Centela

Toxic substances in pulses

2008-12-27T07:51:00.000-08:00

Deleterious substances of various kinds are present in legume grain eaten by man. Among them are:

Trypsin inhibitors
Cyanogenic glucosides
Goitrogenic factors
Hemagglutinins/Haemagglutinins
Saponins
Alkaloids
Tannins
flatulent factors
Antivitamins
Aflatoxin

Contamination with microorganisms could result in the formation of toxins (aflatoxin) which produce adverse effects when ingested.

In most pulses these toxins are destroyed by adequate soaking, removal of the skin and ordinary methods of cooking. In some species removal of the skin and inactivation toxins require prolonged cooking time, pressure cooking or autoclaving, facilities that are available in few households. For any pulse to welcome in a household it should lend itself to ordinary methods of preparation, needing little fuel. Pulses form such an important item of the diet in developing countries that every effort should be made to encourage their consumption by increasing their digestibility.

In the preparation of whole grains, the seeds should be soaked for 24 to 36hoursin a small volume of water, changing the water every 8 to 12 hours. Skins can be removed by rubbing the seeds gently. The grain is then boiled in a little water till it softens. The cooking water should be consumed as it contains water soluble nutrients. When feeding young children, the seeds should be mashed to increase the digestibility. The dhal is more easily cooked than gram. Pulses are the one food that benefits by over boiling.

What are phytohaemagglutinins?

2008-12-27T07:49:00.000-08:00

Introduction

Haemagglutinins are proteins capable of agglutinating red blood cells. Such substances present in plants are called phytohaemagglutinins. They are present in all legumes. About 25% of the growth inhibition produced in rats (experiment level) by Soya beans is due to haemagglutinins. Significant level of haemagglutinins occur also in black beans and kidney beans (varieties of Phaseolus vulgaris).purified hemagglutininsfrom these two pulses, when fed to rats at a level0.5 to 1% result in 100% mortality within two weeks.

Mechanism of toxicity

Phytohaemagglutinins bind with the red cell membrane and makethem more vulnerable to the hemagglutination

Common food items containing phytohaemagglutinins

Soya bean

Black beans and

Kidney beans

Removal of phytohaemagglutinins from those food items

The toxic factor can be destroyed completely by soaking the grain overnight and later autoclaving.

The importance of such factors in human nutrition should not be discounted, as pulses form an important item in most diets.

ACTH stimulation test

2008-12-23T19:06:00.000-08:00

Introduction

The anterior pituitary is often referred to as the “master gland” because, together with the hypothalamus, it orchestrates the complex regulatory functions of multiple other endocrine glands. The anterior pituitary gland produces six major hormones: (1) prolactin (PRL), (2) growth hormone (GH), (3) adrenocorticotropin hormone (ACTH), (4) luteinizing hormone (LH), (5) follicle-stimulating hormone (FSH), and (6) thyroid-stimulating hormone (TSH)

ACTH secretion is pulsatile and exhibits a characteristic circadian rhythm, peaking at 6 A.M. and reaching a nadir about midnight. Adrenal glucocorticoid secretion, which is driven by ACTH, follows a parallel diurnal pattern.

ACTION

The major function of the HPA axis is to maintain metabolic homeostasis and to mediate the neuroendocrine stress response. ACTH induces cortical steroidogenesis by maintaining adrenal cell proliferation and function. The receptor for ACTH, designated melanocortin- 2 receptor, is a GPCR that induces steroidogenesis by stimulating a cascade of steroidogenic enzymes

LABORATORY INVESTIGATION

Biochemical diagnosis of pituitary insufficiency is made by demonstrating low levels of trophic hormones in the setting of low target hormone levels. The diagnosis of adrenalInsufficiency may be established by means of an ACTH stimulation test.

Test

This is a screening test (the so-called rapid ACTH stimulation test) which involvesthe administration of 25 units (0.25 mg) of cosyntropin intravenously or intramuscularly and measurement of plasma cortisol levels before administration and 30 and 60 min after administration, the test can be performed at any time of the day. The most clear-cut criterion for a normal response is a stimulated cortisol level of >500 nmol/L (>18 µg/dL), and the minimal stimulated normal increment of cortisol is >200 nmol/L (>7 µg/dL) above baseline. Severely ill patients with elevated basal cortisol levels may show no further increases following acute ACTH administration.

CPK (creatine phosphokinase) test

2008-12-23T19:01:00.000-08:00

Introduction

CK is a molecule made up of two polypeptide subunits (M and B) coded by different genes. Three major isoenzymes are available.

CK-MM is the major isoenzyme type available. This is present in skeletal and cardiac muscles
CK-MB is the isoenzyme which is primarily found in the cardiac muscles. A small amount is present in the skeletal muscles as well.
CK-BB is the isoenzyme which is mainly found in the brain matter. A small amount is also found in kidney, stomach, colon, and liver as well.

MM is the predominant CK type. Serum of a normal individual contains more than 97% of MM variety whereas rest consists of MB type. Normal CK level is 200-250 u/l There are several causes which can lead to the elevation of CK level in the blood .These include;

Artefactual causes ( Hemolysis)
Physiological causes(neonates, adult male> adult female, exercise)
Pathological causes (e.g. shock & circulatory failure, Myocardial infarction, muscular dystrophy, Rhabdomyolysis, Hypothyroidism, Alcoholism, Head injury and strokes)

Importance in cardiac injuries

Most important aspect of the CK is it’s relevant with cardiac injury. The level of CK rises within 4 to 8 hours after the cardiac event and it returns to normal level by 48 to 72 hours. The peak level can be detected within 16 to 24 hours after the event. The main drawback of measurement of CK level is its lack of specificity for cardiac injuries as it elevates in above mentioned causes as well.

Since the CK-MB is more specific for the cardiac muscle, measurement of CK-MB level can be useful. But the skeletal muscles also contain some amount of CK-MB, which is very small when compare with the amount containing in the cardiac muscles (Table A). Usually in serum the fraction of CK-MB is about 3%. If this fraction is higher than the normal level it will indicate the cardiac injury. But sever skeletal muscles damage can give rise to the higher level of CK-MB therefore sever skeletal muscles damage can mimic acute myocardial infarction. To avoid this false positive scenario, series of ECG should be done with the measurement of CK level. There are some other causes which lead to the rise in CK-MB level such as crush syndrome, Major surgery, Defibrillation and Malignant Hyperthermia.

Table A

Isoenzyme	% in heart muscles	% in cardiac muscles
CK-MM	78	98
CK-MB	22	2

Following condition give elevated CPK level

Hyperthermia
Necrotizing fasciitis caused by S. pyogenes
Legionnaires’ disease (Pneumonia)
Severe Leptospirosis (Weil’s Syndrome)
Complications of influenza infection
Crimean-congo hemorrhagic fever
Trichinellosis
Cardiogenic shock
Hypothyroidism
Hypophosphatemia
As a side effects of HMG-CoA reductase inhibitors
As a side effects of Antipsychotic medications

Subcutaneous worm in humans

2008-12-21T19:46:00.000-08:00

Introduction

There are several worm infections which can affect the subcutaneous tissues of the human. Some time these infections are difficult to eliminate.

Onchocerciasis
Loasis
Dirofilariasis
Dracanculosis
Gnathostomiasis
Mansonella streptocerca
Schistosomiasis
Brugia infection
Sparganosis
Coenurosis

Onchocerciasis

Onchocerciasis (“river blindness”) is caused by a filarial nematode (Onchocera volvulus) which infects an estimated 13 million individuals. The majority of individuals infected with O. volvulus live in the equatorial region of Africa extending from the Atlantic coast to the Red Sea.

Loasis

Loiasis is caused by Loa loa (the African eye worm), which is present in the rain forests of West and Central Africa. Adult parasites (females, 50 to 70 mm long and 0.5 mm wide; males, 25 to 35 mm long and 0.25 mm wide) live in subcutaneous tissues; microfilariae circulate in the blood with a diurnal periodicity that peaks between 12:00 noon and 2:00 P.M.

Dirofilariasis

This is a zoonotic filarial infection that affects primarily dogs, cats, and raccoons occasionally infect humans incidentally, as do Brugia and Onchocerca parasites that affect small mammals. Because humans are an abnormal host, the parasites never develop fully. The worm is known as Dirofilaria ripens.

Dracanculosis

Dracunculiasis, caused by Dracunculus medinensis, is a parasitic infection whose incidence has declined dramatically because of global eradication efforts. Current estimates suggest that there are 56,000 cases worldwide, the majority in Sudan. Humans acquire this infection when they ingest water containing infective larvae derived from Cyclops, a crustacean that is the intermediate host.

Gnathostomiasis

Infection of human tissues with larvae of Gnathostoma spinigerum can cause eosinophilic meningoencephalitis, migratory cutaneous swellings, or invasive masses of the eye and visceral organs.

Mansonella streptocerca

This filarial worm is found in West and Central Africa. It does not show any periodicity. Microfilariae are found in subcutaneous tissues and skin. The vector of this worm is a Culicoides (midges).

Schistosomiasis

Schistosomiasis is an important cause of parasitic myelitis in endemic areas. The myelitis is intensely inflammatory and granulomatous in nature, caused by a local response to tissue-digesting enzymes from the ova of the parasite.

Brugia infection

Zoonotic Brugia infection can produce isolated lymph node enlargement, Excisional biopsy is both diagnostic and curative; these infections usually do not respond to chemotherapy.

Sparganosis

Humans can be infected by the sparganum, or plerocercoid larva, of a diphyllobothrid tapeworm of the genus Spirometra. Infection can be acquired by the consumption of water containing infected Cyclops; by the ingestion of infected snakes, birds, or mammals; or by the application of infected flesh as poultices. The worm migrates slowly in tissues, and infection commonly presents as a subcutaneous swelling. Periorbital tissues can be involved, and ocular sparganosis may destroy the eye. Surgical excision is used to treat localized sparganosis.

COENUROSIS

This rare infection of humans by the larval stage (coenurus) of the dog tapeworm Taenia multiceps or T. serialis results in a space-occupying cystic lesion. As in Cysticercosis, involvement of the central nervous system and subcutaneous tissue is most common. Both definitive diagnosis and treatment require surgical excision of the lesion. Chemotherapeutic agents generally are not effective.

Hepatobilliary drains

2008-12-21T19:43:00.001-08:00

Introduction

Liver is the organ where bile is produced. Then bile is carried through the bile duct to the gall bladder which is the organ where bile is stored .Various stimuli (CCK, presence of food in the gut) can evoke contraction of the gallbladder. These contractions drive bile to the duodenum from gall bladder via common bile duct. More than 90% of the bile is reabsorbed to the blood and rest excretes via faeces. This is the normal bile pathway.

If there is an obstruction to this bile pathway, patient may need bile drainage. Obstruction could be due to gall stones, cancers or strictures.

Obstruction can be in the common hepatic duct, bile duct, common bile duct, etc. To relieve the obstruction, bile drainage may be required.

Drainage procedures are indicated in cases where the bile duct is:

Very dilated
Contains multiple stones
Drains poorly
Has a stone that is impacted at the lower end and all efforts to remove it have failed
Difficult to totally clear for any reason.
Following bile duct exploration

Drainage procedures are especially useful in the elderly and include a choledocho-duodenostomy or transduodenal sphincteroplasty. The former procedure, which involves anastomosing the duodenum to the opened duct, is safe as long as the duct is dilated.

Common draining methods

Percutaneous transhepatic drainage
Endoscopic biliary drainage
T-tube drainage.
Drainage with pigtail stent for large retained stones

Biosensors

2008-12-21T19:42:00.001-08:00

Introduction

A biosensor is a device for the detection of an analyte that combines a biological component with a physicochemical detector component. It should be able to convert a biological response into an electrical signal.

Biosensors represent a rapidly expanding field, at the present time, with an estimated 60% annual growth rate; the major impetus coming from the health-care industry (e.g. 6% of the western world are diabetic and would benefit from the availability of a rapid, accurate and simple biosensor for glucose) but with some pressure from other areas, such as food quality appraisal

and environmental monitoring.

Component of biosensors

It consists of 3 parts:

The sensitive biological element (eg. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc).
The transducer or the detector element.
Associated electronics or signal processors.

Features of a successful biosensor

It must be highly specific for the purpose.
It should be stable under normal storage conditions.
It must have a good stability over a large number of assays.
The reaction should be independent from other physical parameters such as pH and temperature.
The response should be accurate, precise, reproducible and linear over the useful analytical range.
It should be cheap, small and portable.
It should be capable of being used by a semi-skilled person.

Types of biosensors

There are different types of biosensors are available such as Electrochemical, Piezoelectric, and Thermometric and Optical biosensors in the analytical field.

Electrochemical Biosensors

An electrochemical biosensor is a self-contained integrated device, which is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element (biochemical receptor) which is retained in direct spatial contact with an electrochemical transduction element.

Piezoelectric biosensor

The development of a piezoelectric biosensor based on nucleic acids interaction is presented focusing on the methodology for probe immobilization. This is a key step in any DNA biosensor development. Often, the detection limits and, in general, the analytical performances of the biosensor can be improved by optimizing the immobilization of the receptor on the transducer surface.

Thermometric biosensors

Thermometric biosensors are constructed by combining enzymes with temperature sensors. When the analyte is exposed to the enzyme, the heat of reaction of the enzyme is measured and is calibrated against the analyte concentration.

Optical biosensors

Optical Biosensors provides the most comprehensive analysis of optical biosensors and relevant technologies to date. According to the optical configuration, optical sensors have classified into two modes. When light is reflected at an optical interface where there is a change of refractive index, there is a decay of energy from the point of reflection into the surrounding medium. This energy field which extends into the medium depends upon the medium in which the wave guide is dipped. The resultant changes of luminescence, absorption or fluorescence can hence be determined. When the glass surface of the biosensor is coated with a thin layer of metal (silver, gold), the intensity of the resonance angle changes depending on the concentration of the medium in which electrode is immersed. This phenomenon is called the surface plasma resonance (SPR).

Applications of Biosensors

2008-12-21T19:41:00.001-08:00

Applications

There are many potential applications of biosensors of various types. The main requirements for a biosensor approach to be valuable in terms of research and commercial applications are the identification of a target molecule, availability of a suitable biological recognition element, and the potential for disposable portable detection systems to be preferred to sensitive laboratory-based techniques in some situations. Some examples are given below:

Glucose monitoring in diabetes patients.
Biosensors in food analysis.
Biosensors in Forensic Medicine.
Other medical health related targets(ketones body, LDL and HDL)
Environmental applications (the detection of pesticides and river water contaminants)
Remote sensing of airborne bacteria (in counter-bioterrorist activities
Detection of pathogens)
Determining levels of toxic substances before and after bioremediation
Detection and determining of organophosphate
Routine analytical measurement of folic acid, biotin, vitamin B12 and pantothenic acid as an alternative to microbiological assay
Determination of drug residues in food, such as antibiotics and growth promoters, particularly meat and honey.
Drug discovery and evaluation of biological activity of new compounds.
Protein engineering in biosensors
Detection of toxic metabolites such as mycotoxins

Biosensors and Forensic Medicine

2008-12-21T19:39:00.000-08:00

Introduction

A biosensor is a device for the detection of an analyte that combines a biological component with a physicochemical detector component.

Application of biosensors in forensic medicine is an emerging field and it also changes the dimensions of the forensic medicine.

Applications in Forensic medicine

Identification of suspicious substances such as a white powder, contain toxins.
Screening for potentially Toxic Chemicals such as cyanide, pesticides, herbicides, medicinal and illicit drugs.
Identification of toxins and organisms in suspected terrorist attacks.
Identification of offending agents in suspected murder cases.

Advantages

These tests are very rapid.
Useful in emergency situations
Some tests are easy to perform.

Disadvantages

They could be expensive.
Skilled personals may be needed to handle them.
Biosensor itself can be harmful.

HUMAN HELMINTHES INFECTIONS

2008-12-03T18:55:00.000-08:00

INTRODUCTION

Helminthes (worm) are among the major parasites of humans and are classified under two phyla;

Nemathelminthes ( Nematodes or Round worms)
Platyhelminthes (Cestodes or tape worms and Trematodes or flukes)

Majority of helminthes that infect humans belong to the following three classes.

Nematoda (round worms). They are elongated, cylindrical worms. The sexes are separate. A complete alimentary canal is present with some species having well developed buccal capsules. They possess a body cavity ( pseudocele)
Cestoda (tapeworms). They are flattened tape-like segmented worms. Sexes are not separate, each segment having a set of male and female reproductive organs. Alimentary canal is absent. The head end possesses suckers, often with hooks. The body cavity is absent.
Trematoda (flukes). They are flattened and leaf-like. Each fluke has a set of male and female reproductive organs (except blood flukes where sexes are separate). The alimentary canal is incomplete and there is no body cavity. They possess oral and ventral suckers.

NEMATODES

This is a large and highly successful group of organisms found living in all types of habitats. Some are important parasites of human and animals. The parasitic nematodes are remarkable being similar to each other but vary widely in size. They are cylindrical with unsegmented bodies and have false body cavities (pseudocoelomes). The multi-layered cuticle is non-nucleated and allows contraction and expansion of the body. Inner to the cuticle is the muscle layer. Among the major organs are the alimentary, excretory and the reproductive systems, which are suspended in the ‘body cavity’. They have separate sexes.

The cuticle is shed (moulting) four times during development from egg to adult worm. Some species have direct life cycles while others need intermediate hosts. Nematodes do not multiply in humans (except in the form of auto infection with Strongyloides). Parasitic nematodes of humans are found in various tissues such as subcutaneous, muscle, lymphatic tissue and in organs such as the intestinal tract.

Nematode parasites of humans

Small intestine

Large intestine

Tissue nematodes

Subcutaneous tissue (filarial worm, Dracanculosis and animal hookworm larvae)
Muscle ( Trichinella spiralis)
Lymphatics ( Filarial worm)
Visceral organs (Toxocara)
CNS ( Angiostrongylus cantonensis and Toxocara)

Infections due to other nematodes

Cutaneous larva migrans
Visceral larva migrans

CESTODES

They are flat, ribbon-like worms inhabiting the intestinal tract of vertebrates. Their bodies are formed of chains of segments (proglottids) of varying sizes and shapes. The whole chain is called strobila. At the anterior end is the scolex or the ‘holdfast’ organ which is used for the attachment of the worm to the intestinal mucosa. Suckers aid the attachment to the mucosa in some while others use sucking grooves. Hooks also help when present. Behind the scolex is the undifferentiated ‘neck’ region from which growth of new segments takes place continuously. The end of the worm is comprised of gravid (pregnant) segments. They have no alimentary canals and nutrition is getting through the cuticle of the segments. Each segment has male and female reproductive organs (testes, ovaries and uteri).

In the life cycle the larval stages are found in the intermediate hosts. Some have only one intermediate host while others have two intermediate hosts. In humans pathology is caused by either adult worms or by larval stages.

Cestodes parasites in human

Human infection due to adult worms

Taenia saginata (beef tapeworm)
Taenia solium (pork tapeworm)
Hymenolepis diminuta (rat tapeworm)
Hymenolepis nana (The dwarf tapeworm)
Diphyllobothrium latum (fish tapeworm)
Dipylidium caninum (cat/dog tapeworm)
Bertiella studeri (monkey tapeworm)

Human infection due to larval stages

Cysticercosis cellulose (Cysticercosis)
Echinococcus garnulosus (Echinococcosis/Hadatid disease)

TREMATODES

Several trematodes (also known as flukes) are capable of parasiting man. The most important of these are the schistosomes. Other trematodes are also of major medical significance, especially in the Far East, as parasites of the liver, lung and the intestinal tracts.

Trematodes are flat, leaf-like hermaphrodite helminthes (excluding schistosomes). These parasites vary in size from a few millimeters to around 7cm in length. They possess two suckers, one for attachment, and another into which the alimentary tract opens. The rest of the body is occupied by the gut, testes, uterus and yolk glands. The morphology of these structures is used in identification.

In all trematodes infections, man acts as the definitive host harbouring the adult worms. The life cycle is complex, with alternating sexual and asexual reproduction in different hosts. The first intermediate host, however, is always a freshwater snail. Each parasite is specific in the choice of a snail host. The life cycles of trematodes (excluding the schistosomes) are similar: the egg which is excreted by a definitive host needs to reach water/moisture, where the ciliated larva inside the egg (called the miracidium) escapes and finds its way into a snail host. There is prolonged development multiplication in the snail with the formation of sporocysts and radia (2^nd stage larvae) stages. The final larval stages, which are known as cercaria, emerge from the snail and encyst as metacercaria on fish, crustacean or water plants. Human infection follows ingestion of these infected second intermediate hosts.

Trematodes parasites in human

Lung flukes

Paragonimus westermani

Liver flukes

Ophisthorchis (Clonorchis) sinensis (Chinese liver fluke)
Fasciola hepatica (sheep liver fluke)

Intestinal flukes

Fasciolopsis buski

Blood schistosomiasis

Intestinal schistosomiasis

Schistosoma mansoni
Schistosoma japonicum

Urinary schistosomiasis

Schistosoma haematobium

HYMENOLEPIS NANA (The dwarf tapeworm)

2008-12-03T18:53:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The infection is commoner in both temperate and tropical regions of the world such as Egypt, Sudan, Thailand, India, Japan, South America and Southern Europe.

LOCATION IN HOST

The worm is found attached to the mucosa of the small intestine.

MORPHOLOGY

The worm is small and measures 25-45mm*0.5-0.9mm. It consists of 100-200 segments. The small scolex measures 140-480µm and has a rostellum with single row of hooks

There are four suckers on the scolex. The neck is usually long. The segments close to the neck are short while the mature segments are broader than long. The eggs are globular and have thin outer vitelline membranes; 40-60µm separated from the inner which measures about 20-30µm.The latter is the embryophore and encloses the embryo which is ‘lemon’ shaped. On either end is polar thickening from which a few filaments extend.

