicate common enteric pathogens).Specific foods: unpasteurized dairy products (Brucella, Campylobacter, Salmonella), shellfish (vibrios, enteric viruses, viral hepatitis), uncooked beef such as carpaccio )toxoplasma, campylobacter, Escherichia coli), undercooked fish (vibrios), and undercooked pork of game meat (trichinosis).Sexual historyNew sexual partners, needles, or bloodDates of sexual contact, with whomDid they use a condom 100%, 50% or less than 50% of the time

HOPCTravel History: CHOCOLATESTake Jennys HistoryTravel History: CHOCOLATESCountry of birthHousingOccupationContactsOther drugsLeisure timeAnimalsTravel Eating and Drinking Sexual history

8Country of birthHousingDetails of living conditions en route and during the stay (fly screens, near water etc)OccupationContactsClose contact with others such as crowded living and sleeping arrangementsContact with other sick peopleOther drugsSelf-treatment with antibioticsIn particular, malaria may be suppressed by azithromycin, doxycycline, quinolones or clindamycinAsk have you ever injected drugs? as people can take things on holidays they often wouldntLeisure timeExposure to fresh water or surface water in recreational or other settings (schistosomiasis or leptospirosis)Water (swimming, wading, rafting, bathing in streams etc)Exploration of cavesDigging or soil contactAnimalsBites or licks to broken skin, direct contact, proximity to birds/rodentsTravel - Day by day travel itineraryFind out every locale and country visited as well as exact dates spent in each (Determine first possible and last possible dates of exposure. This gives you the shortest and longest incubation periods and therefore can help eliminate many diagnoses.When: season/month/yearAreas visited: urban or rural; altitudeDid they have a pre-travel assessment? Anti-malarial intakePill by pill history name, dose of all drugs.Immunization historyBoth of the last two do not exclude the possibility of the patient having it. Efficacy of the vaccine in the individual, compliance, and local drug resistance all need to be considered.The doctor can check the CDC website which provides country specific up to date information about outbreaksEating and Drinking Detailed dietary history (budget travel high risk eating habits can indicate common enteric pathogens).Specific foods: unpasteurized dairy products (Brucella, Campylobacter, Salmonella), shellfish (vibrios, enteric viruses, viral hepatitis), uncooked beef such as carpaccio )toxoplasma, campylobacter, Escherichia coli), undercooked fish (vibrios), and undercooked pork of game meat (trichinosis).Sexual historyNew sexual partners, needles, or bloodDates of sexual contact, with whomDid they use a condom 100%, 50% or less than 50% of the time Jennys History Ms Jenny Randall, a previously well 23 year old medical student, presents to her local doctor with a cough and fever.Jenny recently returned from a 3 week trip to Thailand, Cambodia and Vietnam. In the 3 days leading up to her presentation at the clinic, Jenny experienced the following symptoms:feversrigoursmyalgiamild non-productive coughmalaisemild headacheNo relevant past medical historyFamily history of CVD- father died of AMI at 58

MedicationsOCPParacetamol for feverNKDA

Social HistorySmokes 10-20 cigarettes/day, no ETOH, one regular and one new sexual partner in past 6 months, uses condoms 100 % of the time

What stands out as a red flag? Why?

9TRAVEL SPECIFIC QUESTIONSBorn in AustraliaTravelled to Vietnam via Thailand and Cambodia for 3 weeks during the hot/rainy seasonReturned for two weeks before becoming unwellStayed in budget, sometimes crowded accommodation throughout recent travelExposure to water, mosquitoes, fliesRecent contact has a 'cold'Took prophylactic Doxycycline for one week before discontinuing Had pre-travel Typhoid and HepA immunisation and previous HepB immunisationOften prepared own food, no GI symptoms

Can we rule out Malaria, Hep A, B and Typhoid? Malaria prophylaxis will suppress Malaria but wont cure itImmunisations arent 100% effective10!~RED FLAG~!

What symptom stands out as a red flag?

RIGORS!

What are rigors?

Episodes of uncontrollable shakes with or without teeth chattering lasting 15 minutes or more.

