Malaria is caused by the Plasmodium parasite and transmitted primarily by female Anopheles mosquitoes, resulting in significant mortality, particularly in sub-Saharan Africa. India contributes significantly to global malaria cases, with various species causing different clinical manifestations and resistance issues. Effective diagnosis and treatment are critical, with recent strategies focusing on elimination by 2030 through awareness, prevention, and chemoprophylaxis strategies.

1. AZEEZIA MEDICAL COLLEGE
DEPARTMENT OF GENERAL MEDICINE

2. MALARIA
Dr JAYASOORYA P G
JUNIOR RESIDENT
DEPARTMENT OF GENERAL MEDICINE

3. Sir RONALD ROSS
Awarded nobel prize
for physiology or
medicine in 1902 for
his work on
transmission of Malaria

4.  Malaria is a results of complex interaction between the host ,plasmodium
parasite ,female anopheles mosquito vector and the environment

5. Epidemiology and aetiology
 Caused by protozoan parasite-genus plasmodium
 150 species of plasmodium-they infect mammals ,birds,reptiles
 Human malaria-only 5 species-P.falciparum,vivax,ovale,malariae,knowelesi
 Transmission-female anopheles mosquito
 >90 % death-in sub-Saharan Africa-young childrens of <5 years
 About 4% cases globally-d/t vivax –but outside Africa continent vivax infection
is 41%
 P knowlesi-monkey parasite-cause of human malariae in forested areas of
malasia and indonesia

6.  India contribute 6% of global malaria cases
 According to NVBDCP -2/3 rd cases in india are due to P falciparum and rest
due to vivax in 2015
 Ovale,malaria,knowlesi –cases reported sporadically from various parts of
india
 India achieved near elimination of cases in 1970-but resurge of cases due to
relaxation of control measures,development of chloroquine resistance to P
falciparum,development of insecticide resistance by mosquito vectors

9.  Two host for malaria.Asexual life cycle in human host (intermediate
host),sexual life cycle in female anopheles mosquito (definite host)
 Infected female anopheles mosquito inoculate few sporozoite into skin—which
circulate in human body and reach liver to intiate exoerythrocytic stage—
within liver hepatocyte,sporozoite mature into hepatic schizont,which
rupture and release merozoite into circulation.
 In vivax and ovale hypnozoite(dormant liver form) form from these merozoite
 Merozoite invade RBC and intiating erythrocytic shizogony,develop into early
trophozoite (ring form),late trophozoite to mature schizont within 48-72
hours,and lead to rupture of RBC and release 6-30 merozoite

10.  They in turn infect new RBC and repeat the process.
 Few merozoite develop to male and female gametocyte within human.
 Upon mosquito bite male and female gametocyte fuse and form zygot within
female anopheles mosquito gut (sexual phase)
 Zygote elongate to ookinete and penetrate the gut wall and forms oocyte
where development of sporozoite takes place.
 Sporozoite then migrate to salivary gland and reside until next human bite
,ready to be inoculated

11.  Sporogony (from ingestion of gametocyte to formation of sporozoite)-takes 8-
21 days depending on temperature
 Thus to transmit malaria-mosquito has to survive >7 days
 Sporogony is not completed at cooler temperature (ie <16 c for vivax and <21
c for falciparum).so transmission does not occur below these temperature or
at high altitude

12. Pathogenesis
 Infected RBCs lose their deformability and results in intravascular haemolysis
 Mechanisms in severe malaria-cytoadherence,agglutination,rosetting,cytokine
network
 Cytoadherence-infected RBCs containing schizonts develop sticky knobs,which
make them adhere to the venular and capillary endothelium of
brain,lungs,liver,kidney,gut
 Agglutination –infected RBCs adhere to other infected RBCs
 Rosetting-infected RBCs adhere to uninfected RBCs
 Because of these phenomin there is microvascular blockage resulting in tissue
hypoxia and organ dysfunction

13.  Cytokine network –proinflamatory and immunomodulatory cytokines are
activated in acute malaria which evoke fever and are implicated in severe
malaria.
 P vivax induces more inflammation compared to P falciparum for given
parasite density