LIFE CYCLE

Man is the definitive host. This is the only tapeworm known to have no intermediate host. The gravid segments are generally disrupted and eggs are passed in the faeces of the infected person. When ingested by man the onchosphere penetrates the small intestinal villi to form the cysticercoid stage. Within a short time (4 days) the cysticercoid re-enter the lumen and mature into adults. Autoinfection is possible.

PATHOGENESIS AND CLINICAL FEATURES

Mild infections are generally asymptomatic. But when large numbers of worms are found (>1000) enteritis with abdominal pain, diarrhea, nausea and vomiting may occur. These symptoms are probably due to the toxemia or allergic reactions to metabolic products of the worms.

EPIDEMIOLOGY

The infection is common in children than adults. The transmission is usually hand to mouth and via food and water. Infection is common in institutionalized children.

DIAGNOSIS

This is done by demonstrating characteristics eggs in the faeces.

PREVENTION AND CONTROL

Treatment of diagnosed cases and improvement of personal hygiene help to reduce the infection prevalence.

TREATMENT

Niclosamide is the drug of choice. The dose should be repeated after 10 days. Large number of persisting cysticercoids makes it difficult to obtain a radical cure. Other option is praziquantel, as it acts against both the adult worms and the cysticercoids in the intestinal villi.

CYSTICERCUS CELLULOSAE (Cysticercosis)

2008-11-30T19:28:00.000-08:00

GEOGRAPHICA DISTRIBUTION

This is common where Taenia solium infection is prevalent especially south and Central America, South and east Africa, India and former Russian Federation countries.

LOCATION IN HOST

Cysticerci may be found in any organ or tissue of the body as they carried by the blood stream on hatching of the onchosphere in the small intestine. Common sites are the brain, skeletal muscles, heart and the eye.

MORPHOLOGY

Cysticercus cellulosae (commonly called ‘bladder worm’) are ovoid white and measure 8*5 mm and are easily visible to the naked eye. Each Cysticercus cellulosae consists of a fluid filled bladder with a small protoscolex invaginated into the lumen. The protoscolex has four suckers and two rows of hooks (Cysticercus bovis of Taenia saginata has no hooks).

TRANSMISSION

Accidental ingestion of Taenia solium eggs which are passed in infected person’s faeces may take place via contaminated green vegetables, fruits or drinking water. Since about 25% of patients with Cysticercosis also harbour adult Taenia solium in small intestine it is possible that autoinfection takes place following regurgitation of segments or eggs into stomach. The eggs need to pass through the stomach, as gastric acid is responsible for the dissolution of the thick wall of the eggs. Infection may take place from anus to fingers to mouth.

PATHOGENESIS

This is related to the organ affected. Generally the cysts are distributed throughout the body roughly in proportion to the weight of the organ. The living cysts cause only mild symptoms unless the path of CSF flow is blocked (cerebral infection). Severe pathology is seen following the death of the cysts due to inflammatory reactions. Allergic manifestations due to leakage of fluid also occur.

CLINICAL FEATURES

The clinical presentation of Cysticercosis depends on the number and location of cysticerci as well as the extent of associated inflammatory responses or scarring.

Cerebral Cysticercosis; minors symptoms related to the Central Nervous System are common but the most serious manifestations are epileptiform fits. These seizures may be generalized, focal, or Jacksonian. Hydrocephalus results from obstruction of cerebrospinal fluid (CSF) flow by cysticerci and accompanying inflammation or by CSF outflow obstruction from arachnoiditis. Signs of increased intracranial pressure, including headache, nausea, vomiting, changes in vision, dizziness, ataxia, or confusion, are often evident. Cysticerci in different part of the brain could give rise to motor, sensory and psychological symptoms. The cysticerci may get calcified.

Muscle Cysticercosis; this is common site. They could sometimes be felt as nodules. Muscle cysts are usually more elongate than others. These cysts get calcified earlier.

Ocular Cysticercosis; The cysts lodged in the eye cause pain and blurring of vision. With time and with encapsulation these cause severe damage to the eye.

Cardiac Cysticercosis; in the heart the cysts can be found in the epicardium, myocardium and endorcadium.

DIAGNOSIS

There are different types of diagnostic methods are available. The method which should be employed depends on the organ system which is suspected be affected. Radiological, histological and serological tests are useful.

Radiological: X-rays are useful to demonstrate calcified cysts in muscles. CT scan is important to detect the cerebral Cysticercosis.
Histological: Palpable cysts in the muscles can be identified by following biopsy.
Serological: Several specific serological tests, including PCR are now available.

PREVENTION AND CONTROL

This is same as for Taenia solium. Improvement of sanitary habits and environmental hygiene are important.

TREATMENT

There is no specific treatment. Various drugs such as albendazole and praziquantel have been used. However, praziquantel can evoke an inflammatory response in the central nervous system. Niclosamide (2 g) is also effective but is not widely available.

The management of neurocysticercosis focuses primarily on symptom-based treatment of seizures or hydrocephalus. Seizures can usually be controlled with antiepileptics. If parenchymal lesions resolve without development of calcifications and patients remain free of seizures, antiepileptic therapy can usually be discontinued after 2 years. High-dose Glucocorticoids can be used during treatment or if symptoms worsen. Since glucocorticoids induce first-pass metabolism of praziquantel and may decrease its antiparasitic effect, cimetidine should be coadministered to inhibit praziquantel metabolism.

For patients with hydrocephalus, the emergent reduction of intracranial pressure is the mainstay of therapy. In the case of obstructive hydrocephalus, the preferred approach is removal of the cysticercus via endoscopic surgery. However, this intervention is not always possible. An alternative approach is initially to perform a diverting procedure, such as ventriculoperitoneal shunting. Historically, shunts have usually failed, but low failure rates have recently been attained with treatment with antiparasitic drugs, chronic administration of glucocorticoids, or use of flow-sensitive shunts. Open craniotomy to remove the cysticerci is now required only infrequently. For patients with subarachnoid cysts or giant cysticerci, glucocorticoids are needed to reduce arachnoiditis and accompanying vasculitis.

HYMENOLEPIS DIMINUTA (The rat tapeworm)

2008-11-30T19:27:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

This is a common parasite rats and mice in many parts of the world. It is an occasional accidental parasite of humans, particularly children.

LOCATION IN HOST

The worm is found in upper part of the ileum. It may move up or down as it is known in rats.

MORPHOLOGY

The worm measures about 300-600 mm* 4 mm. It has about 800-1000 segments. The scolex is small (0.2-0.4 mm). It has a retractable rostellum but no hooks. Four small suckers are also present on the scolex. The mature segments is broader than length and measures 0.75*0.25 mm.

The eggs are ovoid (60-80 µm) and have thick yellowish outer shells and thin colourless inner membranes. The intermediate layer appears granular. The embryo has three pairs of hooklets.

LIFE CYCLE

The adult worm is in the small intestine of rat which is the definitive host. Larval rat fleas ingest the eggs passed in the rat faeces. The embryo grows into a cysticercoid larva (cysticercus like) in the flea. When humans accidentally ingest the rat flea the released cysticercoid larva matures into an adult worm. Four beetles may also act as intermediate hosts.

PATHOGENESIS

Multiple infections are not uncommon. The scolices may damage the mucosa leading to inflammation. Frequent movements of worm may also cause pathology. Metabolic products of the worm mar also cause different clinical manifestations.

CLINICAL FEATURES

Most of the time patients are asymptomatic. Some patients may experience abdominal pain. High degree of clinical suspicious is needed for the diagnosis.

DIAGNOSIS

Demonstration of the characteristics eggs in the stool is the most reliable method.

PREVENTION AND CONTROL

Improvement of personal and environmental sanitation is important. Elimination of household rats helps to reduce the disease.

TREATMENT

Identification of the infected persons is very important. There are few treatments methods available. Praziquantel and Niclosamide can be used as treatment.

DRACANCULUS MEDINENSIS (Dracanculosis/ dracunculiasis/guinea worm disease)

2008-11-30T19:23:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The infection was, at one time, widely but patchily spread across tropical Africa, some parts of the Middle-east countries and India. The involved countries exerted a concerted effort in order to eradicate the infection by 1995. The program has been a success although sporadic cases still occur. The parasite also infects a wide range of animals particularly in North America. There are historical reports on the infection in South America.

MORPHOLOGY

It is a subcutaneous worm closely related to filarial worms. The female is long and appears as a long piece of twine (a piece of white coloured thread), about 60-100cm.The male is small and measures 2-3 cm.

LIFE CYCLE

The adult worms are found in humans (definitive host) while larval stages are found in the Cyclops (a water flea belongs to crustacean group) which is the intermediate host.

Male dies soon after fertilizing the female. The gravid female (uterus filled with larvae) migrates from its usual habitat in connective tissue (eg. Retro-periobital connective tissue) to areas of the skin which usually come in contact with water. As the head end approaches the surface of the skin, a blister develops. This causes intense burning pain. Infected persons tend to place their infected parts (eg. Foot) in water to get rid the pain. On contact with water the blister ruptures and the uterus of the worm protrudes through the ulcer. The contact with water is the stimulus for the uterus to discharge larvae into water.

The larvae (500-700µm) are swallowed by Cyclops. The larvae can live in clean water for about six days while it can last for nearly three weeks in muddy water. After two moults, the larvae develop into the infective stage inside the Cyclops (within2-4 weeks). When the infected Cyclops is ingested via drinking water the larvae penetrate the gut wall to reach suitable site. They become mature in about a year’s time.

Life cycle

PATHOGENESIS AND CLINICAL FEATURES

The adult worms living in the connective tissue of limbs and trunk cause minimal reactions. The blisters formed by migrating gravid females are commonly seen on the feet. They may appear around the knee joint in some and rarely around the scrotal area. In water carriers the blister may appear on the shoulder. A major pathology is seen after the worm dies when a sterile abscess is formed. Secondary infection often leads to inflammation and debility. The blister causes intense burning pain. Patients may experience itching, rash, nausea and vomiting with the appearance of blisters.

Few or no clinical manifestations of dracunculiasis are evident until just before the blister forms, when there is an onset of fever and generalized allergic symptoms, including periorbital edema, wheezing, and urticaria.

a ruptured blister

COMPLICATIONS

Complications include abscesses following secondary infection, arthritis, synovitis and abdominal symptoms due to adult worms migrating to the peritoneal cavity.

DIAGNOSIS

In endemic areas the clinical features are well known. Traditional way of diagnose this condition is by placing a drop of water on the blister or ulcer. This drop of water becomes cloudy due to the extrusion of larvae by the gravid female. A smear made on a slide will show the rapidly moving larvae.

EPIDEMIOLOGY

Although many animals are infected, the human infection is not considered a zoonosis as humans are the main reservoirs of the infection. Cyclops is a crustacean usually found in fresh water and some times in water storage tanks. Infected persons introduce larvae to water when the affected part of the body is immersed in water. Step wells played a major role in the transmission of the infection India.

