malaria review. objectives recognize parasite on thin film understand patterns of illness by species...
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Malaria ReviewMalaria Review
ObjectivesObjectives
Recognize parasite on thin filmUnderstand patterns of illness by speciesBe able to treat a caseBe able to prevent a caseUnderstand the global epidemiology of this
disease
Past ExperiencePast Experience
One of worst ID pathogens in world, clearly expanding range and increasing prevalence
Objective of WHO eradication campaign in 1950’s-60’s, and became one of most impressive public health defeats ever
Target of current “Roll Back Malaria” initiative, in face of resurgence
Recent Issues in MalariaRecent Issues in Malaria
“Monkey malaria”Rise of vivaxChloroquine – an antiviral agent?PF4 – the cause of cerebral malaria?
Baird, J. K. N Engl J Med 2005;352:1565-1577
Risk of Plasmodium falciparum Malaria Worldwide
Malaria EpidemiologyMalaria Epidemiology
2.4 billion people live in malaria endemic countries
Annual incidence of 100 to 300 million cases
About 1.5 to 2.7 million deaths per year from malaria
Malaria EpidemiologyMalaria Epidemiology
Endemicity measured by percentage of 2 to 9 y.o. with splenomegaly or parasitemia– Hypoendemic - 0-10%– Mesoendemic - 10-50%– Hyperendemic - 50-75%– Holoendemic - over 75%
Prevalence/Disease PatternsPrevalence/Disease Patterns
P. falciparumP. falciparum Epidemiology Epidemiology
Only malaria parasite routinely causing death
1.5-2.7 million deaths/yearMost in sub-Saharan AfricaMostly among infants
EpidemiologyEpidemiology
More than 90% of all malaria cases are in sub-Saharan Africa. Two-thirds of the remainder are concentrated in six countries -- India, Brazil, Sri Lanka, Vietnam, Colombia and Solomon Islands, in decreasing order of prevalence.
Malaria Life CycleMalaria Life Cycle
Baird, J. K. N Engl J Med 2005;352:1565-1577
Plasmodium sppPlasmodium spp..
172 Plasmodium species of birds, mammals, reptiles
4 routinely infect humans, 1 every so often– vivax, ovale, falciparum and malariae– knowlesi occasional human pathogen
P vivax and P falciparum are the most important, causing the vast majority of disease
Details of Details of Plasmodium sppPlasmodium spp.. P falciparum P vivax P ovale P malariae
Hepatic phase
5.5 8 9 15
RBC cycle 2 2 2 3
RBC preference
All reticulocyte reticulocyte Old RBC
Hypnozoites No Yes Yes No
Schizont/ merozoites
30,000 10,000 15,000 2,000
Max duration
2 years 4 years 4 years 40+ yrs.
P. knowlesiP. knowlesi
The fifth human malariaMost cases from Malaysia, recognized to
naturally infect humans in 1965May cause fatal disease due to 24 hour
replication cycleDx – difficult to differentiate from Pm; PCRChloroquine is effective rx (for both of the
above)
Incubation PeriodIncubation Period
Case Report 1Case Report 1
7 y.o. African boy with fever, seizures and DIC
Subject well until arrival from Sierra Leone, c/o fever, malaise
2 days after arrival new onset generalized seizure, taken immediately to hospital. Treated for meningitis with ceftriaxone.
Case Report 1Case Report 1
Seizures and fever continue over next 2 days, despite antiseizure medication
On 4th hospital day, lab tech notes malaria parasites on CBC
Patient transferred to tertiary care facility
Case Report 1Case Report 1
On arrival, patient comatose, frank DIC and P.falciparum parasitemia of 20%
Intravenous quinidine/doxy plus exchange transfusion in the intensive care unit (ICU)
Day 1 ICU, subject develops renal and hepatic insufficiency, requires endotracheal intubation for respiratory failure.
