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RESEARCH ARTICLE
Year : 2022  |  Volume : 59  |  Issue : 3  |  Page : 259-264

Changing pattern of severe manifestations of Plasmodium falciparum and Plasmodium vivax malaria: A retrospective study from Bikaner, India


Department of Microbiology, Maharaja Ganga Singh University, Bikaner, Rajasthan, India

Date of Submission05-Oct-2020
Date of Acceptance08-Mar-2022
Date of Web Publication08-Dec-2022

Correspondence Address:
Dharmesh Harwani
Kanav Bhawan, Academic Block 1, Department of Microbiology, Maharaja Ganga Singh University, Bikaner-334004, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9062.342396

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  Abstract 

Background & objectives: Previously there were reports from all over India about the changing spectrum of severe manifestations of Plasmodium falciparum malaria. Consequently, the present retrospective study was conducted to compare the severity of malaria caused by P. falciparum and P. vivax during 2007–08 and 2017–18.
Methods: The present study was conducted on the patients admitted with severe malaria in a classified malaria ward of a tertiary care hospital in Bikaner, Rajasthan (Northwest India) during 2007–08 and 2017–18. It included adult patients of both sexes belonging to all age groups. The diagnosis was done by peripheral blood film (PBF), rapid diagnostic test (RDT), and validated by polymerase chain reaction (PCR). All patients were treated with intravenous oral quinine. The specific individual malaria complications registered in 2007–08 and 2017–18 were treated by following the standard WHO protocol.
Results: In 2007–08, severe manifestations caused by P. falciparum were dominated by thrombocytopenia (25.98%) followed by jaundice (24.39%), multi-organ dysfunction (MODS) (16.66%), severe anemia (16.17%), cerebral malaria (5.39%), bleeding manifestation (3.92%) and shock (0.49%). While in the same year, P. vivax associated clinical spectrum of complications were observed to be dominated by thrombocytopenia (26.47%) followed by jaundice (25.00%), MODS (14.70%), severe anemia (5.88%), cerebral malaria (5.88%), renal failure (4.41%), bleeding manifestation (2.45%), shock (0.98%) and acute respiratory distress syndrome (ARDS) (0.49%). However, in 2017–18, the clinical spectrum of malaria complications caused by both species has changed. Relative to P. falciparum infections, P. vivax individual complications like thrombocytopenia (51.78%) (p<0.001) followed by jaundice (19.13%) (p<0.001) and severe anemia (4.22%) (p<0.05) were found to have increased significantly.
Interpretation & conclusion: Over the last decade there is an apparent spatial and temporal shift in the clinical manifestations of severe malaria caused by the both Plasmodium species. As evident from the patient’s data from 2007–08 and 2017–18, the severity is more inclined towards Plasmodium vivax than Plasmodium falciparum malaria. Moreover, individual P. falciparum-associated complications were decreased significantly in the Bikaner region of Rajasthan, India.

Keywords: Malaria; Plasmodium falciparum; Plasmodium vivax; clinical spectrum; severe manifestations


How to cite this article:
Acharya J, Harwani D. Changing pattern of severe manifestations of Plasmodium falciparum and Plasmodium vivax malaria: A retrospective study from Bikaner, India. J Vector Borne Dis 2022;59:259-64

How to cite this URL:
Acharya J, Harwani D. Changing pattern of severe manifestations of Plasmodium falciparum and Plasmodium vivax malaria: A retrospective study from Bikaner, India. J Vector Borne Dis [serial online] 2022 [cited 2023 Feb 2];59:259-64. Available from: http://www.jvbd.org//text.asp?2022/59/3/259/342396


  Introduction Top


The spectrum of severe malaria has changed worldwide and in India. Plasmodium vivax is more widely distributed than P. falciparum, and is a potential cause of morbidity and mortality among the 2.85 billion people living at risk of infection across the world[1]. Historically, India is highly endemic to P. vivax but recent reports suggest that malaria due to P. falciparum and P. vivax are in equal proportions[2]. However, P. falciparum is responsible for the majority of severe manifestations of malaria and the mortality associated with it. P. vivax is no more considered benign and could also result in severe infections[3]. It has been known to induce P. falciparum-like severe complications including cerebral malaria, renal failure, circulatory collapse, acute respiratory distress syndrome (ARDS), jaundice, severe anemia, thrombocytopenia, multiorgan dysfunction (MODS) potentially leading to life-threatening episodes[3][4]. Clinical and pathological aspects of many severe P. vivax infections have been previously studied across the world including India[5][7].

