Management Issues in MalariaDr Rajesh Deshwal, MD, FHMConsultant in Internal Medicine and HIV MedicineMilitary Hospital, A...
Major killer of mankindMost important parasitic diseaseApproximately one million die each year
Usual Clinical Presentations in Malaria
Incubation PeriodP. vivax 18-40 DaysP. falciparum 9-14 days
Cold stage, onset occurs with     • Lassitude     • Headache,often severe     • Nausea followed by vomiting     • Chilly s...
Hot StagePatient feels hotSkin is hot and dry to touchHeadache is intense but nausea diminishesPulse is full and respirati...
Sweating stageProfuse sweatingBody temperature drops rapidly to normalSkin is cool and moistPulse rate becomes slowerPatie...
Followed by afebrile interval of 48-72 hours hencetypical malarial fever is usually observed onalternate days
Latent periodThe patient is usually free of symptoms butin P. vivax hypnozoites persist in the liver andin P. falciparum i...
RecrudescenceIt is a renewed manifestation of infection withindays or weeksIt is a result of continued survival or presenc...
RelapseIt is the result from maturation of hypnozoites inthe liver with liberation of merozoites in to thebloodIt varies a...
Peripheral smearEssential for the confirmation of the diagnosis ofmalariaConfirming the species of parasite present in the...
Rapid Diagnostic Tests(RDT)- PfHRP2- PMA-aldolase- pLDH
Pattern of feverMay be irregular or continuousWhen more than two breeds of parasites areinvolved daily paroxysms may be ob...
UNUSUAL PRESENTATIONS OFMALARIA
Uncomplicated malaria in adult and olderpatients may present with following symptoms:Bodyache, headache and no feverThroat...
Uncomplicated malaria in children maypresent with following symptoms:Vomiting, cough, urticariaNo rhinitis and clear throa...
Causes of fever where malaria is likely tobe confused are:- URTI- UTI- Influenza- Dengue- Typhoid and paratyphoid fever- T...
When malaria is associated with JaundiceViral HepatitisLeptospirosisCholangiohepatitisThe most important step in diagnosis...
AnaemiaAnaemia is an inevitable consequence of malaria,because of the great proportion of erythrocyteswhich became parasit...
It is more common and more marked inchildren than in adultsMalaria may be the cause of sudden andcatastrophic fall in Hb% ...
JaundiceJaundice with palpable liver and spleen is common finding infalciparum malariaDegree of icterus correlates well wi...
Gastro intestinal involvementVomiting is a common feature of severe malariaparticularly in childrenDiarrhoea in case of ma...
SEVERE COMPLICATED MALARIA
Cerebral MalariaAny manifestation of cerebral dysfunction in apatient with malaria is evident of cerebral malariaOccurs pa...
When the coma is light, patient may be able to talkand answer questions, although later patient will haveno recollection o...
Acute renal failureMalaria with associated dehydration and hypotension may leadto oliguria, anuria, and ultimately acute r...
PULMONARY MANIFESTATIONS INMALARIAMalaria may present with signs and symptomssuggestive of respiratory disease like pneumo...
Hepatomegaly and splenomegaly are for less clinicalobservation. Drop in haematocrit level, but nospecific abnormality tren...
Pulmonary edemaThis could be a grave and fatal complication due to P.falciparum MalariaThe pathogenesis of this condition ...
The respiratory rate goes up - crepitations mayappearHaemoptysis is usually absentSerious signs such as frothing from the ...
HypoglycaemiaIt is a quite frequent observation in malariaIt may contribute to the neurological disturbancesIn pregnant wo...
It may present during early convalescence or patientreceiving 5% dextrose during treatment, not becauseof liver glycogen d...
CIRCULATORY COLLAPSEMarked hypotension where systolic BP less than 80mm of Hg in supine positionCold clammy, cyanotic skin...
Urticaria as an allergic manifestationSinusitisOccasionally retinal and sub conjunctivalhaemorrhage may also present as an...
Common errors in diagnosisFailure to do a malarial blood film (Thick and thinsmear)Failure to take a detail history e.g. t...
MANAGEMENT OF MALARIA
General PrincipleIf parasitiological confirmation of malaria is notreadily available, a blood film should be made and thet...
Do not confuse the doses of salt and base. Quininedoses are prescribed as salt (10 mg of salt 8.3 mg ofbase). Chloroquine ...
AnaemiaKeep haemoglobin level above 7 gm per centIf required a slow transfusion of 5 ml-10 ml/kg pcvor 10-20 ml/kg whole b...
Pulmonary oedemaIt may be caused by fluid overload, so careful fluidmanagement is vitalAlong with strict control of fluid ...
HYPOGLYCAEMIAPrompt IV glucose is essential and life savingPregnant woman with malaria closely monitor both,hypoglycaemia ...
Hyper pyrexia and associated managementCooling by fanning, tepid lukewarm water spongingUse appropriate antipyreticPneumon...
Acute renal failureIt is because of haemoglobinaemia may lead tooliguria and ARFContinue appropriate anti malarial treatme...
If oliguria (below 400 ml/24 hrs.) is presentpreventive measure for the development of ARFshould be institutedPatient with...
DRUG THERAPYQuinineStill it is a drug of choice for the treatment forsevere and complicated malariaIt should always be giv...
Hypoglycaemia is the most frequent adverse sideeffectIM injection of quinine is not recommendedIn suspected quinine poison...
CHLOROQUINEChloroquine is still the more widely prescribed drugin the tropicsIt should always be given by slow rate contro...
Dosage ScheduleDose 5 mg. base/kgInfusion Volume : 10 ml/kg Infusion Time 4.6 hoursInfusion interval 8 hoursIM chloroquine...
Falciparum resistanceacross India
Recommended Combinations 1.   Artemether + Lumefantrine (Lumether) 2.   Artesunate (3 days) + Amodiaquine 3.   Artesunate ...
MefloquineChemically related to quinineIt is a long acting schizontocideIt is effective against multidrug resistant parasi...
Artemisine (Artesunate)It is ancient Chinese herbal medicineArtesunate is a semisynthetic derivative ofartemisineDoseIV /I...
Side effect : GI upsetRelatively safe drug
ArteetherIt is an artemisinin derivativeIt has a ‘reserve status’ in WHO essential drug,means it should be reserved for mu...
Combinations not recommended 1.   Chloroquine based combinations (e.g CQ + SP; CQ +      Artesunate) 2.   Artesunate (sing...
What to give in pregnancy ? •   In 1st trimester     •   Quinine + Clindamycin 7 days •   In 2nd and 3rd trimesters     • ...
PRESUMPTIVE TREATMENT(Before the result of the smear is known)It is given to all fever cases or cases with history offever...
G6 PD deficiencyIt is a myth that person with G6PD deficiency aremore protected from P. falciparum malariaThey suffer more...
RADICAL TREATMENT(All microscopically positive cases)All microscopically positive cases of malariaare to be given radical ...
CHEMOPROPHYLAXIS Chloroquine-sensitiveP.falciparum :Chloroquine :   300 mg base once weekly. Start 1 week before   exposur...
TAKE HOME MESSAGEMalaria continues to be major killer of MankindApproximately one million die each year of malariaaround t...
REFERENCES1. Gilles HM, Warrell DA. Brace Chwatt’s Essential Malariology.Third Edition. Plates: 1, 2, 3, 4, 6, 25 Pg. 44. ...
