Chik Th N tM it B Pl Chikungunya: The Next Mosquito Borne Plague Chikungunya: The Next Mosquito‐Borne Plague Chikungunya: The Next Mosquito‐Borne Plague Chikungunya: The Next Mosquito Borne Plague B Al B dl dR b Ch MD ld By Alex Bradley and Robert Chase McDonald By Alex Bradley and Robert Chase McDonald Opportunities for Further Development Description of Disease Employ a stronger pseudo random number generator than the one used. Transmission Write a script to facilitate automaƟc execuƟon of the simulaƟon with different parameters to obtain greater data sample sizes in less Ɵme. Transmission Transmission is primarily through the bite of Aedes aegypƟ and Aedes albopictus (the Asian Tiger mosquito) Transmission by blood contact (primarily lab and Extend the program to incorporate GIS data to model real‐life scenarios. Transmission is primarily through the bite of Aedes aegypƟ and Aedes albopictus (the Asian Tiger mosquito). Transmission by blood contact (primarily lab and health workers) has been reported as well as in utero infecƟon during the second trimester of pregnancy Infants can become infected when they are born if Rewrite in a different language or with greater use of standard template library to decrease the incidence of bugs. health workers) has been reported, as well as in utero infecƟon during the second trimester of pregnancy. Infants can become infected when they are born if they contact infected blood but the virus does not transmit through breast milk they contact infected blood, but the virus does not transmit through breast milk. References References Chik Vi (2014 M h 26) C t f Di C t l dP Ɵ Rti dM 6 2014 f hƩ // d / hik /i d ht l Chikungunya Virus. (2014, March 26). Centers for Disease Control and PrevenƟon. Retrieved May 6, 2014, from hƩp://www.cdc.gov/chikungunya/index.html October 2010 NewsleƩer (2010 October 14) Oxitec: InnovaƟve Insect Control Retrieved May 6 2014 from hƩp://www oxitec com/october 2010 October 2010 NewsleƩer. (2010, October 14). Oxitec: InnovaƟve Insect Control. Retrieved May 6, 2014, from hƩp://www.oxitec.com/october‐2010‐ newsleƩer/ newsleƩer/ S h M F t ill D T b li C PltC B dA Fl h lt A t l (2010 J 1) I t d Chik Vi If Ɵ Vl 16 Soumahoro, M., Fontenille, D., Turbelin, C., Pelat, C., Boyd, A., Flahault, A., et al. (2010, January 1). Imported Chikungunya Virus InfecƟon ‐ Volume 16, Number 1 January 2010 Emerging InfecƟous Disease journal CDC Retrieved May 6 2014 from hƩp //wwwnc cdc gov/eid/arƟcle/16/1/08 Number 1‐January 2010 ‐ Emerging InfecƟous Disease journal ‐ CDC. Retrieved May 6, 2014, from hƩp://wwwnc.cdc.gov/eid/arƟcle/16/1/08‐ 0776 arƟcle htm 0776_arƟcle.htm Th Ad it hi h t it hik (C t CDC) Signs & Symptoms These are Aedes mosquitoes, which can transmit chikungunya. (Courtesy CDC) Common symptoms include fever, bilateral symmetric joint pain, conjuncƟviƟs, nausea/vomiƟng, body ache, headache, joint swelling, and maculopapular rash. Common symptoms include fever, bilateral symmetric joint pain, conjuncƟviƟs, nausea/vomiƟng, body ache, headache, joint swelling, and maculopapular rash. “Rare complicaƟons include uveiƟs, reƟniƟs, myocardiƟs, hepaƟƟs, nephriƟs, bullous skin lesions, hemorrhage, meningoencephaliƟs, myeliƟs, Guillain‐Barré Rare complicaƟons include uveiƟs, reƟniƟs, myocardiƟs, hepaƟƟs, nephriƟs, bullous skin lesions, hemorrhage, meningoencephaliƟs, myeliƟs, Guillain Barré syndrome, and cranial nerve palsies. (CDC)” In simple language, this means inflammaƟon of the eye, heart muscle, liver, kidneys, brain lining, and spinal cord, as syndrome, and cranial nerve palsies. (CDC) In simple language, this means inflammaƟon of the eye, heart muscle, liver, kidneys, brain lining, and spinal cord, as well as liquid‐filled blister rash, uncontrolled bleeding, and autoimmune disease or loss of funcƟon in peripheral nerves. People at risk for severe disease are well as liquid filled blister rash, uncontrolled bleeding, and autoimmune disease or loss of funcƟon in peripheral nerves. People at risk for severe disease are newborns, the elderly, and people with underlying medical condiƟons. Relapse of inflammaƟon and pain around joints and tendons aŌer the paƟent has newborns, the elderly, and people with underlying medical condiƟons. Relapse of inflammaƟon and pain around joints and tendons aŌer the paƟent has recovered from infecƟon have been reported. recovered from infecƟon have been