Malaria

M.R.Lokeshwar
Consultant Pediatrician, Hinduja Hospital, Mumbai, India.
First Created: 04/02/2001  Last Updated: 04/02/2001

Laboratory Diagnosis

Clinical symptomatology of malaria is not specific and resembles many other diseases and hence there is a necessity of investigations. Malaria is diagnosed by microscopic examination of peripheral blood-thin and thick smears, after staining with JSB stain fields or Giemsa stain.

The thin film is more accurate for parasite counting, however, at low parasitemia (<5 per 100 RBCs), the thick film should be counted. The presence of pigment in neutrophils and monocyte is an important clue to the diagnosis and is even seen after anti-malarial treatment.

Special new techniques include:

  • Indirect flourescent antibody test,

  • Enzyme linked immuno-sorbant assay (ELISA),

  • DNA probe test which is specific for P.falciparum,

  • A solid phase radio immuno-assay,

  • Immunoblot test (Dip stick test) which does not need microscope and detects tropozoite derived histidine rich protein-2 (HRP-2),

  • QBC test (Qualitative Buffy Coat test) which is rapid method for diagnosing of malarial parasite in the blood and is highly sensitive and specific,

  • Malarial parasite staining -green (DNA) and orange (RNA) under the ultraviolet light.

Management of Malaria

The aim in the treatment of malaria is to eliminate the erythrocytic form of malaria from circulating blood and in various organs and tissue and simultaneously to maintain the good general condition of the patient. Hence treatment of malaria should include 1. General measures, 2. Symptomatic and specific therapy, 3. Management of complications.

A high index of suspicion is an important factor for the success of treatment. A blood smear examination is necessary to confirm the diagnosis as well as to identify the species. However, treatment should not be delayed until the results of smears are available as negative smear does not rule out malaria, even cerebral malaria. If facilities are available, the parasitic index should be done as it predicts the prognosis. Parasite count more than 2-10% predicts a poor prognosis with a fatality rate of more than 50% particularly in non-immune persons in spite of the treatment. Parasite count >1% is usually not seen in the non-falciparum type of malaria.

General Measures:
By and large, non-falciparum malaria is not fatal and usually respond to routine line of treatment and routine anti-malarial drugs. In contrast, in P.falciparum malaria the rate of complications and drug resistance is high. Hence, hospitalization is more desirable for patients infected with P.falciparum malaria with high parasite load for proper follow-up and observation as there is a possibility of progression to various complications. Hospitalization for malaria caused by other species should be considered as per illness and the merit of the case. Younger children, unimmunized patients from non-endemic areas are likely to have more complications. Indications for hospitalization should include severe prostration, weakness, persistent vomiting, dehydration, hyperpyrexia, and signs of complications. Young children and pregnant women particularly infected with P.falciparum should be hospitalized. Good nursing care, maintenance of clear airway, turning the position of patient every two hours to prevent the bedsores, nursing inside a position to avoid the aspiration, etc. are required particularly in comatose patients. Proper nutrition, correction of vitamin deficiency, correction of fluid, and electrolyte imbalance should be carried out. An intake and output chart should be recorded. Look for black or dark urine. Symptomatic treatment includes management of fever, vomiting, etc. During hyperpyrexia, high fever should be brought down with the help of paracetamol (oral or rectal) and by tepid sponging. Anti-emetic like Domperidone for vomiting is useful. Anticonvulsants may be used- Inj. Phenobarbitone: 10-20 mg/kg I.V, Inj. Diazepam: 0.2 mg/kg IV, Inj.Phenytoin Sodium 20 mg/kg IV is useful. Hypoglycemia is a common complication in P.falciparum infection, more so in pregnant women and children. If blood sugar is low give 50% Dextrose IV and then 5-10% I.V. Dextrose may be given (80 mg/kg in 24 hours). Blood sugar should be checked repeatedly as hypoglycemia often recurs in patients receiving quinine and untreated hypoglycemia can be fatal. Glucagon 1 mg I.M every 30 minutes is useful for treating hypoglycemia. Packed cell transfusion may be required if associated with severe anemia of Hb less than 5 gm% or HCT <20-30%. To prevent pulmonary edema give 1-2 mg/kg of furosemide IV. Hemoglobinuria is treated by alkalinization of urine and adequate IV fluids keeping in mind to avoid fluid overload. Record of fluid intake and output should be maintained and fluid should be replaced maintaining the CVP at 5 cm of water. Urine output should be more than 30 ml/hr. Urine output <12 ml/kg/24 hours and serum creatinine >3 mg/dl indicates renal failure and may require fluid challenge test and IV Furosemide 1-2 mg/kg. If no response is obtained, a low dose of dopamine 3-5 ug/kg/min may be given. Dialysis may be considered if there is no response.

