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

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
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

Original article / research
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : SC10 - SC15 Full Version

Bedside Prognostic Indicators of Fatal Outcome among Children with Cerebral Malaria at a Tertiary Nigerian Hospital


Published: January 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/56809.17291
Ayobami Oyetunji Alabi, Michael Olaniyan Onigbinde, Ayodele Ojuawo, Victor Idowu Joel-Medewase, Grace Olukemi Alabi, Olanike Taye Oladibu, Bukola Adetutu Sayomi

1. Lecturer 1/ Consultant Paediatrician, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology (LAUTECH) / LAUTECH Teaching Hospital, Ogbomoso, Oyo State, Nigeria. 2. Lecturer 1/ Consultant Paediatrician, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology (LAUTECH) / LAUTECH Teaching Hospital, Ogbomoso, Oyo State, Nigeria. 3. Professor of Paediatric/ Consultant Paediatrician, Department of Paediatrics and Child Health, University of Ilorin / University of Ilorin Teaching Hospital, Ilorin, Kwara, Nigeria. 4. Associate Professor/Consultant Paediatrician, Department of Paediatrics and Child Health, Ladoke Akintola University of Technology (LAUTECH) / LAUTECH Teaching Hospital, Ogbomoso, Oyo State, Nigeria. 5. Chief Medical Officer, Department of Paediatrics and Child Health ,Kwara State Specialist Hospital, Ilorin, Kwara, Nigeria. 6. Lecturer 1/ Consultant Paediatrician, Department of Paediatrics and Child Health, Ladok

Correspondence Address :
Dr. Michael Olaniyan Onigbinde,
Ladoke Akintola University of Technology, P.M.B 4000, Nigeria,
Ogbomoso, Oyo, Nigeria.
E-mail: moonigbinde@lautech.edu.ng

Abstract

Introduction: Cerebral Malaria (CM) is a severe manifestation of malaria and commonly causes poor outcomes. It affects upto one million people per year worldwide predominantly sub-Saharan African children. It is clinically expedient that children with CM are identified promptly and easily to halt fatal outcomes.

Aim: To evaluate bedside prognostic indicators of poor outcome among children with CM.

Materials and Methods: A prospective, observational study was conducted at LAUTECH Teaching Hospital Ogbomoso, Oyo State, Nigeria among children diagnosed with CM from February 2018 to September 2018. Fifty children with age range of 6 months to 12 years were included in the study. Outcome indicators were full recovery, alive with neurological sequelae and death. Nine of the identified clinical factors demonstrable on bedside were assigned score of 1 each and each score summated to form Bedside Prognostic Index (BPI). The median BPI Score ≥4 indicated fatal outcome. Receiver Operating Characteristic (ROC) curve validated the predictive ability of the BPI score on clinical outcomes. Chi-square test and student t-test were used for statistical analysis.

Results: Out of total 50 children, 30 (60%) recovered fully, 11 (22%) participants had neurological deficit(s) and 9 (18%) participants died. The median BPI score among completely recovered, survived with neurological deficit(s) and died was 8, 6 and 4, respectively. BPI score ≥4 was an independent predictor of fatal outcome {Odd’s Ratio (OR)=7.875, p-value=0.013, Confidence Interval (CI)=1.547-40.091} with sensitivity and specificity of 80% and 76.67% respectively. The ROC of the predictive ability of BPI on clinical outcomes was 80.2%.

Conclusion: Poor outcome was significantly associated with BPI of ≥4 in children with CM. The use of this scoring index should be encouraged to promptly manage children with CM at risk of poor outcome.

Keywords

Clinical predictive scores, Neurological sequelae determinants, Paediatric mortality trend

World Health Organisation (WHO) reported approximately 3.3 billion of the world population are at risk of the malaria infection. In year 2020, the estimated number of cases worldwide was 241 million and the WHO African region had about 228 million cases in 2020, accounted for about 95% of cases (1). Severe malaria is one of the most serious infectious disease emergencies in children mostly related to plasmodium falciparum (2),(3). It may be lethal and can lead to cerebral malaria which can rapidly progress to severe illness and lead to fatal outcome especially in children (2),(3),(4). Cerebral malaria affects upto 1 million people per year worldwide, the vast majority being under five-year-old children living in Sub-Saharan African (SSA) and these groups accounted for highest morbidity and mortality rates (5),(6),(7). According to reports, cerebral malaria ranked next to severe malarial anaemia as a common complication of plasmodium falciparum malaria in many hospitalised children (8),(9). According to previous studies, despite optimal treatment 15-22% of children accounts for deaths (8),(9),(10). Prevalence of CM may depend on the geographic area of the study, season of the year, type of health institution and the study design (10),(11),(12).

Studies across regions in Africa, one to two decades ago had reported major differences in the clinical manifestations and outcomes of CM in children at different ages and under different levels of malaria endemicity and patterns of transmission (10),(11),(12),(13). However more emphasis needs to be placed on identifying bedside clinical and laboratory factors that could promptly and reliably detect cerebral malaria children with poor clinical outcome. Identification of bedside prognostic factors at early stage may help to reduce mortality and morbidity associated with CM. Some studies have reported different prognostic factors, but this study formulated a bedside prognostic index score that would involve combination of different factors together so as to strongly predict poor outcome. The bedside prognostic index for CM when determined, will give a better estimate of prognosis than is possible using any single clinical or laboratory feature. These bedside indicators will be highly useful in many low-resource environments where access to optimal healthcare remains a huge task and with challenge of limitations or poor access to high technology facilities. The result of this study is expected to aid paediatricians and all other healthcare providers to quickly recognize children with CM at risk of death or neurological sequelae so as to promptly initiate the appropriate management. Therefore, the present study aimed to formulate a bedside prognostic index score to predict poor outcome among children with cerebral malaria especially in a low-resource community.

Material and Methods

This was a prospective, observational study conducted in the Children’s Emergency Unit (CEU) at Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital Ogbomoso, Oyo State Nigeria, from February 2018 to September 2018. Informed consent was sought and only those that gave their written consent were included in the study. Ethical clearance was obtained from Ethics and Review Committee (Protocol number: LTH/OGB/EC/2017/145).

Inclusion criteria: Children between the age of 6 months to 12 years with unarousable coma lasting more than 30 minutes in the presence of demonstrable peripheral asexual plasmodium falciparum parasitaemia and who develop deterioration in their level of consciousness after admission were included in the study. Consecutive children with cerebral malaria who met the WHO criteria of a patient, who could not localise a painful stimulus, who had peripheral asexual plasmodium falciparum parasitemia and had no other identified causes of an encephalopathy (such as meningitis, hypoglycemia, encephalitis etc.) were included in the study (14).

Exclusion criteria: Children with positive Cerebrospinal Fluid (CSF) biochemical result (elevated CSF protein, low CSF Glucose) and/or CSF microbiological result (positive gram stain/elevated white blood cells and positive CSF culture) were excluded from the study. Those with a previous neurological deficit, who have demonstrable evidence of intracranial infections and whose caregiver declined granting consent for their participation in the study were excluded from the study.

Sample size calculation: The sample size for the study was calculated from the following formulae (15).

NF=N/[1+{(N-1)/Pop}]
NF=Desired minimum sample size for finite population
N=Desired sample size when the population is more than 10,000

Pop=Estimate of the population size (The annual population of children with cerebral malaria in LAUTECH Teaching Hospital Ogbomoso was 70)

However, N= Z2pq/d2

Z=Standard normal deviate usually set at 1.96, which corresponds to the 95% confidence level
p=Proportion in the target population estimated to have a particular characteristic, prevalence of 5.5% was used (16).
d=Degree of accuracy desired, set at the 0.05 level with standard error of 5%
q=1.0-p
Therefore, N= (1.96 x 1.96) x 0.055 (1-0.055)=79.8=80/(0.05 x 0.05)

Applying the formula for the finite population, NF=N/[1+{(N-1)/Pop}]
NF=N/[1+{(N-1)/Pop}]; 80/[1+{(80-1)/70}]; NF=80/[1+{(79)/70}]; 80/{1+(1.2857)}=80/(2.12857)=37.58

With a 10% attrition rate, the minimum sample was 41. The sample size was rounded upto 50 children.

