This document provides an overview of malaria, including its epidemiology, life cycle, symptoms, diagnosis and treatment. Some key points: - Malaria is caused by Plasmodium parasites and transmitted via the bites of infected Anopheles mosquitoes. P. falciparum causes the most severe form of the disease. - It is widespread in tropical and subtropical regions, especially sub-Saharan Africa. An estimated 1-3 million people die from malaria each year. - Symptoms include fever, chills, fatigue and headaches. Severe malaria can lead to coma, organ failure or death if not promptly treated. Diagnosis involves blood smear examination and rapid tests. -

1. OVERVIEW AND MANAGEMENT
Presented by : Capt Vikramjit Singh
Moderator : Lt Col R Sivasubramanian

2. .

3. .
 The word Malaria comes from 18th century
Italian mala meaning “bad” and aria
meaning “air”.
 Also known as jungle fever, marsh
fever, paludal fever.
 According to WHO, the majority of death
occur among children in sub-saharan Africa
killing an African child every 30 second.
 Associated and cause of poverty and
obstacle to economic development.

4. Discovery
 Dr. Alphonse Laveran, a military doctor in
France armed forces health service
discovered malarial parasite M.H. Algeria in
1880.
 Also won a Nobel prize for the same in 1907.
 Later Sir Ronald Ross ,born in India, a
British doctor discovered malarial parasite
in GIT of anopheles mosquito that led to
realization of cause.(Calcutta)

5. EPIDEMIOLOGY
 Malaria is a protozoan disease.
 Transmitted through bite of female
anopheles mosquito.
 most important parasitic ds.
 transmission in 108 countries
 containing 3 billion people
 causing 1-3 million deaths each year

6. .
Problem of resurgence due to
>drug resistance of parasites
>insecticides resistance to vectors

7. .
 Malaria can behave as epidemic in country
like India ,Sri lanka, se asia
 Most prevalent when there are Climate
changes such as heavy rains following
drought or migrations(refugees or workers)
 When there is breakdown in control and
preventive services

8. DETERMINANTS
1.density
2.human biting habits
3.longevity of anopheles
mosquito must survive >7 days to
transmit

9. .
 New control and research are
promising but malaria remains today as
it has been for centuries
 i.e a heavy burden on tropical
communities, a threat to non malarious
or non endemic area , a danger to
travelers

10. ETIOPATHOGENESIS
 Genus : plasmodium
 Species
 :falciparum
 :vivax
 :ovale
 :malariae
 :knowlesi(in macaques,can also in
humans)
 deaths mainly due to falciparum

11. Plasmodium Vivax
 Plasmodium vivax – milder form of disease,
generally not fatal.
 About 60-70% of infections in India
 Has a liver stage and can remain in body for
years without causing sickness.
 and can cause relapse.

12. Plasmodium Falciparum
 Most serious form of disease
 20- 30 % cases in India

13. TRANSMISSION CYCLE
SPOROZOITES
IN MOSQUITO GUT LIVER
GAMETE>
ZYGOTE>OOKINETE MEROZOITES
RBCs
GAMETOCYTES
SHIZONTS

14. BRIEF LIFE CYCLE
 from mosquito Sporozoites into human blood .
 than into liver
 there occurs pre-erythrocytic schizogony.
 Single Sporozoites>10,000-30,000 daughter
Merozoites.>burst>
 released into blood
 Taken up by RBCs
 male female gametes also found into blood

16. PLASMODIUM
 primary development stage in >liver
 also called as Pre Erythrocytic stage
 responsible for cause of malaria
 then enter into rbc
 also called as Erythrocytic stage
 responsible for symptoms

17. SYMPTOMS
 fever
 chills
 rigors
 corresponds to erythrocytic stage
 Severity depend upon
 1.type of parasite
 2.immunity of patient
 3.function of spleen

18. TRANSMISSION
plasmodium > give rise to >
gametes(in blood)
which can be taken up by female
anopheles
responsible for transmission

19. RELAPSE and RECRUDESCENCE
 Some shizonts remain dormant in liver
 called as exo-erythrocytic hepatic stage
 Seen in vivax
 This stage is absent in pl.falciparum(no
dormant(hypnozoite ))
 So relapse don’t occur here
 Recrudescence may occur due to
incomplete clearance of parasites by drug.

