Complicated Malaria - Copy

8/8/2019 Complicated Malaria - Copy

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Complicated malaria

Presenter Dr Amina Mgunya

Facilitator Dr Y Mgonda


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layout

` Introduction

` Pathophysiology

` Clinical presentation

` Clinical management


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Introduction

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` Malaria is the most important parasitic dse in the tropics

` Caused by Plasmodium Spp` Spp in human

` P. malariae` P. vivax` P. falciparum` P. ovale

`

Vector: female mosq Anopheles spp` Severe malaria is commonly caused by P. falciparum

` 1-3 million death ww each year


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High risk groups

` Under fives` travelers

` emigrants

` pregnant women,

` immunosuppressed

protected

` sickle cell trait,(six folds protection compared to normal)

` thalassemia, and

` glucose-6-phosphate dehydrogenase (G6PD) deficiency

` This decrease in risk appears to be related to impairedparasite growth at low oxygen tensions


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pathophysiology

` mosquito inoculates plasmodial sporozoites

liver (hepatic parenchymal)multiplication known as intrahepatic or preerythrocytic

schizogony or merogony10,000 to >30,000 daughter merozoites

enter RBC became trophozoites

Erythroid cycle multiply occupy whole RBC

Schizont rupture to release merozoites RBCsome into (gametocytes) (erythrocytic cycle 48hrs)


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` The disease in human beings is caused bythe direct effects of RBC invasion and destruction bythe asexual parasite

and the host's reaction.

` Mechanism for symptoms and signs not clear buthypothesis

Mechanical hypothesis

Humoral hypothesis


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Mechanical hypothesis

Cytoadherance

` is mediated by strain specific, high MWP. f ErythrocyteMembrane Protein 1 (PfEMP 1)

` It is exported to the surface of infected RBC andanchored through the membrane to a sub-membranousaccretion of parasite derived histidine rich protein (PfHRP)

` These accretions cause humps or knobs on the surface ofthe red cell and these are the points of attachment tovascular endothelium


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` Some parasites are knob -ve and yet show cytoadehrence

` A protein called sequestrin has also been identified recently

` Cytoadherence may be modulated by the spleen and cytoadherencedoes not occur after splenectomy

` Adhesion molecules on the endothelium:` Leukocyte differentiating antigen CD36

` intercellular adhesion molecule 1 (ICAM1)` VCAM

` Thrombospondin

Favours sequestration


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Knobs and cytoadherence

` The parasite exportsPfEMP1 and other proteins(this picture is showing

Knob associated protein)into the RBC and its surfaceto form knobs

` F: in early rings protein is inthe parasites, G,H: in trophs

it is found first within theRBC cytoplasm and then atthe RBC membrane (I).


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` Rosetting

` Agglutination of pfRbc with Non pfRbc within the circulationto form a Rosette

` Rosettes occlude microcirculation and Causes stasisBlocks microcirculation and also favours cytoadherance

` Agglutination (among parasitised)


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HUMORAL MECHANISMS


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Clinical presentation

Celebral malaria unrousable coma 30minprostration, i.e. generalized weakness so that the patient is unable walk or sit up

without assistance

-Change of behaviour kk hallucinations,delusions, agitations.

multiple convulsionsmore than two episodes in 24 h

respiratory distress (acidotic breathing kussmal breathing)circulatory collapse or shock, systolic blood pressure < 70 mm Hg in adults

and < 50 mm Hg in children

clinical jaundice plus evidence of other vital organ dysfunction

haemoglobinuria

abnormal spontaneous bleeding


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Laboratory findings:

hypoglycaemia ( random blood glucose < 2.2 mmol/l or < 40 mg/dl)metabolic acidosis (plasma bicarbonate < 15 mmol/l)

severe normocytic anaemia (Hb < 7 g/dl, packed cell volume < 21%)

haemoglobinuria

hyperparasitaemia >5000 asexual parasites/200WBC (200,000asexual parasites ul)

hyperlactataemia (lactate > 5 mmol/l)

renal impairment (serum creatinine > 265 mol/l).

radiological

pulmonary oedema


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Not define severe malaria` Hyperpyrexia : Rectal temperature above 40 C (104 F


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Cerebral malaria

` This is the most well known manifestationof severe malaria

Defined asunarousable coma persist for at least

30min

with asexual forms of p.falsiparum in theperipheral smearOther causes of encephalopathy excluded


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mechanism

` Not known` Believed to result from cytoadherence , roseting and

sequestration of parasitized RBCs in small blood vesselsof the brain consequence of it being

` blood flow Cerebral hypoxia

` Cytokine release NO neurotoxic a knowndepressor of CNS


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Presentation

` Onset of coma may be sudden following a seizure, or itcould be gradual with drowsiness, confusion,disorientation, delirium, or agitation.

` A seizure could be generalized or focal.

`

Decoticate ,deselebrate and opithotonous postures arepossible

` Cranial nerve abnormalities are rare.

` Tone and deep tendon reflexes (DTR) are

normal, increased, or decreased. Corneal reflex ispreserved, except in deep coma.

` Abdominal reflexes are invariably absent


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` Immunosupression increases risk of cerebral malaria

` Cerebral malaria can rapidly progress to death casefatality 20%- 30%

` In suvivors coma usualy recover within one to two days

` And may be with a neurological sequela in 5%


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Severe anaemia

` DefinedNormocytic normochromic anaemia

with haematocrit < 21 % or haemoglobin < 7 gm/dl

mechanisms

1. Obligatory destruction of RBCs containing parasitesat merogony.

2. Accelerated destruction of non-parasitised RBCs, parallels diseaseseverity.

3. Lowered threshold for splenic clearance of

abnormal erythrocytes. Red blood cell survival is

decreased.


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pathogenesis

4. TNF alpha which contribute to bone marrow

suppression and less protection RBCs destruction.

Mgt

` Haptoglobulinaemia marker of haemolysis, so may beconsidered as a useful indicator of falsiparum

` Majority require BT


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Acute renal failure

Malaria acute renal failure is diagnosed when serum

creatinine level rises above 3 mg/dL ( 265 mol/L)and/orwhen urinary output is less than 400 ml in24 hours.

Despite good hydration

Pathogenesis

Renal ischaemia due to seqestration cytoadhesion

rossetingHypovolemia

DIC


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` The prevalence of ARF due to falciparum malaria wasfound to be 4% in India

J. Prakash1, A. Gupta1, O. Kumar2, S. B. Rout2,V.Malhotra2 and P. K. Srivastava2

Varanasi, India


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mngt

` institution of appropriate antimalarials, at the earliest and

` maintenance of fluid and electrolytes, recording of intakeand output chart,

` Dialysis if indicated .

` In survivors, urine flow resumes in 4 days.

` Creatinine returns to normal in 7 days

` Nephrotic syndrome can occur with P. falciparum.


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Pulmonary oedema

` Graveous and most fatal complication of severe malaria` It has a mortality rate of > 85%.

` Hypeparasitemia, pregnancy, renal failure and metabolicacidosis are recognized risk factors

Mechanism

` Increased capillary permeability not reflected in othercapillary beds,

` selective excessively permeability not known


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` It may develop anytime during course of illness even after

initiation of RX

` Presenting with SOB, frothy sputum, basal crept, low O2

saturation < 95%

Chest xray show increased interstitial shadowing

Mgt

O2 therapy,

IV frusemide


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hypoglysemia

` :Plasma glucose level of < 40 mg/dl (2.2mmol / l

` Pathogenesis

1. Increased glucose demands by parasitized hepatocytesParasites consume upto 70 times as much glucose as

uninfected cells .