Study procedure: Information was obtained on proforma which include details of CM such as bio data, the nature and duration of symptoms, pretreatment history followed by detailed clinical examination including general and neurological examinations (17).

Patients were classified using the presence or absence of selected clinical and laboratory parameters. Such clinical features included fever, loss of consciousness, convulsion, difficulty breathing, paleness of body, jaundice, dark brown urine, reduction in urine output. General physical signs such as pallor, icteric, respiratory distress and degree of dehydration. Others include neurological assessment such as depth of coma, corneal and pupillary reflexes, papilloedema/retinal haemorrhage, posture, tone and deep tendon reflexes. Tone is defined as muscle resistance to passive movement at rest (17).

The selected laboratory factors included Packed Cell Volume (PCV) level, white blood cell count, differential platelet count and parasite density. These were cross-tabulated against patient outcome to determine possibilities of association. Hyperparasitaemia defined as parasite density >250,000/μL (18). and leucocyotosis as level of white blood cell count greater than 12,000 cells/cumm3 as defined by Oluwayemi O et al., (16).

Patients were also grouped based on the possible outcome as (19):

(i) Patients who completely recovered
(ii) Patients survived with neurological deficit(s)
(iii) Patients who died during the treatment.

Level of consciousness was assessed using Blantyre’s Coma Scale (BCS) (18). Only children with an abnormal score (4 or less) were included in the study. Deep coma was defined as Blantyre coma score of 0-2.

At presentation blood was taken from each patient for full blood count, thin and thick film for malaria parasite to detect malaria parasite. The blood films for malaria parasite were examined for the type of species. Parasite density was then estimated as follows (20).

Parasites/μL blood= Number of parasites counted X white blood cells count/μL/Number of white blood cells counted on the smear

Blood film for malaria parasites was monitored daily while other investigations were carried out as the patients’ clinical condition dictated. CSF was also obtained for chemistry and microbiology laboratory examination to exclude intracranial infections.

Based on WHO treatment guidelines of malaria, all patients were treated with intravenous artesunate (21). Associated complications such as seizures, anaemia and raised intracranial pressure were treated appropriately (4),(21). The required supportive therapy was adequately provided such as airway management, oxygen administration, fluid therapy, input and output monitoring and adequate nutrition. Level of consciousness and vital signs were strictly monitored as condition of each patient dictated and patients were discharged from the hospital when they had improved clinically and were able to continue their treatment orally at home. The outcome of each patient was assessed as either alive without neurological sequelae, alive but with neurological sequelae or died.

Bedside prognostic index (BPI): BPI was defined based on the prognostic factors that can be easily determined by the bedside of children with CM (13). There are nine clinical/neurological factors that were found to be easily assessed and demonstrable clinically at the bedside. Each of these clinical findings were assigned score of 1 each. This forms the basis for formulation of BPI score as shown in (Table/Fig 1). BPI was determined and the box plot for the BPI in relation to outcome was then done. The score range of 4-9 was assessed as bad/poor and scores <4 as good.

Statistical Analysis

Statistical analysis was done using IBM Statistical Package for the Social Sciences (SPSS) software version 21.0 (SPSS Inc, Chicago, USA). Chi-square test was used for test of association between variables. Student’s t-test was used to compare means of normally distributed continuous variables. Logistic regression analysis was employed to determine the prognostic significance of various clinical parameters among those who had association at bivariate level. The sensitivity, specificity and the predictive testing of model that was used to predict the outcome were also carried out. The level of significance p-value was set at <0.05.

Results

A total of 25 boys and 25 girls with cerebral malaria were recruited constituting 50 (5.6%) of 892 children admitted into CEU during the study period. Their ages ranged between six months and 12 years with 60% aged less than five years. The mean age was 4.86±3.16 years and mean weight 18.30±11.57 kgs. The mean Plasmodium falciparum parasites density per μL of blood, was 324,006 with 70% of the children recruited having parasite density >250,000/μL (hyperparasitemia).