PREVENTION AND CONTROL

The infection could easily be eradicated by improving drinking water supplies so that dependence on surface is removed. Boiling, filtering and chlorination of drinking water will remove Cyclops if they present in water. The insecticide ‘Temephos’ is an organophosphorus compound that is harmless to man that can be added to wells and storage tanks as slow release granules.

TREATMENT

The removal of the worm quickly is nit possible without chemotherapeutic support. The traditional way is to tie the anterior end of the worm to a stick or a matchstick and roll the worm out gradually over period of several days or weeks. Drugs such as Tinidazole, metronidazole and thiabendazole help with smooth extraction of the worm.

removing of an adult worm

TAENIA SOLIUM (Pork tapeworm)

2008-11-30T19:04:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The infection is prevalent in places where pork or pork products are eaten raw or under-cooked. It is common in East Europe, South and Central America, South Africa, China, India, Korea and Indonesia.

LOCATION IN HOST

The scolex is attached to the mucosa of the jejunum with the rest of the strobila in the intestinal lumen.

MORPHOLOGY

The scolex has a rostellum with two rows of hooks. The segments are similar to those of Taenia saginata. Mature segments are roughly square in shape. Gravid segments have less than 13 primary uterine branches as oppose to the Taenia saginata, which the number of uterine segments are more than 13.

LIFE CYCLE

Man is the only definitive host whereas pig is the only intermediate host. Life cycle is similar to that of Taenia saginata. The larval stage in the pig muscle is called Cysticercus cellulosae. Human infection occurs when pork containing Cysticercus cellulosae is eaten raw or under-cooked.

CLINICAL FEATURES

Clinical features are similar to those of Taenia saginata. Often the infection is asymptomatic except noticing whitish segments in faeces or experience of segments actively moving out of the anus. Vague abdominal symptoms such as pain, nausea, weight loss and anorexia may be present. In some the symptoms are relieved by ingestion of food.

COMPLICATIONS

Unlike in Taenia saginata, if an individual ingests eggs (usually accidentally) life cycle will continue as in the intermediate host, pig. Therefore humans can develop Cysticercosis, a complication due to the presence of pork worm larvae (Cysticercus cellulosae) in the skeletal muscles.

DIAGNOSIS

This is also similar to that of Taenia saginata.

The gravid segments passed in the faeces could be injected with Indian ink to show the lateral uterine branches of the uterus. In Taenia solium there are less than 13 primary branches of the uterus (compare with Taenia saginata).
If the scolex is passed following treatment, presence of hooks distinguishes it from Taenia saginata
If the gravid segments are ruptured eggs may be found in faeces (taenid egg).

EPIDEMIOLOGY

Prevalence of the infection is lower than that of beef tape worm infection. This is because some communities do not eat pork and in others when pork is eaten it is usually well cooked. While Taenia saginata infection occurs both in highly develop and developing countries, Taenia solium infection and its major complication, Cysticercosis, are prevalent in poor communities in which people live in close contact with pigs and eat improperly cooked pork. Uncooked or partially cooked pork products can transmit the infection.

PREVENTION AND CONTROL

Thorough cooking of pork is very important. Heating meat to 50ºC kills the cysticerci but those in the inside of large pieces may not reach the require temperature. At 0ºC the cysticerci can live for 70 days. Freezing at -10ºC for 4 days kills the cysticerci.

TREATMENT

A single dose of praziquantel (10 mg/kg) is highly effective. Niclosamide can also be given. The dose is 2gm for adults and lower doses for the children. The tablets are chewed and washed down with a little water.

TAENIA SAGINATA (Beef tapeworm)

2008-11-25T19:17:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

Infection is common in countries where beef is often eaten raw or under-cooked such as African countries, Brazil, Argentina, USA, former Russian federation countries and Europe.

LOCATION IN HOST

The worm is found attached to the mucosa of the small intestine (ileum) with its scolex. The rest of the worm is free in the lumen of the intestine.

MORPHOLOGY

They are flat, ribbon-like worms. Their bodies are formed of chains of segments (proglottids) of varying sizes and shapes. At the anterior end is the scolex or the ‘holdfast’ organ which is used for the attachment of the worm to the intestinal mucosa.

The scolex is 1-2mm and is pear shaped. There are four suckers on the scolex but no rostellum or hooks. The fully grown worm is exceptionally long, sometimes reaching 20 meters. Usually it measure about 5 meters and has about 1000-2000 segments. The mature segments measure approximately 12 mm wide and 10 mm long. In the mature segments both male and female reproductive organs are found. On the lateral margin are the genital pores, one on each segment. In gravid segments (the last segments of the strobila) the uterus occupies the whole space with primary and secondary uterine branches (twenty uterine branches at one side).

LIFE CYCLE

Humans are the only definitive host of the parasite and cattle are the only intermediate host.

The gravid segments are dislodged and are passed in the faeces of the infected person. The detached gravid segments also have their inherent movement and may actively move down the lumen and out of the anus and sometimes along the thighs.

When the segments are deposited on the ground the eggs are scattered on the soil. Eggs deposited on vegetation can live for months to years until they are ingested by cattle.

Eggs measure 30-45 µm. Each egg has an outer vitelline membrane which is usually lost in the faeces. The inner, thick wall is made up of keratin blocks and appears striated. This is called the embryaosphore. Inside is the embryo and now it is called the onchosphere. It has six embryonic hooklets and because of this it is also known as the hexacanth larva.

The egg when ingested by cattle, the onchosphere hatches out in the duodenum. With the help of the hooklets it penetrates the intestinal mucosa and enters the venous capillaries (or mesenteric lymphatics) within half an hour. Then they reach skeletal muscles. There they lose their hooklets and grow into infective cysticercus bovis larva in about 10-12 weeks. The infective cysticercus bovis is ovoid, white in colour and measures 8*5 mm. It has an invaginated scolex and four suckers but no hooks. Humans acquire the infection when infected beef containing cysticercus bovis is eaten raw or under-cooked.

PATHOGENESIS AND PATHOLOGY

The scolex does not cause much damage to the mucosa. Sometimes inflammation may be present. Several cases of intestinal obstruction and perforation have been reported. The symptoms are often due to metabolic products of the worm.

CLINICAL FEATURES

Often the infection is asymptomatic except noticing whitish segments in faeces or experience of segments actively moving out of the anus. Vague abdominal symptoms such as pain, nausea, weight loss and anorexia may be present. In some the symptoms are relieved by ingestion of food.

DIAGNOSIS

The diagnosis is made by the detection of eggs or proglottids in the stool. Eggs may also be present in the perianal area.

The gravid segments passed in the faeces could be injected with Indian ink to show the lateral uterine branches of the uterus. In Taenia saginata there are more than 13 primary branches of the uterus(compare with Taenia solium).
If the scolex is passed following treatment, the absence of hooks distinguishes it from the Taenia solium.
If the gravid segments are ruptured eggs may be found in faeces (taenid egg).

EPIDEMIOLOGY

This is common infection where beef consumption is high. Infection often occurs when cattle are young. Faeces containing eggs pollute pastures. The role of birds transmitting eggs from sewage to pastures is also possible.

PREVENTION AND CONTROL

Meat infection is the important public health measure. Cycticerci in muscle are usually killed when frozen at minus 10ºC for 10 days or heating thoroughly above 56ºC is also effective.

TREATMENT

TRICHINELLA SPIRALIS (Trichinosis/Trichinellosis)

2008-11-20T18:58:00.001-08:00

GEOGRAPHICAL DISTRIBUTION

The infection is seen in countries such as United States, countries of former Russian federation and Europe. It is rarely seen in tropics. It also occurs in east and west sub-Saharan African region.

MORPHOLOGY

The adult worms are small and measures 2-3mm (females) and 1-2mm (male).

adult Trichinella

LOCATION IN HOST

The worm is found embedded in the small intestine mucosa. The larval stages are also found in the same host. 9 example of man being both definitive and intermediate host)

LIFE CYCLE

Each female matures rapidly and following fertilization lays about 1500 larvae. The larvae make their way by way of lymphatics and the blood stream to reach striated muscles. Each larva enters a muscles fibre and converts it to a characteristic capsule called the ‘nurse cell’. Therefore the larvae can live for long periods. Later they usually get calcified. In humans the muscle phase is a dead end. When this happens in animals such as pigs and horses the meat becomes infective if not properly cooked. The muscle fibres entering the stomach are digested and the liberated larvae quickly gain entry into the small intestinal mucosa and mature rapidly into adult worms.

Life cycle

After about1 week, female worms release newborn larvae that migrate via the circulation to striated muscle. The larvae of all species except Trichinella pseudospiralis and Trichinella papuae then encyst by inducing a radical transformation in the muscle cell architecture. Although host immune responses may help to expel adult worms, they have little effect on muscle-dwelling larvae. Human trichinellosis is most often caused by the ingestion of infected pork products and thus can occur in almost any location where the meat of domestic or wild swine is eaten. Human trichinellosis also may be acquired from the meat of other animals, including dogs (in parts of Asia and Africa), horses (in Italy and France), and bears and walruses (in northern regions). Although cattle (being herbivores) are not natural hosts of Trichinella, beef has been implicated in outbreaks when contaminated or adulterated with trichinous pork.

Encysted larva

Encysted larvae

PATHOGENESIS

In mild infections, adult worms cause minimal pathology. They may cause inflammation and congestion of the mucosa with cell destruction. Major pathology is by larvae due to their presence in the muscle or due to their migration through the central nervous system and the heart.

CLINICAL FEATURES

Clinical symptoms of trichinellosis arise from the successive phases of parasite enteric phase, invasive phase (larval migration), and encystment phase (muscle encystment)

Enteric phase (invasion of the intestine): patients develop nausea, vomiting and abdominal pain resembling an attack of acute food poisoning.
Invasive phase (larval migration): This phase is characterized by severe myalgia, periobital edema and eosinophilia. CNS or myocardial complications may occur during this phase.
Encysment phase (Encysment of larvae in the muscle): Severe infection leads to cachexia, edema and dehydration. Gram negative septicemia due to organisms. introduced by larvae may occur.

DIAGNOSIS

History of ingesting undercooked pork is suggestive. Often groups of people are affected as following parties.

Blood eosinophilia develops in_90% of patients with symptomatic trichinellosis and may peak at a level of 50% between 2 and 4 weeks after infection. Serum levels of IgE and muscle enzymes, including creatine phosphokinase, are elevated in most symptomatic patients.

Muscle biopsy can be used to demonstrate the encysted larvae. A definitive diagnosis requires surgical biopsy of at least 1 g of involved muscle; the yields are highest near tendon insertions. The fresh muscle tissue should be compressed between glass slides and examined microscopically, because larvae may be overlooked by examination of routine histopathologic sections alone.

In early infection serology may be useful (ELISA, western blot, Enzyme immunoassay.)

EPIDEMIOLOGY

Eating of undercooked pork or sometime horse meat is responsible. Feeding pigs with dead or killed rats should be avoided. This is the major avenue of transmission of the infection to pigs by rats, which maintain the infection.