Focal neuro exam ICU day 2 – CT head shows small CVA
Fully recovers, walks out of hospital day 10
Pathogenesis ModelsPathogenesis Models
Sequestration ModelCytokine Model
Fever CurveFever Curve
Clinical PresentationClinical Presentation
The classic flu-like illness Commonly mistaken for influenza, other URI,
travelers' diarrhea, viral hepatitis, or encephalitis Fever, headache, muscle and joint aches,
abdominal pain, diarrhea, etc. Anyone coming from endemic area must be
considered to have malaria until proven otherwise Main reason it’s missed – no travel history taken
SymptomsSymptoms
Symptom Frequency Symptom Frequency
Fever 97% Abd pain 21%
Chills 88% Diarrhea 18%
Malaise 82% Cough 18%
Nausea 36% Vomiting 31% Pharyngitis 25%
SignsSigns
Sign Frequency Temperature > 39C 30% Splenomegaly 26% Hepatomegaly 11% Icterus 7% Rash 4% CNS changes 2%
Laboratory ValuesLaboratory Values
Lab value Frequency Lab value Frequency
LDH >200 78% BUN > 18 20%
Plt < 150K 58% Alk phos > 115
19%
WBC < 5K 37% Creat > 1.2 14%
Proteinuria 33% WBC > 10K 8%
Hb < 12 28%
AST > 40 25%
Differential DiagnosisDifferential Diagnosis
Typhoid feverDengueInfluenzaMeningococcemiaLeptospirosisBacterial gastroenteritisViral encephalitis
DiagnosisDiagnosis
Thick/Thin Blood film– Gold Standard– quantify by parasites/200 WBC, then convert to
parasites/L for thick film– % RBC parasitized in 1000 cells for thin film– films must be repeated every 6-8 hours for 2
days to confirm negative
Newer Diagnostic MethodsNewer Diagnostic Methods
Rapid testing (multiple)Antibody testing (ELISA)PCR testing
– P. malariae
Case Report 2Case Report 2
17 y.o. resident of Ghana visiting as tourist seen for fever, HA, myalgias
Diagnosed with P. falciparum malaria, 2% RBC infected, treated with oral quinine and Fansidar
2 days into therapy develops cough and SOB
Case Report 2Case Report 2
Cough and SOB worsen over next 2 daysSeen at hospital, exam with bibasilar
crackles, CXR with alveolar infiltrate, possible pulmonary edema. Smear neg
Pt decompensates, requires ETTAfter 2 days, extubatedFull recovery in next 2 days
Case number 3Case number 3
25 yo Guyanese gold miner admitted with h/o fever, MS changes.
On admission pt is comatose, Hct=8.0 and glucose=45.
Pt has parasitemia of 25%Given IV Quinidine and doxyStill comatose 24 hours post-Rx
Case number 3Case number 3
Multiple amps D50 given, still intermittently hypoglycemic day 2
QT interval prolongation necessitates reduction of quinidine drip rate
Dramatic recovery after 48 hours of therapy, recovers full neuro function
The AntimalarialsThe Antimalarials
Quinolines– 4-aminoquinolines chloroquine, amodiaquine, pyronaridine– Aryl-amino alcohols quinine and quinidine, mefloquine,
halofantrine, lumefantrine (benflumetol) Artemisinins: dihydroartemisinin, artesunate,
artemether, arteether Antifolates
– sulphonamides and sulphones– pyrimethamine, biguanides and triazine metabolites,
quinazolines 8-aminoquinolines (primaquine)
Treatment – Uncomplicated Not PFTreatment – Uncomplicated Not PF
P. vivax, ovale, malariae, known sensitive Pf
Chloroquine 10 mg base/kg followed by 5 mg/kg at 12, 24 and 36 h (or amodiaquine, see below)
Chloroquine-R but SP-S
SP 3 tablets x 1
Amodiaquine (not Asia) 10 mg/kg qd for 3 days
Treatment-Uncomplicated PFTreatment-Uncomplicated PF
Malarone 4 tabs po qd for 3 daysMefloquine 25 mg/kg (5 tab) for non-
immune; 15 mg/kg semi-immuneQuinine 10 mg/kg 3x/day + doxy 2.5
mg/kg/day x 7 days (or SP, or Clinda)Coartem (not in US) 1.5/9 mg/kg 2x/day for
3 days with foodLapdap (not in US) 1 po qd for 3 days
WHO CRITERIA FOR SEVERE WHO CRITERIA FOR SEVERE MALARIAMALARIA
Cerebral malaria with unrousable coma
Severe normocytic anemia
Renal failure Pulmonary edema Hypoglycemia
Shock (DIC)/spontaneous
bleeding Repeated generalized
convulsions Acidemia/acidosis Malarial
hemoglobinuria
Severe MalariaSevere Malaria
Cerebral Malaria– unrousable coma
Severe Anemia– Hct 15% in 10K para
Renal failure– 400 cc/24 hrs
Pulmonary Edema Hypoglycemia
– <40mg/dl
Shock– sys BP <70 mm Hg
DIC Generalized Seizures
– >2 in 24 hrs Acidemia
– pH<7.25 or HCO3<15 Macrohemoglobinuria Postmortem dx
Severe Malaria: Adult vs. Severe Malaria: Adult vs. ChildChild
Sign/symptom Adult Child
Cough Uncommon early Common early
Duration sx b severe 2-3 days 1-2 days
Duration coma p rx 2-4 days 1-2 days
Jaundice Common Uncommon
Hypoglycemia Uncommon pre-rx Common pre-rx
Renal failure Common Rare
Post-neuro seq Uncommon Common (10%)
Treatment - Severe MalariaTreatment - Severe Malaria
– For chloroquine sensitive P.f.Chloroquine 10 mg base/kg IV over 8 h f/b
15 mg/kg over 24 h OR 3.5 mg/kg q6h OR oral regimen by NG tube– For chloroquine resistant P.f.