All the 50 (100%) patients presented with fever and altered sensorium. Convulsion was observed in 39 (78%) children, 6 (12%) of the children presented with history of paleness of the body and 31 (62%) of them were actually pale, 14 (28%) complained of jaundice but 9 (18%) were found to be icteric upon physical examination. Difficulty in breathing were reported only among 12 (24%) and 24 (48%) were found to be in respiratory distress. Twenty (51.3%) of 39 children with convulsion recovered fully as against 19 (48.7%) of them with poor outcome (neurological sequelae and death). Of the 12 children with difficulty in breathing at presentation, only 3 (25%) had a good outcome while 9 (75%) had poor outcome of either died or had a sequelae. In all participants, convulsion (χ=4.08; p=0.043) and difficulty in breathing (χ=6.25; p-value=0.012) were the presenting complaints significantly associated with poor outcome (Table/Fig 2).

Neurological examination findings at presentation in relation to the clinical outcome showed that deep coma (Blantyre coma score 0-2), prolonged coma recovery time (>26 hours), absent corneal reflex, absent pupillary reflex, papilloedema/retinal haemorrhage, abnormal posturing, hyporeflexia and hyperreflexia were significantly associated with poor outcome (p-value<0.05). Full details on the association are shown in (Table/Fig 3). The mean Coma Recovery Time (CRT) was significantly lower in children who recovered fully (26.77±13.81 hours) compared to children who recovered with neurological sequelae (41.91±28.25 hours) and this was statistically significant, (t-value=2.308, p-value=0.026) (Table/Fig 3).

(Table/Fig 4) shows that the mean leucocyte count is significantly associated with mortality and neurological sequelae, (t-value=- significant2.769; p-value=0.008). Subjects who died or had neurological sequelae also had a higher mean parasite density in relation to those who recovered without sequelae and this was statistically significant with the clinical outcome (t-value=-2.614, p-value=0.001). In fully recovered children parasite count was 12.42±0.606=246,175 per μL, in alive children with neurological sequelae parasite count was 12.78±0.582=353,557 per μL and in dead children parasite count was 12.93±0.417=410,692 per μL. Mean packed cell volume (PCV) was lower among children who died (20±9.41%) as compared to those who recovered fully (24.37±8.34%) but no statistical significant association between PCV level and clinical outcome was recorded.

At bivariable level, association between clinical findings and clinical outcome using Chi-square was determined. Those clinical parameters that showed significant association at this level and which can be assessed at bedside were used for formulation of BPI score. Of total, 16 (32%) children had good score of less than 4 while 34 (68%) children had poor score. The median bedside prognostic index score was higher in children who died (median=8), followed by a median score of 6 among those who survived with neurological deficit and score of 4 among children who survived without neurological deficit (Table/Fig 5).

The sensitivity, specificity and predictive value of the bedside prognostic index score was also determined for each of the score. The Receiver Operating Characteristic (ROC) curve validated the predictive ability of bedside prognostic index score on clinical outcomes.

Sensitivity, specificity and predictive value of bed side prognostic index: The best sensitivity and specificity were obtained for a cut-off greater than or equal to 4 with a sensitivity of 80% and specificity of 76.67% (Table/Fig 6). The ROC of the predictive ability of bed side prognostic index on clinical outcomes is as shown in (Table/Fig 7). The Area Under the Curve (AUC) was 80.2% which indicates that the bed side prognostic index was able to distinguish between children of different outcome.

Clinical outcome was significantly associated with bedside prognostic index. Children with prognostic score less than 4 were about eight times more likely to survive compared to children with a score of 4 or more. Thus bedside prognostic index of 4 or more, was found to be a significant predictor of poor outcome. (Table/Fig 8).

