Exhausted by Illness, and Doubts

By DAVID TULLER
Published: January 3, 2011

Chronic fatigue syndrome causes a host of debilitating symptoms: profound exhaustion, disordered sleep, muscle and joint pain and severe cognitive problems, among others. But what causes the syndrome itself

Since the first cases in the United States were identified in the 1980s, scientists have been divided over that question. Some have suspected that one or more viral infections are likely to play a central role.

But many other researchers — not to mention relatives, friends, employers, doctors and insurers of the million or more Americans estimated to suffer from the illness — have dismissed it as stress-related, psychosomatic or simply imaginary.

Now recent back-to-back announcements have highlighted both the volatility of the issue and the ambiguity of the science, and have alternately heartened and dismayed patients.

On Dec. 14, an advisory panel suggested that the Food and Drug Administration ban blood donations by people with a history of C.F.S., as the illness is often called. The goal was to prevent the possible spread of viruses that two high-profile studies had linked to the condition.

But then, on Dec. 20, the journal Retrovirology published four papers suggesting that key findings in those studies could have resulted from laboratory contamination.

The F.D.A. is not required to accept the opinion of its advisory panel. Yet patients still hailed the recommendation as a sign that their illness was being taken seriously.

“When an F.D.A. panel suggests that patients with C.F.S. not donate blood, that’s going to impact the way doctors think about it,” said Mary Schweitzer, a former history professor at Villanova, who has frequently written about living with the illness. Dr. Schweitzer said she has been unable to work for 16 years because of the syndrome, which was diagnosed after she suffered from a series of flulike illnesses.

The studies that concerned the F.D.A. had reported that people with the syndrome, which is also called myalgic encephalomyelitis or myalgic encephalopathy in Europe, showed higher rates of infection with the virus XMRV or others from the same category, known as MLV-related viruses. (These viruses are all relatives of mouse leukemia viruses, some of which can infect species other than mice; their role in human disease, if any, remains poorly understood.)

But several other research teams in the last year have found no connection between chronic fatigue syndrome and these viruses, although none tried to replicate the exact methods used by researchers who reported an association.

The new papers in Retrovirology reported that contamination of tissue samples or other laboratory items with mouse DNA or viral genetic material could lead to false positive results for XMRV, and by extension other MLV-related viruses, specifically when using polymerase chain reaction technology. The technique rapidly produces millions of copies of genetic segments, so even minute traces of genetic contamination can skew results.

“Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome,” said the senior author of one of the studies, Greg Towers, a professor of virology at University College London, in a statement released by Wellcome Trust Sanger Institute, the British research center that co-sponsored it.

Other scientists and advocates for patients have sharply criticized such certainty as unwarranted, noting that the Retrovirology papers themselves expressed their findings in more cautious terms. The critics agree that contamination can be a serious issue when using polymerase chain reaction technology. But the new papers, said Eric Gordon, a doctor in Santa Rosa, Calif., who treats many patients with the illness, do not evaluate other strategies besides P.C.R., as the technique is known, for detecting the MLV-related viruses, like testing for an immune response and culturing the viruses in cell lines.

“The articles make the point that P.C.R. doesn’t work that well for these viruses, and then they act like that disproves the whole idea,” said Dr. Gordon.

XMRV was first identified in 2006 and has been detected in prostate cancer patients in some studies. It was linked to chronic fatigue syndrome in October 2009 in a paper in the journal Science by researchers from the Whittemore Peterson Institute for Neuro-Immune Disease at the University of Nevada, Reno, the National Cancer Institute and the Cleveland Clinic.

The researchers relied on P.C.R. technology to show that about two-thirds of patients but less than 4 percent of control subjects harbored XMRV. Using other technologies, however, they also documented an antibody response in some chronic fatigue syndrome patients, and reported that XMRV in human blood could infect other human cell lines.

In a statement responding to the new papers in Retrovirology, Judy A. Mikovits, director of research at Whittemore Peterson and the senior author of the Science study, said her team took extensive steps to rule out P.C.R. contamination and also focused on other approaches to finding XMRV. “Nothing that has been published to date refutes our data,” she said.

Even some specialists stumbled over the meaning of the new findings. Vincent Racaniello, a professor of microbiology at Columbia not involved in the research, apologized on his Virology Blog for having stated that it was likely to spell “the beginning of the end” for the proposed connection between the viruses and chronic fatigue syndrome.

After reviewing the issue more thoroughly, he wrote, he realized that the new studies “show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised.” He added, “If I had difficulties interpreting these papers, how would nonscientists fare?”

Federal agencies have come down on different sides of the issue. In a paper published in The Proceedings of the National Academy of Sciences in August, researchers from the National Institutes of Health and the F.D.A. found a link between the fatigue syndrome and MLV-related viruses (although not specifically XMRV). In contrast, a study from the Centers for Disease Control and Prevention was among those not reporting a link.

Federal health officials have organized two research efforts to resolve the inconsistencies, determine whether XMRV and MLV-related viruses are possible human pathogens, and identify reliable ways to detect them. Patients hope the increased attention will quickly lead to research on treatments, including clinical trials of H.I.V. drugs, some of which have been shown in lab studies to inhibit the replication of XMRV.

The unsettled situation has created a quandary for patients with chronic fatigue syndrome and the doctors who treat them. Some patients are seeking to be treated with H.I.V. drugs, which doctors can legally prescribe even though the F.D.A. has not approved them for that purpose.

Many doctors and researchers say it is too early to prescribe the drugs for chronic fatigue because of possible side effects, like bone marrow suppression, gastrointestinal problems and liver or kidney dysfunction, among others. But Michael Allen, a writer and a former psychologist in San Francisco who has been disabled for more than 15 years, said he wouldn’t hesitate to try the medications if he found out he was positive for an MLV-related virus.

“It feels patronizing when the medical establishment says the side effects are too risky and we should keep waiting,” he said. “What that says to me is they have no idea whatsoever how sick people like me have been with this disease.”

Source

Related: The Lingering Mystery of Chronic Fatigue Syndrome

Liver Disease Reported in Three Nitrofurantoin Patients

Date Published: Friday, September 24th, 2010

A new study has linked the use of the antibiotic nitrofurantoin with autoimmune hepatitis, a type of liver injury. Nitrofurantoin, which is primarily used in the treatment and prevention of urinary tract infections, is sold under the brand names Furadantin, Macrobid, Macrodantin, Nitrofur Mac, Nitro Macro, Nifty-SR, Martifur-MR and Urantoin.

According to a case study in the Journal of Medical Case Reports, three women (aged 65, 42 and 74 years old) developed autoimmune hepatitis after treatment with nitrofurantoin. All were receiving long-term nitrofurantoin to prevent recurrent urinary tract infections.

Two of the patients presented with jaundice, and one required a prolonged hospital admission for liver failure. In all three patients nitrofurantoin was withdrawn, and long-term immunosuppressive therapy with prednisolone and azathioprine or mycophenolate was given. Fortunately, the patients responded well, with liver biochemistry returning to normal within a few months.

The authors of the report pointed out that although nitrofurantoin rarely causes autoimmune hepatitis, this antimicrobial is increasingly used as long-term prophylaxis against recurrent urinary tract infection. They cautioned general practitioners and urologists who prescribe long-term nitrofurantoin therapy to be aware of this adverse effect.

Autoimmune hepatitis is a disease in which the body’s immune system attacks liver cells. This immune response causes inflammation of the liver, also called hepatitis. Autoimmune hepatitis is usually quite serious and, if not treated, gets worse over time. Autoimmune hepatitis is typically chronic, meaning it can last for years, and can lead to cirrhosis—scarring and hardening—of the liver. Eventually, liver failure can result. About 70 percent of those with autoimmune hepatitis are female.

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New TB Vaccine Enters Clinical Testing

23 September 2010

Colorized scanning electron micrograph of Mycobacterium tuberculosis bacteria. Source: CDC/ R. Butler; J. CarrAt an international gathering of TB vaccine researchers in Tallinn, the Aeras Global TB Vaccine Foundation announced it will initiate a clinical trial of an investigational live recombinant tuberculosis vaccine to be led by researchers at Saint Louis University in St. Louis, Missouri, USA. The announcement was made at the Second Global Forum on TB Vaccine Development.

Building on more than a decade of global scientific research, Aeras scientists have engineered a new investigational vaccine, called AERAS-422, which will undergo clinical trials to evaluate its properties for interrupting TB at all stages of infection, including initial infection, latency and reactivation.

“Moving our lead in-house vaccine from the laboratory into clinical testing is an important milestone for Aeras and its partners. Finding a potential replacement for the currently available TB vaccine, which was invented almost 90 years ago, is a primary goal in our mission,” said Thomas G. Evans, MD, Aeras’ Chief Scientific Officer. “Based on data from pre-clinical studies, we are cautiously optimistic about the potential of this vaccine candidate to be safer and more immunogenic than the currently available vaccine.”

The new vaccine, called AERAS-422, is a modernized version of the currently used TB vaccine – Bacille Calmette Guérin (BCG). BCG is widely viewed as insufficient in preventing pulmonary TB, and this trial is part of a wider global effort to develop safer and more immunogenic TB vaccines that would be effective against all forms of TB.

AERAS-422 has been modified with an endosome escape mechanism and over-expresses three key proteins: 85A, 85B and Rv3407. The bacterium that causes TB hides inside cells. Therefore, the endosome escape mechanism is designed so that the proteins will escape an internal compartment of the cell and be more efficiently presented to the immune system to elicit a greater protective response in the body.

“The TB epidemic continues to become more complex and difficult to control, especially in South Africa where resistance to available TB treatments is on the rise,” said Bernard Fourie, PhD, Chief Scientific Officer of Medicine in Need and Managing Director of Mend South Africa. “The scientific community has made developing a safer and more effective TB vaccine a priority and we are pleased that there is progress in the field.”

Source

Treating anaemia can boost energy

3 July 2010

Anaemia is not a normal part of ageing, yet it's fairly common in older adults and causes frailness, weakness and increased risk of falls. According to Mayo Clinic Women's HealthSource, more than one in 10 older adults has anaemia. Twenty percent of women are anaemic by age 85.

The June issue of the newsletter provides an overview of anaemia, including symptoms, causes, diagnostic tests and treatment options.

Anaemia occurs when the number of red blood cells in the blood drop below normal, or the red blood cells don't contain enough haemoglobin, the iron-rich protein that gives blood its red colour. The classic anaemia symptoms are pale skin, fatigue and shortness of breath or weakness. In older adults, initial symptoms may be fainting spells, chest pain or confusion. Because many tissues and organs can be affected, other symptoms are possible, too, including dizziness, cold hands and feet, headaches and a fast heartbeat. Highlights from the report include:

Most common cause

Iron deficiency anaemia, caused by blood loss, is the most common type of anaemia. Chronic bleeding in small amounts over a long time depletes the body of iron. In older adults, blood loss usually stems from intestinal diseases, such as ulcers, colon polyps, diverticulitis or cancer. Aspirin or nonsteroidal anti-inflammatory drugs such as ibuprofen can also cause bleeding.

Other causes

Vitamin B-12 and folate are needed to produce healthy blood cells. When these nutrients are missing from the diet, or the body can't absorb B-12 from food, anaemia can result. Some long-term illness can cause anaemia, too. Examples include rheumatoid arthritis, HIV/AIDS, cancer, cirrhosis and other forms of liver disease.

Treatment

Anaemia isn't a disease, but rather a sign of an underlying problem, so treatment is tailored to the cause. For those with iron deficiency anaemia, eating iron-rich foods can help. Examples include fortified cereals and breads, red meat, peas, beans, lentils, eggs, spinach and other dark green leafy vegetables, dried fruits (raisins, apricots and peaches), tofu, chicken and pork. Supplements, when recommended by a doctor, may also be helpful. Severe anaemia may require transfusions, medication to prevent the body's immune system from destroying its own red blood cells, or a synthetic version of the hormone erythropoietin to stimulate the bone marrow to make more red blood cells.

Even mild anaemia can take a toll on energy levels and quality of life. When anaemia is suspected, consult a doctor about a complete blood count to check for the condition. Just a small increase in blood count numbers can boost energy and help maintain an active life.

(Source: Mayo Clinic: Women's HealthSource: June 2010)

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CDC Survey Finds Nine in 10 U.S. Adults Consume Too Much Sodium

For Immediate Release: June 24, 2010
Contact: CDC Division of Media Relations
(404) 639-3286
 
Majority of sodium comes from most commonly eaten foods
 
Less than 10 percent of U.S. adults limit their daily sodium intake to recommended levels, according to a new report, "Sodium Intake in Adults – United States, 2005-2006," published today in CDC's Morbidity and Mortality Weekly Report. The report also finds that most sodium in the American diet comes from processed grains such as pizza and cookies, and meats, including poultry and luncheon meats.
 
According to the report, U.S. adults consume an average of 3,466 milligrams (mg) of sodium per day, more than twice the current recommended limit for most Americans. Grains provide 36.9 percent of this total, followed by dishes containing meat, poultry, and fish (27.9 percent). These two categories combined account for almost two-thirds of the daily sodium intake for Americans.
 
An estimated 77 percent of dietary sodium comes from processed and restaurant foods. Many of these foods, such as breads and cookies, may not even taste salty. "Sodium has become so pervasive in our food supply that it's difficult for the vast majority of Americans to stay within recommended limits," said Janelle Peralez Gunn, public health analyst with CDC's Division for Heart Disease and Stroke Prevention and lead author of the report. "Public health professionals, together with food manufacturers, retailers and health care providers, must take action now to help support people's efforts to reduce their sodium consumption."
 
The 2005 Dietary Guidelines for Americans recommends that people consume less than 2,300 mg of sodium per day. Specific groups, including persons with high blood pressure, all middle-aged and older adults and all blacks, should limit intake to 1500 mg per day. These specific groups comprise nearly 70 percent of the U.S. adult population. This study found that only 9.6 percent of all participants met their applicable dietary recommendation, including 5.5 percent of the group limited to 1,500 mg per day and 18.8 percent of the 2,300 mg per day group.
 
The report examined data for 2005–2006 from the National Health and Nutrition Examination Survey (NHANES), an ongoing study that explores the health and nutritional status of adults and children in the United States. Researchers used information from 24-hour dietary recall and the USDA National Nutrient Database to estimate the daily sodium intake and sources of sodium intake for U.S. adults.
 
The findings add to a growing body of observational research studies on Americans' excessive sodium consumption. Overconsumption of sodium can have negative health effects, including increasing average levels of blood pressure. One in three U.S. adults has high blood pressure, and an estimated 90 percent of U.S. adults will develop the disease in their lifetime. Blood pressure is a major risk factor for heart disease and stroke, the first and third leading causes of death among adults in the United States.
 
For more information about sodium and blood pressure, visit www.cdc.gov/salt.

http://www.cdc.gov/media/pressrel/2010/r100624.htm

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES