I don’t think there is a single person that can claim to have never had the joyous experience (sarcasm intended) of suffering from the influenza.  We all recognize the common symptoms that accompany this infectious little virus taking up residence in our bodies: the chills accompanying a fever, the total body ache, the nausea, and overall feeling of malaise.  Typically this virus comes and goes within a week without serious side effects.  When novel strains of the influenza pop up however, there can be more serious complications as your body lacks a sufficient immune recognition of the virus.  An example of a new strain of influenza that presents a great risk for the human population is the H7N9 influenza, also known as Avian Influenza A.

H7N9 was first recognized earlier this year in China and thankfully has yet to be reported in the US. The majority of the people infected have had direct contact with poultry or an environment that has contained infected poultry.  Some of the people diagnosed however, report having had no direct contact with poultry opening up the possibility of human to human transfer of the disease.  The infected poultry have shown no obvious symptoms of being infected, but when humans become infected it can cause severe respiratory problems and fever.  As of May this year, LiveScience reported that there have been a total of 131 reported human cases of H7N9 with 32 reported deaths.

While all of that may not sound too impressive, here’s what makes H7N9 such a concern as an emerging infectious disease.  The first major concern regarding this specific influenza is the fact that it is the first time the H7N9 virus has been reported in humans.  The H in the name H7N9 stands for hemaglutinin, which is the attachment protein found on influenza viruses.  This protein not only enables the virus to attach to the cells it is trying to infect, it also is provides the host’s immune system a way of recognizing the virus as a foreign threat.  The fact that this is the first time this specific virus has been found to infect humans means that we lack any prior immunity to it and are therefore, more susceptible.

Another factor that raises the alarm for this influenza is the fact that the infected poultry that have been found so far have shown no outward signs of being sick.  This is a huge concern because it makes controlling the spread of the disease much more difficult.  When poultry and livestock exhibit obvious signs of being infected, it allows the infected to be separated out from the healthy and either isolated or culled to prevent further spread of the disease.  In some cases, the disease may have already spread amongst all of the animals in the vicinity requiring the entire herd or flock to be culled.  When it is difficult to distinguish between healthy and infected animals however, any evidence that the disease has been found within the animals will more than likely lead to the entire herd or flock being culled.  This not only results in greater economic losses for the poultry farmers but also a higher number of people being exposed to infected animals before realizing the danger that is present.

Possibly the greatest concern with H7N9 is the fact that it could be jumping from person to person.  The original thought was that the only way it had been spreading was from direct contact with sick poultry, which would limit the at risk human population to people coming into contact with the infected birds.  Some of the people who have been diagnosed with H7N9 however, are claiming to have had no contact with poultry suggesting that the disease may be capable of human to human transmission.  This would greatly increase the reproductive rate of the disease because people would no longer need to come into contact with poultry to be exposed to it.  The reproductive rate, commonly referred to in scientific communities as the Ro, is a way of measuring the predicted number of new infections that one infectious case is likely to create.  Another factor that suggests the possibility of human to human transfer is the fact that there have been three reported family clusters of H7N9.  While this does not necessarily mean that the virus is capable of sustained human to human transfer, it is highly suggestive that human to human transmission has occurred in these particular instances and that with the right (or depending on how you look at it, wrong) mutation, it could transfer between humans with ease.

While all of these things explain why H7N9 is being watched so closely and why it is important to have a healthy respect for just how dangerous it could be, there’s no reason for people to start panicking quite yet.  As mentioned earlier, this strain of influenza has only been reported in people that either live in or have recently traveled to China.  Unless you are planning to travel out of the country in the near future, there is no reason to become overly concerned about H7N9 at the moment.  Also, the majority of the cases have either had direct contact with infected poultry or close contact with someone who has had contact with poultry.  This means that unless the virus becomes proficient at human to human transmission, the majority of the population is at a low risk.

For the germaphobes out there that are still freaking out over the possibility of catching H7N9, there are several ways to reduce the risk of catching it, or any other influenza for that matter.  Good hygiene practices such as frequently washing your hands and avoiding touching your face will help minimize the risk of introducing the influenza virus into your body.  Eating a well-balanced diet and getting plenty of rest will help keep your immune system in tip top shape in the event of a virus managing to get past your innate defense mechanisms.  In regards to reducing the risk of catching a zoonotic strain of influenza, practices such as thoroughly washing your hands after handling any animals and avoiding contact with sick poultry or livestock will reduce the risk of transmission.  So rest at ease, the world isn’t coming to an end due to H7N9…at least not yet.