PREVENTION AND CONTROL

Proper cooking of all meat will eliminate the infection. Cooking of all garbage fed to pig will also help. Deep freezing pork at -18º to -15º C is effective.

TREATMENT

Current antihelmintic drugs are ineffective against Trichinella larvae in muscle. Fortunately, most lightly infected patients recover uneventfully with bed rest, antipyretics, and analgesics. Glucocorticoids like prednisone (1 mg/kg daily for 5 days) are beneficial for severe myositis and myocarditis. Mebendazole and albendazole, like thiabendazole, appear to be active against enteric stages of the parasite, but their efficacy against encysted larvae has not been conclusively demonstrated.

TRICHURIS TRICHIURIA (Whipworm)

2008-11-18T19:05:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

It is widely distributed in warm tropical climates such as South Asia, South East Asia and Africa.

MORPHOLOGY

Female worm is about 30-50 mm in length while the male is about 20-30 mm. The anterior 3/5^th of the body is thin while posterior 2/5^th is thick in both sexes. The posterior end of the male is curved.

LOCATION IN THE HOST

The worm inhabits the large intestine. The entire thin anterior end is threaded into the mucosa while the thick, short posterior end project into the lumen of the large intestine.

LIFE CYCLE

The female lays 2000-10000 eggs per day. The eggs have a characteristic ‘paddy seed’ shape, (50*20 µm) with ‘polar caps’. The eggs are passed in the faeces. They require a period of maturation in the soil. The optimal conditions are similar to those of Ascariasis. Because of this fact trichriasis often co-exist with Ascariasis. When infective eggs are ingested by humans the eggs hatch in the lower part of the small intestine and the larvae pass down into the large gut to mature into adults. The mode of transmission is similar to that of Ascariasis. But there is no pulmonary migration of larvae in trichuriasis.

PATHOGENESIS AND CLINICAL FEATURES

Light infections may be asymptomatic. Heavy infections lead to blood and mucous diarrhea. In children tenesmus and constant straining may lead to ractal prolapse. In some heavily infected children, the infection may result in ‘Trichuris Dysentry Syndrom-TDS’.There can be other clinical features as follows;

Trichuriasis and malnutrition; Both conditions can co-exist and it is difficult to determine a cause and effect. The infection shows a close correlation of the intensity of infection (worm load) and the severity of symptoms such as diarrhea, vomiting and rectal prolapse. TDS is generally seen with worm loads over 500 worms. The symptoms lead to lowering of food intake, which worsen the already existing malnutrition.
Trichuriasis and anemia; Anemia is a constant feature of heavy infection. It is hypochromic and microcytic. Anemia may be due to; blood loss from colonic mucosa: blood loss due to ingestion by worms. It is not certain whether Trichuris is a ‘blood sucker’. Few red cells are often seen in the intestine of the worm.
Growth retardation; This is a distinct association in trichuriasis. This is seen with even mild infections. This feature may be due to severe anorexia, nausea and vomiting associated with the infection.
Finger clubbing; this is another distinct association of the severe infection (TDS)

DIAGNOSIS

Diagnosis is by demonstrating the characteristic eggs in the faeces. A simple wet smear with saline/iodine is often sufficient. Concentration techniques such as formol-ether could be used. Foe quantitative studies Kato-Katz technique is good.

PREVENTION AND CONTROL

Vegetable that are usually eaten raw or undercooked should be washed thoroughly. Fruits fallen under trees should be washed before eating. Washing of hands after working with soil helps in the prevention.

Prevention of indiscriminate defaecation, provision of sanitary latrines, elimination of parasite reservoir by worm treatment and health education are important.

TREATMENT

Mebendazole (500 mg once) or albendazole (400 mg daily for 3 doses) is safe and effective for treatment.

ENTEROBIUS VERMICULARIS (Pinworm)

2008-11-18T19:01:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The parasite has a world wide distribution with a high prevalence in cold climates. This is not a soil transmitted infections.

MORPHOLOGY

The adult worms are small (1cm) with both ends pointed. Males have curved tail ends and are rarely seen. The ‘cervical alae’ extend right down the sides of the body so that in cut sections they are seen as two projections on either side of the body.

LOCATION IN HOST

The worm is found attached to the mucosa of the large intestine particularly the caecal area. They are not blood suckers.

LIFE CYCLE

A gravid female carries approximately 10,000 eggs in the uterus. These females migrate down the large intestine to reach the anus. This occurs during night. The female then lays the eggs on the anal verge. Following egg deposition the female dies.

The eggs are plano-convex in shape and have double walls (50*25 µm). The outer wall is albuminous and sticky. The embryos develop into infective larvae inside the eggs in 6 hours. When these eggs are ingested via contaminated fingers or via fomites they hatch in the lower part of the small intestine. The larvae move down to the large intestine to mature into adult males and females. There is no pulmonary migration of the larvae as in trichuriasis. Some infective eggs may hatch on the anal area and the larvae can move into the large intestine through the anus (retro-infection, a type of auto infection).

PATHOGENESIS AND CLINICAL FEATURES

The damage cause by the worm is not extensive. Some times they produce inflammation of the colonic mucosa leading to granulomatous condition. Complications include perforation of the gut (rarely) and migration to ectopic sites, commonest being into the female vagina. The moving females and the deposited eggs cause severe pruritus ani (itching of the anus). This may lead to loss of sleep. The infected children become irritable and may interfere with schoolwork.

EPIDEMIOLOGY

Since the lightness of the eggs, they are carried by wind and air currents. They are deposited on object found in the environment such as tabletops, doorknobs, chairs and seats. The infection makes no exception to any social class. It is a household infection and is highly prevalent where there is overcrowding such as in refugee camps, armed forces camps, prisons, hostels, orphanages etc. Generally one member of the family gets infected soon the all in the household acquire the infection.

MODES OF TRANSMISSION

Direct infection from the anal and perianal region by fingernail contamination ( a type of autoinfection).
Exposure and ingestion of viable eggs on soiled night clothes and other contaminated objects in the environment.
By way of contaminated dust from bed clothes, toys and furniture.
Retro-infection (see above)

DIAGNOSIS

Old methods include NIH (National Institute of Health, USA) swab and Graham’s Scotch Tape method. A simple ‘cello-tape’ strip can be used. The procedure should be carried out in the morning before washing the anal area or bathing. Precautions against contamination of hands of the examiner should be taken.

PREVENTION AND CONTROL

cut finger nails short
wash hands with soap and water regularly
avoid the scratching the anal region
treat every one in the household including boarders and servants ( in institutions all inmates including staff have to be treated at the same time)
Following treatment all bed linen and personal clothes should be washed and dried in the hot sun.
Mats and mattresses should be exposed to hot sun
Wet mopping of floors and surfaces should be done

TREATMENT

All affected individuals should be given a dose of mebandazole 100 mg,

Albendazole 400 mg, or pyrantel pamoate 11 mg/kg or maximum, 1 g, with the same treatment repeated after 10 to 14 days. Treatment of household members is also advocated to eliminate asymptomatic reservoirs of potential re-infection. But still it is very difficult to cure because it may be impossible to avoid re-infection.

STRONGYLOIDES STERCORALIS (The threadworm)

2008-11-12T19:49:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The parasite has a world wide distribution but more common in tropical and subtropical regions.

LOCATION IN THE HOST

It is found embedded on the mucosa of the small intestine

MORPHOLOGY

Only females are seen in the parasitic cycle (in the intestine of infected persons). These parasites measures 2-2.5 mm in length. In free-living cycle (outside the human body) both males and females are found. Free-living females are smaller and measure 0.95-1.5 mm in length. Males are smaller.

PARASITE

Strongyloides stercoralis is a unique parasite. It is the only nematode or helminth parasite that multiplies in the human body. A process known as ‘internal autoinfection’ accomplishes this. It differs from hookworms in that; no males in the parasitic cycle: no eggs are passed in the faeces but L1 rhabditiform larvae: internal and external autoinfection occurs when L1 larvae undergo accelerated development into rhabditiform L2 and then into L3 which is the filariform/infective larvae while moving down the intestinal tract: has a free-living cycle in the soil: may cause severe disseminated disease with larvae in vital organs in immunocompromised patients.

LIFE CYCLE

The parthenogenetic females lay eggs in the mucosa of the small intestine. Generally they have a low egg output per day. The eggs hatch in the mucosa itself and the L₁ rhabditiform larvae enter the lumen and are excreted in the faeces.

The subsequent development and the rate depend on the internal and the external conditions. When external conditions are unfavorable L₁ larvae rapidly develop into L₂ and to the infective L₃ larvae stage. The infective larvae develop into free-living males and females. The larvae produced by the free-living adults mature into free-living L3 stages. These larvae penetrate the skin of humans and once again start a parasitic cycle. The L3 larva of S.stercoralis differs from that of hookworms in; not having a sheath: having tri-radiate tip of tail.

PATHOGENESIS AND CLINICAL FEATURES

At the site of penetration of the skin, L3 larvae may cause ‘ground itch ( see hookworms). Pulmonary migration of larvae can cause lung symptoms and pneumonitis. But severe symptoms (as in ascariasis) are rare.

In mild infections, catarrhal enteritis is seen with increased amount of mucous secreted into the lumen. The mucosa is congested with hyperplasia of goblet cells with normal looking villi.

In heavy infections the villi become flattened and atrophied. Epigastric pain, nausea, anorexia and finally incessant diarrhea result.

In the hyperinfection syndrome seen in immunocompromised patients L₁ develop rapidly to infective L₃ stage, which penetrate the gut wall and enter the blood stream (internal autoinfection). Larvae in large numbers are carried into various organs resulting in serious damage to respective tissues. Organs and systems that can be damaged by larvae include brain, heart, pancreas, hepatobilliary system, lungs, genitourinary system and the skin.

In external autoinfection where L₁ larvae develop into infective stage in soiled clothes, bed linen or around the anal verge the migrating larvae produce a characteristic epigenous dermatitis starting in the per anal region extending rapidly to the buttocks and lower abdomen. This condition is called ‘larva currens’.

DIAGNOSIS

Diagnosis is difficult. Because of low fecundity female worms produce only small numbers of larvae and it is also not regular. In cases suspected of having strongyloidiasis, negative report on a single wet smear of faeces does not exclude the infection. Several samples over period of 3-7 days may be necessary to exclude the infection. In the faeces rhabditiform larvae are looked for. In old samples sometimes hookworm larvae may be found. Then, the larvae have to be distinguished from those of Strongyloides. Duodenal intubation or ‘entero test’ may be used to obtain larvae directly from the small intestine.

PREVENTION AND CONTROL

Avoidance of indiscriminate defaecation and use of footwear help in prevention. Provision of hygienic latrines, chemotherapy of infected people and health education are important in control of the infection.