reported. Treatment “Imported cases of chikungunya virus infection and known and theoretical geographic distributions of Aedes albopictus and Ae. aegypti mosquitoes. World repartition of Ae. albopictus it (t ) d th ti l di i f A ti i 8 (th b d b t d li hi h t th °C i th ) di t th W ld H lth O i ti A Treatment Th i i d t t t il bl Chik i t td t Ɵ ll ith t fl id NSAIDS t li i d t lt d mosquitoes (tan areas) and theoretical dispersion of Ae. aegypti in 2008 (the band between red lines, which represent the 10°C isotherms) according to the World Health Organization. Areas where imported cases of chikungunya have been reported during 2005 2008 are marked with a purple circle (small: 1 73 cases; medium: 74 300 cases; large: >300 cases) or a purple triangle There is no vaccine or drug treatment available. Chikungunya is treated symptomaƟcally, with rest, fluids, NSAIDS to relieve pain, and paracetamol to reduce f where imported cases of chikungunya have been reported during 2005–2008 are marked with a purple circle (small: 1–73 cases; medium: 74–300 cases; large: >300 cases) or a purple triangle when the number of imported cases was unknown.” (Image and Caption Courtesy CDC) fever. E id il Epidemiology S f Si l i P Symptoms typically begin 3‐7 days aŌer infecƟon, with a range of 1‐12 days. Transmission is most likely during the first week the paƟent shows symptoms, so Summary of Simulation Program prevenƟng mosquito bites during this Ɵme is key to reducing the spread. Acute symptoms resolve within 7‐10 days. PaƟents are immune to reinfecƟon aŌer Language Chosen: C++ they have recovered. Terminology Terminology A t th i di id l lki d l th History of Outbreaks Agents – the individuals walking randomly on the map M t di i l f ll Chikungunya has begun to rapidly spread around the world in recent years. It originated in Africa and rapidly spread to India,southeast Asia, and Italy. As the Map – a two‐dimensional array of cells C ll l Ɵ ith i d iƟ th Chikungunya has begun to rapidly spread around the world in recent years. It originated in Africa and rapidly spread to India, southeast Asia, and Italy. As the maps indicate, it has reached every populated conƟnent in only ten years. The movement of the virus is limited by the distribuƟon of its vectors, the Aedes Cell – a locaƟon with a unique x and y posiƟon on the map Pool a region in which an agent has a probability of being biƩen Each pool has three concentric zones each with a bite probability greater toward the maps indicate, it has reached every populated conƟnent in only ten years. The movement of the virus is limited by the distribuƟon of its vectors, the Aedes aegypƟ and Aedes albopictus mosquitos. These mosquitos bite primarily during the dayƟme, and already live in Texas. In 2010 a group of authors wrote a leƩer Pool – a region in which an agent has a probability of being biƩen. Each pool has three concentric zones, each with a bite probability greater toward the center of the pool There are fi e pools in fi ed niforml distrib ted locaƟons on the map aegypƟ and Aedes albopictus mosquitos. These mosquitos bite primarily during the dayƟme, and already live in Texas. In 2010 a group of authors wrote a leƩer to Emerging InfecƟous Diseases, a journal published by the CDC, about the potenƟal for the spread of the chikungunya virus to previously uninfected areas due center of the pool. There are five pools in fixed, uniformly‐distributed locaƟons on the map. I iti li ti to Emerging InfecƟous Diseases, a journal published by the CDC, about the potenƟal for the spread of the chikungunya virus to previously uninfected areas due to the spread of the vector mosquito species and the possibility of an infecƟous person traveling to areas where the virus isnot endemic and spreading the Initialization to the spread of the vector mosquito species and the possibility of an infecƟous person traveling to areas where the virus is not endemic and spreading the infecƟon to mosquito populaƟons there. The following informaƟon is from the CDC website: The program begins by iniƟalizing a two‐dimensional array of cells to form the map. Each cell stores: infecƟon to mosquito populaƟons there. The following informaƟon is from the CDC website: Chikungunya virus in the United States a type (background, inner zone, infected inner zone, middle zone, infected middle zone, outer zone, infected outer zone) Chikungunya