2. Increased peripheral requirement of glucose

consequent upon anaerobic glycolysis.3. Increased metabolic demands of febrile illness.

4.Obligatory demand of parasites.5. Quinine stimulated insulin secretion from pancreatic

beta cells.


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Metabolic acidosis

` a primary lactic acidosis

may result form renal failure

venous, capillary, and CSF concentration of lactate

Increases

pathogenesis

1. Anaerobic glycolysis due to microvascular

obstruction.

2. Failure of hepatic and renal lactate clearance.

3. Production of lactate by the parasite.

4.hypovolemia

.


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PresentationHyperventilation (Kussmaul breathing)

with a clear chest on auscultation suggest metabolicacidosis

Management

O2 therapy

Correct hypovolemia Most cases resolve without IVHCO3


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Spontaneous bleeding

` Severe haemorrhage is seen in 5% of cases

` Mechanisms

` RBCs containing parasites and released cytokines areprocoagulant.

` Thrombocytopenia is caused by increased splenic clearance.

` There is accelerated coagulation cascade activity with

accelerated fibrinogen turnover, consumption of

antithrombin III, and increased concentration of

fibrinogen degradation products (FDP).

` Prothrombin time (PT) and activated partial prothrombintime are prolonged.


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` presentation.` The patient may develop bleeding gums, epistaxis,

petechiae, subconjunctival haemorrhages.

` Significant bleeding, malena, and haemetemesis occurs in

< 10% cases.


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Black water fever

` Passage of black or dark brown or red urine (coca cola like urine)

` in previously infected subjects and is characterised by sudden intravascularhaemolysis followed by fever and haemoglobinuria

Pathogenesis

Massive intravascular haemolysisIn falciparum malaria intravascular haemolysis occurs periodically at the time

of schizogony.

This probably stimulates the R.E. System to form antibodies of the nature ofhaemolysin and lecitholysin.

Thus in repeated malarial attacks a hyper-sensitised state is produced

when stimulated by any factor, such as heavy P. falciparum infectionadministration of quinine and other precipitating factors leads to anexplosive output of haemolysin


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` not associated with significant renal impairment.` It is usually transient, and resolves without complications.

` In severe cases ATN develops from massive

haemolysis.

Transfused blood is also rapidly

haemolysed where plasma may also be red.

The patient often has a slate grey appearance.


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dx

` Microscopy -Peripheral blood smear` gold standard

Thin and thick smears

gametocytes +schizonts

speciation + counting ,


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` Why parasites are not detected at times in peripheralsmear ?a. sequestration in deep vascular bed

b. partially treated patients

c. prophylactic antimalarial treatmentd. inexperienced microscopiste. poor quality staining


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` Intradermal smearResearchers have found that smears from intradermalblood may contain more mature forms of P.falciparumthan the peripheral blood. It may also show pigmentcontaining leucocytes after blood smear is negative


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Antigen detection method

` Rapid DiagnosticTest (RDT)` Detect protein or enzymes` Simple rapid,` sensitive,` highly specific dipstick or cards

` detect 2 malaria specific antigens in blood, Histidine richprotein (PfHRP2) and parasite lactate dehydrogenase(PfLDH)

` PfLDH is cleared within days after Rx but PfHRP2 last upto 1/12 after acute infection


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other

` Fluorescent dye of plasmodium DNA and RNA` Post mortem brain smear for cerebral malaria

` PCR


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treatment`

Quinine is the drug of choice for the treatment ofcomplicated/severe falciparum malaria.

Antimalarial action

Is highly effective blood schizonticide against the four species.

It does not kill mature gametocytes ofP. falciparum

gametocidal to the other species

It is not active against liver stage parasites.

adm

`

Oral quinine therapy is recommended if the patient is still capableof swallowing

` If not parenteral quinine preferably IV


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` If C/I of IV eg fluid overload it may be intramuscularinjection [IM] (half dose in each anterior thigh).

