- With affordable AIDS drugs arriving in many poor countries,
experts say a startling and worrisome side effect has emerged: in some
patients, the treatment uncovers a hidden leprosy infection.
-
- No one knows how widespread the problem is. Only about
a dozen cases have been described in medical literature since the 1st one
was found, in London in 2003. But AIDS specialists in Brazil, India, Africa,
the Caribbean and elsewhere are reporting that some patients on life-saving
antiretroviral drugs are developing painful facial ulcers or losing feeling
in their fingers and toes. And in the developing world, where 300 000 new
cases of leprosy were discovered in 2005 and where 38 million are infected
with the AIDS virus, the problem will inevitably get worse, experts say.
-
- "This is just the peak of the iceberg," said
Dr. William Levis, who treats leprosy patients at Bellevue Hospital in
New York City. "It's early in the game. Most physicians don't even
think about leprosy, so there's probably much more around than we know."
-
- Dr. Gilla Kaplan, a professor at the University of Medicine
and Dentistry of New Jersey and one of the 1st to study connections between
AIDS and leprosy, agreed. Antiretroviral treatment, she said, "is
going to flush out the silent leprosy by making it symptomatic."
-
- Because leprosy, a bacterial disease, can be treated
with specialized antibiotics that are supplied free by the Novartis pharmaceutical
company, there is little prospect of a worldwide epidemic or large numbers
of deaths. "It's a matter of concern for the individual patients,"
said Dr. Denis Daumerie, who leads the efforts by WHO to eliminate leprosy.
"It's not a matter of concern for public health."
-
- In the mid-1980s, as it became clear that AIDS was not
primarily a disease of gay American men but was killing millions of people
-- men, women and children in poor countries -- many public health doctors
prophesied that it would be a double disaster for those with leprosy. It
seemed a logical assumption, since leprosy is caused by a germ from the
same family of waxy-walled bacteria as those that cause tuberculosis and
_Mycobacterium avium-intracellulare_, 2 major killers of AIDS patients.
But it proved a false alarm.
-
- "People expected a big surge in leprosy, but it
didn't happen," said Dr. Diana N. Lockwood, a leprosy expert at the
London School of Hygiene and Tropical Medicine. When the predictions did
not come true, she said, "we assumed that co-infected people just
died before their leprosy became manifest." The incubation period
for the most easily diagnosed form of leprosy is 8 to 13 years, while the
incubation period for AIDS is 8 to 10.
-
- But leprosy in people known to have been already infected
did not seem to worsen when those patients developed AIDS too, showing
that the 2 diseases can apparently coexist without reinforcing each other.
So it came as a shock to doctors when AIDS treatment caused hidden cases
of leprosy to appear.
-
- The 1st such patient described in a medical journal was
Dr. Lockwood's, a Ugandan exile in London who was being treated for both
tuberculosis and AIDS, and suddenly developed a swollen lesion on his face.
"It took us a while to realize it was leprosy," Dr. Lockwood
said. "Since then, we've seen more cases in people from Brazil and
India."
-
- Depending on symptoms, leprosy is often initially misdiagnosed
as arthritis or lupus. Painful facial lesions, which are less common, can
have many causes; in the Ugandan man's case, doctors said, his immune system
probably formed nodules around bacteria next to a facial nerve.
-
- Dr. Michael S. Glickman, a bacteriologist at Memorial
Sloan-Kettering Cancer Center who treated the only co-infected case known
in New York, said he too had some difficulty diagnosing his patient's leprosy.
-
- Dr. Glickman's patient, a man from Burkina Faso, was
suffering from advanced AIDS when he 1st saw Dr. Glickman 6 years ago,
with a CD4 cell count below 10 (normal is 500 or more). As the patient
recovered on antiretroviral therapy to a CD4 count of 600, he developed
a lighter-colored patch of skin. Dr. Glickman noticed that it was slightly
numb to the touch. Fortunately, he had once visited Dr. Levis's clinic
at Bellevue, and made the connection. "It was so unremarkable that,
if I hadn't seen leprosy patients, I wouldn't have known what it was,"
he said.
-
- Treatment in cities like New York and London is relatively
easy, but the real crisis, experts said, will evolve in poor countries
with dual epidemics. In French Guiana, for example, Dr. Pierre Couppie,
chief of dermatology at the Central Hospital in Cayenne, said he believed
that about one in every 500 AIDS patients would develop leprosy lesions
soon after starting treatment.
-
- Brazil has the world's highest per-capita leprosy rate
and also one of the most effective AIDS treatment programs in the developing
world, and 7 Brazilian cases have been mentioned in medical literature.
No countrywide study has been done, but Dr. Patricia D. Deps, a leprosy
expert at the Federal University of Espirito Santo in Brazil, said it was
"becoming more and more common."