Specific treatment:
antimalarial drug treatment should be started on a high index of suspicion even without demonstrating the parasite on the peripheral smear particularly in small children, pregnant women, and immunocompromised patients. Among the various antimalarial drugs, chloroquine still remains the drug of choice until unless and resistance is suspected or it is associated with a complication. Antimalarial drugs should as far as possible be given orally and drugs must be calculated on mg/kg body weight base/salt.

Treatment of non-falciparum malaria:
As they do not develop resistance, chloroquine is the drug of choice. The loading dose of 10 mg/kg base is followed by 5 mg/kg after 6 hours and repeated on the 2nd and 3rd day. If necessary, therapy may be extended for 7 days. If associated with vomiting and if the child is not taking feeds, the drug may be given parenterally in 5 mg. base per kg body weight per day. If there is a suspicion of resistance then quinine may be given. For P.vivax and P.ovale, primaquine should be given to eradicate the parasites that survive in the liver (Hypnozoites) to achieve a radical cure which prevents relapse. The dose of primaquine is 0.2 to 0.3 mg/kg/day for 14 days and is available in the form of tablets of 2.5 mg and 7.5 mg. Patients with G6PD deficiency are vulnerable to hemolysis, hence it is contraindicated in such patients. However, in mild variants of G6PD deficiency, primaquine may be given 0.8 mg/kg, once a week for 6 weeks. In endemic areas, reinfection is common, and hence radical cure with primaquine is not indicated.

Treatment of P.falciparum:
Though chloroquine is effective in falciparum malaria, recently drug resistance has been reported from all over the world. Routinely chloroquine should be used unless resistance is suspected or associated with the complications, then quinine is desired. Chloroquine when given parenterally is given in the loading dose of 10 mg/kg base in isotonic fluid over 8 hours followed by 15 mg/kg given over the next 24 hours It may also be given in the dose of 5 mg. base/kg in isotonic fluid over 6 hours and repeated every 6 hours for a total of 5 doses. Loading dose should not be used if the patient has received quinine or quinidine within the preceding 24 hours or mefloquine within the preceding 7 days. If an intravenous infusion is not possible, Chloroquine may be given 3.5 mg/kg/ I.M. or S.C. 6 hourly. For chloroquine-resistant malaria, complicated malaria or if sensitivity is not known, quinine dihydrochloride is given in the dose of 20 mg of salt/kg as loading dose by infusion over 4 hours in 5% dextrose over 8-12 hours. The maintenance dose of quinine is 10 mg of salt/kg in dextrose saline over 4 hours and the dose should be repeated every 8-12 hours until the patient can take oral medications. Oral quinine should be started as early as possible. Quinine tablets are given in the dose of 10 mg/kg body weight every 8 hourly for 7 days. Quinidine may be given if parenteral quinine is not available. To shorten the course, a single dose of Sulfadoxine pyrimethamine is given, in the dose of Sulfadoxine 25 mg/kg body weight and pyrimethamine 1.2 mg/kg body weight. This drug is avoided in pregnant women.

In resistant cases (insignificant degree of quinine resistance as reported in Cambodia, Thailand, Vietnam), oral tetracycline 250 mg 4 times a day is given for 7 days (contraindicated in children under the age of 8 years and in pregnant women).

Mefloquine 15 mg/kg (Maximum 1000 mg) is given divided into 2 doses 12 hours apart (1 tablet of Mefloquine contains 250 mg of base). Mefloquine should not be given until 12 hours after the completion of parenteral quinine administration. It should be avoided during the first trimester of pregnancy. It is also an outstanding suppressive prophylactic drug when administered weekly or fortnightly for drug-resistant P.falciparum and P.vivax infection. As it is chemically related to quinine it exhibits cross-resistance with it. The commonest side effect is skin rash.

Halofantrine: It is effective against the erythrocytic stages of all species of malaria. Side effects include abdominal cramps, nausea & diarrhea. This drug should not be given to pregnant women as it is embryotoxic. It has cardiotoxicity and is available as oral preparation only. Dose:8 mg base/kg body weight every 6 hours for 3 doses.

