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Original article

Evaluating Impact of Malaria on clinical, Hematological

and Biochemical Parameters: A Study From ARID
Ecological Region of India
Lt Col Tripti Agrawala,*, Col Sandeep Bhallab
a MD (PSM) DNB (PSM) PGDHHM, Classified Spl (PSM)
b Director AFMS (Medical Research)

A RT I C L E I N F O
Article history:
Received 21 July 2011
Accepted 19 MArch 2012
Available online 17 July 2012
ABSTRACT
Abstract: Introduction: Malaria still remains most important tropicalillness
throughou world. The present study is conducted in aridecological region of India
with an aim to evalate impact of Plasmodiumvivax, falciparum and mixed malaria
on clinical, hematolocal andbiochemical parameter of patients to assist in managing
this tropicalillness of military medicine importance.
Material & Methods: This hospital based longitudinal observationa studyconducted
during Apr 2014 to Mar 2015 included 86 confirmed malarialpatients who attended
the outpatient and inpatient department of aperipheral military hospital and had ei-
dence of asexual phase of malariaparasite P. vivax or P. falciparum infection by pe-
riphera blood film(PBF) and/or rapid diagnostic test (RDT).Results: Peak incidence
of malaria was seen among 30 - 40 yrs. P. vivaxcontributed 66.3% cases; P. falci-
parum 21%; 12.7% mixedcases. 78% caseswere fresh imported. Anemia, Leucope-
nia, neutrophilia, eosinophilia, monocytosis and basophilia was found with no
significant difference in P.falc parum, vivax and mixed cases.
Thrombocytopenia was predominant in P.falciparum (77.78) than P. vivax cases
(44%) with significant difference.Peripheral blood smear was predominantly nor-
mocytic normochromic (54.6%),nucleated RBCS were found in 37.2% while retic-
ulocytosis was evident in33.7% patients. Multi-organ involvement is a feature in
complicated casesof malaria both in P. falciparum as well as P. vivax.Conclusion:
The study concludes that P. vivax infection should no longerbe considered benign
since it has propensity to cause severe malarialinfection with multi organ involve-
ment, if underestimated.

Introduction
Malaria, one of the most important tropical illness in India, lation which is exposed to mosquito bites because of various
with incidence of 2 to 3 million cases every year'. Army per- reasons and also the consequences thereof. The risk for se-
sonnel as such form a highly mobile and non immune popu- vere malaria is greatest among young soldiers especially
* Corresponding author.
E-mail address :
 MEDICAL JOURNAL ARMED FORCES INDIA 68 (2012) 335-338

from non-endemic areas in moderate and high-transmission
areas. Although P. vivax malaria is considered to be benign
malaria with a very low case-fatality ratio, it may still cause
a severe and debilitating febrile illness as in P. falciparum
malaria. The long-held view of vivax malaria as a benign in-
fection predisposes the population at risk due to casual ap-
proach to its clinical management, research and control.
of trend of malaria morbidity experienced at the peripheral
military settings; howsoever it is quite probable that few
cases would have been missed due to non-reporting due to
various reasons, which constitutes an important limitation of
the study. PCR technology was not used to confirm the
species specific diagnosis of plasmodial parasite as this was
beyond the scope of the study.

Results
In arid conditions prevailing in the north western part
of Rajasthan, focal outbreaks of malaria are frequent and
the morbidity and mortality associated with the disease is Peak incidence of malaria was seen among 30 - 40 yrs of
high. Data from research studies on malaria patients in such age group. Out of 86 confirmed cases of malaria 45 (52%)
setting is lacking and therefore this study aims to evaluate were serving while 19 (22%) were dependants of serving
deleterious impact of vivax, falciparum and mixed malaria personnel. Besides 14 (16%) were Ex-servicemen and
on clinical, haematological and biochemical parameters in 8(10%) were dependants of ex-servicemen which included
patients reporting to a peripheral hospital settings and 02 octogenarians. In the set of patients in the current study,
thereby to provide useful insight into the changing natural it was observed that fever was the commonest symptom
course of malaria and its response to anti-malarial therapy present in all cases followed by jaundice. However, the other
in the event of complications. symptoms were varied with more serious symptoms com-
monly present in P. falciparum and mixed cases warranting
continued observation in ICU settings. (Table 1)
Material and methods Table 1 - Clinical Profile of Malaria Positive Case
The present study is a hospital based observational longitu-
dinal study to delineate impact of malaria among the outpa- Symptoms P.vivax (n=57) P.falciparum (n=18) Mixed (n=11)
tient and inpatient at a peripheral hospital during Apr 2014 Fever 57 (100%) 18 (100%) 11 (100%)
to Mar 2015. The study population consisted of serving per- Chills/Rigor 36 (63%) 15 (83%) 11 (100%)
sonnel, ex-servicemen of Army and their dependents who Headache 23 (40%) 14 (77.7%) 9 (82%)
are dependant for curative services on the peripheral military Dizziness 19 (33.3%) 14 (77.7%) 8 (72.7%)
hospital. All consecutive adult patients who presented with
Nausea/Vpmiting 12 (21%) 11 (61%) 9 (82%)
fever at the military hospital during the study period and on
investigation found to have evidence of asexual phase of Jaundice 9 (16%) 6 (33.3%) 2 (18%)
malaria parasite P. vivax infection or P. falciparum infection Disorientation 3 (5.3%) 6 (33.3%) 4 (36%)
by peripheral blood film (PBF) and/or positive by rapid diag- Blurring of Vision 2 (3.5%) 5 (27.7%) 4 (36%)
nostic test (RDT), constituted the study sample. Pregnant
females, paediatric age group, relapse malaria cases and
those with positive history of dengue, enteric fever, chronic P. vivax contributed to 57 (66.3%) cases while P. fal-
liver disease, bleeding disorder, thrombocytopenia, drug in- ciparum 18 (21%) and 11(12.7%) were mixed cases. 78%
take or conditions which might have contributed to blood cases were fresh imported being referred from field hospitals
changes were excluded from study sample. and medical inspection rooms dependent on this peripheral
Total of 86 adult patients having fever along with evi- military hospital for specialist care. Imported cases of malaria
dence of asexual phase of malaria parasite P. vivax infection also imply that subjects might have contracted malarial par-
or P. falciparum infection by peripheral blood film (PBF) asite while travelling, or stay at leave address or during tem-
and/or rapid diagnostic test (RDT) were studied. All studied porary duty to some other duty station. Anemia was present
patients were followed up for a period of up to twelve weeks in 79% cases with no significant difference
which included the period of their hospitalization for the pur- between P. Falciparum, P. vivax and mixed cases. Thrombo-
pose of treatment and further sick leave, if deemed appro- cytopenia was predominant in P. falciparum (77.7%) than P.
priate. World Health Organization guidelines were followed vivax cases (44%) and mixed cases (54.5%) with statistically
for patient categorization on the basis of severity of malaria significant difference. Leucopenia, neutrophilia, eosinophilia,
and adequate treatment was undertaken as per standard monocytosis and basophilia was found in few cases of
guidelines“. malaria with no significant difference in P. falciparum P vivax
The data generated was analyzed to study the socio- and mixed cases. (Table 2)
demographic profile of patients and to compare the clinical
profile including complication of patients with vivax, falci-
parum and mixed malaria. Data Analysis was done using
standard statistical procedures viz rates, proportions, chi
square test, Unpaired t test, ANOVA. It is confessed by au-
thors that the data presented in the study is representative
 MEDICAL JOURNAL ARMED FORCES INDIA 68 (2012) 335-338

Table 21 - Comparison of Hematological Findings Table 14 - Comparison

Biochemical of
findings among Malaria
Hematological Findings
among Malaria Postive cases positive cases Postive cases
among Malaria
Hematological P.vivax P. falciparum Mixed Statistical Biochemical P.vivax P. falciparum Mixed Statistical
profile No(%) No (%) No (%) No (%) results parameters (n=57) (n=18) (n=11) results
Anemia 45 (79%) 15 (83%) 08 x2=0.466 df=2 Serum Bilirubin 1.3 1.5 1.1 p = 1.76
68(79%) (72.7%) p=0.792 (mg/dl) 0.53 0.86 0.67
Leucopenia 07 (13%) 02 (12%) 01 (9%) x2=0.972 df=2 Serum Alanine 35 39 28 p = 0.192
10 (11.6%) p=0.952 aminotransferase (IU/I) 10.2 18.6 5.4
Neutrophhilia 04 (7%) 01 (6%) 02 (18%) x2=1.74 df=2 Serum Asparate 32 36 30 p = 1.35
07 (81.3%) p=0.419 aminotransferase (IU/I) 8.4 14.6 2.8
Lymphopenia 10 (17.5%) 07 (38%) 05 (45.4%) x2=5.89 df=2 Urea 24.9 23.7 25.2 p = 0.138
22 (25.5%) p=0.053 (mg/dl) 2.9 3.6 205
Monocytosis 06 (10.5%) 03 (18%) 03 (27%) x2=2.29 df=2 Creatinine 1.4 1.3 1.4 p = 0.390
12 (13.9%) p=0.318 (mg/dl) 0.19 0.45 0.23
Eosinophilia 04 (7%) 01 (6%) 01 (9%) x2=0.132 df=2 Blood sugar 96.7 89.6 99.8 p = 0.004
06 (6.9%) p=0.936 (mg/dl) 18.2 21.4 9.5
Basophilia 01 (1.7%) 00 (0%) 01 (9%) x2=2.73 df=2
02 (2.3%) p=0.256 The other complications were hypoglycemia (26.7%),
Thrombocytopenia 25 (44%) 14 (77.7%) 06 (54.5%) x2=6.33 df=2
45(52.3%) p=0.042
jaundice (36%), renal failure (4.6%), ARDS (3.4%), cerebral
malaria (3.4%) and death (2.3%). The two death cases were
Peripheral blood smear was predominantly normo- ex-servicemen in their old age, with other co-morbid condi-
cytic normochromic (54.6%), nucleated RBCS were found tions, admitted almost in terminal stages with number of
in 37.2% while reticulocytosis was evident in 33.7% patients. complications involving multiple organs. In complicated P.
Toxic granules were seen in 6 (6.9%) cases, atypical lym- falciparum infection, jaundice with acute renal failure was
phocytes were observed in 2 (2.3%) cases and hyperseg- the commonest presentation; followed by cerebral malaria
mented polymorph was found in 1(1.1%) case with their with jaundice and ARF and severe jaundice alone; while in
predominance among P. falciparum cases. The results were P. vivax infection jaundice with acute renal failure was pres-
statistically significant for Nucleated RBCS and Macrocytic ent, followed by cerebral malaria with jaundice and ARF and
microcytic peripheral blood picture. (Table 3) jaundice, ARF and ARDS. (Table 5) It was also noticed that
the rate of single organ involvement is relatively low while
multi-organ involvement was more common in malaria es-
Table 3 - Distribution of Peripheral smear
pecially in P. falciparum cases than P. vivax. Nonetheless, it
changes in Malaria Postive cases is to be highlighted that multi- organ involvement is not an
Peripheral smear P.vivax P. falciparum Mixed Statistical uncommon finding in P. vivax infection. It was also found
changes No (%) No (%) No (%) No (%) results that there were higher mortality rates in those with multi-
Normocytic normochromic 34 (59.6%) 10 (55.5%) 03 (27.3%) x2=3.91 df=2 organ involvement complicating the entire physiological sys-
47 (54.6%) p=0.142 tem.
Normocytic hypoochromic 22 (38.6%) 05 (27.8%) 06 (54.5%) x2=2.07 df=2
33 (38.4%) p=0.355
Macrocytic microcytic
06 (7%)
01 (1.70%) 03 (16.6%) 02 (18.1%) x2=7.13
p=0.028
df=2 Table 5- Distribution of Malaria cases as per
NRBCs* 22 (38.6%) 09 (50%) 01 (9%) x2=12.6 df=2 incidence of Complications
32 (37.2%) p=0.002
Reticulocytes 18 (31.6%) 08 (44.4%) 03 (27.3%) x2=3.83 df=2 Comlications No. P.vivax P.falcipar Mixed Statistical
29 (33.7%) p=0.147 (%) (n=57) um (n=18) (n=11) all results
Toxic granules 03 (5.2%) 02 (11.1%) 01 (9.0%) x2=0.625 df=2 Thrombocytopenia 45 25 14 6 x2=6.63 df=2
29 (6.9%) p=0.732 (<1,50,000 count) (52.3%) (43.8%) (77.7%) (54.5%) p=0.042
Atypical lymphocytes 01 (1.7%) 01 (5.5%) 00 (0.0%) x2=1.17 df=2 Severe anaemia 11 4 6 1 x2=8.65 df=2
02 (2.3%) p=0.557 (<8mg/dl) (12.8%) (7%) (33%) (0.9%) p=0.013
Hypersegmented 00 (0.0%) 01 (5.5%) 00 (0.0%) x2=3.82 df=2 Hypoglucemia (blood 23 11 9 3 x2=6.658 df=2
polymorphs 01 (1.1%) p=0.148 glucose < 45mg/dl) (26.7%) (19.3%) (50%) (27%) p=0.037
ARDS 03 1 2 0 x2=4.01 df=2
(3.5%) (1.7%) (11.1%) (0.0%) p=0.134
Low glucose levels were found to statistically signifi- Renal failure 04 1 2 1 x2=3.26 df=2
cant with P. falciparum and mixed infections in comparison (4.7%) (1.7%) (11.1%) (0.9%) p=0.196
to P. vivax while rise in liver enzymes, urea, creatinine and Hepatic dysfunction 17 9 6 2 x2=2.67 df=2
(serum bilirubin > 3mg/dl) (19.8%) (15.8%) (33%) (1.8%)
was not statistically significant in three types of infections. p=0.263
Cerebral malaria 03 0 2 1 x2=6.19 df=2
(Table 4) (3.5%) (0.0%) (11.1%) (0.9%) p=0.045
Death 02 0 1 1 x2=4.40 df=2
(2.3%) (0.0%) (5.5%) (0.9%) p=0.111
 MEDICAL JOURNAL ARMED FORCES INDIA 68 (2012) 335-338
Out of 86, 57 (66.2%) cases were admitted for the pe-
riod of hospital stay was less than 10 days while 29 (33.8%)
cases stayed for duration more than 10 days either out of
some complications, or for follow up or observation for nor-
malization of laboratory findings predominantly in P falci-
parum positive cases. (Table 6) Most (85%) of these cases
responded within satisfactory limits to the anti-malarial ther-
apy, howsoever in few cases refractoriness to the treatment
was observed, thereby warranting institution of 2nd /3rd
level of anti-malarial group of drugs more so in mixed group
of plasmodium infections.
Table 6 - Duration of Hospital stay of the study
patients
Duration of P.vivax P. falciparum Mixed Total
hospital stay (n=57) (n=18) (n=11)
10 days 46 6 5 57 (66.2%)
> 10 days 11 12 6 29 (33.8%)
Discussion
It is an established scientific fact that, one of the important
etiological factor for hemolytic anemia among human pop-
ulace is Malaria9-11.19 cycle of malarial infestation is re-
sponsible for manifestation of common signs and
symptoms viz fever with chills followed by sweating, inter-
mittent episodes of headache, vomiting, diarrhea, at times
complicated by abdominal pain with distension,
splenomegaly and hepatomegaly. Jaundice is an impor-
tant manifestation in The extra corpuscular malaria attrib-
uted by hemolysis of affected erythrocytes, concurrent
hemoglobinopathies, altered and complex immunological
reactions to hemolysed products by spleen. Thus the
patho-physiological of malarial parasite infestation is most
commonly manifested as anemia and thrombocytopenia
in the background of nutritional profile, socio-demographic
status and pre existent aquired malarial immunity by af-
fected locals.
The present study shows that anemia was present
in 79% and it was normocytic normochromic type in 56.4%
of these cases, a finding which is parallel with various
studies. 3.4.5,6,7,8 and reticulocytosis was evident in
33.7% cases which was more so in P. falciparum cases
than P. vivax cases, howsoever there was no significant
difference in occurrence of these findings in the two types
of malaria. Findings also included presence of Nucleated
RBCS in 37.2% cases.
Anemia ia a common complication in malarial infec-
tion, it is caused by a variety of pathophysiologic mecha-
nism. Most of the proposed theories were in favour of the
fact that anemia in malaria results due to combination of
phagocytosis of infected red blood cells along with inef-
fective erythropoiesis°. Other factors which contribute in
the process of development of anemia are reduced plia-
bility and increased splenic phagocytosis. Some theories
put forward the role of immunological factors (including
TNF-a) in development of anemia in malaria°. Presence
of nucleated Red Blood Cells (NRBCS) and Reticulocytes
in peripheral blood smear reflects the increased erythroid
activity in the marrow which is due to compensatory ery-
throid in severe type of malaria infections.
It ie evident from study findings that thrombocytope-
nia is not an uncommon finding in benign P. vivax infec-
tion, howsoever severe thrombocytopenia is not a
common finding in comparison to P. falciparum
infection.T5,19 45 patients (52.3%) developed thrombo-
cytopenia, which are figures comparable to study findings
of Bhalwar et al (53%) Kochar et al6 (57%) while higher
reporting by Shamin et al (86.4%).
