Plasmodium falciparum malaria is a protazoal infection transmitted by female anopeles mosquito. This can be commonly seen in tropical and subtropical countries. Following the mosquito bite plasmodium protazoa enters to the human circulation in the stage of Sporozoites and with in few minutes they enters the liver. Nearly for next 2 week they multiply with in hepatocytes and released to the circulation as the stage, merozoites. these thousands of merozoites enters to the red blood cells and start further multiplication producing schizonts. These schizonts are ruptured and released in to the circulation promoting furter multiplication by entering to new red blood cells (erythrocytic stage). Female anopeles mosquito can infect at this stage and can spread to the other humans.
Fever and chills
Fever occurs with the rupture and release of red blood cell contents which are pyrogens. So the fever pattern will usually depend on the length of the erythrocytic stage. But in plasmodium falciparum malaria there will be aperiodic fever pattern called malignant fever
Non specific constitutional symptoms like headache, malaise, myalgia, anorexia
These are associated with the fever and occur with the release of inflammatory contents to the circulation with the rupture of erythrocytes
Easy fatiguability, lethargy and shortness of breath With the excessive premature destruction of erythrocytes, patient will develop anaemia
Yellowish discoloration of eyes With the excessive red cell destruction there will be increased bilirubin production causing jaundice. With the hepatocyte destruction at initial stage also will have some contribution for this.
Abdominal pain/discomfort
Patient will develop hepato-splenomegaly with the excessivered cell destruction[18][19][20]. Rarely splenic rupture can occure with the acute massive splenomegally. So there will be features of peritonitis such as sudden onset sever abdominal pain, ill health and faintishness secondary to circulatory collapse.
Evidence of cerebral malaria
There will be confusion, drowsiness, coma, seizures, body weakness and sensory loss. Cerebral malaria is one of life threatening complication associated with plasmodium falciparum malaria. This is due to the sequestration effect of infected red blood cells which stick to each other anf to the endothelium of the blood vessels (cytoadherence) blocking cerebral circulation.
Evidence of metabolic acidosis
This is also another life threatening complicaltion patient will present with sudden onset difficulty in brathing. This is due to the lactic acid production with the infection causing lactic acidosis.
Features of hypoglycaemia
Patient will present will symptoms like faintishness, sweating and development of seizures. With the excessive usage for cell turnover leads to hypoglycaemia. This is usually associated with the severe disease and common among children, during pregnancy and in patients currently on anti malarial drugs like quinine.
Symptoms of acute renal failure
Generalized body swelling and reduced or absent urine output are the symptoms which patient can present with. This is secondary to acute tubular necrosis which occur as a complication of sequestration causing hypoperfusion . Some time acute renal failure occurs with another severe complication called blackwater fever. This is due to the haemoglobin urea associated with excessive red cell destruction. The condition is associated with symptoms like red coloured urine, rapidly developed anaemia features as mentioned above and high fever and chills. So this haemoglobinuria can finally leads to acute renal failure.
Evidence of pulmonary oedema
Shortness of breath, chest pain, cough, wheezing and pink frothy sputum are the main symptoms associated with pulmonary oedema. This also resulting from the pulmonary vessel occlusion with sequestration. This can finally leads to Acute Respiratory Distress Syndrome
Evidence of increased bleeding tendency
Bleeding from puncture sites, cannula can be seen. With the excessive erythropoiesis, other blood cell production from bone marrow will be depleted. So there will be low platelet counts. With the excessive workload on liver, there will be poor clotting factor production. So both of these conditions finally resulting increased bleeding tendency
Evidence of shock
This is another complication which can be seen in severe malaria (algid malaria). The primary causes are super added bacterial infection causing septicaemia, dehydration causing hypovolaemia and splenic rupture causing peritonitis. Symptoms will be ill health, dizziness, unresponsiveness, coma
Obstetric history
As pregnant mothers and fetuses of infected mothers are at risk of getting severe complication even death and in pregnacy treatment options are different, Obstetric history is very important. Plasmodium falciparum malaria will be associated with miscarriages, pre term deliveries, still births and IUGR
Evidence of vascular occlusion on other organs With the effect of sequestration and adherent of red blood cells to vascular endothelium thrombi formation can take place in any organ with symptoms of hypoperfusion. eg: Myocardial infarction/ anginan (chest pain, shortess of brath, faintishness), acute limb ischemia (acute limb pain especially during moving, skin discoloration), mesenteric ischmia (abdominal pain), retinal ischemia (visual disturbances).
Examination
General examination
look for general well being of the patient, hydration, any features of nutritional deficiency (angular stomatitis, chelitis), rashes and lymphadenopathy (in malaria there will be no rashes or lymphadenopathy).
