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Case Reports Indian Pediatrics 2002; 39:585-588 |
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Resistant Malaria in a Neonate |
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Archana B. Patel
There is a paucity of reports of resistant malaria in neonates. There has been very little experience in the use of drugs such as quinine, halofantrine, artesunate and mefloquine in neonates. These drugs have been used effectively in older children. We report a case of a neonate with resistant malaria and our experience with oral artesunate and mefloquine in its treatment. Case Report A one-month-old female child was brought with history of high-grade fever since two-days and feeding poorly since the same morning. There was no history of abdominal distention, oliguria, alteration of conscious-ness, convulsions or prolonged jaundice in the neonatal period. The baby was severely pale, had hepatosplenomegaly with no signs of bleeding diathesis and impending cardiac failure. She had a hemoglobin of 5 g/dL, a reticulocyte count of 4% with normal hemoglobin electrophoresis. The blood group of both the mother and baby was A-Rh positive. This patient had a presentation of neonatal sepsis therefore blood, urine, and cerebrospinal fluid (CSF) culture were also done but were sterile. The peripheral smear showed multiple ring and gamete forms of Plasmodium falciparum. The blood counts were normal with adequate platelets. Although a week prior to the delivery, the mother had a history of fever for a day, there was no laboratory documentation of malaria. This fever had subsided with antipyretics. The baby received antimalarial syrup chloroquine in the recommended dose and duration and was administered a blood transfusion. The peripheral smear was sent on days 2,3 and 4 of treatment. It still showed ring forms and gametes of Plasmodium falciparum. Oral quinine was then administered in the dose of 10 mg/kg/dose 8 hourly, and was continued for 7 days. Despite a full course of quinine the daily peripheral smear showed persistence of ring forms and gametes of Plasmodium falciparum. There was also persistence of fever and splenomegaly. This baby was thus diagnosed as a case of resistant malaria. The child was then treated with a combination course of oral artesunate (total dose of 12 mg/kg given as 2 mg/kg/day for 5 days and 1 mg/kg/day for 2 days) and oral mefloquine on day 2 in split dose of 15 mg/kg and 10 mg/kg 12 hours apart. The patient was afebrile and aparasitemic at the end of 48 hours and by 72 hours of starting artesunate and mefloquine, the splenomegaly regressed from an intial size of 4 cm below subcostal margin to 1 cm. A week after receiving artesunate the spleen was not palpable. No adverse effects of drug therapy were observed in this baby. This baby remained aparasitemic at the end of one month also. Discussion Drug resistance in malaria has been defined as ability of the parasite strains to survive and/or multiply despite administration and absorption of a drug given in doses equal to or higher than those usually recommended but within the limits of tolerance of the subject. The World Health Organization (WHO) has categorized resistance in malaria as S, R1, R2, R3 based on in vivo test(1). In 1996, WHO replaced this test with the Therapeutic Efficacy Test based on clinical and parasitological criteria. This is a pragmatic test for National Malaria Control Program. This test is categorized as adequate clinical response, early and late therapeutic failure(2). Based on these two tests (in vivo and therapeutic efficacy test) this patient demonstrated R3 resistance (in vivo test) and early therapeutic failure (Therapeutic Efficacy Test). There is a paucity of reports of neonatal malaria. Few case series and reports have been published. Their clinical presentation has been similar to babies with septicemia such as fever, anemia, jaundice and hepatosplenomegaly, but with sterile blood, CSF, and urine culture(3-7). One case report has also documented diarrhea as a manifestation(8). This baby also had a similar presentation with sterile cultures. The diagnosis was based on peripheral smear, which demonstrated malarial parasite. Most neonates in the previous reports have responded to oral chloroquine(7,8). There are three reports in which chloroquine resistance was encountered(3,4,9). Quinine was used as second line drug for chloroquine resistant cases and for some babies with quinine resistance, halofantrine was used(5,8). This case was a treatment dilemma because halofantrine is not easily available in India, and drugs which are easily available, such as artesunate and mefloquine, have not been documented for use in neonatal malaria. These drugs also have an advantage because of their simplicity in use, i.e. oral administration or rectal administration(9). Trials of these drugs have been reported only in infants more than 6 months of age (6,10). The recrudescence rate of Plasmodium falciparum malaria assessed at day 42 has been reported to be significantly less when a combination of artesunate and mefloquine is used rather than artesunate alone in areas of high level multidrug resistance(6). Combination therapy of artesunate with a long acting antimalarial prevents emergence of resistance against either of the drug(9). Hence combination therapy was used in this patient. Oral artemisinin derivatives are safe and highly effective in the treatment of resistant falciparum malaria(6). Artemisinin, artesunate and artemether are well tolerated in both children and adults, with no evidence to date of serious clinical toxicity. They also have an advantage of rectal administration especially in children with difficult intravenous access and in rural areas where less expertise is available(9). There is no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity when used in humans(11). However, artesunate has been found to decrease glomerular filtration rate in rats(12). Artesunate has also been found to induce tremor, gait disturbances, and lethargy(13). Young children are more at risk of experiencing side effects like anorexia, nausea, vomiting, dizziness, and sleeping disorders due to higher doses of mefloqine, but when it is given in split doses the drug is well tolerated(6). In this case also the drug was given in split doses (15 mg/kg and 10 mg/kg 12 hours apart), which reduced the likelihood of side effects. This patient responded well to this combination therapy and no side effects were observed. One and three months after this episode this patient continued to be aparasitemic and clinically well. To the best of our knowledge the use of combination therapy of oral artesunate and mefloquine for management of resistant falciparum malaria in a baby of one month of age has not previously been reported. We hope that our experience would be helpful in case management of similar cases and also for larger trials in this age group in endemic areas with falciparum resistance. Contributors: ABP decided the management plan and supervised the work. She helped in drafting the paper and will act as a guarantor. HSB did the literature search and drafted the manuscript. Funding: None. Competing interests: None stated.
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