14. RBC changes,Haemoglobin variants and protection
against malaria
 Haemoglobin S, haemoglobin C, haemoglobin E, alpha thalassemia-protection
from severe life threatening P falciparum malariae
 Risk is reduces 70% by homozygous HbC and 90% by heterozygous HbS (SICKLE
CELL TRAIT)
 This protection is from severe malaria and largely absent for P falciparum
infection
 Mechanism-haemoglobinopathies interfere with parasite metabolism,restrict
the growth of parasite or expression of adhesion molecule
 Duffy blood group antigen is the receptor for P vivax binding of RBCs.
 Most west Africans and people with duffy negative phenotype are resistant to
P vivax

15. Clinical features
 Hippocrates –first explain symptoms of malaria and periodicity of fever
 Periodicity –depends on duration of erythrocytic phase of life cycle,febrile
paroxysms-coincide with rupture of erythrocytic shizont
 P knowlesi-quotidian fever-every day
 P falciparum,vivax,ovale-tertian fever-fever occur every third day
 P malariae-quartan fever-fever every 4th day


16. Typically malarial fever paroxysm has
 A)cold stage(20-60 min)-where individual experience intense chills and rigors
 B)Hot stage (2-6 hours)-where temperature may reach upto 40 c
 C)Wet stage/Diaphoresis(20-30 min) associated with profuse sweating

17. Other symptoms
 Nonspecific
 Head ache,bodyache,cough,vomiting,diarrhea

18. Clinical examination
 Pallor,mild jaundice,hepatomegaly,splenomegaly

19. Atypical presentation seen in
 Extremes of age
 Pregnancy
 Immunocompromised individuals
 Individuals with comorbidities
 Hence high index of suspicion is warranted in endemic areas and malaria must
be rule out in all febrile patients

20. Severe malaria
 Malaria with evidence of any organ dysfunction as per WHO defined severity
criteria anytime during acute illness is severe malaria
 c/f-altered sensorium,convulsions,oliguria,deep jaundice,shock,DIC,bleeding
manifestations,breathlessness
 Mortality (in severe falciparum malaria) if untreated-100%,mortality with
treatment-10-20 %

22. Cerebral malaria
 Present with impaired consciousness with or without convulsions in the
absence of hypoglycemia
 Usually focal neurological deficit and neck stiffness are absent
 More common in children
 Due to cytoadherence and sequestration

24. Severe anaemia
 Children>adult
 Due to intravascular haemolysis

25. Jaundice
 Commonest complication in patients with severe malaria
 Mild jaundice and indirect hyperbilirubinemia-due to haemolysis
 Some severe malaria-deep jaundice,conjugated
hyperbilirubinemia,transaminitis-d/t liver dysfunction
 Due to cytoadherence and sequestration in vital organs in addition to
inflammatory mediators

26. Hypoglycemia
 Results from failure of hepatic gluconeogenesis and increased consumption of
glucose by both host and malarial parasite
 Quinine and quinidine are powerfull secreatagogue and compound the
problem
 Hypoglycemia is asignificant problem in children and pregnant women

27. ACUTE KIDNEY INJURY
 Due to hypovolemia d/t vomiting,dehydration,sequestration of
parasite,sepsis,hypotension,haemoglobinuria (d/t Intravascular haemolysis)
 M.c in adult
 Non-oliguric,metabolic acidosis,hyperlactemia
 Black water fever-severe intravascular haemolysis resulting in dark coloured
urine haemoglobinuria,and is often precipitated by quinine
 Early dialysis enhances the likely hood of a patients survival

28. ARDS
 Noncardiogenic pulmonary oedema is due to leaky capillaries
 M.C with P vivax > P falciparum
 ARDS may develop as a late manifestation even after parasite clearance

29. Severe P vivax malaria
 Complications-cerebral malaria,spontaneous bleeding,pulmonary
oedema,ARDS,circulatory collapse/shock,hyperbilirubinemia,severe
anaemia,hemoglobinuria,renal failure,respiratory distress,metabolic
acidosis,hypoglycemia
 Unlike P falciparum,vivax doesnot produce hyperparasitemia.And rarely reach
parasitemia of 2% in the periphery,as it predominantly infect reticulocyte
 Significant P vivax biomass in extra vascular compartment such as bone
marrow and spleen
 Splenic rupture is more common with P vivax

32. Malaria due to P ovale
 Mild acute attack
 Parasitemia persist for several years with occasional recrudescence of fever
 Cause glomerulonephritis and nephrotic syndrome in children

