leishmaniasis

Cutaneous leishmaniasis in a 12-year-old Syrian immigrant

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A 12-year-old girl, who had immigrated from Syria 7 months prior, presented to her general practitioner with a 6-month history of nonpainful papules over her right hand that had increased in size and eventually ulcerated. Over a follow-up period of 2 months, she did not improve despite receiving topical corticosteroids, mupirocin, and oral trimethoprim–sulfamethoxazole for suspected superinfected atopic dermatitis. When we saw her in our tropical diseases clinic, she was afebrile and systemically well, but had erythematous plaques, edema, ulcerations and restricted mobility on her right hand (Figure 1A).

Figure 1:

A) Erythematous scaly and crusted plaques with edema over the proximal interphalangeal joints of the second, fourth and fifth right fingers of a 12-year-old girl with cutaneous leishmaniasis, with an ulcer overlaying the lesion of the fourth finger. B) Complete reepithelialisation and healing of the lesions 4 months later, with residual postinflammatory hyperpigmentation.

Giemsa staining from an ulcer scraping specimen showed numerous amastigotes. The culture was positive for Leishmania species, and polymerase chain reaction (PCR) identified Leishmania tropica. Because we were concerned about the functional mobility of the patient’s hand, we prescribed systemic therapy with liposomal amphotericin B, based on local guidelines, which she tolerated well. At follow-up 4 months later, her lesions had resolved (Figure 1B) and joint mobility was restored.

Cutaneous leishmaniasis is a protozoan infection transmitted by the female sandfly. This tropical disease affects 700 000 to 1 million new people annually.1 Nonhealing ulcers in travellers and migrants from endemic regions, such as Central and South America, the Mediterranean basin, the Middle East and Central Asia, should raise suspicion of cutaneous leishmaniasis. Lack of physician knowledge about the acquisition of cutaneous leishmaniasis, even during short stays abroad, has historically led to delayed diagnosis.2,3

Differential diagnoses include Nocardia species, mycobacteria, endemic fungi, vasculitis, neoplasia, sarcoidosis and pyoderma gangrenosum. Identification of parasites on smear, histopathology, culture or PCR confirm the diagnosis.4 The type of Leishmania species, concomitant mucosal involvement, the size, number and location of the lesions, and host immune status are important guides to individualized management.5 Treatment may be local (e.g., paromomycin preparations, cryotherapy, heat therapy) or systemic (e.g., pentavalent antimonials, miltefosine, azoles and amphotericin B).6

Clinical images are chosen because they are particularly intriguing, classic or dramatic. Submissions of clear, appropriately labelled high-resolution images must be accompanied by a figure caption. A brief explanation (300 words maximum) of the educational importance of the images with minimal references is required. The patient’s written consent for publication must be obtained before submission.

Acknowledgement

The authors would like to thank Faheel Naeem for proofreading the manuscript.

Footnotes

  • Competing interests: None declared.
  • This article has been peer reviewed.
  • The authors have obtained parental consent.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

References

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This new drug could fight 3 of the deadliest infections in developing nations

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A single drug has shown potential in fighting three major infections – sleeping sickness, Chagas disease, and leishmaniasis – that infect 20 million people each year in developing countries.

The drug has so far only been tested on animals, but the results have been so postivite, researchers are ready to start human trials once the current round of safety testing is complete.

“What makes [the drug] special is the fact it is targeting all three parasites. That’s the first time it has been done, so it is quite special,” one of the researchers, Elmarie Myburgh from the University of York in the UK, told James Gallagher from the BBC.

“To me, this is obviously a big deal, I’m in this field to try and make a difference, to get to a cure, and we’re working hard in the hope that it gets to patients,” she added. “There’s been very little incentive to spend a lot of money on these diseases as they affect a very poor, and yet large, population.”

For now, the drug is known as GNF6702.

The team investigating its effects, led by researchers from the Novartis Research Foundation in San Diego, says that it could treat all three of the infections by seeking out and destroying the similar parasites that cause them – all of which are a type of single-celled organism called kinetoplastids.

Sleeping sickness – an infection that can result in a prolonged coma – is caused by the Trypanosoma brucei parasite, and spread via tsetse flies.

Chagas disease, which can enlarge a person’s heart, is caused by the Trypansosoma cruzi parasite, and spread by assassin bugs.

The third disease, leishmaniasis, is caused by the Leishmania parasite, which is spread by sand fly bites. You only need to Google this one to know how devastating it is.

All three diseases are responsible for 50,000 deaths a year in developing nations.

The team designed the drug to seek out and destroy something called the proteasome – a protein complex that recycles waste proteins and is found inside most eukaryote and archaea species, including humans.

In the past, researchers had thought it was impossible to target these proteasomes because it would be too hard to differentiate between the species. But the researchers were able to find a target that was remarkably similar across the three parasites, but distinct enough from the human version.