-
- "We don't have good numbers, but we think about
2 percent of the leprosy cases in Brazil are co-infected with HIV,"
Dr. Deps said. The country that most worries experts is India. Not long
ago, it had 70 percent of the world's leprosy cases. Its official caseload
is a bit of a mystery now. After an aggressive 20 year campaign to find
and treat new cases, India officially declared leprosy "eliminated
as a public health issue" in 2005. However, that statement was carefully
crafted: it means there is a national average of lower than one case per
10 000 citizens, which could be as many as 100 000 new cases a year.
-
- At the same time, with about 5.2 million people infected
with the AIDS virus, India is poised to outstrip South Africa as the country
with the most AIDS victims. But its epidemic began much later than South
Africa's or Brazil's, and it has been slow to roll out AIDS treatment.
As treatment grows, leprosy may surge along with it. Other countries with
high numbers of leprosy victims are Myanmar, Madagascar, Nepal and Mozambique.
-
- Doctors have long known that dormant diseases can surge
as a weak immune system recovers. The recovering immune system regains
its ability to create fevers, flood infected tissue with white blood cells,
break bacteria down into toxic waste products and build nodules around
bacteria it cannot kill.
-
- -- ProMED-mail <promed@promedmail.org>
-
- [What the posting describes -- a paradoxical exacerbation
of disease, when, due to antiviral therapy, an HIV-infected patient's CD4
cell count rises -- is usually referred to as an immune reconstitution
inflammatory syndrome (IRIS) or immune reconstitution reaction. IRIS is
not necessarily related to ongoing infection per se but can be due to an
immune system that has "woken up" and is now reacting, for example,
to residual bacterial (such as _M. avium-intracellulare_), viral (such
as cytomegalovirus) or fungal (such as _Cryptococcus neoformans_) antigens.
-
- Whether these reactions described in the posting as occurring
after the initiation of antiviral therapy represent an IRIS is not entirely
clear. As summarized by Diana Lockwood's group in a review in Lancet Infectious
Diseases (1), some individuals (they review 9 such cases) develop post-HAART
reactions as described in the posting, which are similar in most cases
to the so called Type 1 "reversal" reactions that are associated
with activation of T-cell reactivity to _M. leprae_ antigens, CD4 cell
migration into the lesions and production of Th1-type cytokines, such as
interferon-gamma, IL-2 and IL-12. These type 1 reversal reactions can occur
after the institution of therapy for _M. leprae_.
-
- It is important to note, however, that these reactions
have now been described in _M. leprae_/HIV co-infected individuals who
have not been treated with antiviral medications. In an in-press manuscript
(2) from Sao Paulo, Brazil, 2 such cases are reported that cannot be classified
as IRIS in origin. These reactions, in a setting of very low CD4 cell population,
underscore the real paradox previously recognized and now discussed by
Lockwood's group.
-
- The paradox relates to the observation that, despite
dramatic effects of HIV/AIDS infection on the clinical manifestations and
histopathological findings of _M. tuberculosis_ infection, there is no
such effect with _M. leprae_. Even in individuals with profoundly low CD4
levels who are HIV/_M. leprae_ coinfected, there are granulomas formed
in tuberculoid leprosy and the number of CD4 cells in the granuloma were
no different than in cases without HIV (3). The underlying mechanism for
this dramatic difference is discussed at length in the Ustianowski paper
(1) and may be related to differences in the mechanism of granuloma formation
in the 2 mycobacterial infections, or compartmentalization of the cellular
immune response, but still has to be clearly established.
-
- 1. Ustianowski AP, Lawn SD, Lockwood DNJ: Intereactions
between HIV infection and leprosy: a paradox. Lancet Infect Dis 2006; 6:
350-60.
-
- 2. Trindade MAB, Valente NYS, Manini MIP, et al: Two
Mycobacterium leprae and human immunodeficiency virus type-1 coinfected
patients naive for antiretroviral therapy with type 1 leprosy reactions
mimicking the immune reconstitution inflammatory syndrome. J Clin Microbiol
(in press). Accessed at <http://jcm.asm.org.newproxy.downstate.edu/cgi/reprint/JCM.01425-06v1>.
-
- 3. Sampaio EP, Caneshi JR, Nery JA, et al: Cellular immune
response to Mycobacterium leprae infection in human immunodeficiency virus-infected
individuals. Infect Immun 1995;63: 1848-54. - Mod.LL]
-
- http://www.nytimes.com/2006/10/24/health/24lepr.html?pagewanted=2&ref=health
-
- Patricia A. Doyle DVM, PhD
- Bus Admin, Tropical Agricultural Economics
- Univ of West Indies
-
- Please visit my "Emerging Diseases" message
board at:
- http://www.emergingdisease.org/phpbb/index.php
- Also my new website:
- http://drpdoyle.tripod.com/
- Zhan le Devlesa tai sastimasa
- Go with God and in Good Health
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