Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
546
In e na ional Jou nal o Medical
and Pha maceu ical Resea ch
Online ISSN-2958-3683 | P in ISSN-2958-3675
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O iginal A icle
E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s
Sowjanya Rakam1, Sandeep Thi una ukka asu 2, Mallika jun Suliga i3, Ramesh Kandimalla4
1Associa e P o esso , Depa men o Pa hology, Go e nmen Medical College, Na sampe , Wa angal, Telangana, India
2Associa e P o esso , Depa men o Mic obiology, BGS Medical College and Hospi al, Adichunchanagi i Uni e si y (ACU), Naga u ,
Bengalu u, Ka na aka, India.
3Associa e P o esso , Depa men o Biochemis y, BGS Medical College and Hospi al, Adichunchanagi i Uni e si y (ACU), Naga u ,
Bengalu u, Ka na aka, India.
4Associa e P o esso , Depa men o Biochemis y, Go e nmen Medical College, Na sampe , Wa angal, Telangana, India.
A B S T R A C T
Co esponding Au ho :
D . Kandimalla Ramesh
Associa e P o esso , Depa men o
Biochemis y, Go e nmen Medical
College, Na sampe , Wa angal,
Telangana, India.
Recei ed: 15-10-2025
Accep ed: 14-11-2025
A ailable online: 20-11-2025
Backg ound: Mala ia con inues o be a majo public heal h bu den in endemic
egions, and anemia is one o i s mos equen and clinically signi ican
complica ions. In lamma o y cy okines eleased du ing he acu e phase o in ec ion
may con ibu e o hemolysis, impai ed e y h opoiesis, and disease se e i y. This
s udy e alua ed he hema ological al e a ions and ci cula ing cy okine pa e ns
among labo a o y-con i med mala ia pa ien s.
Me hods: A c oss-sec ional s udy was conduc ed among pa ien s diagnosed wi h
Plasmodium alcipa um o Plasmodium i ax mala ia be ween 2023 and 2024 a
Kaka iya Medical College/MGM Hospi al. Hemoglobin, ed cell indices, and
pe iphe al smea indings we e eco ded. Se um concen a ions o IL-6, TNF-α, and
IL-10 we e quan i ied using s anda dized ELISA ki s. Age- and sex-ma ched
heal hy indi iduals se ed as con ols. S a is ical compa isons we e made using
S uden ’s - es o Mann–Whi ney U es , while co ela ions be ween cy okines and
hemoglobin le els we e assessed using Pea son’s .
Resul s: A o al o 120 mala ia pa ien s and 60 con ols we e included. Mean
hemoglobin was signi ican ly lowe in mala ia pa ien s (9.2 ± 1.8 g/dL) compa ed
wi h con ols (13.1 ± 1.4 g/dL, p < 0.001). IL-6 and TNF-α le els we e ma kedly
ele a ed in mala ia cases (IL-6: 52.4 ± 18.6 pg/mL s 12.7 ± 4.9 pg/mL; TNF-α:
41.3 ± 15.1 pg/mL s 9.8 ± 3.2 pg/mL, bo h p < 0.001). IL-10 was also highe
among pa ien s (28.5 ± 10.2 pg/mL) compa ed wi h con ols (6.4 ± 2.5 pg/mL, p <
0.001). Hemoglobin showed a signi ican nega i e co ela ion wi h IL-6 ( = –0.62,
p < 0.001) and TNF-α ( = –0.58, p < 0.001), sugges ing an in lamma o y
con ibu ion o anemia se e i y.
Conclusion: Mala ia is associa ed wi h subs an ial educ ions in hemoglobin and
ma ked ele a ions in p o- and an i-in lamma o y cy okines. The s ong in e se
ela ionship be ween hemoglobin and cy okines highligh s hei po en ial ole in
anemia pa hogenesis and may aid isk s a i ica ion in clinical se ings.
Copy igh © In e na ional Jou nal o
Medical and Pha maceu ical Resea ch
Keywo ds: Mala ia, Anemia, Cy okines, IL-6, TNF-α, In lamma ion.