TREATMENT

Even in the asymptomatic state, strongyloidiasis must be treated because of the potential for fatal hyperinfection. Ivermectin (200 µg/kg daily for 1 or 2 days) is more effective than albendazole (400 mg daily for 3 days, repeated at 2 weeks) and is better tolerated than thiabendazole (25 mg/kg twice daily for 2 days), whose common adverse effects include nausea, vomiting, diarrhea, dizziness, and neuropsychiatric disturbances. Because thiabendazole is not uniformly effective, stool examinations, eosinophil counts, and monitoring of clinical symptoms should be continued after treatment. For disseminated strongyloidiasis, treatment with Ivermectin should be extended for at least 5 to 7 days or until the parasites are eradicated.

NECATOR AMERICANUS & ANCHYLOSTOMA DUODENALE (Hookworms)

2008-11-12T19:39:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The parasite is widely distributed in the tropics and sub-tropics. In cold climates with suitable microclimates (such as in coal mines) the parasite may be found. Two species infect humans. Necator americanus is the species found in South Asia, Africa, pacific and in North and South America whereas Ancylostoma duodenale is the main hookworm of Eastern Europe, North Africa, India, Northern China and Japan. Both species can be found together in South East Asia, the pacific and West Africa.

MORPHOLOGY

The worms measure 1-2cm in length. The head ends of the worm are sharply bent backwards like a hook. In the case of N. americanus the buccal cavity bears a pair of ventral cutting plates used in biting the mucosa for feeding. A. duodenale is larger with the head end bending backwards smoothly. The buccal cavity has two pairs of curved teeth. In both species, the tail end of the male is flattened and expanded to form the copulatory bursa.

LOCATION IN THE HOST

The hookworms inhabit the small intestine of humans. Unlike Ascariasis it is attached to the mucosa of the intestine of the intestine with the buccal capsule.

LIFE CYCLE

Each female N.americanus lays about 3000-6000 eggs per day (A. duodenale lays about 10,000-20,000 per day). The eggs are oval in shape and have thin, glass-like egg-shells. The embryo is usually divided when the eggs are passed in faeces. On reaching soil and under optimum conditions the eggs hatch into L₁ larva within 24 hours. The optimum conditions are; shade, warmth’ moisture and sandy type soil.

L₁is an actively feeding rhabditiform larva (esophagus with a posterior bulb, like in the Rhabtid species).These larvae grow rapidly and moult on about the 3^rd day into L₂ rhabditiform larvae. On or about the 5^th day the second moult transform them into long, non-feeding L₃ infective or filariform larvae. These larvae have long, narrow esophagi and retain the cuticle of L₂as a sheath. The infective larvae move on to the topsoil and on to low vegetation seeking hosts. Under favorable conditions they remain alive for 3-6 weeks. When they come into contact with human skin, the activated larvae shed the sheath and penetrate the skin (usually between toes).

The larvae are carried in the blood or lymphatics and finally reach the lungs. They penetrate the alveoli and start ascending along small bronchioles to bronchi and then to trachea (unlike Ascariasis there are no moults in the lungs). At the pharynx they are swallowed. On reaching the small intestine the final moult transform them in to young males and females. The time taken between larval penetration and the formation of mature worms is 4-7 to weeks. Infective A.duodenale larvae ingested with contaminated food can establish in the intestine without undergoing lung migration. Ancylostoma is a unique parasite as it can go into a phase of ‘arrested development’ when the external conditions are not favorable and restart the life cycle when the conditions are good.

PATHOGENESIS AND CLINICAL FEATURES

In the acute infection the initial sings and symptoms are due to the penetration and migration of larvae in the skin. At the site of entry, a transient dermatitis with intense pruritus can result. This condition is called ‘ground itch’. The lesions may get secondarily infected. The lung migratory phase of hookworms is short and the pulmonary symptoms are either assent or minimum.

The pathogenesis of hookworm disease is directly related to the attachment of the worms to the mucosa. They attach to the mucosa by biting in plugs of mucosa (including 7-9 villi), which are stripped off the lamina propria. The pool of blood thus created is sucked in using the muscular pharynx. Only part of the sucked blood is used for food and oxygen, a large part being excreted continuously. This leads to blood loss and results in hypochromic, microcytic (iron deficiency) anemia. Each N.americanus sucks about 0.03 ml of blood per day while A.duodenale sucks about 0.26 ml per day.

The degree of anemia is related to the worm load and the nutritional status of the host. Hypoproteinemia seen in severe hookworm disease may be related to poor food intake (poverty, anorexia), impaired absorption, increased loss and a combination of all. Impairment of nutrient absorption, intestinal protein loss and lowered food intake collectively result in stunting (growth retardation). The pathogenesis of impaired mental and physical development in hookworm disease is not clear.

DIAGNOSIS

This is done by demonstrating characteristic eggs in the faeces. The eggs can be cultured into infective larval stage to distinguish between Necator and Ancylostoma.

PREVENTION AND CONTROL

TREATMENT

Hookworm infection can be eradicated with several safe and highly effective antihelmintic drugs, including albendazole (400 mg once), mebandazole (500 mg once), and pyrantel pamoate (11 mg/kg for 3 days). Mild iron-deficiency anemia can often be treated with oral iron alone. Severe hookworm disease with protein loss and malabsorption necessitates nutritional support and oral iron replacement along with deworming.

ASCARIS LUMBRICOIDES (The large round worm)

2008-11-09T19:19:00.000-08:00

GEOGRAPHICAL DISTRIBUTION

The worm has a world wide distribution but prevalence is high in warmer climates in tropical region where personal and environmental sanitation are poor. It is prevalent in countries like India, Nepal, Pakistan and Sri Lanka.

MORPHOLOGY

Adult female worms are 20-40 cm in length while the adult male worms measure 15-30 cm. The tail end of male is curved.

LOCATION IN THE HOST

The worms are found free in the lumen of the small intestine.

LIFE CYCLE

The fertilized female lays about 200.000 eggs per day. The eggs are oval in shape (65*45µm). The egg has an outer mammilated, ailbuminous coat that appears brown due to bile pigments. Some eggs may be decorticated (with outer coat missing). A certain portion of eggs (15%) is unfertilized and appear longer and rectangular (90*40µm) with no embryo. The embryo is unsegmented when eggs are passed in faeces.

The eggs develop further in soil with the first moult taking place (within the egg) to form the 1^st stage larva in about 7 days. With the second moult the infective 2^nd stage larva is formed inside the egg in 2-3 weeks under optimal conditions of development such as moist, warm (25-30 ºC) clay type soil. The infective eggs can remain viable in suitable soil for long periods of time.

When ingested the eggs hatch in the upper part of the small intestine liberating the larvae which penetrate the intestinal mucosa to enter the blood stream (or the lymphatics). The larvae are carried into the lungs via the liver and the heart. The larvae develop further in the lungs moulting twice (5^th and 7^th days). They penetrate the alveolar walls to move along the bronchioles, bronchi and trachea and are swallowed. On reaching the small intestine they mature into males and females. The time taken for an egg to develop into a mature is about 60 days. Adult worms may live up to 2 years.

PATHOGENESIS AND CLINICAL FEATURES

Many infected persons remain asymptomatic. However the presence of a small number of worms may lead to complications. The pathogenesis and clinical features can be categorized into; pulmonary ascariasis: intestinal ascariasis: complications of ascariasis and allergy to Ascaris species.

Pulmonary ascariasis: An intense host reaction occurs in the lungs as a result of larval migration, 5-6 days after the ingestion of infective eggs. Larval antigens released by moulting larvae elicit an inflammatory reaction associated with moderate eosinophilia, pneumonitis, bilateral pulmonary infiltration, cough, dyspnea, substernal pain, fever, skin rashes and often asthma. These signs and symptoms are collectively called the “Loffler’s Syndrome”. The severity of the host reaction depends on the number of larvae migrating and the previous infection history: hypersensitive individuals show severe reactions with other allergic manifestations. Loffler’s syndrome is usually transient, lasted about 2-5 days. Pulmonary pathology is primarily immunological in nature.
Intestinal ascariasis: Adult worms in the small intestine may cause mild abdominal pain and restlessness. Some asymptomatic persons are known to be harbour large worm loads. However, the clinical consequences of the infection are generally dependent on the number of worms present (worm load). It is difficult to say whether ascariasis is a direct cause of malnutrion as the infection is common in areas where malnutrion co-exist. But the infection certainly precipitates severe malnutrition (even kwashiorkor or marasmus) in undernourished children. Ascariasis as also known to lead to vitamin A deficiency. Improvement of growth in areas where protein energy malnutrition is prevalent has been demonstrated following worm treatment. Similarly worm treatment has been shown to improve physical fitness and educational abilities of malnourished children.
Complications of ascariasis: The commonest complication of ascariasis is intestinal obstruction, particularly in persons with heavy worm loads. They may also cause intestinal perforation leading to peritonitis. Adult worms may wander into orifices such as the opening of the bile duct, pancreatic duct causing obstruction bile and pancreatic secretion respectively. Some drugs, chemicals and food items may cause worms to get abnormally activated and migrate to distant site.
Allergy to Ascaris species: Allergic manifestations are common during the acute phase of larval migration and due to the presence of adult worms in the small intestine. Many allergic and infected persons experience asthma. The relationship of asthma, allergy and ascariasis is not clearly known. However it is well known that adult Ascaris worms are highly allergic and their handling may cause serious reactions in sensitive individuals.

DIAGNOSIS

The simplest diagnostic method is the demonstration of characteristic eggs in the faeces.

PREVENTION

CONTROL

Prevention of indiscriminate defaecation, provision of sanitary latrines, elimination of parasite reservoir by worm treatment and health education are important.

TREATMENT

Broad spectrum antihelminthetic drugs like albendazole and mebandazole can be used. Usual drug course is 500mg stat for adults and the dose for children depends on the weight and the age.

MEDICALLY IMPORTANT MOSQUITOES

2008-11-06T19:06:00.000-08:00

INTRODUCTION

Mosquitoes are the most important group of insects. They are important as vectors of human diseases. In addition they cause a considerable biting nuisance to man. Mosquitoes are found world wide with over 3000 species included in 34 genera, distributed from the tropics to the arctic regions. However, the medically important species belong to only a few of these genera.

MORPHOLOGY

These are small slender flies with one pair of wings; forwardly projecting mouth parts; scales covered the body, legs and wings. The body is divisible to head, thorax and abdomen. The head bears the characteristic mouth pars suited for piercing and sucking. The mouth parts are collectively called the proboscis. It consists of a labium (lower lip), a labrum (upper lip) enclosing two pairs of cutting apparatus (mandibles and maxillae) and a stylet (hypopharynx) through which the salivary duct opens. The food channel is formed the labrum and the hypopharynx. The head bears a pair of palps and long segmented antennae. In the female the antennae have only few hairs, while in the males they are bushy and feathery. Internally trilobed salivary gland is situated ventrally in the thorax. Powerful flight muscles are also present in the thorax. The body cavity (hemocele) is bathed in fluid.

LIFE CYCLE

Only female mosquitoes suck blood, while the males thrive on plant and fruit juices. The blood meal is essential in providing nutrients for the maturation of eggs. The time taken from the blood meal to oviposition is referred to as the gonotrophic cycle (2-3 days in the tropic). The life cycle has a complete metamorphosis with egg, larva, pupa and adult stage.

