From Plague to Leprosy: 7 Diseases We'd Forgotten About Leprosy, polio and TB are among diseases that plague millions worldwide.

Aug. 14, 2009 -- The bubonic plague, leprosy and polio are thought of as diseases of the past -- things that might have had a part in history, but aren't around to infect us any longer.

But a recent incident in China, where a town was quarantined for 10 days after three people died of a variant of bubonic plague, was just one of many reminders that these diseases have not vanished from the face of the earth.

While many think of these diseases as completely eradicated -- and they occur far less frequently than they used to in the United States -- they have managed to hang on.

"The microbes have hopes, dreams and aspirations just like human beings. In their case, it's to infect other people," said Dr. Howard Markel, a pediatrician and medical historian at the University of Michigan.

Smallpox was the first disease for which a vaccine was developed. While the British doctor Edward Jenner gave the first injection in 1796, the World Health Organization did not declare the disease eradicated until 1980.

But replicating the success of the smallpox effort with any other disease has yet to happen.

"There are a number of diseases about which we hear very little in this country but prospects for actually eliminating/eradicating any of them are slim," said Dr. D. A. Henderson, author of "Smallpox: the Death of a Disease," who led the WHO's initiative to eradicate the virus.

Other diseases, he said, present challenges not faced with smallpox.

"Why not the others?" Henderson said. "Some, because there is an animal reservoir, like plague, or long-term carriers of the disease who can excrete the organism -- tuberculosis and leprosy -- or diseases for which the vaccine is inadequate to accomplish what we would like to achieve -- diphtheria and, to some degree, polio. It is not a simple subject to address."

For some of these diseases, treatment is difficult to administer because of the economic conditions of people suffering from the disease.

Emerging infections -- such as bird flu and SARS -- command headlines, but many other diseases still plague humans around the world, if not generally the United States.

"There's a group of infections that have been with us forever," said Dr. Peter Hotez, professor and chair of the department of microbiology, immunology and tropical medicine at George Washington University, who calls them neglected infections -- because they are often ignored, or biblical diseases, because ancient accounts describe their presence.

"Most of these neglected infections or biblical diseases occur more in rural settings than in urban settings," he said. "You will always find these diseases wherever you find extreme poverty, and that is the most common determinant."

In the following pages, we present seven infections from the past that still plague us today.

Pneumonic/Bubonic Plague

The pneumonic and bubonic plagues are caused by the bacterium Yersinia pestis, the difference being that pneumonic plague can spread from person to person -- without infected fleas.

While the pneumonic form struck China earlier this month, bubonic plague still persists in the United States, in the Southwest. Wild rats and fleas carry the disease, and when in proximity to humans, fleas will spread it to them rather than simply among rats.

"The U.S. reports around a dozen cases a year," Hotez said.

Some cases have received publicity, but the disease tends not to be well known here. Part of the reason is that the disease is very treatable with the administration of antibiotics.

But, while the disease is controlled, it is unlikely to be eliminated completely.

"Getting rid of Yersinia pestis completely from nature, that's unlikely," Markel said. "It's still in the flea population and it's still in the rat populations, and I don't know how you're going to kill all of the fleas and all of the rats."

Spanish and Swine Flu -- H1N1

The outbreak of so-called Spanish flu in the winter of 1918-19 caused tens of millions of deaths. While the current strain, known as swine flu or influenza A, has claimed 1,462 lives to date, according to the most recent numbers from the WHO.

But flu season has yet to arrive, and the possibility of more deaths from the pandemic has many worried. And despite the different names given to the influenza strains, both have the same basic structure, H1N1. The virus has mutated -- and survived -- despite efforts to eliminate it.

"We don't know exactly where these viruses hide in the time that they aren't active in the population," said Dr. Patricia Winokur, a professor of internal medicine at the University of Iowa who is working on developing a vaccine for swine flu. "Somewhere they lay dormant and then get into the human population at different times."

While 1918 marked, perhaps, the most deadly worldwide pandemic of influenza attributed to H1N1, Markel noted that accounts of influenza date as far back as the Renaissance, although it's difficult to determine which strains were responsible.

"We just have these old accounts, but it's not the same kind of data that we'd use today," he said.

But influenza has managed to adapt over time, changing each year to beat the human immune system.

"Each year, they're just a little bit different," Winokur said. "Those proteins have shifted just a little bit over time, and our immune system isn't perfect about capturing those new genetic variants."

She noted that scientists have developed a vaccine to help prevent flu and antivirals to lessen the impact of an infection, but, "They're not flat-out cures."

