Wednesday, February 3, 1999

Artificial “mother’s milk” & infants’ future
MOTHER’S milk has been humankind’s first food for as long as the human race has existed. Dr Satish M. Sood, a non-resident Indian scientist who is at present on the faculty of the School of Medicine, Biochemistry Department of Loma Linda University, Loma Linda, California, is probably the only scientist in the world who has studied the milk of nine different species — human, cow, buffalo, sheep, goat, mare, dog, sow and camel.

Cheese helps your teeth!
By Sarah Hall
IT CLOGS up your arteries, causes catarrh and allergies, and is even rumoured to induce nightmares. But the reputation of cheese took a turn for the better the other day as it emerged as a fine food for staving off tooth decay.

Chickenpox — finally a preventable disease
By Dr A.B. Desai

Smallpox, chickenpox and measles, all highly infectious diseases commonly affecting children, have been traditionally considered to be divine visitations.

IN India, when diseases such as smallpox, chickenpox and measles affect children, it is traditionally considered that a goddess has paid a visit. Smallpox was regarded as a visit by a major goddess because it was associated with severe complications like blindness, deep scars on the face and other parts of the body — and even death.

Measles is considered as the visit of a minor goddess; when compared with smallpox it was milder, did not leave any permanent marks, yet caused death due to pneumonia, encephalitis, diarrhoea and malnutrition. Chickenpox is the mildest of the three in children. The illness is usually not serious, rarely leading to complications such as scarring or death.

No treatment exists for these diseases even today. Perhaps that is why our ancestors put their children at the mercy of God. However, the scenario has changed. Vaccination has helped eradicate smallpox and deaths because of measles are few. Thanks to recent advances in science now we have a vaccine against chickenpox too.

Epidemiology: Chickenpox is a highly infectious disease caused by the varicella zoster virus (VZV). When this virus affects an individual for the first time, it causes chickenpox in him or her. The virus then remains latent in the body of the infected person for many years and may cause herpes zoster when he or she becomes an adult.

In India, chickenpox cases usually occur in winter — from December to April. It affects almost everyone. Except in regions with hot, humid climate, it usually affects 90% of the children. In the southern states of Kerala and Tamil Nadu, 20 to 25% of the children escape the infection but suffer from the disease during adolescence and adulthood.

The transmission of the disease is from person to person by direct contact or by airborne droplets of secretions during coughing or sneezing. Chickenpox is especially dangerous when pregnant women get the infection. This can lead to the Congenital Varicella Syndrome causing various malformations in the foetus. It can also cause chickenpox in the new-born baby.

The symptoms of the disease in children are usually mild. It starts with fever, lasting for one to three days, followed by red nodules on the abdomen, the chest and the back. The red nodules quickly get converted into vesicles which may contain pus, and are followed by scab formation. The rash spreads to all other parts of the body including the mouth, the eyes, the nose and the genitals.

All stages of the rash can be seen at one time. The crusts form in one or two weeks and then fall off within another week. The child is infectious from two days before the rash till all the lesions have converted into crusts. It is desirable that he or she is isolated for one week from the onset of the illness.

A common and distressing symptom of chickenpox is itching. Complications and death are rare in children but chickenpox infection in adults can take a severe turn. Encephalitis and pneumonia are the most common causes of death. Haemorrhagic vesicles, bleeding and infection of the rash are other complications. The disease may also involve organs like the liver, lungs, kidneys, muscles, bones and joints.

Treatment can be offered only for symptoms like itching and for the complications. The rash cannot be prevented. Once the disease starts, it takes its own course. The incubation period varies from two to three weeks.

Acyclovi, an antiviral drug, has been found to be useful for the treatment of very severe cases. It tends to prevent complications. It can also be given to the children or adults who have not suffered from chickenpox in the past. If given within 48 hours of the exposure, it can limit the course of the disease in 90% of the exposed susceptibles. However, prevention is the best remedy.

Varicella vaccine: A live attenuated chickenpox vaccine is now available in India for selective use. The varicella vaccine was first tried in Japan 25 years ago. It was used mainly for children with leukaemia and other such illnesses to prevent chickenpox infections in them. Many countries all over the world are now using the vaccine for healthy children. The USA has included it in its vaccination schedule for routine use since 1994.

The vaccine is freeze-dried in pellet form. It can be stored at 2° to 8°C in an ordinary refrigerator. The pellet should be dissolved with a special dilutent. The reconstituted vaccine should be administered immediately in the upper arm (subcutaneously). Children of all ages, as well as those adults who have not suffered from chickenpox infection in childhood, can be vaccinated. One dose of the vaccine is sufficient for children from the age of one year up to and including that of 12 years.

Two doses are recommended for all those above 13 years of age, with an interval of six to 10 weeks between the two doses.

The vaccine protects 95-98% of all those vaccinated. Breakthrough infections can occur in 2-5% of vaccines. A very mild rash like a natural infection may occur in eight to 10 days following the vaccination. Studies in Japan and the USA have shown that the efficacy lasts for up to 10 years. Only further follow-up studies can tell us how long protection with the vaccine will last.

Local pain, mild redness and fever never can occur in 3 to 10% of the children after vaccination. The contraindications are few. It should not be given to very sick children. Vaccination should also be avoided in children sensitive to neomycin. It cannot be given to pregnant women. After the vaccine is administered, pregnancy should be avoided for about three months. The use of aspirin in children with varicella may increase the risk of development of the Reye Syndrome.

Since chickenpox is a universal disease, the vaccine is needed by everyone. It has worked out to be highly cost-effective in the USA where it has been used for routine vaccination. In Japan, it is being used effectively for the past 20 years.

In India too, the vaccination of all susceptible children and adults will be a good strategy.

Dr (Mrs) A.B. Desai, MD; D.C.H.; is a former Director of Postgraduate Studies and Medical Education, and Professor and Head of the Department of Paediatrics, B.J. Medical College, Ahmedabad. She was also elected President of the IAP.

Questions and answers

Why you and your family should be aware of chickenpox (Varicella) and shingles (herpes zoster)

What does the varicella-zoster virus cause?

The primary manifestation of the varicella zoster virus is varicella, commonly known as chickenpox, which is a viral disease caused when an individual is first exposed to the virus. It presents as fever with a characteristic vesiculo-papular (blistered), highly pruritic (itchy) rash and is highly contagious. The infection of the lesions can result in permanent scarring.

The virus then remains latent in the body and can later be reactivated and cause herpes zoster (shingles).

What is the difference between varicella and herpes zoster?

During a varicella infection (chickenpox), the sensory nerve cells become infected with viral particles, an association that persists throughout the individual’s life. The viral particles then stay dormant in the sensory nerve cells. The virus can be reactivated later in life because the efficiency of the immune system declines with age. Hence herpes zoster (shingles) is more common in older people.

The main physical difference between the two infections is the rash and the pain associated with it. In shingles, the skin blisters form in red, inflamed groups along a nerve or group of nerves, and are extremely painful. In chickenpox, the rash is much more diffused, spreading over the body and the face.

How is varicella transmitted?

The varicella virus is specially adapted to attack the mucous tissues of the upper respiratory tract. The virus spreads easily from person to person by airborne droplets, generally from the mucous secretions of the respiratory tract during coughing or sneezing. It also spreads by direct contact with varicella or herpes zoster lesions.

Who catches varicella?

Everybody who has never had chickenpox before. They can be children, adolescents or adults.

What are the clinical signs of chickenpox?

The characteristic symptom is an irritating itchy rash which starts on the trunk and gradually spreads over the face, where it can involve the scalp, mouth and ears, and also the upper arms and legs. Most children have 250-500 lesions, which form a crust after four to five days and remains for one to two weeks. Children may be quite distressed by the itching and can develop fever, chills, nausea and vomiting.

What happens if an adolescent or adult contracts varicella ?

Varicella is more serious in adolescents and in adults than in children. The fever is higher and continues for a longer period and the rash is much more severe. There is also a greater likelihood of complications such as pneumonia.

Why is chickenpox important to you and your family ?

There are three reasons. First, the full impact of childhood varicella on patients and on their families is often not appreciated. Physically, chickenpox is very uncomfortable for patients and may have long-term disfiguring consequences or serious (even fatal) consequences.

Secondly, varicella can cause financial problems because of lost earnings when working parents have to stay at home to look after their children, or because older patients need to stay away from work. Sometimes, children get infected with the chickenpox virus during crucial times like examinations or planned holidays. Medical costs may also be high, especially if complications set in and the sufferer — whether child, adolescent or adult — needs hospitalisation. However, now there is good news regarding the prevention of chickenpox. For the first time, a vaccine has been developed which can prevent the burden of disease and provide long-lasting immunity from varicella in healthy children, adolescents and adults.

An effective and long-term means of prevention against chickenpox is through vaccination. Protection against chickenpox may be achieved using a singledose subcutaneous injection of a live-attenuated varicella vaccine.

(For more information, consult your doctor and the nearest office of SmithKline Beecham Pharmaceuticals, the leading vaccine- makers.)

Artificial “mother’s milk” & infants’ future

MOTHER’S milk has been humankind’s first food for as long as the human race has existed. Dr Satish M. Sood, a non-resident Indian scientist who is at present on the faculty of the School of Medicine, Biochemistry Department of Loma Linda University, Loma Linda, California, is probably the only scientist in the world who has studied the milk of nine different species — human, cow, buffalo, sheep, goat, mare, dog, sow and camel.

Dr Sood found that mother’s milk is really unique — specially designed for the infant. The major protein is the human beta-casein (nearly 75%) which is phosphorelated at five different levels, a rare phenomenon in nature.

The second important protein is the human kapa-casein (nearly 15%) which is highly glycosolyated to make it sweeter and probably more desirable for the infant. Alpha-casein is present in small amounts (nearly 5%). Beta-casein goes into the formation of “casein micelles”.

Kapa-casein plays a dual role — first to stabilise the micelles and then to limit their size. “Casein micelles” are the colloidal particles of milk proteins which help the otherwise insoluble calcium, phosphate.

Of all the milks studied human milk has the smallest-sized casein micelles.

In the gut of the infant, mother’s milk gets digested as curd which is very soft. This different level of phosphorelation of the human beta-casein is the reason for the formation of this soft and fine curd which is readily digested by the infant system and, therefore, supplies calcium phosphate and other nutrients such as zinc magnesium and Iron etc, which are otherwise insoluble in addition to the proteins. There are reasons for not going in for breast-feeding:

* Women’s choice.

* Not enough milk.

* Pesticides and other pollutants like methyl mercury, lead cadmium, etc, which find their way into milk supply and even into mother’s milk.

* Drugs (such as antibiotics to treat physical illnesses, or illegal chemicals for mind-altering, or taken for recreational purposes_.

* Smoking.

The substitute is the infant’s formula which as of now has very serious problems:

* Incomplete digestion (because cow’s milk proteins or soya proteins are being mainly used as the basis of infant formulations; the curd formed is entirely of a different structure and size and leads to incomplete digestion).

* Lack of many biologically active components that is human beta-casein and its fragments — lactoferrin, etc.

* Opioid peptides i.e. beta-casomorphins, etc.

* Allergies to both cow’s milk and soya milk. The major protein in the whey of cow’s milk is beta lactoglobulin. This protein is essentially absent from human milk and has been determined to be the one of the main cause of cow’s milk allergy in infants. Many infants that are allergic to cow’s milk are also allergic to soya-based milk. Thus if we can produce more human beta-casein, it can be used on basis of the infant formula instead of cow’s milk proteins, whey proteins or soya proteins and the net product will have properties of mother’s milk. It will also contain a number of components which are either biologically active or produce an active substance during digestion.These include components in defence against infection and components that facilitate the uptake of nutrients from the milk.

In addition to its use as the basis of the infant formula, lately beta-casein and its biologically active fragments have been reported to exhibit various effects on body functions:

* Gastro-intestinal motility

* Gastric acid secretion

* Appetite

* Hormone release

*Behavioural effects

* Physchobiological implications

* Antihypertension

* Immunomodulation

* Bioconversion of metalions (i.e. Ca+2)

* Antithrombotic activity

* Antibacterial properties.

Again, if we can produce enough human beta-casein, and for its fragments, these can be used in further studies on mineral uptake to treat pathological conditions.

Dr Satish Sood, in collaboration with Dr Charles W. Slattery, Chairman of the Biochemistry Department at Loma Linda University, is working on the human milk casein system for about 20 years. Their’s is the only lab which has isolated, purified and characterised all the six different forms of human beta-casein and kapa-casein.

They have also reported very important findings on the native human milk explaining the role of hydrophobic and electrostatic interactions in the formation or casein micelles. Recently, in their lab, the major protein of mother’s milk (i.e. “beta-casein”) has been produced in significant amounts from E.coli by cloning its gene, thanks to biotechnology.

This recombinant protein has been studied by Dr Sood’s group and has been found to fold into structures similar to those of the native molecule so that the digestibility, the delivery of minerals and other nutrients and the production of the biologically active fragments are functions being maintained. The recombinant molecule has the desired amino acid sequence also.

Using one litre of E.coli culture about 40 mg of crude protein and 28 mg of the pure beta-casein can be easily produced and is most cost effective.

Dr Sood and his group are trying to express biologically active peptides in E. coli by multiple cloning.

(Research observations summarised and presented by K.P.S.)

Cheese helps your teeth!
By Sarah Hall

IT CLOGS up your arteries, causes catarrh and allergies, and is even rumoured to induce nightmares. But the reputation of cheese took a turn for the better the other day as it emerged as a fine food for staving off tooth decay.

A three-year review of scientific data on the subject, by the British Nutrition Foundation, found that rounding off a meal with, say, stilton or cheddar counteracted the damage caused by guzzling puddings.

When we eat sweet foods the sugar reacts with bacteria in the mouth to create acid, which erodes tooth enamel. But the salt and fat in cheese stimulate production of saliva, which neutralises the acid. Calcium and the milk protein casein, both found in cheese, also strengthen the enamel.

Ursula Arens, a nutrition scientist at the foundation, which published its findings, said: “There is no one reason why cheese is so good in curbing tooth decay but a host of explanations. The main one being that it counters the production of acids at the tooth surface that occurs after eating sugar-containing foods.’’

The findings were greeted with enthusiasm by the cheese industry. Jane Maskew, Secretary of the UK’s Specialist Cheesemakers’ Association, said: “It’s good that someone is saying something positive about cheese for a change”.
(The Guardian, London)