Discussion

This study evaluated bedside prognostic index of poor outcome of children with cerebral malaria. Fever, altered sensorium and convulsions were found to be the most prevailing symptoms and these findings were similar to clinical features documented in other studies but the prevalence varied across different studies (19),(16),(22). Fever was present in all the children recruited for this study, this is similar to reports by Oluwayemi O et al., and Lesi FE et al., (16),(22). In similar to presence of fever, loss of consciousness/altered sensorium was present in 100% of children with CM in this study, this is in consonance with reports by many authors (13),(16),(23),(24). Out of total, 79% patients in this study had convulsion at presentation. It was similar to 82% and 79.6% found in studies in Malawi and Nigeria, respectively but lower than 89.3% and 95% found in studies in Oluwayemi O et al., and Oninla S et al., Nigeria, respectively (13),(12),(16),(19). (Table/Fig 9) is showing the comparison of prognostic features of CM in various studies with the present study (16),(22),(24),(25).

The findings of short duration of fever and unconsciousness among children with CM prior presentation suggest that an uncomplicated malaria can progress rapidly to cerebral malaria, this supported the findings reported by Jiya MN et al., and Molyneux ME et al., (24),(13). Thus, a strong need arises for clinicians to be very observant in monitoring the patients and prompt in the management of uncomplicated malaria to prevent rapid progression to CM. Despite the prevailing incidence of children with fever in CM, children with CM had also been documented to present with subnormal to normal temperature but this was not found in this study as all children studied had varying degree of fever (16),(24).

Respiratory distress was a less prevalent clinical findings in this study with regard to fever, loss of consciousness and convulsion. It was recorded in about half of the subjects (48%) in this study. This doubles reports of 22.7% and 20% from studies by Oluwayemi O et al., and Oninla S et al., respectively (16),(12). This difference may be partly due to the heterogeneous populations of different studies and different definition used for respiratory distress across children with cerebral malaria. Other important clinical signs in this study were pallor, jaundice and dark brown urine as observed in 62%, 28% and 12% respectively and they were found not to be associated with poor outcome. The report of pallor and jaundice in this were in contrast with study by Lesi FE et al., who reported 70.1% and 50.4% respectively for pallor and jaundice (22). However, the finding of 12% for dark brown urine is very similar to 10% reported in a retrospective study by Oninla S et al., (12). The notable variance in prevalence of jaundice, pallor and passage of dark brown urine in this study and others may be a pointer to other undetected underlying causes of haemolysis (such G6PD deficiency and other enzymopathy, haemoglobinopathy e.t.c) which may be a co-morbid (26).

Cerebral malaria has been reported to present with non specific features of diffuse, symmetrical, neurological and some specific neurological features that were associated with poor prognosis (25). Neurological findings of poor pupillary reflex, absent corneal reflex, papilloedema and retinal haemorrhage in this study were generally similar to, but in varying rate of occurrences as some previous studies (12),(16),(24). Twenty-two percent patients had absent cornea reflexes in this study which was higher than 14% in study by OlumesePE et al., (25) and doubles findings of 10% documented by Oluwayemi O et al., (16). Papilloedema/retinal haemorrhage has been reported to be predictors of poor outcome across studies (13),(16),(27),(28). It was found in 28% of children with CM in the current study and it form part of bedside prognostic index score. Forty percent(40%) of children in this study were deeply comatose (Blantyre’s score 0-2), this is higher than 12% reported by Genton B et al., (23), but lower than 68.2% documented by Oluwayemi O et al., (16). Furthermore, deep coma (Blantyre’s score 0-2) was also found to be poor predictors of poor outcome of CM in this study, similar to previous reports (13),(16),(22),(23),(29). Seventy percent of children with CM in this study had abnormal deep tendon reflex and 84% presented with abnormal tone, this is comparable to report of abnormal tone of 70% and abnormal deep tendon reflexes of 74% from other study (25). The variation in the pattern of neurological findings and the prognostic ability may generally be explained by different age range of the patient across studies, severity of the symptoms, associated co-morbidities as well as management modalities (12),(13),(14),(15),(22).