` For IM use, quinine should be diluted in normal saline to

a concentration of 60 mg/ml.

` This concentration appears to be less irritant than theundiluted concentration of300 mg/ml.


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` Initial loading dose must be given by slow intravenousinfusion.` The dosage is quinine dihydrochloride salt (20 mg/kg

body weight) in` 5% dextrose saline (5-10 ml/kg )

` depending on the patient's fluid balance, intravenously,over 4 hours


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` A maintenance dose of10mg/kg.` until pt can take orally then oral Q for 7 days or a full

course of ALU` patients with impaired renal function) require a

reduction in maintenance quinine dihydrochloride salt to5-7 mg/kg every 8 hours

`

Non response to quinine should be given im artmether3.2mg/kg followed by1.6mg/kg od for 6 days.


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Artesunate

` Randomized trials

comparing artesunate and quinine from South-East Asiashow clear evidence of benefit

` with artesunate mortality was reduced by 34.7% in theartesunate group compared to the quinine group.


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In prosses guidelines adopt from WHO

` artesunate 2.4 mg/kg body weight IV or IM given onadmission (time = 0), then at 12 h and 24 h, then once aday is the recommended treatment.

` Quinine is an acceptable alternative

if parenteral artesunate is not available:


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SUPPORITIVE &

ADJUNCTIVE THERAPY

`

Nursing Care` Catherization

` Nasogastric tube

` Fluid & Electrolyte

` Monitor level of coma & vital signs

` Antipyretics` Anticonvulsants

` Correction of Hypoglycaemia

` Correction of - Anaemia, Acidosis, Dehydration


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LONGTERM COMPLICATION


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Hyperreactive malarial splenomegaly

(Tropical splenomegally syndrome)

`

Chronic or repeated malarial infections produce hypergammaglobulinemiasplenomegaly.

` Some residents of malaria-endemic areas in tropical Africa and Asia exhibitan abnormal immunologic response to repeated infections

` This syndrome has been associated with the production of cytotoxic IgMantibodies to CD8+T lymphocytes

` This causes inhibition of suppressorT cells, which normally regulate IgMproduction.

` This leads to uninhibited B cell production of IgM and the formation of

cryoglobulins (IgM aggregates and immune complexes).

` The need to clear these macromolecular aggregates stimulates thereticuloendothelial system, resulting in hyperplasia.


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` Clinical features` Abdominal swelling

` Pain due to splenic infarction can occur.

` Liver is also enlarged.

` There is pancytopenia and increased susceptibility toinfection.

` Peripheral smear is usually negative for parasites.


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Treatment` Size of spleen and liver regresses with antimalarial

treatment.

Splenectomy is recommended in severe hypersplenism andtreatment failure, i.e., when treatment has been given for6 months.


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B.Quartan nephropathy

:

` Repeated or continuous P. malariae infection is associated with childhoodnephrotic syndrome

.

` immune-complex injury to the renal glomeruli, resulting in the nephrotic syndrome.

` Other, unidentified factors must contribute to this process since only a very smallproportion of infected patients develop renal disease.

` The histologic appearance is that of focal or segmental glomerulonephritis withsplitting of the capillary basement membrane

-The pattern varies from asymptomatic proteinuria to fullblown nephrotic syndrome :

It usually progresses inexorably to renal failure over 3yrs


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` Spontaneous remission is rare. Some cases respond` to cytotoxics, but antimalarials and corticosteroids do

` not prevent progression


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` C.Burkitts lymphoma` There is a strong association between Burkitts

lymphoma and malaria.

` Progression of EBV (Epstein-Barr virus) infection in B

lymphocytes is controlled by virus specific cytotoxicTcells.

` This response is significantly decreased during malarialinfection.

` This may predispose to malignant transformation.


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` Malaria kills millions each year ww` InTANZANIA

`MALARIAHAIKUBALIKI

`THANKS

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Complicated Malaria - Copy