CHILDHOOD AUTISM – Definition and General Characteristics

The term autism denotes a state of absorption into ones own world of phantasy with loss of contact with the reality. Reported incidence of childhood autism is 2-5/10,000 live births.

 Childhood autism was originally described by Leo Kanner in 1943 as Early Infantile Autism. Autistic aloneness, language abnormality and restricted and compulsive behavior are the main three features of this disorder. Boys are more affected than girls. The disorder is unmasked by the third year of life. The child is abnormally quiet, lacks the usual emotional warmth and likes to be left alone. Eye-to-eye contact is avoided. He does not communicate through conversation. Pronouns are reversed. ‘You’ is used to mean ‘I’ Echolalia is common. Words and behavior are stereotypic. The child is fond of sameness in everything. Bizarre behavior such as rocking, whirling the head and flapping of hand may be present. Impulsive violence is common. The arithmetic skill is relatively high. IQ may be around 70 in most cases. Some have normal IQ. Many cases may be attributable to birth trauma. Autism is strongly a genetic disorder, and probably arises from multiple genetic defects. Recurrence within families with one affected child is high.

There is no specific treatment. Antipsychotics are given to control violence and hyperactivity. Behavior therapy may be helpful. Parents are to be counseled regarding management of the child at home. Many improve spontaneously and may be able to attend normal school. A few may require training in special schools. Some require special residential care.

CHIKUNGUNYA – Etiology, Distribution and Incidence, Transmission and Epidemiology, Clinical Features, Course and Prognosis, Diagnosis, Treatment, Prevention and Control

General Characteristics

Chikungunya (CHIK) fever is an acute infective disease, characterized by symmetric polyarthropathy, fever, rash, and rarely, generalized hemorrhages and CNS symptoms. The disease derives its name from the sudden onset of severe joint pain, which cripples the victim. The disease was first described in 1955 following an outbreak in Africa in 1952.

Etiology

CHIK virus is an alphavirus in the Semliki Forest complex (Togaviridae) and most closely related to o’nyong nyong(ONN) virus.

Distribution and Incidence

CHIK is widely distributed in Africa, the middle east, and Asia. The disease has now become endemic in several parts of India. In recent years as extensive epidemic affected several African and Asian countries, affecting millions of people. It is possible that the original virus has undergone genetic mutation.

Transmission and Epidemiology

In India, Aedes aegypti mosquito is the main vector. Aedes albopictus is also implicated. In Africa there is a sylvian cycle involving forest mosquitoes, humans and possibly other mammals. In Asia, sylvatic viral reservoirs have not been defined.

CLINICAL FEATURES

The incubation period varies from 2-10 days, usually 3-7days. The onset is sudden with abrupt fever (above 40oC), chills and rigor, headache,  body pains and joint pains. There may be mild conjunctivitis, pharyngitis an erythematous rash over the body and face. The joints may be so inflamed that normal activities, standing and walking become painful. Arthropathy is symmetric, affecting the extremities and less often the shoulders and hips. Definite joint effusion is seen in 10% of cases. Small joints of the hands and feet and major joints of the lower limbs are affected most. Pain may be excruciating, crippling the patient quite out of propotion to the general disability. Fever and joint pains persist for up to six days after which they subside. Residual arthropathy lasting for months may occur in up to 30% of adults; especially in elderly patients. Morning stiffness and pain may persist for even a few months. Pre-exsisting joint problems and neurological disorders considerably worsen the disability and delay recovery. Joint pains are milder and may be even entirely absent in children.

A faint maculopapular rash may appear concurrently with defervescence. Complications such as hyperpyrexia, hemorrhagic manifestations, encephalitis, polyneuropathy of the Guillain-Barré type and ECG chages suggestive of myocarditis were recorded in the Madras outbreak. Hyperpyrexia caused death in one patient. Among asymptomatic subjects 38.4% showed hemagglutination (HI) antibodies to chickungunya virus, confirming the presence of the virus in the community.

Hemorrhagic manifestations occur occasionally. CNS manifestations like meningism, convulsions and acute polyneuropathy has been reported in a minority of patients, especially children and infants.

Course and Prognosis

The diseases many run a benign course with slow recovery even if untreated. Arthropathy may persist for varying periods and can be disabling. The acute illness in children and infants and elderly persons can be fatal. The primary role of uncomplicated chickungunya as a cause of death is not established. It produces considerable morbidity and impairment of the quality of life for prolonged periods.

Diagnosis

Routine laboratory investigations are not specific. The ESR may be elevated to 20-50 mm/hr and CRP may also be elevated. Isolating the virus or identifying genomic products by PCR in acute phase blood specimens can confirm the diagnosis. Serologically specific IgM or other antibodies can be demonstrated by IgM capture ELISA test. This test will distinguish the condition form dengue which is also transmitted by the same vector.

Treatment

Rest and symptomatic treatment with non-steroidal anti-inflammatory drugs give relief. Prolonged arthropathy demands symptomatic treatment. Chloroquine given in a dose of 250 mg od or bd has been reported to be useful. In any case results are not impressive.

Prevention and Control

An experimental live attenuated vaccine has been shown to produce high levels of neutralizing antibody in human volunteers but efficacy has not been tested. Anti-mosquito measures and personal protection with mosquito repellants will reduce the spread.

