2008 TFA State: The Bernsen-Schaefer Bubonic Plague Affirmative
Resolved: the United States Federal Government should substantially increase its public health assistance to Sub-Saharan Africa.
Undoubtedly the most ingenious and innovative affirmative case at TFA State (held at Dallas’s Coppell High School). [And since counter-plans are so popular, nobody bothered to look at the fact that honestly, our global warming link is ludicrous.]
For a synopsis, skip down to the plantext.
Inherency:
There hasn’t been enough scientific awareness of rodents as the primary vector for the Bubonic Plague, and a case that targets rats will be more effective than a case that targets humans.
Bubonic Plague: A Metapopulation Model of a Zoonosis, M. J. Keeling; C. A. Gilligan, Proceedings: Biological Sciences, Vol. 267, No. 1458. (Nov. 7, 2000), pp. 2219-2230.
By far the vast majority of historical information on the spread of bubonic plague is concerned with the number of human cases, and these outbreaks tend to be short lived, even in large communities (Sharif 1951; Shrewsbury 1970; Twigg 1993). Until now the standard assumption has been that each human outbreak was triggered by some external source, for example, infected rats arriving by ship (Appleby 1980; Slack 1980). While this is undoubtedly it true for many small populations, the model developed here offers an alternative explanation. In large towns and cities it is likely that the plague was endemic in some sections of the rat population and this could trigger sporadic epidemics in other areas; such a pattern of behaviour was speculated for bubonic plague in India during the early 20th century (Sharif 1951). This persistence in the rat population may explain why human epidemics were still experienced, even in cities such as Venice, when stringent quarantine measures were in effect (Appleby 1980). To date, much of the historical interpretation has concentrated on human cases, ignoring the true epizootic in rodents, and therefore neglecting the full dynamics.
Harms: Disease
1. Global warming is happening now, and there will be an increase in overall temperature in the next few years.
Drew McKeen: Producer/Director of onthebrink.org, 2002, <http://www.onthebrink.org/evidencerisk.html>
“Any time you get into projections, you get into a lot of uncertainties. But the [climate] models are getting a lot stronger,” said Jay Gulledge, a senior research at the Pew Center on Global Climate Change in Arlington, Virginia.
Gulledge says some current projections point to a rise in average global temperature of 0.5°C (slightly less than 1°F) by the year 2030.
2. Global warming is significantly linked to insect populations and diseases.
Brian Handwerk, for National Geographic News, July 27, 2005 <http://news.nationalgeographic.com/news/2005/07/0727_050727_globalwarming.html> “Global Warming: How Hot? How Soon?”
Pests And Vector Borne Diseases:
* Conditions created by global warming including warmer temperatures, milder winters, excessive rains, and drought provide fertile breeding grounds for pests.
* Insect populations are extremely sensitive to temperature changes and even a slight increase in temperatures can result in an explosion of pest-borne diseases including malaria, West Nile virus, yellow fever, cholera, dengue fever, hanta virus, and bubonic plague.
3. The plague poses a unique threat to sub-Saharan Africa, hitting small villages with more mortality than large towns.
Morbidity in Historical Plague Epidemics, O. J. Benedictow, Population Studies, Vol. 41, No. 3. (Nov., 1987), pp. 401-431.
During the last pandemic of plague similar observations were made in India and China. Hankin noted in 1905 that ‘the intensity of plague in towns and villages in the Bombay Presidency has been in inverse proportion to their size’. This statement is supported by a table based on data from the plague epidemics of 1897-8 (Table 8). Hankin wished to test his surprising finding and turned to history for his data. It turned out that in the Indian plague epidemics of 1812 and 1836 the same pattern of inverse correlation between population densities and mortality rates was found. Hankin even consulted research on the late-mediaeval plague epidemics in England and produced interesting evidence to the same effect.“
A few years later Greenwood reached the same ‘curious and interesting’ conclusions in his statistical studies of plague in the Punjab: ‘the rate of plague mortality tends to increase as the absolute population of the infected community diminishes’. Inspired by Hankin, Greenwood gathered and analyzed studies of plague in England during the late mediaeval and early modern periods. Again his conclusions confirmed Hankin’s findings.
Almost 30 years later Wu Lien-Teh reached the same conclusion for China: ‘the smaller the community the greater the rate of mortality.” Two historians, Gottfried and Cipolla, have also noted the basic point: the effects of plague epidemics were at least as severe in rural as in urban areas in spite of lower population densities. They do not, however, seem to have grasped the ‘curious and interesting’ epidemiological aspects of this observation.
4. The plague has significant morbidity rates, up to and exceeding 80%.
Morbidity in Historical Plague Epidemics, O. J. Benedictow, Population Studies, Vol. 41, No. 3. (Nov., 1987), pp. 401-431.
