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Are pigs carrying flu superbug?

The Avian flu that has claimed 22 lives in the Far East has now been found in pigs. Because the animals are vulnerable to both bird and human flu, scientists fear the virus could mutate inside them into a superstrain like the one that killed up to a fifth of the world's population in 1918

The storyline of the current outbreak of avian flu in the Far East, which started unfolding in December 2003, is equally disturbing, and the days of calm are not yet ending with good news. Of 31 people who are confirmed to have caught the current strain of bird flu (H5N1) in the Far East, according to the World Health Organisation (WHO), 22 have died. Although deaths have been reported only in Thailand and Vietnam, the flu outbreak is spreading through poultry in eight other countries, most of which have never reported this strain before. Tens of millions of birds have been culled in an effort to stem the tide of infection.

Now a United Nations organisation in Vietnam has reported that the virus has been found in pigs in Hanoi, although the news has been played down by the authorities and not yet confirmed by the WHO. The pigs, which showed no symptoms, apparently tested positive for H5N1 in nasal swabs; the WHO says that the presence of the virus in nasal cavities means the pigs may simply be contaminated but not infected (the virus has to defeat the animal’s immune system to take hold).

Although the virus does not yet appear to be able to jump from human to human — all those infected have caught it by handling poultry — its appearance in pigs is bad news. At best, it could mean that we are unlikely to see H5N1 consigned to the history books just yet. At worst, it is a nightmarish plot twist that has the potential to create a flu virus that can spread like wildfire in people. The most famous pandemic — the outbreak of Spanish flu in 1918 — killed at least 20 million people and more likely double that. At the time, the world population was only around 1.8 billion and mass tourism — which has spread diseases around the world at incredible rates — did not exist.

Pigs are a crucial part of the story because they can catch both bird flu and human influenza: it is possible that a pig could become a cocktail shaker for the avian and human strains. That creates a chance of the two strains genetically rearranging themselves into one highly pathogenic (disease-causing) hybrid virus. This daughter virus could be the worst of all worlds, combining extraordinary virulence with easy transmissibility. The current strain seems exceptionally nasty: it has killed 70 per cent of those infected, including young, fit individuals. Moreover, flu viruses are known to have poor photocopying machinery: each replication increases the odds that a nasty virus will emerge.

A hybrid virus would be transmitted not through the food chain — the virus is harboured in airways and lungs rather than muscle — but through the handling of live pigs. A pig with flu secretes the virus in the spray from its airways. A person in close proximity, for example during feeding, can then inhale the spray and become infected (just as human flu is passed on in the aerosols from sneezing). This scenario need happen only a few times to pose a risk: each infected person then starts a chain of infection among their friends and family. The transport of live infected animals would also spread the disease, both to other animals and the people handling them.

Karl Nicholson, Professor of Infectious Diseases at Leicester Royal Infirmary, says that farming practices in the affected countries raise concern that, even if the latest twist is unconfirmed, pigs could catch bird flu. He adds that, as far as the birds are concerned, it is also an outbreak of unprecedented virulence. “Viruses show a degree of fastidiousness, in that bird viruses tend to infect birds and human viruses tend to infect humans.”

Birds and people, he explains, have different receptors in their airways, and a virus primed to infect one species will generally not be able to infect the other. Pigs, however, are vulnerable to both.

Nicholson says: “The idea is that these viruses can mix together in pigs, because pigs are susceptible to both. Farming practices being what they are, you often have pigs and poultry close to each other. Sometimes they even live in the same household, with the farmer living upstairs and the animals living downstairs. There’s the fear that there will be some mixing in pigs.”

Previous research by Jeffery Taubenberger at the US Armed Forces Institute of Pathology has shown that the 1918 flu strain is unlike any other human strain but is very similar to a swine virus. That has lent support for the so-called “mixing vessel” theory — that to become really deadly in humans, avian flu must go via pigs, where it combines with portions of the human flu virus already present. However, there is no proof of this.

Virologists note a similarity between the 1918 virus and swine fever, but they cannot rule out the possibility that people infected pigs rather than the other way round.

Nicholson points out that pigs-as-mixing-vessels remains just a theory and that it’s just as plausible that people could be mixing vessels. After all, the current outbreak, and previous ones, show that people can catch bird flu directly from birds. That suggests that human beings would be capable of hosting the kind of genetic reassortment that could lead to a vicious virus.

The journal Science recently reported that biologists at the Scripps Research Institute in California confirmed that the 1918 strain was almost certainly avian in origin. The question is whether it jumped directly into human beings or went into pigs first. Either way, it is a salutary finding.

Bird Families Have Issues

June 20, 2006 — Bird parents, like human couples, may fight over parental duties and some mothers and fathers even favor certain offspring over others, according to a new study on territorial songbirds.

The finds suggest humans are not the only ones that prefer certain young and struggle with the difficulties of parenthood. Like divorced parents, some bird pairs even split up and divide offspring between the mother and father. Such splits may even benefit the birds in the long run.