Temperature
Temperature need to be recorded and a temperature card should be be maintained to see the fever pattern. this is important in differentiating various types of malaria (p. vivax and p.ovale- tertian fever pattern, p.malariae- quartan fever pattern, p. falciparum- aperiodic fever pattern).
Pallor
Patient will be pale due to excessive destruction of red blood cells.
Jaundice
With the excessive red cell destruction causing increase in bilirubin production and hepatocyte destruction at initial stage leads to the jaundice.
Abdominal examination
This will reveals the massive hepato-splenomegly (especially with chronic disease) due to the excess workload on both organs [13][14][15]. Examination should be done carefully as the massive spenomegally is at risk of rupture.
Central nervous system examination
With the cerebral malaria t5here will be confusion, drowsiness, coma, development of seizures and focal neurological signs like motor and sensory impairment and cranial nerve palsy. In a case of cerebellar involvement there will be signs of imbalance and incordination.
Signs of metabolic acidosis
Patient will be rapidly and deeply breathing (Kussmaul's breathing), vomiting due to lactic acidosis.
Signs of hypoglycaemia
There will be signs of autonomic nervous system involvement, like excessive sweating and tremor. patient will be anxious. Due to the neurological involvement there will be signs like confusion, drowsiness, coma and development of seizures. Rarely transient focal neurological signs (eg: body weakness) can occur
Signs of acute renal failure
There will be generalized oedema associated with oliguria or anuria in blackwater fever there will bedark red coloured urine(haemoglobinuria) on examination
Signs of pulmonary oedema
On examination patient will be dyspnoic and there will be coughing and wheezing. Sputum will be pink and frothy. Lung examination will reveals rhonchi and bibasal end-inspiratory crackles. In the presence of Acute Respiratory Distress Syndrome there will be cyanosis, tacycardia, tachypnoea and bilateral end-inspiratory crackles.
Signs of increased bleeding tendency
There will be excessive bleeding from puncture sites and and cannula sites. Spontaneous bleeding can occur causing gum bleeding, nasal bleeding,, Per Vaginal bleeding, haematuria and Per Rectal bleeding
Signs of shock
In shock patient will be pale, tachycardic, capillary refilling time < 2 seconds, dyspnois and oliguric with evidence of primary cause
Signs of pregnancy complications
In a miscarriage there will be per vaginal bleeding and abdominal pain, In a pre term delivery watery/ blood stained vaginal discharge will be present with pre term labour pains. Still birth there will be absent foetal movements and foetal heart sounds
Signs of other vascular occlusion
Signs will depend on the organ affecting with the vascular occlusion. eg: Myocardial infarction/ angina there will be chest pain, shortess of brath and faintishness), In acute limb ischemia patient will be in a severe pain with limited movements, limb will be cold and there will be skin discoloration mesenteric ischmia there will be adominal tenderness Fundoscopic examination in retinal ischemia will show pale disk, exudate and retinal hemorrhages like signs
Differential diagnoses
Other types of malaria
Other types of malaria are plasmodium vivax, plasmodium ovale and plasmodium malariae. pathophysiology of all malarial infections are common with some changes of the behaviour of various parasites.
In plasmodium vivax and plasmodium ovale incubation period is 8-25 days, asexual phase is 48 hrs giving a tertian periodic fever pattern.Exo-erythrocytic cycle will persist as hypnozoites and relapses are common up to 2 years.
In plasmodium malariae incubation period is 15-30 days, asexual phase is 72 hrs giving a quartan periodic fever pattern. hypnozoites will not present and recrudescence can occur many years later.other types of malaria sequestration will not present and complicatons are not much severe as plasmodium falciparum malaria. thick and thin blood film examination will helpful in differentiating the various types.
Dengue infection
Dengue infection need to be consider mainly in tropical countries as it also spread by mosquitoes. In simple uncomplicated dengue fever there will be only fever, severe headache, myelgia, arthralgia associated with leucopenia and thrombocytopenia. In complicated stages (eg: dengue haemorrhagic fever) there will be complications like severe thrombocytopenia with spontaneous bleeding, fluid leakage causing pleural effusion and ascites, hypovolaemic shock and hepatic encephalopathy. Dengyue antigen tests will useful in diagnosing and differentiating the condition from malaria.
Leptospirosis
This is a common zoonotic disease (caused by rodents especially common rat) caused by leptospira interrogans. patient will develop fever, weakness, muscle pain and tenderness, severe headache and photopobia like symptoms. complications associated with the disease are aseptic meningitis, pulmonary syndrome and weil's disease causing fever, haemorrhages, jaundice and acute renal failure. Microscopic agglutination test will confirm te disease and differentiate it from malaria.