INTRODUCTION
Mala ia con inues o pose a majo h ea o public heal h in many opical and sub opical egions, wi h millions o
indi iduals s ill expe iencing ecu en in ec ions despi e he a ailabili y o e ec i e an imala ial he apies and ec o -
con ol s a egies [1]. India emains one o he key con ibu o s o he global mala ia bu den, wi h s a es such as
Telangana and neighbou ing egions epo ing seasonal su ges d i en la gely by Plasmodium alcipa um and
Plasmodium i ax ansmission [2]. Al hough clinical ou comes a y widely, hema ological abno mali ies—pa icula ly
anemia— emain among he mos consis en and clinically signi ican mani es a ions o he disease.
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
547
Anemia in mala ia is a mul i ac o ial p ocess ha e ol es h ough se e al in e connec ed mechanisms. Pa asi ized ed
blood cells a e lysed du ing schizon up u e, while non-in ec ed e y h ocy es a e also a ge ed by immune-media ed
des uc ion, oxida i e s ess, and splenic clea ance [3]. Meanwhile, e y h opoiesis in he bone ma ow may be ma kedly
supp essed due o dyse y h opoiesis, i on seques a ion, and impai ed e y h opoie in esponse [4]. These mechanisms do
no occu in isola ion; ins ead, hey a e hea ily in luenced by he hos ’s in lamma o y esponse.
Cy okines se e as cen al media o s o he immune eac ion o mala ia in ec ion. P oin lamma o y cy okines such as
in e leukin-6 (IL-6) and umo nec osis ac o -alpha (TNF-α) su ge du ing acu e illness and play a dual ole: while hey
con ibu e o pa asi e con ol, hey can also in e e e wi h i on me abolism, inhibi e y h oid p ogeni o ma u a ion, and
p ecipi a e anemia o in lamma ion [5]. An i-in lamma o y cy okines like in e leukin-10 (IL-10) a e up egula ed o
coun e balance excessi e in lamma ion, bu hei in luence on hema ological eco e y is no s aigh o wa d, o en
depending on he iming, magni ude, and species o Plasmodium in ol ed [6]. The in e play be ween hese cy okines and
hemoglobin le els may o e impo an clues ega ding disease se e i y and p ognosis.
Al hough se e al s udies ha e explo ed cy okine dynamics in mala ia, he ela ionships be ween in lamma o y ma ke s
and anemia exhibi egional a iabili y, in luenced by nu i ional s a us, gene ic backg ound, endemici y, and pa asi e
species dis ibu ion [7]. E idence om Telangana and simila demog aphic se ings emains limi ed, despi e he high
clinical bu den obse ed in go e nmen hospi als. Unde s anding hese pa e ns is c ucial o ea ly isk s a i ica ion,
a ge ed moni o ing, and imp o ed managemen o ulne able pa ien s such as child en, p egnan women, and hose wi h
ch onic illnesses.
In his con ex , he p esen s udy aims o e alua e anemia pa e ns and quan i y key in lamma o y cy okines—IL-6, TNF-
α, and IL-10—in labo a o y-con i med mala ia pa ien s. By examining hei co ela ions wi h hemoglobin and ed cell
indices, he s udy seeks o p o ide deepe insigh in o he in lamma o y con ibu o s o mala ial anemia and o s eng hen
he clinical ele ance o cy okine p o iling in endemic popula ions.
METHODOLOGY
S udy Design and Se ing
This esea ch was designed as a hospi al-based c oss-sec ional s udy aimed a assessing he hema ological al e a ions and
in lamma o y cy okine le els in mala ia pa ien s. The s udy was conduc ed join ly by he Depa men s o Pa hology,
Biochemis y, Gene al Medicine, and Mic obiology a Kaka iya Medical College and MGM Hospi al, Wa angal,
Telangana. This e ia y ca e hospi al ca e s o a la ge popula ion om bo h u al and u ban a eas, making i an ideal
se ing o s udying in ec ious diseases such as mala ia. The s udy was ca ied ou om Janua y 2023 o Decembe 2024,
co e ing wo consecu i e mala ia ansmission seasons. This allowed he inclusion o pa ien s ac oss a ious s ages o
in ec ion, ensu ing a ep esen a i e sample.
