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Malaria Clinical features and diagnosis
EPIDEMIOLOGY Malaria  is a major public health problem Malaria is the fifth most common infectious cause of mortality 3.3 billion ( half of world’s population ) are at risk of malaria in 109 countries In 2009  ,[object Object]
deaths -7.81 millionwww.searo.who.int
Disease Burden in South East Asia Region Out of 11 countries of the Region 10 countries are malaria endemic 15% of the global reported confirmed cases and 2.7% of the global mortality. In southeast Asia region India accounts for 80% of cases                                                                      www.searo.who.int
India 80.5% of the population lives in malaria risk areas In 2010 ,[object Object]
 No of deaths- 1023                                                                         nvbdcp.gov.in
KSCH data(2010-2011) Total no of slides examined -7092 Total no of positives- 336 P vivax-291 P falciparum-45 Deaths- 10
Clinical features Children are asymptomatic during the initial phase– the incubation period ,[object Object]
P vivax---- 12-17 days
P ovale----  16-18 days
P malariae--- 18-40 days
Prolonged in p vivax, partial immunity and incomplete chemoprophylaxis.,[object Object]
Clinical features (cont..)    The classic presentation is paroxysms of fever alternating with periods of fatigue but otherwise relative wellness
Clinical features (cont…) Fever is the cardinal symptom of malaria Febrile paroxysms associated with rigors , headache, myalgia , back pain, abdominal pain, nausea and vomiting. Paroxysms coincide with rupture of schizonts P vivax:  every 48 hours( benign tertian malaria) P falciparum and mixed infections: no periodicity or less appparent.
Presentation Fever					96% Chills					96% Headache				79% Muscle Pain				60% Palpable liver				33% Palpable Spleen			28% Nausea or vomiting			23% Abdominal pain/diarrhea		  6% (According to the working group of WHO,2001)
     On the basis of severity malaria can be  				classified as                      uncomplicated                            complicated
Uncomplicated malaria Uncomplicated malaria is defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction.  The signs and symptoms of uncomplicated malaria are nonspecific.  Malaria isusually suspected clinically on the basis of fever or a history of fever. Guidelines for the treatment of malaria – 2nd edition World Health Organization, 2010
Complicated or severe malaria In a patient with P. falciparumparasitaemia presence of certain clinical features or laboratory parameters classify the patient as severe or complicated malaria
Complicated malaria (cont..) Clinical features Impaired consciousness or unrousable coma prostration Failure to feed Multiple convulsions (more than 2 episodes in 24 h) Deep breathing, respiratory distress
Complicated malaria (cont..) Clinical features (cont..) Circulatory collapse or shock, systolic blood pressure < 70 mm Hg in adults and < 50 mm Hg in children Clinical jaundice ( serum bil > 3 mg/dl) plus evidence of other vital organ dysfunction Haemoglobinuria Abnormal spontaneous bleeding Pulmonary oedema (radiological)
Complicated malaria (cont…) Laboratory parameters Hypoglycemia (blood glucose < 2.2 mmol/l or < 40 mg/dl) Metabolic acidosis (plasma bicarbonate < 15 mmol/l) Severe normocytic anaemia (Hb < 5 g/dl) Haemoglobinuria Hyperparasitaemia(> 2%in low intensity transmission areas or > 5%  in areas of high stable malaria transmission intensity) Hyperlactataemia (lactate > 5 mmol/l) Renal impairment (serum creatinine 3 mg/dl)
Clinical profile of Severe malaria in India Indian Pediatrics 2003; 40:939-945 
Cerebral malaria Cerebral malaria is the most severe neurological complication of Plasmodium falciparum It is a major cause of acute non-traumatic encephalopathy in tropical countries
cerebral malaria (cont..) Clinical syndrome characterised by  Coma (inability to localise a painful stimulus) at least 1 h after termination of a seizure or correction of hypoglycaemia Detection of asexual forms of P falciparum malaria parasites on peripheral blood smears, and exclusion of other causes WHO. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000
cerebral malaria (cont...) Seizures      Seizures are commonly reported and occur in over 60% of children  causes of seizures ,[object Object]
Sequestration of infected erythrocytes
Parasite-derived toxins
Immune mechanisms,[object Object]
coma is potentially reversible.Brainstem signs ,[object Object]
Disorders of conjugate gaze and eye movements.