Other causes of haemolytic anaemia
In malarial infection there is an extensive haemolytivc anaemia. So other causes of aemolytic anaemia need to be excluded:. Eg,Hereditory causes- hereditory spherocytosis, G6PD deficiency, genetic abnormalities of haemoglobin
Acquired causes- autoimmune haemolytic anaemia, drug induced haemolysis, red cell fragmentation syndrome, march haemoglobinuria, paroxysmal nocturnal haemoglobinuria.
septicaemia caused by systemic infections
Septicaemia secondary to various infections like Urinary tract infections, pulmonary infections, wound infections, gastrointestinal tract infections and central nervous system infections can present with septic shock. These causes need to be excluded in a septic shock of a malaria patient.
Other causes of strokes
In a patient with cerebral malaria other causes of cerebral hypoperfusion need to be consider like diabetes mellitus, hypertension, hyperlipidaema, connective tissue disorders like SLE, thrombotic thrombocytopenic purpura and congenital thrombophilic conditions.
Other causes of acute renal failure
In a case of acute renal failure other causes need to be excludes. In a non septic, haemodynamically stable patient urinary tract obstruction, vascular occlusion( by trombi, drugs like ACEI), rapid progressive glomerulonephritis, drug induced and acute interstitial nephritis (eg; drug induced, immune mediated, secondary to infections and toxins.
Investigations - Diagnosis
Full blood count
This will give evidence of anaemia with low haemoglobin levels, WBC count will be important in a case of super added infection and Platelet count assessment will needed in the presence of spontaneous bleeding.
Thick and thin blood films
Thick blood film- will show lysed red blood cells and useful in identifying the level of parasitaemia.
Thin blood film is important in diagnosing the type of malaria according to the stages and number of stages available. in early stages of the plasmodium falciparum malaria there will be only ring forms and gametocytes appear after 2 weeks (they will persist even after treatments
Rapid stick test
This an immunochromatographic test for plasmodium falciparum malaria antigens. This test is rapid and diagnose the disease with out microscopic look. But the test is 100 times less sensitive than a careful blood film examination.[4][5][6][13] [14]
Investigations
Blood grouping and cross matching
As these patients can develop severe anaemia blood grouping and cross matching will be needed in a case of blood tramnsfusion
Clotting profile with PT/INR and APTT
As these patients are at risk of developing spontaneous bleeding and coagulopathy clotting profile useful in identifying the clotting defects.
Renal function tests like UFR, serum creatinine, blood urea and serum electrolytes
Renal function assessment is useful in these patients as they are at risk of going in to acute renal failure. So there tests are useful in diagnosing as well as during the follow up.
Liver function tests like AST, ALT, Serum proteins, direct and indirect bilirubin levels
At the beginning of the malarial infection in primary exo-eruthrocytic cycle parasites are multiply with in hepatocytes so liver cells can rupture and die with the release of merozoites. So assessment of liver funcction is important. With the excessive red cell destruction patient can develop jaundice causing increased unconjugated bilirubin. So assessment of bilirubin level and type (direct/ indirect) will be useful.
With the excessive workload on liver, production of protein will be affected. So serum protein level will give a rough idea about the compromised function of the liver.
Random blood glucose level
For early Hypoglycaemia identification will help in management. Capillary blood sugar level assessment can be done during continuous monitoring of the patient.
Arterial blood gas analysis
This is useful in a suspected case of metabolic acidosis.
Blood/ urine culture and ABST
In clinically suspected septicaemia these are useful before starting antibiotics
Ultrasound scan
In the presence of hepatosplenomegaly ultrasound scan of the abdomen will be useful.Also antenatal ultrasouns scan with doppler will useful in pregnant patients to assess the foetal well being and the placental condition.
Chest X ray
As these patients are at risk of developing pulmonary oedema, ARDS and aspiration pneumonia with development of cerebral malaria Chest X ray is useful
CT/MRI brain
In cerebral malatria these are useful in diagnosing and managing the patient.
Investigations - Followup
In the follow up continuing the same investigations mentioned in the fitness assessment will be helpful.
In follow up also regular full blood count capillary blood sugar monitoring, renal function tests, liver function tests, serial ultrasound scans with doppler in anteneatal follow ups, Chest Xray will be useful
Management - General
Health education
Educate the patient and family members about the disease, possible complications, investigations which need to be done, treatments available, way of spreading, importance of prophylaxis and prevention
Prevention
1) Avoid mosquito bites is one of measure to prevent the disease. wearing long sleeves and trousers to especially at night (time of anopheline mosquito bites), use of mosquito repellents like mosquito coils, sprays, creams and so on and use of mosquito nets will help in aviding mosquito bites.
