Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case Series
Year : 2022 | Month : December | Volume : 16 | Issue : 12 | Page : OR01 - OR04 Full Version

Variable Presentations of Enteric Fever, beyond Fever and Pain Abdomen: A Case Series


Published: December 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/59841.17185
Somnath Maitra, Kaushik Hazra, Sunetra Roy

1. Associate Professor, Department of General Medicine, Jagannath Gupta Institute of Medical Sciences and Hospital, Budge, West Bengal, India. 2. Assistant Professor, Department of General Medicine, Jagannath Gupta Institute of Medical Sciences and Hospital, Budge, West Bengal, India. 3. Senior Resident, Department of Paediatrics, Jagannath Gupta Institute of Medical Sciences and Hospital, Budge, West Bengal, India.

Correspondence Address :
Dr. Sunetra Roy,
Flat 1A, Jasmine Block, Pelican Gardens, 3208 Nayabad, Kolkata-700099, West Bengal, India.
E-mail: sunetra.jhumjhum@gmail.com

Abstract

Enteric Fever (Typhoid and Paratyphoid fever) is an illness that presents with marked pyrexia, abdominal pain and other gastrointestinal symptoms. Symptoms and complications primarily involve gut. But sometimes it involves other organ systems like heart, and brain. It thus poses a great diagnostic challenge in diagnosing these extraintestinal manifestations. The three cases depicted in this case series had unusual presentations in the form of dilated cardiomyopathy, non haemophagocytic lymphohistiocytosis (HLH) dyslipidaemia and encephalopathy. The first case is a case of reversible cardiomyopathy in a 26-year-old male patient presenting with fever for seven days with headache, loose motions and vomiting with audible third heart sound (S3) and bibasal crepitations without oedema. The patient responded to ceftriaxone and azithromycin. On echocardiography, dilated cardiomyopathy was diagnosed after which treatment with Ramipril and Metoprolol was started. The second case was of a 30-year-old female patient presenting with fever, vomiting, and abdominal pain. There was hypertriglyceridaemia with normal ferritin levels. The patient responded to ceftriaxone. High Density Lipoprotein (HDL) level was low. Statin and fenofibrates were added after which the triglyceride levels came down. This was an interesting case of non-HLH dyslipidaemia which responded to therapy. The third case was of a 40-year-old female patient presenting with fever for six days with impairment of consciousness. Bilateral plantar responses were extensor and there was no papilloedema or any cranial nerve palsy. Magnetic Resonance Imaging (MRI) Brain and Cerebrospinal Fluid (CSF) study were normal. The patient responded to ceftriaxone and dexamethasone proving beneficial effects of steroids in enteric encephalopathy. The purpose of the case series was to make clinicians aware of these uncommon presentations of a common disease so that early diagnosis and treatment with anti-salmonella antibiotics can be initiated quickly to prevent complications.

Keywords

Dilated cardiomyopathy, Dyslipidaemia, Encephalopathy, Non haemophagocytic lymphohistiocytosis, Reversible cardiomyopathy

Enteric fever (Typhoid and Paratyphoid fever) are systemic febrile illness caused by bacteria Salmonella enterica serotype- Typhi and Paratyphi A, B, C (1). It commonly presents with marked fever, abdominal pain, diarrhoea and altered bowel habits. The highest incidence of enteric fever is found in South Central and South East Asia. lt is transmitted by feco-oral routes and is endemic in those countries with poor public health and low socio-economic indices (2). The clinical diagnosis is difficult due to vague presentations. Gold standard for diagnosis of enteric fever is isolation of Salmonella from a patient commonly by blood culture (3). The commonly used serological test is Widal test. Widal test has various limitations. Various rapid dot blot test like Typhi dot test are gaining popularity now-a-days for rapid detection of enteric fever (3).

Typhoid fever presents with various uncommon features like encephalopathy, HLH, myocarditis, cardiomyopathy which have been discussed here. Apart from that, it may present as bilateral parotid enlargement with epididymoorchitis (4). The prevalence of uncommon presentations usually occur in Multidrug Resistance (MDR) typhoid fever. Parotid may be enlarged in enteric fever in Human Immunodeficiency Virus (HIV) patients, but is uncommon in immunocompetent patients (5),(6). Atypical features include severe headache mimicking meningitis, acute pneumonia and arthralgia. Sometimes in India and Africa, it may present as delirium, parkinsonism or Acute Demyelinating Polyneuropathy (AIDP). Pancreatitis osteomyelitis, orchitis, meningitis and abscesses may also be the uncommon manifestations (7),(8). The associated typical clinical features with the positive blood culture tests and IgM antibody tests help to explain and correlate the uncommon manifestations which help to initiate appropriate and timely treatment to prevent complications.

