|Year : 2013 | Volume
| Issue : 4 | Page : 482-485
A case of Plasmodium vivax malaria with spontaneous subarachnoid hemorrhage and acute renal failure, severe thrombocytopenia, with anemia
Govind S Shiddapur, Jagannath S Dhadwad, Sukanya Kumar, Abhijeet B Gaikwad
Department of Medicine, Padmashree Dr. DY Patil Medical College, Hospital and Research Centre, Dr. DY Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||17-Sep-2013|
Department of Medicine, Padmashree Dr. D Yashwantrao Patil Medical College, Hospital and Research Centre, Dr. D Y Patil Vidyapeeth, Pimpri, Pune-411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
When we talk about severe malaria, we usually think of Plasmodium falciparum. However, in recent times, Plasmodium vivax has also been reported to cause severe multi-organ dysfunction and life-threatening disease similar to P. falciparum. We report here a case of P. vivax malaria in a young boy from an endemic zone, who developed acute renal failure, severe thrombocytopenia, and anemia and later developed spontaneous subarachnoid hemorrhage. Multisystem involvement in a patient with P. vivax is rare, and subarachnoid hemorrhage is an unusual presentation.
Keywords: Malaria, plasmodium vivax, subarachnoid hemorrhage
|How to cite this article:|
Shiddapur GS, Dhadwad JS, Kumar S, Gaikwad AB. A case of Plasmodium vivax malaria with spontaneous subarachnoid hemorrhage and acute renal failure, severe thrombocytopenia, with anemia. Med J DY Patil Univ 2013;6:482-5
|How to cite this URL:|
Shiddapur GS, Dhadwad JS, Kumar S, Gaikwad AB. A case of Plasmodium vivax malaria with spontaneous subarachnoid hemorrhage and acute renal failure, severe thrombocytopenia, with anemia. Med J DY Patil Univ [serial online] 2013 [cited 2021 Jun 22];6:482-5. Available from: https://www.mjdrdypu.org/text.asp?2013/6/4/482/118300
| Introduction|| |
Plasmodium vivax is known to cause relapsing malaria but rarely causes severe malaria. In recent times, studies have shown that it can cause complications like acute renal failure, thrombocytopenia, jaundice, severe anemia, acute respiratory distress syndrome, shock, cerebral malaria, hypoglycemia, and death. 
Cerebral malaria manifests as diffuse symmetric encephalopathy; focal neurologic signs are unusual. Convulsions, usually generalized and often repeated, occur in 10% of adults and up to 50% of children with cerebral malaria.  Cerebral hemorrhages causing focal neurological signs, such as hemiplegia and aphasia, are known to occur in association with P. falciparum malaria. Intracranial hemorrhages with P. vivax are rare. There are reports in the literature on P. vivax with thalamic bleed  but we were unable to find a single case report on subarachnoid hemorrhage with P. vivax, Subarachnoid hemorrhages are more common with P. falciparum and have been reported in the literature.
Over the past few years, many cases of severe P. vivax malaria were seen and some cases even resulted in death. This severe form of disease involving multisystem can be due to increase in resistance, indiscriminate use of anti-malarial drugs, delayed treatment, lack of primaquine alternative to attack dormant liver stage. ,
Epidemiologic studies, clinical description, and comparison of P. vivax with P. falciparum is needed to understand the dynamics and its interaction with the immune system.
| Case Report|| |
A 28-year-old male, admitted with history of intermittent high grade fever with chills and rigors for last 5 days associated with headache, body ache, and reduced urine output. There was no history of petechial hemorrhage, rash, hematuria, loose stool, cough, burning micturition, seizures or altered sensorium. There was no history of diabetes and hypertension. He was non alcoholic, non smoker, and had no past history of any major illness.
On examination, patient was conscious, oriented, febrile (100°F), pulse 110 beats per minute (bpm), blood pressure 100/60 mmHg, had pallor with mild icterus. There was no sub-conjunctival hemorrhage. Abdominal examination revealed mild hepatosplenomegaly. Other systemic examinations were normal. From the day of admission, we observed decreasing levels of hemoglobin, platelet count, and increasing levels of urea, creatinine, . Peripheral blood picture showed schizonts of P. vivax.
Course in the hospital
To confirm no evidence of mixed infection, we did rapid malarial test on three consecutive days, which showed only evidence of P. vivax. Dengue antibody and Leptospira IgM test were also done which were negative.
Patient was put on Chloroquine, Doxycycline, parenteral Artesunate, and Primaquine along with broad spectrum antibiotics. Proper fluid intake and nutrition were maintained.
His urine output decreased with worsening of renal parameters. Urea and creatinine levels increased to 141 mg% and 7 mg% respectively. He underwent hemodialysis daily for 7 days, subsequently renal function improved with urea and creatinine 83 mg% and 5 mg%, respectively, with improvement in urine output. On day 3 of admission, patient developed petechial rash and subconjunctival hemorrhage. Platelet count and hemoglobin dropped to 18,000 and 6.3 mg/dl, respectively. With multiple platelet and packed cell transfusions, platelet count and hemoglobin increased to 1.4 lakhs/cumm and 10.4 gm/dl respectively. Chest X-ray was normal. Ultrasonography (USG) abdomen and pelvis showed: 1) Early renal parenchymal disease, 2) Hepatosplenomegaly, 3) Minimal ascites.