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
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Management issues in malaria

  1. 1. Management Issues in MalariaDr Rajesh Deshwal, MD, FHMConsultant in Internal Medicine and HIV MedicineMilitary Hospital, Agra Cantonment, India
  2. 2. Major killer of mankindMost important parasitic diseaseApproximately one million die each year
  3. 3. Usual Clinical Presentations in Malaria
  4. 4. Incubation PeriodP. vivax 18-40 DaysP. falciparum 9-14 days
  5. 5. Cold stage, onset occurs with • Lassitude • Headache,often severe • Nausea followed by vomiting • Chilly sensation followed by rigors • Skin feels cold; later it becomes hot • Parasite is usually demonstrable in the blood • Pulse rapid and may be weak
  6. 6. Hot StagePatient feels hotSkin is hot and dry to touchHeadache is intense but nausea diminishesPulse is full and respiration rapid
  7. 7. Sweating stageProfuse sweatingBody temperature drops rapidly to normalSkin is cool and moistPulse rate becomes slowerPatient feels relieved and often falls asleep
  8. 8. Followed by afebrile interval of 48-72 hours hencetypical malarial fever is usually observed onalternate days
  9. 9. Latent periodThe patient is usually free of symptoms butin P. vivax hypnozoites persist in the liver andin P. falciparum infection, followinginadequate treatment parasites persist inthe blood
  10. 10. RecrudescenceIt is a renewed manifestation of infection withindays or weeksIt is a result of continued survival or presence in theblood of asexual forms of parasite because of notreatment or inadequate treatment
  11. 11. RelapseIt is the result from maturation of hypnozoites inthe liver with liberation of merozoites in to thebloodIt varies according to the species and even accordingto the group or strainIt can occur even three years after the primaryinfection
  12. 12. Peripheral smearEssential for the confirmation of the diagnosis ofmalariaConfirming the species of parasite present in thebloodThick film is reliable in searching for parasiteThin is valuable for identification of species
  13. 13. Rapid Diagnostic Tests(RDT)- PfHRP2- PMA-aldolase- pLDH
  14. 14. Pattern of feverMay be irregular or continuousWhen more than two breeds of parasites areinvolved daily paroxysms may be observedThe pattern may be varied by use of antipyretics andchemoprophylaxis
  15. 15. UNUSUAL PRESENTATIONS OFMALARIA
  16. 16. Uncomplicated malaria in adult and olderpatients may present with following symptoms:Bodyache, headache and no feverThroat pain, bodyache and mild feverSevere headacheDiarrhoea, jaundice, urticariaPain in epigastrium
  17. 17. Uncomplicated malaria in children maypresent with following symptoms:Vomiting, cough, urticariaNo rhinitis and clear throatChild becomes irritable, crying and not lookinghealthy
  18. 18. Causes of fever where malaria is likely tobe confused are:- URTI- UTI- Influenza- Dengue- Typhoid and paratyphoid fever- Tuberculosis- Amoebic liver abscess- Brain abscess, endocarditis
  19. 19. When malaria is associated with JaundiceViral HepatitisLeptospirosisCholangiohepatitisThe most important step in diagnosis is to think ofthe possibility that malaria may be the cause ofpatient’s illness
  20. 20. AnaemiaAnaemia is an inevitable consequence of malaria,because of the great proportion of erythrocyteswhich became parasitized in malarial infectionRelease of more malaria antigens result into markedimmunohaemolytic anaemiaGrowth of parasite within erythrocyte leads toconsistent drop in the haematocrit level which leadsto shortening of the life span of RBC even in theabsence of overt infection
  21. 21. It is more common and more marked inchildren than in adultsMalaria may be the cause of sudden andcatastrophic fall in Hb% in pregnant womenRememberIn any illness with or without fever sudden orpersistent fall in Hb%, think of malaria first
  22. 22. JaundiceJaundice with palpable liver and spleen is common finding infalciparum malariaDegree of icterus correlates well with the amount ofhaemolysisClinical signs of hepatic failure are rarely seenRaised serum bilirubin, SGPT, SGOT level in the liver profilestudy is also observed in malariaBile pigment in the urine usually increased during the malariaRemember Fever in the presence of jaundice suggest malaria rather thanviral hepatitis in which the fever has usually resolved by thetime jaundice develops