Abnormal respiratory patterns (such as hyperventilatory, ataxic, and periodic breathing)
posture (decerebrate, decorticate, or opisthotonic posturing), and motor abnormalities of tone and reflexes,[object Object]
Cerebral Malaria Lancet Neurol2005; 4: 827–40
Neurological sequelae Hemiplegia Cortical blindness Aphasia  Ataxia Cognitive impairment Richard Idro ,Lancet Neurol 2005; 4: 827–40
Malarial Retinopathy Common  in children with cerebral malaria(60%) and may be related to pathological changes Malarial retinopathy consists of four main components: retinal whitening, vessel changes(whitening of retinal vessels), retinal hemorrhages, and papilledema Bad prognostic indicator Lancet Neurol2005; 4: 827–40
Anemia of Malaria ,[object Object],Abdalla S, Weatherall D, Wickramasinghe SN and Hughes M (1980). The anaemia of P. falciparum malaria. Br. J. Haematol. 46: 171 ,[object Object],WHO (2000). Severe falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 94: Suppl. 1.
Pancytopenia Pancytopenia can occur in both falciparum and vivax infections. Can be due to microangiopathic hemolytic anemia, hypersplenism Few cases due to bone marrow suppression have and hemophagocytosis have been reported                        J Fam Community Med. 2009;16:71-73
Hepatic dysfunction In patients with severe malarial infestation, the incidence of jaundice is reported to be around 2.5%  Transient abnormalities of liver enzymes are most commonly seen If serum bil > 3 mg/dl---- severe malaria Hepatic encephalopathy is almost never seen. Bhalla A J Postgrad Med 2006 Oct-Dec;52(4):315-20.
Renal failure ,[object Object],Defined as Urine output <400 ml/24 hours in adults (<12 ml/kg/24 hours in children) and a serum creatinine >265 µmol/l (> 3.0 mg/dl) despite adequate volume repletion Renal failure is rare in children ,[object Object],                Indian Academy of Clinical Medicine  Vol. 3, No. 2  April-June 2002
Renal failure contd.. The vulnerable group of patients are: with high parasitaemia with deep jaundice with prolonged dehydration patients receiving NSAIDs Manifests as ATN ,renal cortical necrosis never develops
Metabolic acidosis Venous lactate concentration at 4 hours after admission to hospital is the BEST PROGNOSTIC INDICATOR in severe malaria. (>5mmol/l has bad prognosis) ,[object Object],Trans R Soc Trop Med Hyg. 1994 Jan-Feb;88(1):67-73.
Hypoglycemia Hypoglycemia occurs in 30% of children Hypoglycemia is a sign of poor prognosis with a mortality rate as high as 40%.
Pulmonary edema/adult respiratorydistress syndrome (ARDS) May develop even after several days of antimalarial therapy Mortality >80%
P vivax…. neglected and not benign In recent years, complicated and even fatal cases of malaria due to P. vivax have been increasingly reported
Complications of p vivaxcontd.. Severe anemia Acute respiratory distress syndrome (ARDS) ,[object Object],Coma Malnutrition Splenic  rupture Thrombocytopenia Acute renal failure and shock mortality rate -   1.6% among hospitalized patients Trends in Parasitology Vol.25 No.5

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Malaria clinical features

  • 2.
  • 4. Disease Burden in South East Asia Region Out of 11 countries of the Region 10 countries are malaria endemic 15% of the global reported confirmed cases and 2.7% of the global mortality. In southeast Asia region India accounts for 80% of cases www.searo.who.int
  • 5.
  • 6. No of deaths- 1023 nvbdcp.gov.in
  • 7. KSCH data(2010-2011) Total no of slides examined -7092 Total no of positives- 336 P vivax-291 P falciparum-45 Deaths- 10
  • 8.
  • 10. P ovale---- 16-18 days
  • 12.
  • 13. Clinical features (cont..) The classic presentation is paroxysms of fever alternating with periods of fatigue but otherwise relative wellness
  • 14. Clinical features (cont…) Fever is the cardinal symptom of malaria Febrile paroxysms associated with rigors , headache, myalgia , back pain, abdominal pain, nausea and vomiting. Paroxysms coincide with rupture of schizonts P vivax: every 48 hours( benign tertian malaria) P falciparum and mixed infections: no periodicity or less appparent.
  • 15. Presentation Fever 96% Chills 96% Headache 79% Muscle Pain 60% Palpable liver 33% Palpable Spleen 28% Nausea or vomiting 23% Abdominal pain/diarrhea 6% (According to the working group of WHO,2001)
  • 16. On the basis of severity malaria can be classified as uncomplicated complicated
  • 17. Uncomplicated malaria Uncomplicated malaria is defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction. The signs and symptoms of uncomplicated malaria are nonspecific. Malaria isusually suspected clinically on the basis of fever or a history of fever. Guidelines for the treatment of malaria – 2nd edition World Health Organization, 2010
  • 18. Complicated or severe malaria In a patient with P. falciparumparasitaemia presence of certain clinical features or laboratory parameters classify the patient as severe or complicated malaria
  • 19. Complicated malaria (cont..) Clinical features Impaired consciousness or unrousable coma prostration Failure to feed Multiple convulsions (more than 2 episodes in 24 h) Deep breathing, respiratory distress
  • 20. Complicated malaria (cont..) Clinical features (cont..) Circulatory collapse or shock, systolic blood pressure < 70 mm Hg in adults and < 50 mm Hg in children Clinical jaundice ( serum bil > 3 mg/dl) plus evidence of other vital organ dysfunction Haemoglobinuria Abnormal spontaneous bleeding Pulmonary oedema (radiological)
  • 21. Complicated malaria (cont…) Laboratory parameters Hypoglycemia (blood glucose < 2.2 mmol/l or < 40 mg/dl) Metabolic acidosis (plasma bicarbonate < 15 mmol/l) Severe normocytic anaemia (Hb < 5 g/dl) Haemoglobinuria Hyperparasitaemia(> 2%in low intensity transmission areas or > 5% in areas of high stable malaria transmission intensity) Hyperlactataemia (lactate > 5 mmol/l) Renal impairment (serum creatinine 3 mg/dl)
  • 22. Clinical profile of Severe malaria in India Indian Pediatrics 2003; 40:939-945 
  • 23. Cerebral malaria Cerebral malaria is the most severe neurological complication of Plasmodium falciparum It is a major cause of acute non-traumatic encephalopathy in tropical countries
  • 24. cerebral malaria (cont..) Clinical syndrome characterised by Coma (inability to localise a painful stimulus) at least 1 h after termination of a seizure or correction of hypoglycaemia Detection of asexual forms of P falciparum malaria parasites on peripheral blood smears, and exclusion of other causes WHO. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000
  • 25.
  • 28.
  • 29.
  • 30. Disorders of conjugate gaze and eye movements.
  • 31. Abnormal respiratory patterns (such as hyperventilatory, ataxic, and periodic breathing)
  • 32.
  • 33. Cerebral Malaria Lancet Neurol2005; 4: 827–40
  • 34. Neurological sequelae Hemiplegia Cortical blindness Aphasia Ataxia Cognitive impairment Richard Idro ,Lancet Neurol 2005; 4: 827–40
  • 35. Malarial Retinopathy Common in children with cerebral malaria(60%) and may be related to pathological changes Malarial retinopathy consists of four main components: retinal whitening, vessel changes(whitening of retinal vessels), retinal hemorrhages, and papilledema Bad prognostic indicator Lancet Neurol2005; 4: 827–40
  • 36.