2) Control mosquitoes is another method and can be done in community level in endemic areas.eg; Destroying mosquito breading places
Destroy mosquitoes with chemicals (eg; permethrine) Biological control of early stages with special fish species.
3) Chemoprophylaxis can be use to prevent the disease occurrence.eg; Proguanil- useful in pre erythrocytic forms Atovaquone with Proguanil/ doxycycline/ chloroquine/mefloquine - useful in erythrocytic stage
The choice of drug and doses will be depend on living area/traveling area, length of exposure, level of disease transmission, drug resistance, presence of any underlying disease and medications currently on.
Close monitoring
patient's vital parameters like temperature, blood pressure, pulse rate, respiratory rate, urine out put need to be monitor. Maintaining a temperature chart and input output chart will be more useful.
Antipyretics
Antipyretics like paracetamol, ibuprofen will be useful in controlling the fever. Other than that measures like tepid sponging and fanning will also useful
Exchange transfusion in severe disease
Exchange transfusion will be useful in reducing the parasitic load and infected red blood cells
Blood transfusion for severe anaemia
Blood transfusion can be consider according to the haemoglobin level and the anemic symptoms of the poatient in severe disease.
Management of acute renal failure Main thing is to start antimalarial treatment then symptomatic management can be done to protect the renal function. Monitoring the fluid balance, fluid replacement combine with diuretics/dopamine and if serum creatinine level is high/ hyperkalaemia features present dialysis can be consider.
Management of respiratory complications like pulmonary oedema and ARDS
In pulmonary oedema prop up the patient in 45 degree angle, give oxygen, stop IV infusions and use IV diuretics and intubate is hypoxia is severe.
In ARDS ITU admission, supportive therapy (respiratory support- eg: CPAP, circulatory support- eg; fluid management, inotropes) and specific treatment for underlying cause are the main treatment options.
Management of shock
Secure ABC, give high flow oxygen, establish two IV accesses with wide bore cannulas, send blood for investigatins to identify the causative factors and rapid fluid infusion will be needed to secure haemadynamic stability. Identify and treat the primary cause as soon as possible.
Management of hypoglycaemia As mentioned in the history hypoglycaemia occur in severe disease and with quinine therapy. So people who are at risk of developing hypoglycaemia must educate about the risk, symptoms and first aid.
CBS need to monitor frequently for early identification.
Management of hypoglycaemia
As mentioned in the history hypoglycaemia occur in severe disease and with quinine therapy. So people who are at risk of developing hypoglycaemia must educate about the risk, symptoms and first aid.
CBS need to monitor frequently for early identification.
Management of hypoglycaemia:
Give oral dextrose to replace the deficiency.
Management of hypoglycaemic coma:
Give IV 20-30g dextrose, If not recovering can give IV/IM glucagon 1mg. Dextrose IV infusion will be useful in prolonged hypoglycaema.
Management of metabolic acidosis
Give oxygen. Look for the primary cause (hypoglycaemia/ hypovolaemia/ septicaemia) and treat it.
Management of spontaneous bleeding and coagulopathy Transfusion of FFP/ cryoprecipitate and platelets will be useful in spontaneous bleeding. Vitamin K injection will also be useful.
Management - Specific
Uncomplicated Plasmodium falciparum malarial management oral Quinine dihydrochloride/ sulphate 600mg (10mg/Kg) 8hrly for 3-5 days until clinical improvement with blood free from parasites. This should be followed by a single dose of sulfadoxine 1.5mg combine with pyrimethamine 75mg.
Other combinations available are (in case of decreased quinine efficasy),
1) Atovaquone 250mg with proguanil 100mg 4 tablets once daily for 3 days
2) oral artemether200mg daily for 5 days followed by mefloquine 500mg 2 doses 2 hours apart
3) Oral artemether 80/480 mg twice a day for 3 days
Cerebral malaria management
Patient should be admitted to ITU and monitoring need to be done while managing associated complications (eg: giving diazepam for seizures).
proper antimalarial treatment should be included from below options,
1) Antimal Artesunate/ quinine 20mg/kg (maximum 1.4g) over 4 hours every 8 hourly (or can be given as an IVI of 30mg/kg/ day after loading dose)
2) Artemether 3.2mg/Kg followed by 1.6mg/Kg daily.
Malaria management in pregnancy quinine alone for 7 days need to be given. If needed doxycycline 100mg daily for 7 days can be added.[
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