"This strain will likely stay in our population for quite some time, and eventually it will be replaced by new strains," Winokur said. "A lot of it has to do with this type of virus being able to mutate quite quickly. Each year it mutates and creates a slight variation on itself, and that allows it to survive and continue to infect humans."

Compounding the problems with wiping out influenza is the fact that it can live in animals, such as birds and pigs.

"It's been traditionally very hard to eradicate diseases that have broad animal reservoirs," Winokur said. "We can't vaccinate all birds and all swine the way we could, for example, [vaccinate people against] smallpox."

Polio

Like smallpox, polio has a vaccine and, therefore, many have high hopes that it can be eradicated. It is virtually gone from the United States but is still a problem abroad.

"There is an elimination strategy being led by the World Health Organization," Hotez said. "There was great optimism it could be eradicated just like smallpox."

But polio has some distinctions from smallpox that make such an outcome less likely.

Polio can cause paralysis, in the legs and even the lungs.

"You could stop breathing," Hotez said. "That's why during polio epidemics in the United States, they used to put people in iron lungs."

But, he noted, "It's only one out of 100 that are infected with polio that actually develop paralysis. Many people would have no symptoms at all."

To eradicate smallpox, doctors used what is known as "ring vaccination," giving the vaccine to anyone who lived around a victim of the disease.

But because polio has only subtle signs, it is much more difficult to determine who has the virus. Complicating matters, Hotez said, is that symptoms of polio can often mimic those of other viruses.

"You have to be much more aggressive in how you do surveillance for the virus," he said.

So the ambiguity and the subtlety of polio make it a trickier target than smallpox.

A similar effect can take place with pertussis, or whooping cough, simply because the immunity from the vaccine given can wear off over time and the disease does not affect adults as harshly as it does children.

"Many people who were immunized as children may no longer be immune as adults," Markel said.

If they become infected, they can pass that infection to children, who tend to have more serious cases of whooping cough than adults.

Chagas Disease

Until a few years ago, Chagas disease was not really found in the United States. But conditions in post-Katrina Louisiana and immigration from areas where the disease is endemic have brought more cases to the United States.

The disease is spread by the bug known as the kissing bug and the assassin bug. It bites its human victim, defecating and causing an itch, which becomes Chagas disease when the victim scratches the area, allowing the infection to enter the body.

"Chagas disease is a parasitic infection. It's a disease of poverty," said Dr. Carlos Franco-Paredes, who treats infectious diseases at Atlanta clinics through Emory University. The bug typically lives in poor quality housing, feasting on host victims at night.

Hotez notes that 8 million to 9 million people in Latin America are infected, and he estimates that 400,000 people in the United States have the disease. Patients who get a blood transfusion may be infected, although a test was created in 2006, and Franco-Paredes noted that it is possible to get the infection by drinking some juices in South America, since the sugar cane used is the nesting place of the kissing bug.

The infection attacks the heart, but over the course of many years. Five percent of people will develop symptoms early on, such as liver or spleen enlargement.

But the other 95 percent will show no signs for 20 or 30 years.

"You have heart failure, or you have dilation of the esophagus or the colon," Franco-Paredes said.

People will lose the ability to eat.

"There's really no treatment of Chagas after you have developed all those complications," he said.

Hotez notes one treatment is possible. "Once it gets beyond a certain point, the only treatment is heart transplantation," he said, but once the disease reaches that stage it becomes chronic and incurable.

"You have to catch it early," Hotez said.

Franco-Paredes notes that a patient needs heart treatment or a pacemaker, but patients who would get Chagas disease, for the most part, could never afford the treatments.

Calling the disease "a biological expression for social inequality," he said, "If there's not redistribution of wealth in Latin America, we won't be able to eliminate Chagas disease."

Leprosy

Leprosy is among the oldest human diseases, with descriptions of a similar illness in the Bible, afflicting people who spoke ill of others.

"Many of these biblical diseases have a stigma attached to them, because they can be very disfiguring," Hotez said.

He said mock funerals were often held for people with leprosy. "They thought it was a punishment for God," Hotez said.

Franco-Paredes treats roughly 300 cases each year, some of whom have not left the United States.

"It continues to be a problem, but it's also a disease of vulnerable populations from a socioeconomic perspective," he said. "Even nowadays, we don't know how leprosy is transmitted."

The disease attacks the skin and ultimately the body's nerve cells. It is caused by a bacterium similar to the one responsible for tuberculosis.

