Malaria clinical features

1. Malaria Clinical features and diagnosis

2. 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 Cases-225 million deaths -7.81 million www.searo.who.int

3. 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

4. India 80.5% of the population lives in malaria risk areas In 2010 15.9 million cases were reported No of deaths- 1023 nvbdcp.gov.in

5. KSCH data(2010-2011) Total no of slides examined -7092 Total no of positives- 336 P vivax-291 P falciparum-45 Deaths- 10

6. Clinical features Children are asymptomatic during the initial phase– the incubation period P falciparum ---- 9-14 days P vivax ---- 12-17 days P ovale ---- 16-18 days P malariae --- 18-40 days P rolonged in p vivax , partial immunity and incomplete chemoprophylaxis.

7. Prodromal symptoms Headache Fatigue Anorexia Myalgia Pain in joints Chest and abdominal pain

8. Clinical features (cont..) The classic presentation is paroxysms of fever alternating with periods of fatigue but otherwise relative wellness

9. 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 .

10. 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)

11. On the basis of severity malaria can be classified as uncomplicated complicated

12. 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 is usually suspected clinically on the basis of fever or a history of fever. Guidelines for the treatment of malaria – 2nd edition World Health Organization, 2010

13. Complicated or severe malaria In a patient with P. falciparum parasitaemia presence of certain clinical features or laboratory parameters classify the patient as severe or complicated malaria

14. 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

15. 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)

16. 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 ar eas of high stable malaria transmission intensity) Hyperlactataemia (lactate > 5 mmol /l) Renal impairment (serum creatinine 3 mg/dl)

17. Clinical profile of Severe malaria in India Characteristics Frequency(46) Mortality Cerebral malaria 76% 22% Severe anemia 34% 56% Hypoglycemia 21% 40% Jaundice 15% 57% Renal failure 8% 75% Blackwater fever 6% 66% Algid malaria 4% 50% Indian Pediatrics 2003; 40:939-945 

18. 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

19. cerebral malaria (cont..) C linical syndrome characterised by C oma (inability to localise a painful stimulus) at least 1 h after termination of a seizure or correction of hypoglycaemia D etection 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

20. cerebral malaria (cont...) Seizures Seizures are commonly reported and occur in over 60% of children causes of seizures In children not associated with fever at the time of the seizure or electrolyte disturbances. Sequestration of infected erythrocytes Parasite-derived toxins Immune mechanisms

21. Cerebral malaria (cont..) Coma Cerebral malaria is a diffuse encephalopathy characterised by coma and bilateral slowing on Electroencephalography coma is potentially reversible. Brainstem signs Changes in pupillary size and reaction D isorders of conjugate gaze and eye movements. A bnormal respiratory patterns (such as hyperventilatory , ataxic, and periodic breathing) posture ( decerebrate , decorticate, or opisthotonic posturing), and motor abnormalities of tone and reflexes

22. Cerebral malaria (cont..) Cerebral malaria should be considered in the differential diagnosis of any patient who has a febrile illness with impaired consciousness who lives in or has recently travelled to malaria endemic areas The mortality rate in children is about 20%, and most deaths happen within 24 h of admission.

23. Cerebral Malaria Clinical feature Children (African) Adults Onset Rapid Insidious Seizures More common (in 80%) In 20 % Neurological signs Brainstem signs, raised ICP,retinal changes Symmetrical upper motor neuron signs Mortality 18.6% 20% Sequelae 11% <5% Lancet Neurol 2005; 4: 827–40

24. Neurological sequelae Hemiplegia Cortical blindness Aphasia Ataxia Cognitive impairment Richard Idro , Lancet Neurol 2005; 4: 827–40

25. 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 Neurol 2005; 4: 827–40

26. Anemia of Malaria Hemoglobin less than 8 g/dl, which is equivalent to a hematocrit of less than 24% in a parasitemic individual Abdalla S, Weatherall D, Wickramasinghe SN and Hughes M (1980). The anaemia of P. falciparum malaria. Br. J. Haematol. 46: 171 World Health Organization has defined severe malarial anemia (SMA) as a hemoglobin less than 5 g/ dL or a hematocrit less than 15% seen in the context of malaria but without specifying parasitemia . WHO (2000). Severe falciparum malaria. Trans. R. Soc. Trop. Med. Hyg . 94: Suppl. 1.

27. 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

28. 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 .

29. Renal failure In P. falciparum malaria, acute renal failure may develop in 0.1-0.6% of the patients 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 H igh mortality ( upto 45%) Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002

30. 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

31. 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) This may result form renal failure, but more commonly there is a primary lactic acidosis T rans R Soc Trop Med Hyg . 1994 Jan-Feb;88(1):67-73.

32. Hypoglycemia Hypoglycemia occurs in 30% of children Hypoglycemia is a sign of poor prognosis with a mortality rate as high as 40%.

33. Pulmonary edema/adult respiratory distress syndrome (ARDS) May develop even after several days of antimalarial therapy Mortality >80 %

34. P vivax …. neglected and not benign In recent years, complicated and even fatal cases of malaria due to P. vivax have been increasingly reported

35. Complications of p vivax contd.. Severe anemia Acute respiratory distress syndrome (ARDS) Incidence is less in children compared adults Coma Malnutrition Splenic rupture Thrombocytopenia Acute renal failure and shock mortality rate - 1.6% among hospitalized patients Trends in Parasitology Vol.25 No.5

36. 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.

37. 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 indian pediatrics volume 42 november 2005

38. EXAMINATION OF BLOOD FILM A minimum of 100 fields should be examined before concluding the slide to be negative. S amples may be examined for at least three consecutive days where clinical suspicion of malaria persists.

39. 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

40. 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

41. 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 lactate dehydrogenase ( pLDH ) pan-specific aldolase Commercially available kit can detect falciparum , vivax and other malaria but cannot differentiate ovale and malarie malaria.

42. 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

43. ADVANTAGES OF RDTS IN COMPARISON TO MICROSCOPY 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

44. DISADVANTAGE OF RDTS IN COMPARISON TO MICROSCOPY RDTs that target HRP-II of P. Falciparum is 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

45. 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