"Brood division could possibly result from a conflict between the two sexes over the parental investment: each parent should try and do less work and push the other parent to work harder, in order both to maximize current reproductive success and to save energy for future reproductive events," said Tudor Draganoiu, lead author of the study.

Draganoiu, a post doctoral researcher at Leiden University in the Netherlands, explained to Discovery News that he and his colleagues focused on bird communication, and specifically how avian parents relate to their offspring.

The researchers spent five summers studying black redstarts, Phoenicurus ochruros, in the small mountain village of La Valla sur Rochefort, France. Draganoiu and his team first noticed that couples among these birds would sometimes "divorce," due to conflicts or when one of the birds would abandon the brood.

In such cases, the birds would often move with favored offspring to a different location. Each parent, therefore, wound up preferentially feeding and caring for certain fledglings.

The researchers recorded begging calls from all of the fledglings and determined that parents responded more to the calls of individuals they doted on. The study, recently published in the journal Animal Behavior, provides the first direct evidence that birds acoustically discriminate between two categories of their own offspring: those that they preferentially feed and those that are cared for by the other parent.

It remains a mystery as to why some bird parents gravitate towards certain fledglings. Size does not seem to be a factor, nor does the sex of the chick. Male parents, however, tended to care for fewer chicks than mothers did.

In broods of three to five fledglings, fathers usually took care of one chick by feeding it insects while mothers fed the rest.

Such brood division occurs in a number of other songbirds, including blackbirds, robins, bluethroats, dunnocks, prairie warblers, song sparrows, white-throated sparrows and even some aquatic species, such as the great crested grebe and the coot.

"I suspect that brood division could be a common characteristic across bird species and not only for insectivorous birds (there are examples also among nocturnal raptors and waders), but parent-offspring interactions after the fledgling (stage) are difficult to observe for many species," said Draganoiu.

In another paper accepted for publication in the same journal, Iain Woxvold and colleagues from the University of Melbourne, Australia, studied apostlebirds, Struthidea cinerea. For these birds, parenting commune-style, where individuals other than the parents help to take care of offspring, seems to benefit old and young alike.

"Mothers and female helpers, and to some extent fathers, provisioned less when in larger groups," the researchers said. Feeding rates per nestling actually increased under such an arrangement because of all of the available extra help.

The researchers hope additional studies will be conducted in future to determine more about bird family arrangements and the interactions between avian parents and their broods.

Medical Progress

Once foods were fortified with vitamin d and rickets appeared

to have been conquered, many health care professionals thought the major

health problems resulting from vitamin D deficiency had been resolved. However,

rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact,

vitamin D deficiency remains common in children and adults. In utero and during

childhood, vitamin D deficiency can cause growth retardation and skeletal deformities

and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults

can precipitate or exacerbate osteopenia and osteoporosis, cause osteomalacia and

muscle weakness, and increase the risk of fracture.

The discovery that most tissues and cells in the body have a vitamin D receptor and

that several possess the enzymatic machinery to convert the primary circulating form

of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has

provided new insights into the function of this vitamin. Of great interest is the role

it can play in decreasing the risk of many chronic illnesses, including common cancers,

autoimmune diseases, infectious diseases, and cardiovascular disease. In this

review I consider the nature of vitamin D deficiency, discuss its role in skeletal and

nonskeletal health, and suggest strategies for its prevention and treatment.

Sources and Metabolism of Vitamin D

Humans get vitamin D from exposure to sunlight, from their diet, and from dietary

supplements (Table 1).1-4 A diet high in oily fish prevents vitamin D deficiency.3 Solar

ultraviolet B radiation (wavelength, 290 to 315 nm) penetrates the skin and converts

7-dehydrocholesterol to previtamin D3, which is rapidly converted to vitamin D3

(Fig. 1).1 Because any excess previtamin D3 or vitamin D3 is destroyed by sunlight

(Fig. 1), excessive exposure to sunlight does not cause vitamin D3 intoxication.2

Few foods naturally contain or are fortified with vitamin D. The “D” represents

D2 or D3 (Fig. 1). Vitamin D2 is manufactured through the ultraviolet irradiation

of ergosterol from yeast, and vitamin D3 through the ultraviolet irradiation of 7-dehydrocholesterol

from lanolin. Both are used in over-the-counter vitamin D supplements,

but the form available by prescription in the United States is vitamin D2.