Sources

Cong Dai, Min Jiang, “Understanding H7N9 Avian Flu,” BMJ, Available online 3 May 2013.  <http://www.bmj.com.proxy.lib.uiowa.edu/content/346/bmj.f2755?view=long&pmid=23645899>.

“Frequently Asked Questions on Human Infection Caused by the Avian Influenza A (H7N9) Virus.”

World Health Organization. WHO, 30 Apr. 2013. Web. 12 June 2013. <http://www.who.int/

influenza/human_animal_interface/faq_H7N9/en/>.

Guang-Wu Chen, Michael M.C. Lai, Suh-Chin Wu, Shih-Cheng Chang, Li-Min Huang, Shin-Ru Shih, “Is avian influenza A (H7N9) virus staggering its way to humans?”, Journal of the Formosan Medical Association, Available online 3 June 2013, ISSN 0929-6646, 10.1016/j.jfma.2013.04.015. <http://www.sciencedirect.com/science/article/pii/S0929664613001654>.

“H7N9: Frequently Asked Questions.” Centers for Disease Control and Prevention. Centers for Disease

Control and Prevention, 22 Apr. 2013. Web. 12 June 2013. <http://www.cdc.gov/flu/avianflu/

h7n9-faq.htm>.

Kannan Tharakaraman, Akila Jayaraman, Rahul Raman, Karthik Viswanathan, Nathan W. Stebbins, David Johnson, Zachary Shriver, V. Sasisekharan, Ram Sasisekharan, “Glycan Receptor Binding of the Influenza A Virus H7N9 Hemagglutinin,” Cell, Available online 6 June 2013, ISSN 0092-8674, 10.1016/j.cell.2013.05.034. <http://www.sciencedirect.com/science/article/pii/S0092867413006405>.

Rettner, Rachael. “H7N9 Bird Flu Cases Declining, Health Officials Say.” LiveScience. N.p., 10 May

2013. Web. 12 June 2013. <http://www.livescience.com/

29515-bird-flu-h7n9-case-decline.html>.

A Dangerous Paradise

From jungles with jaguars to crystal blue lakes with freshwater sharks, Nicaragua is one of the most beautiful and dangerous countries in Central America. The brilliant biodiversity attracts millions of tourists each year and the looming volcanoes that pepper the landscape can be an exciting yet unsettling sight. However, in reality much of the danger in Nicaragua comes from the risk of infectious diseases. For example, if you’re planning to travel to this tropical paradise anytime soon, the Center for Disease Control (CDC) states that international travelers are at risk of contracting Typhoid fever, hepatitis A, hepatitis B, Leishmaniasis, malaria, dengue, rabies, and more! As a dual degree veterinary medical and public health student, I am fascinated by these infectious diseases and want to learn how they interact with the environment, people and animals. Many of the diseases that the CDC listed are called zoonotic diseases, or diseases that are transmissible between animals and humans. Other zoonotic diseases you may know include ringworm, Lyme disease, and Cat scratch disease. Whether you own a pet, like to travel, or simply enjoy spending time outdoors, you are at risk of infection because these zoonotic diseases are increasingly emerging worldwide and are becoming a serious public health threat. During the spring break of my first year of veterinary school, I traveled to Nicaragua on a mission trip and got first-hand experiences of these frightening infectious diseases.

Bed Nets and Bug Spray

Planning for this trip was time-intensive and reminded me of planning for my semester study abroad adventure to Tasmania, Australia. However, unlike my semester Down Under, this trip was coordinated through the national non-profit Christian Veterinary Mission (CVM) whose goal has been to help veterinarians serve others and live out their Christian faith for more than 30 years. Out of all the fundraising and logistics meetings we had, the meeting that stands out the most was when the Iowa State University travel nurse described the laundry list of potential pathogens we could encounter. Our team of 8 veterinary students, 3 veterinarians, and 1 pharmacist would be treating animals in a remote village called Espavel in the jungles of eastern Nicaragua. When I saw that my destination was in the middle of the red zone for malaria on the CDC map, my eyebrows escalated and my stomach dropped.

I was going to fly to an unstable, earthquake-prone country of approximately 5.7 million Spanish-speaking people where malaria was endemic. My Spanish was scarce, but my drive to serve was strong. After I heard that malaria was essentially eliminated from Nicaragua, my blood pressure dropped a few millimeters of mercury. Approximately 84% of the Nicaraguan population is at risk of contracting malaria, according to a UCLA study. However, Nicaragua has experienced a 97% decrease in reported malaria cases between 2000 and 2010. This significant decrease in prevalence was a result of Nicaragua partnering with the Pan American Health Organization (PAHO) in 2006 which heavily implemented stronger surveillance, prevention, vector control, and treatment. Despite this progress, I learned from my undergraduate Lyme disease Honors project that there are always numerous challenges to completely eliminate vector-borne diseases like malaria. For instance, controlling mosquito breeding populations is particularly vexing due to the complex ecology of the parasite life-cycle. In addition, you may have heard about the controversy surrounding toxic pesticides like DDT. My colleagues and I were fortunate for our DEET bug spray and Permethrin treated clothes and bed nets that we brought after skyping our host-country missionaries. I was also relieved that our trip in March 2013 was during the dry season and not during the September-to-January rainy season, when disease transmission is highest.

Rambunctious Rabies

Escaping the endless hours in the frigid, formaldehyde laden anatomy lab and flying to a third-world tropical country to practice preventative medicine was slightly shocking, but totally worth it. On our first day, we drove through the littered streets of Catarina to an outdoor shelter where we set up a temporary clinic. The local children brought their pet dogs and we treated them with Ivermectin and other anti-parasitic medication. Many animals were very thin and infested with fleas and ticks. However, it was rewarding to interact with the children and walk them through a brochure that described both healthy animal care and the Gospel of Jesus Christ. Then suddenly one of my colleagues was bitten by a dog! He was trying to give a rambunctious mixed-breed a pill to protect against heartworm disease and the next thing he knew, the dog bit him in the hand. He quickly washed the wound with soap and water and bandaged it. Fortunately, everyone on our veterinary team was already vaccinated for rabies prior to the trip because it’s a requirement to enter veterinary school. He also followed up with post-exposure rabies prophylaxis when he returned home.

Rabies is one of the deadliest and most notorious zoonotic diseases in the world. Rabies is endemic to Nicaragua, often occurs in poor rural communities, and the most common source of transmission is when a dog bites a human and delivers the fatal RNA virus. According to the World Health Organization, potentially any mammal can contract rabies, and common reservoirs in the USA include skunks, foxes, raccoons, and bats. Although rabies cases can be successfully treated, it still persists worldwide killing more than 55, 000 people each year. The Center for Food Security and Public Health (CFSPH) at Iowa State University is an excellent resource that provides more information on rabies and preventing zoonotic diseases. Reducing the prevalence of rabies globally requires a multinational effort and the World Rabies Day Initiative was founded solely for this mission and has already collaborated with 150 countries and vaccinated over 7.7 million dogs.

Tasting Iguana and Tackling Typhoid

It’s a good thing I like rice and beans, because that was the bread and butter of most of my meals every day. Hiking to farms builds an appetite and one day we had to traverse across a narrow blank that stretched precariously over a ravine. After we arrived, we vaccinated over 100 head of cattle for clostridium, anthrax, and Dectomax. Dectomax is an injectable drug used to control parasites like hookworms, round worms, grubs and mites. When we returned to the main village and got out of the blazing 90+ degree sun, the crispy, plantain chips with a glass of freshly squeezed tamarind juice was an irresistible snack. However, the most memorable meal of all was the morning the villagers surprised us with two 5 foot long iguanas! A few hours later, I was savoring some delicious iguana meat seasoned with local spices and vegetables. Cooking wild reptiles is foreign to us in the developed world; likewise, the way many Nicaraguans prepare their food is also different.

Sayings like, “Don’t drink the water,” or ‘Boil it, cook it, peel it or forget it,” come to mind when traveling abroad, and they couldn’t ring more true for my experience. Food-borne illnesses are another great example of how veterinary medicine and public health overlap. I’m enrolled in the dual DVM-MPH degree program at the University of Iowa’s College of Public Health and learned that food-borne epidemics are a major focus of research in epidemiology. From mild cases of spoiled potato salad on romantic picnics to church dinner outbreaks from contaminated home-made ice cream, food-borne illnesses can range in their severity depending on your pre-existing health and the dose and type of microorganism ingested. One of the Nicaraguan diseases that I was vaccinated for before my trip was a food-borne illness known as Typhoid fever. Thankfully I avoided this illness; however, I couldn’t escape the wrath of Montezuma’s revenge, or traveler’s diarrhea, most commonly caused by enterotoxigenic Escherichia coli.

Typhoid fever is transmitted through contaminated food or water and is unique among food-borne pathogens because it only affects humans. In fact, some individuals can unwittingly become carriers of the bacterium and transmit the disease to others through improperly prepared food, like the infamous Typhoid Mary. This disease is caused by the bacterium Salmonella typhi, which is one of over 2,300 species of Salmonella and can be treated with antibiotics, according to the USDA. Other Salmonella species are also common among household, cold-blooded critters like turtles, frogs, iguanas, and snakes, so it’s important to always wash your hands after handling these pets.  Like malaria and rabies, Typhoid fever presents challenges for eradication in developing countries where poverty limits accessibility to clean water, pasteurization, and proper sanitation and hygiene. For example, I had never taken a well-water bucket shower before, and although the murky water felt refreshing after a long days’ work, I came to more deeply appreciate the luxuries of everyday plumbing and electricity.

Collaboration is Key

An empowering lesson that continues to inspire me was when I participated in a humanitarian collaboration. Before our departure, we communicated with another mission team from an Arkansas Baptist church that would work at the same time as our Iowa State Christian veterinary mission team would work over spring break. The goal of the Arkansas team was to provide humanitarian care while the goal of the Iowa State team was to provide veterinary care. For instance, the Arkansas team brought donated shoes and eyeglasses, provided nutrition education and had a dentist and nurse that pulled teeth. On the other hand, the Iowa State team vaccinated dogs, cats, horses, cattle, and pigs, performed surgeries and provided agricultural advice to farmers. Even though the two teams set up separate clinics to work on different species, we still felt united as one team because we traveled together, ate meals together, and worshiped together.

One sunny afternoon, we asked the human dentist to come over to our animal clinic to pull a rotten tooth out of a horses’ mouth. The dentist had hardly been around horses in his life, let alone stuck his hand in one’s mouth before, but after the novelty wore off, he quickly agreed to help our team. The sedated horse was lying on its side surrounded by curious villagers and veterinary students. The dentist was nervous and the 3 inch long decayed molar kept wiggling out of his grip. Finally, he extracted the tooth and everyone was amazed and overjoyed. It’s a simple story like this that showcases the successful collaboration between veterinarians and other medical professionals that is the goal of the One Health Initiative or the new concept of interdisciplinary healthcare collaboration. In order for us to eradicate these infectious diseases and save lives, it is vital that veterinarians, physicians, dentists, and epidemiologists collaborate and communicate to find solutions.

A Future Fighting Infections

Going on this short-term veterinary mission trip put me in harm’s way, but it gave me real-life experience with infectious diseases, deepened my faith, and strengthened my clinical skills. It was bittersweet to say adios to my amigos, but I know I’ll return to that perilous paradise.  I enjoyed the international fieldwork and cross-cultural partnership because it embodies the One Health Initiative that I highly esteem. From hiking in the jungle on my 23^rd birthday to taste-testing iguana to teaching children about pet care and the Word of God, this trip was a remarkable adventure that has forged a new trail for me. I don’t believe it’s an impossible mission, and I am committed to pursue veterinary public health as a career and control zoonotic diseases in developing countries.

All photos courtesy and copyright Brandon Woods. 

Resources:

http://www.who.int/en/

http://new.paho.org/hq/

http://www.merckmanuals.com/vet/index.html

http://www.cfsph.iastate.edu/Zoonoses/

https://www.cia.gov/library/publications/the-world-factbook/geos/nu.html

http://www.fsis.usda.gov/factsheets/foodborne_illness_&_disease_fact_sheets/index.asp

http://amestrib.com/sections/news/ames-and-story-county/student-traces-lyme-disease-ames.html

http://wwwnc.cdc.gov/travel/destinations/traveler/none/nicaragua

http://www.fda.gov/forconsumers/consumerupdates/ucm048151.htm

http://www.cvmusa.org/Page.aspx?&pid=183

http://en.wikipedia.org/wiki/Zoonosis

http://www.worldrabiesday.org/

http://www.onehealthinitiative.com/

http://www.public-health.uiowa.edu/epi/

During the summer of 2010 I spent two months in Ghana studying a parasite called schistosomiasis. We worked in a small town called Adasawase to determine prevalence and treat the schoolchildren who were infected. We were told that schistosomiasis was not a major health concern for the people in the town because they were often faced with other diseases that had more immediate and severe health consequences than a parasitic infection. It became apparent that if we wanted the people of this small town to take this health threat seriously, we needed to stress the long term health sequelae that could arise due to schistosome infections.

(Personal photo taken in Ghana in 2010)

Our research group decided to implement an educational portion to our schistosomiasis control program. Through a Knowledge Attitudes and Practices survey, we found that most schoolchildren in the town reported learning about health from their teachers in school. We held a meeting with all teachers and administrators from Adasawase to educate them on the transmission, symptoms, and long term implications of schistosomiasis infections. When the possibility of greater transmission of HIV to individuals with schistosomal infections came up in discussion, we suddenly had everyone’s complete attention. You could have heard a pin drop on the cement floor of the school room.

Recently, the BBC reported that over 25% of schoolgirls between the ages of 10 and 14 in South Africa are infected with HIV. The World Health Organization has shown that HIV prevalence is much higher in females living in urban areas than in any other demographic group. More than 2/3 of the world’s population living with HIV/AIDS lives in Sub-Saharan Africa. Many efforts have been made to decrease the prevalence of HIV in Africa but few people have looked at the possibility of a parasitic infection possibly contributing to the transmission of HIV.

(http://www.who.int/gho/urban_health/outcomes/hiv_prevalence/en/index.html)

Schistosomiasis haematobium is a species of waterborne parasite that specifically affects the urogenital system of infected individuals. When people with S. haematobium urinate in stagnant water, they deposit schistosome eggs. The eggs develop into larvae which then enter a freshwater snail to continue its life cycle and mature. It leaves the snail and matures into its infective stage while in the water. The mature larval form of the parasite burrows through the skin of an individual who has contact with contaminated water. Once inside the body, the mature larva develops into an adult worm and then travels to the blood vessels surrounding the bladder. The male and female will mate to produce eggs which penetrate through the bladder wall and are passed in the urine to continue the cycle.

The treatment for a schistosomiasis infection is an inexpensive anti-helminthic medication called Praziquantel. Common signs of a S. haematobium infection are bloody and cloudy urine. Damage to the bladder wall is inevitable and if the infection becomes chronic, damage to the kidneys can also ensue. Chronic genital sores can develop in females with S. haematobium infections when the schistosome eggs are deposited in the uterus, vulva, cervix, and vagina. These lesions are believed to put the females with S. haematobium infections at a greater risk of contracting HIV. A study conducted in Zimbabwe showed that women ages 20-49, who had genital lesions due to a urogenital schistosomiasis infection, had a 3-fold higher risk of having HIV than women without a schistosomal infection.

There are 207 million cases of Schistosomiasis worldwide, and 112 million of those cases are urogenital Schistosomiasis found in Sub-Saharan Africa. This creates a significant overlap between areas of Africa that are endemic to HIV/AIDS and Schistosomiasis. This has caused many scientists to question whether a greater effort to control S. haematobium infections would be an effective method of decreasing the prevalence and transmission of HIV/AIDS in Africa.

(http://blogs.plos.org/speakingofmedicine/2013/05/06/female-genital-schistosomiasis-fgs-sub-saharan-africas-secret-scourge-of-girls-and-women/)

