Newer Trends In The Diagnosis And Management Of Malaria
Dr. R.K.Mehra*, Dr. A.K.Rawat**
Professor and Head Department of Pediatrics, S.S. Medical College, Rewa (M.P.) *, Professor and Head Department of Pediatrics, S.S. Medical College, Rewa (M.P.) **

Malaria

continues to be a major global health problem, with over 40% of World's Population, more than 2400 million people exposed to varying degrees of malaria risk in some 100 countries. Malaria resurgence has made it a most devastating human parasite infection responsible for 1.7 to 2.5 million deaths per year. Most of these deaths are due to plasmodium falciparum, occurring in non immune children below 5 years of age and in pregnant women. P. falciparum is responsible for severe manifestations, drug resistance, treatment failure and increased mortality. In some areas P.falciparum is responsible for 60-80% cases of malaria.
DIAGNOSIS OF MALARIA
The

objectives of malaria diagnosis

are it should be rapid, the report should be available within one hour of arrival of case, it should be highly sensitive and specific. It is not important only to detect parasite in blood but it is also important to count their number and identify complication of severe forms of malaria. Malaria can be diagnosed by clinical features and parasitological diagnosis with light microscopy and rapid diagnostic tests.

Clinical Diagnosis


This is symptom and sign based. For the diagnosis of malaria a high index of suspicion is essential in all cases of fever and without any evidence as to cause of fever and history of exposure to malaria particularly in children below 5 year of age.

Light Microscopy


It has high sensitivity, specificity and low direct cost. It can differentiate species, calculate parasite densities and useful in indenting other abnormalities. Light microscopy still remains gold standard for malaria diagnosis. It has certain limitation like difficulty in maintaining good quality microscopy, training and supervision of lab staff, delay in communicating.

Rapid Diagnostic Tests (RDT)


These are immunochromatographic tests depend on detecting parasite specific antigen, for one, two or four species of malaria, they are available as dipsticks, cards or cassettes. The advantages of RDT are - simple to use and interpret, does not require electricity or special equipment, reports available in short time and have high patient confidence; RDT should have a high sensitivity (>95%) for 100 parasite / L of blood. Antigen tested is HRP2 (Histidine rich protein 2 pf) and species parasite lactate dehydrogenase (pLDH).

Disadvantages of RDTs are HRP2 may persist for 3 weeks after effective treatment; the test kit may be affected by environmental temperature.

Pf HRP2 is 99% sensitive and 95% specific PCR based molecular detection methods though routinely not available, are useful for epidemiological purposes, can help to differentiate recrudescence and relapse. PCR can detect <10 parasites per 10 ml blood. Tests based on detection of antibodies to parasites are not sensitive specific or rapid enough to be of use in the management of malaria. These are ELISA, RIA assay and immunofluorescence. Intra Leucocyte malaria pigment can help to measure disease severity. There are also changes in various lab values but they are not specific for malaria e.g., fall in Hemoglobin, platelets, Neutrophils, Albumin, Glucose and potassium levels and arise in Monocytes, Alkaline phosphatase, SGPT,Bilirubin, Urea and lactate.
IDENTIFICATION OF SEVERE FALCIPARUM MALARIA
The severe falciparum malaria is diagnosed on the basis of: (a) Asexual Parasitemia (b) no evidence of other causes (c) one or more of following (Clinical = Prostration, impaired consciousness, respiratory distress, acidotic breathing, convulsion, shock, bleeding, jaundice and hemoglobinuria. Lab findings - severe anemia (Hb<4gm%) hypoglycemia (<45mg%) radiological evidence of pulmonary edema, acidosis, renal impairment, hyperlactemia and hyper parasitemia (>10% RBC infected)). Deaths occur usually within hours of hospitalization hence early and adequate treatment is vital.

Hyperparasitemia - Hyperparasitemia is associated with falciparum malaria, leads to more chances of complications, treatment failure and mortality. In hyperparasitemia parasite
count is
  • 100,00/ L blood in non-immune
  • >250,000/ L blood in semi-immune
  • 5-10% RBC are infected

Risk of death is high when malaria is associated with shock, deep coma, respiratory distress, hypoglycemia and severe anemia.
TREATMENT OBJECTIVES

I. Uncomplicated malaria


Primary objective is to cure infection which means no parasites in blood for 28 days. Secondary objective is to prevent development of drug resistance.

II. Severe malaria


Primary objective is to prevent death. Secondary objective is to prevent recrudescence, resistance and disabilities.

III. Resistance to drugs


Ability of parasite to survive and or multiply despite proper administration and absorption of good quality drugs in recommended doses.