33. Malaria due to P ovale
 Mild malaria with potential to cause relapses

34. Malaria due to P knowlesi
 Full spectrum of illness including severe malaria(exception-cerebral malaria)

35. Chronic complications of malaria
 Tropical splenomegaly(hyperactive malarial splenomegaly)
 Quartan malarial nephropathy
 Recurrent malaria
 Malarial relapses

36. Tropical splenomegaly
 Its Hyperractive malarial splenomegaly
 Exposure to r/c malarial infection in endemic areas-abnormal immunological
response-massive splenomegaly and hepatomegaly
 Defective CD8 lymphocyte function-marked stimulation of B lymphocyte-
elevation of IgM and malarial antibodies
 Rx –long term Proguanil

37. Quartan malarial nephropathy
 Chronic or repeated infection with P malaria causes immune complex
mediated glomerulonephritis and resulted in nephrotic syndrome
 Poor response to antimalarial agents,glucocorticoids,cytotoxic drugs

38. Recurrent malaria
 Reappearance of parasitaemia after a clearance following acute malaria
 Recrudescence –appearance of parasitaemia from blood stage of parasite
 Relapse –appearance of parasitaemia from the activation of dormant
hypnozoites from the liver
 Reinfection –appearance of parasitaemia because of new infection following a
mosquito bite

39. Malarial relapses
 Hypnozoites,the dormant liver forms in P vivax and ovale –produce relapses
upto 2 years
 Frequent relapses can induce severe anaemia ,especially in children and
pregnant women

40. Differential Diagnosis
 Dengue fever
 Scrub typhus
 Leptospirosis
 Influenza
 Viral hepatitis
 Meningoencephalitis
 Sepsis

41. Diagnosis
 Perepheral smear examination
 QBC(quantitative buffy coat) examination
 Immunochromatographic test
 Molecular diagnosis
 Other lab test
 Glucose 6 phosphatase dehydrogenase activity

42. Perepheral blood smear examination
 Gold standerd for diagnosis-demonstration of asexual forms of parasite in
stained peripheral blood smear
 After a negative smear,if suspicion of malaria is high,repeat smear should be
made
 Stains using-romanowsky stains like leishman stain and giemsa stain-both
thick and thin smears are making
 Thick smears has more diagnostic sensitivity than thin smears-thick smear
concentrate the parasite by 40-100 fold than thin smear
 Before thick smear is judged negative-minimum of 200 field should be
examined under oil immersion

47. QBC examination
 Based on acridine orange staining of centrifuged peripheral blood sample in a
micro haematocrit tube and examination under UV light source (flurescence
microscopy)
 Principle-centrifugation concentrate RBCs in a predictable area of QBC tube
,making detection easy and fast
 RBCs containing plasmodia –concentrate just below the leukocytes,at the top
of erythrocyte coloumn-because RBC containing plasmodia are less dense than
normal ones
 RBC which takes acridine orange stain-appear as bright specks of light among
nonflurescing RBCs

48. Immuno chromatographic test
 These are rapid diagnostic test-detection of plasmodium antigen
 It’s a rapid and easy way to diagnose malaria in remote areas where
microscopy is not available
 Parasite LDH(plasmodium antigen)-in P falciparum,vivax,ovale,malaria
 Plasmodium falciparum histidine rich protein 2 (PfHRP2) antigen is specific for
P.falciparum
 Bivalent RDTs –differentiating vivax and falciparum

49. Molecular diagnostics
 PCR are more specific and sensitive for different species of plasmodia
 Costly
 So presently not indicated for case management of fever
 Using in –asymptomatic malaria in malaria control and elimination settings
 Antibody based malaria test has no role in diagnosis of acute malaria

50. Other lab test
 Normocytic normochromic anemia
 Thrombocytopenia
 Leukocytosis
 LFT-indirect hyperbilirubinemia with normal transaminase-s/o haemolysis
 Severe malaria-total bilirubin (>3) with elevation of direct bilirubin and mild
elevation of liver enzyme
 RFT-usually normal,severe malaria RFT elevated with metabolic acidosis
 Coagulopathy with abnormal PT/APTT-S/o DIC-in severe malaria

51. G6PD Activity
 RBC G6PD activity <30 % of normal mean have G6PD deficiency and will
experience haemolysis with primaquine