Franco-Paredes notes that recent efforts have simply prevented the disease from occurring more often, without preventing it from happening.

"The incidence of the disease has remained the same," he said.

The most common cause within the United States is exposure to armadillos, largely in eating them, he said, as well as having a farm of them or hunting them.

"The bacteria has been identified in armadillos, and the few cases we see that have never travelled, they have that risk factor of being in contact with armadillos," Franco-Paredes said.

He also noted that there is no evidence of human-to-human transmission, because people in the same household who have it tend to also share other risk factors.

"To acquire leprosy, compared with tuberculosis, you need a very long exposure," he said.

The problem in treating it that people tend to go for treatment when they reach later stages of the disease.

"We have good treatments and they're widely available, but the problem again is the late identification of these cases," Franco-Paredes said. "Until we understand better the epidemiology of leprosy and the transmission, I think leprosy will continue to be around.

"I'm sure we will continue to see cases over the next few centuries. With leprosy at this point, I don't think we can talk about elimination."

Hookworm

"In many respects, the rural American South at the beginning of the 20th century resembled a developing country, with high rates of hookworm infection. … Indeed, the pejorative concept of the "lazy Southerner" was partly a consequence of the toxic combination of chronic parasitism and nutritional deficiencies that plagued the region, as the [neglected tropical diseases] kept the southern population mired in poverty just as they do today in Africa, Asia, and elsewhere," Hotez wrote at the beginning of his chapter on tropical diseases in the United States in his book "Forgotten People, Forgotten Diseases."

The nutritional deficiencies and parasitic infections that plagued the U.S. South at the beginning of the 20th century have largely been dealt with, but the diseases still plague many living in rural poverty throughout the world.

The hookworm parasite, which lives in the soil, causes severe anemia in its victim and the infection can prove difficult to get rid of. Hotez has developed a vaccine for hookworm, but notes that further work will be needed.

While the infection may once have hurt the economy of the South, Hotez said, it now has the same effect in other parts of the world. Getting a hookworm infection has been correlated with lower income later on.

"A lot of these neglected diseases are poverty promoting -- they not only occur in poverty but they promote poverty," he said.

Franco-Paredes notes that interventions have helped reduce cases, including vaccines and having people wear shoes.

It remains unclear how long this disease will persist, since much of its root cause lies in poverty -- well off people do not get hookworm infections.

"Any of these diseases … these are diseases that occur mostly in the setting of extreme poverty, and exposure as a result," Hotez said.

Tuberculosis

As a few prominent cases in recent years have shown, tuberculosis is still around, even if it isn't as deadly as it once was. But TB still poses a major problem for doctors, even if most cases do not occur in the United States.

"It's very difficult to eradicate and it's been with human beings … since before written history," said Dr. Douglas Hornick, a professor of internal medicine at the University of Iowa who is consulted by the Iowa Department of Public Health for tuberculosis-related matters.

"It's an insidious, slow-onset disease that patients develop a cough over time," he said. Ultimately, patients can develop a persistent fever and lose energy and weight.

While patients may not know they have the disease, they can be spreading it to other people during that time.

"Most tuberculosis is still susceptible to the standard drugs that we have available," Hornick said.

But tuberculosis has become more of a threat than it once was with the development of forms that are resistant to the drugs typically used to treat the disease.

While tuberculosis was once fatal to 40 to 50 percent of people who caught it, that number remains the same for people with resistant forms.

"We can cure tuberculosis, but it is extremely difficult to treat in drug-resistant forms," Markel said. "It's a terrible disease, and particularly with drug-resistant or multi-drug-resistant tuberculosis, a real fear. You're instantly jerked back into the 19th century, where we didn't have these wonderful antibiotics to treat these terrible diseases."

Compounding the problem is surveillance. People in the United States often receive a skin test to see if they have ever had the disease, but that is not done around the world, where such screening may prove impractical or unaffordable -- and where a great number of cases exist.

Some estimates place up to a third of the world's population as having tuberculosis.

"Eighty to 90 percent of those people don't know they're infected, because it's latent," Hornick said, referring to the phase when TB does not show symptoms. "The majority of people that are infected never have active disease; they just carry it in their system."

And tuberculosis still presents a challenge in some areas of the United States. "Even in the U.S., there are so many cases in local areas, like the major cities," Franco-Paredes said.

He said rates where he works, in Fulton County, Ga., are "as high as some of the rates of a country in Africa, like Uganda or Kenya."

"I'm not very optimistic," he said. "I think TB will remain with us forever."