PHARMACOLOGY MOCK TEST
Full marks 40 Time – 2 hours
Attempt all questions. Supplement your answer with charts and diagrams as needed.
1. Name the drugs that can be administered by rotahaler. What is the basic difference between a rotahaler and a metered dose inhaler (MDI)? What are the advantages and disadvantages of nebuliser over MDI? Discuss the management of acute severe asthma indicating the doses of individual drugs. [2 + 1 + 2 + 5]
Or, Classify β adrenoceptor antagonists. State the contraindications of non-selective β adrenoceptor antagonists. What is the role of β blockers in AMI? Name the drugs used in the management of hypertension in pregnancy with their doses. [3 + 2 + 2 + 3]
2. Explain why: (Any FIVE) [2 x 5]
a) Neostigmine is preferred over Physostigmine for the treatment of myasthenia gravis
b) Omeprazole is not given concurrently with antacids
c) Spironolactone is used in cirrhosis of liver
d) Atropine substitutes are used in Haloperidol induced acute dystonias
e) Acetazolamide should be avoided in hepatic failure
f) Enalapril is contraindicated in bilateral renal artery stenosis
g) Class III anti-arrhythmic drugs can themselves precipitate arrhythmias
h) Pirenzepine is not used in treatment of peptic ulcer
3. Describe the mechanism of action of: (Any 4) [2 x 4]
a) Castor oil as purgative
b) Adenosine in PSVT
c) Ketotifen in asthma
d) Thiazide in diabetes insipidus
e) Glucocorticoids in chemotherapy induced vomiting
f) Pralidoxime in organophosphate compound poisoning
g) Propranolol in hyperthyroidism
4. Write short notes on: [4 x 3]
a) Management of acute angle closure glaucoma OR Management of mushroom poisoning
b) Classification of drugs used in diarrhea OR Classification of drugs used in peptic ulcer
c) Glyceryl trinitrate OR Digoxin (Mechanism of action, Use, Dose, Adverse effect)
November 21, 2008
Mock test on Bacteriology (General and Systemic)
MICROBIOLOGY (BACTERIOLOGY) MOCK TEST
Full marks 40 Time – 2 hours
Attempt all questions. Supplement your answer with charts and diagrams as needed.
1. A middle aged lady attended the skin OPD with complaints of hypopigmented patch over the right elbow with progressive loss of sensation. What is your provisional diagnosis? How would you proceed to confirm the clinical diagnosis in the laboratory? How is the efficacy of treatment evaluated in such cases? [1 + 7 + 2]
Or, A middle aged person attended the STD clinic with a solitary painless ulcer with hard base on the glans penis. What is the commonest organism that causes such a lesion? What are the methods of isolation and demonstration of the organism in the laboratory? Discuss the role of serological tests in diagnosing late stages of the disease. [1 + 4 + 5]
Or, Name the bacteria responsible for diarrheal diseases in man. How would you proceed to investigate a case of bacterial diarrhea in the laboratory if you are supplied with the fresh fecal matter of the infected individual collected in a sterile plastic bottle? [2 + 8]
2. Write short notes on any THREE: [3 x 4 = 12]
a) Acid fast stain OR Bacterial growth curve
b) Plasmids OR Bacterial flagella
c) El Tor Vibrio OR Shiga toxin producing E. coli
d) Importance of ASO titer OR Interpretation of Mantoux test
3. Comment on any THREE: [3 x 4 = 12]
a) The choice of specimen for diagnosis depends on the stage of Enteric fever.
b) Koch’s postulates have many exceptions.
c) Morphology of the colonies of motile bacteria depends on the concentration of agar agar in Nutrient agar medium.
d) Bacteriological profile of purulent meningitis varies with the age of the patient.
e) Slide and tube coagulase tests are based on different biological principles.
f) Both chromosomal and extra-chromosomal factors are involved in the origin of bacterial drug resistance.
4. Differentiate between any THREE: [3 x 2 = 6]
a) Staphylococcus aureus and S. saprophyticus
b) Autoclaving and Tyndallisation
c) Streptococcus pneumoniae and Streptococcus pyogenes
d) Chlamydia and bacteria
e) Blood agar and chocolate agar
Full marks 40 Time – 2 hours
Attempt all questions. Supplement your answer with charts and diagrams as needed.
1. A middle aged lady attended the skin OPD with complaints of hypopigmented patch over the right elbow with progressive loss of sensation. What is your provisional diagnosis? How would you proceed to confirm the clinical diagnosis in the laboratory? How is the efficacy of treatment evaluated in such cases? [1 + 7 + 2]
Or, A middle aged person attended the STD clinic with a solitary painless ulcer with hard base on the glans penis. What is the commonest organism that causes such a lesion? What are the methods of isolation and demonstration of the organism in the laboratory? Discuss the role of serological tests in diagnosing late stages of the disease. [1 + 4 + 5]
Or, Name the bacteria responsible for diarrheal diseases in man. How would you proceed to investigate a case of bacterial diarrhea in the laboratory if you are supplied with the fresh fecal matter of the infected individual collected in a sterile plastic bottle? [2 + 8]
2. Write short notes on any THREE: [3 x 4 = 12]
a) Acid fast stain OR Bacterial growth curve
b) Plasmids OR Bacterial flagella
c) El Tor Vibrio OR Shiga toxin producing E. coli
d) Importance of ASO titer OR Interpretation of Mantoux test
3. Comment on any THREE: [3 x 4 = 12]
a) The choice of specimen for diagnosis depends on the stage of Enteric fever.
b) Koch’s postulates have many exceptions.
c) Morphology of the colonies of motile bacteria depends on the concentration of agar agar in Nutrient agar medium.
d) Bacteriological profile of purulent meningitis varies with the age of the patient.
e) Slide and tube coagulase tests are based on different biological principles.
f) Both chromosomal and extra-chromosomal factors are involved in the origin of bacterial drug resistance.
