A discussion of Malaria

1. HX
●34 y/o Pakastanian male
●3d hx/o rigors, drenching sweats, & fever
●Croatia X14d’s
●Punjab Province

2. Physical Examination
●T 102.7° F
●Ill but nontoxic
●No specific findings on P.E.
●(-) spleenomegaly

3. Malaria
Frank Meissner,MD,FACP,FACC,FCCP
Emergency Medicine

4. Geo-epidemiology Pakastan
●Prevelance highest in Northwest Frontier
Province (6.5 % vs 3% baseline)
●Plasmodium falciparum increasing (54%
countrywide)
○33 % Punjab Province
○77% Sindh & Baluchistan Provinces

5. Transmission/Vector Ecology
●An. culicifacies
○Indoor feeder, breeds rice fields, channels, &
edges rivers/streams
●An. stephensi
○Indoor feeder, breeds polluted, fresh, and
brackish water

6. Transmission/Vector Ecology
●An. superpictus
○primarily outdoor feeder, breeds in rocky
streams and rivers
●An. sergenti
○Outdoor feeder, breeds in ditches, marshes,
ponds, & wells

7. Malaria- Worldwide
●60 million cases per annum
●Malaria increasing throughout tropics,
esp Indian subcontinent

8. Malaria- USA
●1988, 1,023 cases of malaria reported in
the United States
●43 % were Plasmodium vivax
●46 % P. falciparum
●Three % P. malariae
●Two % P. ovale

9. Malaria- USA
●All but 32 of the 1,023 cases acquired
outside of United States
●Six fatalities

10. Malaria- USA
●Malaria acquired by mosquito incrsing
●14 cases occurred USA 1950-1985
●Epidemiologic surveys California - 27
cases in 1987
●30 cases in 1988
●Eight cases in 1989
●All caused by P. vivax

11. Malaria - Life Cycle
●Incubation Period 12 to 14 days
●Sporozoites enter via bite of infected
female anopheline mosquito
●Parasites carried to the liver, where they
multiply inside parenchymal cells
○Preerythrocytic tissue phase

12. Malaria - Life Cycle
●Progeny released from ruptured
hepatocytes => RBC’s
●Inside RBC
●Progency degrade protein fraction of
hemoglobin

13. Malaria - Life Cycle
●Undergo asexual maturation from
trophozoite to merozoite
○Process known as schizogony
●Cycles of intracorpuscular multiplication,
rupture, and reinvasion responsible for
paroxysms of chills & fever

14. Malaria - Life Cycle
●Some parasites differentiate into
macrogametocytes or
microgametocytes, the sexual forms
●These infect mosquitoes that feed on the
victim

15. Malaria - Life Cycle
●In the gut of the mosquito, the definitive
host
○fertilization
○zygote formation
○production of new sporozoites take place

16. Clinical Features
●Malaise & Myalgias
●Headache
●Chills (with or without rigor)

17. Clinical Features
●Temperature to 41.5° C (106.7° F)
●Profuse sweating & Prostration may
appear
●Mild jaundice, hepatosplenomegaly, and
anemia often develop

18. Fever Patterns
●P. vivax & P. ovale infections cause QOD
(tertian) febrile paroxysms
○After maturation cycles synchronize
○Usually at end of first week
●P. malariae infection marked by
paroxysms Q3D (quartan periodicity)

19. P. falciparum
●Has capacity to obstruct microcirculation
in various organs
●Fever continuous or intermittent
●Cerebral involvement may lead to
delirium, focal disorders (e.g., seizures),
& coma

20. P. falciparum
●Splanchnic involvement may cause
protracted nausea, vomiting, diarrhea,
melena, & abdominal pain
●GI syndrome can be mistaken as
traveler's diarrhea
●Since there may be little or no fever

21. P. falciparum
●Lung involvement may cause pneumonia
& ARDS
●Hypoglycemia may be severe
●Rare syndrome of blackwater fever
○Massive intravascular hemolysis
○=> hemoglobinuria and ARF

22. P. malariae
●Can persist as an asymptomatic infection
for years or decades
●Usually responsible for late relapses
●This species likely to be cause of malaria
induced by transfusion

23. Laboratory Diagnosis
●Parasites in properly stained smears
peripheral blood
●Smears taken repeatedly for several
days because cyclic nature parasitemia
●Morphologic features of parasites (and
the infected host erythrocytes) useful in
species ID

24. Laboratory Diagnosis
●Indirect fluorescent antibody test- CDC
●Blood smear used to establish a Dx
●Serologic test useful in ID infected
donors in cases of transfusion malaria
●DNA probe being developed Dx P.
falciparum infection

25. Drug Resistance
●Chloroquine-resistant strains in all
countries with P. falciparum malaria
except
○Haiti & the Dominican Republic
○Central America west of the Panama Canal
○Middle East & Egypt

26. Chloriquine Resistant Malaria

27. Drug Resistance
●Resistance to
pyrimethamine-sulfadoxine (Fansidar)
widespread
○Thailand, Burma, Cambodia, and the
Amazon River basin
○Has been reported in sub-Saharan Africa
●Mefloquine-resistant strains- P.
falciparum identified Thailand

28. PO Treatment
●1,250 mg of mefloquine in a single dose
●Mefloquine is a schizonticidal agent
structurally related to quinine
●Primaquine 15mg po qd X 2wks
●If G-6-PD deficient than 45 mg po 1X/wk
X 8wks

29. IV Therapy-Indications
●Intolerant oral therapy
●Neurologic symptoms
●Peripheral asexual parasitemia > 5%
RBC’s infected

30. IV Therapy-Regimen
●Life-threatening P. falciparum malaria
●Intravenous quinidine gluconate
○Loading dose 10 mg/kg (maximum 600 mg)
NS infused over 1 to 2 hrs
○Then continuous infusion of 0.02 mg/kg/min

31. IV Therapy-Cautions
●Slow infusion rate
○Plasma quinidine levels > 6 mg/ml
○QT interval greater than 0.6 second
○QRS widening beyond 25 percent of
baseline
●Hypoglycemia, may be exacerbated
●Parenteral therapy until parasitemia <1%

32. Transitions to PO Therapy
●In most cases, PO Rx can be substituted
within 48 - 72 hrs
●Oral therapy, usually with quinine,
continued for 3-7 d’s
●Add additional agent (e.g., TCN 250 mg
p.o. Q6h X 7 d’s)