Malaria threat to Galapagos birds


Blue-footed booby
The blue-footed booby was first extensively studied by Charles Darwin on his visit to the Galapagos

The Galapagos Islands may have inspired Charles Darwin’s theory of evolution, but scientists fear some of the species he observed may not be capable of adapting to new environmental challenges.

Experts say the introduction of foreign parasites to the islands and the increase in frequency of El Nino events, which scientists recently attributed to global warming, could push bird species in the Galapagos towards extinction.

“The situation is precarious,” says Dr Patricia Parker, Endowed Professor of Zoological Studies at the University of Missouri St Louis (UMSL), “particularly for species such as the Galapagos penguin, which live in very small populations.”

The Galapagos Islands

  • The Galapagos Islands comprise a volcanic archipelago west of Ecuador
  • Together the islands have an area of just over 8,000 sq km (3,000 sq mi)
  • They are well known for a huge number of species that are unique to the islands (endemic)
  • Charles Darwin studied the islands’ wildlife during the voyage of the Beagle
  • His observations made a significant contribution to his theory of evolution by natural selection

Foreign parasites have contributed to mass extinctions in Hawaii, which has lost up to 30% of its endemic birds.

Hitherto, the Galapagos Islands have avoided a similar fate. But Dr Parker, who contributed towards a new report about avian malaria on the archipelago, believes it could be just a matter of time before the virus claims its first species.

The disease is already prevalent in the yellow warbler and Galapagos penguin, which has an estimated population of just 3,000 individuals.

The parasite that causes avian malaria (Plasmodium) requires passage through the digestive and circulatory systems of a biting insect in order to reproduce.

“The insect is considered the primary host of the parasite,” explains Dr Parker.

Suitable hosts

However, for the Plasmodium parasite to complete its life-cycle it must then be transmitted to a suitable bird host through the saliva of the biting insect.

“The parasite then goes through a massive multiplication phase in the liver of the animal before entering the bloodstream,” says Dr Parker. “From there, the next biting insect that takes a blood meal picks them up.”

But not all birds are competent hosts.

“We are trying to identify which species of mosquito is responsible for vectoring it and which bird species is the reservoir for this parasite,” says Dr Parker.

After studying 3,726 samples from 22 endemic birds, Dr Parker and her team – scientists from UMSL, Galapagos National Park, Charles Darwin Foundation and Saint Louis Zoo – believe the parasite is not completing its life-cycle in endemic birds.

Yellow warbler The disease is already prevalent in the yellow warbler

“We don’t think Galapagos natives are part of the transmission cycle,” says Dr Parker. “They become infected but they don’t actually allow the parasite to complete its life-cycle.”

Attention has now shifted to three introduced birds; the domesticated fowl, the cattle egret and the smooth-billed ani, a species thought to have been brought here by farmers because it removes ticks from cattle.

“If we discover that one of these introduced species is responsible for the transmission of this potentially dangerous parasite then the Galapagos National Park would consider whether they want to mount an eradication effort,” says Dr Parker.

“There is a sense of urgency about this because it’s only a matter of time until one of the endemic birds will become a successful host – all host and parasite relationships evolve.”

Scientists suspect an introduced mosquito is acting as the primary host and, if this is confirmed, authorities will also consider eradicating the insect.

The Galapagos National Park has experience exterminating foreign species, having successfully eliminated disease-spreading rock pigeons.

El Nino year

However, preserving native species could prove trickier; scientists say global warming is likely to increase the frequency of El Nino events, which can have a devastating effect on Galapagos wildlife.

“In the El Nino events of 1982 and 1996 the population of penguins declined to approximately 300 and 400 individuals respectively,” says Gustavo Jimenez, wildlife veterinarian at the Charles Darwin Foundation.

“The increased frequency of El Nino could mean there is not enough time for the recovery of the species that are affected, which would lead not only to their populations reaching critically low numbers but possibly extinction.”