CANDIDIASIS – General Characteristics, Diagnosis and Treatment

General Characteristics

Candida albicans is a common inhabitant of the oropharyngeal, genital and intestinal cavities of man. Candidiasis is infection by Candida albicans. In most of the cases it remains as a local infection affecting the skin or mucous membranes of the mouth or genitalia. In the mouth it presents as oral thrush which is seen at the extremes of ages, those on antibiotic therapy or in immunosuppressed individuals. In the genitalia it usually presents as vulvovaginitis in diabetic women who are not well-controlled. Cutaneous candidiasis usually affects the intertriginous areas.

Systemic candidiasis occurs in immunocompromised individuals and in drug addicts who share needles. The fungus becomes invasive and spreads through the blood stream to produce several lesions.

1. Localized lesions: Urinary tract, liver, heart valves, meninges and peritoneal cavity.

2. Widely disseminated: Associated with septicemia (candidemia). In disseminated candidiasis also the main targets of attack are the kidneys, brain, liver, gastrointestinal tract, eye (endophthalmitis) and heart valves.

Extensive, recurrent and persistent oropharygeal and esophageal candidiasis is a common AIDS associated infection.

Diagnosis

The organism can be demonstrated microscopically by examining samples from local lesion. In tissues, PAS staining or methenamine silver staining reveals the organism.

The fungus can be grown in Sabouraud’s medium. Antibodies to Candida can be detected by ELISA or immunodiffusion. The candidal antigen can be demonstrated by ELISA or radioimmunoassay.

Treatment

Amphotericin B, fluconazole, ketoconazole and itraconazole are all effective in appropriate dosage to control the systemic infection. Local surgical therapy should be aimed at removal of the source of infection.

Dose: Amphotericin B up to 50 mg/day IV for 1-2 weeks and more.

Fluconazole 400 mg/day.

Ketoconazole 400 mg/day for several weeks.

Itraconazole 200-400 mg/day.

Itraconazole and fluconazole are less adrenosuppressive compared to ketoconazole. Superficial skin and mucous membrane lesions respond well to nystatin  ointment or nystatin mouth washes. Fluconazole given orally is very effective to cure vaginal candidiasis.

BRONCHIAL ASTHMA – General Characteristics, Pathology, Clinical Features, Diagnosis, Treatment and Prevention

General Characteristics

The term ‘asthma’ in Greek means ‘breathless’ or ‘breathe with open mouth.’ Asthma is a common chronic inflammatory condition of the airways whose mechanism is not completely understood yet. Epidemiological studies suggest that multiple genetic and environmental factors contribute to the causation of asthma, a clinical condition that is viewed as a cluster of related disorders. Genetic factors contribute to the variability with regard to age of onset, sensitivity of environmental causes and response to treatment.

Airway inflammation is associated with airway hyperresponsiveness, airflow limitation, and respiratory symptoms. Airway inflammation leads to limitation of airflow by acute bronchoconstriction, edema of the airway wall, formation of mucus plugs, and airway remodelling.

The tracheobronchial tree reveals increased responsiveness to immunological and non-immunological factors. Several organic dusts, fumes, and chemicals precipitate immunological mechanisms. Non-immunological stimuli include thermal, chemical or psychological factors.

Bronchial asthma used to be classified into the extrinsic (atopic) and intrinsic (cryptogenic) types. In the former an external precipitating factor is identifiable, whereas in the latter, it is not. The antigens include ingested, inhaled or parenterally administered substances.

The serum of such individuals may show elevated levels of specific antibodies belonging to the IgE and sometimes IgG classes. Persons developing extrinsic asthma have other atopic manifestations like eczema. The dermatological and respiratory manifestations show a see-saw relationship. In many cases family history of bronchial asthma may be present. Extrinsic asthma generally sets in by the age of 10-15 years. This type has a better prognosis from the point of response to therapy and mortality. The age of onset for intrinsic asthma is after 30 years. Precipitating causes or raised antibody levels are not evident but these patients show a higher frequency of eosinophilia, aspirin sensitivity, and nasal polyposis. Common stimuli which precipitate extrinsic asthma are inhaled allergens like house dust, pollens, fungi, animal hairs, insect scales and industrial fumes, and foods and drugs which are consumed in day-to-day life. Once sensitization occurs, these antigens release chemical mediators from the mast cells by interacting with the IgE molecules on their surface. Type I hypersensitivity reaction ensues. Asthma can also be caused by Type III (delayed) hypersensitivity mechanism mediated by IgG. In some individuals both Type I and Type III reactions occur, the former leading to an immediate asthmatic paroxysm and the latter leading to a delayed episode.

Exercise-induced asthma is a problem in children and young adults, in which bronchoconstriction is provoked by various forms of exercise such as running or climbing stairs, but others such as swimming may not do so. Provocation of bronchoconstriction by cold inspired air is a possibility in such cases. In many cases the attacks are brought on straight by the exercise, but in the others asthma sets in several hours after the exercise. The mechanism is a Type I hypersensitivity reaction. Short acting β2-agonists are used to prevent exercise- induced asthma. Inhaled steroids are indicated and are useful. Systemic steroids are seldom necessary.

PATHOLOGY

Inflammation of the airways is brought on by several factors. Eosinophils, T-lymphocytes (CD4+), macrophages and mast cells infiltrate the bronchial wall. The epithelium is vacuolated and the ciliated cells desquamate. Several cellular factors play their roles in the inflammatory process. Neuropeptides such as bradykinins, substance P and neurotensin A lead to bronchoconstriction and excessive secretion of mucus.