4. Differentiate between any THREE: [3 x 2 = 6]
a) Staphylococcus aureus and S. saprophyticus
b) Autoclaving and Tyndallisation
c) Streptococcus pneumoniae and Streptococcus pyogenes
d) Chlamydia and bacteria
e) Blood agar and chocolate agar
Mock test on Pathology Paper I
PATHOLOGY PAPER I
Full marks 40 Time – 2 hours
Attempt all questions. Supplement your answer with charts and diagrams as needed.
Group A
1. A 30 year old lady presented with multiple petechial spots on skin and easy bruisability for the last one year. On examination, temperature, pulse and BP were within normal limits. How would you proceed to investigate the case in the laboratory? [10]
Group B (Answer any ONE)
2. Classify Diabetes Mellitus according to causes. What are the acute complications of DM? Enumerate the investigations that you may use to evaluate the glycemic control in a patient of DM who is under treatment. Discuss the diagnostic importance of oral glucose tolerance test. [3 + 2 + 2 + 3]
3. Classify acute leukemia based on bone marrow findings and cytochemistry. What may be the causes of dry tap in acute leukemia? Enumerate the clinical conditions caused by organ infiltration in acute leukemia. [5 + 2 + 3]
Group C (Answer any ONE)
4. Discuss the various routes of spread of a malignant tumor. Name 4 occupational cancers with their associated occupations. Name 4 premalignant conditions and their resultant cancers. Name 4 tumors that can present with Cushing’s syndrome.
[4 + 2 + 2 + 2]
5. Discuss the steps of healing of a clean surgical incision well apposed by sutures. Mention four complications that may develop due to infection of the surgical wound. Discuss the pathogenesis of septic shock. [4 + 2 + 4]
Group D
6. Write short notes on: (Any FIVE) [5 x 2]
a) Peripheral blood picture in vitamin B-12 deficiency
b) Myeloid leukemoid reaction
c) Plummer Vinson syndrome
d) Target cells
e) Staining of amyloid
f) Turner’s syndrome
g) Reed Sternberg cells
Full marks 40 Time – 2 hours
Attempt all questions. Supplement your answer with charts and diagrams as needed.
Group A
1. A 30 year old lady presented with multiple petechial spots on skin and easy bruisability for the last one year. On examination, temperature, pulse and BP were within normal limits. How would you proceed to investigate the case in the laboratory? [10]
Group B (Answer any ONE)
2. Classify Diabetes Mellitus according to causes. What are the acute complications of DM? Enumerate the investigations that you may use to evaluate the glycemic control in a patient of DM who is under treatment. Discuss the diagnostic importance of oral glucose tolerance test. [3 + 2 + 2 + 3]
3. Classify acute leukemia based on bone marrow findings and cytochemistry. What may be the causes of dry tap in acute leukemia? Enumerate the clinical conditions caused by organ infiltration in acute leukemia. [5 + 2 + 3]
Group C (Answer any ONE)
4. Discuss the various routes of spread of a malignant tumor. Name 4 occupational cancers with their associated occupations. Name 4 premalignant conditions and their resultant cancers. Name 4 tumors that can present with Cushing’s syndrome.
[4 + 2 + 2 + 2]
5. Discuss the steps of healing of a clean surgical incision well apposed by sutures. Mention four complications that may develop due to infection of the surgical wound. Discuss the pathogenesis of septic shock. [4 + 2 + 4]
Group D
6. Write short notes on: (Any FIVE) [5 x 2]
a) Peripheral blood picture in vitamin B-12 deficiency
b) Myeloid leukemoid reaction
c) Plummer Vinson syndrome
d) Target cells
e) Staining of amyloid
f) Turner’s syndrome
g) Reed Sternberg cells
November 10, 2008
October 15, 2008
Web snippets about Japanese B Encephalitis
JAPANENE ENCEPHALITIS
Japanese encephalitis (Japanese: , Nihon-nōen; previously known as Japanese B encephalitis to distinguish it from von Economo's A encephalitis) is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. One of the most important vectors of this disease is the mosquito Culex tritaeniorhynchus. This disease is most prevalent in Southeast Asia and the Far East.