Galapagos penguin An increased frequency of El Nino events and avian malaria could consign the Galapagos penguin to history

During El Nino, the Humboldt Current, which brings cold, nutrient-rich waters from Antarctica, is reversed.

“Instead what hits the islands are warm equatorial waters,” explains Dr Parker. “So the birds that rely on marine life; their numbers plummet.”

Scientists fear future El Nino events coupled with an outbreak of avian malaria could consign species such as the Galapagos penguin and flightless cormorant to the history books.

“It is possible that in a situation where there are multiple environmental stresses – less food, strange weather conditions and so on – these Plasmodium infections might be much more damaging than they appear to be under more benign circumstances,” says Dr Parker.

On the edge

Concern is also mounting for the critically endangered mangrove finch, which is being ravaged by an introduced fly called Philornis downsi.

“In 2013, 37% of mangrove finch nestlings were killed by Philornis downsi,” says conservationist Francesca Cunninghame, of the Charles Darwin Foundation.

“This is a loss which cannot be sustained in a population as reduced as that of the mangrove finch – in the same year, there were only 14 breeding pairs.”

Philornis downsi colonises nests and finds its way into the nasal cavities of fledglings, where it can cause beak deformation and blood loss leading to death.

It was first identified in the 1990s and recent tests indicate that fumigating nests with permethrin, an insecticide which is not harmful to birds, can dramatically improve the health of a brood.

Scientists are also experimenting with captive breeding programmes in an attempt to boost numbers.

“The Galapagos has had zero bird extinctions and we want to keep it that way,” says Dr Parker. “We need to find answers now while the potential exists to do something about it – before Galapagos becomes another Hawaii.”

Fighting Prostate Cancer with Radium-223 — Not Your Madame’s Isotope.


As each year ushers in new and innovative survival-enhancing treatments for castration-resistant prostate cancer with bone metastases, patients and their physicians have a sense of empowerment associated with this growing therapeutic arsenal.1-5 Nonetheless, nearly 30,000 men still die from prostate cancer every year, and many have debilitating illness from osseous involvement. For this latter group, Alpharadin in Symptomatic Prostate Cancer Patients, a randomized, placebo-controlled study reported by Parker et al. in this issue of the Journal, focuses on a new weapon in anticancer therapy.

Radium-223 dichloride (radium-223), the first alpha emitter to undergo phase 3 testing and receive approval for clinical use, acts independently of cell cycles, surface markers, and tumor types. The simplicity of the alpha emitter radium-223 lies in its winning combination of a convenient half-life (11.4 days) and its inherent bone-seeking and potent DNA-damaging properties. The authors describe a well-executed international, multicenter trial showing an overall survival benefit associated with radium-223 in more than 900 patients with prostate cancer. The real-world applicability is undeniable; these patients had symptomatic skeletal disease and had received previous or concurrent complementary therapies.

No discussion of radium is complete without first acknowledging Madame Marie Curie, who with her husband Pierre first isolated radium-226 from pitchblende. Despite the current widespread availability of radiopharmaceutical agents, short-lived alpha emitters that are suitable for intravenous medical therapy have been limited until recent advances in radiochemical separation and cyclotron-based production of alpha emitters made their generation feasible. Yet, obstacles to their use may still exist. Alpha particles traditionally provoked fear in the lay public and nervousness in the medical community (including some radiation safety officers) because of their enhanced relative biologic effectiveness. The concept of relative biologic effectiveness combines physical linear energy transfers with the radiobiologic effects of ionizing radiation in tissue to provide a medically relevant scale for comparing the potencies of various forms of ionizing radiation. The relative biologic effectiveness of alpha emitters, which is several times that of traditional x-rays (depending on the tissue type), is their most and least attractive feature. Alpha particles are efficient, and they cause cell damage with a single knockout as compared with gamma rays and beta particles. Such killing power is rendered unattractive if it is coupled with an unforgiving half-life.