I. EGG: A female mosquito carefully selects the breeding site, each species having its own preferred habit, 100-200 eggs are laid at a time on water or moist surface, either singly or in batches. Eggs hatch in around 2-5 days.

II. LARVA: Larvae are legless with prominent thorax. It is actively feeding with four larval stages (7-14 days). Larvae breathe air through spiracles found in the posterior ends. In general almost any collection of permanent or temporary water can be a larval habit, but larvae are not found in large expanses of water such as lakes and in fast flowing rivers (except at margins).

III. PUPA: They are ‘comma’ shaped with a large cephalothorax (fused head and thorax). Although non-feeding, they show active movements. Pupal stage lasts 2-3 days.

IV. ADULT: They emerge by splitting the pupal skin. In the tropics adults live for 2-3 weeks but in colder climates they live much longer.

ADULT BEHAVIOUR

Mosquitoes are rather selective in their choice of hosts for their blood meals. Some species prefer human blood to animal and are called anthropophilic while others feeding only on animals are termed zoophilic. The biting and resting behavior of adults are important in the epidemiology of disease transmission.

Medically important mosquitoes can be divided into two groups;

Anophelines
Culicines

ANOPHELINES

MORPHOLOGY

Length of the Palps of the females is equal to the length of the proboscis whereas palps of the male are clubbed in shape. Adults usually rest with body forming an angle to the resting surface. Larvae lie parallel to the surface of water with the help of palmate hairs on the abdomen. They do not have siphon tubes. Eggs are laid singly and usually have floats.

THE GENUS ANOPHELES

The genus Anopheles is the only mosquitoes that are medically important among Anophelines. Anopheles is the only known vectors of human malaria. In some countries they transmit Filariasis (Africa and SE Asia), and viruses as well (Africa).

Anopheles has world wide distribution. The genus contains about 400 species, but only about 30 species are efficient natural vectors of human malaria. Natural susceptibility of Anopheles to human malaria is largely unexplained. The frequency of feeding on man, mosquito density and longevity are some features of importance in determining the efficiency of a vector in nature. Further, the habits of a given species vary from country to country. Thus a particular species may be an important vector in one area and not in another.

Anopheles is crepuscular (around sunset) or nocturnal in habits such as mating, blood feeding and ovipositioning. They are generally not found at altitude above 2000-2500 m.

Anopheles culicifacies, Anopheles subpictus, Anopheles minimus, Anopheles vagus, Anopheles maculates and Anopheles annularis are some members of the genus Anopheles. They all are vectors of human malaria but distribution varies. Anopheles culicifacies is the only malarial vector in Sri Lanka whereas others are found as vectors in Africa.

Anopheles culicifacies

This is an important malarial vector in Sri Lanka, Pakistan, Bangladesh, India and Nepal. Adults are small or medium in size with characteristic light and dark spots on the wing margin; the palps are branded .Resting position is ‘culicine’.It breeds in small collections of clean, sunlit water: in slow running streams or rain water collections in clayey or sandy soil (eg. Sand pool/rock pools in riverbeds; hoof marks; cart tracks; gem pits).This is not usually found breeding with other species expect with An. Subpictus. Eggs are laid singly with floats.

Biting habits: feeds readily on man and cattle; indoor and night biter; enters houses at dusk and rests indoors after a blood meal. Thus principal control measure is the spraying of residual insecticide on walls.

CULICINE MOSQUITOS

MORPHOLOGY

Length of the palps of the females are much shorter than that of proboscis and palps of male are pointed ( not clubbed).Adults usually rests with body parallel to resting surface. Larvae hang down from water surface and have siphon tubes. Eggs may be in clusters or singly but do not have floats.

Culicine mosquitoes include around 30 genera of which the medically important ones are Aedes, Culex, Mansonia and Armigeres.

AEDES

Aedes are world wide distribution extending up to the Arctic Circle where they are a serious biting nuisance to man during summer months. However their major medical importance is as vector of arboviruses. Aedes aegipti and Aedes albopictus are members of this family.

Aedes aegypti & Aedes albopictus

The adults are small, dark, delicate mosquitoes. They have patterns on their thorax due to silvery/white scales. Legs are banded, but wings are clear. Eggs are laid singly on damp surfaces just above water level and can withstand desiccation for long periods.

Aedes aegypti is recognized by the characteristic markings on the dorsum of the thorax (two curved lines enclosing two straight lines), while Aedes albopictus has a single line.

Aedes aegypti is a domestic mosquito common with urbanization. It is a container breeder laying eggs in rain water collections in discarded tin cans, coconut shells, tires and also in vegetation such as leaf axils, bamboo stumps, etc. it even breeds indoors: in flower vases and ants traps.

Aedes albopictus is a less urban species and they breed outdoors. Adults are day bitters, both indoors and outdoors. Larvae have short barrel shaped dark siphon tubes.

These two species are medically importance as they are the vectors of many diseases. Dengue, Chikungunya, Filariasis (Dirofilaria ripens) and yellow fever are the some importance diseases transmitted by these mosquitoes.

CULEX

These mosquitoes are importance as vectors of Filariasis and arboviruses. Culex quinquefasciatus, Culex fatigans, Culex tritaeniorhynchus, Culex gelidus, Culex fuscocephala and Culex pseudovishnui are some importance members of this group.

Culex quinquefasciatus

It is a very common urban mosquito throughout the tropics. It is the most important vector of Bancroftian Filariasis. Adults are small brown mosquitoes without any prominent markings. Adult female is a night biter, both indoors and outdoors and it is highly anthropophilic. Following the blood meal, rests on the clothes and dark places, under furniture or if outdoors in the shade.

It breeds in polluted, stagnant water with high organic content (eg. Catch pits of bucket latrines, cess pools, blocked drains, gutters and septic tanks). Eggs are long, cylindrical, laid upright on water surface and place together (300) to form rafts. Larval siphon tube is usually long.

Other Culex species

Culex tritaeniorhynchus, Culex gelidus, Culex fuscocephala and Culex pseudovishnui are important vectors of Japanese encephalitis.

Culex gelidus breeds in water containing much organic matter such as husk pits and muddy ground pools.

Culex tritaeniorhynchus breeds in clear water habits specially paddy fields and marshes. These mosquitoes are late evening outdoor biters and are principally bird and animal feeders. However, they readily bite man on contact.

MANSONIA

They are principally found in wet tropical areas. They are important as vectors of Brugian Filariasis in South and South East Asia. Mansonia uniformis and Mansonia annulifera are some important members of this group.

Body, legs and wings of adults are covered with light and dark, broad asymmetrical scales. This gives characteristic speckled appearance. Adults are night biters mainly outdoors but they are known to enter houses. Eggs are dark, cylindrical and laid in a mass on under surface of floating vegetation (eg. Pistia, Salvinia). Eggs cannot withstand desiccation. Larvae are characteristic, found attached to aquatic plants with their siphon tubes to obtain air. The siphon tubes are conical, dark and possess serrations. Pupa is also attached to roots of plants with the respiratory trumpets.

ARMIGERES

This is a very common group of mosquitoes and is found in everywhere. It brings considerable biting nuisance.

Armigeres subabatus

This is a member of Armigeres group and they are found in urban areas. It is not known to transmit major pathogens in nature. However, evidence suggests that it transmits Dirofilaria ripens. Adults are dark, medium sized with prominent banded abdomen and a bent proboscis. It breeds in polluted collections of water in urban situations.

TUMOUR SUPPRESSOR - p53

2008-11-04T19:13:00.000-08:00

INTRODUCTION

p53 has a short history starting from 1979. Arnold Levine, David Lane, and Lloyd Old, working at Princeton University, Imperial Cancer Research Fund (UK), and Sloan-Kettering Memorial Hospital respectively were the scientists who identified this protein

p53, the “guardian of the genome,” is a sequence-specific transcription factor whose activity is regulated through tight control of p53 protein levels. This transcription factor is encoded by the gene called TP53.p53 implies that its mass is 53 kDa but its actual size is smaller than that and it is about 43.7 kDa. This is due to the high content of praline amino acid in the p53 protein.

Gene responsible for the production of p53 is located in the short arm of the chromosome 17.Activity of the p53 depends on its concentration therefore the concentration is kept under tight control. Normally, levels of p53 are kept low by its association with the mdm2 oncogene product, which binds p53 and keep it away from the nucleus for proteolytic degradation. If there is any stimuli which can damage DNA such as irradiation, p53 will be phosphorylated by several kinases. This will regulate the DNA damage check point. This causes dissociation of p53 from mdm2, leading to increased p53 protein levels. This activates transcription of genes leading to cell cycle arrest (p21^Cip1/Waf1) or apoptosis.

STRUCTURE

Human p53 has 393 amino acids and it consists of seven domains.

Activation domain1 activates transcription factors: residues 1 to 42.
Activation domain 2 has the apoptotic activity; residues 43 to 63.
Proline rich domain is also important for the apoptotic activity of the p53: residues 80 to 94.
DNA core binding domain (DBD) is the central portion of the protein and it contains one Zn atom and several arginine amino acids : residues 100 to 300
Signaling domain : residues 316 to 325
Oligomerisation domain : residues 307 to 355
C-terminal domain is involved in down regulation

FUNCTIONS OF p53

This transcription factor has many functions. The main objective of all those functions is to ensure the maintenance of physiologically normal cell cycle thereby prevention of the occurrence of malignancies. Main functions are;

Activation of DNA repair system
Recognition of DNA damage
Initiation of apoptosis

p53 AND DISESSES

p53 plays a significant role in occurrence of many genetic and acquired diseases. p53 is a transcription factor encoded by a gene whose disruption is associated with approximately 50 to 55 percent of human cancers.p53 can be damaged either by genetically or by environmental causes ( chemicals, irradiation or viruses).

Damage to the gene which encodes p53 can lead to development of many childhood tumours. Li-Fraumani syndrome is a condition which occurs due to the some derangement in the TP53 gene. Human Papiloma Virus is a known virus which can damage TP 53 gene therefore it can make the person more vulnerable for carcinoma of the cervix.

RECENT DEVELOPMENT

There are thousands of researchers going on to describe the value of p53 in cancer management. The present invention relates to a new method for the treatment of cancer. More particularly, it relates to a method of treating cancer by regulating the cellular levels of the p53 protein. It also relates to vectors for gene therapy which make it possible to regulate the p53 protein, as well as the pharmaceutical compositions containing them.

MEDICALLY IMPORTANT SNAKES

2008-11-02T20:43:00.000-08:00

INTRODUCTION

Snakes are elongate limbless reptiles, with bodies that are covered with scales. They are medically important because the bites of some snakes can cause systemic poisoning. Basically there are two types of snakes found; sea snakes and land snakes. The land snakes include the elapids, vipers, colubrids, earth snakes, water snakes and constrictors. Depending on the degree of toxicity to man, poisonous snakes are classified as deadly venomous, moderately venomous and mildly venomous. Usually sea snakes, elapids and vipers are deadly venomous, but some vipers are only moderately venomous. Colubrids are mildly venomous or non-venomous. Constrictors, water snakes and earth snakes are non-venomous.

