Case Description
A 43 years old male patient was admitted to the general ward with a history of intermittent fever with chill and rigor for the last 7 days. He was initially treated by his GP with paracetamol SOS for fever. He started feeling dizzy and nausea with a decrease in urine output despite taking adequate fluid. He has no history of cough, expectoration, rash, joint pain, weight loss, bleeding gum, bleeding per rectum. His bowel and bladder habits are normal. Neither he had any significant past medical history, nor he was taking any medicines on a regular basis. His home temperature chart shows a twice-daily spike of fever without any diurnal variation, the maximum recorded temperature being 102 ℉. On examination, he had a fever, pallor without any icterus, and mild splenomegaly. No neck rigidity could be demonstrated. Other systemic examination reveals no abnormality. After sending blood for culture – aerobic Bactec, CBC, LFT, Urea and creatinine, malarial parasite, malaria antigen, IgM dengue antibody, IgM typhoid antibody, he was put on intravenous fluid and paracetamol SOS. Urine was collected and sent for routine and culture. The chest X-ray was normal, and the ultrasonography of the abdomen revealed splenomegaly. The patient was adequately hydrated as no collapse of the inferior vena cava demonstrated in bedside ultrasonography. After six hours of admission in the hospital, his urine output started to decline. Initial laboratory reports suggest Haemoglobin - 8.7 g %, Total WBC count – 3000/cc, platelet count – 1.1 lac/cc, serum urea - 28 mg/dl, serum creatinine - 0.87 mg/dl, LFT with GGT – normal. Peripheral thick and thin blood smear revealed schizont and trophozoite of plasmodium vivax (Figures 1 and 2). The pathologist’s comment on peripheral smear suggests anemia to be normocytic and normochromic (MCV - 86 fl, MCH - 27 pg, MCHC - 30.6 gm/dl). Blood for malaria antigen- positive for vivax, negative for falciparum. IgM dengue and typhoid antibody were negative. Urine routine examination shows pus cells 1- 2/hpf, no RBC, no cast, no protein. The patient was given tablet chloroquine 600 mg on day 1,600 mg on day 2 and 300 mg on day 3. Tablet primaquine started at a dose of 15 mg daily from the next day after getting normal blood for the G6PD result. The patient was hemodynamically stable and did not complain of nausea and vomiting. But his urine output was at the range of 15-20 ml/hour. The total urine output on day 1 was 380 ml. The possibility of co-existent sepsis was considered because the initial C-reactive protein was 136 mg/dl (Normal up to 6 mg/dl). But initial blood culture and urine culture did not show any growth of bacteria. Blood for LDH and haptoglobin – normal, reticulocyte count was 1.5 %. Serum vitamin B12 & folate level – normal. Blood for serum ferritin and fibrinogen was normal and there was no schistocyte in a peripheral blood smear. On day 2 the patient was febrile, but the range of temperature was gradually declining. His urine output showed marginal improvement to 600 ml in the last 24 hours. But the serum creatinine level increased to 1.7 mg/dl though serum urea decreased to 24 mg/dl. Clinically there were no signs of uremia like a pericardial rub. Fractional excretion of sodium in urine was calculated and found to be 1.4 suggestive of an intrinsic renal cause of acute kidney injury. On day 3, he had one episode of fever and his urine output started to rise, total 860 ml in the last 24 hours. Foley's catheter was removed. His total intake was maintained as previous days output plus 500ml.On day 3 serum creatinine was 1.6 mg/dl. He was completely afebrile from day 4 onwards. His hemoglobin level, total leucocyte count and platelet count has started to improve from day 4 onwards. His final report of blood and urine culture did not reveal any growth. He was discharged on day 7 after satisfactory improvement of the haematological and renal profile. Serial laboratory parameters were shown in the following table 1.

Mortality in cases with vivax malaria and AKI has been reported from 11 to 16 % [2,6,10]. Prolonged disease duration, low hemoglobin counts, oliguria or anuria on admission, hyponatremia, hypotension, metabolic acidosis, acute respiratory distress syndrome were the more predictors of mortality. Haemodialysis is an effective treatment for malarial AKI. Early referral of malarial AKI patients to dialysis facility units and early institution of hemodialysis in complicated P.vivax malaria may further reduce mortality and enhance recovery of kidney functions. Anuria, refractory metabolic acidosis, refractory Hyperkalaemia, rising trend of serum creatinine, uremic encephalopathy, and uremic pericarditis are indications for renal replacement therapy [11]. In our case, because of early diagnosisand prompt treatment, the patient recovered spontaneously without renal replacement therapy.

Pancytopenia- It is a rare complication of vivax malaria. There are several mechanisms including microangiopathic hemolytic anemia, hemophagocytic syndrome [12] hypoplasia of bone marrow [13]. Hemophagocytic syndrome (HPS) starts because of inappropriate or excessive immunologic responses of T cells. In HPS, high levels of IFN-gamma, soluble IL - 2 receptors, TNF - a IL-1, and IL - 6 have been demonstrated, suggesting that elaboration of activating cytokines by T helper cells promotes activation of macrophages in this disease. These cytokines depress the proliferation of progenitor cells, which aggravate the pancytopenia because of phagocytosis of the blood cell [12]. Wickramasinghe and colleagues proposed that P. vivax has a direct toxic effect on erythroblasts or their precursors [13]. Alternatively, P. vivax may exert its effect on bone marrow macrophages leading to increased phagocytic activity and/or release of locally cytotoxic molecules damaging surrounding hematopoietic cells [13]. Whatever the cause, some degree of impaired erythropoiesis has been shown to persist for at least two weeks after treatment of vivax malaria and therefore the effects of these putative factors must be long-lasting [13].

The bone marrow in P. vivax malaria is also characterized by dyserythropoietic, increased macrophages (some showing hemophagocytosis), increased plasma cells, and sometimes increased eosinophils. In hyper-reactive malarial splenomegaly, there may be a marked increase in bone marrow lymphocytes [14].