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ORIGINAL ARTICLE
Year : 2013  |  Volume : 12  |  Issue : 3  |  Page : 155-159  

Complications associated with Plasmodium vivax malaria: A retrospective study from a tertiary care hospital based in western Uttar Pradesh, India


1 Department of Medicine, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 Department of Pathology, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Web Publication5-Sep-2013

Correspondence Address:
Imran Rizvi
Rifa Guest House, Near Andhra bank, Medical Road, Aligarh - 202 001, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1596-3519.117624

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   Abstract 

Background: Plasmodium vivax (p. vivax) malaria was traditionally considered as benign tertian malaria, however, recent studies have pointed out that p. vivax have potential to cause all severe complications previously attributed to p. falciparum infection only. The aim of this report is to study the incidence of various clinical and biochemical complications associated with severe p. vivax malaria.
Methods: A retrospective analysis was performed on all patients with p. vivax malaria admitted to our center between January 2009 and December 2011. Severe malaria was defined as per World Health Organization (WHO) criteria. Clinical and laboratory parameters were recorded. Patients with evidence of p. falciparum, mixed malarial infection and chronic systemic diseases were excluded from the study.
Results: Sixty-two patients met the criteria for severe malaria during the study period. The complications observed were Hepatic dysfunction in 18 (29%), renal dysfunction in 13 (21%), cerebral malaria in 10 (16.1%), acute respiratory distress syndrome (ARDS) in 6 (9.7%), shock in 10 (16.1%), severe anemia in 16 (25.8%), thrombocytopenia in 35 (56.5%), and hypoglycemia in 3 (4.8%) patients. Three mortalities were observed.
Conclusions: P. vivax has immense potential to cause life threatening complications and even death, more research is required to understand the exact pathogenesis of various complications encountered in vivax malaria.

   Abstract in French 

Contexte: ppaludisme à vivax (vivax p.) lasmodium a été traditionnellement considéré comme bénigne paludisme relia, toutefois, des études récentes ont souligné que p. vivax sont susceptibles de causer des complications graves tous précédemment attribuées à une infection à p. falciparum seulement. Le présent rapport vise à étudier l'incidence de diverses complications cliniques et biochimiques associées à sévère paludisme à p. vivax.
Méthodes: Une analyse rétrospective a été réalisée chez tous les patients avec le paludisme à p. vivax admis dans notre centre entre janvier 2009 et décembre 2011. Paludisme grave a été défini selon les critères de l'Organisation mondiale de la santé (OMS). Les paramètres cliniques et de laboratoire ont été enregistrés. Les patients avec le témoignage de p. falciparum, mélangé le paludisme et les maladies systémiques chroniques ont été exclus de l'étude.
Résultats: Soixante-deux patients répondaient aux critères de paludisme grave au cours de la période d'étude. Les complications observées étaient une dysfonction hépatique en 18 (29 %), la dysfonction rénale dans 13 (21 %), le paludisme cérébral dans 10 (16,1 %), aigu syndrome de détresse respiratoire (SDRA) à 6 (9,7 %), les chocs en 10 (16,1 %), anémie sévère en 16 (25,8 %), thrombocytopénie dans 35 (56,5 %) et l'hypoglycémie chez 3 patients (4,8 %). Trois cas de mortalité ont été observées.
Conclusions: P. vivax a un immense potentiel pour causer potentiellement mortelles des complications et même la mort, plus de recherche est nécessaire pour comprendre la pathogénie exacte de diverses complications rencontrées dans le paludisme à vivax.
Mots-clés: Neuropaludisme, dysfonctionnement hépatique, p. vivax, paludisme grave, dysfonctionnement rénal

Keywords: Cerebral malaria, hepatic dysfunction, p. vivax, severe malaria, renal dysfunction


How to cite this article:
Rizvi I, Tripathi DK, Chughtai AM, Beg M, Zaman S, Zaidi N. Complications associated with Plasmodium vivax malaria: A retrospective study from a tertiary care hospital based in western Uttar Pradesh, India. Ann Afr Med 2013;12:155-9

How to cite this URL:
Rizvi I, Tripathi DK, Chughtai AM, Beg M, Zaman S, Zaidi N. Complications associated with Plasmodium vivax malaria: A retrospective study from a tertiary care hospital based in western Uttar Pradesh, India. Ann Afr Med [serial online] 2013 [cited 2019 Oct 15];12:155-9. Available from: http://www.annalsafrmed.org/text.asp?2013/12/3/155/117624


   Introduction Top


Malaria is a major public health problem, endemic in over hundred countries across the world. [1] A total of 2.6 billion people are reported to be living at risk of plasmodium vivax (p. vivax) malaria. [2] A total of 130-435 million people are estimated to get p. vivax infection annually. [3]

In the Southeastern Asian Region of World Health Organization (WHO), of ~1.4 billion people living in 11 countries 1.2 billion are exposed to the risk of malaria most of whom live in India. [4] Among the four species of plasmodium, p. falciparum and p. vivax are commonly found in India.