The main chemical transmitters, which alter the airways, are histamine, prostaglandin and leukotrienes. These lead to contraction of bronchial muscle, increase in vascular permeability and excessive secretion of abnormal mucus. Airway inflammation persists for several years. Its severity correlates with the severity of asthma. Hyperresponsiveness of the inflamed airways is aggravated by autonomic and neural mechanisms. The final result is obstruction of the small and medium sized airways brought about by mucosal edema, tenacious mucus and bronchoconstriction.

CLINICAL FEATURES

The attacks start with dyspnea (often at rest), expiratory wheeze, and cough. The onset is abrupt in most cases. These attacks may occur seasonally or during all times of the year (perennial asthma). The attacks may last for several hours if untreated. Severity of the paroxysm varies. In the moderately severe case the patient is orthopneic and cyanosed, and the accessory muscles of respiration are active. There may be ineffective cough with only very scanty and tenacious mucoid expectoration. The asthmatic paroxysm in many individuals is ushered in by a bout of coughing and sneezing on exposure to the allergen. The pulse is rapid. Blood pressure is normal or elevated. In severe cases  pulsus paradoxus may occur. Expansion of the chest is considerably diminished, often to less than 2 cm during the attack. The diagnostic feature of bronchial asthma is the presence of expiratory wheeze heard all over the chest.

DIAGNOSIS

Diagnosis of bronchial asthma is clinical. The history of sudden attack of paroxysmal dyspnea, cough, and the auscultatory hallmark of expiratory wheeze heard all over the chest are diagnostic. Long duration of complaints, history of allergy, and positive family history are other helpful clinical points.

Clinical features which indicate severe ventilatory Impairment

1. Inability to narrate history continuously or severe distress even on mild exertion,

2. Cyanosis, flapping tremors,

3. Mental confusion,

4. Respiratory rate above 25/minute,

5. Heart rate persistently above 110/minute.

6. Inspiratory fall in blood pressure exceeds 16 mm Hg,

7. PEFR less than 40% of predicted value, and

8. Feeble breath sounds.

Differential diagnosis:

Bronchial asthma has to be differentiated from other causes of paroxysmal dyspnea. These include chronic bronchitis emphysema syndrome (CBES), acute left-sided heart failure, acute bronchitis, tropical pulmonary eosinophilia, metabolic acidosis, and tracheal obstruction by foreign bodies or tumours.

It is important to distinguish left-sided heart failure (cardiac asthma) from bronchial asthma. Left-sided heart failure complicates valvular heart disease, systemic hypertension or ischemic heart disease. It causes paroxysmal dyspnea in the first half of the night whereas bronchial asthma is more common in the early hours of the morning.

In bronchial asthma there is generalized wheeze all over the chest, whereas in cardiac failure, basal crepitations are more prominent, though generalized bronchospasm may also be evident at times. In heart failure, gallop rhythm may be evident. Careful search for the underlying disease may reveal the etiology.

TREATMENT

Treatment may be described under three heads: (1) treatment of the acute attack; (2) treatment in between attacks; and (3) treatment of acute severe asthma.

TREATMENT OF THE ACUTE ATTACK

At present the drugs of choice employed to stop an acute attack are beta 2-agonist drugs. They act mainly on the bronchial muscle as relaxants without much effect on the cardiovascular system. These include salbutamol, terbutaline, salmeterol, bambuterol and others. These can be given orally, as inhalations (aerosol or powder) or parenterally. The oral dose is effective within 15-20 minutes and the action lasts for 4-6 hours.

Nebulizers, which can be carried by the patient or operated in the emergency room, are available for administration of these drugs. These can deliver larger doses as required. The drug solution is nebulized by passing oxygen or air under pressure through it.

PREVENTION

It is important to avoid known allergens, which can be identified. In the case of some allergens like house dust and pollen, desensitization can be achieved by repeated challenges.

Inhaled corticosteroids 200-800 micro g per day has been recommended as the treatment of choice for regular preventive therapy of asthma.

Yoga and controlled breathing exercises are of considerable benefit in allaying the paroxysms.

BARBITURATES – General Features, Clinical Features and Treatment

GENERAL FEATURES

Till recently, barbiturates were the most common drugs used for suicide. Accidental poisoning is seen in epileptics, psychiatric patients and children who get regular prescription for these drugs.

The most widely used barbiturate is phenobarbitone and it is used as an anticonvulsant. Absorption and metabolism of phenobarbitone are slow. About 10% of the drug is excreted in urine unchanged. The lethal dose for adult is about 5 gm. Simultaneous administration of alcohol aggravates its effects.

CLINICAL FEATURES

Central nervous, respiratory and cardiovascular systems are affected the most. Drowsiness, slowing of respiration and hypotension follow. Pupils are small and react to light.

In severe poisoning, when medullary centers are depressed, the pupils are dilated and fixed, which indicates a poor prognosis. Tendon reflexes are sluggish or absent. Necrosis of sweat glands and bullous lesions over the skin develop in a few as a hypersensitive reaction. These lesions heal slowly.

Diagnosis can be confirmed by detection of barbiturates in the gastric contents and estimation of barbiturate in blood.

Treatment

In addition to general measures, forced alkaline diuresis and dialysis are helpful. Bemegride (megimide) is considered to be a specific antidote but subsequent research has disproved this assumption.

Repeated doses of activated charcoal and hemoperfusion are the modalities described. Since pneumonia is a fatal complication, these patients should be observed for a week till recovery is complete.

AVIAN FLU (INFLUENZA GROUP A H5N1 VIRUS) – General Characteristics, Clinical Features, Diagnosis and Management

General Characteristics

The subtype H5 N1 influenza virus is a natural pathogen of chicken, ducks, turkeys and others. Though it was thought to be pathogenic only to them, the subtype H5N1 has crossed over to infect humans and caused small outbreaks. Hong Kong (1977) Thailand, Cambodia, Indonesia and several other Asian countries have reported outbreaks in poultry by H5N1 virus.

If human to human transmission of the virus becomes efficient, devastating pandemic more severe than the previous ones is likely to breakout. Pathologically the lesions resemble those of classic influenza, but hemophagocytic histiocytosis may also be seen.

Clinical Features

The incubation period for human influenza viruses is short-2 to 3 days (range 1-7 days). However with influenza A H5N1 the median time between exposure and onset of illness is 3 days (range 2 to 4 days). Most cases have occurred in previously healthy children and young adults. Symptoms of bird flu in humans include fever, cough, and sore throat, pneumonia, acute respiratory distress, and lifethreatening complications. The symptoms of bird flu may vary depending on the type of virus. Primary viral pneumonia and multi-organ failure are common. In the present outbreak, more than half of those infected with the virus have died. Death is due to respiratory failure and multi-organ failure especially respiratory, renal and cardiac failure.

Criteria for suspecting avian flu

Persons with illness characterized by fever, (temperature > 38oC), cough and/or sore throat, severe respiratory symptoms and one or more of the following:

1. Contact with a confirmed case of influenza A H5N1 during the infectious period,

2. Recent (less than 1 week) visit to a poultry farm in an area known to have outbreaks of HPAI (highly pathogenic avian influenza), or

3. Worked in a laboratory that is processing samples from persons or animals suspected to be having HPAI infection.

DIAGNOSIS

Procedure to Establish the Diagnosis

1. Suspect the disease and start investigations. Virus can be isolated from pharyngeal secretions 2-15 days after the onset of illness. Nasal secretions, blood, CSF and feces also contain the virus. Children may continue to shed the virus in nasal discharges for over 2 weeks after recovering from the acute attack.

2. Positive immunofluorescence antibody (IFA) using H5N1 monoclonal antibodies can be demonstrated in serum.

Diagnosis is confirmed by the following tests:

1. Positive viral culture for influenza A H5N1.

2. Positive real time PCR for influenza A H5N1.

3. and/or four-fold rise in H5N1-specific antibody titer.

MANAGEMENT

Avian influenza virus is resistant to amantadine and rimantadine. Oseltamivir 75 mg orally twice daily for 5 days and zanamivir would probably be useful if started as early as possible. No vaccine is available now to protect against H5N1 virus for general use.

A 2 dose regimen of 90 μg of sub-virion influenza A (H5N1) given IM over the deltoid muscle at 28 days interval generates neutralizing antibody. This vaccine is under trial.

Infection Control Precautions for Hospital Staff

Patients who have visited endemic regions within 10 days and who present with severe febrile illness and respiratory symptoms should be observed for avian influenza, with isolation, barrier nursing and other precautions.

1. Proper hand washing before and after contact with the patient.

2. Use gloves and gowns for all patient contacts. Use separate equipment for individual patients.

3. Protection of the eyes with goggles or face shields.

4. Precautions against droplet infection: Patients should be isolated in monitored negative air pressure ventilation systems. Health care staff should use a fittested respirator, or approved N-95 filtering mask when entering the room.

5. Suspected poultry meat and eggs should be properly cooked so that the whole item reaches a minimum temperature 70oC which is needed to destroy the virus.

ASPERGILLOSIS – General Characteristics and Treatment

General Characteristics

The species of aspergillus pathogenic to man are A. fumigatus, A. niger, A. flavus, A. terrens and A. nidulans. Of these A. fumigatus is most common. Infection occurs when general resistance is lowered or local disease favours superinfection. Aspergillus is very widespread in nature and their spores are found in dust. Both superficial and systemic lesions may develop. The commonest superficial lesion is otomycosis. Systemic infection may be pulmonary or disseminated. Major portal of entry is the respiratory tract.

Pulmonary form: Allergic alveolitis may develop due to inhalation of fungal spores in sensitized individuals. Aspergillus may grow in the bronchi to produce bronchopulmonary disease. The hyphae may obstruct the lumen. Healed tuberculous cavities or other types of cavities may be the seat of colonization by the fungus.

The mycelia grow to form a tangled fungal ball which is recognizable in X-rays (aspergilloma). It may remain asymptomatic or may cause massive hemoptysis. Invasive aspergillosis occurring in immunosuppressed individuals leads to widespread pulmonary necrosis with marked systemic symptoms.

Other sites of lesion are the central nervous system and naso-orbital cavities. Diagnosis can be made by histological demonstration of the fungus and isolation of the organism from the exudates. Since Aspergillus is a common contaminant in respiratory secretions, mere isolation does not prove its pathogenic role. Precipitating antibodies can be demonstrated by gel diffusion test and this test is of great value in diagnosis.

Treatment

Amphotericin B in a dose of 1 mg/kg/day is effective in systemic aspergilloma. Amphotericin B and 5-fluocytosine are effective in CNS disease. The underlying predisposing factor should be attended to. Cavities containing aspergilloma producing intractable hemoptysis have to be removed surgically. Other drugs like clotrimazole which are also effective in vitro are being evaluated. Other drugs effective against aspergillus include oral fluconazole itraconazole, voriconazole and posaconazole. Posaconazole can be given prophylactically against aspergillus and other fungal infections in neutrophilic patients. The dose is 200 mg tds oral. Capsofungin a new antifungal drug effective against aspergillus and other yeast species.

ASCORBIC ACID – SCURVY (ANTISCORBUTIC VITAMIN – VITAMIN C)

James Lind, a Scottish naval physician, recognized the antiscorbutic properties of citrus fruits in 1753 and this was considered an important discovery with far-reaching effects.

Dietary sources Ascorbic acid is present in a wide variety of foods. In the process of cooking about 50% of vitamin C passes into water and 20% gets destroyed. Fresh fruits, green leafy vegetables and germinating pulses are rich in ascorbic acid. The Indian gooseberry and guavas are particularly rich sources. Animal food like milk and meat contain only small amounts of this vitamin. The vitamin is present in potato in the layer just below the skin. If the potatoes are boiled whole with the skin, the vitamin diffuses into the deeper layers.

The minimum daily requirement for an adult is 30-40 mg and for infants 5 mg per kg body weight. Normal plasma levels vary between 0.7 and 1.5 mg per dL. Leukocytes, platelets, and adrenal glands contain large amounts of vitamin C. Deficiency of vitamin C causes scurvy.

Physiological actions

Vitamin C is a strong reducing agent. It takes part in biological oxidation-reduction reactions. Vitamin C is required for the formation of collagen by the hydroxylation of proline. It takes part in the formation of hemoglobin, erythrocyte maturation and the conversion of folic acid to tetrahydrofolate. Ascorbic acid reduces ferric iron to ferrous iron which is more easily absorbed. Body stores of ascorbic acid are small and, therefore, dietary deficiency leads to the development of scurvy.

SCURVY

Deficiency of vitamin C in the diet over a few weeks or months will lead to scurvy.

Clinical features of scurvy

Classic scurvy is seen only infrequently in India since small amounts of vitamin C are obtained in vegetables and pickled berries which form essential items of the Indian diet. Cases do occur among inmates of mental homes, elderly persons and among the very poor.

Manifestations of scurvy vary in children and adults. Early symptoms include weakness, lassitude, and normocytic normochromic anemia. In infancy and childhood subperiosteal hemorrhages occur, which lead to painful swellings over long bones. Scurvy in infancy produces pseudoparalysis owing to pain. This condition may mimic arthritis, osteomyelitis, or poliomyelitis. X-ray abnormalities may develop over the sternal ends of ribs and ends of long bones. Bleeding from the gums occurs commonly at the sites of erupted teeth.

Retrobulbar, subarachnoid, and cerebral bleeding may develop in a few cases. In adults early manifestation is follicular hyperkeratosis over the skin of the lower limbs. The lesions are papular with perifollicular hemorrhages which appear as purpura. Hemorrhage into the deep tissues of the thighs and legs cause tense induration (“woody leg”). Other sites of hemorrhage include joints, nail beds and viscera. The gums are hypertrophied and the interdental papillae are red and prominent (scurvy-buds). They bleed easily. Edentulous subjects do not get gingival abnormalities. The gum changes are aggravated by infection. The teeth become loose and may fall off. The hair assumes corkscrew shape since the follicles are obstructed by keratin plugs. Wound healing is delayed and resistance to infection is reduced. The condition is fatal if untreated.

Treatment

Scurvy is a potentially fatal disease and sudden death may occur unexpectedly. Treatment should be started without delay. In infants and children 25-50 mg of ascorbic acid given daily three times a day is sufficient to replete the body stores. In adults 500 mg is given daily in divided doses up to a total of 4 g. A diet rich in vitamin C should be given to prevent relapse.

Prevention

Infant foods should contain fruit juices or vitamin C supplements. Children, convalescent subjects and elderly people who are liable to be neglected, should receive 25 mg of vitamin C daily. As an alternative, 500 mg may be given once a month.

Adverse effects of vitamin C

Side effects like digestive upsets and hypoglycemia occur if the drug is given in doses exceeding 3 g/day. Oxaluria and oxalate stone formation in the urinary tract may result from prolonged overdosage.

ASCARIASIS – General Characteristics, Life Cycle, Pathogenesis, Clinical Features, Diagnosis, Treatment and Prevention

General Characteristics

Ascariasis is worldwide in distribution and is caused by the nematode Ascaris lumbricoides. The worm measures 20-35 cm in length. The female is larger than the male. The females lay several thousand eggs every day. The eggs are elliptical, 30-40 μ x 50-60 μ in size with an outer dense mammilated shell and a smooth translucent inner shell. They are passed in feces. They become embryonated and infective in the soil in 2- 3 weeks and they can remain viable under optimum conditions for years.

Life Cycle

Embryonated eggs are ingested with food or water and the larvae hatch out in the small intestine. They penetrate the intestinal mucosa to enter the venules or lymphatics and travel to the lungs, where they develop for about 10 days. They then enter the alveoli to be coughed up and swallowed. During the pulmonary phase the larvae undergo four moultings and become resistant to gastric acid. The larvae grow and mature in 2-3 months. Life span of this worm is 6-15 months.