Historically, safety concerns stemmed from the 1601-year half-life of radium-226 and its decay into volatile radon gas. These concerns were further fueled by horror stories that included lost radium sources that underwent accidental heat sterilization and vaporization and closed down entire hospitals.7 However, alpha disintegrations are in fact remarkably easy to shield because of the particles’ heavy mass and limited penetration — picture a minimal-range heavy missile stopped by a sheet of paper. Universal precautions generally suffice. Radium-223 is transportable worldwide in shielded, screw-cap vials. Unlike its older cousin, it rapidly decays into stable compounds — meaning that after several half-lives, one can discard any waste with ordinary trash. Logistically, alpha-emitter therapy is feasible for most centers whose staff members are well-trained in radionuclide therapy as long as there is some initial investment to update existing safety procedures and to acquire alpha-tailored assay and survey devices, as well as an ongoing investment in training for radiation safety personnel.

As for patients’ safety, Parker et al. report remarkable tolerability of radium-223 in a population that had a baseline risk of progressive complications from underlying disease.6 The decay kinetics of radium-223 and its use in patients with metastatic disease also suggest that the legacy of second cancers observed in the days of the “radium girls” (female factory workers who had radium poisoning in the early 20th century) and the common medical use of thorium dioxide.The Past, Present, and Future Role of Alpha Emitters in Medicine.) will not be repeated.

In 1996, a workshop sponsored by the Department of Energy on the development of alpha emitters for medical use identified multiple priority areas for future clinical research, including applications for nonmalignant conditions such as immune disorders and degenerative joint disease.8 Astatine-211 and bismuth-213 were deemed the most promising agents at the time. Yet in 2013, barriers to their adoption remain. Few alpha emitters are actively being tested in the clinic, and these tests are limited to cancer trials Radionuclide therapy is not a new concept in oncology. The trick is to deliver the radiation dose to the right target with minimal collateral damage; the trick with antibody therapy is that target engagement on the cell surface is not always sufficient to have a cytocidal effect. Radioimmunotherapy is a successful approach in cancer therapy that marries a homing antibody of choice to a lethal radioisotope. As newer targeting molecules emerge, we can envision alpha emitters as a potent partner to further enhance radioimmunotherapy and create the ultimate “smart bomb.”

But questions certainly remain. Bone-seeking beta emitters such as phosphorus-32, strontium-89, and samarium-153 lexidronam have been tested, yet the alpha emitter is the only one to show a survival advantage. Is the higher relative biologic effectiveness of alpha particles the sole cause, or did differences in study design, patient selection, or isotope localization contribute? Although some gamma emission permits imaging of the whereabouts of radium-223,9 established and validated methods to quantify the dose delivered to the body and to each lesion are lacking.10 As compared with non–alpha emitters, alpha particles, which have high linear energy transfers and limited-range paths, necessitate a greater emphasis on elucidating their biodistribution and microdosimetry (the measurement of energy deposition and distribution at the cellular and subcellular levels after radiation exposure). Nonetheless, this study imparts some long-awaited momentum to research on the use of alpha emitters and shows an overall survival advantage with a compound that is safe and manageable for both patients and providers. Radium-223 will both complement and contend with existing therapies. While its most appropriate “fit” is actively investigated, the first-line role of taxanes in metastatic castration-resistant prostate cancer may be reexamined and the viability of alpha particles in medicine may be newly explored 115 years after their discovery.

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Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363:411-422
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de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005
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Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368:138-148[Erratum, N Engl J Med 2013;368:584.]
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Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-1197
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de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376:1147-1154
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Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-223
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Cross FH, Miller H, Mussell LE. An unusual radium accident. Br J Radiol 1951;24:122-122
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Feinendegen LE, McClure JJ. Alpha-emitters for medical therapy: workshop of the United States Department of Energy: Denver, Colorado, May 30-31, 1996. Radiat Res 1997;148:195-201
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Nilsson S, Larsen RH, Fossa SD, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res 2005;11:4451-4459
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Huang C-Y, Guatelli S, Oborn BM, Allen BJ. Microdosimetry for targeted alpha therapy of cancer.Comput Math Methods Med 2012;2012:153212-153212

 

Source: NEJM