Bikaner is situated in the Thar desert between longitude 71°54’ and 74°12’ east and latitude 27°11’ and 29°3’ north. Its altitude is 237m above the sea level and the temperature ranges from a minimum of 2°C in winter to a maximum of 48°C in summer. It is situated in the northwestern part of Rajasthan, India, near the India-Pakistan border. The region is characterized by a hot summer and a cold winter with a low annual rainfall of 25 cm. The rain occurs in a single period between July and September. Malaria surveillance is a regular and continuous activity in the region, regulated by the state and central government malaria control programmes[7]. The scenario of both disease morbidity and mortality has altered to a great extent during the past two decades. In the present work, a systematic study was undertaken to understand the changing spectrum of severe manifestation of malaria caused by both the species in adult patient’s ward of the PBM hospital, S.P. Medical College, Bikaner during 2017–18. The data obtained in 2017–18 was compared with the data observed during the malaria epidemic in 2007–08 which included adult patients admitted to the PBM hospital, S.P. Medical College, Bikaner[8].


  Material & Methods Top


The present study includes adult malaria patients admitted to the S.P. medical college and associated group of hospitals, Bikaner, India during 2007–08 and 2017–18. The patients who were willing to give their written consent were only included in the study. The diagnosis of malaria was done by peripheral blood film (PBF) and rapid diagnostic test (RDT). Confirmation of all samples was done by polymerase chain reaction (PCR).

Diagnosis

Conventional thick and thin peripheral blood film (PBF) stained with 4% Giemsa stain were examined under oil immersion. The slides were considered negative when there were no parasites at higher magnification (100X) [Figure 1]. The rapid diagnostic tests (RDTs) were based on the detection of Plasmodium sp. specific lactate dehydrogenase (LDH) (OptiMal test; Diamed AG, Cressier sur Morat, Switzerland) and histidine-rich protein-2 (HRP-2) (Falcivax test; Zephyr Biomedical Systems, Goa, India).
Figure 1: (A) Tethering stage and trophozoites of P. vivax and (B) ring stage and gametocytes of P. falciparum.

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Polymerase Chain Reaction (PCR) based diagnosis

The PCR studies were targeted against the 18S ribosomal RNA gene of the parasite that included one genus-specific 5’ primer and two species-specific 3’ primers in the same reaction mixture as described in the previous study[9]. PCR confirmation of the species was done for all the patients with malaria [Figure 2].
Figure 2: The PCR was targeted against 18S ribosomal RNA gene of the parasite, Lanes 2 represent DNA amplicon of P. vivax (~500bp), Lanes 3 represent DNA amplicon of P. falciparum (~1400bp), Lane 1 represents 1Kb DNA ladder.

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Statistical analysis

Statistical analysis was performed using software SPSS (SPSS Incorporation, Chicago, USA) version 18.0. p-values<0.05 or <0.001 were considered significant. Pearson’s chi-square test was used to compare percentages.

Other clinical measures

Laboratory investigations included complete blood count, bleeding time, clotting time, blood glucose, blood urea, serum creatinine, serum bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum alkaline phosphatase, complete urine analysis, electrocardiogram, and skiagram chest. Depending upon the clinical manifestations, other specific tests included urine and blood culture, cerebrospinal fluid (CSF) examination, computed tomography (CT) of the head, ultrasonography of the whole abdomen, and other relevant examinations to rule out typhoid fever, hepatitis B, and C, leptospirosis, and dengue infection. All patients were categorized under various complications strictly as per WHO criteria and specific investigations for each complication were carried out as and when required for its proper management.

Drug schedule

All patients received a uniform drug regimen in the form of a loading dose of intravenous quinine sulfate 20mg/kg in four hours followed by 10mg/kg intravenously every eight hours until the patient was able to take the prescribed drug orally. Adequate dose correction was done in patients with renal failure and those requiring prolonged intravenous therapy. The specific complications were managed according to WHO protocol. The patients of hepatic encephalopathy received 25% glucose, lactulose along with the judicious control of serum electrolytes. Patients were kept in the hospital until the parameters related to haematological, renal, or hepatic abnormality became normal and were discharged only after a good clinical recovery. To study the changes in the spectrum of complications related to both species of malaria, the data recorded in 2017–18 were compared with the data recorded in a similar study on the patients admitted to the PBM hospital, S.P. Medical College, Bikaner during 2007–08 malaria epidemic. The study was conducted at the same place by using similar methods for diagnosis and management.