The mean PCV in this study was found to be similar among those who recovered fully and survivors with sequelae (24%), but marginally lower (20%) among those that died. The mean PCV is within the range of 23.9% reported by Oninla et al., however, the report from Oninla et al., did not compare among different outcome parameter of CM (12). The mean PCV level showed no association with poor outcome as similar to other studies (13),(16). However leucocytosis was found to be an indicator of poor outcome in this study. This was also reported by researchers across Africa (13),(16),(23). In this study, the children had a high mean parasite counts as demonstrated amongst 70% of them. These far outweighed what was reported from many studies in Nigeria (16),(19),(24). The explanation for this was not clearly understood. The malaria parasites count in the blood films could vary based on timing of the sample collection in respect to the peak of fever, which may positively affect the yield [12,30]. There could also be deep tissue sequestrations leaving the peripheral blood of few or no malaria parasite thus affecting the parasite count (12).

In general, demonstrable bedside signs such as convulsion, difficulty in breathing, deep and prolonged coma, absent corneal and pupillary reflexes, papilloedema/retina haemorrhage, abnormal deep tendon reflex and abnormal posturing were found in this study to be predictors of poor outcome. These findings are consistent with previous studies in Nigeria (16),(19),(24) and across Africa (10),(13),(23).

The bedside prognostic index score formulated in this study was more accurately predictive of outcome than any single clinical feature among children with CM. The children with CM who had BPI score of 4 or more have about eight times risk of dying or developing neurological sequelae as those with BPI score of less than 4 and this is similar to report by Molyneux ME et al., (13). The reported prognostic index score by Molyneux ME et al., have different components as in this study (13). No other study to the best of authors’ knowledge had reported prospective study on bedside prognostic index score for cerebral malaria in children as in this study. Furthermore, in this study, the bedside prognostic index score has a sensitivity of 80% and specificity of 76.67%, this sensitivity is higher than 66% recorded in a previous study but specificity was not reported in that study (13). Furthermore bedside prognostic index of score ≥4 was found to be an independent predictor of poor outcome of death and development of neurological sequelae. The presence of these independent predictors of poor outcome in children with CM calls for a strict monitoring among them to prevent poor outcome. Identifying easily accessible prognostic factors that may predict bad outcome will go a long way to stem down the mortality and sequelae from cerebral malaria in developing countries like Nigeria and other sub-Saharan Africans. The presence of any or all of the clinical parameters findings that form the bedside prognostic index score may assist clinicians in quick assessment and prompt management of CM in children to prevent poor outcome. A combined prognostic index of this kind could provide a measure of the severity of the presenting illness similar to report from other study (13). Furthermore, bedside assessment score will be relevant in regions where malaria is endemic; and resources, in terms of qualified healthcare providers, appropriate medication, prompt testing, and monitoring equipment, are often not sufficient to meet all the needs. Identification of bedside risk factors also help to set up priorities right in such treatment centres.

Limitation(s)

Some of the limitations of this study included the inability to exhaustively study all factors that may serve as predictors in the outcome of the disease. The influence of all possible concomitant diseases could not be fully investigated and this may impact negatively on the outcome.

Conclusion

The bedside prognostic index scoring is a good predictor of outcome in the children with BPI score ≥4, as an independent predictor of poor outcome (death and development of neurological symptoms). Children with CM with BPI score less than 4 had 8 times chance of survival than those with poor outcome. The aggregation of signs summed to form BPI score will likely be useful for prediction of outcome in children with CM than any single clinical or laboratory factors. This is to promptly predict outcome of CM with the aim of initiating early appropriate treatment with potential to improving outcomes in those with potentially poor outcome. Utilization of this bedside scoring index should be encouraged for children with CM among health workers especially in low resource countries.

Acknowledgement

The authors are greatly indebted to Professor O.A Oyedeji for taking time to read and correct this manuscript before final submission.

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DOI and Others

DOI: 10.7860/JCDR/2023/56809.17291

Date of Submission: Apr 10, 2022
Date of Peer Review: May 14, 2022
Date of Acceptance: Sep 05, 2022
Date of Publishing: Jan 01, 2023

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

PLAGIARISM CHECKING METHODS:
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