20. SPECIES DIFFERENCES
Pl. Pl.vivax Pl.ovale Pl.malaria
falciparum
No. of 30,000(>2%pa 10,000 15,000 15000
merozoites rasitemia is
release/inf s/o Pl.falci
hepatocytes
Duration of 48 48 50 72
erythrocytic
cycle
Rbc pref YOUNG RETICULO RETICULO OLDER
CYTES CYTES CELLS
RELAPSE NO YES YES NO
Incubation 9-14 12-18 12-18 18-40
period(days)

21. CLINICAL FEATURES
 lack of sense of well being
 headache
 fatigue
 abdominal pain or discomfort
 muscle ache
 followed by fever (may look like viral )
 nausea ,vomiting ,orthostatic hypotension

22. HEADACHE
 may be severe in malaria
 no photophobia
 no neck rigidity

23. MYALGIA
 not usually as severe as dengue
 not tender as in leptospirosis/typhus

24. FEVER
 classical finding of spikes, chills, rigors
at regular interval are unusual
 may suggest P.vivax or P.ovale
 P.Falciparum fever is irregular .and
generalized seizure associated with it
 fever may rise above 40 degree Celsius
 tachycardia , delirium

25. Cerebral malaria
 Coma
 Death rate~20%
 Diffuse symmetric encephalopathy
 ~15% of patient have retinal hemorrhages on
fundoscopy
 Generalized convulsions
 10% of adults(<3% with sequelae)
 50% of children(>5% with sequelae like
hemiplegia, cerebral palsy, cortical
blindness, deafness, language defects, increased
epilepsy incidence, decreased life span.

26. SEVERE FALCIPARUM MALARIA
SIGNS
 unarousable coma
 acidosis
 severe anemia(normochromic/normocytic)
 renal failure
 pulmonary edema
 ARDS
 hypoglycemia
 shock or hypotension
 DIC
 convulsions
 Haemoglobinuria(black water fever)

27. POOR PROGNOSTIC FACTORS
 CLINICAL
 marked agitation
 respiratory distress
 hypothermia
 bleeding
 deep coma
 repeated convulsions
 anuria
 Shock(algid malaria)

28. POOR PROGNOSIS
 {LAB VALUES}
 Hypoglycemia(<40mg/dl)
 Acidosis(ph<7.3 , hco3<15 mmol/l)
 Elevated s.creatinine(>3mg/dl)
 Elevated bilirubin
 Elevated liver enzymes(AST/ALT >3X)
 Elevated CPK
 Elevated urate

29. Poor prognosis
 wbc >12000/ul
 severe anemia(pcv<15%)
 Coagulopathy
 decreased platelet
 prolonged PT >3 sec
 prolonged PTT
 decreased fibrinogen(<200 mg/dl)

30. INVESTIGATION
 Hb
 Total leukocytes count
 Differential leukocytes count
 platelets
 Peripheral blood film
 Rapid malarial test
 Serum urea
 Serum creatinine

31. Diagnosis
 Thick blood film
 Thin blood film
{rapid ,species specific inexpensive}
 Rapid pfhrp2(monoclonal antibody)
{+ means illness in falciparum}
 Plasmodium ldh rapid test
 Microtubule conc. method with Acridine
Orange Stain

32. RMT

33. DRUGS
 1.schizonticides
>> Primary tissue(prophylaxis)
>> Erythrocytic(for acute attacks and
prophylaxis)
>> Exo-erythocytic(radical cure)
 2.gametocides(prevent transmission)

34. CHEMOPROPHYLAXIS
 Atavaquone(250mg)/Proguanil(100mg)
po with milky drink and food
 begin 1 day before travel to malarious area
 take o.d.
 continue up to 7 day after leaving
Contra indication
 in renal failure, pregnancy n breastfeeding

35. .
 Chloroquine 300mg base once weekly
 begin 1 week before
 take weekly
 continue up to 4 weeks after leaving

36. .
Doxycycline 100 mg qd
 begin 2 day before
 take daily
 Continue up to 4 week after leaving
Contraindication :
 in child <8yr ,pregnant
Side effects :
 photosensitivity, diarrhea

37. .
 Mefloquine 250mg salt po weekly
 begin a week before
 take weekly
 continue up to 4 weeks after leaving
Contra indication:
 allergic history to this drug, psychiatric
conditions, cardiac conduction
abnormalities

38. .
Primaquine 30mg of base po qd
 begin 1 day before travel
 take daily
 continue up to 7 days after leaving
 also used for presumptive anti relapse
therapy(terminal prophylaxis)
Contra indication:
g6pd def icienc y
pregnanc y and lactation

39. UNCOMPLICATED MALARIA
 Chloroquine sensitive
 Dose
10 mg of base /kg stat f/b
5 mg /kg at 12,24,36 hour
or
10 mg/kg at 24 hour >>5 mg/kg at 48 hour
or
 Amodiaquine 10 mg of base/kg qd for 3
days

