Parameters Influencing Disease Outbreaks: Real World Examples

Great fleas have little fleas upon their back to bite ’em, and little fleas have lesser fleas, and so ad infinitum”. In other words, almost all living organisms are parasites, even parasites have parasites. Parasites are ubiquitous thus creating an impending threat to humans.

This motivated us to establish Brainpan Innovations, a healthcare startup in India, with a vision to combat contagious diseases and save numerous lives. Our journey from computer science to computational science to epidemiology has been exciting. Epidemiology is a new application domain for me. We are still learning the scales, foci, and multidisciplinary nature of infectious diseases. In this article, we will cover the various parameters that influence outbreak, with real world examples. We became familiar with these parameters while developing our product named ‘Disease Atlas’. Disease Atlas is an early warning system for epidemics and pandemics.

Let us start by addressing the most intuitive parameters, and end with the complex ones.

1. Vector: Vector such as mosquitos, flies, ticks, sand flies, cows, cats to name a few, plays an active role in the transmission of pathogen from one host to the other. Vector-borne diseases rely upon such organisms for disease transmission.

Aedes aegypti

Aedes aegypti is one of the most common vector known to transmit dengue, yellow fever, chikungunya and recently notorious Zika virus. It is considered to be a potential vector of Venezuelan Equine Encephalitis virus, and is also capable of transmitting West Nile virus. Aedes aegypti, unlike Aedes albopictus is unable to undergo winter diapause as eggs, and this fortunately limits their ability to exploit more northerly temperate regions.

As the threat of mosquito-borne diseases continues to haunt majority of populace, another deadly, but not apparent tropical disease (classified as Neglected Tropic Diseases i.e. NTD) is also on the move: Leishmaniasis. An infection spread by sand flies is contagious and highly threatening in nature. Currently, it endangers estimated 350 million people around the world [1].

Sand fly: Phlebotomus Papatasi

While mosquito and flies are obvious, this vector is less apparent, and is the center piece of 2014 Ebola puzzle! How did the deadliest strain of Ebola travel from Central Africa to West Africa in 2014? What is more intriguing is to answer how did the virus travel hundreds of miles to Guinea? According to the scientist working on Ebola, it is unlikely that the person infected with Zaire Ebola boarded a plane in Central Africa and carried the virus to Guinea. The first cases occurred in extremely remote regions that are difficult to reach. Could the answer lie in an unknown species of fruit bat that harbored the virus?

Guess the culprit! This time it is the fruit bat!

2. Location: Assessing the location of individual cases may reveal patterns that provide hints about the source. This process is not new, it’s been in use long before Google maps became a reality. In 1854, there was a cholera epidemic in London.

Cholera and the Death
John Snow on Cholera [2]

John Snow, an English physician determined the residence /place of business for the victims and plotted them on a street map. He noted that the cases were clustered around the Broad Street community pump. On the contrary, workers in a local workhouse and a brewery in the same community were not affected since they had their own well. Through this approach he laid the foundation for modern epidemiology.

One of the most obvious and common examples is malaria. It is transmitted in tropical and subtropical areas, where Anopheles mosquitoes can survive and multiply. In cooler regions, transmission will be less intense and seasonal.

However, diseases like Oropouche, rise from uncorrelated regions. In May 2016, Oropouche virus gained ground in the district of Pichari, Peru with 57 confirmed infected. It was the first time an outbreak occurred in the Cusco jungle region. It generally occurs in Madre de Dios and the neighboring country of Brazil.

3. Environment: Environment is closely related to its location. Climate and weather, including climate variables (e.g. temperature, precipitation, humidity), or large-scale extreme weather events (e.g. El Nino), or meteorological hazards (e.g. drought, flood, heat waves) all influence disease dynamics. According to our findings, the most important environmental parameters that influence outbreaks include climate, water supply, sanitation facilities, and food.

Take for example, malaria. Malaria is transmitted among humans by female mosquitoes of the genus Anopheles. The successful development of the malaria parasite inside the mosquito i.e. from the gametocyte stage to the sporozoite stage depends on various factors. The most crucial factors are ambient temperature and humidity. It is found that higher temperatures accelerate the growth of Plasmodium falciparum inside the mosquito.

Diseases like cholera can take place because of broken water supply and marred sanitation facilities. It is often witnessed that floods following heavy rains can result in sewage overflow and lead to widespread water contamination, thus increasing the risk of gastroenteritis. At times nature combines forces for worse. Earthquake (i.e. often breaks sewage infrastructure) followed by rains or storms (i.e. cause water overflow) tremendously increase the chances of outbreaks. In April 2015, two earthquakes of magnitudes 7.8 and 7.3 shook Nepal. It were the worst earthquakes to hit the country in more than 80 years. Hadn’t be the endeavours of the British and Spanish Red Cross and UK water engineer Jo Read, Nepal would then had faced cholera epidemic.

What is exciting in epidemiology is the challenging nature of the cases we encounter. Take for example, Sikkim in India. Recently, Sikkim has emerged as the next big concern on India’s already riddled tuberculosis (TB) map. 11 percent of the new tuberculosis cases in the state have been found to be multi-drug-resistant (MDR), a figure almost on par with the country’s TB capital, Mumbai. For the rest of India, multi-drug-resistance in new TB cases is pegged at around 2 percent. Mumbai, with a population of 13 million, recorded over 27,000 TB cases last year (2015), of which 3,300 were MDR-TB cases. In comparison, Sikkim, with a population of 610,000, recorded less than 2,000 cases last year, of which over 200 cases were of MDR-TB.

Mumbai in India
Sikkim in India

What is remarkable is that both Mumbai and Sikkim have vastly different geographies. Mumbai is a port city known for its clustered living and high density slums. On the other hand, Sikkim is a picturesque state in the Himalayan range and has no overcrowding, even has high nutrition levels.

4. Season: The course of season is relatively obvious in many cases. For example, vector-borne diseases circulate most widely when vectors are most abundant. Similarly, water-borne diseases are driven by environmental conditions.

Take for example, cholera in Bangladesh which shows two peaks per year, a smaller epidemic in the spring just before the monsoon followed by larger epidemic in the fall towards the end of the monsoon.

Another example is flu. In the Northern hemisphere, the flu season typically runs from early December through March. The Southern hemisphere is the mirror image of this pattern. We also found that the antigenic variations in influenza A virus tended to have the same seasonal characteristics.

However, a few diseases are endemic. Dengue for instant is now an endemic in India. Although, Dengue no longer has a season in India (especially in the northern, central and eastern regions), a sharp spike in the number of dengue cases in the months after monsoons (late August and September) has been observed.

5. Migration: Migration in this context will imply human, animal, and bird movement. We are often astonished by the occurrence of a new virus popping up in an unexpected locality where it has never occurred before.

The Old World meets the New World

In the 15th and 16th centuries, exploration and colonization increased human migration. Successive waves of Europeans after Columbus brought many devastating diseases to the new world, what is euphemistically called the Columbian Exchange. In exchange for potato, corn, and other crops, not to mention gold and silver, the colonizing nations of Europe gave the native people of the Americas smallpox, malaria, TB, measles, influenza, bubonic plague, and whooping cough.

Today, globalization and air travel has accelerated this process. In May 2015, the PAHO issued an alert regarding the first confirmed Zika virus infection in Brazil. It was surprising because the Zika virus until now was only identified in Africa and Asia; the virus was first isolated in 1947 in the Zika forest near Lake Victoria in Uganda. It spreads by the Aedes aegypti mosquito. One could hypothesize that it came during the FIFA World Cup in 2014 by an infected traveller. Since then the virus has spread to neighbouring countries because of its proximities and high influx of people across the border and to North America and Europe.

MERS (Middle East Respiratory Syndrome) is another good example. It is a respiratory illness caused by a virus called MERS-Cov (CoV abbreviation for Coronavirus). The first reported case was in 2012 in Saudi Arabia. In 2015, the largest known outbreak of MERS outside the Arabian Peninsula occurred in the Republic of Korea. The outbreak was associated with a traveler returning from the Arabian Peninsula.

Like human migration, animals and bird migration often leads to the onset of epidemics. Animal migrations are often linked to land usage (i.e. mining, deforestation, agriculture) by humans while bird migration is often linked to forage, shelter, and breeding. The most common example is the influenza A which is spread by aquatic birds.

Presently (December 2016), Avian Flu (H5N8) is spreading across Germany, Denmark, and France.

6. Geology: Geology is one of the important parameters for water-borne disease like cholera and dysentery. Geology influences the quantity and movement of groundwater. Geological parameters like porosity, permeability, hydraulic head, water content, hydrodynamic dispersion etc together influence the flow of water in aquifers or conduits and can lead to water quality problem if contaminants seep in.

7. Land Use: Recent studies show that land use change is coming up as a significant driver of disease outbreaks, particularly from wildlife. Deforestation and land conversion for agriculture or mining are one of the biggest drivers of pandemics. Deforestation may increase the prevalence of diseases like malaria, dengue, SARS, leptospirosis, schistosomiasis, leishmaniasis, and even Ebola.

Deforestation of the Amazon Rainforest

It is because it affects the high-risk reservoirs i.e. primates, bats, rodents, mosquitoes and even snails and causes them to diffuse and migrate within the human population. Take for example, the Nipah virus (neurological disease), emerged in the late 1990s in Malaysia after burning to create pig farms. The sty was located near bats population. Bats and pigs feed fruits in the same orchards and the virus made its way into humans. The outbreak infected roughly 250 and killed 105 people. Hollywood 2011 movie Contagion had a similar plot.

8. Human Conflicts: As we ventured further in developing the ‘World’s First Early Warning System for Epidemics and Pandemics’, we realized that we have to broaden the parameter space beyond the ones mentioned above. Initially, the most unobvious parameter was human conflict. Soon we realised that conflicts have devastating effects like weak government institutions, faltering health services, forced human migration, environmental degradation, broken roads and failed development thus creating the perfect storm of conditions for contagious outbreaks. Decades long conflicts in Sudan and Congo led to the emergence of leishmaniasis and sleeping-sickness, respectively.

Nigeria for instant, which was celebrating two years without a wild polio case, recently (August, 2016) reported two cases of polio. The country and the neighbouring region is marred by militancy thus preventing vaccination and detection of the polio virus.

The same cycle of conflict, political, and economic instability is now prevailing in the Middle East. Thousands of refugees are leaving the Middel East for neighbouring safe havens like Turkey and Europe thus creating an impeding danger. According to Dr. Hotez, schistosomiasis, a parasitic disease classified as an NTD prevalent in Africa and the Middle East, has already made an appearance in France (Corsica).

To conclude, modeling an epidemic or a pandemic is fairly complex because of huge parameter space. We presented few of the parameters which our platform considers. Parameters such as basic reproduction number, poverty, health of population, vaccination were not discussed in this article, but are also crucial to model outbreaks. What makes disease modeling even more intriguing and challenging is the interplay and the correlation of one parameter with the other. We hope to discuss this interplay of the parameters in the near future.

Please feel free to leave comments. If you believe there are other important parameters, please let us know. Your comments and insights can help us better understand the challenges of quantifying epidemics and pandemics. Together, we can address this crucial and high impact problem for humanity.

REFERENCES:

[1] http://www.who.int/leishmaniasis/en/

[2] https://fankhauserblog.wordpress.com

[3] http://nationalinterest.org/

Healthcare Entrepreneur, Computational Scientist

Healthcare Entrepreneur, Computational Scientist