What causes them?Bacterial sepsis e.g. From biliary sepsis or pyelonephritis, visceral abscesses, pneumoniaMalariaInfluenza

Why can we not ignore rigors?Causes can be immediately life threatening and are treatable!! !~Admit patient with rigors to hospital~!

Pyrexia of Unknown Origin (PUO)Approach: - identify causeDetailed history and regular examinationConfirm temperature objectively, ?admission, ?physiological with circadian patternGuide investigation based on initial test resultsBlind investigation may be necessaryFBE, ESR, U+E, CRP, LFT, ANA, Rh Fx, TFTRegular cultures (any fluid blood, sputum, urine, stool, CSF)CXR, CTA, echoCT, IVP, MRI, PETTreatment ideally symptomatic prior to DxEmpirical A/B therapy may mask an infectious DxEmpirical steroid therapy may mask inflammatory response w/o treating cause Undiagnosable PUO Sx usually spontaneously resolve, good prognosisExcluded from case differential

Definition: In adults: T>38.3 for>3 weeks with no known origin despite appropriate Ix.CausesInfectionPyogenic AbscessTBIEToxoplasmosisEBVCMVHIVBrucellosisLyme DiseaseMalignancyLymphomaLeukaemiaRCCHCCCTDAdult Stills diseaseRASLEWegeners granulomatosisGiant cell arteritisMiscDrug FeversThyrotoxicosisIBDSarcoidosisGranulomatous hepatitisFactitious feverFamilial Mediterranean feverIdiopathicExamination of a Returned TravellerSpecial points for an ID ExGen InspectionRoomSputum cupO2IV anything runningDrain tubeCatheter check urineTemp chartPatientDistress (RR, diaphoretic, conscious state)Rash blanching/non-Track marks IVDUAny lines sepsis?Weight loss chronic illnessHandsJanewaySplintersOslers nodesErythemaTrack marksBruising, petechiaePhlebitisArthropathy, raynauds - CTD

FaceEyes Roth spots (fundoscopy), pallor, jaundice (BW fever)Mouth hygeine, ginigivitis, abscessNeck lymphadenopathyChestCrepitations, consolidationPraecordiumNew murmurAbdomenTenderness? localised?OrganomegalyrashesGenitourinaryStool sampleUrinalysisDischargeorchitisLegsRashulcers

Signs in a returned TravellerOn examination:

Chest clear. Full CVS, respiratory and abdominal examinations NADNo rashes, joints appeared normal.VitalsHR 72BP 120/60RR 16T 36.2With these history and examination findings, Jenny was sent home with a suspected viral URTI.The next day, Jenny re-presents with continuing fevers, having taken her own temperature measuring 36.9 that morning.

Timeline of Jennys feverDay 1 onset of disease T?Day 4 visit doctor 36.2Day 5 10am 36.9Day 5 afternoon 36.9Day 5 night 38.5

*NO FEVER RECORDED until day 5*Doesn't always follow typical pattern in all patientsTypically may be afebrile for daysAtypically (common) may be febrile or afebrile the entire length of the diseaseAccurate recording procedureHx of fever given by reliable witness should not be ignored even if it is recorded as afebrile.

Typical malarial fever patterns- not necessarily useful diagnosticallyThe Pattern of FeverOn day 4 after her first presentation to the doctor, Jenny is sent home with a suspected viral URTIOn day 5, Jenny re-presents with continuing fevers17DDx??DDx!!Malaria (parasite) Typhoid (bacteria)Dengue fever (virus)Hepatitis AWe want to rule these out before progressing to investigate for other conditions common in returned travellers.