On the 13 th day of admission, the patient had one episode of seizure which was generalized tonic clonic. He was afebrile. There was no focal neurological deficit. Platelet count was adequate (1 lakh). Blood sugar levels were normal. No history of fall. Following that a non-contrast computed tomography (CT) scan of brain [Figure 1] was done, which showed Left frontal subarachnoid hemorrhage and subsequently patient was put on Tab. Nimodipine (60 mg Three times a day (TDS)) and Inj. Eptoin (100 mg TDS). Patient showed improvement but unfortunately patient took discharge against medical advice and was lost to follow-up. Diagnosis was made as severe malaria due to P. vivax with spontaneous subarachnoid hemorrhage, acute renal failure, severe thrombocytopenia, and anemia.
| Discussion|| |
Malaria is caused by five species of Plasmodium: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. 
Out of the five, P. falciparum is responsible for the severe and fatal malaria.  It is known to cause severe thrombocytopenia, acute tubular necrosis, acute respiratory distress syndrome (ARDS), cerebral malaria, hypoglycemia, hypotension, shock, and death.  In comparison to P. falciparum, P. vivax runs a more benign course. P. vivax typically causes relapsing fever due to presence of dormant hypnozoites in the liver and is term as 'Benign tertian malaria'. 'Benign tertian malaria implies, P. vivax malaria is usually an uncomplicated disease that runs a benign course and is rarely fatal.  In recent times, trends have been changing and there are reports of severe malaria due to P. vivax infection.
There are several theories for development of severe malaria, which results from a combination of parasite-specific factors, such as adhesion and sequestration in the vasculature and the release of bio-active molecules, together with host inflammatory responses. P. vivax preferentially infects young red blood cells (RBCs), parasitemia rarely exceed 2% of circulating RBCs, and high parasite burdens are not a feature of severe disease.  However, cytokine production during P. vivax infections is higher than P. falciparum infections of similar parasite biomass. 
Andrade et al.,  found a strong linear trend between increased levels of C-reactive protein, Tumor necrosis factor alpha (TNF-α), Interferon gamma (IFN-γ), IFN-gamma/Interleukin (IL)-10 ratio and the disease severity of vivax malaria. Price et al.,  reported that the plasma concentrations of TNF-α are higher in P.vivax as compared to P. falciparum malaria with similar degree of parasitemia.
Studies have shown that P. vivax can cause both sequestration-related complications such as cerebral malaria, renal dysfunction, hepatic dysfunction, and ARDS and non-sequestration-related complications such as anemia and thrombocytopenia. 
In our patient, we have found multi-organ involvement with unusual presentation of subarachnoid hemorrhage and also acute renal failure, severe thrombocytopenia, anemia with P. vivax malaria.
Intracerebral hemorrhages are usually a feature of complicated P. falciparum malaria. This is the first case report of spontaneous subarachnoid hemorrhage in P. vivax malaria. Intracerebral hemorrhage usually affects the white matter. Different architectural types of hemorrhages are seen, simple, petechial, zonal ring hemorrhages and Duck's granulomata.  Large hemorrhages or infarcts are rare. There is usually no evidence of tentorial or foramen magnum herniation.  Capillaries and venules are distended and packed with mature forms of erythrocyte. The histological hallmark is widespread cerebral vasculopathy due to sequestration of parasitized erythrocytes in vascular endothelium with increase endothelial permeability, perivascular infiltrations and cerebral edema.  Subarachnoid hemorrhages have been described in patients with cerebral malaria. They occur due to the rupture of small vessels which get plugged by red cells in combination with severe thrombocytopenia and associated disseminated intravascular coagulation. , It is unlikely that the subarachnoid hemorrhage in our patient was, at least in part, contributed by the thrombocytopenia. However, symptoms became evident in this patient much after the platelet count started improving. Enhanced inflammatory responses as well as the sequestration of parasitized red cells in microcirculation may be considered to be possible mechanism.
Many cases of severe thrombocytopenia caused by P. vivax malaria have been reported in literature. , A few postulated mechanisms include macrophage activation, increased levels of cytokines, platelet destruction, and sequestration in non-splenic area.  A rare case of idiopathic thrombocytopenic purpura triggered by P. vivax infection has also been described by Lacerda et al. 
Acute renal failure caused by vivax malaria has been reported earlier in literature. , Acute tubular necrosis due to renal ischemia is the predominant mechanism.  Several hypotheses have been described including mechanical obstruction caused by cytoadherence and sequestration of infected erythrocytes, immune-mediated glomerular pathology, and release of cytokines. 
| Conclusion|| |
In recent times, there has been change in clinical picture of P. vivax with wide range of presentation similar to P. falciparum. No longer is it considered as benign malaria. Every effort should be taken to reduce the mortality and morbidity caused by P. vivax. Further studies are required to understand the pathogenesis and organ specific morbidity with P. vivax and its dynamics with subarachnoid hemorrhage.
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