Epidemiology:
Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Rare outbreaks in U.S. territories in Western Pacific have occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, Korea, Japan, Taiwan and Thailand. Other countries that still have periodic epidemics include Vietnam, Cambodia, Myanmar, India, Nepal, and Malaysia. Japanese encephalitis has been reported on the Torres Strait Islands and two fatal cases were reported in mainland northern Australia in 1998. The spread of the virus in Australia is of particular concern to Australian health officials due to the unplanned introduction of Culex gelidus, a potential vector of the virus, from Asia. However, the current presence on mainland Australia is minimal.[1]
Human, cattle and horses are dead-end hosts and disease manifests as fatal encephalitis. Swine acts as amplifying host and has very important role in epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. Infection in Humans occur in the ear, particularly the cochlea. The most important vector is C. tritaeniorhynchus, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation can divert the mosquito away from humans and swine.[2] The natural host of the Japanese encephalitis virus is bird, not human, and many believe the virus will therefore never be completely eliminated.
Clinical features:
Japanese encephalitis has an incubation period of 5 to 15 days and the vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis.
Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Transplacental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had central nervous system involvement. In known cases some effects also include, nausea, headache, fever, vomiting and sometimes swelling of the testicles.
Virology:
The causative agent Japanese encephalitis virus is an enveloped virus of the genus flavivirus; it is closely related to the West Nile virus and St. Louis encephalitis virus. Positive sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER)[3][4] and rapidly accumulates substantial amounts of viral proteins for the JEV.
Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISA.
Prevention:
Infection with JEV confers life-long immunity. All current vaccines are based on the genotype III virus. A formalin-inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanisation has led to control of the disease in Japan, Korea, Taiwan and Singapore. The high cost of the vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunisation programme.
In the UK, the two vaccines used (but which are unlicensed) are JE-Vax and Green Cross. Three doses are given at 0, 7–14 and 28–30 days. The dose is 1ml for children and adult, and 0.5ml for infants under 36 months of age.
The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Because the vaccine is produced from mouse brain,[6] there is a risk of autoimmune neurological complications of around 1 per million vaccinations.
Neutralising antibody persists in the circulation for at least two to three years, and perhaps longer.[7][8] The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every two years for people who remain at risk.
There are a number of new vaccines under development. The mouse-brain derived vaccine is likely to be replaced by a cell-culture derived vaccine that is both safer and cheaper to produce. China licensed a live attenuated vaccine in 1988 and more than 200 million doses have been given; this vaccine is available in Nepal, Sri Lanka, South Korea and India. There is also a new chimeric vaccine based on the yellow fever 17D vaccine that is currently under development.Treatment:
There is no specific treatment for Japanese encephalitis and treatment is supportive. There is no transmission from person to person and therefore patients do not need to be isolated.
The use of arctigenin has been proposed.[9]
Reference:
http://en.wikipedia.org/wiki/Japanese_Encephalitis
Article 2:
JAPANESE ENCEPHALITIS: CLINICAL FEATURES AND LABORATORY DIAGNOSIS
(Japanese B encephalitis)
Definition
Japanese encephalitis (JE) is an arthropod-borne virus disease affecting the central nervous system (CNS) of human beings and, less frequently, horses. The infection also results in the birth of litters of pigs with a high percentage of stillbirths or pigs affected with encephalitis.
Etiology
The JE virus is a member of the family Flaviviridae and is in the genus Flavivirus. Host range and other characteristics are described in detail in the International Catalogue of Arboviruses (1).
Host Range
People and horses are victims of the JE virus infection but appear to be dead-end hosts from an epidemiologic standpoint. Viremia levels in infected human beings and equine species are generally too low to provide potential mosquito vectors with an infective blood meal. Under experimental conditions, however, Gould et al. (9) demonstrated horse to horse transmission by Culex tritaeniorhynchus. Cattle are frequently infected in enzootic areas (24) but do not develop sickness or viremia (14).
Swine in Japan and Taiwan are both victims of disease as well as amplifiers of infection in nature. This is particularly true when swine are bred to farrow at a time when infected mosquitoes make their first appearance. This type of breeding program is practiced in Japan where, because of immunity or natural seasonal lows in transmission, gilts resist infection during pregnancy, and thus losses due to abnormal litters resulting from JE infection are reduced. However, normal newborn piglets soon lose maternally acquired antibody and are fully susceptible to infection from arthropod vectors.
Although JE infection in shoats is subclinical, viremias are sufficiently high to provide emerging broods of Cu. tritaeniorhynchus, which feed readily on swine, with a plentiful source of virus-containing blood. Following a period of extrinsic incubation of virus, the mosquitoes are able to transmit the infection to susceptible vertebrate hosts.
In Japan, herons and egrets play a role in the spread of infection to man and other vertebrates and may be responsible for carrying the virus from rural to urban areas. Cu. tritaeniorhynchus feeds readily on herons and egrets and ranges sufficiently high off the ground to feed on the young nesting birds.
Geographic Distribution
Human encephalitis in Japan was recognized as early as 1871, and Japanese encephalitis in epidemic form has been known since 1924 when 4,000 human deaths were recorded in Japan. The epidemiology of the disease was studied extensively after World War II in Japan by scientists of the U.S. Army's 406th Medical General Laboratory (2). Concurrent with vaccination of people and extensive use of agricultural pesticides in the last three decades, the disease has practically disappeared from Japan.
Japanese encephalitis virus infection is widespread throughout temperate and tropical Asia; increasing numbers of human and equine cases have appeared in India, Nepal, China, Philippines, Sri Lanka, and northern Thailand. The disease in humans is sporadic in Indonesia and northern Australia but is not known in the rest of the world.