POISONOUS OR VENOMOUS SNAKES

All venomous snakes possess a pair of venom producing glands and maxillary teeth called “fangs” which inject venom into the prey. The venom glands lie below and behind the eye, one on each side .Two types of venom glands are found;

True venom glands: These are found in elapids, sea snakes and vipers. It is a large gland and the fangs are situated anteriorly.
Duvernoy’s gland: These are found some colubrids. It is a small gland situated posteriorly and venom is injected through a posterior fang. Snakes with well developed Duvernoy’s glands and posterior fangs are mildly poisonous.

FANG:

It is a curved maxillary tooth modified to conduct and inject venom, either by having a posterior groove (closed or open) or a central canal. Sea snakes and elapids have anterior fixed fangs (proteroglyphous) while vipers have movable fangs (solenoglyphous) which are kept folded backwards when the mouth is closed. Snakes with Duvernoy’s glands and posterior fans are termed back fanged (opisthoglyphous) snakes.

SCALATION:

The arrangement of scales is termed scalation. This is important in identification of snakes.

Head; Scales on the head may be equal and smaller in size or some may be enlarged. Enlarged head scales are called shield.

Body; Scales on the top midline of the body are called vertebrals and scales on the lateral and under side are called costals and ventrals respectively.

Tail; the segment between the anal verge and the posterior end of the snake is the tail. Dorsal scales of the tail are called caudals and ventral scales of the tail are called subcordals ( uniserial or biserial)

IDENTIFICATION FEATURES AND HABITS

1.SEA SNAKES

All sea snakes are venomous, but reports of envenomation in man are rare. Sea snakes are well adapted for life in the sea. They have a characteristics tail which is laterally flattened and rudder-like (allows movements in the water) while body is dorso-ventrally flattened. Sea snakes are found in coastal waters and river mouths, but they can also be found swimming several miles upstream in rivers.

Pelamis platurus (Yellow bellied sea snake)

This species is thought be the commonest sea snake. It needs to be differentiated from eels, which are gill breathing fish with cylindrical bodies and pectoral fins

2.ELAPIDS

Elapids are slender snakes with long tails. The head is spatula-shaped (spoon shaped) with no distinct neck. Some are oviparous (lay eggs) whilst others are viviparous (lay young). Scales on the dorsum of the head are enlarged. Vertebrals are also enlarged. Subcordals are single (Uniserial). Common elapids are;

I. Cobra

II. Ceylon krait

III. Common (Indian) krait

IV. Ceylon coral snake

2.1) Cobra (Naja naja)

The cobra is one of the largest elapids. Average length is one meter. This snake is commonly found in South Asian countries. It is easily recognized by the characteristics “hood” which is a loose fold of skin below the head. On the dorsal surface, the hood bears a spectacle marking, while there are two black spots on the ventral aspect in the Sri Lankan Cobra. Colour varies from very dark brown, black or olive to light reddish brown. It is a diurnal snake, living near human habitation. These are slow moving and generally not aggressive. On provocation it erects the forebody off the ground, spreads its hood, hisses, sways from side to side and strikes. The striking radius depends on the raised forepart. This is deadly venomous snake. Young cobras are very irritable and aggressive. Female lays eggs.

2.2) Ceylon Krait (Bungarus ceylonicus)

This is the smallest of the known kraits. It measures up to one meter. It possesses the general features of elapids and in addition it has some characteristic markings. It is a dorsally black snake with single wide white band bands on the body which continues onto the belly. Generally they are found in the wet and intermediate zones. They are nocturnal, sluggish and inoffensive. It usually lives in and around human dwellings. The victim is often bitten during sleep. This is deadly venomous snake. The female is oviparous.

2.3) Common (Indian) Krait (Bungarus caeruleus)

It is a fairly long snake (average length about 140 cm).It is a shiny blue black snake with narrow white double bands on the dorsum. The belly is clear white. It is highly poisonous and nocturnal in habits. They are usually found in dry zones and very closely associated with human dwellings. The female is oviparous.

2.4) Ceylon coral snakes (Calliophis melanarus)

It is a small slender snake, which has a head, neck and body of uniform width. Average length is about 30 cm. Head and tail is black in colour. The colour of the body is yellowish brown with orange coloured spot near the vent. This snake is nocturnal in habit. It spends most of the day underneath fallen leaves and tree trunks .Recorded human bites are very low.

3.VIPERS

All vipers possess true venom glands with movable fangs. They have thick bodies with short tails. The head is triangular with a distinct neck (viperine head). Head scales are usually small and equal in size. Generally females lay young.

Vipers can be divided into two groups on the presence or absence of a pit, the loreal pit, which is located on the each side of the head between the nostril and the eye. The loreal pit is a thermoreceptor which can detect warm blooded prey in the dark.

3.1) True vipers (pits are absence)

I. Russell’s viper

II. Saw scaled viper

3.2) Pit vipers

I. Green pit viper

II. Hump nosed viper

3.1) True vipers

3.1.1) Russell’s viper (Vipera russelli)

This is the largest viper found in Sri Lanka, measuring up to150 cm. It is easily recognized by its characteristic markings, viz. three rows of chain like markings along the length of the body. In addition it has an inverted ‘V’ mark on the dorsum of the head. Colour varies from grey-brown to reddish-brown. It is mainly nocturnal in its habits. During the day it remains concealed in the undergrowth, coiled up with its head lying in the centre of the coil. The Russell’s viper strikes man only on provocation. When it is provoked, the tongue quivers, the head is raised, the body sways rhythmically and the snake hisses loudly and continuously. When it strikes it does with force and determination, throwing itself violently at the victim. It is found all climates, especially in the dry zones. The female is oviparous.

3.1.2) Saw-scaled viper (Echis carinatus)

It is a small viper. The average length is less than 50cm. It has a rough appearance due to the presence of saw-edged scales on the body. When the snake moves the scales rub against each other, to produce a sound almost like continuous hiss. It has a characteristic mark on the head which is described as a bird’s foot or a cross. The colour is known to vary to merge with the colour of the surroundings. Usually colour is sandy with dark blotches. It is nocturnal in habits. It is commonly found in sandy costal areas. Fatal bites are not reported commonly. The female is oviparous.

3.2) Pit vipers

3.2.1) Green pit viper (Trimeresurus trigonocephalus)

The green pit viper has a large broad flat triangular head with a loreal pit. It grows up to about 130 cm. It is dorsally blue green with black markings from head to tail. Usually it is arboreal and appears to be active during the day and night. This snake is widely distributed and found up to about 6000 feet elevation.

3.2.2) Hump nosed viper (Hypnale hypnale)

The hump nosed viper has a viperine head with enlarged head scales. Its snout is actually pointed and turned up. Average length ranges from 30 to 40 cm. This snake is highly variable in colour. The most commonly dorsal aspect is brown with darker markings. It is a nocturnal snake which hides under leaves and stones during the day.It are a common snake and widely distributed, but commoner in plantation districts. Fatal bites are uncommon.

4.COLUBRIDS

Colubrids are a commonest type of snakes found everywhere. The members of this family show a wide range of diversity and adaptation to different habitats. The majority are ground dwellers while others are arboreal, aquatic or burrowing. In contrast to the elapids the vertebral are not enlarged. Subcordals are usually divided or biserial. Most of the colubrids are non-poisonous. There are a few which are mildly poisonous. These mildly poisonous snakes are back fanged with grooved fang.

4.1) mildly poisonous colubrids

I. Cat snake

II. Whip snake

III. Water snake

IV. Sri Lanka keel-back

V. Flying snake

4.2) non-poisonous colubrids

I. Rat snake

II. Ceylon wolf snake

4.1) mildly poisonous colubrids

4.1.1) Cat snake (Boiga forsteni)

The head is more or less triangular in shape with a distinct neck. Head scales are enlarged. The cat snake can be wrongly identified as a hump-nosed viper but it can be differentiated by the absence of a loreal pit and a humped snout. Colour varies from light brown to reddish brown. They are nocturnal in habits and mainly arboreal.

4.1.2) Whip snake (Ahaetulla nasuta)

The head is narrow and elongated. The body is log and slender. The tail is long and cylindrical. It grows to a length of 190cm. It is an aggressive, fierce snake that darts at the eye, hence its name (Eye puckers). The common species is dorsally green in colour, with a pale yellow belly. Brown coloured species are also found. It is a diurnal snake, commonly found in low shrubs and hedges. It is found up to an altitude of 15000m.

4.1.3) Water snake (Cerberus rhynchops rhynchops)

It is common aquatic snake, with average length of about 60 cm. Dorsally it is grayish or chocolate brown with short dark bars broken up into spots. It is usually quiet and inoffensive but on provocation hisses, bites and produces a strong odour per anum. It is commonly found in costal areas, especially lagoons, streams and rivers.

4.1.4) Sri Lankan keel back (Ahara kukka)

It is an uncommon snake and is found mainly in hill country. It has a small head with large eyes. It is slow moving snake, found under decaying logs and leaves. It is reddish brown with a white or yellow belly.

4.1.5) Flying snake (Golden tree snake)

It is an uncommon snake. It is arboreal and it can glide and is fast moving. It bites fiercely. It is brightly coloured beautiful snake .It is diurnal in habits. It is found in wet and dry zones up to 460m.

4.2.1) Rat snake (Ptyas mucosus)

These are the largest among the Sri Lankan colubrids, some reaching a length of 8 feet. They are characterized by dark-edged scales, colour variable, dorsally olive green to olive brown. Some have a yellow belly. These are diurnal, fast moving. Commonly found almost anywhere, especially in jungle tracts or paddy fields. It is also found ceilings of houses.

4.2.2) Ceylon wolf snake

It rarely exceeds 2 feet in length. Colour is variable dorsally brown or purplish with a series of whitish to yellow bands. These bands are similar to those of the Ceylon krait, but in the wolf snake. The vertebrals are not enlarged.

5.CONSTRICTORS

They are a group of large snakes and non-venomous. They crush their prey.

I. Python

II. Sand boa

5.1) Python

The python is the largest of Sri Lankan snakes. It has characteristic quadrate markings on the dorsal surface. It feeds mainly on birds and mammals.

5.2) Sand boa

It is smaller than the python, being about 3 feet in length. Body colour is yellowish, brownish or grayish, with a series of large dark brown, black edged dorsal spots, usually confluent with one another.

6.EARTH SNAKES

Primitive snakes live under the soil. They are Timid and harmless. Some are blind and very small (about 4 inches in length) while others like the pipe snake could be 2 feet in length. The body scales are smooth.

7.WATER SNAKES

They are aquatic snakes which inhabit rivers, river mouths and coastal waters. They are completely adapted to aquatic life. They are unattractive and sluggish, with rough body scales. They are nocturnal and feed on fish. If they are handled roughly, the sharp teeth can inflict deep wounds.