THE BIG FOUROther Infections To Be Considered in Returned TravellersDeveloping CountriesBacterial sepsis other than typhoid (such as meningococcal sepsis, sepsis from abdominal organ perforation, pneumonia, urosepsis)TBDysentrySchistosomiasisAmoebic liver abscessTick typhusViral haemorrhagic fevers other than DengueWorld WideInfluenzaAtypical pneumoniaURTI/viral infectionSTI including acute HIV infectionUTIPyelonephritis

Bacterial sepsis- no focal signs and rigoursTB- no haemoptysisDysentry- no diarrhoeaSchistosomiasis- no abdo pain, D or VAmoebic liver abscess- no RUQ pain

Influenza- presentation matchesPneumonia- rigours can occur in typical but resp exam NAD which could point to atypicalURTI-presentation matchesSTI- unlikely considering sexual history and condom useUTI- no urinary symptomsPyelonephritis- no loin pain or urinary symptomsViral haemorrhagic fevers- more common in travellers from Africa, no bleeding obvious20

MalariaDengue FeverTyphoid FeverHepatitis ADefinitionProtozoa injected by Anopheles mosquitoes multiply in RBCs causing haemolysis, sequestration and cytokine release.RNA flavivirus (4 types) causing sudden fever, extreme myalgias and arthralgias.Bacterial infection with salmonella typhi (G- bacillus), causing severe diarrhoea Hepatits A virus (HAV), that is not chronic or progressive and has no permanent effect on liver, acutely causes liver damage using bodys own immune response rather than viral cytotoxicity.Mode of TransmissionMosquito vector, transfusion, vertical, needlestickAedes mosquitoesFaecal-oral route, complicated by asymptomatic typhoid (unknowing carriers)Faecal-oral route,DIFFERENTIALSSymptoms and signs MalariaDengueTyphoidHepatitis Anon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers (periodic)chillsfaintsrigors initially

jaundicehepatomegalysplenomegaly

MALARIA ask audience if they are familiar with any malaria signs or symptoms malaria symptoms are very vague and non-specific, they could be attributed to many diseases and this proves diagnosing malaria difficult an important point to note is that malaria often presents atypically malaria is not often associated with GI symptoms (which as you are about to see our other big four commonly present with) reiterate: fever in a returned traveller is malaria until proven otherwise23Symptoms and signs MalariaDengueTyphoidHepatitis Anon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers (periodic)chillsfaintsrigors initially

jaundicehepatomegalysplenomegaly

feverheadachemyalgiaabdominal painnauseavomitingdiarrhoearash

DENGUE ask audience if they are familiar with any dengue signs or symptoms dengue rash is not always (maculopapular with islands of sparing) A hemorrhagic rash of characteristically bright red pinpoint spots, known as petechiae can occur later during the illness and is associated with thrombocytopenia (lower limbs and chest commonly) milder cases of dengue fever are often misdiagnosed as influenza24Symptoms and signs MalariaDengueTyphoidHepatitis Anon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers (periodic)chillsfaintsrigors initially

jaundicehepatomegalysplenomegaly

feverheadachemyalgiaabdominal painnauseavomitingdiarrhoearashfever (progresses slowly)malaise headacheabdominal painsdry coughconstipation or diarrhoearose spots on trunk

bradycardialymphadenopathysplenomegaly

25Symptoms and signs MalariaDengueTyphoidHepatitis Anon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers (periodic)chillsfaintsrigors initially

jaundicehepatomegalysplenomegaly

feverheadachemyalgiaabdominal painnauseavomitingdiarrhoearashfever (progresses slowly)malaise headacheabdominal painsdry coughconstipation or diarrhoearose spots on trunk

bradycardialymphadenopathysplenomegaly

fevermalaiseanorexianauseaarthralgiaabdominal paindiarrhoea itching

jaundicehepatomegalysplenomegalyHEPATITIS A symptoms may reappear over the subsequent 6 9 months

WHAT DID JENNY PRESENT WITH?? > next slide26Jennys symptoms and signs MalariaDengueTyphoidHepatitis Anon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers chillsfaintsrigors

jaundicehepatomegalysplenomegaly

feverheadachemyalgiaabdominal painnauseavomitingdiarrhoearashfevermalaise headacheabdominal painsdry coughconstipation or diarrhoearose spots on trunk

bradycardialymphadenopathysplenomegaly

feversmalaiseanorexianauseaarthralgiaabdominal paindiarrhoea itching

jaundicehepatomegalysplenomegalyJENNY RANDALL Jenny presented with rigors, fever, myalgia and chills, so essentially she could have been infected with any of our big four however, she displayed most symptoms in common with malaria she reported a clear history of rigors which also indicates that it was most likely to be malaria as none of the others present with rigors reiterate: fever in a returned traveller is malaria until proven otherwise27Fever in the tropical traveller 6 weeksundifferentiated feverMalariaTyphoidLeptospirosisDengue feverRickettsiaeAcute HIV infectionMalariaTyphoidLeptospirosisHepatitis A or EAcute schistosomiasisAcute HIV infectionMalariaHepatitis B or EKala-azarLymphatic filariasisSchistosomiasisAmoebic liver abscessfever with CNS signsViral/bacterial meningitis + encephalitisEast African TrypanosomiasisPoliomyelitisEast African TrypanosomiasisRabiesRabiesfever with chest signsInfluenzaLegionellosisQ feverAcute histoplasmosisSARSTuberculosis Q feverTuberculosisIncubation PeriodsIncubation period: time elapsed between exposure to a pathogenic organism and the onset of symptoms Jenny returned home 2 weeks prior to feeling unwell (14 day incubation)no actual fever recorded until 5 days later however atypical presentation is commonIncubation PeriodsMalariaDengueTyphoidHepatitis AP. falciparum 6-21d (typically 7-10d)P. vivax 10-17dP. ovale 10-17dP. malariae 18-40d3-14 days3-21 days

2-6 weeks

most patients with malaria present within 2 monthsIf fevers start >2wks after leaving a dengue areaor lasts >2wks dengue can be ruled out

typically 8-14 days

typically 28 days

WHEN DID JENNY PRESENT? Jenny reported feeling unwell 2 weeks after returning from Vietnam (14 days) Her first fever was recorded on day 19, but she reported a clear history of rigors, chills and fevers previouslyWHAT DOES THIS RULE OUT? NOTHING Despite that fact that Plasmodium Falciparum usually presents within 10 days, a later presentation like Jennys is often a barrier to early diagnosis Thick and thin blood films among further investigations are needed to determine what exactly Jenny has been infected with

30MalariaDengue FeverTyphoid FeverHepatitis ADefinitionProtozoa parasite.RNA flavivirus Bacterial infection Hepatits A virus (HAV)Mode of TransmissionMosquito vector, transfusion, vertical, needlestickAedes mosquitoesFaecal-oral route, complicated by asymptomatic typhoid (unknowing carriers)Faecal-oral route,Incubation periodP. falciparum 6-21d (typically 7-10d)P. vivax 10-17dP. ovale 10-17dP. malariae 18-40d3-14 days3-21 days2-6 weeksSigns and Symptomsnon-specific flu-like symptoms: headachemalaisemyalgiaanorexiafevers (periodic)chillsfaintsrigors initially

jaundicehepatomegalysplenomegalyfeverheadachemyalgiaabdominal painnauseavomitingdiarrhoearashfever (progresses slowly)malaise headacheabdominal painsdry coughconstipation or diarrhoearose spots on trunk

bradycardialymphadenopathysplenomegalyfevermalaiseanorexianauseaarthralgiaabdominal paindiarrhoea itching

jaundicehepatomegalysplenomegalyDIFFERENTIALS31Falciparum Causes almost all severe disease (~85%). Characterised by systemic complications such as cerebral malaria and anaemia.

2) Vivax Uncommonly causes severe disease, but overall infection rates are as common as Falciparum. Can cause chronic relapsing malarial disease.

3) Ovale Uncommon cause of disease, and even then clinical picture is not as severe. Can cause relapsing disease as well.

4) Malariae Similar to Ovale.

BASIC PATHOPHYS.STRAINS OF MALARIATHE MALARIAL CYCLE

1) MOSQUITO VECTOR

2) EXTRA-ERYTHROCYTIC3) ERYTHROCYTIC PHASEImmunological evasion by Malaria Malaria avoids WBCs by invading the bodys own cells and using these self antigens as a mask for infection. The body only has a chance of reacting during a lysis cycle when the parasites are free in the blood, though time is limited.Splenic removal is the only effective method of removal. Protozoal aggregation in small capillaries counters this causes complications

Malarial Immunology34Investigations of a Returned TravellerMalariaDengue FeverTyphoid FeverHepatitis ADefinitionProtozoa parasite.RNA flavivirus Bacterial infection Hepatits A virus (HAV)Mode of TransmissionMosquito vector, transfusion, vertical, needlestickAedes mosquitoesFaecal-oral route, complicated by asymptomatic typhoid (unknowing carriers)Faecal-oral route,Incubation period P. falciparum 6-21d (typically 7-10d)3-14 days3-21 days2-6 weeksSigns and symptomsnon-specific flu-like symptoms: headachemalaisemyalgiafeverheadachemyalgiaabdominal painnauseafever (progresses slowly)malaise headacheabdominal painsfevermalaiseanorexianauseaarthralgiaIx and Common Findings

Basic principles:Parasite = microscopyBacteria = cultureVirus = serologyThick and Thin Blood filmsSerology (e.g. arbovirus serology) and PCR studiesCultures - bone marrow, blood, stool, urine - bone marrow culture has highest yield Serology for anti HepA IgMDIFFERENTIALSUnder Ix and common findings:MALARIAOther Common Findings: FBE (anaemia, thrombocytopenia, rarely leukocytosis), LFT derangement, parameters suggestive of haemolysis (haptoglobin, LDH, reticulocyte count), hypoglycemia, ABG (lactic acidosis), UEC (renal failure), Urinalysis (hemoglobinuria, proteinuria, casts).Note: Rapid ward serology tests e.g. ParaSight F, can be performed to identify P. Falciparum, however they are not as sensitive as microscopy, nor do they provide a parasite count (required for management).

DENGUE FEVEROther Common Findings: FBE (thrombocytopenia, leukopenia, hematocrit increased due to plasma leakage), LFT (AST elevated, decreased albumin), deranged coag profile (prolonged PT, APTT and decreased fibrinogen), UEC (electrolyte imbalances-hyponatremia, elevated BUN), ABG (acidosis if dengue shock syndrome), positive tourniquet test (determines capillary fragility/hemorrhagic tendency, by applying blood pressure cuff and inflating it to a point between systolic and diastolic BPs for 5 mins. The test is positive if there are 10 or more petechiae per square inch). CXR may reveal pleural effusions.

TYPHOID FEVEROther Common Findings: FBE (thrombocytopenia, leukopenia, hematocrit increased due to plasma leakage), LFT (AST elevated, decreased albumin), deranged coag profile (prolonged PT, APTT and decreased fibrinogen), UEC (electrolyte imbalances-hyponatremia, elevated BUN), ABG (acidosis if dengue shock syndrome), positive tourniquet test (determines capillary fragility/hemorrhagic tendency, by applying blood pressure cuff and inflating it to a point between systolic and diastolic BPs for 5 mins. The test is positive if there are 10 or more petechiae per square inch). CXR may reveal pleural effusions.

HEPATITIS AOther Common Findings: serum transaminases/ALT rise 22-40d after exposure, IgM rises from approx. day 25 and signifies recent infection. IgG remains detectable for life and appears soon after IgM - IgG means immunity has been acquired and appears normally in immunized patients. LFT (raised ALT, AST and raised ALP in the acute stages of infection, raised bilirubin, decreased serum albumin), Coag derangement (raised PT = very bad - may indicate hepatic failure, particularly in the setting of encephalopathy), FBE (lymphocytosis, rarely pancytopenia)

36Jennys Ix FindingsFBEHB 110, WCC 7.0, Plt 110HB 100, WCC 7.3, Plt 90HB 90, WCC 7.2, Plt 96HB 95, WCC 7.2, Plt 115UECsNa 140, K 4.0, Ur 7.0, Cr 110LFTsMildly elevated ALT and bilirubin, otherwise normalAtypical pneumonia - Legionella, Chlamydia species, Mycoplasma pneumoniae, Pneumocystis jiroveci serology - pendingCXR - clearMalarial Thick and Thin FilmNegativePositive for plasmodium falciparum, parasite count 0.2%parasite count 0.1%parasite count 0%Hep A serology - Total Ab positive, IgM negativeHep B serology - Surface Antibody positive, surface negativeArbovirus (dengue) serology - negativeHIV serology - negativePregnancy Test - negative37Malarial Thick and Thin Blood Films3 thick and thin smears 12-24hrs apart should be obtainedHighest yield of peripheral parasites occurs during or soon after a fever spike; however smears should not be delayed to await a fever spike.Thin Films - qualitative (speciation)Thick Films - quantitative (parasite count)

THIN FILMSDrop of blood on specimen slideClean spreader slide held at an angle of 45 degrees over droplet of bloodSpread the blood along the specimen slide evenly and thinlyWait until blood sample is dry before you fix the sample using methanol, then stain.THICK FILMSDrop of blood on specimen slideUse another clean slide to spread the droplet of blood in a circle approx. 1-2cm in diameterWait until blood sample is dry before staining (should not be fixed)

38FindingsP falciparumP vivaxP ovaleP malariaeOnly early forms present in peripheral bloodYesNoNoNoMultiply-infected RBCsOftenOccasionallyRareRareAge of infected RBCsRBCs of all agesYoung RBCsYoung RBCsOld RBCsSchffner dotsNoYesYesNoOther featuresCells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms.Late trophozoites develop pleomorphic cytoplasm.Infected RBCs become oval with tufted edges.Bandlike trophozoites are distinctive.Determining types of malariaHistological Differences39

SlidesPlasmodium falciparumP vivaxP ovaleP malariaeNormal

Epidemiology and Risk Factors of MalariaIncidence3 billion people (1/2 worlds population) living in areas at risk

1-2 million deaths per year

5th most common cause of death from infection worldwide

2nd most common cause of death from infection in AfricaMalaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries.Approximately 3 billion people (1/2 of the worlds population) are living in areas at risk of Malaria transmission.Each year Malaria causes approximately 1-2 million deaths.Malaria is the 5th most common cause of death from infectious diseases worldwide (after respiratory infections, HIV/AIDS, diarrheal diseases, and tuberculosis)Malaria is the 2nd leading cause of death from infectious diseases in Africa, (after HIV/AIDS)43Where malaria occurs

Most countries in the tropics107 countriesWhere malaria occursMalaria occurs throughout most countries in the tropicsIn total there are 107 countries in which Malaria is transmitted.This map shows an approximation of the parts of the world where malaria transmission occurs

The red shows the countries where Malaria transmission occurs throughoutYellow indicates the countries in which Malaria transmission only occurs in some parts. Generally this is in rural areas44Transmission patternsStable transmissionUnstable transmissionFluctuationYear round infectionLower levels of infectionClimateWarmer conditionsLess seasonal variationCloser to the equatorTemperature a bit coolerClimate varies with seasonClinical manifestationChildren affected the mostMostly asymptomatic in adultsSymptomatic disease occurs at all agesImmunity HighLowEpidemicUnlikelyLikelyEfficiency of mosquitoEfficient vectorInefficient vectorMain parasiteP. falciparumP. vivaxSocial and Economic TollCost to individualsCost to governmentWhere malaria is found depends mainly on climatic factors: The temperature, humidity, and rainfall must be suitable for anophelesmosquitoesto survive and multiply.Transmission can be categorised as either stable or unstable depending on the climate of the region.Stable transmissionYear round infection is termed stable transmissionStable transmission generally occurs in regions closer to the equator where temperature is warmer and there is less seasonal variation. As this is a suitable environment for mosquitoes to thrive year longIn these areas children are infected repeatedly from a young ageConsequently the morbidity and mortality is highest amongst childrenHowever, regular exposure leads to the acquisition of some immunity and by adulthood most malarial infections are asymptomaticStable transmission is most significant in tropical Africa and coastal New Guinea. Unstable transmissionIn areas where the temperature is a bit cooler and where the climate varies with season the environment is less suitable for mosquitoes and therefore the transmission is lower.As the transmission is lower, full protective immunity is not acquired and symptomatic disease occurs at all ages.Malaria behaves like an epidemic in areas with unstable malariaAn epidemic can develop when there are changes in environment, economic or social conditionsP. vivax might be more prevalent because it is more tolerant of lower temperatures.