Pf resistant to chloroquines- Amodiaquines Sulfadoxine-pyrimethamine, Mefloquine and Quinine. Almost all the antimalarials except artemisinin derivatives. Pv resistant to Sulfadoxine- pyrimethamine, remains sensitive to chloroquine. Follow up for 28 days essential to differentiate recrudescence and reinfection.
TREATMENT OUTCOME

Early treatment failure (ETF)


- Development of danger signs or severe malaria on day 1-3 in the presence of parasitemia.
- Parasitemia on day 2 higher than day 0 count.
- Parasitemia on day 3 with axillary temperature> 37.50C
- Parasitemia on day 3 i.e.,>25% of count on day 0

Late treatment failure (LTF)


A. LTF-Clinical development of danger signs or severe malaria after day 3 with parasitemia.

Presence of parasitemia on any day from 7 to 28 days with Axillary tempt> 37.50C.

LTF-Parasitological

Presence of parasitemia 7-28 days.
TREATMENT FAILURE
Treatment failure within 14 days is mostly due to recrudescence confirm parasitologically and treat with second line drugs.
Treatment failure > 2 wks treat with primary line drugs. But don't repeat MQ with in 28 days.

2nd line drugs


A. Artesunate 2 mg/kg/day x 7 days + Tetracycline 4 mg/kg/day x 7 d or Doxycycline 3.5 mg/kg/day x 7d or Clindamycin 10 mg/kg/day x 7d
B. Quinine 10 mg/kg x 7d + Tetra/Doxy/clindamycin

Causes of Failure

- Incorrect doses, vomiting of drug poor compliance and drug quality.
Treatment of Uncomplicated Vivax malaria
Chloroquine + Primaquine 0.25 to 0.5 mg/kg/day with food x 14 days. In moderate G6PD deficiency primaquine 0.75 mg/kg weekly for 8 wks. In severe G6PD deficiency - No primaquine. ACT + Primaquine may be used.
Treatment of severe Vivax malaria
Features of severe P vivax malaria are cerebral malaria, severe anemia, severe thrombocytopenia, severe pancytopenia, jaundice, spleen rupture, ARF or ARDS. Treat as severe Pf malaria. Mixed malaria infection should be treated as Pf.
Treatment of uncomplicated falciparum malaria

Criteria for diagnosis

are symptomatic malaria without signs of severe malaria or organ dysfunction, but be alert as children below 5 years can deteriorate rapidly. Combination of two blood schizonticidal drugs acting independently is used to counter resistance and improve outcome. Artesunate + Lumefantrine BD x 3 days
  1. Artemether (20 mg) + Lumefantrine (120 mg )BD x 3days
  2. Artesunate (50 mg) 3mg/kg/day x 3 days + Mefloquine (250 mg) 25 mg/kg total dose split in 2 doses, started on day 2
Treatment of severe falciparum malaria

Areas of Management


  1. Clinical Assessment
  2. Specific antimalarial therapy
  3. Adjunctive therapy
  4. Supportive care

Clinical Assessment
ABC, record weight, establish IV line, measure blood glucose and count parasite density

Specific antimalarial
Quinine for 7 days or Artesunate for 7 days (2.4 mg/kg IV 0 Hr, 1.2 mg/kg IV 12 Hr, 1.2 mg/kg IV 24 Hr. daily x 6 days)

Adjunctive Treatment


To reduce high mortality adequate and prompt treatment of coma, hyperpyrexia, convulsions, hypoglycemia, severe anemia, acute pulmonary edema, ARF, bleeding, metabolic acidosis, shock and hyper parasitemia. Give Iron folic acid for 2 weeks.

Continuing supportive care. Monitoring & Nursing
Monitoring by Nurses - 3 Hourly
Monitoring by Doctors - 12 hourly
For I.V. infusion - Hourly
Tempt/HR/RR/BP - 6 hourly for 2 days.
Blood glucose - 3 hourly till child becomes conscious
Record of fluid intake and output.
PRE-REFERRAL TREATMENT
Risk of death higher in first 24 hours hence

prereferral treatment

is essential, which can be quinine or artesunate by I.V./IM/per rectal/oral route.

To reduce Transmission:

Use gametocytocidal drugs with effective schizonticidal therapy. Primaquine 0.75 mg/kg maximum is 45 mg, but avoid it during All trimesters
TREATMENT OF MALARIA DURING PREGNANCY
Malaria is usually asymptomatic during pregnancy, according to gestation period drugs selected are as follows:

All trimesters - Chloroquine, Quinine
- -II & III Trimesters - Artemisinin derivatives.
Abbreviations
Pv = P. vivax
Pf = P. falciparum
MQ = Mefloquine
ACT = Artemisinin based combination therapy
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R.K.Mehra D, A.K.Rawat D.. Available From : http://www.pediatriconcall.com/fordoctor/ Conference_abstracts/report.aspx?reportid=413
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