Ethical statement

The patients who were willing to give their written consent were only included in the study. Clearance and approval were obtained from the Institutional Ethical Committee.


  Results Top


The present study was conducted on 112 adult patients of both sexes of defined severe malaria admitted during the year 2017–18 [Table 1]. All patients had positive evidence of malaria as confirmed by PBF, RDT, and PCR. The study was compared with a similar study conducted on 204 adult patients of both sexes admitted in the PBM hospital of S.P. Medical College, Bikaner during the 2007–08 malaria epidemic. In 2017–18, out of total of187 malaria cases observed for both species, 146 (78.07%) had P. vivax and 41 (21.92%) had P. falciparum infections [Table 2]. The majority of the malaria cases were observed in both species in the age group 18–30 years in both years [Table 3]. Based on WHO guidelines, in 2017–18, the severe manifestations of malaria were observed in 112 (59.89%) patients (n=187) [Table 1]. The severity ratio of P. falciparum infections was observed to be 70.73% in 2017–18 as compared to 55.30% in 2007–08. While for P. vivax infections the severity ratio was observed to be 56.84% and 47.08% in 2017–18 and 2007–08 respectively [Table 3].
Table 1: Sex-wise distribution of patients with severe malaria

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Table 2: Distribution of patients according to severity and non-severity of malaria

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Table 3: Age-wise distribution of patients

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The spectrum of various complications caused by both species was compared using chi-square test to study the significance of these values [Table 2] & [Table 4]. Cerebral malaria was one of the major manifestations in 2007–08 but thereafter, almost after a decade, it was observed to have almost diminished in 2017–18 and it was seen only in 1 patient (0.89%) in the case of P. falciparum malaria and three patients (2.67%) in case of P. vivax malaria. As compared to 2017–18 cerebral malaria was observed in 11 patients (5.39%) in the case of P. falciparum and 12 patients (5.88%) in the case of P. vivax malaria in 2007–08. There was a significant decrease in the incidence of jaundice in P. falciparum (p<0.05) and P. vivax (p<0.001) associated with malaria in both years [Table 4]. In the case of P falciparum associated thrombocytopenia, there was no significant difference (p=0.86) observed but with P. vivax associated cases it was found to be increased significantly (p<0.001) in 2017–18 (51.78%) compared to 2007–08 (26.47%) [Table 4]. Moreover, the incidence of other complications like severe anemia was decreased in 2017–18 in the case of P. falciparum (8.92%) as compared to 2007–08 (16.17%) but in the case of P vivax, it increased from 5.88% in 2007–08 to 16.17% in 2017–18. Another severe manifestation like P. vivax associated renal failure was also recorded to increase in 2017–18 (5.35%) as compared to 2007–08 (4.41%). However, in case of P. falciparum, it was observed to be the opposite, the cases with renal failure were recorded to be less in 2017–18 (2.67%) relative to 2007–08 (6.86%). MODS patients associated with P. vivax were observed slightly higher in 2017–18 (19.64%) whereas, in 2007–08, MODS manifestation was recorded with 14.70% of patients associated with P vivax malaria. In both years, ARDS manifestation was observed to be associated with only P. vivax infections [Table 4].
Table 4: Severe manifestations of P. falciparum and P. vivax malaria

