Journal of Infection and Public Health (2011) 4, 91—95

Plasmodium vivax malaria: Is it actually benign?

Harpal Singh ∗, Ankit Parakh, Srikanta Basu, Bimbadarh Rath

Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children’s Hospital, New
Delhi 110001, India

Received 12 December 2010 ; received in revised form 7 March 2011; accepted 9 March 2011

KEYWORDS Summary Plasmodium vivax (Pv) malaria is being increasingly recognized as a

Children; cause of severe malaria in children.
Plasmodium vivax; Objectives: To describe the various severe manifestations associated with vivax
Severe malaria malaria by retrospective analysis of records.
Methods: Children between the ages of 0 and 18 years with a confirmed diagnosis
of Pv malaria monoinfection done by peripheral blood film (PBF) and/or rapid diag-
nostic test (RDT) admitted between June and September 2009 were included. Their
clinical, hematological and biochemical manifestations were analyzed.
Results: Twenty-three patients of Pv malaria were retrospectively analyzed. Throm-
bocytopenia was present in 22 (96%) patients with counts less than 50,000/␮L in 9
patients. Severe anemia (hgb < 5 mg/dl) was present in 8 (34%) patients. Cerebral
malaria was present in 3 patients. Liver enzymes were elevated (>3 times normal)
in 4 (17.3%) patients while jaundice (bilirubin > 2.5 mg/dl) was present in 2 patients
(total bilirubin 5.2 mg/dl and 14.3 mg/dl). Renal dysfunction (creatinine > 3 mg/dl)
was present in 6 (26%) patients with 2 patients showing severely deranged renal func-
tions (blood urea 168 mg/dl, 222 mg/dl and serum creatinine 5.0 mg/dl, 5.6 mg/dl,
respectively). Hypernatremia was present in one patient. One patient expired within
12 h of presentation because of severely deranged hepatic and renal dysfunction.
Conclusion: Pv malaria can lead to unusual and fatal complications. All new guide-
lines should include ‘‘Severe Vivax malaria’’ as a clinical entity. Further research
into the etiopathogenesis and treatment would be important.
© 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier
Ltd. All rights reserved.

∗ Corresponding author at: Room No. 20, New Registrar Block,

Lady Hardinge Medical College, New Delhi 110001, India.

E-mail address: dr harpal81@yahoo.co.in (H. Singh).