Transmission
The virus is maintained in nature in a cycle involving Culex mosquitoes of the genera tritaeniorhynchus, annulus, fuscocephala, gelidus, and vishnui complex. Mosquitoes transmit the virus to many species of birds and to swine (2,25).
The sequence of events in temperate Asia is initiated by appearance of virus in mosquitoes in late spring followed by the infection and disease in susceptible horses and swine. This is followed by the appearance of disease in man in August and September. In tropical and semitropical areas of Asia, the seasonal nature of the disease is less marked.
Basically, however, it appears the Culex mosquitoes and birds are common factors in the epidemiology of JE, regardless of the region of occurrence, and that swine are involved where they are numerous in Asia (15).
The mechanism of maintaining the virus over the winter in temperate areas has not been elucidated. Overwintering in mosquitoes is a possibility either in infected hibernating mosquitoes or by transovarial passage (23). It is also possible that bats may carry the virus for prolonged periods (18,6).
Incubation Period
In horses, the incubation period is 8 to 10 days. The time between exposure of pregnant swine to an infectious dose of JE virus and delivery of abnormal litters does not seem to be clearly established, although exposure early in gestation appears more likely to result in abnormal litters than later exposure.
Clinical Signs
In horses, initial signs are fever, impaired locomotion, stupor, and grinding of teeth. Blindness, coma, and death follow in more severe cases. Although the clinical signs resemble those seen in horses with Western equine encephalomyelitis and Eastern equine encephalomyelitis, mortality is relatively low. Inapparent or subclinical infections in horses are far more common than cases of recognizable encephalitis.
The principal manifestation of disease in swine is the expulsion of litters of stillborn or mummified fetuses, usually at term. Viable piglets frequently die shortly after birth and exhibit tremor and convulsions before expiring. Experimental infection of boars leads to diminished sperm count and decreased mobility of sperm. Virus has been transmitted to gilts by way of infected semen (11).
Gross Lesions
In horses, gross lesions are similar to those observed in animals dying from Eastern equine encephalomyelitis and Western equine encephalomyelitis virus infections and are not specific enough to establish an etiologic diagnosis. Litters from infected pigs contain fetuses that are mummified and dark in appearance (24,4). Hydrocephalus, cerebellar hypoplasia, and spinal hypomyelinogenesis have been noted (20).
Morbidity and Mortality
The equine mortality caused by JE has been reported at about 5 percent in Japan and may actually be less than this in Southeast Asia. Mortality in adult pigs is close to zero. Litters of pigs from infected sows may be dead at delivery or, if living, may be quite weak and apt to succumb to encephalitis shortly after birth.
Diagnosis
Field Diagnosis
Presumptive diagnosis can be made in horses that manifest CNS disease accompanied by fever, particularly in an epizootic period. It has been observed that illness in horses at race tracks in Malaysia is frequently due to JE infection. The infection is manifested only by fever and a short period of lethargy (16,12,22). In temperate zones, the disease appears during late summer and early fall.
A presumptive diagnosis in swine is based on the birth of litters with a high percentage of stillborn or weak piglets.
Specimens for Laboratory
One half of a brain from animals having signs of encephalitis should be submitted unfixed and the other half fixed in 10 percent formalin. Paired serum samples collected at least 14 days apart should be submitted from animals that survive. Cerebrospinal fluid from horses with CNS signs should be submitted for detection of JE-specific IgM.
Laboratory Diagnosis
Confirmation of JE can be accomplished by demonstrating seroconversion in animals that survive long enough to yield properly spaced blood samples. Neutralization, complement fixation, hemagglutination inhibition, immunofluorescence, and enzyme-linked immonosorbent assay tests are used to show a rise in titer from the acute stage to death or recovery. Reliance on seroconversion or IgM as a means of diagnosis in horses is not definitive because seroconversion may have resulted from exposure to another nonpathogenic Flavivirus.
Demonstration of JE-specific IgM in serum of an encephalitic equine is presumptive evidence of the diagnosis.
Further confirmation of JE in horses can be obtained by examination of the cerebrospinal fluid and the brain. Specific IgM in the spinal fluid is excellent evidence of CNS infection. Although microscopic lesions of the brain are of value, definitive confirmation is based on isolation and identification of the virus from the brain. Virus isolations are more likely to be successful from brains of animals that died after a short course of the disease.
Confirmation of JE in diseased litters of pigs is accomplished by isolation of the virus from fetal brains or brains of piglets that die after manifesting signs of encephalitis. Demonstration of antibody increase in dams bearing affected litters is probably not a reliable measure because seroconversion in such animals would probably have occurred earlier in infection.
Differential Diagnosis
The disease in horses must be differentiated from other viral encephalitides. In Asia, JE is the only recognized arboviral infection causing encephalitis in horses. Because there are many mild or subclinical infections, laboratory confirmation is essential.
Various forms of toxic encephalitis must be considered in differential diagnosis. In temperate-zone Asia, the midsummer seasonal occurrence of JE in horses aids in differential diagnosis.
Japanese encephalitis in pigs must be differentiated from a hemagglutinating DNA virus infection that appears to be as commonplace in Japan as JE (21) and causes the same pattern of disease. There is evidence that the DNA virus infection is established in gilts in the middle or last trimester of pregnancy. Seasonal patterns of DNA virus infection need more complete study, but the disease does appear concurrently with Japanese encephalitis and therefore requires laboratory tests for differentiation.
Another hemagglutinating virus, myxovirus parainfluenza 1 (Sendai), has been shown capable of producing stillbirth in swine under experimental conditions (20). Encephalitis in neonatal pigs is also associated with a coronavirus infection. This agent is known to cause encephalitis in piglets in at least North America and Europe (19).
Vaccination
A live attenuated vaccine produced in hamster kidney tissue culture is in widespread use in horses in China (13). This vaccine reduced disease by about 85 percent. An inactivated vaccine prepared in mouse brain is licensed in Japan, Korea, Taiwan, India, and Thailand for use in humans. A similar inactivated product made in hamster kidney tissue culture has been used to immunize children annually in China since 1965. Live attenuated vaccines are used to immunize pigs in Japan and Taiwan (8) and humans in China (13A).
Control and Eradication
Options for control include elimination of the vectors, prevention of amplification of the infection cycle in birds and pigs, or immunization of horses, pigs, and people. Although some success in vector control was achieved by modification of irrigation methods to minimize breeding of Cu. tritaeniorhynchus in Southeast Asia and coincidentally by the use of agricultural pesticides, vector control has never been more than marginally successful. Reduction of the avian reservoir hosts does not appear feasible.
The most promising approach to reducing livestock losses and at the same time reducing the totality of infection in nature is widespread immunization of swine. Live attenuated vaccines are in use in Japan and Taiwan (8). Immunization of shoats prevents infection in vaccinees and neutralizes their role as amplifiers of infection in nature. It is anticipated that those animals retained for breeding will remain immune, and, because of immunity or natural seasonal lows in transmission resist infection during pregnancy and therefore bear normal litters. Although controlling the disease in swine dampens the spread of infection in nature, there is a continued threat to horses and human beings from other sources.
The introduction of JE virus into the United States is always a possibility, but whether the infection, once introduced, would become established in nature is difficult to assess. Animal health authorities must continue to be alert to detecting and identifying agents associated with encephalitis in horses and with abnormal litters of pigs. The means for rapid diagnosis and identification of JE are available, although it is doubtful that control of the disease in Asia will be achieved in the near future.
Japanese encephalitis (Japanese: , Nihon-nōen; previously known as Japanese B encephalitis to distinguish it from von Economo's A encephalitis) is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. One of the most important vectors of this disease is the mosquito Culex tritaeniorhynchus. This disease is most prevalent in Southeast Asia and the Far East.
Epidemiology:
Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Rare outbreaks in U.S. territories in Western Pacific have occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, Korea, Japan, Taiwan and Thailand. Other countries that still have periodic epidemics include Vietnam, Cambodia, Myanmar, India, Nepal, and Malaysia. Japanese encephalitis has been reported on the Torres Strait Islands and two fatal cases were reported in mainland northern Australia in 1998. The spread of the virus in Australia is of particular concern to Australian health officials due to the unplanned introduction of Culex gelidus, a potential vector of the virus, from Asia. However, the current presence on mainland Australia is minimal.[1]
Human, cattle and horses are dead-end hosts and disease manifests as fatal encephalitis. Swine acts as amplifying host and has very important role in epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. Infection in Humans occur in the ear, particularly the cochlea. The most important vector is C. tritaeniorhynchus, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation can divert the mosquito away from humans and swine.[2] The natural host of the Japanese encephalitis virus is bird, not human, and many believe the virus will therefore never be completely eliminated.
Clinical features:
Japanese encephalitis has an incubation period of 5 to 15 days and the vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis.
Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Transplacental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had central nervous system involvement. In known cases some effects also include, nausea, headache, fever, vomiting and sometimes swelling of the testicles.
Virology:
The causative agent Japanese encephalitis virus is an enveloped virus of the genus flavivirus; it is closely related to the West Nile virus and St. Louis encephalitis virus. Positive sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER)[3][4] and rapidly accumulates substantial amounts of viral proteins for the JEV.
Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISA.
Prevention:
Infection with JEV confers life-long immunity. All current vaccines are based on the genotype III virus. A formalin-inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanisation has led to control of the disease in Japan, Korea, Taiwan and Singapore. The high cost of the vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunisation programme.
In the UK, the two vaccines used (but which are unlicensed) are JE-Vax and Green Cross. Three doses are given at 0, 7–14 and 28–30 days. The dose is 1ml for children and adult, and 0.5ml for infants under 36 months of age.
The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Because the vaccine is produced from mouse brain,[6] there is a risk of autoimmune neurological complications of around 1 per million vaccinations.
Neutralising antibody persists in the circulation for at least two to three years, and perhaps longer.[7][8] The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every two years for people who remain at risk.
There are a number of new vaccines under development. The mouse-brain derived vaccine is likely to be replaced by a cell-culture derived vaccine that is both safer and cheaper to produce. China licensed a live attenuated vaccine in 1988 and more than 200 million doses have been given; this vaccine is available in Nepal, Sri Lanka, South Korea and India. There is also a new chimeric vaccine based on the yellow fever 17D vaccine that is currently under development.Treatment:
There is no specific treatment for Japanese encephalitis and treatment is supportive. There is no transmission from person to person and therefore patients do not need to be isolated.
The use of arctigenin has been proposed.[9]
Reference:
http://en.wikipedia.org/wiki/Japanese_Encephalitis
Article 2:
JAPANESE ENCEPHALITIS: CLINICAL FEATURES AND LABORATORY DIAGNOSIS
(Japanese B encephalitis)
Definition
Japanese encephalitis (JE) is an arthropod-borne virus disease affecting the central nervous system (CNS) of human beings and, less frequently, horses. The infection also results in the birth of litters of pigs with a high percentage of stillbirths or pigs affected with encephalitis.
Etiology
The JE virus is a member of the family Flaviviridae and is in the genus Flavivirus. Host range and other characteristics are described in detail in the International Catalogue of Arboviruses (1).
Host Range
People and horses are victims of the JE virus infection but appear to be dead-end hosts from an epidemiologic standpoint. Viremia levels in infected human beings and equine species are generally too low to provide potential mosquito vectors with an infective blood meal. Under experimental conditions, however, Gould et al. (9) demonstrated horse to horse transmission by Culex tritaeniorhynchus. Cattle are frequently infected in enzootic areas (24) but do not develop sickness or viremia (14).
Swine in Japan and Taiwan are both victims of disease as well as amplifiers of infection in nature. This is particularly true when swine are bred to farrow at a time when infected mosquitoes make their first appearance. This type of breeding program is practiced in Japan where, because of immunity or natural seasonal lows in transmission, gilts resist infection during pregnancy, and thus losses due to abnormal litters resulting from JE infection are reduced. However, normal newborn piglets soon lose maternally acquired antibody and are fully susceptible to infection from arthropod vectors.
Although JE infection in shoats is subclinical, viremias are sufficiently high to provide emerging broods of Cu. tritaeniorhynchus, which feed readily on swine, with a plentiful source of virus-containing blood. Following a period of extrinsic incubation of virus, the mosquitoes are able to transmit the infection to susceptible vertebrate hosts.
In Japan, herons and egrets play a role in the spread of infection to man and other vertebrates and may be responsible for carrying the virus from rural to urban areas. Cu. tritaeniorhynchus feeds readily on herons and egrets and ranges sufficiently high off the ground to feed on the young nesting birds.
Geographic Distribution
Human encephalitis in Japan was recognized as early as 1871, and Japanese encephalitis in epidemic form has been known since 1924 when 4,000 human deaths were recorded in Japan. The epidemiology of the disease was studied extensively after World War II in Japan by scientists of the U.S. Army's 406th Medical General Laboratory (2). Concurrent with vaccination of people and extensive use of agricultural pesticides in the last three decades, the disease has practically disappeared from Japan.
Japanese encephalitis virus infection is widespread throughout temperate and tropical Asia; increasing numbers of human and equine cases have appeared in India, Nepal, China, Philippines, Sri Lanka, and northern Thailand. The disease in humans is sporadic in Indonesia and northern Australia but is not known in the rest of the world.
Transmission
The virus is maintained in nature in a cycle involving Culex mosquitoes of the genera tritaeniorhynchus, annulus, fuscocephala, gelidus, and vishnui complex. Mosquitoes transmit the virus to many species of birds and to swine (2,25).
The sequence of events in temperate Asia is initiated by appearance of virus in mosquitoes in late spring followed by the infection and disease in susceptible horses and swine. This is followed by the appearance of disease in man in August and September. In tropical and semitropical areas of Asia, the seasonal nature of the disease is less marked.
Basically, however, it appears the Culex mosquitoes and birds are common factors in the epidemiology of JE, regardless of the region of occurrence, and that swine are involved where they are numerous in Asia (15).
The mechanism of maintaining the virus over the winter in temperate areas has not been elucidated. Overwintering in mosquitoes is a possibility either in infected hibernating mosquitoes or by transovarial passage (23). It is also possible that bats may carry the virus for prolonged periods (18,6).
Incubation Period
In horses, the incubation period is 8 to 10 days. The time between exposure of pregnant swine to an infectious dose of JE virus and delivery of abnormal litters does not seem to be clearly established, although exposure early in gestation appears more likely to result in abnormal litters than later exposure.
Clinical Signs
In horses, initial signs are fever, impaired locomotion, stupor, and grinding of teeth. Blindness, coma, and death follow in more severe cases. Although the clinical signs resemble those seen in horses with Western equine encephalomyelitis and Eastern equine encephalomyelitis, mortality is relatively low. Inapparent or subclinical infections in horses are far more common than cases of recognizable encephalitis.
The principal manifestation of disease in swine is the expulsion of litters of stillborn or mummified fetuses, usually at term. Viable piglets frequently die shortly after birth and exhibit tremor and convulsions before expiring. Experimental infection of boars leads to diminished sperm count and decreased mobility of sperm. Virus has been transmitted to gilts by way of infected semen (11).
Gross Lesions
In horses, gross lesions are similar to those observed in animals dying from Eastern equine encephalomyelitis and Western equine encephalomyelitis virus infections and are not specific enough to establish an etiologic diagnosis. Litters from infected pigs contain fetuses that are mummified and dark in appearance (24,4). Hydrocephalus, cerebellar hypoplasia, and spinal hypomyelinogenesis have been noted (20).