  23. 23. Gastro intestinal involvementVomiting is a common feature of severe malariaparticularly in childrenDiarrhoea in case of malaria may be seen as a resultfrom necrosis and damage to the intestinal wallSweating, vomiting and diarrhoea may combine toproduce dehydrationRemember : Any GIT symptoms can be caused bymalaria, but a blood film to exclude malaria shouldalways be taken
  24. 24. SEVERE COMPLICATED MALARIA
  25. 25. Cerebral MalariaAny manifestation of cerebral dysfunction in apatient with malaria is evident of cerebral malariaOccurs particularly when nonimmune persons haveremained untreated for 3 to 7 days after thedevelopment of primary feverPatient’s condition may deteriorate rapidly withincreasing headache and drowsiness which latermerge into confusion and comaInspite of treatment given the condition maydeteriorate further into deep coma
  26. 26. When the coma is light, patient may be able to talkand answer questions, although later patient will haveno recollection of having done soIn severe infections, delirium and coma may developsuddenly and may even occur early during the courseof the febrile illnessPatients with cerebral malaria may present withconvulsions, hallucinations and a state of agitationHyperpyrexia is not unusual, focal neurologicaldeficits and signs of meningeal irritation are rareCSF is usually normal on examination
  27. 27. Acute renal failureMalaria with associated dehydration and hypotension may leadto oliguria, anuria, and ultimately acute renal failureIntravascular haemolysis and secondary infection may furtheraggravate the situationA reduction in urine output 400 ml or less per day indicaterenal failureRaised blood urea and serum creatinineIf effective treatment not employed may reach high levelsRemember A careful clue in the early watch on a urinary out put andraised blood urea and serum creatinine is a good diagnosis ofARF due to malaria
  28. 28. PULMONARY MANIFESTATIONS INMALARIAMalaria may present with signs and symptomssuggestive of respiratory disease like pneumonia,bronchial asthma, bronchitis and more grave ARDSMost commonest presentation are fever with orwithout chills, cough with expectoration or drycough, chest pain and dyspneaHaemoptysis is uncommon
  29. 29. Hepatomegaly and splenomegaly are for less clinicalobservation. Drop in haematocrit level, but nospecific abnormality trends seen in total ordifferential leucocyte countPeripheral blood film examination reveals the type ofmalariaIf not treated in time ARDS is the most commoncomplication in pulmonary manifestations and wheremanagement is extremely difficult and prognosis isalso poor
  30. 30. Pulmonary edemaThis could be a grave and fatal complication due to P.falciparum MalariaThe pathogenesis of this condition remains unclearThe first indication of pulmonary edema is coughusually dry, difficulty in breathing, tightness in thechestDyspnoea may increase rapidly in severity
  31. 31. The respiratory rate goes up - crepitations mayappearHaemoptysis is usually absentSerious signs such as frothing from the mouth,cyanosis, convulsions, deterioration in the level ofconsciousness may lead to grave complication likeARDSRememberIncidence of respiratory manifestations in malariaare far more than described in the literature.Suspicion of malaria should be kept and peripheralsmear examination help in decreasing morbidity andmortality
  32. 32. HypoglycaemiaIt is a quite frequent observation in malariaIt may contribute to the neurological disturbancesIn pregnant woman suffering from malariahypoglycaemia appears to be a common clinicalobservation
  33. 33. It may present during early convalescence or patientreceiving 5% dextrose during treatment, not becauseof liver glycogen depletion or starvation but due toglucose consumption by the malaria, and stimulationof insulin secretion by quinineRememberAny patient with symptoms of hypoglycaemia may bemisdiagnosed as a case of cerebral malariaGlucometer is a more powerful tool in visit bag or in aclinic than stethoscope
  34. 34. CIRCULATORY COLLAPSEMarked hypotension where systolic BP less than 80mm of Hg in supine positionCold clammy, cyanotic skinConstricted peripheral vessels may occur in severefalciparum malariaCirculatory collapse may occur suddenly if it isassociated with severe dehydration, gram negativesepticaemia and massive GI haemorrhageThis grave emergency in past was also known as‘Algid Malaria’
  35. 35. Urticaria as an allergic manifestationSinusitisOccasionally retinal and sub conjunctivalhaemorrhage may also present as an unusualpresentation in malaria
  36. 36. Common errors in diagnosisFailure to do a malarial blood film (Thick and thinsmear)Failure to take a detail history e.g. travel history,previous malarial infectionMisjudgement of severity of the diseaseFalse parasitological diagnosisMissed hypoglycaemiaMissed diagnosis e.g. influenza, viral hepatitis,typhoid feverFailure to perform fundoscopic examination to ruleout presence of retinal haemorrhage
  37. 37. MANAGEMENT OF MALARIA
  38. 38. General PrincipleIf parasitiological confirmation of malaria is notreadily available, a blood film should be made and thetreatment started on the basis of clinicalpresentationIn severe malaria, anti malarial therapy must begiven Intravenously or Intramuscularly, oraltreatment should be substituted as early as possibleDoses must be calculated in on a mg/kg of bodyweight. It is important to weigh the patient, this isparticularly important for children
  39. 39. Do not confuse the doses of salt and base. Quininedoses are prescribed as salt (10 mg of salt 8.3 mg ofbase). Chloroquine and mefloquine are prescribed asa baseGood nursing care is vitalMaintain adequate fluid balance, to avoidoverhydration or underhydrationInitial check of blood glucose is vitalFrequent monitoring for hypoglycaemia are importantFrequent monitoring of the therapeutic response isimportant
  40. 40. AnaemiaKeep haemoglobin level above 7 gm per centIf required a slow transfusion of 5 ml-10 ml/kg pcvor 10-20 ml/kg whole blood may be givenIn children with severe anaemia with associatedtachycardia inj. frusemide (1-2 mg/kg) may be givenAdminister appropriate anti malarial therapy withproper dosage calculationSupplement iron and folic acid during convalescentperiod is helpful
  41. 41. Pulmonary oedemaIt may be caused by fluid overload, so careful fluidmanagement is vitalAlong with strict control of fluid intake proppedpatient at an angle of 45⁰Maintain CVPGive high concentration of oxygen by any convenientmethodIV frusemide (40-120 mg) should be tried first, ifCVP does not fall use other vasodilators in wellequipped ICUIf required fluid can be removed by dialysis
  42. 42. HYPOGLYCAEMIAPrompt IV glucose is essential and life savingPregnant woman with malaria closely monitor both,hypoglycaemia and foetal distress50% glucose (up to 1.0 ml/kg) followed by IV infusionof 10-20% dextrose should be givenThe possible recurrence of hypoglycaemia, whenpatient on IV quinine should be kept in mind
  43. 43. Hyper pyrexia and associated managementCooling by fanning, tepid lukewarm water spongingUse appropriate antipyreticPneumonia, urinary tract infection, typhoid fevershould be treated with appropriate antibioticsBe careful in using nephrotoxic drugs such assulphonamides, aminoglycosides and tetracycline ifthere is renal insufficiency or hepatotoxic antibioticin case of complicated jaundice or altered LFT
  44. 44. Acute renal failureIt is because of haemoglobinaemia may lead tooliguria and ARFContinue appropriate anti malarial treatmentMaintain haematocrit level above 20% or 7 gmCorrect fluid and electrolyte deficitTreatment of hypotension and shock is of vitalimportance
  45. 45. If oliguria (below 400 ml/24 hrs.) is presentpreventive measure for the development of ARFshould be institutedPatient with G6PD deficiency should be screenedcarefullyARF demands skillful management hence referpatient to a well equipped centre, because thesepatient may require peritoneal/hemo-dialysis
  46. 46. DRUG THERAPYQuinineStill it is a drug of choice for the treatment forsevere and complicated malariaIt should always be given by rate controlled infusionnever by bolus IV injectionSwitch on to oral administration as early as possibleCommon side effect are tinnitus, hearing loss,nausea, uneasiness, restlessness and blurring ofvisionSerious CVS and neurological toxicity is rare
  47. 47. Hypoglycaemia is the most frequent adverse sideeffectIM injection of quinine is not recommendedIn suspected quinine poisoning activated charcoalgiven orally or by nasogastric tube accelerateseliminationDosage Schedule : Dose 10 mg salt/kg InfusionVolume : 10 ml/kg if pt is normally hydrated. 20ml/kg if pt is dehydrated.5 ml/kg. if the pt. isoverhydratedInfusion time : 2.5 hours. Infusion interval : 8 hours
  48. 48. CHLOROQUINEChloroquine is still the more widely prescribed drugin the tropicsIt should always be given by slow rate controlled IVinfusion, and never by bolus injectionOral therapy should be substituted as early aspossibleSide effects include headache, nausea, vomiting,uneasiness, blurred vision, hypotension and pruritis
  49. 49. Dosage ScheduleDose 5 mg. base/kgInfusion Volume : 10 ml/kg Infusion Time 4.6 hoursInfusion interval 8 hoursIM chloroquine injection may be given as 5 mgbase/kg in two divided doses of 2.5 mg/kg in thegluteal region at an interval of one hour and repeatedevery 12 hours, never to be given in single doseAvoid in infants and in children
  50. 50. Falciparum resistanceacross India
  51. 51. Recommended Combinations 1. Artemether + Lumefantrine (Lumether) 2. Artesunate (3 days) + Amodiaquine 3. Artesunate (3 days) + Mefloquine 4. Artesunate (3 days) + SP 5. Amodiaquine + SP (as interim option)
  52. 52. MefloquineChemically related to quinineIt is a long acting schizontocideIt is effective against multidrug resistant parasiteSingle oral dose is sufficient to effect cureDose 20 mg to 25 mg/kg taken as a single doseSide effect may include GI upset, dizziness, fatigue,asymptomatic bradycardia and occasionally acutepsychosis
  53. 53. Artemisine (Artesunate)It is ancient Chinese herbal medicineArtesunate is a semisynthetic derivative ofartemisineDoseIV /IM 2.4 mg/kg and 1.2 mg/kg after 12 hrs andthen daily for 5 daysOral : 100-200mg initially then 100 mg daily for 4-5days
  54. 54. Side effect : GI upsetRelatively safe drug
  55. 55. ArteetherIt is an artemisinin derivativeIt has a ‘reserve status’ in WHO essential drug,means it should be reserved for multi drug resistantmalariaSo far no significant toxicity or drug resistance tothese compound has been reportedCompliance of patient is excellentCost of therapy is comparable to other second lineantimalarial drugsDose : 150 mg deep IM once daily on threeconsecutive days
  56. 56. Combinations not recommended 1. Chloroquine based combinations (e.g CQ + SP; CQ + Artesunate) 2. Artesunate (single dose) + SP 3. Chloproguanil-Dapsone (LapDap)
  57. 57. What to give in pregnancy ? • In 1st trimester • Quinine + Clindamycin 7 days • In 2nd and 3rd trimesters • Any ACT combination as per rec. or • Artesunate + Clindamycin 7 days or • Quinine + Clindamycin 7 days • Lactating women same ACT
  58. 58. PRESUMPTIVE TREATMENT(Before the result of the smear is known)It is given to all fever cases or cases with history offever during the preceding 15 days immediatelyafter the blood smear is collected and also to fevercases where blood smears are not collectedChloroquine base Day 1, 10 mg/kg (600 mg adult)Primaquine Day 1, 0.75 mg/kg (45 mg adult)Chloroquine base Day 2, 10 mg/kg (600 mg adult)Chloroquine base Day 3, 5 mg/kg (300 mg adult)
  59. 59. G6 PD deficiencyIt is a myth that person with G6PD deficiency aremore protected from P. falciparum malariaThey suffer more frequently from P. vivax malariaIntravascular haemolysis may occur in G6PDdeficient person, due to action of anti malarial drugson older erythrocytesAs a physician one should be careful of G6PDdeficiency in certain ethnic group e.g. Parsi, Khatri,SindhisPrimaquine can produce massive haemolysis and maycause severe anaemia, and renal failure
  60. 60. RADICAL TREATMENT(All microscopically positive cases)All microscopically positive cases of malariaare to be given radical treatment withPrimaquine for its anti-relapse properties
  61. 61. CHEMOPROPHYLAXIS Chloroquine-sensitiveP.falciparum :Chloroquine : 300 mg base once weekly. Start 1 week before exposure Chloroquine-resistant P.falciparum       a)Mefloquine 250 mg base once weekly. Start 1 week before exposure b)Doxycycline 100 mg daily. Start 2 days before exposure c)Chloroquine 300 mg base weekly. Start 1 week before exposure plus Proguanil 200 mg daily. Start 2 days before exposure
  62. 62. TAKE HOME MESSAGEMalaria continues to be major killer of MankindApproximately one million die each year of malariaaround the globeWe must take note of changing pattern of malariaThe malaria prone areas are now the metro cities andurban IndiaNewer development of ‘Resistant Malaria’ has to bekept in mind
  63. 63. REFERENCES1. Gilles HM, Warrell DA. Brace Chwatt’s Essential Malariology.Third Edition. Plates: 1, 2, 3, 4, 6, 25 Pg. 44. 3 rd ed.2. The Clinical Management of Acute Malaria. WHO regionalpublications. South East Asia - Series No. 9. Pgs. 19, 27, 37, 46,47, 50, 51, 54, 68.3. Management of severe and complicated malaria practicalhandbook. HM Gilles WHO Geneva. Pg. 20, 35, 46. 2 nd ed.4. A closer look at Malaria’ General Practitioners’ AssociationSurat Publication. Pg. 67, 68.5. Guidelines for Diagnosis and Treatment of Malaria in India2011.

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