A Nasty Fly Bite

A sore marks the telltale path of a troublesome parasite.

By Claire Panosian Dunavan|Sunday, September 01, 2002
RELATED TAGS: INFECTIOUS DISEASES

As a child, I was fascinated by a scar on my grandfather’s cheek. “How’d you get that?” I asked, touching the shallow depression as we settled into a comfortable chair to read a book.

“Where I grew up, everyone had a scar like that,” replied my grandfather, a native of southern Turkey. “First a fly would bite, then you got a sore. After a few months, the skin healed, and you never got the sore again.”

Twenty-five years later, as a researcher in Boston, I learned that my grandfather, with no science education, had grasped the biology and immunology of that sore surprisingly well. But I’m getting ahead of my story.

Kabul, Afghanistan, 2000. To escape the heat, Majeeba and Naieda Fazly flopped down on a striped mattress in the large, open-air balcony of the family home they had not seen for almost a decade.

Seven years earlier the Fazly family had suffered a blow. Mr. Fazly, 58, died of a heart attack, leaving behind a widow and 11 daughters. Only one good thing came of the tragedy. Lacking a male protector in a harshly conservative society, the Fazly women were eligible for international asylum. For several years they waited in Pakistan. Finally, the family was granted refugee status, and they returned to Kabul one last time before leaving forever.

Majeeba and Naieda were the youngest Fazly daughters and mere schoolgirls when they left Kabul for the first time in the early 1990s. Things were bad enough then. But now the streets were filled with trash, mangy dogs, and loud men with beards. And insects. Majeeba and Naieda had never seen so many sand flies in the city. Even in the covered sleeping porch, their bites were incessant.

A year later in Los Angeles, that memory of sand flies was the final clue to their diagnosis. Why? On their hands and forearms, both girls had fleshy, crusted ulcers. Just like the ulcer my grandfather once described.

Leishmaniasis is a protozoan infection transmitted by the bite of a sand fly. Protozoa are single-celled microbes that can develop exotic shapes and accessories: amoebas with crawling pseudopods, ciliates bristling with hairs, and flagellates sporting wavy antennae.

Leishmania assume two shapes during their life cycle. In the first stage, they take the shape of a flagellate that multiplies in the sand fly’s gut and eventually swims free in sand fly saliva. In the second stage, found exclusively in humans and animals, they lose their tails and become ovoid bull’s-eyes inhabiting immune cells called macrophages. The cycle starts anew when a virgin sand fly siphons parasitized macrophages from a skin ulcer or blood. During the next several days, the ovals morph back into creatures with tails, replicate in the sand fly’s gut, and finally migrate to the fly’s proboscis, ready to enter their next mammalian host.

The earliest descriptions of skin ulcers containing microscopic bull’s-eyes can be found in medical journals from the late 1800s. Then, in 1903, a Scottish army pathologist named Leishman described the same bull’s-eye pattern in cells taken from the spleen of a soldier who died after trying to fight off a fever for seven months while stationed at Dum Dum, outside Calcutta. The 23-year-old recruit, Private J. B. of the Second Royal Irish Rifles, became the first-ever reported case of a distinct strain of Leishmania that invades blood, bone marrow, and internal organs. Today the disease is known as visceral leishmaniasis. While people can recover without treatment from leishmaniasis that affects only the skin, untreated visceral leishmaniasis is still fatal.

Following Leishman’s discovery, names like “dum dum fever” and “kala azar” (both referring to visceral leishmaniasis) and “Baghdad boil,” “Biskra button,” “Aleppo evil,” and “oriental sore” became synonyms for subtypes of Old World leishmaniasis. On the other side of the globe, “uta,” “bay sore,” and “forest yaws” were linked with New World leishmaniasis of the skin. In time, even the scalloped scar that followed leishmaniasis of the outer ear acquired its own nickname. Because this ragged defect was common in Latin American men who harvested chicle for making chewing gum, it was called “chiclero’s ulcer.”

One reason that the form affecting the skin, cutaneous leishmaniasis, thrives in so many locales worldwide is its large range of reservoir hosts. In Central and South America, rodents, marsupials, sloths, and anteaters carry local species such as L. mexicana, L. brasiliensis, L. panamensis, and L. guyanensis. In Old World urban settings like Kabul, dogs often harbor L. tropica. And in less populous areas of the Old World, rats and gerbils are commonly infected with L. major. In dry, desert areas of central Asia, Iran, and Iraq, up to 30 percent of gerbils have ulcerative skin lesions of L. major affecting their head, ears, and the base of the tail.

Fortunately, localized infections of L. tropica—the canine cutaneous strain that infected my grandfather as well as Majeeba and Naieda—often heal without specific treatment, although it may take many months. As a young researcher, I tried to understand why. I did so by inoculating lab mice with Leishmania and observing their skin lesions.

Depending on the genetic and immunologic makeup of the mouse, the sore would either mushroom or cure itself over time. Other investigators went further, pinpointing specific lymphocytes and products they released that governed healing in mice and humans. Just as my grandfather said, once bitten and healed, you were virtually always protected against repeat infection by the same strain.

But Majeeba and Naieda had a different dilemma. One year had passed, and they still hadn’t healed their primary infections. Their diagnosis wasn’t in question. Aside from the evidence staring me in the face, skin biopsies sent by their referring dermatologist showed unmistakable bull’s-eyes. Could they have an underlying illness or immune deficiency to explain their persistent infection? My clinical instincts said no. Sure enough, after testing, the sisters proved perfectly healthy, merely frustrated by their ugly nodules and scabs rimmed with scarlet.

In the end, I never did figure out why their ulcers were chronic. It could have been the stress of moving or perhaps repeated infection through multiple bites. No matter what the reason, the girls needed treatment. The good news was that we had options. When I was doing bench research on leishmaniasis in the 1980s, a 20-day series of daily injections of intramuscular or intravenous antimony, a metal that has long been used as a medical treatment, was standard first-line therapy. In 2001, I chose instead  itraconazole, a modern drug taken by mouth that often speeds healing in mild to moderate cases of leishmaniasis that affect the skin.

My gamble paid off. Months later the ugly scabs were flat, mauve stains, well on their way to disappearing completely. More important, the two sisters from Kabul were making a happy adjustment to their new life in America. Majeeba was working at a local department store, and Naieda was finishing high school.

Throughout history, war and civil strife have often played a role in outbreaks of leishmaniasis. One recent example is the devastating epidemic of visceral leishmaniasis that began in 1988 in the western Upper Nile province of southern Sudan. Fueled by famine and a brutal government-led campaign against civilians, it has claimed more than 100,000 lives. Cutaneous leishmaniasis, although less dangerous, is still a problem for military personnel in areas like the Middle East and Panama. And an epidemic of leishmaniasis is raging in Afghanistan; no doubt a few troops will return from the region bearing crusts and scars of infection.

Meanwhile, leishmaniasis continues to surprise researchers. For example, a handful of U.S. soldiers who served in the Gulf War came down with visceral infection due to L. tropica, a species previously confined to the skin. This unprecedented event triggered a temporary ban on blood and organ donations by all Desert Storm veterans. Visceral leishmaniasis has also emerged as an opportunistic infection among patients with HIV in Spain, Italy, and southern France. And, in rodents and test tubes, leishmaniasis is still an ideal model system to study immune responses.

Would any of this have interested my grandfather? Probably not. My guess is that as far as he was concerned leishmaniasis was simply one more thing life dished out, like the common cold or the irksome bite of a sand fly.

Claire Panosian Dunavan diagnoses and treats tropical diseases at UCLA Medical Center. The case described in Vital Signs is based on a true story. Some details have been changed to protect the patients’ privacy.


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