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Severe falciparum malaria with hyperparasitaemia: management without exchange blood transfusion
C. J. F. Fontes and S. Munhoz Hospital Universrtario Julro Muller, School
of

M e d m n e , Eederal Unrversrty of M a t o Grosso, Cuzaha, M a t o Grosso, Brazil

Summary

The risk of complication in falciparum malaria is associated with parasite load. Drug therapy alone may be insufficient, and blood exchange transfusion is indicated when more than 10%of erythrocytes are parasitized with concurrent pulmonary, renal, cerebral or haemostatic complications; without complications, when the parasitized erythrocytes exceed 30%. The successful use of conventional malaria therapy without exchange transfusion in a young woman with severe falciparum malaria is reported.
keywords Plasmodium falciparum hyperparasitaemia, conventional drug therapy correspondence Cor JCsus F. Fontes, Av. Miguel Sutil, 5721, 78048-800, Cuiabi, MT,

Brazil

Introduction

The risk of complication in falciparum malaria is reported to be related to the parasite load and fatalities result mainly from a delay in diagnosis and/or from inappropriate therapy. Malaria drug therapy alone is believed to be insufficient to prevent a fatal outcome when more than 5 % of erythrocytes are parasitized and the death rate rises steeply as parasitaemia exceeds 50% (Warrell et al. 1990). Exchange blood transfusion has been recommended for the treatment of severe and complicated falciparum malaria in patients who are severely ill or who have deteriorated on conventional treatment Roncoroni & Martino 1979; (NeiIson et al. 1979; Kramer et al. 1983; Cook 1988; Warrell et al. 1990). However, considering only clinical and therapeutic findings, a definitive recommendation as to when exchange blood transfusion should be initiated is not possible. In reported cases in which exchange transfusion was successfully used in the therapy for acute falciparum malaria, the percentage of parasitized erythrocytes ranged from 10to 75 (Neilson et al. 1979; Roncoroni & Martino 1979;

Kramer et al. 1983; Warrell et a/. 1990). Several reports have indicated this procedure when the parasite concentration in peripheral blood is more than 10% in the presence of pulmonary, renal, cerebral or haemostatic complications, and more than 30% in their absence (Neilson et al. 1979; Cook 1988; Wilkinson et al. 1994).We here report the successful use of conventional malaria therapy without exchange transfusion in a pregnant young woman who had severe Plasmodium falciparum malaria with 46.6% of her erythrocytes parasitized. T o our knowledge there is only one previous report of a patient with a parasitaemia >Lo% who survived without exchange transfusion (Marik 1 9 8 9 ) and this is the first similar case involving malaria transmitted in the Americas.
Case report

The patient, a 16-year-old primigravida at 32 weeks gestation presented to the hospital of the Mato Grosso School of Medicine (Brazil) with a ro-day history of headache, malaise, fever, and chills that had worsened in the last z days. Physical

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C. J F Fontes and S. Munhoz Severe falciparum malaria with hyperparasitaemia

Figure I

Giemsa-stained blood

smears showing P. falciparum hyperparasitaemia with schizont (S) and multiple infected erythrocyte

(MI.

examination at that time showed an acutely ill patient, moderately lethargic, but responsive to verbal commands. Her temperature was 37C; pulse rate, I 10b.p.m.; respiratory rate, 6o/min; blood pressure, 90/5o mmHg. Pallor and mild jaundice were noted. The fetal heart rate was 150 b.p.m. and there were no signs of spontaneous bleeding. Malaria infection was promptly suspected as this disease is endemic in the area where the patient lived. Her thick blood smear was positive for P. falciparum malaria and intravenous chloroquine, glucose and fluids were immediately administered. During the first 12 hours of hospitalization the patient worsened and became more lethargic and disoriented. Her temperature reached 40C. Her heart rate increased to 134 b.p.m. and her blood pressure sank to 90/3o mmHg. Fetal death was detected by auscultation and ultrasonography. Vomiting was not present and during the entire time in hospital the patient tolerated oral feeding. Laboratory findings included haemoglobin of 65 g/l and a white cell count of 11.6 x ~ o " /with l 50% neutrophils. The serum sodium was I 34 mmol/l and serum potassium was 3.9 mmol/l; serum urea and creatinine were 45.7 mmol/l and 194./5 pmol/l, respectively; blood glucose, 2.9 mmol/l, and serum alaniiie aminotransferase, 3 2 U/l; total bilirubin, 42.8 pmol/l with a direct

bilirubin of 13.7 pmol/l and an indirect o f 29.1 pmol/l; the total serum protein was 44 g/l and the albumin 19 g/l. Arterial blood oxygen pressure was 7.3 kPa and the chest X-ray showed small bilateral pulmonary infiltrate. Urinalysis disclosed a specific gravity of 1.015; protein, 3 g/l; and 8-10 WBCs per high-power field. Giemsa-stained thin blood smears showed a parasitaemia of 46.6% by asexual forms of P. fulczpurum, with rings, mature trophozoites, schizonts and multiple infection of red blood cells (Figure I ) . Exchange blood transfusion was deferred because hospital facilities were not available. Chloroquine was substituted by intravenous quinine dihydrochloride 10 ingikg in 2 5 0 mi of 5% glucose solution every 8 h. In addition, an oral course o f tetracycline 5 0 0 mg every 6 h was initiated, since no more fetal risk was involved. Due to the low level of haemoglobin, 2 units of blood packed cells werc administered. To avoid circulatory overload small intravenous doses of furosemide 20 mg were given during blood transfusion. Modest volumes of 0 . 9 % saline and 5% glucose solutions were maintained by intravenous infusion to avoid dehydration and hypoglycaemia. A high concentration of oxygen was given by nasal catheter to correct hypoxaemia. The patient showed a rapid and progressive recovery of the symptoms and signs, her respiratory