In this paper we have presented 48 instances of plague epidemics for which it has been possible to establish morbidity rates at good or reasonable levels of validity. In 23 of these epidemics, that is in almost half of our cases, the morbidity rates exceeded 50 per cent. Even the average morbidity rate in southern France in 1720-2 was significantly higher than 50 per cent, the median lying between 60 and 69 per cent. Only in six of the 23 instances were the morbidity rates between 50 and 59 per cent, while in at least eight instances they exceeded 80 per cent. The median level was again between 60 and 69 per cent with seven cases.
However, it is important to remember that these are gross morbidity rates which do not take account of the number of refugees who left the epidemic areas. Net morbidity rates showing the diffusion of plague in the populations actually resident during the epidemics, must have been higher, and the proportion of morbidity rates which exceeded 50 per cent must have been significantly higher. While Schofield’s general view on morbidity rates may be correct, the material presented above shows that plague stands out as a disease with unique powers of diffusion in the material circumstances prevailing in Europe in the past.
5. The Plague poses a severe threat to humanity.
Reuters, Jan. 14, 2008, “Plague a growing and overlooked threat.”
Plague, the disease that devastated medieval Europe, is re-emerging worldwide and poses a growing but overlooked threat, researchers warned on Tuesday.
While it has only killed some 100 to 200 people annually over the past 20 years, plague has appeared in new countries in recent decades and is now shifting into Africa, Michael Begon, an ecologist at the University of Liverpool and colleagues said.
A bacterium known as Yersinia pestis causes bubonic plague, known in medieval times as the Black Death when it was spread by infected fleas, and the more dangerous pneumonic plague, spread from one person to another through coughing or sneezing.
“Although the number of human cases of plague is relatively low, it would be a mistake to overlook its threat to humanity, because of the disease’s inherent communicability, rapid spread, rapid clinical course, and high mortality if left untreated,” they wrote in the journal Public Library of Science journal PloS Medicine.
Rodents carry plague, which is virtually impossible to wipe out and moves through the animal world as a constant threat to humans, Begon said. Both forms can kill within days if not treated with antibiotics.
“You can’t realistically get rid of all the rodents in the world,” he said in a telephone interview. “Plague appears to be on the increase, and for the first time there have been major outbreaks in Africa.”
Globally the World Health Organization reports about 1,000 to 3,000 plague cases each year, with most in the last five years occurring in Madagascar, Tanzania, Mozambique, Malawi, Uganda and the Democratic Republic of Congo. The United States sees about 10 to 20 cases each year.
More worrying are outbreaks seen on the rise after years of relative inactivity in the 20th century, Begon said. The most recent large pneumonic outbreak comprised hundreds of suspected cases in the Democratic Republic of Congo in 200.
Thus the PLAN: The United States Federal Government should substantially increase its public health assistance to sub-Saharan Africa by providing F1-V transgenic tomatoes to Mastomys natalensi (African rats) to prevent the proliferation of Yersina Pestis a.k.a. the bacterium that causes the Plague. We reserve the right to clarify.
Solvency:
1. Most instances of the plague are in Africa, but the F1-V vaccine prevents the plague in mice.
Jarrett CO, Sebbane F, Adamovicz, et al. Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague. Infect Immun Mar 25, 2004;72(4):2052-6
Successful replication of the natural transmission route of bubonic plague through the bites of infected fleas means scientists can conduct more realistic tests of other experimental plague vaccines, the NIAID said in a news release yesterday.
The study was published in the April edition of Infection and Immunity, now available online. It was authored by B. Joseph Hinnebusch, PhD, and two colleagues at the NIAID laboratory in Hamilton, Mont., along with two collaborators at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Md.
Plague is on the federal list of “class A” potential biological weapons. A plague vaccine was available in the United States until 1999, when the manufacturer stopped making it. The vaccine prevented bubonic plague (the most common form of plague, associated with flea bites and leading to swollen lymph nodes, fever, and other symptoms) but did not protect against pneumonic plague (lung infection, usually from inhaling the pathogen).
“Replicating the natural transmission of plague from flea to host in this model is tedious and unusual work,” NIAID Director Anthony Fauci, MD, commented in the news release. “This creative approach, however, brings researchers much closer to answers to real-life questions.”
The researchers used a vaccine called F1-V, which was invented at USAMRIID and has been shown to protect mice, ferrets, and monkeys against injected plague, the NIAID said. The vaccine also has protected mice and monkeys against pneumonic plague.
In the study, the investigators infected fleas by feeding them blood containing Yersinia pestis, the plague bacteria. The fleas then were allowed to feed on 15 mice that had been inoculated with the experimental vaccine, which contained an adjuvant (immune booster). The fleas also were allowed to feed on 15 mice that had received only the adjuvant. The vaccinated mice all remained well, while 14 of the 15 unvaccinated mice fell ill with plague.
“This research shows that the vaccine worked in a real world context,” Hinnebusch stated in the NIAID release. He said that in previous successful tests of the vaccine, the animals “received laboratory-grown plague bacteria and were artificially exposed to it by needle and syringe.”
Hinnebusch said it “wasn’t a given” that the vaccine would work in a natural setting, because in natural transmission, the bacteria are deposited with flea saliva into the animal’s skin in a way that can’t be duplicated artificially. In a natural infection, the digestive tract of some fleas becomes blocked with clumps of bacteria. When the fleas attempt to feed, the host animal’s blood is exposed to the highly infectious clumps and is regurgitated back into the animal.
The researchers will use the natural challenge model to test other experimental plague vaccines and will try to learn how Y pestis spreads through an animal after being transmitted by a flea, the NIAID said. The investigators hope to develop treatments to counteract the spread of plague in an infected person.
Bubonic plague killed an estimated 200 million people in pandemics in the 6th, 14th, and late 19th centuries. The World Health Organization now reports about 2,500 cases annually, with 180 deaths, the NIAID said. About 75% of the cases occur in Africa.
2. Using tomatoes bred with the vaccine is the best way to confer immunity.
Vaccine. Volume 24, Issue 14, 24 March 2006, Pages 2477-2490. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. M. Lucrecia Alvareza, Heidi L. Pinyerda, Jason D. Crisantesa, M. Manuela Riganoa, Julia Pinkhasova, Amanda M. Walmsleya, Hugh S. Masona, and Guy A. Cardineaua. Center for Infectious Diseases and Vaccinology (CIDV), The Biodesign Institute at Arizona State University, Tempe, AZ, USA. The School of Life Sciences, Tempe, AZ, USA. Received 15 October 2005; revised 9 December 2005; accepted 14 December 2005. Available online 13 January 2006.
There have been previous initiatives to devise an alternative plague vaccine that could be administered needle-free and they are currently being tested in animal trials by different research groups. One of these is a micro-encapsulated preparation of F1 and V antigens, delivered intranasally to mice, that protects against parenteral and inhalation challenges with Y. pestis [33]. Another utilizes oral immunization with a recombinant Salmonella enterica expressing Y. pestis’ antigens that has also been reported to provide protection against a subsequent challenge with the bacteria [34], [35] and [36].
The production of therapeutic proteins in plants represents an economical alternative to fermentation-based expression systems, especially for the manufacturing of high-volume reserves of subunit vaccines (for a review see [37]). Plants have been shown to provide both an encapsulated antigen and an oral delivery system. Plant-made vaccine antigens can be delivered to a mucosal surface (for example, when provided orally or intranasally). Additionally, plants can be grown locally and inexpensively using the standard growing methods of a given region and can also be produced virtually indefinitely from seeds [38]. Oral delivery is made possible because it is believed that the plant cell wall provides enough protection against degradation to allow much of the vaccine antigen expressed in the cells to reach the gut-associated lymphoid tissue (GALT) in an intact and immunogenic state. Since plant-made vaccines were first described by Curtis and Cardineau [39], different groups have experimented with transgenic plants for expression and oral delivery of recombinant vaccine antigens. The six human clinical trials accomplished with plant-made vaccines have shown the potential of using the plant-made vaccine technology [40], [41], [42], [43], [44] and [45].
In this paper, we describe the development and evaluation of an alternative oral subunit vaccine candidate against plague, produced by expressing the F1-V fusion protein in tomato. To our knowledge, this is the first report of a plant made, orally delivered plague-vaccine. Tomato has many advantages over other host plants for the production of oral vaccines. Tomato yields large masses of palatable fruit that are edible raw (avoiding heat denaturation of the antigens) and has well established industrial greenhouse culture and fruit processing. Unfortunately, a vaccine expressed in fresh tomato fruit has a short shelf-life. For this reason, fresh tomato fruits expressing the fusion protein F1-V were pooled and freeze-dried. Freeze-drying is a well-established technology that is inexpensive and provides antigen stability at room temperatures, batch consistency and concentrated antigen. The integrity and antigenicity of the F1-V fusion protein in the freeze-dried, tomato fruit powder was confirmed by ELISA and Western-blot analyses.
Using the tomato plants is a better alternative to current strategies.
Using transgenic tomato plants to produce an oral vaccine in fruit without any protein purification and with minimal processing may provide a cost-effective alternative to current vaccine production strategies. In this paper we show that an antigen from a non-enteric human pathogen (Y. pestis) can be orally immunogenic when produced and delivered in plant tissues. Plant-expressed F1-V has the potential to be useful as a booster vaccine against plague since it is able to elicit specific mucosal sIgA and serum IgG1 responses. A prime-boost vaccine for plague also has practical implications. In an imminent or post-release bioterrorism event, the ability to dispense a parenteral priming dose with the distribution of tomato powder pills that could be self administered would greatly improve national preparedness.