Case Report

Case 1

A 26-year-old male patient presented with fever for seven days with chill and rigor relieved with sweating associated with headache with history of intermittent loose motions and history of vomiting. There was no history of skin rash, joint symptoms or any history of burning sensation during micturition, nor any history of pain abdomen. On examination, the patient was alert, conscious and co-operative. He had fever of 101.0° F with mild headache but there were no signs of meningeal irritation. Pulse was 102 beats per minute (bpm) with Blood Pressure (BP) of 110/70 mm of Hg. There was mild pallor without any icterus, lymphadenopathy, clubbing and skin rash. There was bilateral vesicular breath sounds with S1, S2, S3 was also audible at the apex with bibasal crepitations without any pedal oedema. Malaria and typhoid fever were the differential diagnosis.

Treatment was started with intravenous fluids normal saline:Ringer lactate (1:1) iv 8 hourly with paracetamol, injection Proton Pump Inhibitors (PPI), injection ondansetron with injection ceftriaxone 2 gm iv twice a day (after skin test) with azithromycin 500 mg one tablet twice a day with probiotic supplementation.

Blood samples were drawn to test for Malaria Parasite (MP) with dual antigen, Typhi Dot M, IgG and IgM Dengue Antibody (Ab), Scrub typhus IgM Antibody (Ab), urine for routine examination and culture sensitivity. Typhi Dot M came positive. Other tests of fever profile were negative and the urine report was unremarkable. Complete Blood Count (CBC) revealed mild normocytic normochromic anaemia with normal White Blood Cells (WBC) and platelet counts with Erythrocyte Sedimentation Rate (ESR) of 30 mm in first hour. Urea and creatinine were mildly raised. There was mild hyponatraemia and hypokalaemia. Magnesium level was normal. Arterial Blood Gas (ABG) and chest x ray were normal (Table/Fig 1), and echocardiography revealed global Left Ventricle (LV) hypokinesia with Ejection Fraction (EF) of 45% with systolic dysfunction although the cardiac biomarkers were normal. Ultrasonography (USG) whole abdomen revealed mild hepatosplenomegaly and serology was unremarkable. Liver Function Test (LFT) revealed mild transaminitis (SGOT>SGPT) with normal bilirubin, albumin, globulin and Alkaline Phosphatase (ALP) levels. The Coronavirus Disease-2019 (COVID-19) Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was negative Blood culture-sensitivity was positive for Salmonella typhi. Cardiac MRI could not be done as it was not available in the institute.

Patient started improving from second day of ceftriaxone and azithromycin administration and fever subsided on day 5 of admission. The intravenous (i.v.) fluid was stopped on day 5 of admission. Sodium and potassium supplementation were given to correct dyselectrolytaemia. The patient was started on Ramipril 1.25 mg od with Metoprolol XL 12.5 mg od as a diagnosis of typhoid cardiomyopathy was done.

Repeat echocardiography done after seven days of the first echocardiography revealed Left Ventricular Ejection Fraction (LVEF) of 55-60% with normalisation of systolic abnormality (Table/Fig 2). Urea and creatinine levels were also normalised. The patient was diagnosed as reversible cardiomyopathy due to enteric fever. The patient was discharged and advised to attend cardiology Outpatient Department (OPD).

Case 2

A 30-year-old female patient presented with fever with chill and rigor for three days associated with vomiting, headache with pain abdomen for the same duration. There was no history of joint symptoms, skin rash or any bladder bowel complaints. The pain abdomen was localised in the right upper quadrant. There was no travel history and menstrual history was unremarkable. On examination, the patient was febrile with mild pallor without any icterus and was haemodynamically stable. There was mild hepatomegaly with tenderness in the right upper quadrant of the abdomen with mild splenomegaly. On examination of the cardiovascular and respiratory and neurological system, no abnormalities were detected. A differential diagnosis of enteric, malaria and urinary tract infection were considered. Investigations conducted were Complete Blood Count (CBC), Fasting Blood Sugar (FBS), urea, creatinine, Renal Function Test (RFT), Malarial Parasite (MP) slide and dual antigen, Nonstructural protein 1 (NS1) antigen, Typhi Dot M, urine for examination and culture. Blood for culture/sensitivity aerobic single hand, and Liver Function Test (LFT).