Pathogenesis

During the stage of larval migration, pulmonary symptoms like cough, wheezing and hemoptysis may occur (Loeffler’s syndrome) and used to be a common cause of respiratory symptoms in children. The adult worms ingest nutrients from the small intestine and lead to nutritional deprivation. Large number of adults may form tangled masses and obstruct the small intestines. The worm may migrate to ectopic sites like the stomach, nasal cavity, biliary tree, pancreatic ducts, respiratory passages, female genital tract or others. Absorption of the products of living and dead worms leads to the development of allergy and toxic symptoms.

Clinical Features

Those due to larvae: Respiratory symptoms such as cough, hemoptysis or wheezing may develop 1-5 days after swallowing the eggs. Eosinophilia may be present. Clinical severity depends upon the worm load and reactivity of the host. The liver may be enlarged and histology may show centrilobular necrosis. Rarely larvae may reach the brain, giving rise to convulsions. Other organs may also be affected.

Those due to adult worms: Light infestations are asymptomatic. Moderate worm loads produce abdominal  pain, pica, diarrhea, abdominal distention and grinding of the teeth (bruxism). Infected children have voracious appetite but they remain malnourished despite adequate intake of food. Migration of worms to biliary ducts or pancreatic ducts leads to obstruction. In heavy infection the masses of worms may lead to intestinal obstruction and they may be palpable.

Diagnosis

It is made from the history of passing round worms in the stool or the children may vomit round worms. Diagnosis is confirmed by demonstrating the characteristic ova in feces. In the rare event of infection by male worms alone, ova may not be present in feces. During the stage of larval migration, the diagnosis has to be presumptive

Treatment

The adult worms respond to a variety of anthelmintics. Effective, safe and polyvalent anthelmintics are preferred at present. In more than 30% of patients multiple helminths occur, common combination being roundworm, whipworm and hookworm and broad spectrum anthelmintics are more advantageous in them.

Benzimidazole drugs which include albendazole and mebendazole bind to nematode β tubulin and inhibit parasite microtubule polymerisation which causes death of adult worms which may take a few days to complete.

Prevention

Improvement in nutritional status of children, health education, especially pertaining to personal hygiene and environmental sanitation reduce the infection rates. Mass deworming campaigns are helpful in endemic areas to reduce worm loads temporarily but reinfection withinmonths is the rule.

AMEBIASIS – General Characteristics, Pathology, Clinical Manifestations, Acute Amebic Dysentery, Hepatic Amebiasis and Treatment of Amebiasis

General Characteristics

The term amebiasis includes all lesions caused by infection by the protozoan parasite Entameba histolytica. These amebae cause ulcerative lesions in the large intestine causing dysentery and from there they spread to several organs to produce necrotic lesions.

There is a great tendency for the intestinal infection to become chronic and persistent for long periods. E.dispar is morphologically identical to E.histolytica, but nonpathogenic. It is genetically different. It is a commensal. However, E. histolytica can also remain in the bowel for many years without causing major symptoms.

Amebiasis is worldwide in distribution, but it is very prevalent in tropical climates. Chronic carrier state, poverty, insanitary disposal of excreta, unhygienic food handling, and proliferation of flies are responsible for this high prevalence. Though all age groups are susceptible, adults suffer more often.

Amebae are widely distributed in nature. The common pathogen is E. histolytica. It exists in two forms—the cyst and the trophozoite. The cysts are round or oval in shape and measure 10 to 15 μ in diameter. In iodine-stained preparations the cysts show one, two or four nuclei depending on their maturity. Cysts resist adverse environment. In addition to the nucleus, one or more rodlike structures called chromidial bars, and a glycogen mass are also seen. Cysts are formed in the bowel when the environment becomes unfavorable for the trophozoite and are then passed out in feces. Cysts are responsible for transmission of the disease from person to person. The vegetative form (trophozoite) is actively motile by the aid of pseudopodia. It measures 20 to 50 μ in diameter.

Invasive trophozoites are identified by the presence of ingested erythrocytes within them. Amebae multiply by binary fission. The trophozoite is the invasive form and is responsible for all lesions. A large number of trophozoites is seen in the feces of dysenteric patients. Trophozoites and cysts occur in the feces of carriers. Outside the body, the trophozoites survive only for an hour or so. Normal gastric juice destroys them in the stomach. Cysts survive external environment for long periods.

Transmission

Humans are the only reservoir for E.histolytica. Cysts are passed in the feces of cases and carriers. These are ingested along with food or water. Cysts resist acid digestion in the stomach. Excystation occurs in the intestines, Trophozoites develop from cysts and they establish themselves in the colon, feeding on the bacteria and desquamated epithelial cells. They multiply by binary fission. These non-invasive forms may persist for long periods without producing any symptoms. Under favourable conditions these become invasive.

PATHOLOGY

Intestinal amebiasis: The invasive trophozoites adhere to colonic mucosa with the help of specific lectins and ulcerate the mucous membrane and penetrate deep into the submucosal layers of the colon. The basic pathological process is a lytic necrosis of tissue. This is due to an extra cellular cysteine kinase enzyme causing proteolytic destruction of the tissue, producing flask shaped ulcers.

E. hystolytica which produce lytic enzymes kills host cells which come into contact with them. The host cells become immobile on contact with E. histolytica, and the cells die. E. histolytica can also induce apoptosis in host cells. The cellular response consists of mononuclears and a few polymorphs. Amebae are seen in the invading margins of the lesions. Cecum, ascending and descending colon, and rectum are the sites of predilection.