S udy Popula ion
The s udy popula ion consis ed o clinically suspec ed mala ia cases who epo ed o he ou pa ien and inpa ien uni s o
MGM Hospi al. A e clinical e alua ion, hose wi h symp oms such as e e , chills, headache, malaise, and
splenomegaly we e sc eened o mala ia using labo a o y es s. Pa ien s be ween he ages o 18 and 65 yea s who es ed
posi i e o Plasmodium species we e included. Bo h Plasmodium alcipa um and Plasmodium i ax in ec ions we e
conside ed, as hese species a e commonly encoun e ed in his egion. Fo compa ison, an equal numbe o age- and sex-
ma ched heal hy olun ee s wi h no his o y o ecen in ec ion, e e , o ch onic illness we e ec ui ed as con ols. These
indi iduals we e sc eened o ensu e no mal hema ological alues and absence o pa asi ic in ec ion.
Inclusion C i e ia
Pa icipan s who had labo a o y-con i med mala ia by pe iphe al smea examina ion o apid diagnos ic es s we e
eligible o inclusion. Only hose willing o p o ide w i en in o med consen we e en olled in he s udy. Pa ien s we e
included only i hey had no ecei ed an imala ial d ugs o i on supplemen a ion in he p eceding se en days, as hese
in e en ions could in luence hema ological and cy okine p o iles.
Exclusion C i e ia
To minimize con ounding ac o s, pa ien s wi h condi ions known o in luence hema ological indices o cy okine le els
we e excluded. These included p egnan women, indi iduals wi h hemoglobinopa hies, ch onic kidney disease, ch onic
li e diso de s, au oimmune diseases, HIV in ec ion, o any ch onic in lamma o y condi ion. Pa ien s ecei ing
co icos e oids, immunosupp essi e agen s, o i on he apy we e also excluded. In addi ion, indi iduals wi h co-exis ing
in ec ions such as dengue, chikungunya, yphoid, o sepsis we e excluded a e app op ia e labo a o y e alua ion,
ensu ing ha he indings we e speci ic o mala ia.
Sample Size
The sample size was de e mined based on expec ed di e ences in hemoglobin and cy okine le els be ween mala ia
pa ien s and con ols as epo ed in ea lie s udies. A minimum o 100 cases and 50 con ols was es ima ed o achie e
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
548
adequa e s a is ical powe . To u he s eng hen he analysis, he s udy included 120 con i med mala ia pa ien s and 60
heal hy con ols, p o iding a obus da ase o compa a i e and co ela ion analyses.
Da a and Sample Collec ion
A e ob aining consen , de ailed demog aphic and clinical in o ma ion was eco ded using a s uc u ed p o o ma. This
included age, sex, p esen ing symp oms, du a ion o e e , and physical examina ion indings. Venous blood samples
we e collec ed unde asep ic p ecau ions. A o al o 5 mL o blood was d awn om each pa icipan ; 2 mL was used o
comple e blood coun analysis, and he emaining 3 mL was ans e ed in o s e ile plain ubes. Se um was sepa a ed by
cen i uga ion a 3000 pm o 10 minu es and s o ed a –20°C un il cy okine es ima ion. Pe iphe al smea s we e p epa ed
immedia ely and s ained using Giemsa s ain o con i m he species o Plasmodium and quan i y pa asi emia.
Hema ological Analysis
Hema ological pa ame e s, including hemoglobin concen a ion, ed cell indices (MCV, MCH, MCHC), o al leukocy e
coun , di e en ial leukocy e coun , and pla ele coun , we e analyzed using an au oma ed hema ology analyze
(Sysmex/Beckman Coul e ). The me hodology ensu ed consis en , high-p ecision measu emen o all pa ame e s.
Pe iphe al smea examina ion p o ided mo phological de ails and species con i ma ion, suppo ing he au oma ed esul s
and o e ing a mo e comp ehensi e assessmen .
Cy okine Es ima ion
Se um le els o key in lamma o y cy okines—in e leukin-6 (IL-6), umo nec osis ac o -alpha (TNF-α), and in e leukin-
10 (IL-10)—we e measu ed using comme cially a ailable sandwich ELISA ki s. All ELISA p ocedu es s ic ly ollowed
he manu ac u e ’s p o ocols o ensu e ep oducibili y. Samples we e un in duplica e o enhance accu acy, and s anda d
cu es we e gene a ed o each cy okine using known calib a o s. Abso bance was measu ed using a mic opla e eade a
450 nm, and cy okine concen a ions we e ob ained by plo ing he op ical densi y alues on he s anda d cu e.
Quali y Con ol Measu es
Quali y con ol was main ained h oughou he s udy o ensu e he eliabili y o esul s. Hema ology analyze s we e
calib a ed daily, and in e nal quali y con ol checks we e pe o med be o e p ocessing samples. ELISA assays included
posi i e and nega i e con ols, blank wells, and s anda ds o con i m assay alidi y. Se um samples showing hemolysis,
clo ing, o lipid in e e ence we e ejec ed. All labo a o y p ocedu es adhe ed o na ional quali y s anda ds, ensu ing he
accu acy and in eg i y o he esul s.
S a is ical Analysis
All collec ed da a we e en e ed in o Mic oso Excel 2021 and analyzed using SPSS e sion 26.0 (IBM Co p., USA).
Con inuous a iables we e exp essed as mean ± s anda d de ia ion, and ca ego ical a iables as equencies and
pe cen ages. The independen - es o Mann–Whi ney U es was used o compa e hema ological and cy okine
pa ame e s be ween g oups based on da a dis ibu ion. Pea son’s co ela ion coe icien was applied o e alua e he
associa ion be ween cy okine le els and hemoglobin concen a ion. A p- alue o <0.05 was conside ed s a is ically
signi ican .
E hical Conside a ions
P io app o al o he s udy was ob ained om he Ins i u ional E hics Commi ee o Kaka iya Medical College and
MGM Hospi al. All pa icipan s we e in o med abou he na u e and pu pose o he s udy, and w i en consen was
collec ed be o e sample p ocu emen . Pa icipan s’ iden i y and clinical in o ma ion we e kep s ic ly con iden ial, and
all p ocedu es ollowed e hical guidelines o human esea ch.
RESULTS
Baseline Cha ac e is ics o he S udy Pa icipan s
A o al o 180 indi iduals we e included in he inal analysis, comp ising 120 mala ia pa ien s and 60 heal hy con ols.
The mean age o mala ia pa ien s was 34.8 ± 12.6 yea s, and he age dis ibu ion was compa able be ween pa ien and
con ol g oups (p = 0.62), indica ing ha he g oups we e well ma ched. Males cons i u ed 52.5% (n = 63) o he mala ia
g oup and 50% (n = 30) o he con ols, showing no signi ican di e ence in gende dis ibu ion (χ² = 0.11, p = 0.74).
Among he pa ien s, Plasmodium i ax was iden i ied in 68 cases (56.7%), whe eas Plasmodium alcipa um accoun ed
o 52 cases (43.3%), consis en wi h epidemiological ends epo ed in his egion. Mos pa ien s p esen ed wi hin he
i s 3–5 days o symp om onse , wi h e e , chills, body pain, and a igue being he p edominan complain s.
Hema ological Al e a ions in Mala ia Pa ien s
Mala ia pa ien s demons a ed ma ked hema ological dis u bances, wi h anemia being he mos p ominen inding. The
mean hemoglobin le el among pa ien s (9.2 ± 1.8 g/dL) was signi ican ly lowe compa ed wi h heal hy con ols (13.1 ±
1.4 g/dL, p < 0.001). Nea ly 74% o pa ien s exhibi ed hemoglobin alues below 10 g/dL, e lec ing he high bu den o
anemia in acu e mala ia.