The patient was treated with iv fluids, injection PPI, ondansetron, paracetamol and injection ceftriaxone 2 gm iv bd (Aminopropylsilanetriol (APST)) was started. Typhi Dot M came positive and other reports of fever profile were negative. A diagnosis of typhoid fever was made. RFT were normal with LFT showing mild transaminitis (SGOT>SGPT) with normal levels of albumin, globulin and ALP. CBC revealed mild normocytic normochromic anaemia with leukopenia Total Leukocyte Count (TLC)-3900/mm3) and normal platelet counts. The COVID-19 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) was negative. Ferritin and triglycerides were sent of which ferritin was normal, but triglycerides were elevated with levels of 485 mg/dL. High Density Lipoprotein (HDL) levels were low (30 mg/dL). Considering HLH, bone marrow was advised which the patient refused. USG revealed mild hepatosplenomegaly with acalculous cholecystitis but chest radiograph and echocardiography were normal. Blood cultures revealed Salmonella typhi. The thyroid profile tests were normal.

As triglycerides were elevated, statin and fenofibrates were added. Antibiotics were continued for seven days. She started improving with therapy, triglycerides decreased to 200 mg/dL after five days and transaminitis also subsided. The patient was discharged after eight days from day of admission. She was requested for follow-up visit after seven days.

Case 3

A 40-year-old female patient presented with fever for six days with chill and rigor with mild impairment of consciousness. There was no history of vomiting, loose motions, pain abdomen, nor were there any joint symptoms, skin rash or bladder bowel complaints. She had headache for the last five days without any localising signs. Last menstrual period was 20 days earlier than usual. There was no history of weakness of any side of the body, nor involuntary movements. Travel history, vaccination history were unremarkable and she was not on any medicines.

On examination, the patient was drowsy with disorientation and fever. Neck was supple and there were no signs of meningeal irritation. No false localising signs depicting bilateral sixth cranial nerve palsies were detected. Tone and reflexes were normal, but plantar responses were extensor bilaterally. Ophthalmoscopy was unremarkable and examination of other systems did not reveal any abnormality except mild hepatosplenomegaly.

A differential of fever with encephalopathy was made with possibilities of septic or metabolic encephalopathy. CBC showed neutrophilic leukocytosis (12,300/mm3) with 75% neutrophils. Haemoglobin and platelet counts were normal with mildly raised ESR. The Fasting Blood Sugar (FBS), RFT, LFT, International Normalised Ratio (INR) were normal. MP slide and dual antigen, NS1 antigen were negative, but Typhi DOT M was positive. The COVID-19 RT-PCR, urine analysis did not reveal any abnormality. Chest x ray, echocardiography were normal and USG revealed mild hepatosplenomegaly. MRI brain, CSF study, CPK, Creatine phosphokinase-MB (CPK-MB) were normal. Electroencephalography (EEG) revealed encephalopathy. A diagnosis of enteric encephalopathy was made.

The patient was admitted in the Intensive Care Unit (ICU) with Ryle’s tube and catheterisation was done. Intravenous fluids was started with injection PPI, injection ceftriaxone 2 gm iv bd (APST), injection ondansetron and paracetamol and injection doxycycline 100 mg iv bd (APST) and dexamethasone were also started.

She started to recover after 16 hours and intensity of fever decreased from 102° F to 100° F. The patient was conscious and oriented from third day after starting antibiotics after which catheter and Ryle’s tube were removed. Blood culture sensitivity was positive for Salmonella typhi. Steroids were tapered within seven days by reducing thrice daily dose to twice daily and then once daily. The patient was discharged on day 15 of admission. The patient came for follow-up after 10 days of discharge and was doing well.

Discussion

Myocarditis is an unusual complication of Typhoid fever with only few reported cases. A case study of typhoid cardiomyopathy by Majid A et al., reported a young male presented with incompletely treated typhoid fever with raised cardiac enzymes and features of dilated Cardiomyopathy on Echocardiography. The condition gradually improved with adequate treatment (9). Similarly, Shah S and Dubrey SW reported a case of young male presented with myocarditis and chest pain mimicking myocardial infarction was found to be associated with typhoid fever in a traveller returning to United Kingdom (UK). The fever and other symptoms completely subsided with treatment with third generation cephalosporin for two weeks (10).

The patients here were fruit sellers and students staying in slums. They had poor hand hygiene and sanitation habits. This could be the predisposing reason for increased infection. The first patient was a young male of reversible cardiomyopathy. He was febrile so all relevant investigations were done. The result was only positive for Typhoid fever (Typhi dot M). The common causes of cardiac dysfunctions (hypertension, diabetes, electrolyte disturbances) were also ruled out. Finally, a diagnosis typhoid cardiomyopathy was made.

The second case was a young female patient with fever, vomiting, and abdominal pain. Investigation was positive for Typhi dot M, blood culture was positive for Salmonella typhi. The laboratory reports revealed normocytic normochromic anaemia with leukopenia and normal platelet count but liver enzymes and triglyceride level were raised though ferritin levels were normal.

A suspicion of typhoid associated HLH was thought of but none of the other criteria (hyper ferritinemia, hypofibrinogenemia etc) were present. Moreover, the patient responded very well to treatment with antibiotics. Fever subsided, the triglyceride and liver enzyme levels gradually approached baseline levels with treatment with antibiotics alone.

There are various studies which established a correlation between enteric fever and abnormal lipid profile (raised triglyceride levels). Tissue dyslipidaemia was studied in Salmonella- infected rats (11). Tissue dyslipidaemia was studied in various studies in human and animal model like Salmonella- infected rats (11). Estimation of serum lipid levels typhoid patients was studied by Shafiq A et al., where there was elevated triglycerides and reduced HDL levels due to lipid peroxidation (12). Assessment of lipid profile and enteric fever was also studied by Ifoema CI et al., (13).

Studies also showed various haematological abnormalities associated with enteric fever infections and it explains the atypical findings present in the case. In the study by Uplaonkar SV et al., 20 (34.48%) patients had anaemia, 13 (22.41%) had leukocytosis, 23 (39.65%) had neutrophilia, and 10 (17.24%) had thrombocytopenia (14). Typhoid-induced HLH is extremely rare. All patients had pancytopenia in the study by Sánchez-Moreno P and half of the patients were children (15). However, in the present case series where the first patient presented with anaemia without significant haematological findings and all were adult patients.

The third case is a middle aged female patient who presented with fever and impaired consciousness. There was headache but no neck rigidity and all neurological examinations were normal except bilateral upgoing plantar reflex. All other causes of febrile encephalopathy were ruled out. Based on positive Typhi dot M test, a diagnosis of Typhoid encephalopathy was made. The patient responded very well to treatment with susceptible antibiotics and steroids.

Typhoid fever is associated with various neurological findings like spasticity, clonus, seizures, ataxia, ophthalmoplegia, cerebellar dysfunctions, neuro-psychiatric manifestations Typhoid encephalopathy poses a diagnostic dilemma among various other aetiologies that causes acute febrile neurological illness (16). Though reversible, typhoid encephalopathy is a well-known entity, lack of clinical suspicion makes the diagnosis difficult. Typhoid presents with various unusual manifestations.

Cardiovascular System (CVS) manifestations were seen in approximately 4.6% of patients in a study by Singh S and Singhi S (17). Myocarditis was the most common, but pericarditis and endocarditis may occur rarely (exact incidence is unknown). Venous thrombosis (0.83%) and arterial thrombosis (only case reports available) were also reported (17). Long-term follow-up is needed in these patients for monitoring of cardiovascular function and to detect any adverse outcomes in future (17),(18). It is also important to detect any genetic predisposition in the development of enteric cardiomyopathy.

The second case with non-HLH dyslipidaemia is a rare presentation with probable impact on lipid absorption in enteric fever. Though the hypertriglyceridaemia was reversible in the patient, but long-term follow-up is needed to determine its impact on cardiovascular morbidity and mortality. Moreover, more studies should be done to determine the incidence and impact of enteric dyslipidaemia. According to Jiang XC et al., Salmonella altered the metabolism of lipids in rats in different organs. There may be down regulation or up regulation of various lipids. Hepatic Hydroxymethylglutaryl-coenzyme A(HMG-coA) reductase activity was upregulated due to Salmonella and its treatment. HDL cholesterol levels may be decreased due to impairment of apolipoprotein induced cholesterol removal as was evident in this case (19).

Enteric encephalopathy responds to steroids and antibiotics. Antibiotics with high dose of dexamethasone reduces morbidity and mortality in patients of typhoid fever with encephalopathy (20). If the steroid is not initiated promptly, there is increase in mortality and relapse (21),(22). Enteric encephalopathy may occur within 7-9 days as mentioned in an Indonesian study (23). Steroids act by reducing the generation of free oxygen species and prostaglandins by macrophages induced by typhoid endotoxin (20).

Conclusion

Enteric fever presents with various atypical manifestations beyond fever and pain abdomen. It may affect multiple systems of the body and poses a diagnostic challenge. The cases presented here had atypical manifestations in the form of reversible cardiomyopathy, non HLH dyslipidaemia and reversible encephalopathy responding to antibiotics and steroids. The importance of the case series lies in the fact that high index of clinical suspicion is needed for early diagnosis and initiation of appropriate antibiotics to treat these reversible complications and also further studies are required for long-term impact of these reversible complications.

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DOI and Others

DOI: 10.7860/JCDR/2022/59841.17185

Date of Submission: Aug 26, 2022
Date of Peer Review: Oct 14, 2022
Date of Acceptance: Nov 06, 2022
Date of Publishing: Dec 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Sep 06, 2022
• Manual Googling: Oct 28, 2022
• iThenticate Software: Nov 04, 2022 (5%)

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