To find a drug that would attack this target, the team tested some 3 million compounds before finding one that would attack the parasite proteasome, while leaving the human version alone.

They then took this compound and manipulated it to make it more potent,reports Gallagher.

While a single drug for all three diseases would obviously be the best option, because it’d be cheaper and easier to distribute, the researchers are also looking into the possibilty of developing the drug into three specialised, to achieve more efficient results.

“It may be a single drug for all three diseases may not be the best strategy,” one of the team, Richard Glynne from the Novartis Research Foundation, told the BBC.

“The biology of the diseases is different. For example, in sleeping sickness the parasite is in the brain, so you need a drug that gets into the brain, so there are tweaks that may be required.”

The current method of treatment for these infections is to administer toxic chemicals – typically through an IV – to patients.

But since many people in the affected nations don’t have access to IV facilities, many patients aren’t properly treated, so finding a more effective drug – or drugs – would be a huge step forward.

The new parasite-fighting drug will have to undergo human testing before we know for sure if it really is the “new hope” people are branding it, but the researchers are cautiously excited.

“We continually face challenges getting medicines to those people and making affordable medicines is an important first step. This is quite an important piece of research, I’m excited by it, but there’s still a long way to go,” said Wellcome Trust researcher, Stephen Caddick, who was not involved in the research.

Taking a Shot at a Tropical Killer

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A vaccine against the disease leishmaniasis could save tens of thousands of lives every year. Now, scientists report that they have used snippets of DNA to spur mice to fight back against the parasites responsible for the illness, an approach they hope to soon begin testing in people.

Leishmaniasis is caused by microscopic parasites of the genus Leishmania; some 20 different species can sicken humans. Leishmaniasis hits poor residents of tropical countries the hardest. The sandflies that spread the disease are silent and smaller than a mosquito. After a sandfly’s bite injects them into the body, Leishmania cells can attack the skin or mucous membranes, causing ulcers or disfiguring lesions. In an often lethal variety of the disease, they damage the liver, spleen, and bone marrow. Although the disease’s toll isn’t certain, estimates suggest there are about 1.3 million new cases and up to 40,000 deaths each year.

Leishmania parasites are tricky foes, and so far no vaccine has received approval for use in humans. One challenge is that the parasites lay low inside our cells, out of reach of the antibodies triggered by most other vaccines. The key to eradicating these sheltered invaders, researchers suspect, is stimulating the immune cells known as T cells. Although two experimental leishmaniasis vaccines that use this strategy have undergone preliminary safety and effectiveness tests in people, the best method for enlisting T cells isn’t clear.

Immunologist Peter Walden of Charité University Medicine Berlin and colleagues decided to try a DNA vaccine, a type of vaccine that is good at inciting T cells. Such vaccines contain DNA strands coding for proteins from a pathogen. Cells in the vaccine recipient’s body absorb the DNA and start churning out the proteins—also called antigens—which alert the immune system and prime it to attack if a real infection occurs.

First, the researchers had to choose the right antigens. They settled on five different proteins that vary little across Leishmania samples from a range of species found around the world. To determine whether the antigens galvanize human T cells, the team obtained blood samples from people in India and Tunisia who had recovered from the disease or had been exposed to it without getting sick. They found that portions of all five proteins sparked a response by T cells from the blood samples.

The researchers’ final vaccine mixture, which they tested in mice, contained five kinds of DNA strands, each coding for all or part of one of the proteins. The vaccine stimulated the mice to produce defenses against leishmaniasis parasites, Walden and colleagues report online today in Science Translational Medicine. T cells from the vaccinated animals reacted vigorously to Leishmania antigens. To confirm that the vaccine helped the animals combat the invaders, the researchers injected the mice with cells of one Leishmania species. Three weeks later, mice that received the highest vaccine dose carried 94% fewer parasites in their liver than did mice that received a control shot. Although some parasites remained in the mice that received the largest dose, Walden says there weren’t enough of them to cause disease symptoms.

Colorful killers. A new vaccine protects mice against parasites that cause leishmaniasis.

“We are ready for human trials,” he says. The vaccine should provide protection against different human Leishmania species, he adds, because the selected antigens are the same across species.

Immunologist Paul Kaye of the University of York in the United Kingdom agrees that the time for human trials has come. “There is every reason to believe that they should move forward as soon as possible,” says Kaye, who’s excited that there are now three vaccines to try in humans. Kaye and colleagues’ own vaccine candidate, which stimulates T cells with a harmless virus that carries sections of two Leishmania genes, has already undergone a safety study in people, but the results have not yet been published.

“This is a significant advance,” says vector biologist Jesus Valenzuela of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland. Walden’s group deserves credit for using human blood samples to identify the antigens, he says; other vaccine developers have used rodents.

Leishmaniasis is one of the neglected tropical diseases for which research cash is hard to obtain. Still, Walden is hopeful that he and his colleagues will find financing for safety trials.