1876-0341/$ — see front matter © 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.jiph.2011.03.002
92
Introduction
Plasmodium vivax (Pv) also called as benign tertian
malaria accounts for more than 50% of infection
in South East Asia region [1]. Although it is usu-
ally associated with benign course recent literature
suggests that Pv can lead to serious manifestations
[2—12] similar to Plasmodium Falciparum (Pf). The
present report highlights the serious manifestation
of Pv malaria in children from India.
Methods
Case records of children between 0 and 18 years of
age with diagnosis of Pv malaria between June and
September 2009 were retrospectively analyzed.
Children with mixed infection with Pf/any other
malarial species or any other associated infection
were excluded. Diagnosis of Pv was confirmed by
peripheral blood film (PBF) examination and/or
rapid diagnostic test (RDT). Severe manifestations
of malaria [13] like seizure, jaundice, coma, severe
pallor, bleeding, oliguria, hypoglycemia, acidosis
and ARDS were reviewed. Routine hematological
and biochemical investigations were done in all
patients.
Results
Among 232 patients of malaria infection presented
to our hospital during study period, 110 (47%) were
of Pf monoinfection, 108 (46%) of Pv monoinfec-
tion and 14 (6%) of mixed infection. Thirty-two
patients of Pf monoinfection, 23 patients of Pv
monoinfection and 5 patients of mixed (Pf and Pv)
infection presented with severe manifestation were
admitted. The record of these 23 patients of Pv
Table 1 Manifestations of severe malaria positive for Plasmodium vivax.
S. no. Manifestation
1 Severe anemia (<5 mg/dl)
2 Thrombocytopenia (<150 × 103 /␮L)
3 Jaundice (bilirubin > 2.5 mg/dl)
4 Renal failure (creatinine > 3 mg/dl)
5 Cerebral malaria (Glasgow coma score < 9/14)
6 Disseminated intravascular coagulation
7 Deranged liver enzymes (>3 fold elevation)
8 Leucocytosis (>12,000/cumm)
9 Persistent vomiting
10 Multi organ dysfunction
11 Repeated generalized convulsions
H. Singh et al.
monoinfection was retrospectively analyzed. Ten
(44%) of these patients were female and mean age
of presentation was 5.4 years (±3.67) with range
from 1 month to 12 years [<1 year 4 (17%); 1—5
years 9 (39%); 5—10 years 7 (30%); >10 years 3
(14%)]. Seventy percent of the children had moder-
ate malnutrition (as per World Health Organization
classification) but there was no child with severe
malnutrition. In four patients PBF was negative but
RDT was positive while one patient had positive PBF
but negative RDT.
Gastrointestinal symptoms (diarrhea, vomiting)
were present in significant number (43.4%) of
patients while seizures presented in 4 (17.3%)
patients. Three patients with seizures had cere-
bral malaria but in fourth patient it was because of
hypernatremia (173 meq/L). Hepatosplenomegaly
was present in all patients with mean size of liver
and spleen being 2.7 cm (SD ± 1.19 cm) and 2.4 cm
(SD ± 1.6 cm) below costal margins, respectively.
Various severe manifestations of vivax malaria
have been described in Table 1. Severe anemia
(<5 mg/dl) was present in 8 (34%) cases. Throm-
bocytopenia (less than 150 × 103 /␮L) was a very
common (95.6%) manifestation while severe throm-
bocytopenia (<50 × 103 /␮L) was present in 9 (39%)
patients. Three patients who had platelet counts
less than 10 × 103 /␮L presented with bleeding man-
ifestation in the form of petechiae and purpura
which improved after platelet transfusion. Five
(21%) patients presented with pancytopenia.
Two patients presented with jaundice. One of
those had indirect hyperbilirubinemia (total bil.
6.2 mg/dl, indirect bil. 5.1 mg/dl) with normal liver
enzymes (AST 35 IU/L, ALT 18 IU/L, ALP 240 IU/L)
who improved subsequently. This patient had no
feature suggestive of hemolytic anemia in the form
of increased reticulocyte count, hemoglobinuria
or decreased haptoglobin. The one with direct
hyperbilirubinemia (total bil. 14.3 mg/dl, direct bil.
No. (%) of patients (n = 23)
8 (34.7)
22 (95.6)
2 (8.6)
6 (26)
3 (13)
1 (4)
4 (17.3)
3 (13)
4 (17.3)
1 (4)
4 (17.3)
Plasmodium vivax malaria: Is it actually benign?
9.3 mg/dl) had severely deranged liver and renal
parameters. Liver enzymes were elevated (>3 fold
of normal) in 4 (17.3%) patients. Deranged coag-
ulation parameters were present in two patients.
In one patient (INR-1.8, aPTT — 78 s) it improved
conservatively while in other (INR — 3.2, aPTT —
140 s) it required FFP (fresh frozen plasma) trans-
fusion. Deranged renal functions (serum creatinine
>2.5 mg/dl) were present in 6 patients. One of
these had complete renal shutdown (urine output
<0.1 ml/kg/h, serum creatinine −5.6 mg/dl) and
required peritoneal dialysis while other (urine out-
put — 0.3 ml/kg/h, serum creatinine — 5.0 mg/dl)
improved conservatively in 5 days. None of these
patients with renal involvement had albuminuria,
hematuria or hypertension. In one neonate cold
antibody Coomb Test positive hemolytic anemia,
with the peripheral smear showing Red blood cells
(RBC) agglutinates around the parasitized RBC was
present. We found no patient with hypoglycemia,
acidosis and acute respiratory distress syndrome
(ARDS). Three patients presented with cerebral
malaria had seizures and altered sensorium without
any focal neurological deficit. Their cerebrospinal
fluid examination findings were normal. Neuroimag-
ing (CECT Scan) showed diffuse cerebral edema
without any focal infarct or hypoattenuation.
All patients were treated with intravenous qui-
nine and supportive care as per standard guidelines.
Repeat PBF after 2 days showed clearance of par-
asite. Follow up which is routinely done in severe
malaria patients, showed no residual neurological
deficit in any patient with cerebral malaria.
One nine-year-old boy expired with compli-