Morbidity and Mortality
The equine mortality caused by JE has been reported at about 5 percent in Japan and may actually be less than this in Southeast Asia. Mortality in adult pigs is close to zero. Litters of pigs from infected sows may be dead at delivery or, if living, may be quite weak and apt to succumb to encephalitis shortly after birth.
Diagnosis
Field Diagnosis
Presumptive diagnosis can be made in horses that manifest CNS disease accompanied by fever, particularly in an epizootic period. It has been observed that illness in horses at race tracks in Malaysia is frequently due to JE infection. The infection is manifested only by fever and a short period of lethargy (16,12,22). In temperate zones, the disease appears during late summer and early fall.
A presumptive diagnosis in swine is based on the birth of litters with a high percentage of stillborn or weak piglets.
Specimens for Laboratory
One half of a brain from animals having signs of encephalitis should be submitted unfixed and the other half fixed in 10 percent formalin. Paired serum samples collected at least 14 days apart should be submitted from animals that survive. Cerebrospinal fluid from horses with CNS signs should be submitted for detection of JE-specific IgM.
Laboratory Diagnosis
Confirmation of JE can be accomplished by demonstrating seroconversion in animals that survive long enough to yield properly spaced blood samples. Neutralization, complement fixation, hemagglutination inhibition, immunofluorescence, and enzyme-linked immonosorbent assay tests are used to show a rise in titer from the acute stage to death or recovery. Reliance on seroconversion or IgM as a means of diagnosis in horses is not definitive because seroconversion may have resulted from exposure to another nonpathogenic Flavivirus.
Demonstration of JE-specific IgM in serum of an encephalitic equine is presumptive evidence of the diagnosis.
Further confirmation of JE in horses can be obtained by examination of the cerebrospinal fluid and the brain. Specific IgM in the spinal fluid is excellent evidence of CNS infection. Although microscopic lesions of the brain are of value, definitive confirmation is based on isolation and identification of the virus from the brain. Virus isolations are more likely to be successful from brains of animals that died after a short course of the disease.
Confirmation of JE in diseased litters of pigs is accomplished by isolation of the virus from fetal brains or brains of piglets that die after manifesting signs of encephalitis. Demonstration of antibody increase in dams bearing affected litters is probably not a reliable measure because seroconversion in such animals would probably have occurred earlier in infection.
Differential Diagnosis
The disease in horses must be differentiated from other viral encephalitides. In Asia, JE is the only recognized arboviral infection causing encephalitis in horses. Because there are many mild or subclinical infections, laboratory confirmation is essential.
Various forms of toxic encephalitis must be considered in differential diagnosis. In temperate-zone Asia, the midsummer seasonal occurrence of JE in horses aids in differential diagnosis.
Japanese encephalitis in pigs must be differentiated from a hemagglutinating DNA virus infection that appears to be as commonplace in Japan as JE (21) and causes the same pattern of disease. There is evidence that the DNA virus infection is established in gilts in the middle or last trimester of pregnancy. Seasonal patterns of DNA virus infection need more complete study, but the disease does appear concurrently with Japanese encephalitis and therefore requires laboratory tests for differentiation.
Another hemagglutinating virus, myxovirus parainfluenza 1 (Sendai), has been shown capable of producing stillbirth in swine under experimental conditions (20). Encephalitis in neonatal pigs is also associated with a coronavirus infection. This agent is known to cause encephalitis in piglets in at least North America and Europe (19).
Vaccination
A live attenuated vaccine produced in hamster kidney tissue culture is in widespread use in horses in China (13). This vaccine reduced disease by about 85 percent. An inactivated vaccine prepared in mouse brain is licensed in Japan, Korea, Taiwan, India, and Thailand for use in humans. A similar inactivated product made in hamster kidney tissue culture has been used to immunize children annually in China since 1965. Live attenuated vaccines are used to immunize pigs in Japan and Taiwan (8) and humans in China (13A).
Control and Eradication
Options for control include elimination of the vectors, prevention of amplification of the infection cycle in birds and pigs, or immunization of horses, pigs, and people. Although some success in vector control was achieved by modification of irrigation methods to minimize breeding of Cu. tritaeniorhynchus in Southeast Asia and coincidentally by the use of agricultural pesticides, vector control has never been more than marginally successful. Reduction of the avian reservoir hosts does not appear feasible.
The most promising approach to reducing livestock losses and at the same time reducing the totality of infection in nature is widespread immunization of swine. Live attenuated vaccines are in use in Japan and Taiwan (8). Immunization of shoats prevents infection in vaccinees and neutralizes their role as amplifiers of infection in nature. It is anticipated that those animals retained for breeding will remain immune, and, because of immunity or natural seasonal lows in transmission resist infection during pregnancy and therefore bear normal litters. Although controlling the disease in swine dampens the spread of infection in nature, there is a continued threat to horses and human beings from other sources.
The introduction of JE virus into the United States is always a possibility, but whether the infection, once introduced, would become established in nature is difficult to assess. Animal health authorities must continue to be alert to detecting and identifying agents associated with encephalitis in horses and with abnormal litters of pigs. The means for rapid diagnosis and identification of JE are available, although it is doubtful that control of the disease in Asia will be achieved in the near future.
