- 34 year old male from Pakistan presents with fever, rigors, and sweats for 3 days after travel to Croatia 14 days prior. Physical exam is notable for fever of 102.7F but otherwise unremarkable. - Malaria is endemic in parts of Pakistan, transmitted by several mosquito species. P. falciparum is increasing and causes the most severe disease. - The patient likely has malaria acquired in Pakistan or Croatia, with P. falciparum or P. vivax being the most common causes. He will be treated with intravenous quinidine followed by oral therapy if parasites decrease sufficiently.

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)