RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
SYNOPSIS FOR REGISTRATION OF
SUBJECT FOR DISSERTATION
TITLE OF THE TOPIC“JAUNDICE AS A CLINICAL MARKER IN SEVERE FALCIPARUM MALARIA”
By
DR HABEEB UR RAHMAN
PG GENERAL MEDICINE,
AL-AMEEN MEDICAL COLLEGE,
BIJAPUR
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
01 / Name of the candidate and Address (in block letters) / HABEEB UR RAHMANPG GENERAL MEDICINE
DEPT. OF MEDICINE
AL-AMEEN MEDICAL COLLEGE, BIJAPUR.
02 / Name of the Institution / AL-AMEEN MEDICAL COLLEGE, BIJAPUR
03 / Course of study and Subject / M.D GENERAL MEDICINE
04 / Date of admission to course / MAY 2011
05 / Title of the topic / “JAUNDICE AS A CLINICAL MARKER IN SEVERE FALCIPARUM MALARIA”
06 / Brief resume of the intended work
6.1 Need for the study
6.2 Review of literature
6.3 Objectives of the Study / Vide Annexure – I
Vide Annexure – II
Vide Annexure – III
07 / Material and Methods
7.1 Source of Data
7.2 Method of collection of data
(including sampling procedure, if
any )
7.3 Does the Study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
7.4 Has ethical Clearance been obtained from your institution in case of 7.3
7.5 Sample informed consent form / Vide Annexure – IV
Vide Annexure – V
Vide Annexure – VI
Yes
(Certificate has been enclosed herewith )
08 / List of References / Vide Annexure – VII
09 / Signature of the Candidate
10 / Remarks of the Guide / This study will help in detecting early complications and prognosis of patient with falciparum malaria presenting with jaundice.
11 / Name and Designation of ( in block letters )
11.1 Guide / DR ASHOK P. YENKANCHI
MD.GENERAL MEDICINE
PROFESSOR
DEPARTMENT OF MEDICINE
AL-AMEEN MEDICAL COLLEGE, BIJAPUR
11.2 Signature
11.3 Co-Guide (if any)
11.4 Signature
11.5 Head of the Department / Dr. BILAL BIN ABDULLAH
MD GENERAL MEDICINE
PROFESSOR AND H.O.D.
DEPARTMENT OF MEDICINE
AL-AMEEN MEDICAL COLLEGE, BIJAPUR
11.6 Signature
12 / Name of the Dean
12.1 Remarks of the Chairman and dean
12.2 Signature / DR. B. S. PATIL
We will provide the necessary facilities for this study.
ANNEXURE – I
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY
The global malaria situation is intensifying. Over two billion people now reside in areas where plasmodium falciparum (PF) is transmitted and each year 300-500 million new infections with this parasite result in 1.5-2.7 million deaths.1
Each year 25-30 million people from non-tropical countries visit areas in which malaria is endemic, of whom between 10,000 and 30,000-contract malaria.2
In recent years, the clinical pattern of severe malaria has changed. Over a decade ago cerebral malaria was the predominant feature of severe malaria.3Cases of severe falciparum hepatitis and malarial acute renal failure were few and far between. Whereas today hepatic and renal involvement is seen more frequently and their mode of presentation has undergone a change, posing a diagnostic dilemma with other ailments particularly acute viral hepatitis or fulminant hepatic failure, especially in endemic areas.4
Presence of jaundice in Falciparum Malaria (FM) indicates a more severe illness with higher incidence of complications and poor prognosis.5 The disease is more commonly seen in adults and in those areas of the tropics where transmission of malaria is low or unstable, especially in Asian countries, and where symptomatic disease occurs at all ages.6Jaundice in severe malaria is multi-factorial and can result from hemolysis of parasitized and non-parasitized red blood cells, hepatic dysfunction and possibly an element of microangiopathic hemolysis associated with disseminated intravascular coagulation (DIC) .It may be present alone or with other complications of falciparum malaria and may vary from mild to very severe.7
Awareness of this entity is important not only in endemic areas, but also for non-endemic areas, as easy global travel allows severe imported FM to reach any part of the world.
Over the years there has been a rise in the incidence and severity of jaundice in patients diagnosed as FM. The present study is to be conducted with the objective to describe clinical characteristics, biochemical parameters and prognostic factors in patients of FM with jaundice.
ANNEXURE – II
6.2 REVIEW OF LITERATURE
Malaria is the most important parasitic infection of human beings which still produces considerable morbidity and mortality worldwide especially in tropical countries. There are four species of genus plasmodium that infects humans. They are plasmodium vivax, plasmodium falciparum, and plasmodium ovale and plasmodium malariae. Though most of the complications and deaths were caused by plasmodium falciparum, plasmodium vivax is also reported to produce complications in the recent past.
There are about 400 species of anopheline mosquitoes throughout the world, approximately 80 can transmit malaria, 66 are considered natural vectors, and about 45 are important vectors.8 In India 9 species out of 45 anopheline species have been incriminated as malaria vectors.9
The principal determinants of epidemiology of malaria are the number (density), the human – biting habits, and the longevity of the anopheles mosquito vectors. More specifically, the transmission of malaria is directly proportional to the density of the vector, the square of the number of human bites per day per mosquito, and tenth power of the probability of the mosquito’s surviving for 1 day. Mosquito longevity is particularly important; it must survive for > 7 days.10
PATHOGENESIS OF JAUNDICE
· Hemolysis & increased Bilirubin production.
· Hepatocyte injury due to ischemic damage caused by microcirculatory block.
· Cholestasis is major factor leading on to jaundice in malaria.Cytokines inhibits the active excretion of conjugated bilirubin into the biliary canaliculi. So the bilirubinemia is predominantly direct with very mild elevation of transaminases.
DEFINITION OF SEVERE MALARIA BY WHO:
The criteria of Multi organ dysfunction syndrome (MODS) in malaria are given below
1. Renal failure: Serum Creatinine> = 3mgs/dl
Urine out put <400ml/24hrs or <12ml/hr
2. Severe anemia: Hemoglobin <5gms%
Hematocrit <15%
3. Cerebral malaria: Unarousable coma with peripheral parasitemia
4. Pulmonary edema
5. Hypoglycemia: Blood sugar <40mg/dl
6. Shock: Systolic BP <70mmHg (in adults) <50mmHg (in children 1-5 years)
7. Acidemia: PH <7.35, HCO3 <15 mq/L
8. Spontaneous bleeding: gums, nose and GIT due to DIC
9. Macroscopic hemoglobinuria
10. Seizures: More than two episodes
11. Hyperparasitemia: More than 20%
12. Jaundice: serum Bilirubin > 3mgs/dl-marker of severe malaria only when
Combined with other vital organ dysfunction (cerebral malaria and renal failure)
DIAGNOSIS OF MALARIA
Light microscopy – Thin and Thick Smear
· Cost effective, fairly sensitive & highly specific.
· Thin smear is used for quick diagnosis and thick smear used for species identification.
· False negative - Very low parasitemia, sequestration of parasitized RBC, technical error.
· False positive - in highly endemic areas.
QBC for malaria (Quantitative Buffy Coat)
Nuclear material of parasite (DNA& RNA) stained with fluorescent dyes and visualized under UV light microscopy. When blood in specialized capillary tube containing acridine orange stain and a float is centrifuged, the infected RBC’s which have a higher buoyant density than uninfected cells, become concentrated around the float.Sensitivity is equal or slightly more than thick smear.
Paracheck- F ( Dipstick method)
· Detects falciparum specific Histidine Rich Protein released from RBCs using monoclonal antibody.
· Simple and rapid.
Optimal – Parasite specific LDH detection
· Sensitivity – 92 to 98%
· Specificity - 92 %
Polymerase chain reaction
· Highly sensitive
· Costly and not available easily
Recent study from Rajasthan, by Kochar , had revealed a major shift in clinical presentation and complications of falciparum malaria. In 1994 cerebral malaria was the commonest complication encountered and also the commonest cause of death in PF malaria where as in 2001 jaundice, anemia, renal failure and MODS were the commonest presentation of severe malaria and cause of death.
This statistically significant shift in presentation of severe malaria from a solitary complication of cerebral malaria in 1994 to MODS in 2001 should alert the physician regarding diagnosis of severe malaria when a patient presents with fever with Jaundice and Renal failure.
ANNEXURE – III
6.3 OBJECTIVES OF THE STUDY
1. To study the clinical profile of severe Falciparum malaria with jaundice.
2. To study the biochemical parameters and prognostic factors in patients of severe Falciparum Malaria with jaundice.
ANNEXURE – IV
MATERIAL AND METHODS
7.1 SOURCE OF DATA
Population:
Patients attending the out-patient clinic & who will be admitted in “Al Ameen Medical College Hospital, Bijapur” presenting with clinical jaundice and confirmed to have Falciparum Malaria by demonstration of asexual forms of PF in the peripheral smear will be selected for the study (50 patients).It included adult patients of both sexes and different age groups after obtaining the formal consent from the patients or relatives.
Period of the study: DEC 2011-MAY 2013.
DESIGN OF STUDY: Prospective Study.
ANNEXURE – V
7.2 METHOD OF COLLECTION OF DATA
INCLUSION CRITERIA:
Patients presenting with clinical jaundice and confirmed to have FM by demonstration of asexual forms of PF in the peripheral smear.