The four main strains of Malaria are found in different proportions in each region.P.falciparum predominates in Africa, New Guinea and HaitiP.vivax is more common in Central AmericaThe prevalence of these two species is approximately equal in South America, India, eastern Asia and Oceania.P. malariae is found in most endemic sites (esp. through sub-Saharan Africa) but is much less commonP.ovale is unusual outside of Africa and where it is found, comprises 2% of RBCs Acidotic

Australian Therapeutic GuidelinesSevere P. falciparumIV therapy

1. Artesunate 2.4mg/kg on admissionRepeat at 12hr, 24hr, then once daily

2. Quinine dihydrochlorideLoading dose, then maintenance dose

TreatmentArtemisinin and derivativesAtovaquone + proguanil Quinine salt + Doxycycline or ClindamycinComplications of MalariaCNS: cerebral malariaRenal: blackwater fever: haemoglobinuria + haemolysis + renal failure, uraemia (acute tubular necrosis)Blood: severe anaemia (haemolysis, dyserythropoiesis, splenomegaly with sequestration and folate depletion)Respiratory: acute respiratory distress syndrome (ARDS)Metabolic: hyperglycaemia, metabolic acidosisGI: diarrhoea, jaundice, splenic rupture haemorrhageOther: shock/hypotension (especially with secondary bacterial infection), hyperpyrexiaComplications of MalariaComplications of MalariaCNS: cerebral malariaRenal: blackwater fever: haemoglobinuria + haemolysis + renal failure, uraemia (acute tubular necrosis)Blood: severe anaemia (haemolysis, dyserythropoiesis, splenomegaly with sequestration and folate depletion)Respiratory: non-cardiogenic pulmonary oedema/ acute respiratory distress syndrome (ARDS)Metabolic: hyperglycaemia, metabolic acidosisGI: diarrhoea, jaundice, splenic rupture haemorrhageOther: shock/hypotension (especially with secondary bacterial infection), hyperpyrexiaCerebral Malaria- recognised by a decreased conscious state not a headache- causes 80% of deaths from Malaria and will kill 15-20% of the people who have it even with treatmentNon-cardiogenic Pulmonary Oedema- caused by overhydration, increased permeability of pulmonary vessels in response to the infection or by the clogging of pulmonary microcirculation by infected red cells - 50% mortalityRenal Failure- caused by dehydration, increased blood viscosity and the products of haemolysis- adequate rehydration neededPrognosisCriteria for a poor prognosis:

< 3 years oldPregnancyFitsComasNo corneal reflexPapilloedemaPulmonary oedema/ARDSHCO3- 5mmol/LHyperparasitaemia (>5%RBCs or 250,000/mL)Hb 265mmol/LMalaria pigment >5% neutrophilsComplicating infectionDIC>20% of parasites are mature trophozoites or shizonts

The main criteria for poor prognosis:

The species of Malaria:P. Falciparum

The number of parasites:>5% of RBCsPre-Travel AdviceTravellers AdviceRisk assessmentAdminister vaccinationsMalaria preventionEssential preventive behavioursRisk assessment:Itinerary (country / regions / dates of travel)Urban / ruralAgePast vaccination HxComorbiditiesCurrent MedicationsPregnancy statusAllergiesPurpose of tripRisk exposures (blood, body fluids, extreme sports, outdoors)Types of accomodationTravel insuranceLevel of aversion to riskAdminister ImmunisationsRoutine vaccinationsTravel vaccinations

Malaria Prevention

Essential preventive behavioursFood and water safetyProtection against STDs (always use condom)Motor vehicle safetyPersonal safety (appropriate dress, crime, recreational activities, local customs, etc.)Altitude / motion sickness / jet-lag

OBJECTIVESRED FLAGSRigors = hospital admissionHOW TO TAKE A HISTORY IN A RETURNED TRAVELLERAfebrile doesnt rule out infectionMALARIADiagnosisPathophysiologyManagementCOUNSELLING A PROSPECTIVE TRAVELLER