Future Pathologies

Can contemporary medical economics combat the growing threat of microbes?

Have we created sufficient evolutionary pressures that the microbe diseases of yesteryear and the neglected pathogens of today become a threat for us tomorrow? Whilst I don’t yet have the answers I intend to test my hypotheses and opinions expressed below as part of a review, which I also intend on making  into a science communication presentation, (I will share if it’s of sufficient quality). I aim to tie in a few ideas below, to prevent my introducing any biases of my own, or false preconceptions I hope this will generate discussion from those with relevant experience and knowledge.

Sulphonamides may have been the first antibiotic agents, but the golden age of antibiotics starts with the mass production of penicillin. Gram positive infections of Staphylococcus and Streptococcus as well as what is believed to be the first human pathogen Treponaema pallidum are optimistically believed to be treatable and diseases of the past. Whilst we were successfully defeating the life shortening infections of old from septicaemia to rheumatic fever, we weren’t aware yet of the optimal treatment protocols. With limited knowledge comes great irresponsibility, and what some of us may regard as poor use today was standard practise in eras past. Without complete knowledge of dosage efficacy, or clearing time, the push to gain return on investment from pharmaceutical companies with limited regulation or guidelines for prescription meant antibiotics were prescribed for inappropriate illnesses. In part the placebo effect that the average person receives from being given what is believed to be an effective treatment further reinforced the overprescribing tradition in our community’s culture, and in our human fallibility some will succumb to the pressure to prescribe.

Once the prescription is filled, we entrust the patient with the responsibility to properly administer the remedies recommended. With limited knowledge, therapies are often discontinued when the patient “feels” normal. Before the understanding of clearing time, it was assumed that once a patient regained healthy features, the treatment could be ceased. The first attempt to treat a Staphylococcal septicaemia with penicillin unfortunately failed as the subject soon relapsed and insufficient antibiotic had been produced to properly resolve the infection, resulting in the rapid decline and death of the patient. Whilst we are now more than aware of the persistence of infection, in minor illness patients are liable to discontinue full dose upon feeling they have benefited from therapy. The patient may feel they are healthy, depending on the pathogen, the host-pathogen relationship will determine whether the organism is overcome, or returns to commensal status. Whilst the host immune system may return to sufficient functionality to balance out pathogenicity from commensal flora, commensal organisms may not be fully eradicated, the selection pressures exerted by antibiotics may be sufficient to produce, or select for resistant strains. Currently, 10-15% of S. aureus infections in the community are resistant. Given what we know of the immune suppression that comes with age, and the demographic forecasts of the future, could our aged population die earlier as a result of opportunistic infections for which we have no treatments? Whilst host factors will determine matters of adhesion and virulence (as was found with Neisseria meningitidis B there are a series of host genes that if present determine colonisation or invasion) unfortunately with many opportunistic infections our mainline of adaption extends only so far as our immune system, and once this line of defence is sub-optimal, disease is a likely outcome. Further, given the age of onset for these diseases it is highly unlikely that the human species will have any significant change in gene frequency that will confer any form of protection from these ailments.

Parallel to aging population are lifestyle factors of the as yet not geriatrics. An increasingly sedentary lifestyle coupled with increased calorie consumption has seen an obesity epidemic. With obesity comes problems including cardiovascular disease, diabetes and some increased cancer risks. These conditions should they increase in frequency will place increased pressure on hospitals to provide surgical services as the population continues to age. With increased average population age comes a decline in the average income, paradoxically health infrastructure requires more funds to cope with the aged (this may be exacerbated by the above neglecting of health), whilst the lack of funds means cuts are an inevitability. According to a presentation given by Andy Simor, hospitals typically react in two ways when cuts are forced, decrease in cleaning or attempt to cut back on chemotherapeutics (including antibiotics). Unfortunately, the money saved is usually quickly lost as infection control stringency goes south. Cuts to antibiotic treatment could again result in adequate resolution of infection and therefore resistance. Perhaps longer or more combination therapies should be deployed to act as a series of changed host factors which are too great for the infection to overcome, and hope we make a return on investment in the future from a long term savings dividend? Those with diabetes, cancer and CVD suffer from a decreased immune status, which again adds more gravity to the situation of resistant opportunistic infections, particularly the already difficult gram negative anaerobes.

Alcohol and smoking also contribute to the host susceptibility. According to Australian Bureau of Statistics data, indicates that many young Australians are engaging in binge drinking. Drinking heavily is associated with immuno-suppression and therefore leaves a host open to numerous pathogens including Klebsiella pneumoniae and other aspiration pneumonias. In Western Australia 1.3% of jobs are in the mining sector. With fly in fly out workers from remote areas potentially in a less than healthy state, could diseases like rheumatic faver and Acinetobactor pneumonias become more common, and possibly endemic in hospitals? Further, will we see more cases of melliodosis?

Preventable childhood illnesses are again on the rise. This trend is mirrored across the developed world, cases in point being California where a whooping cough epidemic and England where a measles epidemic are already claiming the lives of children. For the main, complacency on the behalf of parents who no longer believe these diseases are circulating in their particular region of the world is to blame. However, the concept of an isolated region is one now confined to the annals of history.  Another contributing factor is the fictional representation of these ailments as harmless childhood illnesses with limited adverse outcomes. Whooping cough may cause an epiglottitis and measles an aseptic encephalitis both of which are rapidly fatal in children. Anti-vaccination groups dangerously deny these facts, dangerous and evident untruths that place communities at risk (as has lately been highlighted by NSW health tribunal decision to have the AVN state that their content does not constitute medical advice). Adverse sequalea (chicken pox and measles in particular) of some of these childhood diseases are much worse in adults who contract these ailments. For measles to remain in a population it is estimated that 500,000 unprotected individuals must be present. Might we see increased mortality from childhood diseases in more adults as the unvaccinated children enter adulthood, and these diseases enter endemicity?

Additionally, the continued lack of regulation of pharmaceuticals in underdeveloped countries combined with a lack of sanitation, population growth, and increased population density in urban areas are a dangerous combination, providing evolutionary opportunities for the selection and propagation of highly resistant mutant strains. The problem of third world health is further compounded by a lack of return on investment for the creation of new treatments and vaccines for some of the most deadly pathogens. The resurgence of nationalism has and always will pose a barrier to adequate funding of foreign aid programmes. Measles, malaria, dengue, Yersinnia pestis, HIV, yellow fever, Mycobacterium tuberculosis and various waterborne diseases will ever find a reservoir in the third world for a long time yet, and diseases have a very cosmopolitan outlook. One only needs to look at the spread of West Nile virus to the USA, and the case of the South American raspberries that infected consumers with Ballintidium hominis in non-endemic areas to realise that with an increasingly internationalised world (travel, trade, etc) we should never believe that a disease will remain exclusive to one region of the world.

Climate change and environmental degradation are factors that are set to broaden the distribution of several pathogens and associated vectors. Whilst not a human pathogen, it is believed that the disruption of many microrhiza opened up an ecological niche for the jarrah dieback disease. Could other environmental pathogens like Burkholderia psuedomallei move into such a vacant spot in a depleted ecosystem? With climate’s change, some of the environmental barriers will cease to exist for diseases and vectors to become endemic in an area. It is predicted that dengue fever and the Aedes egypti mosquito will move further south in Australia over the coming decades. Likewise, malaria and its Anopheles vectors will continue to become endemic in more regions of the world. As we never invested in vaccines or new treatments, first world countries still be just as vulnerable to these diseases (pending vector control attempts, however as with West Nile virus in the US there may be little that can be done to prevent spread once they are at detectable levels). In the case of bacteria, with increased geographic distribution comes new environmental pressures to direct the evolution of new traits. Traits such as adhesion to chitin in Vibrio cholerae are the very genes that determine virulence in the human small intestine (ironic example as it was this organism that struck down the daughter of Charles Darwin). Other examples would include the ability to survive inside amoeba (Legionella, Burkholderia) conferring them with the ability to survive in macrophages, and environmental iron chelating proteins overcoming anaemia of inflammation. What niches are we selecting for through climate change, and how could these affect pathogenicity? The human side of climate change can be seen in Pakistan. Increased frequency of adverse weather related disasters in concentrated foci of dense human populations (like a Hurricane Katrina scenario) would have devastating implications for the spread of infectious diseases (melliodosis being one in our region). Additionally could disaster relief teams act as unwitting carriers of diseases from one region to another? However with clean water and sanitation in the Western World the threat of a reemergence of water borne disease remains unlikely. As sanitation is estimated to have led to 25 years of the 30 year increase in human life expectancy since 1850, perhaps the decrease in future life expectancy will be modest (factoring out lifestyle factors)?

Evolving alongside to the antibiotic resistant commensals, livestock and aquaculture’s use of antibiotics have produced antibiotic resistant strains of many bacteria including E.coli, Vibrio spp. Vegetables may not be much safer as night soil remains in use in some countries as increasingly, Australia consumes food entering from the third world, are we at the mercy of the lowest common denominator of food safety? Are we liable to more E. coli O157-H7 and other food borne pathogens (see B. hominis entering US on South American raspberries)? People living with their livestock in rural areas of the South East Asian region also open the door to many new zoonoses like SARS and H1N1. Fish sources becoming exhausted and the rise of aquaculture too may change the nature of infectious diseases. Fish lack lymph nodes and therefore receptor revision making vaccinology of fish a challenge. Being an intensive industry, Vibrio spp being a common pathogen for which there are few effective fish vaccines, could future fish consumption be associated with increased risk of haemolytic food poisoning, and Streptococcus iniae infections especially as oceans warm?

So, what does the future hold in store?

I would like to acknowledge Dr. Tim Inglis for his inspiring lectures and conversations which fostered my interest in this topic.