Vitamin D from the skin and diet is metabolized in the liver to 25-hydroxyvitamin

D (Fig. 1), which is used to determine a patient’s vitamin D status1-4; 25-hydroxyvitamin

D is metabolized in the kidneys by the enzyme 25-hydroxyvitamin D-1α-

hydroxylase (CYP27B1) to its active form, 1,25-dihydroxyvitamin D.1-4 The renal production

of 1,25-dihydroxyvitamin D is tightly regulated by plasma parathyroid

hormone levels and serum calcium and phosphorus levels.1-4 Fibroblast growth factor

23, secreted from the bone, causes the sodium–phosphate cotransporter to be

internalized by the cells of the kidney and small intestine and also suppresses

1,25-dihydroxyvitamin D synthesis.5 The efficiency of the absorption of renal calcium

and of intestinal calcium and phosphorus is increased in the presence of 1,25-dihy

droxyvitamin D (Fig. 1).2,3,6 It also induces the

expression

of the enzyme 25-hydroxyvitamin

D-24-hydroxylase (CYP24), which catabolizes both

25-hydroxyvitamin D and 1,25-dihydroxyvitamin

D into biologically inactive, water-soluble

calcitroic acid.2-4

Definition and Prevalence

of Vitamin D Deficiency

Although there is no consensus on optimal levels

of 25-hydroxyvitamin D as measured in serum, vitamin

D deficiency is defined by most experts as

a 25-hydroxyvitamin D level of less than 20 ng per

milliliter (50 nmol per liter).7-10 25-Hydroxyvitamin

D levels are inversely associated with parathyroid

hormone levels until the former reach 30 to

40 ng per milliliter (75 to 100 nmol per liter), at

which point parathyroid hormone levels begin to

level off (at their nadir).10-12 Furthermore, intestinal

calcium transport increased by 45 to 65% in

women when 25-hydroxyvitamin D levels were increased

from an average of 20 to 32 ng per milliliter

(50 to 80 nmol per liter).13 Given such data,

a level of 25-hydroxyvitamin D of 21 to 29 ng per

milliliter (52 to 72 nmol per liter) can be considered

to indicate a relative insufficiency of vitamin D,

and a level of 30 ng per milliliter or greater can be

considered to indicate sufficient vitamin D.14 Vitamin

D intoxication is observed when serum levels

of 25-hydroxyvitamin D are greater than 150 ng

per milliliter (374 nmol per liter).

With the use of such definitions, it has been

estimated that 1 billion people worldwide have vitamin

D deficiency or insufficiency.7-12,15-22 According

to several studies, 40 to 100% of U.S. and

European elderly men and women still living in

the community (not in nursing homes) are deficient

in vitamin D.7-12,15-22 More than 50% of

postmenopausal women taking medication for

osteoporosis had suboptimal levels of 25-hydroxyvitamin

D — below 30 ng per milliliter (75 nmol

per liter).12,22

Children and young adults are also potentially

at high risk for vitamin D deficiency. For example,

52% of Hispanic and black adolescents in a study

in Boston23 and 48% of white preadolescent girls

in a study in Maine24 had 25-hydroxyvitamin D

levels below 20 ng per milliliter. In other studies,

at the end of the winter, 42% of 15- to 49-year-old

black girls and women throughout the United

States had 25-hydroxyvitamin D levels below 20 ng

per milliliter,25 and 32% of healthy students, physicians,

and residents at a Boston hospital were

found to be vitamin D–deficient, despite drinking

a glass of milk and taking a multivitamin

daily and eating salmon at least once a week.26

In Europe, where very few foods are fortified

with vitamin D, children and adults would appear

to be at especially high risk.1,7,11,16-22 People living

near the equator who are exposed to sunlight

without sun protection have robust levels of 25-

hydroxyvitamin D — above 30 ng per milliliter.27,28

However, even in the sunniest areas, vitamin D

deficiency is common when most of the skin is

shielded from the sun. In studies in Saudi Arabia,

the United Arab Emirates, Australia, Turkey, India,

and Lebanon, 30 to 50% of children and adults had

25-hydroxyvitamin D levels under 20 ng per milliliter.

29-32 Also at risk were pregnant and lactating

women who were thought to be immune to

vitamin D deficiency since they took a daily prenatal

multivitamin containing 400 IU of vitamin D

(70% took a prenatal vitamin, 90% ate fish, and

93% drank approximately 2.3 glasses of milk per

day)33‑35; 73% of the women and 80% of their

infants were vitamin D–deficient (25-hydroxyvitamin

D level, <20>

of birth.34

Calcium, Phosphorus,

and Bone Metabolism

Without vitamin D, only 10 to 15% of dietary calcium

and about 60% of phosphorus is absorbed.2‑4

The interaction of 1,25-dihydroxyvitamin D with

the vitamin D receptor increases the efficiency of

intestinal calcium absorption to 30 to 40% and

phosphorus absorption to approximately 80%

(Fig. 1).2-4,13

In one study, serum levels of 25-hydroxyvitamin

D were directly related to bone mineral density

in white, black, and Mexican-American men

and women, with a maximum density achieved

when the 25-hydroxyvitamin D level reached 40 ng

per milliliter or more.8 When the level was 30 ng

per milliliter or less, there was a significant decrease

in intestinal calcium absorption13 that was

associated with increased parathyroid hormone.10‑12

Parathyroid hormone enhances the tubular reabsorption

of calcium and stimulates the kidneys to

produce 1,25-dihydroxyvitamin D.2-4,6 Parathyroid

hormone also activates osteoblasts, which stimulate

the transformation of preosteoclasts into mature

osteoclasts (Fig. 1).