Quinghaosu: It is an antimalarial drug extracted from the Chinese herb artemisia anna. It is effective on the asexual form of malarial parasite and can be used orally as well as parenterally. Various preparations available are Artesunate: given orally 5 mg/kg stat as on 1st day followed by 2.5 mg for the next 4 days. Artemisinin: given orally 25 mg/kg stat on 1st day followed by 12.5 mg for the next 4 days. Inj.Artemether (Inj.Paluther 80 mg): 3.2 mg/kg on 1st day, followed by 1.6 mg/kg for 5 days, until the patient can take orally or 3 days treatment at a dose of 1.6 mg/kg twice daily for a total of 9.6 mg/kg. It has good schizonticidal activity. Although there is little information about its use in pregnancy, the general consensus is that it can be used in mefloquine-resistant falciparum malaria. However, in early pregnancy, quinine is still preferred. It destroys the membrane of the parasite and inhibits the parasite growth. It reacts with protein (known as Hermione) in the membrane of the red cells and of the parasite. Within 12 hours, a 15% reduction in parasite load is obtained and in 24 hours there is an 80% reduction in parasite load. Side effects are minimal. There is no serious impact on cardiac function and hypoglycemia is not reported. It has excellent systemic tolerance. There is no tinnitus, dizziness, or blurring of vision and no known allergic reactions.

Malarial Vaccine

Despite massive investment towards the development of material vaccines, a safe, effective, and long-lasting vaccine is still a dream. The various vaccine tried are:

  • Liver stage vaccine or sporozoite stage vaccine:
    • Circumsporozoite surface protein (CS protein) which covers the sporozoites. However, it is found to be unprotective.

    • Cytotoxic lymphocyte fragment vaccine.
    • Sporozyte surface protein II (SSP-II): This is another major sporozoite protein and antibodies against the peptide strongly inhibit hepatocyte invasion of sporozoite.
    • Liver stage antigen I: begin tried

  • Blood stage vaccines:
    • Though this vaccine will be incapable of preventing infection, they will be definitely successful in reducing parasite load or transmission of infection.
    • Merozoite surface antigen - (MSA) I & II are polypeptide in the merozoite membrane and found to be highly immunogenic.
    • Ringed erythrocyte surface antigen and erythrocyte binding antigen- They are again merozoite proteins. Antibodies against this antigen can inhibit the invasion of erythrocytes.

Though it will be a long time before the malaria vaccine becomes a reality, the ideal malarial vaccine should be discovered which should not only reduce morbidity and morality but be also cheap and stable.

Prevention

Malaria is an epidemic disease in certain parts of the world and also endemic in a number of places. It is a significant public health problem. The age-old saying "Prevention is better than cure" is absolutely true for this disease as the morbidity and mortality can be brought down by stringent preventive measures which include -

  • Measures to prevent mosquito bites:
  • use of bed net (preferably treated with mosquito repellent like Permethrin), wire gauze screen for windows and doors, use of mosquito repellants like citronella oil, neem oil, creams like Dimethyl phthalate (DMP), DEET, use of coils (active ingredient is generally synthetic pyrethroid) or use of mats.

  • Mosquito control measures
    • Insecticide sprays like DDT, BHC, aldrin, etc. or Genophosphorus components, malathion, chlorthion and fumigants like SO2 and methylbromide. to kill the mosquitos
    • Antilarval measures like use of larvivorous fishes.
    • Removal of breeding places by a proper drainage system. Covering of stored water, spraying of oil.

  • Chemoprophylaxis and use of vaccines:
    • Chemoprophylaxis is recommended only for pregnant women, non-immune travelers and in children below the age of 4 years. Drugs used for this purpose are :
    • Proguanil - 3 mg/kg daily orally but not preferred as parasites are by and large resistant.
    • Chloroquine - 5 mg. base/kg/wt (max 300 mg) daily and is drug of choice in non-resistant cases.

However side effects need monitoring and for resistant cases Pyrimethamine + dapsone or sulphadoxine + pyrimethamine, doxycycline and mefloquine may be used. Travelers from the non-endemic areas who want to visit should be asked to start at least 1 week before the journey and should be continued at least 4-6 weeks after leaving the endemic area.

Conclusion

Successful management of malaria in children requires a high index of suspicion in clinical diagnosis, prompt & early initiation of the treatment, and anticipation & management of various complications with proper supportive care. However, the most important issue is the control of malaria through vector control and environmental sanitation. The malarial vaccine is the hope for the future.

Chronic Complications

Tropical splenomegaly - This syndrome occurs in malaria-endemic regions. WHO criteria for the diagnosis are:-

Major criteria: (a) Gross splenomegaly, (b) Immunity to malaria, (c) Serum IgM elevation >2 SD i.e.1000 IU/ml. (d) Clinical & immunological response to antimalarial drugs

Minor criteria: (a) Hepatic sinusoidal lymphocytosis & Kupffer cell hyperplasia. (b) Cellular and humoral immune response to antigenic challenge. (c) Normal phytohaemagglutinin,

(d) Hypersplenism, (e) Lymphoid proliferation, (f) Occurrence in the family.

Quartan Malarial Nephropathy: This entity is seen with P.malariae infection following an immune complex injury to glomeruli resulting in nephrotic syndrome. Prognosis is guarded.


Malaria Malaria Malaria 07/01/2015
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