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
549
Red cell indices u he e ealed mic ocy ic and hypoch omic pa e ns. The mean co puscula olume (MCV) was
signi ican ly educed in pa ien s (71.4 ± 6.8 L) compa ed o con ols (82.3 ± 5.4 L, p < 0.001). Simila ly, he mean
co puscula hemoglobin (MCH) and mean co puscula hemoglobin concen a ion (MCHC) showed subs an ial
educ ions (p < 0.001 o bo h). These indings highligh he combined e ec s o hemolysis, dyse y h opoiesis, and
in lamma ion-d i en dis u bances in ed cell syn hesis.
Pla ele coun s we e also signi ican ly lowe in pa ien s, wi h a mean alue o 118 ± 52 ×10³/µL, nea ly hal o he
no mal alues seen in con ols (262 ± 68 ×10³/µL, p < 0.001). Th ombocy openia was obse ed in 72 pa ien s (60%), a
ea u e mo e equen ly no ed in P. alcipa um in ec ions. To al leukocy e coun showed a mixed pa e n: 21.6% o
pa ien s had leukopenia, while 14.1% showed leukocy osis, e lec ing a ying immune esponses and possible seconda y
eac ions o pa asi e load (Table 1).
Table 1: Compa ison o Hema ological Pa ame e s be ween Mala ia Pa ien s and Con ols
Pa ame e
Mala ia Pa ien s (n=120)
Con ols (n=60)
p- alue
Hemoglobin (g/dL)
9.2 ± 1.8
13.1 ± 1.4
<0.001
MCV ( L)
71.4 ± 6.8
82.3 ± 5.4
<0.001
MCH (pg)
22.1 ± 3.1
27.6 ± 2.8
<0.001
MCHC (g/dL)
29.8 ± 2.2
33.1 ± 1.9
<0.001
Pla ele coun (×10³/µL)
118 ± 52
262 ± 68
<0.001
To al WBC coun (×10³/µL)
5.7 ± 2.8
6.8 ± 1.9
0.012
Se um Cy okine Le els in Pa ien s and Con ols
Cy okine p o iling showed a obus in lamma o y esponse in mala ia pa ien s. Se um IL-6 was ma kedly ele a ed (52.4
± 18.6 pg/mL) compa ed o con ols (12.7 ± 4.9 pg/mL, p < 0.001). TNF-α le els we e simila ly high among pa ien s
(41.3 ± 15.1 pg/mL) ela i e o con ols (9.8 ± 3.2 pg/mL, p < 0.001). In e es ingly, IL-10— hough an an i-in lamma o y
cy okine—was also signi ican ly highe in pa ien s (28.5 ± 10.2 pg/mL) han in heal hy indi iduals (6.4 ± 2.5 pg/mL, p <
0.001), indica ing a compensa o y an i-in lamma o y esponse o coun e excessi e immune ac i a ion.
When cy okine le els we e compa ed be ween species, P. alcipa um in ec ions showed signi ican ly highe IL-6 (58.9 ±
19.3 pg/mL) and TNF-α (45.6 ± 14.8 pg/mL) compa ed o P. i ax (47.1 ± 16.8 pg/mL o IL-6; 36.9 ± 13.9 pg/mL o
TNF-α). The di e ence o IL-6 eached s a is ical signi icance (p = 0.004), e lec ing he well- ecognized agg essi e
in lamma o y p o ile associa ed wi h P. alcipa um (Table 2).