40. RADICAL TREATMENT FOR OVALE
AND VIVAX
 in addition to Chloroquine and
Amodiaquine
 Primaquine 0.50mg of base/kg qd for 14
days
 prevents relapse
 In mild g6pd deficiency 0.75 mg of base /kg
given weekly for 7 weeks

41. SENSITIVE FALCIPARUM
 Artesunate 4mg/kg qd for 3 days
+
 Sulphadoxine 25 mg/kg, Pyrimethamine
1.25 mg /kg as single dose
or
 Artesunate 3 days + Amodiaquine 3 days
(4mg/kg ) (10mg/kg)

42. MULTI DRUG RESISTANT
FALCIPARUM
 Artemether-Lumefantrine b.d for 3
day 1.5mg/kg 9 mg/kg
or
 Artesunate plus
 Mefloquine
8mg/kg for 3 days
or
15mg/kg 2nd day f/b
10mg/kg 3rd day

43. 2nd line t/t or t/t of imported
malaria
 Artesunate or Quinine for 7 days
(2mg/kg) (10mg/kg)
 plus one of following
1.Tetra4/Doxycycline 3mg/kg for 7 days
2.Clindamycin 3mg/kg for 7 days
or
 Atavaquone-proguanil qid for 3 days
20 mg/kg 8 mg/kg

44. SEVERE FALCIPARUM MALARIA
 Artesunate (2.4mg/kg) intravenous stat
followed by
 same dose at 12 and 24 hour
 It is drug of choice when available
or
 Artemether (3.2mg/kg)stat intramuscular
f/b 1.6 mg/kg qd

45. Severe Falciparum
 Quinine dihydrochloride(20 mg
/kg)infused over 4 hour f/b slow
infusion of 10mg/kg infused over 2-8 hour
q8h(8hourly)
or
 Quinidine(10mg/kg)infused over 1-2hour
f/b 1.2mg/kg per hour with ECG monitoring

46. Supportive Treatment
• General care of the unconscious patient,
• Careful fluid balance,
• Control of seizures,
• Naso-gastric tube feeding,
• Correction of metabolic derangements
(e.g. hypoglycaemia, metabolic acidosis)
• Blood transfusion for severe anaemia.
• Bacterial infection: antibiotics

47. WHO RECOMMENDED ACTs
 Artemether-lumefantrine{COARTEM}
 Artesunate-mefloquine
 Artesunate-amodiaquine
 Artesunate-sulfadoxine-pyrimethamine
 Dihydroartemisinin-piperaquine

48. COMPLICATIONS
 Acute renal failure(tubular necrosis)
 Acute pulmonary edema
( non cardiogenic)
 Hypoglycemia(hepato gluconeogenesis
failure)
 DIC (only in <5%)
 Aspiration pneumonia in comatose

49. OTHER COMPLICATIONS
 Mild jaundice to severe in falciparum .
 Hepatic dysfunction contributes to
hypoglycemia, lactic acidosis, impaired drug
metabolism
 Anemia (accelerated RBC removal by spleen ,
obligatory destruction due to schizogony ,
ineffective erythropoiesis)
 Transfusion malaria due to needle stick injury
and transfusion(short incubation period due
to absence of pre erythrocytic stage of
development

50. DEGREE OF RESISTANCE
WHO SCHEME
 study of parasitemia over 28 days
 smears on day 2,7 and 28 days
 grade r1,r2,r3
 normal response >if parasite count falls
to <25%of pre treatment value by 48
hours and smears be negative by 7 days

51. Factors
1.longer half life
2.single mutation for resistance.
3.poor compliance
4.host immunity
5.number of people using these drug

52. Possible points which help to
reduce emergence of resistance
 1.use conventional drugs first in uncomplicated cases
 2.avoid drug with longer half life
 3.avoid basic antimalarials for conditions like RA in
endemic area
 4.ensure compliance
 5.monitor resistance and early treatment to prevent
spread
 6.clear policy of using new drugs
 7.use of combinations

53. Preventing malaria
 Avoiding mosquito bites
 -vector control .
 -reducing contact between people and vectors
 -improving living standards, screened windows, air
conditioning.
 -ITNs(insecticide-treated bed nets)

54. References
 HARRISON’S PRINCIPLES OF INTERNAL MEDICINE
18th edition
 Centers for Disease Control and Prevention (website)
 WHO(website)

55. .
THANK YOU

56. DISCUSSION