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rate decreased and the arterial blood oxygen pressure became normal. After 36 hours, the parasitaemia had dropped to 8 % and thereafter the parasite count showed a progressive reduction until day 6, when no more parasites could be seen in peripheral blood. Spontaneous delivery of the dead foetus occurred on day 4 and two more units of blood packed cells were transfused in order to maintain the haematocrit above 20%. By day 5 , as serum urea had fallen and n o other important laboratory abnormalities were detected, quinine was given orally together with tetracycline for 5 more days. She was discharged on day 9.
Discussion

The patient had several indications of complicated malaria, such as impairment of consciousness, hypoglycaemia, biochemical evidence of renal dysfunction, jaundice, hypoxaemia and a high level of parasitaemia. The development of severe malaria in this patient and the unfortunate stillbirth outcome were likely: P. falciparum infection is especially dangerous during the last trimester of pregnancy (Cook 1988); primigravidae have a greater risk of higher parasitaemia and a poorer outcome compared to multigravidae (Cook 1988; Brabin 1983); the main feature of malaria transmission in the Brazilian Amazon region is the variability of its incidence from place to place and from year to year. In areas with this unstable pattern of malaria transmission people have a poor degree of acquired immunity and malaria may be an important cause of maternal death, abortion, stillbirth, premature delivery and low birthweight (Brabin 1983; Warrell et al. 1990); and the patient sought medical care only after 10 days of symptoms. The high parasitaemia detected plus the presence of all stages of P. falciparum including schizonts, which are seen only in massive infections, are further evidence of delayed diagnosis and severe disease (Roncoroni & Martino
1979). In Brazil, malaria is endemic only in the Amazon area where it mostly affects migrant populations who come from malaria-free areas of the country. Severe and complicated infections occur almost invariably as a result of delay or inadequate treatment of uncomplicated attacks. Management of most cases

of falciparum malaria includes quinine plus an antibiotic like tetracycline. However, for pregnant patients the Brazilian Ministry of Health recommend starting therapy with chloroquine, in spite of the well known widespread resistance of P. falciparum to this drug (Ministetio da Saude 1994). The use of chloroquine in the present case probably contributed to making the patients evolution serious during the first hours of treatment. Several reports have indicated that exchange blood transfusion may produce a sufficiently rapid clearance of parasitized red blood cells from the body to abort an otherwise fatal falciparum infection (Neilson et al. 1979; Roncoroni & Martino 1979; Kramer et al. 1983). However, this i s a therapeutic method indicated only if hospital facilities are adequate. For example, to reduce parasitaemia below I % from as much as 7 5 % , the volume of red blood cells to be exchanged varies from r o to 27 units (Warrell et al. 1990; Wilkinson et a/. 1994). Considering the critical condition of our patient and the reported fatality rate in heavily parasitized patients, exchange transfusion was considered. However, we opted for a conservative strategy because whole blood was not available in the patients blood group. Although repeated blood transfusions may be required in severe malaria treatment, suggesting abnormally rapid haemolysis of donor erythrocytes (Warrell et a/. 1990), this did not occur in our patient. On the contrary, there was a progressive increase in packed erythrocyte volume. The presence of quinine and tetracycline probably prevented infection of transfused red cells, as transfusions were performed only after this drug therapy had been started. Perhaps the fluid and blood administration contributed to dilute the parasitaemia, benefiting patient evolution. The favourable outcome without exchange transfusion may also be due to institution of antimalarial and support treatments, with careful fluid, blood, glucose, electrolyte and oxygen management.

References
Brabin BJ ( 1 9 8 3 ) An analysis of malaria in pregnancy in Africa. Bulletin of the World Health Organization 61, 1005-I 0 1 6.

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Cook GC (1988) Prevention and treatment of malaria. Lancet i, 32-37. Kramer SL, Campbell C C & Moncrieff RE (1983) Fulminant Plasmodium falciparum infection treated with exchange blood transfusion. lournal of the American Medical Association 249, 244-245. Marik PE (1989) Severe falciparum malaria: survival without exchange transfusion. American /ournal of Tropical Medicine and Hygiene 41, 627-629. Ministerio da Saude (1994)Manual de TerapCutica de Malaria. Brasilia: MinisteJio da Saude. Neilson RL, Kohler RB, Chin W, McCarthy LJ & Luft FC (1979)The use of exchange transfusions: a potentially useful

adjunct in the treatment of fulminant falciparum malaria. American Journal of Medical Science 277, 3 25-3 29. Roncoroni AJ & Martino OA (1979)Therapeutic use of exchange transfusion in malaria. American lournal of Tropical Medicine and Hygiene 28, 440-444. Warrell DA, Molyneux ME & Beales PF (1990) Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 84 (Supplement 2 ) ,
1-65. Wilkinson RJ, Brown JL, Pasvol G, Chiodini PL & Davidson R N (1994) Severe falciparum malaria: predicting the effect of exchange transfusion. Quarterly ]ournal of Medicine 8 7 , 553-557.

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