Table 2: Cy okine Le els Among Mala ia Pa ien s and Con ols
Cy okine
Mala ia Pa ien s (n=120)
Con ols (n=60)
p- alue
IL-6 (pg/mL)
52.4 ± 18.6
12.7 ± 4.9
<0.001
TNF-α (pg/mL)
41.3 ± 15.1
9.8 ± 3.2
<0.001
IL-10 (pg/mL)
28.5 ± 10.2
6.4 ± 2.5
<0.001
Figu e 1: Sca e Plo s Showing Co ela ion o Hemoglobin Wi h IL-6 and TNF-α
Co ela ion be ween Cy okines and Hemoglobin Le els
A clea in e se ela ionship was obse ed be ween in lamma o y cy okines and hemoglobin concen a ion. IL-6 showed a
s ong nega i e co ela ion wi h hemoglobin ( = –0.62, p < 0.001), sugges ing ha ele a ed IL-6 le els may con ibu e o
anemia h ough supp ession o e y h opoiesis and al e a ion o i on homeos asis. TNF-α also demons a ed a signi ican
nega i e co ela ion ( = –0.58, p < 0.001), consis en wi h i s known inhibi o y e ec on e y h oid p ogeni o s.
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
550
IL-10 showed a weake ye s a is ically signi ican in e se co ela ion ( = –0.31, p = 0.002), indica ing ha e en an i-
in lamma o y cy okines may e lec o e all disease bu den and con ibu e indi ec ly o educed hemoglobin (Figu e 2).
Figu e 2: Species-wise IL-6 Dis ibu ion and Rela ionship wi h Pa asi emia-A) Sca e plo showing he ela ionship
be ween hemoglobin concen a ion and se um IL-6 le els, s a i ied by Plasmodium species. Pa ien s in ec ed wi h P.
alcipa um display highe IL-6 le els compa ed wi h hose in ec ed by P. i ax, e lec ing a s onge in lamma o y
esponse; B) Sca e plo demons a ing he associa ion be ween pa asi emia pe cen age and IL-6 le els among mala ia
pa ien s. A posi i e end is e iden , wi h highe pa asi emia co esponding o ele a ed IL-6 concen a ions, indica ing
ha inc easing pa asi e bu den may d i e heigh ened in lamma o y ac i i y.
Associa ion be ween Plasmodium Species and Anemia Se e i y
Anemia se e i y a ied signi ican ly wi h species ype. Among P. i ax pa ien s, 58.8% had mild anemia, 30.9%
mode a e anemia, and 10.3% se e e anemia. In con as , P. alcipa um pa ien s showed mo e se e e illness: 23.1% had
se e e anemia, and 42.3% had mode a e anemia. The associa ion be ween species and anemia se e i y was s a is ically
signi ican (χ² = 9.84, p = 0.007), e lec ing he s ong hema ological impac o P. alcipa um (Table 3).
Table 3: Se e i y o Anemia Among P. i ax and P. alcipa um Pa ien s
Anemia Se e i y
P. i ax (n = 68)
P. alcipa um (n = 52)
χ²
p- alue
Mild
40 (58.8%)
18 (34.6%)
Mode a e
21 (30.9%)
22 (42.3%)
9.84
0.007
Se e e
7 (10.3%)
12 (23.1%)
O e all In e p e a ion
The esul s collec i ely indica e ha mala ia signi ican ly dis up s hema ological pa ame e s and is accompanied by
p onounced ele a ions in in lamma o y cy okines. The s ong nega i e co ela ions be ween hemoglobin and cy okines
unde sco e he pi o al ole o in lamma ion in he pa hogenesis o mala ial anemia. Mo eo e , P. alcipa um in ec ions
display a mo e se e e in lamma o y and hema ological p o ile han P. i ax, aligning wi h known clinical pa e ns.
DISCUSSION
The p esen s udy p o ides a comp ehensi e assessmen o hema ological abno mali ies and in lamma o y cy okine
pa e ns in mala ia pa ien s om a e ia y ca e se ing in Telangana. The indings ein o ce ha anemia emains a
pe asi e and clinically signi ican complica ion o mala ia, in luenced no only by he di ec des uc ion o in ec ed and
unin ec ed e y h ocy es bu also by he b oade in lamma o y milieu gene a ed du ing acu e in ec ion. The signi ican ly
lowe hemoglobin le els obse ed in mala ia pa ien s compa ed o heal hy indi iduals e lec his in ica e in e play o
hemolysis, ed cell memb ane agili y, splenic clea ance, and supp essed e y h opoiesis. These esul s closely mi o
p e ious obse a ions om endemic egions in India and Sou heas Asia, whe e anemia cons i u es one o he s onges
p edic o s o clinical se e i y and hospi aliza ion [7,8].
The dys egula ion o ed cell indices in ou coho —mani es ed h ough low MCV, MCH, and MCHC alues—sugges s
ha in lamma ion-d i en i on seques a ion and impai ed hemoglobin syn hesis play majo oles. IL-6 is inc easingly
ecognized as a cen al media o in his p ocess due o i s abili y o induce hepcidin, a ho mone ha es ic s i on
mobiliza ion om s o es. Ele a ed hepcidin, in u n, leads o unc ional i on de iciency despi e adequa e o al body i on,
he eby limi ing hemoglobin p oduc ion and exace ba ing anemia [10]. The s ong in e se co ela ion be ween IL-6
le els and hemoglobin obse ed in ou s udy suppo s his mechanism and aligns wi h ecen molecula s udies ha
documen he hepcidin– e i in–IL-6 axis as a d i e o mala ia- ela ed anemia [17].
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
551
Simila ly, TNF-α, which showed a signi ican nega i e co ela ion wi h hemoglobin, con ibu es o anemia h ough
mul iple pa hways. I supp esses e y h oid p ogeni o p oli e a ion, inc eases ni ic oxide p oduc ion, and p omo es
mac ophage ac i a ion—each con ibu ing o p ema u e des uc ion o e y h ocy es. Se e al immunological
in es iga ions ha e shown ha excessi e TNF-α le els a e s ongly associa ed wi h se e e ou comes such as me abolic
acidosis, ce eb al mala ia, and mul i-o gan in ol emen [11,14]. The p esen s udy ein o ces i s ele ance as a
p ognos ic ma ke by demons a ing i s associa ion wi h hema ological decline e en in uncomplica ed cases.
The ele a ion o IL-10 obse ed in his s udy ep esen s a compensa o y immuno egula o y mechanism aimed a cu bing
excessi e in lamma ion. While IL-10 is p o ec i e in mode a ing p o-in lamma o y cy okine ou pu , pe sis en ele a ion
may also signi y high disease bu den. Simila indings ha e been epo ed in A ican and Malaysian coho s, whe e IL-
10 le els end o ise selec i ely in in ec ions associa ed wi h high pa asi emia o mixed-species disease [12,13,18]. The
weake in e se co ela ion be ween IL-10 and hemoglobin in ou s udy likely e lec s i s seconda y ole in he
in lamma o y cascade, ac ing mo e as an indica o o immunological balancing han a p ima y d i e o anemia.
Species-wise di e ences be ween P. alcipa um and P. i ax in ec ions we e dis inc in ou coho . Pa ien s wi h P.
alcipa um in ec ion exhibi ed signi ican ly highe IL-6 le els and a g ea e p e alence o mode a e- o-se e e anemia.
These indings suppo he well-es ablished no ion ha P. alcipa um has g ea e pa hogenic po en ial because o i s
capaci y o cy oadhe ence, seques a ion in mic o ascula u e, and in ense s imula ion o in lamma o y cy okines
[14,15]. Eme ging molecula esea ch sugges s ha P. alcipa um–in ec ed e y h ocy es exp ess a ian su ace an igens
(VSAs) ha speci ically ac i a e endo helial cells and immune pa hways, ampli ying cy okine p oduc ion
disp opo iona ely [19]. This may explain he heigh ened in lamma o y and hema ological dis u bances obse ed in ou
subg oup analysis.
The ela ionship be ween pa asi emia and cy okine le els p o ides addi ional insigh in o disease pa hophysiology. As
no ed in his s udy, IL-6 le els inc eased s eadily wi h ising pa asi emia, sugges ing ha pa asi e biomass di ec ly
in luences in lamma o y ac i a ion. Simila pa e ns ha e been desc ibed in s udies om Ghana, Myanma , and Papua
New Guinea, whe e pa asi emia h esholds equen ly co ela e wi h cy okine su ges and isk o complica ions [16–18].
These indings highligh he impo ance o assessing cy okine p o iles as adjunc bioma ke s o ea ly ecogni ion o
se e e mala ia, especially in esou ce-limi ed se ings.
O e all, he esul s o he p esen s udy unde sco e ha mala ia-induced anemia is no me ely a hema ological p oblem
bu a complex immuno-hema ological synd ome d i en by widesp ead cy okine ac i i y. Unde s anding hese cy okine–
e y h opoiesis in e ac ions may pa e he way o a ge ed in e en ions in he u u e, such as modula ion o hepcidin,
an ioxidan he apies, o cy okine-di ec ed app oaches in high- isk pa ien s. Fu he mo e, he species-speci ic di e ences
obse ed may assis clinicians in an icipa ing complica ions and ailo ing moni o ing s a egies based on he in ec ing
Plasmodium species.
CONCLUSION
The p esen s udy highligh s he signi ican in e play be ween hema ological dis u bances and in lamma o y cy okine
ac i a ion in mala ia. Pa ien s demons a ed ma ked educ ions in hemoglobin and ed cell indices, alongside subs an ial
ele a ions in IL-6, TNF-α, and IL-10. The s ong in e se co ela ions be ween hemoglobin and key cy okines unde sco e
he cen al ole o immune-media ed mechanisms in he de elopmen o mala ial anemia. Species-speci ic di e ences,
pa icula ly he mo e p onounced abno mali ies obse ed in P. alcipa um in ec ions, u he emphasize he impo ance
o ea ly ecogni ion and close moni o ing. O e all, hese indings con ibu e o a deepe unde s anding o he immuno-
hema ological dynamics o mala ia and sugges ha cy okine p o iling may se e as a suppo i e ool o assessing
disease se e i y and iden i ying high- isk pa ien s in clinical p ac ice.
Acknowledgemen s
The au ho s since ely hank he acul y and echnical s a o he Depa men s o Biochemis y, Gene al Medicine, and
Mic obiology a Kaka iya Medical College and MGM Hospi al, Wa angal, o hei in aluable assis ance h oughou he
s udy. We acknowledge he coope a ion o all pa ien s and heal hy olun ee s who gene ously pa icipa ed. The au ho s
also app ecia e he e o s o he labo a o y pe sonnel who con ibu ed o sample p ocessing, ELISA assays, and
hema ological analyses. Thei dedica ion played a c ucial ole in he success ul comple ion o his wo k.
Au ho Con ibu ions:
Sowjanya Rakam concep ualized he s udy, coo dina ed clinical da a collec ion, pe o med pe iphe al smea e alua ions,
assis ed wi h hema ological in e p e a ion, and con ibu ed o da a accu acy. Sandeep Thi una ukka asu also
concep ualized he s udy, da a in e p e a ion and manusc ip d a ing. Mallika jun Suliga i led he o e all s udy design,
coo dina ed da a in e p e a ion, pe o med s a is ical analysis, and in e p e ed cy okine–hema ological co ela ions.
Ramesh Kandimalla ca ied ou he biochemical analyses, including ELISA-based cy okine es ima ion, main ained
labo a o y quali y con ol, suppo ed da a in e p e a ion, and assis ed in p epa ing he me hodology and esul s sec ions,
d a ed majo sec ions o he manusc ip , and inalized he a icle o submission.
Sowjanya Rakam, e al. E alua ion o Anemia and In lamma o y Cy okines in Mala ia Pa ien s. In . J Med. Pha m.
Res., 6 (6): 546‐552, 2025
552
Funding Sou ce
This esea ch did no ecei e any speci ic g an om go e nmen al, comme cial, o no - o -p o i unding agencies. All
s udy p ocedu es, labo a o y analyses, and ma e ials we e suppo ed h ough depa men al esou ces.
Con lic o In e es
The au ho s decla e ha he e a e no con lic s o in e es — inancial, academic, o pe sonal— ha could ha e in luenced
he conduc o epo ing o his s udy.
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