  • 37. Pancytopenia Pancytopenia can occur in both falciparum and vivax infections. Can be due to microangiopathic hemolytic anemia, hypersplenism Few cases due to bone marrow suppression have and hemophagocytosis have been reported J Fam Community Med. 2009;16:71-73
  • 38. Hepatic dysfunction In patients with severe malarial infestation, the incidence of jaundice is reported to be around 2.5% Transient abnormalities of liver enzymes are most commonly seen If serum bil > 3 mg/dl---- severe malaria Hepatic encephalopathy is almost never seen. Bhalla A J Postgrad Med 2006 Oct-Dec;52(4):315-20.
  • 39.
  • 40. Renal failure contd.. The vulnerable group of patients are: with high parasitaemia with deep jaundice with prolonged dehydration patients receiving NSAIDs Manifests as ATN ,renal cortical necrosis never develops
  • 41.
  • 42. Hypoglycemia Hypoglycemia occurs in 30% of children Hypoglycemia is a sign of poor prognosis with a mortality rate as high as 40%.
  • 43. Pulmonary edema/adult respiratorydistress syndrome (ARDS) May develop even after several days of antimalarial therapy Mortality >80%
  • 44. P vivax…. neglected and not benign In recent years, complicated and even fatal cases of malaria due to P. vivax have been increasingly reported
  • 45.
  • 46. Diagnosis Symptom-based (clinical) diagnosis Not possible to accurately diagnose malaria using any one set of clinical criteria Microscopy Microscopy of stained thick and thin blood smears remains the gold standard for confirmation of diagnosis of malaria.
  • 47. Diagnosis(cont..) In profound anemia ---parasite --often absent malaria pigment in polymorphonuclear leukocytes and monocytes-- malaria If more than 5% of PNM contains visible pigment it denotes poor prognosis. Recommendations and IAP plan of action indianpediatrics volume 42 november 2005
  • 48. EXAMINATION OF BLOOD FILM A minimum of 100 fields should be examined before concluding the slide to be negative. Samples may be examined for at least three consecutive days where clinical suspicion of malaria persists.
  • 49. ADVANTAGE OF MICROSCOPY Advantages of microscopy are: The sensitivity is high. It is possible to detect malaria parasites at low densities. It also helps to quantify the parasite load. It is possible to distinguish the various species of malaria parasite and their different stages WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health Organization, 2000
  • 50. Diagnosis (cont..) Rapid diagnostic tests are immunochromatographic tests that detect parasite-specific antigens in a finger-prick blood sample WHO recommends that such tests should have a sensitivity of > 95% in detecting plasmodia at densities of more than 100 parasites per μl of blood
  • 51. Diagnosis RDT.. Current tests are based on the detection of histidine-rich protein 2 (HRP2), (specific for P. Falciparum) pan-specific or species-specific Plasmodium lactatedehydrogenase (pLDH) pan-specific aldolase Commercially available kit can detect falciparum, vivax and other malaria but cannot differentiate ovale and malarie malaria.
  • 52. Diagnosis RDT.. HRP-II tests can remain positive for 7-14 days following malaria treatment even when blood doesn't show parasitemia by microscopy p LDH is produced by only viable parasite so the tests detecting this antigen becomes negative within 3-5 days of treatment
  • 53. ADVANTAGES OF RDTS IN COMPARISON TOMICROSCOPY simple, straight forward ,less time consuming, requiring no special equipment or skill/training They can detect P. falciparum infection even when the parasite is sequestered This test can exclude mixed falciparum and vivax malaria where the former may not be evident microscopically
  • 54. DISADVANTAGE OF RDTS IN COMPARISONTO MICROSCOPY RDTs that target HRP-II of P. Falciparumis unsuitable for assessment of treatment failure and monitoring of drug resistance. They do not quantify the parasite load so they do not have prognostic value
  • 55. Disadvantages RDT cont... Under optimal conditions an expert microscopist can detect even 5-10 parasite per μl of blood, detection threshold of RDTs are 40- 60 parasite per μl of blood Currently, available RDT kits are required to be stored up to or under 30ºC