September 05, 2008
Selected Images on Infective Endocarditis
FIG 1. Infective vegetations on heart valves (diagrammatic)
FIG 2. Vegetations in Infective endocarditis
FIG 3. Uninfected prosthetic heart valves
FIG 4. Roth spots: pale center with red periphery; Right (The one on top and left are splinter hemorrhage)
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FIG 5. Osler's node
Topic of the month September 2008: Infective Endocarditis
INFECTIVE ENDOCARDITIS: A RAPID REVIEW
What is Infective endocarditis (IE)?
-Infection of the endocardium, valve cusps or prosthetic valves
-May occur as acute infection (e.g. <24hrs after surgery)
-More commonly runs an insidious course : Subacute Bacterial Endocarditis (SBE)
Endocarditis is an infection that invades the innermost lining of the heart - the endothelium. It can damage the heart valves, the rings of connective tissue that surround the valves, as well as the inner linings of the heart chambers themselves.
In some congenital cardiac diseases, infection can also occur in the lining of the arteries that come out of the heart.
CONDITIONS PREDISPOSING TO IE
1. Structural cardiac abnormalities:
• AS
• AR
• MR
• VSD
2. Factors altering immunity:
• Immunosuppression
• AIDS
• Diabetes
• Chronic alcoholism
3. External factors:
• Prosthetic valves
• Indwelling vascular catheters
• Pacing wires (IV)
4. Factors causing bacteraemia:
• Oral/Dental surgery
• IV drug use
• Urogenital/GI operations
CARDIAC DISEASES IMMUNE TO IE
-ASD
-Heart failure
-VSD with reversal of shunt
-MS
WHAT ARE THE SIGNS AND SYMPTOMS?
The signs and symptoms of infective endocarditis depend on the causative organism. Symptoms may include fever, fatigue, weight loss, new rashes (either painful or painless), headaches, backaches, joint pains, and confusion.
A new heart murmur as well as new skin, fingernail, and retinal lesions are typical physical findings in endocarditis. We can make the diagnosis by finding microbial organisms in the blood and by performing an echocardiogram that shows evidence of endocarditis in the heart.
WHAT ARE THE COMPLICATIONS?
If not treated, most patients with infective endocarditis will die. Depending on when treatment is begun, there can be various complications. The infection can destroy the heart valves, resulting in congestive heart failure.
Small masses of bacteria or fungus, as well as platelets and fibrin can flick off the valves and cause problems throughout the body. These are called emboli. They can result in strokes, kidney failure, heart attacks, and damage to the gastrointestinal organs. Endocarditis can also result in heart arrhythmias and inflammation of heart tissue.
Finally, infective endocarditis can result in abscesses in the heart that are very hard to treat.
SUMMARY OF CLINICAL FEATURES AND COMPLICATIONS
A. General
1. Malaise
2. Fever
3. Night sweats
4. Anaemia
5. Clubbing
6. Weight loss
B. Eyes
1. Roth spots
2. Conjunctival splinter haemorrhages
C. Arthralgia
D. Splenomegaly
E. Skin
1. Osler’s nodes
2. Janeway lesions
3. Splinter haemorrhages
4. Petechiae
F. Cardiac
1. Murmurs
2. Cardiac failure
G. Cerebral emboli/abscess
H. Kidney
1. Glomerulonephritis
2. Haematuria
HOW IS INFECTIVE ENDOCARDITIS DIAGNOSED USING DUKE’S CRITERIA?
Duke clinical criteria
2 major criteria
Or
1 major & 3 minor criteria
Or
5 minor criteria
Major
i) Typical organism in 2 separate cultures or persistently +ve blood cultures (>3, >12 hrs apart)
ii) +ve echocardiogram (vegetation, abscess) or new valvular regurgitation
Minor
i) Predisposition
ii) Fever >38˚C
iii) Vascular/ immunological phenomena (splinter haemorrhages, Osler’s nodes)
iv) +ve blood cultures (not meeting major criteria)
v) +ve echocardiogram (not meeting major criteria)
INVESTIGATIONS FOR THE DIAGNOSIS OF IE
A. Routine – Blood, Urine, Ur, Cr, CXR, ECG
B. Special –
a. Blood culture
b. Echo-cardiography
c. Rheumatoid factor
HOW IS ENDOCARDITIS TREATED?
Infective endocarditis is treated with antibiotics and with surgery in some situations. Intravenous antibiotics are used for several weeks to eradicate the organism that caused the condition. But in more serious cases, urgent cardiac surgery is indicated to treat some patients.
Surgery is considered particularly when a patient has an artificial heart valve. However, there is new evidence to suggest that certain kinds of bacterial infections of prosthetic valves can be treated with just antibiotics.
IS ENDOCARDITIS PREVENTABLE?
Yes. As described above, infective endocarditis occurs when there is an infection in the blood. Antibiotics can prevent such an infection from occurring in the first place. Antibiotic prophylaxis is recommended before medical procedures with a high probability of introducing bacteria into the blood.
Dental procedures that cause bleeding from the gums (even a simple cleaning); rigid bronchoscopy; and surgery of the upper respiratory tract, urinary tract procedures, and gastrointestinal procedures all confer an increased risk of bacteremia, and therefore, an increased risk of infective endocarditis in those individuals with predisposing cardiac lesions.
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