P. vivax malaria is traditionally referred to as "benign tertian malaria" and it is expected to follow a relatively benign course as compared with p. falciparum malaria. However, recent studies and case reports have documented clearly that p. vivax infection has the potential to cause all complications associated with severe falciparum malaria. [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27]

The aim of our study was to study the incidence of various clinical and biochemical complications associated with severe p. vivax malaria.


   Materials and Methods Top


Records of all adult patients with a confirmed diagnosis of p. vivax malaria admitted to our hospital between January 2009 and December 2011 were analyzed retrospectively. Confirmed diagnosis of p. vivax included only those patients who were tested positive for p. vivax mono infection by peripheral blood smears, quantitative buffy coat test, or rapid diagnostic test (SD bioline, Standard diagnostic Inc. Korea). Clinical history, examination findings and laboratory data including blood counts, general blood picture, liver function tests, renal functions tests, blood gas analysis, serum electrolytes, and blood glucose were recorded. Severe malaria was defined according to WHO definition, that is, presumptive diagnosis of malaria with documented plasmodium asexual parasitemia and one or more of the following features: impaired consciousness/unarousable coma, prostration (inability to walk/sit without assistance), failure to feed, multiple convulsions, acidotic breathing, circulatory collapse or shock, clinical jaundice, hemoglobinuria, abnormal spontaneous bleeding, pulmonary edema, hypoglycemia (blood glucose <40 mg/dl), metabolic acidosis (bicarbonate <15 mmol/l), severe anemia (hemoglobin <5 gm/dl), hyperlactatemia (lactate >5 mmol/l), renal impairment (serum creatinine >3 mg/dl), and hyperparasitemia. [28]

Patients with any evidence of p. falciparum or mixed malarial infections, and patients with other chronic systemic illnesses were excluded from the study.


   Results Top


A total of 172 patients were admitted to our hospital with confirmed diagnosis of p. vivax malaria during the above mentioned study period, 62 (36.04%) of these patients presented with severe malaria as per the definition.

The patients with severe malaria were in age group ranging from 18 to 72 years, mean age was 31.11±13.14 years. Thirty seven (59.7%) out of these 62 patients were males and 25 (40.3%) were females.

Hepatic dysfunction defined as serum bilirubin >3 mg% and raised liver enzymes were seen in 18 (29%) patients, in these patients mean bilirubin was 5.18±2.71 mg/dl (minimum bilirubin was 3.0 mg/dl and maximum was 12.5 mg/dl). Mean Aspartate aminotransferase and Alanine aminotransferase was 140.33±47.34 IU/L and 142.61±45.11 IU/L, respectively.

Renal dysfunction with serum creatinine >3 mg% was present in 13 (21%) patients, mean serum creatinine and blood urea of these patients were 4.12±2.14 mg/dl and 96.38±26.26 mg/dl, respectively. Maximum serum creatinine and blood urea observed were 10.8 mg/dl and 150 mg/dl, respectively. Two of the patients required hemodialysis.

Cerebral malaria was seen in 10 (16.1%) patients. Severe anemia hemoglobin <5 gm% was seen in 16 (25.8%). Shock was seen in 10 (16.1%) and acute respiratory distress syndrome (ARDS) in 6 (9.7%) patients. Hypoglycemia (blood glucose <40 mg/dl) was observed in 3 (4.8%) patients.

Thrombocytopenia was present in 35 (56.5%) patients. Out of these 35, 8 patients presented with spontaneous bleeding in the form of epistaxis, gum bleed, or petechial rashes on skin.

A total of three mortalities were observed, the first one had ARDS and shock, the second had severe anemia and cerebral malaria and third one had hepatitis, renal failure, and ARDS.


   Discussion Top


P. vivax malaria was traditionally referred to as benign tertian malaria as it was not associated with complications and had a low case fatality ratio. It is widely believed that p. vivax is incapable of causing cytoadherence and microvascular sequestration and therefore unable to cause organ dysfunction, however, several recent reports have emphasized the point that p. vivax has the potential to cause severe manifestations. [16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27] Two large studies from Papua New Guinea and Indonesia also highlighted the malignant potential of vivax malaria. [5],[6] Recently few Indian studies have also found that p. vivax can cause all complications previously attributable to falciparum malaria only. [8],[9],[10],[11],[12],[13],[14],[15] The findings of these studies conducted in various part of India are summarized in [Table 1].
Table 1: Table summarizing findings of various Indian studies related to severe p. vivax malaria

Click here to view


In this retrospective study records of all patients with confirmed diagnosis of p. vivax malaria admitted at our center between January 2009 and December 2011 were analyzed, cases of severe malaria were selected as per WHO definition with the exception that asexual parasitemia with p. vivax was taken into account instead of p. falciparum. We found 62 cases of p. vivax malaria satisfying the definition of severe malaria these cases were studied to determine the incidence of various complications.