Quinine or Quinidine IV + doxy/clinda/SPArtemether IM/artensunate IV or IM,
artemisinin PR
Management of Severe Management of Severe MalariaMalaria
A Few PointsA Few Points Exchange transfusion - controversial Fluid balance
– avoid pulm edema or azotemia (dialysis in severe overload, acidosis, electrolyte changes)
Watch for Gram - sepsis and pneumonia Monitor serum glucose Aggressive antiseizure therapy Intubation may be necessary
Other Aspects of Severe Other Aspects of Severe MalariaMalaria
Other Manifestations– Impaired consciousness but rousable– Prostration, extreme weakness– Hyperparasitemia (>5%)– Jaundice (3 mg/dL)– Hyperpyrexia (>40C rectal)– Secondary infections
Goal of Exchange TransfusionGoal of Exchange Transfusion
Parasitemia >10%Exchange transfusion until
Parasitemia 1-5%
Parasitemia <5%Altered mental status
or
Parasitemia 5-10%
plus
IV Quinidine
until
Parasitemia <1% ANDNormal mental status
Malaria in PregnancyMalaria in Pregnancy
Consider “complicated”Severe malaria a risk in pregnant women
from areas of unstable or mesoendemic disease
Women in holoendemic areas: infant with low birth weight
Personal Protective MeasuresPersonal Protective Measures
Protective clothing (covers arms, legs)Skin repellent (DEET)Insecticide-impregnated bednetPermethrin on clothesAvoid outdoor exposure during prime
mosquito biting times (dusk to dawn)Insect repellent/spray in room at night
Why We Give ProphylaxisWhy We Give Prophylaxis
Prophylaxis - Chloroquine RProphylaxis - Chloroquine R
Personal Protective Measures Mefloquine (250 mg weekly 2 weeks b to 4 weeks a) Doxycycline (100 mg qd 1 day b to 4 weeks a) Malarone (250/100 mg qd 1 day b to 1 week a) Primaquine – terminal prophylaxis for some and… New Agents - Not yet licensed
– Azithromycin, Tafenoquine
SBT – Malarone (unless taking)
Chemoprophylaxis to avoidChemoprophylaxis to avoid
Fansidar– Fatal Stevens-Johnson syndrome, other
Halofantrine– EKG abnormalities, early studies stopped
Maloprim– Fatal agranulocytosis, dapsone T1/2=28 hours
Amodiaquine– Agranulocytosis, hematologic problems
Babesia InfectionsBabesia Infections
Mostly US illness, transmitted by deer ticks NE US (Martha’s Vinyard), WI, CA, WA Incubation 1-4 weeks Illness of fever, myalgias, anemia, hematuria,
jaundice – many with minimal or no sx Worse in splenectomized/compromised patients Diagnose with blood smear or PCR; Ab levels
may dx, but usually low during acute infection (variants like WA-1 will not react with CDC test)
Babesia microtiBabesia microti
Babesia TherapyBabesia Therapy
Clindamycin 300-600 mg IV q6 plus quinine 650 mg po q8
For less severe infection, may give clinda 600 mg po q8 + quinine
Atovaquone + azithromycin may be effective
Most antimalarials may no effect