Medley of infections-a diagnostic challenge

Abstract

We present a rare case of multiple infections coexisting together. This is one of the rarest cases of four infections which coexisted together in our patient. It is an alarming for the physicians to be aware of such infections as early prompt diagnosis can be lifesaving.

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Document heading doi: ©2015 by the Asian Pacific Journal of Tropical Biomedicine. All rights reserved.
Medley of infections-a diagnostic challenge
Raghavendra Bhat, Parul Kodan, Meenakshi A Shetty
Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, India
Asian Pac J Trop Biomed 2015; 5(5): 418-420
Asian Pacific Journal of Tropical Biomedicine
journal homepage: www.elsevier.com/locate/apjtb
Contents lists available at ScienceDirect
*Corresponding author: Raghavendra Bhat, Professor and Head, Department of
Medicine, Kasturba Medical College, Mangalore, India.
Tel: +919845083094
E-mail: nita2005bhat@yahoo.co.in
1. Introduction
Presence of multiple co-infections can pose a diagnostic and
therapeutic dilemma for the diagnosis and treatment of the patient.
Literature search shows only a handful of case reports with multiple
existing concurrent infections[1]. We present a rare case with four
infections which is the first of its kind to be reported. We share our
experience of the diagnostic and therapeutic challenges encountered
with multiple co-infections.
Rarity of the case, unusual associations, good recovery of the
patient and possibility of similar or other co-infections which can be
lifesaving if timely diagnosed prompted us to report the case.
2. Case report
A 22-year-old male resident of Mangalore, a coastal city in India
presented with fever for one week, progressively increasing yellowish
discoloration of skin, eyes and urine for 4 d and loose stools for
1 d. He was conscious and oriented with stable vitals. Icterus was
present. He had no rash or bleeding from any site. On per abdomen
examination he had hepatomegaly and mild splenomegaly
with no evidence of ascites. Other systemic examination was
unremarkable. Initial investigations revealed low platelet counts
(12 000/øL), deranged liver functions (total bilirubin: 3 076.32
ømol/L, direct bilirubin of 2 192.32 ømol/L and mildly elevated
liver enzymes) and deranged renal function test (creatinine 3.1,
urea 125, Na 129, K 4.7). Chest X-ray and electrocardiogram was
within normal limits. An ultrasonography of the abdomen showed
mild splenomegaly and mild hepatomegaly with normal kidney
echo texture. A differential diagnosis of malaria was considered.
On evaluation peripheral smear was suggestive of mixed malaria.
The patient was transferred to the Intensive Care Unit and treated
PEER REVIEW ABSTRACT
KEYWORDS
Co-infections, Dengue, Malaria, Hepatitis A, Hepatitis E
We present a rare case of multiple infections coexisting together. This is one of the rarest cases
of four infections which coexisted together in our patient. It is an alarming for the physicians to
be aware of such infections as early prompt diagnosis can be lifesaving.
Peer reviewer
Chiara Pelillo, Post Doc, Callerio
Foundation Onlus, Via A.Fleming 22-31
34124 Trieste, Italy.
E-mail: Chiara.pelillo@libero.it
Comments
This case report is of extremely importance,
since: 1) itÊs the first case in literature of
a 4 co-existing acute infections, two of
them mosquito borne diseases and all very
common in endemic areas; 2) it shows
how a rapid diagnosis is lifesaving in this
context; 3) it demonstrates that is essential
not to neglect any symptom in a patient to
reach the right diagnosis.
Details on Page 420
Article history:
Received 4 Jan 2015
Received in revised form 26 Feb 2015
Accepted 15 Mar 2015
Available online 26 Mar 2015