virus in the United States From 2006 through 2009, 106 cases of chikungunya were idenƟfied in travelers visiƟng or returning to the United States. None of these cases resulted a flag to indicate infecƟon in local transmission or outbreaks in the United States. a flag to indicate the presence of an agent at its locaƟon With the recent outbreaks in the Caribbean, the number of chikungunya cases among travelers visiƟng or returning to the United States will likely i a pointer to a pool (NULL if a background cell, not in any pool) increase. These imported cases could result in local spread of the virus in the United States and unique x and y coordinates. These imported cases could result in local spread of the virus in the United States. The map is a fixed 1000 by 1000 cells, all iniƟalized to the background type. Next, the pools are iniƟalized. The five pools are iniƟalized by changing the type of the cells in circular regions around five central points to the appropriate zone. The outer zone radius is 150 cells, the middle radius is 100, and the inner zone 50. Pointers to cells are stored in five arrays, one for each pool. Finally, an array of agents is iniƟalized. Each agent stores: a pointer to the cell where it is located, and a flag to indicate infecƟon. The Run Loop Every step, each infected agent is biƩen or not biƩen, and moves to a neighboring cell. Cells and agents are infected as appropriate. A random number is generated to determine if a bite occurs. No bite occurs if the agent is in a background cell, or if the random number is greater than the bite rate for the pool cell the agent occupies. A bite does occur if the random number is less than the bite rate for the pool cell occupied by the agent. When a bite occurs, an infected agent infects an uninfected pool cell it may be occupying, or an uninfected agent is infected by an infected pool cell it may be occupying. Nothing happens if an infected agent is biƩen in an infected pool cell, or if an uninfected agent is biƩen in an uninfected pool cell. If a pool cell is infected, a funcƟon is called to infect all cells in the same pool. A second random number is generated to determine the next step of the agent in one of four direcƟons: up, down, leŌ, or right. If an agent is determined to move to a posiƟon occupied by another agent, or a posiƟon outside the map, then the agent remains in place for that step. Output Output The program writes output to four files: The program writes output to four files: runReports csv – AŌer each run the program appends to this comma‐separated value file the following data: total steps in run total number of agents iniƟal runReports.csv AŌer each run, the program appends to this comma separated value file the following data: total steps in run, total number of agents, iniƟal agents infected total agents infected bite rates for the three pool zones total bites in run total infected pools the step when all pools are infected (‐1 if not all agents infected, total agents infected, bite rates for the three pool zones, total bites in run, total infected pools, the step when all pools are infected ( 1 if not all pools infected) average bites per agent average bites per step average infecƟons per step pools infected), average bites per agent, average bites per step, average infecƟons per step. runReports txt – AŌer each run the program appends to this file a text report of that run runReports.txt AŌer each run, the program appends to this file a text report of that run. stepReports.txt – AŌer each step the program writes a textual step report to this file describing the current step the total agents infected the new agents stepReports.txt AŌer each step, the program writes a textual step report to this file describing the current step, the total agents infected, the new agents infected that step new bites that step bites per agent that step and total bites The program rewrites this file each run infected that step, new bites that step, bites per agent that step, and total bites. The program rewrites this file each run. charMaps txt – AŌer each step the program outputs a 1000 by 1000 character map of the simulaƟon with characters represenƟng the posiƟons of uninfected charMaps.txt AŌer each step, the program outputs a 1000 by 1000 character map of the simulaƟon with characters represenƟng the posiƟons of uninfected agents infected agents background cells uninfected inner pool zone cells infected inner pool cells uninfected middle poolzone cells infected middle pool agents, infected agents, background cells, uninfected inner pool zone cells, infected inner pool cells, uninfected middle pool zone cells, infected middle pool cells uninfected outer pool zone cells and infected outer pool cells cells, uninfected outer pool zone cells, and infected outer pool cells. User Manipulation User Manipulation h i fil d h i l Ɵ diff d i l i h i l Ɵ iiƟ li Ɵ f Ɵ From the main.cpp file, one can adapt the simulaƟon to test different dynamics. By altering arguments to the simulaƟon iniƟalizaƟon funcƟon, a user h Countries and territories where chikungunya cases have been reported (as of April 7, 2014) Th d ti ld i td l l lt i i hi h i may change: th ttl b f t 2014). These maps do not include imported cases, only local transmission, which is what we are modeling (Courtesy CDC) the total number of agents th b f t iiƟ ll if td what we are modeling. (Courtesy CDC) the number of agents iniƟally infected h bit t f th th l (i iddl t ) each bite rate of the three pool zones (inner, middle, outer) h f th h t d h iƟ th t b t h t t h M tt each of the characters used when wriƟng the step‐by‐step character maps to charMap.txt B lt i t t th Si f Ɵ th t i b f t d bl /di bl iƟ th h t th t t d By altering arguments to the runSim funcƟon, the user may set a maximum number of steps, and enable/disable wriƟng the character map, the step reports, and th t t l t Th l t t th td l t the textual run reports. The program always outputs the comma‐separated value run reports. D Data V Bit Rt I Z Vary Bite Rate: Inner Zone Outer Bite Rate Mid Bite Rate Inner Bite Rate Average Bites/Step 0 001 0 002 0 0003 0 4478084 0.001 0.002 0.0003 0.4478084 0.001 0.002 0.003 0.5474474 0 001 0 002 0 03 1 609972 0.001 0.002 0.03 1.609972 0.001 0.002 0.3 12.36684 V IiƟ lI f d (1000 l ) Vary IniƟal Infected (1000 total agents) l f d Step When All Pools Infected IniƟal Infected A Step When All Pools Infected A Mi M Agents Average Min Max 500 45.1 18 76 250 87 6 51 139 250 87.6 51 139 100 337.4 67 670 100 337.4 67 670 0 8 228 20 50 817 228 2077 10 25092.2 12687 37933 10 25092.2 12687 37933 This simple map shows the rapid spread of chikungunya from Africa to Asia and Europe (Courtesy Oxitec) This graph shows how varying the bites rate logarithmically within a zone around the pond changes infection rates Data collected about mosquito density and bite rates at varying distances 1 101060 52186 210865 This simple map shows the rapid spread of chikungunya from Africa to Asia and Europe. (Courtesy Oxitec) This graph shows how varying the bites rate logarithmically within a zone around the pond changes infection rates. Data collected about mosquito density and bite rates at varying distances from a water source could be input into the program, allowing for more accurate mapping of major disease risk areas. Sample maps, progressing from leŌ to right, show the movement of an infected individual. Ponds are represented by the blue areas, with lighter areas having a lower risk of mosquito bite. Pond locaƟons approximately match those used in the program, which used a 1000 x 1000 grid as a map. Here the grid is simplified, with each grid square represenƟng ten units of the programming grid. Healthy individuals are green, infected individuals are red. These maps do not represent actual data; they are designed to show the concepts used in designing the program. Figure 1 A single, randomly selected individual is infected. People begin moving around randomly. The infected individual happens to head into the zone around a pond where the mosquitos live. Figure 2 The infected individual is biƩen by a mosquito from the central pond. The mosquito returns to the pond and passes the disease to its offspring, infecƟng the pond. Mosquitos from this pond will now infect people when they bite. Figure 3 A healthy individual who was hanging around the central pond gets biƩen and becomes infecƟous. Figures 4 & 5 The newly infected individual wanders over to the northeast pond. Figure 6 A mosquito from the northeast pond bites the infected individual there and infects the northeast pond. Figures 7 & 8 A healthy individual enters the area of the infected northeast pond. Figure 9 The healthy individual is biƩen and infected. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9