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  Discussion Top


The presence of one or more complications in malaria patients infected with P falciparum is defined by WHO as severe malaria. Recently, the severe cases due to P vivax infection have increased significantly which is an important aspect of current malaria research[4]. The severity of malaria infections caused by P. falciparum and P. vivax species has changed spatially and temporally. The present study describes and confirms the changing pattern of severe manifestations of P. vivax-associated malaria. The study was performed by taking into consideration the data from 2007–08 wherein the burden of malaria was observed to be very high[8] and to infer and demonstrate the changing spectrum of malaria infections more effectively, it was compared with the data recorded in 2017–18, exactly after a decade. To design various control measures it is highly important to be acquainted with the changing spectrum ofclinical manifestations of P falciparum and P. vivax malaria for a particular region. Previously, in the last decade, many complications like jaundice, renal failure, and cerebral malaria were associated with P. falciparum infections[7]. In the present study, we show that the clinical spectrum of severe manifestation of malaria in the Bikaner region has shifted from P. falciparum to P. vivax infections. There have been a lot of studies reporting the contribution of P vivax to severe malaria burden, challenging the idea that vivax malaria is benign[13],[14]. Several P vivax associated severe cases have been reported in Brazil, Peru, and Venezuela[15],[17]. Intriguingly, Plasmodium vivax is responsible for about 100 to 300 million cases in each year[18],[19]. The observations from the present study indicate that in 2007–08, 55.30% severe P falciparum malaria cases were reported while 47.08% cases were observed to have P. vivax infection. However, in 2017–18, P. vivax associated malaria infections dominated wherein 56.84% cases were registered. The situation was quite different previously when P. vivax infections were considered to be benign without many consequences, but at present increasing case reports have emerged worldwide emphasizing the changing pattern of increased P. vivax infections as observed in the present study as well.

According to the reports published by WHO, thrombocytopenia is considered to be the most common manifestation of malaria[5]. Thrombocytopenia is a common hematological finding in patients with P. falciparum infection. However, in the present study thrombocytopenia was represented in 51.78% (p<0.001) patients infected by P. vivax in 2017–18. Moreover, among the two species, the infections caused by P. vivax leading to thrombocytopenia were found to be on a significantly, higher side. Similar to our observations, the comparison of thrombocytopenia manifestation in patients with severe malaria caused by the two Plasmodium species has revealed that it is strongly associated with P. vivax[10],[12],[20]. Jaundice may present in all forms of malaria but is more severe in the case of P. falciparum infection[11]. However, in 2017–18, there was a significant decrease in the observed jaundice cases for both P. falciparum (p<0.05) and P. vivax (p<0.001) species. Likewise, cerebral malaria was the most common complication represented by both species in 2007–08 while it was observed with only 0.89% P. falciparum and 2.67% P. vivax cases in 2017–18. Besides, only a few P. vivax cases with ARDS manifestation were identified in 2007–08 (0.49%) and 2017-18 (1.78%) respectively while for both years no case was represented by P. falciparum species. The ARDS associated P. vivax malaria probably results from the cytokine-related increase in the alveolar permeability[21],[22]. Severe anemia is strongly related to malaria infections and anemia alone is not associated with increased mortality. But interestingly, in the last decade, the incidence of P. vivax associated anemia has been observed to be increased by 16.07% (p<0.05) in 2017–18 compared to 2007–08 (5.88%). But contrary to this, the relationship was identified to be opposite in the case of P. falciparum infections in both years.

The clinical spectrum of severe manifestations of malaria caused by P. falciparum in the Bikaner region was previously studied[23] but for P. vivax associated malaria these were not studied to this extent. It has been observed that the clinical spectrum of severe manifestations of malaria caused by both species has changed worldwide. The overall observations from the present study highlight that there is an apparent spatial and temporal shift from P. falciparum malaria to P. vivax associated malaria.


  Conclusion Top


The results of the present study indicate that during the last decade the severity of P. vivax associated malaria has dramatically increased in the Bikaner region of Rajasthan, India. Over the past decade, the overall cases of severe manifestations of P. falciparum-associated malaria have significantly decreased. The reported cases of P. vivax malaria are directly related to the involvement of severe clinical manifestations such as thrombocytopenia, multi-organ dysfunction, acute respiratory distress syndrome, shock, and anemia in patients. Therefore, awareness about the changing the clinical spectrum of severe manifestation of P. vivax malaria is of great importance. This can provide lasting benefits to all stakeholders including central and state governments for running effective health care programs for malaria diagnosis, prevention, and management in the affected areas of not only Bikaner but other regions in India.

Conflict of interest: None


  Acknowledgements Top


Jyoti Acharya (JA) gratefully acknowledges the financial support from DST, New Delhi, India for providing WOS-A research grant (SR/WOS-A/LS-29/2017(G) dated 29/12/2017).





 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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