Bay Area Reporter - October 5, 2000
Bob Roehr

People living and working with HIV disease have long known that coinfection with another disease is not a good thing. The added burden on the immune system often results in one or both of the diseases progressing faster. Even a cold or a vaccination can produce a short-term upward blip in HIV viral load.

Watt's team of U.S. military and Thai researchers at Chiangrai in northern Thailand looked at four tropical diseases of public health importance - malaria, dengue, leptospirosis, and scrub typhus-for possible interactions with HIV coinfection.

One patient stood out like a super-nova among the blood screening data gathered that first month. His HIV viral load was a staggering 2.5 million copies. He also showed the high fever and other symptoms of acute scrub typhus infection. Standard medication cleared up this infection in a few days. Thai government policy did not provide anti-HIV drugs at the time.

Two weeks later when they ran another blood test, the patient's HIV viral load had disappeared. It was undetectable with the assay used. "This was so surprising, so unexpected that it prompted us to begin a full-scale prospective search for other HIV-infected patients who came in with acute scrub typhus infection," said Watt.

Scrub typhus

Scrub typhus is an obscure disease to most people in the West, but it is a major health problem in Asia with an estimated 1 million new infections a year. Chiggers and mites pass the bacteria from rodents to people with their bite. Symptoms of the disease are a lot like the flu, with fever and respiratory problems, sometimes a scar at the site of the bite and maybe a rash. It is difficult to diagnose and 10-30 percent of those infected will die if not treated.

Earlier work found that the drugs used to treat scrub typhus could not prevent the disease, nor would they be effective if used too early. The body had to be given about a week to mount an immune response to the invader as part of the total effort to defeat it.

A 1986 study had shown that coinfection with HIV did not increase the severity of scrub typhus infection. It also found that the organism could be cultured out of the blood of about half the Thais who were HIV seronegative.

The curious fact was that these researchers could find the organism in only 14 percent of those who were HIV-positive. "This was the opposite of what one would have predicted," said Watt. "With salmonella or TB [tuberculosis], bacteremia is more common in HIV infected individuals.

"Looking back on this observation now, we think that just as scrub typhus inhibits HIV, HIV also inhibits Orientia tsutsugamushi," the specific bacteria that causes scrub typhus.

Watt's team went looking for more people with acute scrub typhus infection on top of their HIV. They screened more than 38,000 patients and found 31 who fit the bill. Most of those had a third or fourth ongoing infection as well, so they culled the number to 10 patients who looked like they had just scrub typhus and HIV.

This group had very advanced HIV disease, with a median of only 161 CD4 cells. Blood samples were taken when they first appeared at the hospital and again seven, 14, and 28 days later. The baseline used was the last measurement, day 28, when all signs pointed to the scrub typhus infection having been cured.

Four patients had significant decreases in their HIV viral load during acute scrub typhus infection, two became detectable by the assay used.

"Not every scrub typhus infection is associated with a change in HIV viral load," said Watt. He explained that there is broad genetic variation in the bacteria.

"One of our tasks is to figure out what it is about certain strains of scrub typhus that produce this kind of results rather than no change."

That means learning more about the basic science of the little studied microbe.

Back to the lab

Lab work revealed another very interesting fact about the scrub typhus patients, none of them had the syncytia-inducing (SI) phenotype, or variation of HIV, that is dominant in late stage disease and is responsible for massive cell death.

When researchers put the blood of a mouse infected with scrub typhus into tissue culture, it reduced the formation of the SI phenotype, and it reacted with HIV-infected human lymphocytes. Something in the blood was either directly inhibiting HIV or causing some other part of the immune system to inhibit HIV.

Watt outlined similarities between HIV and Orientia tsutsugamushi in their life cycles and the way they cause disease. He speculated that perhaps one difference might explain why the human immune system can mount an effective attack against scrub typhus but not against HIV.

Both infections spread by "budding" off of infected cells. Tissue culture studies show that the process is rapid with HIV, but with scrub typhus they "are literally hanging out on the cell surface for several days," Watt explained. He suggested that the longer exposure helps the body generate a more potent immune response.

Watt offered this hypothesis: "Perhaps what we are seeing in patients infected with HIV who acquire scrub typhus is that this very powerful immune response raised to the scrub typhus is somehow being turned against the HIV. Perhaps [it is] because of antigenic similarities which have evolved during coinfections of wild monkey populations."

Work continues to try to identify the factor or factors resulting from scrub typhus infection that can inhibit HIV replication in humans. Such a factor may prove useful both as therapy for HIV and as a vaccine to prevent infection.

001005
BR001001

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .