Outlining a Project: Human Plague

I’ve had a bit of a blogging slump lately. I came back from the medieval congress with too many things on my mind to settle down to write a post. Nevertheless, it has been a productive couple of weeks. I’ve been working on an outline for one of the book projects that I mentioned quite a while back. I think its time to share some of those plans. I’m eager for feedback, criticism, suggestions… It won’t hurt my feelings at all and will be much appreciated! So here goes with the outline.

Working title: Human Plague: Natural History & Crisis Management

Introduction

Part I: A Natural History of Yersinia pestis

1. Origin, Evolution and Biogeography (also including bacteriology and reservoirs)

2. Anatomy of an Epidemic (transmission and epidemiology)

3. Natural History of an Infection (diagnosis, pathophysiology, immunology)

Part II: Crisis Management

4.Government Response (legal, economic, & political)

5. Medical Care

6. Mortuary Care

7. Children and the Plague

8. Crises of Faith and Response

9. Scapegoating the Other

10. Signs of Resilience

Part III: Modern Concerns

11. Weaponizing the Plague

12. Plague Today

Appendix: Chronology

The theory here is that the first part is a natural history from the point of view of biologists, public health, and medicine. ‘Human plague’ because a natural history of Yersinia pestis or ‘the plague’ would primarily be about rodents. These chapters will work in the entire history of human plague from evolution of the bacterium in central Asia to its movements for the next 1500 years. Certainly most of the epidemiology will include pre-modern epidemics.

The second maybe two-thirds of the planned book is influenced by my biosecurity training. It’s hard to think about the plague without thinking about the 1500 years of crisis management with the same organism. I expect that this section will change dramatically as I work on it. This outline is really just some of the elements of crisis management: government reaction, medical care, mortuary care, special populations (here represented by children), religious crises as the most evident social impact, and religious and racial persecution, and evidence of resilience.

The last section is pretty self-explanatory. It will review evidence of plague as a biological weapon and continuing concerns that it will be used as a weapon. It will end with an assessment of where we are today with plague as re-emerging disease.

My goal is to write this at about the same level of technical difficulty as this blog. I hope that it is useful to all of the many disciplines involved in plague research and response in the sciences and humanities.

It seems like I’m trying to put an awful lot in one book but I don’t really have a baseline to judge that by. Feedback would be much appreciated in the comments below or by email!

Looking Back at Kalamazoo 2012

Reblogged from Heavenfield:

This was a really good Congress. It was pretty laid back and things seem to go pretty smoothly. I met lots of new history of medicine folks that I hope to keep in touch with (and barely got to chat with a certain geek I saw a lot of, sniff). I had great luck in picking sessions. Just about every session I went to either had interesting info for my research or gave me ideas for blog posts (even the ones I picked just for general information).

Read more… 2,295 more words

Leptin: Linking Malnutrition and Vulnerability to Infection

The correlation between malnutrition and vulnerability to infection has been well established (discussed previously here). While the immune dysfunction could be characterized it was not until the last 10-15 years that an exact mechanism began to resolve.

It all began with the discovery of a new hormone called leptin from an unexpected place, adipose tissue (fat cells). Leptin, a product of the obese (ob) gene, was discovered while looking for factors that regulate body fat. As a consequence of manipulating this gene in an attempt to regulate body fat, it was discovered that mice deficient in leptin had profound immune deficiencies.

The amount of leptin produced by adipose cells (fat cells) is directly proportional to the amount of fat in the cells. (The number of fat cells in adults does not change,  their size just shrinks or swells.) Leptin levels drop as body fat decreases or during fasting. Once leptin levels fall below a threshold, the lack of leptin puts the mammalian body into a starvation response. Areas of leptin activity are signaled by the production of the leptin receptor (OBR gene). Tissues producing the leptin receptor include areas of the hypothalamus that regulate body weight, bone mass, and appetite; ovarian cells, beta-cells of the pancreas, endothelial cells, and bone marrow stem cells, macrophages, and lymphocytes (1). Leptin influences cellular function by directly interacting with peripheral tissues including immune cells in lymph nodes, bone marrow, pancreatic function and bone homeostasis, but also by triggering hormonal changes in the brain, specifically in the hypothalamus. Study of leptin levels has opened previously unsuspected linked between central nervous system control and the development of the immune system.

The Hormonal Trigger of the Starvation Response

Leptin’s control of metabolism and the  immune system. (Ref. 2)

As long as leptin levels stay within normal levels, all of the functions displayed above function normally. As the leptin levels drop, many of these functions are adversely effected. It is a wide-spread trigger for a starvation response.  Why cripple the immune response during starvation? My best guess would be because of the huge energy expenditure required to keep the immune response running normally, especially in cellular proliferation.

When leptin levels drop too low, physiological dysfunction occurs in haematopoiesis (blood cell production), bone metabolism, glucose metabolism and angiogenesis (blood vessel production and maintenance) and immune suppression involving both the innate (non-specific) and adaptive immune system. During malnutrition, the size of the thymus gland shrinks with diminished T cell development. This may be one of the long-term consequences of childhood malnutrition. Children with congenitally low leptin levels have a higher mortality rate due to childhood infections (2).

Leptin modulates immune function (ref. 1)

With all the functions illustrated above, it’s not very surprising that malnutrition is the second most common cause of secondary immune suppression today (2). Alternatively, high leptin levels in obese people have also been linked with increased vulnerability to infection possibly through the development of leptin resistance due to prolonged exposure to excessively high levels of leptin (2). Food for thought considering that obesity was one of the only risk factors for a poor outcome during the recent H1N1 influenza pandemic. We have come to expect malnutrition induced immune suppression, but we may also have to consider over-nutrition induced immune suppression and/or autoimmunity as outcomes of immune dysregulation due to leptin resistance.

References:

[1] La Cava, A., & Matarese, G. (2004). The weight of leptin in immunity Nature Reviews Immunology, 4 (5), 371-379 DOI: 10.1038/nri1350

[2] Procaccini C, Jirillo E, & Matarese G (2012). Leptin as an immunomodulator. Molecular aspects of medicine, 33 (1), 35-45 PMID: 22040697