OVERVIEW AND MANAGEMENT     Presented by : Capt Vikramjit Singh    Moderator : Lt Col R Sivasubramanian
.
. The word Malaria comes from 18th century  Italian mala meaning “bad” and aria  meaning “air”. Also known as jungle fev...
Discovery Dr. Alphonse Laveran, a military doctor in  France armed forces health service  discovered malarial parasite M....
EPIDEMIOLOGY Malaria is a protozoan disease. Transmitted through bite of female  anopheles mosquito. most important par...
.Problem of resurgence due to>drug resistance of parasites>insecticides resistance to vectors
. Malaria can behave as epidemic in country  like India ,Sri lanka, se asia Most prevalent when there are Climate  chang...
DETERMINANTS1.density2.human biting habits3.longevity of anophelesmosquito must survive >7 days to transmit
. New control and research are  promising but malaria remains today as  it has been for centuries i.e a heavy burden on ...
ETIOPATHOGENESIS Genus : plasmodium Species          :falciparum          :vivax          :ovale          :malariae...
Plasmodium Vivax Plasmodium vivax – milder form of disease,  generally not fatal. About 60-70% of infections in India H...
Plasmodium Falciparum Most serious form of disease 20- 30 % cases in India
TRANSMISSION CYCLE                  SPOROZOITESIN MOSQUITO GUT                        LIVER   GAMETE>ZYGOTE>OOKINETE      ...
BRIEF LIFE CYCLE from mosquito Sporozoites into human blood . than into liver there occurs pre-erythrocytic schizogony....
PLASMODIUM primary development stage in >liver also called as Pre Erythrocytic stage responsible for cause of malaria ...
SYMPTOMS fever chills rigors corresponds to erythrocytic stage Severity depend upon 1.type of parasite 2.immunity o...
TRANSMISSIONplasmodium > give rise to > gametes(in blood)which can be taken up by female anophelesresponsible for trans...
RELAPSE and RECRUDESCENCE Some shizonts remain dormant in liver called as exo-erythrocytic hepatic stage Seen in vivax...
SPECIES DIFFERENCES               Pl.            Pl.vivax   Pl.ovale   Pl.malaria               falciparumNo. of         3...
CLINICAL FEATURES lack of sense of well being headache fatigue abdominal pain or discomfort muscle ache followed by ...
HEADACHE may be severe in malaria no photophobia no neck rigidity
MYALGIA not usually as severe as dengue not tender as in leptospirosis/typhus
FEVER classical finding of spikes, chills, rigors  at regular interval are unusual may suggest P.vivax or P.ovale P.Fal...
Cerebral malaria Coma Death rate~20% Diffuse symmetric encephalopathy ~15% of patient have retinal hemorrhages on  fun...
SEVERE FALCIPARUM MALARIA            SIGNS unarousable coma acidosis severe anemia(normochromic/normocytic) renal fail...
POOR PROGNOSTIC FACTORS CLINICAL marked agitation respiratory distress hypothermia bleeding deep coma repeated conv...
POOR PROGNOSIS {LAB VALUES} Hypoglycemia(<40mg/dl) Acidosis(ph<7.3 , hco3<15 mmol/l) Elevated s.creatinine(>3mg/dl) E...
Poor prognosis wbc >12000/ul severe anemia(pcv<15%) Coagulopathy decreased platelet prolonged PT >3 sec prolonged PT...
INVESTIGATION Hb Total leukocytes count Differential leukocytes count platelets Peripheral blood film Rapid malarial...
Diagnosis Thick blood film Thin blood film  {rapid ,species specific inexpensive} Rapid pfhrp2(monoclonal antibody)   {...
RMT
DRUGS 1.schizonticides>> Primary tissue(prophylaxis)>> Erythrocytic(for acute attacks and prophylaxis)>> Exo-erythocytic(...
CHEMOPROPHYLAXIS Atavaquone(250mg)/Proguanil(100mg)  po with milky drink and food begin 1 day before travel to malarious...
. Chloroquine 300mg base once weekly begin 1 week before take weekly continue up to 4 weeks after leaving
.Doxycycline 100 mg qd begin 2 day before take daily Continue up to 4 week after leavingContraindication : in child <8...
. Mefloquine 250mg salt po weekly begin a week before take weekly continue up to 4 weeks after leavingContra indicatio...
.Primaquine 30mg of base po qd begin 1 day before travel take daily continue up to 7 days after leaving also used for ...
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 ...
RADICAL TREATMENT FOR OVALE         AND VIVAX in addition to Chloroquine and  Amodiaquine Primaquine 0.50mg of base/kg q...
SENSITIVE FALCIPARUM Artesunate 4mg/kg qd for 3 days              + Sulphadoxine 25 mg/kg, Pyrimethamine  1.25 mg /kg   ...
MULTI DRUG RESISTANTFALCIPARUM Artemether-Lumefantrine        b.d for 3  day 1.5mg/kg         9 mg/kg           or Artes...
2nd line t/t or t/t of importedmalaria Artesunate or Quinine for 7 days    (2mg/kg)        (10mg/kg) plus one of followi...
SEVERE FALCIPARUM MALARIA Artesunate (2.4mg/kg) intravenous stat  followed by same dose at 12 and 24 hour It is drug of...
Severe Falciparum Quinine dihydrochloride(20 mg  /kg)infused over 4 hour    f/b slow  infusion of 10mg/kg infused over 2-...
Supportive Treatment• General care of the unconscious patient,• Careful fluid balance,• Control of seizures,• Naso-gastric...
WHO RECOMMENDED ACTs Artemether-lumefantrine{COARTEM} Artesunate-mefloquine Artesunate-amodiaquine Artesunate-sulfadox...
COMPLICATIONS Acute renal failure(tubular necrosis) Acute pulmonary edema  ( non cardiogenic) Hypoglycemia(hepato gluco...
OTHER COMPLICATIONS Mild jaundice to severe in falciparum . Hepatic dysfunction contributes to  hypoglycemia, lactic aci...
DEGREE OF RESISTANCE          WHO SCHEME study of parasitemia over 28 days smears on day 2,7 and 28 days grade r1,r2,r3...
Factors1.longer half life2.single mutation for resistance.3.poor compliance4.host immunity5.number of people using these d...
Possible points which help to    reduce emergence of resistance 1.use conventional drugs first in uncomplicated cases 2....
Preventing malaria Avoiding mosquito bites -vector control . -reducing contact between people and vectors -improving l...
References HARRISON’S PRINCIPLES OF INTERNAL MEDICINE  18th edition Centers for Disease Control and Prevention (website)...
.    THANK YOU
DISCUSSION
Malaria
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Malaria

  1. 1. OVERVIEW AND MANAGEMENT Presented by : Capt Vikramjit Singh Moderator : Lt Col R Sivasubramanian
  2. 2. .
  3. 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. 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. 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. 6. .Problem of resurgence due to>drug resistance of parasites>insecticides resistance to vectors
  7. 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. 8. DETERMINANTS1.density2.human biting habits3.longevity of anophelesmosquito must survive >7 days to transmit
  9. 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. 10. ETIOPATHOGENESIS Genus : plasmodium Species :falciparum :vivax :ovale :malariae :knowlesi(in macaques,can also in humans) deaths mainly due to falciparum
  11. 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. 12. Plasmodium Falciparum Most serious form of disease 20- 30 % cases in India
  13. 13. TRANSMISSION CYCLE SPOROZOITESIN MOSQUITO GUT LIVER GAMETE>ZYGOTE>OOKINETE MEROZOITES RBCs GAMETOCYTES SHIZONTS
  14. 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
  15. 15. 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
  16. 16. SYMPTOMS fever chills rigors corresponds to erythrocytic stage Severity depend upon 1.type of parasite 2.immunity of patient 3.function of spleen
  17. 17. TRANSMISSIONplasmodium > give rise to > gametes(in blood)which can be taken up by female anophelesresponsible for transmission
  18. 18. 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.
  19. 19. SPECIES DIFFERENCES Pl. Pl.vivax Pl.ovale Pl.malaria falciparumNo. of 30,000(>2%pa 10,000 15,000 15000merozoites rasitemia isrelease/inf s/o Pl.falcihepatocytesDuration of 48 48 50 72erythrocyticcycleRbc pref YOUNG RETICULO RETICULO OLDER CYTES CYTES CELLSRELAPSE NO YES YES NOIncubation 9-14 12-18 12-18 18-40period(days)
  20. 20. 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
  21. 21. HEADACHE may be severe in malaria no photophobia no neck rigidity
  22. 22. MYALGIA not usually as severe as dengue not tender as in leptospirosis/typhus
  23. 23. 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
  24. 24. 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.
  25. 25. 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)
  26. 26. POOR PROGNOSTIC FACTORS CLINICAL marked agitation respiratory distress hypothermia bleeding deep coma repeated convulsions anuria Shock(algid malaria)
  27. 27. 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
  28. 28. Poor prognosis wbc >12000/ul severe anemia(pcv<15%) Coagulopathy decreased platelet prolonged PT >3 sec prolonged PTT decreased fibrinogen(<200 mg/dl)
  29. 29. INVESTIGATION Hb Total leukocytes count Differential leukocytes count platelets Peripheral blood film Rapid malarial test Serum urea Serum creatinine
  30. 30. 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
  31. 31. RMT
  32. 32. DRUGS 1.schizonticides>> Primary tissue(prophylaxis)>> Erythrocytic(for acute attacks and prophylaxis)>> Exo-erythocytic(radical cure) 2.gametocides(prevent transmission)
  33. 33. 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 leavingContra indication in renal failure, pregnancy n breastfeeding
  34. 34. . Chloroquine 300mg base once weekly begin 1 week before take weekly continue up to 4 weeks after leaving
  35. 35. .Doxycycline 100 mg qd begin 2 day before take daily Continue up to 4 week after leavingContraindication : in child <8yr ,pregnantSide effects : photosensitivity, diarrhea
  36. 36. . Mefloquine 250mg salt po weekly begin a week before take weekly continue up to 4 weeks after leavingContra indication: allergic history to this drug, psychiatric conditions, cardiac conduction abnormalities
  37. 37. .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
  38. 38. 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
  39. 39. 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
  40. 40. 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)
  41. 41. MULTI DRUG RESISTANTFALCIPARUM 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
  42. 42. 2nd line t/t or t/t of importedmalaria 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
  43. 43. 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
  44. 44. 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
  45. 45. 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
  46. 46. WHO RECOMMENDED ACTs Artemether-lumefantrine{COARTEM} Artesunate-mefloquine Artesunate-amodiaquine Artesunate-sulfadoxine-pyrimethamine Dihydroartemisinin-piperaquine
  47. 47. COMPLICATIONS Acute renal failure(tubular necrosis) Acute pulmonary edema ( non cardiogenic) Hypoglycemia(hepato gluconeogenesis failure) DIC (only in <5%) Aspiration pneumonia in comatose
  48. 48. 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
  49. 49. 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
  50. 50. Factors1.longer half life2.single mutation for resistance.3.poor compliance4.host immunity5.number of people using these drug
  51. 51. 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
  52. 52. 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)
  53. 53. References HARRISON’S PRINCIPLES OF INTERNAL MEDICINE 18th edition Centers for Disease Control and Prevention (website) WHO(website)
  54. 54. . THANK YOU
  55. 55. DISCUSSION

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