While studying total and differential leucocyt e
count, in the present study the findings (8.1%),monocyto-
sis (13.9%), eosinophilia (6.9%) and basophilia (2.3%)
was found in few cases of malaria with no significant dif-
ference in P. falciparum and vivax. Peripheral blood smear
changes in severe cases with superadded infection and
multi-organ involvement in the present study also showed
that toxic granules (6.9%), atypical lymphocytes (2.3%)
and hyper-segmented polymorphs (1.1%) were present.
Howsoever, there was statistically no significant difference
among occurrence among P. falciparum and P. vivax in-
fection. The percentage figures are variable on these find-
ings across various studies*8 which depends on study
background, stage of infection, level of parasitemia, sever-
ity of infection, secondary infection and perusing compli-
cations in malaria cases under study. include leucopenia
(11.6%), lymphopenia (23%), neutrophilia 4-8
Various studies document that in Malaria, White
blood cell (WBC) counts remain normal to low17,18,19
marginal pool, amonngst all WBCS neutrophils comonly
found within normal limits. It is aso documented that neu-
trophil count is found elevated in cases of concurrent bac-
terial infection becuase of lowered immunity.
Hypersplenism is generally manifested as leucopenia and
neutropenia while reactive eosinophilia is evident as spec-
trum effects of malarial chemotherapy. Monocytosis is ev-
ident invariably during convalescences which is
suggestive of hyperactive reticulo-endothelial system
(RES). Peripheral smear feautures like toxic granules, hy-
persegmented neutrophils, atypical lymphocytes acknowl-
edges multi-organ involvement in the background of
superimposed infection with compromised immuno-phys-
iological state of the body. since majority of these cells are
contributed from the pre existing/
During the period of admission of these malaria pa-
tients in hospital there was gradual improvement in lab pa-
rameters after administration of anti malarial therapy along
with appropriate symptomatic and supportive therapy. re-
sponse to chloroquine administration was dependable in
almost 95% of uncomplicated cases. It was complicated
vivax, severe and malignant falciparum cases, the drug of
choice was artemisin based combination therapy. It was
observed that thrombocytopenia gradually responded to
anti malarial therapy. None of the subjects in this study
had clinical or laboratory evidence of a bleeding event and
 MEDICAL JOURNAL ARMED FORCES INDIA 68 (2012) 335-338
none of the subjects required platelet transfusion. Malaria
cases with severe anemia responded well to anti-malarial
treatment and five needed blood transfusion therapy. Hy-
poglycemia in severe malaria responded to single dose of
parenteral dextrose therapy. Degree of hypoxemia im-
proved well after being managed with oxygen therapy and
non invasive ventilation in addition to anti malarial therapy.
Renal function was monitored on a daily basis and it nor-
malized rapidly. Correction of hypovolemia and withdrawal
of implicating drugs, when required. Hepatic dysfunction,
this complication was adequately treated with antimalarials
and withdrawal of implicating drugs, if any. Infection with
hepatotropic viruses was excluded. Cerebral malaria was
managed with parenteral antimalarial therapy2 and anti
epileptic agents (short acting benzodiazepines) to which
it responded well. 18-21 In the present study,
Review of literature documents renal and hepatic
dysfunction; acute respiratory distress syndrome (ARDS),
cerebral malaria as sequestration related complications of
malaria while anemia and thrombocytopenia as non se-
questration hematological profile. P vivax is known to fre-
quently present with non sequestration related
complications while sequestration related complications
are commoner in P. Falciparum infection or mixed cases
and therefore blood film is contributed with typical features
of heavy sequestration. 15-19
Essentially clinical features of all patients with ane-
mia in malaria remains the same, with minute differences.
However, many studies have concluded that P. falciparum
as well P. vivax causes significant morbidity and mortality
due to significant anemia and higher occurrence of throm-
bocytopenia along with neutropenia. Thus most of present
strategies aiming to eliminate malaria must target P. vivax
and P. Falciparum".
Conclusions
In all military health care settings, therefore malaria must
be considered as a leading differential diagnosis in an
acutely febrile patient with one or more of these abnormal-
ities including pallor, splenomegaly, thrombocytopenia,
leucopenia, anemia, raised bilirubin and alanine trans-
ferase levels. The medical officers at unit medical inspec-
tion rooms should genuinely utilize their clinical judgment
skills and must institute presumptive treatment for malaria
in suspected fever cases keeping malaria as diffrential di-
agnosis, before referring to military hospitals. The study
highlights that P. vivax malaria infection, although consid-
ered benign, can have severe and complicated course, if
underestimated.
Intellectual contribution
?????????????????????
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