School Papers

“…they both the microbes and humans and the

“…they rather went to the grave by thousands than into
the fields in mobs by thousands.” Daniel Defoe’s, ‘A Journal of the Plague Year’,
expresses the helpless state of men in the second visitation of plague, famously
called Black Death, that hit London from 1350 to 1490. Since time immemorial,
man has been plagued by such vicious widespread diseases. They’ve influenced
science, politics, religious thoughts, arts, literature, and in fact the very
course of human life on earth. It’s an ongoing struggle for survival for both
the microbes and humans and the former almost always seem to take us by
surprise. The post antibiotic era was one of 
over optimism, encapsulated  in
the words attributed to the then  US
Surgeon General William H. Stewart (1967),’ It’s time to close the books on
infectious diseases, declare the war against pestilence won, and shift national
resources to such chronic problems as cancer and heart disease.’ But the years
that followed witnessed several visitations by old as well as new foes and the
emerging failure of our key weapons against them.

                          An epidemic is a geographically localized occurrence
of disease at an expected frequency over a certain time period3. An
outbreak is restricted to a small geographical area or population while a
pandemic involves different countries and a large population3. There has been a
fourfold increase in outbreaks globally since 19801. The number of
diseases causing epidemics has also increased by 20 percent.1
The WHO
recognizes the following as diseases with the potential to cause epidemics:

•        Chikungunya

•        Cholera

•        CCHF

•        Ebola virus disease

•        Hendra virus infection

•        Influenza

•        Lassa fever

•        Marburg virus disease

•        Meningitis

•           MERS-CoV

•           Monkeypox

•           Nipah virus infection

•           Plague

•           Rift Valley fever

•           SARS

•           Tularaemia

•           Yellow fever

•           Zika virus disease                     

 

                How do these diseases different from other
infectious diseases? The simple mathematical model of SIR- Susceptible,
Infected and Removed is a good tool to understand the dynamics of diseases
causing epidemic, though in reality disease dynamics is multi-dimensional and
variable.  An epidemic starts in a
susceptible population (S) as isolated cases. The infected (I) transmit the
disease to individuals who affect more individuals, setting up a chain
reaction. The rate of spread depends on the average number of secondary
infections from a primary case in a susceptible population which is called the
reproduction number (R0). For R0 to be high, the disease must be acute, have a
low latent period (the period between infection and disease manifestation) ,
considerable infectious period (when the patient is infectious), have an
effective mode of transmission and exposure between susceptible and infected. If so, there will be an
exponential increase in the number of people affected causing an explosive epidemic.
Another important characteristic is that such diseases cause debility and
mortality. This depends on the virulence of the organism. A widespread disease
which causes only mild self-limiting illness like self-limiting gastroenteritis
by Norovirus is not of much concern as there is not much harm to human life.  

            60% of diseases that cause
outbreaks are found to be zoonoses: transmitted to humans from animals1. And it
is highly probable that a new pandemic that is caused will also be zoonotic.
HIV spilled over from chimpanzees, Coronaviruses, Niaph and Ebola from wild
bats, Avain influenza from aquatic birds and chicken, Lassa fever from rats and
so on. Bats and rodents are the most common reservoirs. Phylogenetically
related organisms have a greater possibility of harboring organisms capable of
cross- transmission10. Animals capable of flight can cross borders and bring in
strange diseases to new places. This is one of the main concerns with avian
influenza where wild aquatic birds, especially migratory birds, can transmit a
new strain across the globe11. PREDICT, a program that is funded by the U.S.
Agency for International Development tries to predict future zoonoses by
discovering new viruses and collecting data 12. A similar initiative is the
Global Virome Project a venture to identify and sequence potential zoonotic
viruses. Vector-borne diseases pose a major threat in endemic areas and can
possibly spread worldwide. Zikka viruses, linked to congenital neurological
complications including microcephaly, has caused outbreaks in Africa, the
Americas, Asia and the Pacific.who Climate change expands the territories
inhabited by vectors and animals carrying diseases. Permissive climatic
conditions for Aedes mosquito in Brazil due to the effects of El Nino on the
climate was implicated in the explosive spread of Zikka13. Excessive
deforestation and loss of habitat is also associated with emerging and
re-emerging zoonosis. In short, it’s an interplay between the agent,
vector/reservoir, environment and man and we are more susceptible than ever.

                  The dawn of civilization
would probably have been a defining moment in the history of pandemics as there
was increased ease of spread and increased chance for getting infections from
animals. Today with the population growing at a global rate of 1.09% per year13,
with the grossly varying population density across the globe, we are more at
risk than ever. This coupled with increased international travel brings back
memories of rats with Yersinia pestis (causative agent of plague) aboard on
merchant ships, a seemingly simple prequel to the Black Death. Effective measures to check
travelers from places endemic for potentially dangerous diseases must be in
place. The Plague outbreak in Madagascar from the 1 August through 22 November
2017 caused a total of 2348 probable and suspected cases of plague, including
202 deaths (case fatality rate 8.6 %). But effective surveillance of travelers
and follow up of contacts helped check its spread beyond the country.   

                  An epidemic is usually self limiting.
This can again be describe using the SIR model. The affected people die or develop
protective immunity and go into the removed population (R). Hence the
susceptible population decreases over time, decreasing the rate of spread and
finally it ceases. If R0 <1 it would indicate decline of an epidemic. Isolation and quarantine limits R0, vaccination decreases susceptible population and treatment reduces debility and mortality and often brings more people into the removed group. Hence prevention by vaccination and immediate isolation and treatment of isolated cases can prevent a pandemic but all of these interventions pose challenges.                     Alteration in genetic content resulting in antigenic variation is a cause for organisms against which prior vaccines and drugs become ineffective. So we can never be truly be prepared. Classic example is the influenza virus which can change due to antigenic drift: mutational changes or antigenic shift: re assortment of its 8 segments of RNA between animal and human species in animal reservoirs and then spillover into humans. The HINI influenza pandemic of 1918, often termed as the greatest medical holocaust in history 'claimed 50 to 100 million lives. Many epidemics and pandemics of influenza have followed. The dangerous strain that arose in the H1N1 pandemic of 2009 or swine flu was due to re assortment between human, avian, and swine influenza strains. The 2013 outbreak of a new dangerous strain, H7N9 in China raised fears of another pandemic.  The re assortment took place between strains of migratory aquatic birds, ducks and chicken14. Spillover took place between chicken and people. Despite its limited ability to spread from person to person it infected 87 people and killed 17 people14. In the beginning of 2018, the potential threat is seen to be H3N2. In short, despite it being over a hundred years of recorded pandemics, man has no permanent solution to Influenza. Preparedness with generic measures and rapid response once an epidemic starts is what we rely on.                 Research and development of vaccines and drugs for diseases which rarely emerge is inadequate. Ongoing and pressing issues take precedence over epidemic preparedness. Pharmacological companies would not find it lucrative enough. And even if effective drugs and vaccines do get approved they must be made available for free or at minimal expense which again poses the same problem. Candidate interventions which have not passed through clinical trials will have to be administered if the situation becomes severe. This is a subject of international debate. This was the case with 2014 Ebola.  When there was an increased death toll among west Africans,  two US aid workers and a Spanish priest who contracted the disease were treated with the investigational drug ZMapp.15 Many questions on ethics were raised but the most important was why it took nearly 40 years after the first outbreak in 1976 to launch clinical trials. The Zikka virus was also known to us since 1940's but there are no effective drugs which are ready to use. Hence, funds should be allocated for pandemic preparedness in advance. In case of a crisis funds must be forthcoming and prompt. The case of Ebola can be cited as an example for the dire consequences of a delay in the international community response to an outbreak.                Lack of  health infrastructure and limited resources to handle cases is another cause of concern.  As again seen in the case of Ebola, only 11 reported cases were reported in the United States and they required advanced intensive care. This is not feasible in underdeveloped countries and hence the mortality rate was high in African countries. Sierra Leone, from where over 4,000 deaths from Ebola were reported was ranked least in a health infrastructure survey by WHO. Travel can spread such deadly diseases to other countries posing a security threat to these places. Hence, developed countries should invest in health care of developing countries.                        Drug resistant bacteria pose a huge threat today.  There is also always a fear of bioterrorism. And with the development of methods to manipulate microbes there's every possibility to create weapons of destruction. There should be strict policies in place for research with such microbes. But this  did not stop the Anthrax outbreak of 2001 in the US which occurred despite strict restrictions in place.                      Hence it is beyond doubt that a next pandemic is inevitable. The question is what, when and where? As Bill gates rightly put's it," The Ebola epidemic can serve as an early warning wake-up call to get ready. If we start now, we can be ready for the next epidemic."