The appendix may be involved. The terminal ileum may be affected rarely. The ulcers have undermined edges and are covered by dense yellow or brown slough. The mucous membrane between ulcers is healthy. Ulceration may extend to blood vessels causing severe hemorrhage at times. Perforation of the bowel may occur, but it is rare. Sometimes ameboma or amebic granuloma develop due to repeated infection by ameba and bacterial pathogens. The acute inflammatory process has a tendency to subside spontaneously.

In many patients chronic infection persists with microscopic lesions which harbour E. histolytica for many years. The lesions may heal in a few cases. Persistence of the chronic lesions accounts for the carrier state. E. histolytica infection is associated with transient immunosuppression. Activated macrophages form the major defence against invasive amebae. The resistance against invasive amebiasis is mainly cell mediated immunity.

Extra-intestinal Lesions

Amebic liver abscess: Invasive amebae reach the liver through the portal blood stream from the colon which is the primary seat of infection. In the liver they multiply and cause colliquative necrosis of liver cells to produce abscess.

Possibly malnutrition, alcoholism and consequent immunosuppression favour the development of liver abscess. Unlike pyogenic abscess, the wall of the amebic abscess is made up of necrotic and compressed liver tissue and it is devoid of granulation tissue. Active amebae are found near the expanding margins. The pus is made up of necrotic tissue which shows amorphous material and erythrocytes. It is sterile on culture.

In most cases the colour of the pus is reddish brown or chocolate. Amebae are seen only rarely in the pus aspirated from the center of the abscess, they are more often demonstrable in the pus aspirated from near the walls on subsequent occasions. The site of the abscess is more commonly the right lobe. It is usually single and may attain very large size.

The abscess may enlarge progressively and spread by contiguity to the chest wall, colon, diaphragm, pleura, and pericardial cavities. Amebic abscess does not impair hepatic-function significantly. Jaundice is generally mild or absent, but pressure over a major hepatic duct can give rise to obstructive jaundice. On aspirating the pus the liver tissue comes into apposition and complete healing occurs without structural damage or fibrosis.

During acute amebic dysentery, the liver may enlarge as a result of diffuse inflammation caused by the products of inflammation of the colonic tissue and bacteria reaching the liver in the blood stream. The hepatic lesion clears up with cure of the dysentery. This lesion should not be mistaken for liver abscess.

Other foci for embolic lesions include the lungs, brain, spleen and other tissues. Direct invasion of the skin by active vegetative amebae leads to extensive spreading necrotic ulceration-cutaneous amebiasis.

CLINICAL MANIFESTATIONS

The incubation period varies from a few weeks to months.

Spectrum of illnesses caused by E. histolytica

Intestinal amebiasis

1. Asymptomatic infection

2. Symptomatic non-invasive infection

3. Acute proctocolitis (Dysentery)

4. Toxic megacolon

5. Chronic non dysenteric colitis

6. Ameboma

7. Peri anal ulcers

Extra intestinal amebiasis

1. Liver Absces

2. Pleuro -Pulmonary involvement

3. Pericarditis

4. Peritonitis

5. Brain abscess

6. Genito urinary disease

ACUTE AMEBIC DYSENTERY

This presents with sudden or subacute onset of lower abdominal pain and diarrhea with blood and mucus in stools. The frequency ranges from 3 to 10 in a day. At times watery diarrhea with large amounts of blood and mucus may occur. Constitutional symptoms are mild and these include low grade fever and vague discomfort.

Palpation of the abdomen reveals colonic tenderness and mild hepatomegaly. The feces are semisolid or liquid, showing fecal matter mixed with blood and mucus. Microscopic examination shows erythrocytes, a smaller number of leukocytes and trophozoites of E. histolytica. In the majority of cases, the condition subsides after several weeks even without treatment, to exacerbate again with dietary irregularity, psychological stress or other factors.

Complications are rare but in a few cases extensive destruction of mucosa and submucosa may lead to severe hemorrhage and occasionally perforation. Rectalprolapse, intussusception and colonic stricture may develop in some. Amebomas may develop in the cecumor other parts of the colon and these may be mistaken for tumours. These resolve completely with specific treatment.

Non-dysenteric Amebiasis

This is a common mode of presentation in endemic areas. The condition starts insidiously with abdominal discomfort, flatulence, intermittent diarrhea with constipation, and the presence of mucus in stools. Asymptomatic intervals and periods of dyspepsia alternate for many months or years. Vague general symptoms like feverishness, mild depression, fear and anxiety may be prominent. Physical examination may reveal palpable tender cecum and sigmoid and sometimes tender hepatomegaly. An amebic granuloma (ameboma) may be felt as a sausage-shaped mass in the right iliac fossa and this may be mistaken for malignancy or tuberculosis.

Mucosal ulcers may be seen on sigmoidoscopy. Examination of the mucus collected by sigmoidoscopy may show the active trophozoites. Repeated examination of fresh stool or sigmoidoscopic specimen may be necessary to establish the diagnosis. Sigmoidoscopic biopsy reveals the ulceration and the parasite in the mucosa.

HEPATIC AMEBIASIS

Hepatic involvement used to be very common, almost all patients give a history of alcoholism. Around 50% of patients suffering from hepatic amebiasis give history of dysentery. Liver involvement manifests as insidious onset of pain in the right hypochondrium or right lower chest with fever, chills and sweating. Loss of weight and anemia may be pronounced.

In the early stage the liver is enlarged as a whole. The pathological process is not inflammatory, but it consists of multiple necrotic lesions caused by amebae diffusely distributed in the liver. In this stage the organ is enlarged as a whole and it is acutely tender. This stage may persist for varying periods and may resolve either spontaneously or with treatment, without proceeding to abscess formation.

At present the occurrence of liver complications has come down. In those in whom abscess develops, the liver is considerably enlarged and tender. When the abscess spreads to the abdominal wall, there is superficial edema and severe local tenderness. The majority of liver abscesses are in the right lobe. Left lobe lesions are palpable over the epigastrium. Diaphragmatic involvement causes pleuritic pain in the right lower chest.

Physical examination reveals diminished air entry, impaired percussion note and crepitations over the lower part of the right chest. Jaundice is rare. Blood shows mild tomoderate leukocytosis (about 12-14.000/cmm) with polymorphonuclear cells dominating the field. The ESR is usually high. Fluoroscopy reveals elevation of the right dome of the diaphragm and diminished movement. Ultrasound, CT scan and isotopic scanning help to locate the site of the abscess.

Complications of liver abscess include rupture into neighbouring organs or cavities leading to peritonitis, right sided empyema, bronchohepatic fistula, and pericarditis. Untreated, the mortality may go up to 10%.

Cutaneous amebiasis occurs over the genitalia, perianal region, opening of sinuses and around colostomy wounds. Rarely metastatic lesions from the liver develop in the lungs and brain. Rupture of a liver abscess into the peritoneum causes the clinical picture of an acute abdominal emergency with shock.

Differential Diagnosis

Amebic dysentery has to be differentiated from bacillary dysentery, ulcerative colitis and tuberculous enterocolitis. Ameboma may closely resemble carcinoma. Chronic intestinal amebiasis may be mistaken for irritable bowel syndrome, diverticulitis, neurasthenia or malabsorption state. Hepatic amebiasis is a common cause of prolonged fever in the tropics and when liver enlargement and tenderness are not marked, it resembles enteric fevers, brucellosis or tuberculosis.

In an endemic area, enlargement and tenderness of the liver should suggest the diagnosis of amebic liver abscess. Other conditions such as alcoholic liver disease, primary and secondary tumours of the liver, subdiaphragmatic abscess and pyogenic liver abscess have to be differentiated. In case of doubt the diagnosis is confirmed by ultrasonography and later, aspiration. Prompt response to antiamebic drugs is a point suggesting a diagnosis of hepatic amebiasis.

Laboratory Diagnosis

Examination of the feces – Fresh stool examination by light microscopy invariably reveals E.histolytica in dysentery. Active E. histolytica shows characteristic ameboid movement and ingested erythrocytes. In chronic amebic colitis cysts are present in feces in varying numbers. These can be identified in saline preparations but cellular details are better demonstrable in iodine stained specimen. Unlike bacterial dysentery, the feces does not contain innumerable leukocytes. Plenty of erythrocytes are present. Stool occult blood may be present in invasive intestinal disease. Stool enzyme immunoassay also will be useful.

Apart from feces, vegetative E. histolytica can be demonstrated in the following specimen.

1. Liver abscess pus.

2. Sputum in pulmonary amebiasis.

3. Discharge from cutaneous amebiasis.

Serological tests – These tests are mainly used in extraintestinal disease. Indirect hemagglutination antibody test is positive in 95% of extraintestinal and 70% of intestinal amebiasis. Other tests also have been developed.

Indirect immunofluorescence is positive in more than 60% of cases. Countercurrent electrophoresis and agar gel diffusion are other methods employed.

Imaging studies:

ultrasonography – A single lesion in the posterosuperior aspect of the right lobe of the liver is commonly seen. But, multiple abscesses may also occur in some patients. Deep seated abscess may be missed on clinical evaluation. Multiple abscesses should suggest the possibility of pyemic etiology.

CT scan – In cerebral amebiasis, CT may show irregular lesions without surrounding capsule or enhancement.

Other investigations – Blood counts may show mild anemia, leucocytosis, elevated ESR and elevated alkaline phosphatase.

Endoscopy – Rectosigmoidoscopy and colonoscopy may reveal small mucosal ulcers covered with yellowish exudates, and the intervening mucosa appears normal. For demonstrating vegetative amebae the fresh mucus exudates should be examined as a saline preparation, microscopically.

In chronic intestinal amebiasis the feces show amoebic cysts, when the disease is quiescent. With acute exacerbation, trophozoites appear from time to time. Charcot-Leyden crystals may be seen as a result of chronic bleeding foci. These crystals are needle shaped, refractile, and are made up of lysophopholipase.

TREATMENT OF AMEBIASIS

Drug treatment consists of amebicidal drugs. These may act on the parasites found in the lumen of the gut or on the invasive forms seen in the tissues. They are grouped as luminal amebicides and tissue amebicides. Some drugs, however, have action on both sites.

Prevention:

The most important steps are to observe food hygiene, provide safe drinking water and arrange for sanitary disposal of human excreta. Ordinary chlorination of drinking water does not kill the cysts. Cooks and food handlers should be periodically examined and the infection eradicated. Fruits and vegetables can be rendered safe by washing with soap and peeling off the skin wherever possible.