Jaundice is defined as an icteric sclera and or total bilirubin levels >3m g/dl (50µ mol/ L).
World Health Organization (WHO) criteria were used to describe the systemic complications
EXCLUSION CRITERIA:
· Patients below the age of 15 years.
· Pregnant and Lactating women.
· Patients with negative peripheral smear for PF
· Patients having mixed plasmodium infection.
· Patients who had evidence of any other disease or condition leading to jaundice or affecting the outcome of FM with jaundice.
· Patients with leptospirosis, enteric fever and hepatitis were excluded by doing appropriate investigations.
STATISTICAL ANALYSIS
The information collected regarding all the selected cases will be recorded in a Master Chart.
Data analysis will be done with the help of computer using Epidemiological Information Package (EPI 2002).
Using this software,
1. Frequencies
2. Percentage
3. Mean
4. Standard deviation
5. x2 chi square
6.'P' values will be calculated.
ANNEXURE – VI
7.3 INVESTIGATIONS REQUIRED FOR THE STUDY
1. Blood Peripheral smear (Giemsa stain) / QBC (Quantitative Buffy Coat) for malarial parasites.
2. Liver function tests.
3. Hemogram – Hb, TLC, DLC, platelet count.
4. Renal function tests.
7.4 ETHICAL COMMITTEE
The following study entitled “JAUNDICE AS A CLINICAL MARKER IN SEVERE FALCIPARUM MALARIA” By Dr HABEEB UR RAHMAN, PG General Medicine, and 2011batch has been cleared from the ethical committee of this institution for the purpose of dissertation work.
Date:
Place:
Chairman,
Ethical Committee,
Al Ameen Medical College,
Bijapur
7.5 SAMPLE INFORMED CONSENT FORM
RESEARCH INFORMED CONSENT FORM
TITLE OF THE STUDY: - “JAUNDICE AS A CLINICAL MARKER IN SEVERE FALCIPARUM MALARIA.”
PRINCIPAL INVESTIGATOR: DR HABEEB UR RAHMAN
P.G. GUIDE’S NAME: DR. ASHOK P. YENKANCHI
PURPOSE OF STUDY
I have been explained about the reason for doing the study and selecting me as a subject of this study. This study is for better understanding of the clinical characteristics, biochemical parameters and prognostic factors in patients of Falciparum Malaria with jaundice.
RISKS AND DISCOMFORTS
I understand that I may experience some pain or discomfort during the examination or during my treatment. This is mainly the result of my condition and the procedure of the study is not expected to exaggerate these feelings which are associated with the usual course of treatment. The risk and possible complications surgically and anesthetically have been explained to me.
BENEFITS
I understand that my participation in the study will have no direct benefit to me other than the potential benefit of treatment.
ALTERNATIVES
The various alternative modes of treatment available to me in my disease with merits and demerits have been explained to me.
CONFIDENTIALITY:
I understand medical information produced by this study will become part of my hospital record and will be subject to the confidentiality and privacy regulations of the hospital.
If the data are used for publication in the medical literature for teaching purposes, no names will be used, and other identifiers, such as photographs and audio or video tapes, will be used only with my special written permission. I understand I may see the photographs and video tapes and hear the audio tapes before giving this permission. For this purpose every effort will be made by publishing person to contact me in the address furnished by me through postal communication. If no response is received within a reasonable time, all the identities will be removed from the photographs and case report before being submitted for publication.
REQUEST FOR MORE INFORMATION:
I understand that, I may ask more questions about the study at any time. Researcher is available to answer my questions or concern in this research period. I understand that I will be informed of any significant new findings discovered during the course of this study, which might influence my continued participation.
REFUSAL OR WITHDRAWL OF PARTICIPATION:
I understand that my participation is voluntary and I may refuse to participate or discontinue participation in the study at any time without prejudice to my present or future care at this hospital. I also understand that researcher may terminate my participation in the study at any time after I have been explained the reasons for doing so.
INJURY STATEMENT
I understand that in the unlikely event of injury to me resulting directly from my participation in this study. If such injury were reported promptly, then medical treatment would be available to me, but no further compensation would be provided. I understand that my agreement to participate in the study I am not waiving any of my legal rights.
Explained to ______
(Patient’s Name)
The purpose of research, the procedures required and the possible risk and benefits have been explained to the best of my ability.
Investigator ------Date:
I have been explained clearly about the reason for doing this study, reason for selecting me as a subject in the study. I also have been explained about the risks, benefits and confidentiality of the study. Alternative procedures that might be used in the treatment of my disease also explained to me. I am willing to attend any follow up requested to me at a future date. Freedom is given to me for the participation in the study or discontinues participation at any time without prejudice.