cation of Pv. This boy presented with severe
pallor, GI bleeding and oliguria who had severely
deranged hepatic (AST 288 U/L, 340 U/L, total bil.
14.3 mg/dl, direct bil. 6.7 mg/dl) and renal func-
tions (urea 222 mg/dl, creatinine 5.6 mg/dl) with
abnormal coagulation profile. The child developed
disseminated intravascular coagulation (platelet
count 20 × 103 /␮L, INR — 3.2, aPTT — 140 s, D dimer
— positive) and expired within 12 h of presentation.
Discussion
Pv which was initially thought to cause a mild
infection with a benign course is now increasingly
being recognized as a cause of severe malaria sim-
ilar to Pf in adults and children including infants
[14] and neonates [15]. Serious complications like
severe anemia [2], thrombocytopenia [3,4], bleed-
ing, jaundice, hepatic dysfunction [5—7], renal
dysfunction [8,9], cerebral malaria [10], ARDS [11],
93
severe neutropenia, hydrocephalus [12] and multi-
organ dysfunction [16,17] also have been reported
in children. All patients fulfilled the criteria of
severe malaria [13] except that the parasites seen
on PBS examination were of Pv and parasite load
was not determined.
Our clinical data strongly indicate that Pv
malaria can cause sequestration related compli-
cation of severe malaria like cerebral malaria,
hepatic dysfunction, renal dysfunction, all of which
usually associated with Pf malaria. Other non-
sequestration related complications like severe
anemia, thrombocytopenia, DIC are multifactorial,
were more commonly seen. Possible mecha-
nism underlying the anemia includes hemolytic
effect of parasites, decreased deforming capac-
ity of parasitized cells and parasite product
mediated effect on erythropoisis. Newer mecha-
nisms like invasion of erythroblasts by parasites
have also been reported [18]. Thrombocytopenia
has been attributed to increased splenic clear-
ance, reduction of platelet survival, decreased
platelet production and increased splenic uptake
of platelet. Immunological reaction [19] and oxida-
tive stress [20] are also suggested mechanisms of
thrombocytopenia.
Although derangement of liver enzymes was
a common finding, severe malarial hepatitis was
found in only one child. Malarial hepatitis is known
to be caused by direct injury to hepatocytes by the
parasite [5—7]. There may be a wide variety of renal
manifestation associated with malaria but these
are more common with Pf infection. Acute renal
failure, electrolyte abnormality, increased urinary
protein excretion and abnormal urinary sediments
have been reported in patient with Pv malaria [8,9].
We also observed deranged renal functions in sig-
nificant number of patients however severe renal
failure was seen in only two patients.
Our results are similar to other published data
from Indonesia, Pakistan and other studies from
India. In a large study from Papua New Guinea,
Indonesia which included both inpatient and
outpatients of malaria found that risk of severe
disease in the terms of severe anemia, respiratory
distress and coma were more common in Pv (23%)
as compared to Pf (20%) [21]. Another prospective
study conducted in two rural health facilities in
Papua New Guinea reported 9537 cases of malaria,
the risk of severe malaria was comparable in Pv
and Pf especially in children less than 5 years of
age [22]. One more study from Indonesia which
included 1560 infants of less than 3 months of age
of malaria. In these young infants, infection with Pv
was associated with a greater risk of severe anemia
(odds ratio, 2.4; 95% CI 1.03—5.91) and severe
94
thrombocytopenia (odds ratio, 3.3; 95% CI
1.07—10.6) compared to PF [23]. A retrospec-
tive analysis of 221 patients of Pv malaria from
India by Sharma et al. [24] found thrombocy-
topenia, hepatic dysfunction, renal dysfunction in
significant number of patients (96%, 27% and 7%,
respectively). Three maternal deaths occurred due
to ARDS. In another study from Bikaner (India) of
456 adult Pv malaria patients, 40 showed severe
manifestations. Complications observed were
hepatic dysfunction and jaundice in 23 (57.5%)
patients, renal failure in 18 (45%) patients, severe
anemia in 13 (32.5%) patients, cerebral malaria
in 5 patients (12.5%), acute respiratory distress
syndrome in 4 patients (10%), shock in 3 patients
(7.5%) and multi-organ dysfunction was detected
in 19 (47.5%) patients [16]. A study on young adult
females comparing the severe manifestations of Pv
malaria among pregnant (n = 25) and non-pregnant
(n = 144) groups found complications like severe
anemia (60% vs. 27%), hepatic failure (12% vs.
7.6%), renal failure (8% vs. 3.4%), ARDS (4% vs.
2.7%) and multiorgan dysfunction (4% vs. 3.4%)
more common in pregnant females [17]. There
is no larger study on pediatric patients regarding
severe manifestation of Pv malaria. A case series
by Parakh et al. of Pv malaria (n = 6) have shown
severe anemia (2 patients), altered renal functions
(2 patients) and cerebral malaria (3 patients) in
pediatric patients [25].
Our study highlights the fact that Pv can lead
to serious fatal complications similar to Pf. All
national and international guidelines should incor-
porate the term ‘‘severe vivax malaria’’ and
describe it further.
Conflicts of interest
Nothing to disclose.
Acknowledgements
We thank Dr. Praveen Kumar for his involvement
towards patient’s management and critical review
of the manuscript.
Funding: None.
Competing interests: None.
Contributions: HS collected the data, performed
the statistical analysis and wrote the manuscript;
AP conceptualized the idea, contributed toward
writing and statistical analysis and would act
as guarantor. All other authors were involved in
patient management.
H. Singh et al.
Ethical approval: All authors approved the final
version.
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