Raghavendra Bhat et al./Asian Pac J Trop Biomed 2015; 5(5): 418-420 
with artesunate, intravenous infusion fluids in view of acute kidney
injury and symptomatic treatment. PatientÊs fever did not subside
despite treatment, he developed petechiae in the lower limbs and
had decrease urine output. Renal functions worsened and patient
required hemodialysis in view of oliguria and worsening renal
parameters. His platelet counts dropped further and fever was
continuous which made us think of additional co-infection, and
also disproportionately altered liver function tests prompted us
to investigate further for any concurrent infections. The patient
was found to be positive for dengue, (dengue IgM capture ELISA),
hepatitis E virus infection (EIAgen HEV IgM kit) and hepatitis A
(HAV IgM kit). He was negative for HIV, enteric fever, leptospirosis,
rickettsia infection, HbsAg and anti-HCV antibodies. Blood culture
had no growth. He was managed with i.v. antibiotics, hemodialysis,
antimalarial, blood and platelet transfusion. Patient improved
clinically however blood pressure recordings were persistently
on higher side despite no history of hypertension, initial normal
cardiac evaluation and normal electrocardiogram. He was started on
antihypertensive (Tab amlodipine 5 mg OD) On the 7th day, he was
discharged afebrile, hemodynamicaly stable with normal laboratory
parameters. On follow up after 2 weeks, patient was asymptomatic
and continued on only antihypertensive medication.
3. Discussion
Overlapping clinical presentations, simultaneous transmission of
multiple infections can pose diagnostic dilemma to the clinicianÊs.
A timely diagnosis and optimal laboratory evaluation remains the
mainstay in making correct diagnosis which may be lifesaving in
patients with concurrent infections[1].
Dengue and malaria are both mosquito borne diseases and
there concurrent infection tends to be more severe than either
single infection notably for hematological abnormalities like
thrombocytopaenia[2]. Prompt diagnosis of acute dual infection
can be lifesaving for the patient. Ever since the first case of dual
infection reported in 2005[3], possibly because of the growing
population, frequent travels, better laboratory services and growing
awareness we are witnessing an era of emerging co-infections as
a major concern in tropical areas especially. The growing number
of case reports reporting the concurrent dual infection should alert
the physicians in endemic areas where both infections are rampant,
to systemically examine for both diagnosis even if one or other is
positive[3-6].
However, what was more alarming in our case was not just the
presence of the two deadly mosquito borne co-infection but a
shocking presence of four acute infections at the same time. Our
experience with such co-infections is scarce. Chaudhary et al.
reported first case report of a mixed infection due to leptospirosis,
dengue, malaria and hepatitis E virus[1]. A similar case of triple
co-infections with leptospira, dengue and hepatitis E by Behera et
al. was a similar knocking evidence for the medical fraternity to
be aware of existence of concurrent infection which causes higher
morbidity and mortality if not timely detected and treated[7].
Case reports of dengue and typhoid coinfections have also
been reported where in both the cases were timely managed and
recovered completely on out-patient basis. In another rare case of
triple infection with falciparum, vivax and dengue in a pregnant
female timely diagnosis proved lifesaving and patient recovered and
was discharged within a week with fetal well being, underscoring
the importance of timely management[8]. Our case to the best of
our knowledge is the first reported case of four co-infections with
malaria, dengue, hepatitis A and hepatitis E and its timely diagnosis
with laboratory evidence and treatment with good recovery of the
patient further emphasizing the fact that timely management can
yield good results and early recovery.
Although unexplained development of hypertension which may
be unassociated still remains enigmatic as our experience with
such infections is not reported or unknown. Although patient may
be having preexisting hypertension but is unlikely in the light of
regular medical checkups which patient routinely underwent. The
possibility of any of the infection presenting as nephritic syndrome
or due to autoimmune reaction can be possible hypothesis for
such a presentation. Limited studies show evidences that renin<
angiotensin<aldosterone system, and more specifically angiotensin
II influence severity of malaria[9]. Although more evidence to
consider this association and explore the role of coinfections and
immunological pathway is required. No convincing evidence or
firm hypothesis can be established at present for this association,
but it is a fact that a lot more needs to be researched about multiple
coinfections to broaden our insight about it.
The presence of coinfections have shown unusual presentations
such as in a recent case reported in a toddler, Epstein Barr virus
and Leishmenia coinfection presented as rare hemophagocytic
lymphohistiocytosis syndrome[10]. Another case of coinfection
of malaria and dengue has been reported with unusual presence
of rhabdomylosis with normal creatinine kinase level and non
oligouric acute kidney injury[11]. A review article exploring the
mystifying relation of coinfections with malaria conclude that
presence of multiple infections can have significant challenges
in diagnosis as well as treatment and such synergistic infections
although often associated with deleterious effects may also have
positive effect in few cases due to unique interactions between
host and multiple microbes[12]. A lot more needs to be explored
about such interactions and a more keen attempt to promptly look
and search for multiple infections will not only improve clinical
outcome but will also unveil a lot more about immunology,
pathology ,microbiology and realms of other facts about such
multiple infections.

Raghavendra Bhat et al./Asian Pac J Trop Biomed 2015; 5(5): 418-420
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4. Conclusion
The above case aims to underscore the importance of awareness
of possibility of concurrent infections and appropriate laboratory
evidence to search for co-infections which can be crucial in
appropriate diagnosis and treatment. More awareness and reporting
of such co-infections may open more doors about unknown clinical
spectrums and associations when multiple pathogens act together!
Conflict of interest statement
We declare that we have no conflict of interest.
Comments
Background
The authors stated that this is the first reported case of four co-
infections in a patient. Simultaneous transmission of multiple
infections can pose diagnostic dilemma and problems on the choice
of the effective treatment for clinicians. Prompt diagnosis and optimal
laboratory exams can be lifesaving for patients.
Research frontiers
The current research presents a rare case of four acute co-existing
infections in 22-years-old male: he was affected by malaria, dengue,
hepatitis B and A with altered liver and renal functions, promptely
diagnosed with rapid laboratory analysis and cured.
Related reports
The authors state that this is the first reported case of a multiple
(more than 2) infections spreaded in a patient. There is a growing
number of case reports on the concurrent dual infection that should
keep the attention of the clinicians in endemic areas and move for a
rapid diagnosis with effective laboratory exams.
Innovations and breakthroughs
In this case report the authors highlight the possibility of multiple
acute infections at the same time in a single patient living in endemic
areas and how their prompted diagnosis was the only chance to save
the patient. They demonstrated as well that taking into account all the
symptoms detected in the patient, let them investigate on all possible
concurrent infections, performing all useful laboratory exams to
identify the right cause of disease and finally the right treatment.

Applications
This article support the importance of a rapid diagnosis in a multiple
acute infections scenario, such as that presented in this article.
To achieve this aim it is extremely important to consider all the
symptoms in a patient and make all the useful analysis to investigate
on them. Focusing on the simultaneous infections presented in this
case report, the article shows what kind of laboratory analysis must
be performed in the presence of the symptoms described in the article
and suggest a possible treatment against malaria, dengue, hepatitis A
and B infections at the same time.
Peer review
This case report is of extremely importance, since: 1) itÊs the first
case in literature of a 4 co-existing acute infections, two of them
mosquito borne diseases and all very common in endemic areas;
2) it shows how a rapid diagnosis is lifesaving in this context; 3) it
demonstrates that is essential not to neglect any symptom in a patient
to reach the right diagnosis
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