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Guidelines Indian Pediatrics 2008; 45:731-735 |
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Management of Malaria in Children : Update 2008 |
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Introduction Malaria is one of the leading cause of morbidity and mortality in developing countries. Nearly 2.48 million malaria cases are reported annually from South Asia of which 75% cases are contributed by India alone(2). It is heartening to know the total number of laboratory confirmed cases have declined from 3 million reported in 1997 to 1.84 million in early 2000(3). At the same time, it is perplexing that the number of falciparum cases is constantly on the rise and in recent years they contribute nearly 50% of the total cases(3). Falciparum malaria resistant to chloroquine (CQ) was identified in the districts of North East along the International border from 2003 onwards. According to National Vector Borne Disease Control Program, high treatment failure to CQ has been detected in 44 districts of 18 states in the country for which second line treatment with sulphadoxine – pyrimethamine (SP) was suggested(4). Resistance to SP combination at various levels has also been reported in the districts of seven North Eastern States. It has been seen that the introduction of a single new drug leads to rapid development of resistance. To overcome this, WHO has recommended Artemisinin based combination therapy (ACT) for the treatment of uncomplicated falciparum malaria(5). We had previously provided a detailed guideline on diagnosis and management of malaria(1). The present update incorporates our policy on ACT on the treatment of falciparum malaria, in addition to providing the standard treatment protocol. A full course of effective treatment should always be given once it is decided to give antimalarial treatment(6). Recommendations Artemesinin Combination Therapy Antimalarial combination therapy is simultaneous use of two or more blood schizontocidal drugs with different mode of action in unrelated biochemical targets in the parasite. According to WHO, one of the partner in combination therapy should be an artemisinin derivative due to its high killing rate (reduces parasite number 10,000 fold per cycle whereas other antimalarial reduces 100 to 1000 fold per cycle), lack of serious side effects, relatively low level of resistance and rapid elimination rate, which ensures that the parasites are not exposed to subtherapeutic levels of the drug. When administered in combination with rapidly eliminated antimalarials (clindamycin, tetracycline), a seven days course of treatment is required and adherence to treatment is usually poor. If artemesinin derivatives are combined with slowly eliminated antimalarials [SP, mefloquine (MQ), lumefantrine], shorter courses of treatment (3 days) are effective which ensures better treatment adherence. These combinations also protect against emergence of drug resistance despite the fact that they do leave the slowly eliminated tail of long acting drugs unprotected. Resistance could arise within the residual parasite that have not yet been killed by the artemisinin derivative. However, number of parasites exposed to long acting drug alone is a tiny fraction (less than 0.00001%) of those present in the acute infection. Furthermore, these residual parasites are exposed to relatively high levels of long acting drugs and even if susceptibility was reduced, these levels may be sufficient to eradicate the infection. Uncomplicated Malaria Treatment regimes are to be tailored specifically according to the resistance pattern of the region under consideration (Tables Ia, Ib, Ic, Id). Table Ia Recommended Treatment in Chloroquine Sensitive Malaria
* Chloroquine should not be given on an empty stomach and in high fever. Bring down the temperature first. If vomiting occurs within 45 minutes of a dose of chloroquine, that particular dose is to be repeated after taking care of vomiting by using antiemetic (domperidone/ondansetron).†According to National Anti Malarial Program, a 5 days course of primaquine is advocated because of risk of toxicity and operational feasibility. Whereas other authorities advocate 14 days course of primaquine due to lack of evidence to support shorter courses(7). As primaquine can cause hemolytic anemia in children with G6PD deficiency, they should be preferably screened for the same prior to starting treatment. As infants are relatively G6PD deficient, it is not recommended in this age group and children with 14 days regime should be under close supervision to detect any complication. In cases of borderline G6PD deficiency, once weekly dose of primaquine 0.6 – 0.8 mg/kg is given for 6 weeks. TABLE Ib Recommended Treatment in Chloroquine Resistant P. falciparum
(i) Under the previous National Drug Policy, SP monotherapy in a single dose was used in areas of chloroquine resistance. Countries where SP was introduced following CQ resistance showed its rapid decline in efficacy within few years. (ii) Currently there are insufficient safety and tolerability data on mefloquine at its recommended dosage of 25 mg/kg body weight in children. Mefloquine shares cross resistance with quinine which is still a effective drug in our country. Health planners of our country do not advocate use of menfloquine. (iii) Advantage of artemether lumefantrine combination is that lumefantrine is not available as monotherapy and has never been used by itself for the treatment of malaria. Lumefantrine absorption is enhanced by coadministration with fatty food like milk. Table Ic
(i) Doxycycline is preferred to tetracycline as it can be given once daily and does not accumulate in renal failure. (ii) One of the drawbacks of quinine therapy is its long course. Unsupervised and ambulatory setting may decrease patients compliance and many patients might not complete the full course of prescribed therapy. (iii) Fortunately children tolerate quinine better than adults. TABLE Id
(i) Treatment failure within 14 days of receiving an ACT is unusual. It should be confirmed parasitologically by blood slide examination. It is important to determine whether patient has vomited previous treatment or did not complete a full course. (ii) Failure after 14 days of treatment can be re-treated with first line ACT. Severe and Complicated Malaria The main objective of treatment is to prevent death. Prevention of recrudescence, transmission or emergence of resistance and prevention of disabi-lities are of secondary importance. Untreated severe malaria has a mortality of 100% but with proper treatment it can be reduced to 15-20%. As death due to severe malaria often occurs within hours of admission it is essential to ensure therapeutic concentration of antimalarial drugs as soon as possible. Hence, antimalarial drug should be given initially by intravenous infusion, which should be replaced by oral administration as soon as condition permits. According to the National Anti Malaria Program (NAMP), drug policy in all cases of severe malaria is either IV quinine or parentral artemisinin derivatives to be given irrespective of chloroquine resistance status(8). Treatment Guidelines are summarized in Table II. TABLE II Drug and Dosage of Antimalarials in Complicated and Severe Malaria
(i) Loading dose of quinine should not be used if the patient has received quinine, quinidine or mefloquine within the preceding 12 hours. Alternatively, loading dose can be administered as 7mg salt/kg by IV infusion pump over 30 minutes, followed immediately by 10mg salt/kg diluted in 10 ml isotonic fluid/kg by IV infusion over 4 hours. (ii) Quinine should not be given by bolus or push injection. Infusion rate should not exceed 5 mg salt/kg/hour. (iii) If there is no clinical improvement after 48 hours of parenteral therapy, the maintenance dose of quinine should be reduced by one third to one half i.e., 5-7 mg salt/kg. (iv) Quinine should not be given subcutaneously as this may cause skin necrosis. (v) Previous maintenance dose of parenteral artesunate of 1.2 mg/kg has been modified by WHO to 2.4 mg/kg. (vi) Artesunate, 60mg per ampoule is dissolved in 0.6mL of 5% sodium bicarbonate diluted to 3–5 mL with 5% dextrose and given immediately by IV bolus (push injection). (vii) Artemether is dispensed in 1 mL ampoule containing 80mg of artemether in peanut oil.
Members of the revised committee: Raju C Shah – Chairperson; Ritabrata Kundu – Convener; Amitava Nandy; Deepak Ugra; Nigam P Narain; Nitin K Shah; Nupur Ganguly; Panna Choudhury; Shivananda; Tapan Kumar Ghosh; and M Govindaraj. Writing Committee: Ritabrata Kundu, Nupur Ganguly and Tapan Kumar Ghosh. | |||||||||||||||||||||||||||
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