Thrombocytopenia was seen in 35 (56.5%) patients with 8 patients having spontaneous bleeding. Thrombocytopenia was the most common complication seen in our study. Previous Indian studies have also reported thrombocytopenia as a common complication of p. vivax malaria. Naha et al., [10] reported thrombocytopenia in 86.4%, George et al., [11] found 93.3% of their patients to be having thrombocytopenia, Singh et al., [12] and Sharma et al., [13] reported thrombocytopenia in 96 and 96.3% of patients, respectively. In studies conducted by Kochar et al., [8] and Mohapatra et al., [14] thrombocytopenia was not as common as in the above mentioned studies it was found to be in 12.5% and 3.6% patients, respectively. Some case reports have also described cases of p. vivax malaria with thrombocytopenia. [18],[19],[24] Proposed mechanism of thrombocytopenia are macrophage activation, increased levels of cytokines and antiplatelet immunoglobulin resulting in accelerated destruction of platelets.

Hepatic dysfunction in the form of serum bilirubin >3 mg/dl and elevated liver enzymes was the second most common complication seen in our study, it was observed to occur in 18 (29%) patients. Kochar et al., [8] reported hepatic dysfunction in 57.5% of patients, George et al., [11] found liver dysfunction in 43.3%. Singh et al., [12] Sharma et al.,[13] Mohapatra et al., [14] and Hazra et al., [15] found liver dysfunction in 17.3%, 27.1%, 7.2%, and 9.09% of patients, respectively. Few case reports also describe hepatic dysfunction in case of p. vivax malaria. [20] Malarial hepatitis is proposed to be caused by direct injury to the liver cells by the parasite. [20]

Renal dysfunction (serum creatinine >3 mg/dl) was another common complication observed in our study. It occurred in 13 (21%) of patients. Kochar et al., [8] Naha et al., [10] George et al., [11] Singh et al., [12] and Sharma et al., [13] reported renal dysfunction in 57.5%, 27.5%, 26.7%, 26%, and 7% patients of vivax malaria. In a retrospective study on 93 patients of malarial ARF 19 (20.4%) were found due to p. vivax infection. [21] Etiology of renal failure in malaria is multifactorial, volume depletion, intravascular hemolysis, and hyperbilirubinaemia are factors considered responsible for renal injury. [22]

Cerebral malaria due to p. vivax infection has been documented in various case reports. [23],[24],[26] Kochar et al., [8] observed cerebral malaria in 12.5% of patients. George et al., [11] Mohapatra et al., [14] , Hazra et al., [15] and Singh et al., [12] found cerebral malaria to be occurring in 6.7%, 0.9%, 1.3%, and 13%, respectively. In our study cerebral malaria was seen in 10 (16.1%) of the patients. Cerebral dysfunction in vivax malaria may occur through generation of nitric oxide. [23]

Severe anemia (hemoglobin <5 gm/dl) was seen in 16 (25.8%) patients in our study. Previous studies have also documented severe anemia in association with vivax malaria. [8],[9],[10],[11],[12],[13],[14]

Six patients in our study developed ARDS. Some case reports have described patients of vivax malaria who developed ARDS. [16],[17] Indian studies described above have also observed occurrence of ARDS in their study groups. [8],[9],[11],[13] Proposed mechanism of development of pulmonary complications in these patients are small airway obstruction, impaired gas exchange, increased phagocytic sensitivity, and accumulation of pulmonary mononuclear cells. [25]

Shock was observed in 10 (16.1%) of our patients. Kochar et al. found 2 patients with shock in their study. [9] Naha et al. found hypotension in 10 (4.69%) patients in their study. [10] Postulated mechanism for hypotension in malaria include gastrointestinal bleeding, metabolic acidosis, dehydration, splenic rupture, and secondary bacterial septicemia. [10]

Three (4.8%) of our patients had hypoglycemia (blood glucose <40 mg/dl). Kochar et al. observed hypoglycemia in 1 (2.5%) patient. [8]

Three patients in our study group died due to combination of various complications like ARDS, shock, renal failure, cerebral malaria, and severe anemia. Previous studies have also documented mortalities in patients with p. vivax malaria. [8],[9],[11],[12],[13]

It is clear from our study that P. vivax has immense potential to cause life threatening complications and even death, more research is required to understand the exact pathogenesis of various complications encountered in vivax malaria. Every patient of p. vivax malaria should be evaluated thoroughly for clinical or biochemical evidence of any complication and patients presenting with complications should be admitted and managed as per guidelines of severe malaria.

 
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    Tables

  [Table 1]


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