53. TREATMENT
 Treatment has to be intiated after confirmation of malaria by microscopy or
RDT.Treatment is according to infecting species and severity

54. A)Treatment of uncomplicated malaria
1)Treatment of uncomplicated Falciparum malaria
2)Treatment of uncomplicated vivax malaria
3)Treatment of P.ovale ,P malariae,P knowlesi
B)Treatment of severe Malaria
C)Treatment of recurrent malaria
D)Treatment of malaria in pregnancy

56. Treatment of uncomplicated Falciparum
malaria
 Resistance to chloroquine
 Artemisin combination therapy (ACT) is indicated for Falciparum malaria
 Artemisin monotherapy banned in india-emergence of resistance
 Artemisinin with short half life has to be administrated with a partner drug
with longer half life ,to prevent recrudescence
Acute treatment of P.Falciparum should be followed by a single dose of
primaquine 0.5mg/kg to kill the gametocyte to prevent transmission

57.  ACT is not to be given in first trimester of pregnancy.
 SP-is not prescribed for children <5 month,and should treat with alternative
ACT
 Primaquine is contraindicated in infants,pregnant women,G6PD deficiency
 In North Eastern india,P falciparum has developed resistance to SP. Hence SP
cannot be used along with artemisinin (SP-Sulfadoxine + pyrimethamine)

58. Treatment of uncomplicated vivax malaria
 Areas where P vivax sensitive to chloroquine ,its treated with chloroquine
 P vivax in india remains sensitive to chloroquine
 10 countries(Papua,new guinea,Thailand) developed resistace to P vivax.such
cases are managed with ACT.Sulfadoxine pyrimethamine is ineffective against
P vivax
 Schizonticidal treatment with chloroquine should be followed by primaquine(a
hypnozoitocidal)drug for 14 days to prevent relapses in all cases of P vivax
malaria
 In G6PD deficiency individual,primaquine may induce haemolysis.In such
patients ,primaquine 0.75mg/kg administered weekly for 8 week with
supervision and adequate patient counciling about symptoms of haemolysis

60. Treatment of P.ovale ,P malariae,P
knowlesi
 P ovale should be treated as P vivax
 P malariae,P knowlesi should be treated as P falciparum

61. Treatment of severe Malaria
 It’s a medical emergency
 All severe malaria due to all plasmodia species are treated similarly
 DOC- parentral ACT

62. Treatment of severe falciparum malaria

63. Adjunct treatment of severe malaria
 Fluid management,oxygen and ventilator support –to prevent ARDS
 Prevention and treatment of hypoglycemia,transfusion of blood component
therapy,management of kidney injury with dialysis
 Management of convulsions with diazepam and broad spectrum antibiotics in
suspected bacterial infection until cultures are negative

64. Treatment of recurrent malaria
 Its not resistant malaria
 Its due to reinfection/recrudescence/relapse
 Currently no test to accurately identify the cause
 Recurrence due to vivax-high dose of primaquine (0.5-0.75 mg/kg/day) for 14
days
 Failure to take full course of primaquine –one of the reason for relapse-so
ensure compliance to 14 days course of primaquine

65. Malaria in pregnancy
 ACT- contraindicated in first trimester
 Primaquine,doxycycline-contraindicated in throughout pregnancy and
lactation

70. Prevention of malaria
 National frame work for elimination of malaria by 2030-programme by gov of
india-it’s a multimodal approach to prevention
 1)promoting awareness of malarial transmission,breading sites and preventive
measures
 2)Bite prevention-integrated vector control,bed nets and mosquito repellents
 3)chemoprophylaxis for at risk individuals including travelers and intermittent
preventive therapy in infants and pregnant women (practiced in Africa)
 4)Diagnosis and early treatment of cases to reduce gametocyte production
and transmission.Ensuring radical therapy in P vivax cases with primaquine

72. Malaria vaccine
 Immunity in malaria is species and stage specific

73. RTS,S/AS01 Vaccine( trade name-Mosquirix)
 Against P falciparum malaria,
 Recombinant vaccine against pre-erythrocytic stage of the parasite
 Here P falciparum circumsporozoite protein are fused to hepatitis B surface
antigen
 Three doses -IM –minimum 4 weeks between doses
 4th dose-recommended by WHO for large scale pilot implementation in sub-
Saharan Africa

74. Thank you