There is a Schistosomiasis Control Initiative (SCI) based out of London which is attempting to implement schistosome control methods in areas that are endemic. A study done in Burkina Faso showed that a single mass treatment with Praziquantel was shown to decrease the prevalence of S. haematobium by 84% in girls and 78% overall for up to 2 years. The WHO has a strategy of mass drug administration (MDA) in which school aged children in areas that have a greater than 10% prevalence of schistosomiasis would receive Praziquantel on a biannual basis, and areas that have greater than 50% prevalence would receive treatment on an annual basis. Treatment with Praziquantel results in a parasitological cure but will not heal genital lesions that have already developed from a S. haematobium infection. For this reason, prophylactic treatment starting at a young age is crucial in using this method as a means to decrease HIV prevalence.
It only costs about 32 cents to treat one child with Praziquantel. In most developing countries Praziquantel is distributed through bulk sales to the government. From there, the government dispenses its allotted Praziquantel out to different programs. The organizations that supply developing countries with Praziquantel include UNICEF and the World Health Organization among many other international organizations. Data has shown that a schistosomiasis infections increase susceptibility to HIV, elevate viral replication, exacerbate immunosuppression and increase transmission of HIV. Due to these findings, greater emphasis on schistosomiasis control is being pursued as a means of decreasing the ever growing HIV/AIDS prevalence in Africa. Widespread distribution of Praziquantel to schoolchildren in countries endemic to both schistosomiasis and HIV/AIDS could potentially prevent 120,000 new cases of HIV/AIDS in the next decade.

If treatment with Praziquantel for one child costs $0.32, then treating 70 million children would cost $22 million for one year. If a 10 year plan was implemented that treated every one of those 70 million children biannually, that would cost approximately $112 million. Compare that with the $18.8 billion that has been proposed to be spent over the next 5 years by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). The cost of treating 70 million children for schistosomiasis over a 10 year span is dwarfed by the projected costs of the PEPFAR and could potentially make a significant change in the rising trend of HIV infections in Africa.
All of the research points towards mass treatment with Praziquantel as being the most cost effective and successful method of decreasing the number of schistosomiasis infections and HIV/AIDS transmission. The cooperation between HIV and schistosomiasis control programs is critical in ensuring the success of such a program. Combatting two of Africa’s top health concerns with one simple low cost medication would do wonders for lowering the morbidity and mortality rates of many African countries.

References:
“HIV and AIDS Statistics: Worldwide.” Statistics: Worldwide. AmfAR, Nov. 2012. Web. 10 June 2013. <http://www.amfar.org/about_hiv_and_aids/facts_and_stats/statistics__worldwide/>.
Hotez PJ, Fenwick A (2009) Schistosomiasis in Africa: An Emerging Tragedy in Our New Global Health Decade. PLoS Negl Trop Dis 3(9): e485. doi:10.1371/journal.pntd.0000485
Hotez, Peter J., Alan Fenwick, and Eyrun F. Kjetland. “Africa’s 32 Cents Solution for HIV/AIDS.” PLoS Neglected Tropical Diseases 3.5 (2009): E430. Print.
“International Strategies for Tropical Disease Treatments – Experiences with Praziquantel – EDM Research Series No. 026: Chapter 5: The International Supply of Praziquantel*: Global Distribution of Praziquantel.”

International Strategies for Tropical Disease Treatments – Experiences with Praziquantel – EDM Research Series No. 026: Chapter 5: The International Supply of Praziquantel*: Global Distribution of Praziquantel. World Health Organization, 2013. Web. 10 June 2013.
Kosinski, Karen C., Kwabena M. Bosompem, Miguel J. Stadecker, Anjuli D. Wagner, Jeanine Plummer, John L. Durant, and David M. Gute. “Diagnostic Accuracy of Urine Filtration and Dipstick Tests for Schistosoma Haematobium Infection in a Lightly Infected Population of Ghanaian Schoolchildren.” Acta Tropica 118.2 (2011): 123-27. Print.
“Schistosomiasis.” World Health Organization. Web. 10 June 2013. <http://www.who.int/mediacentre/factsheets/fs115/en/>.
“Schistosomiasis: Epidemiological Situation.” World Health Organization. N.p., n.d. Web. 10 June 2013. <http://www.who.int/schistosomiasis/epidemiology/en/>.
Secor, Evan W. “The Effects of Schistosomiasis on HIV/AIDS Infection, Progression, and Transmission.” Current Opinions on HIV and AIDS 7.3 (2012): 254-59. Print.
Simon, Gregory. “Combined Schistosomiasis and HIV Control Programs: Saving Lives AND Money”. End the Neglect. N.p., 7 May 2013. Web. 11 June 2013. <http://endtheneglect.org/2013/05/combined-schistosomiasis-and-hiv-control-programs-saving-lives-and-money/>.
“South Africa: ‘Over 25% of Schoolgirls HIV Positive’” BBC News. BBC, 14 Mar. 2013. Web. 10 June 2013. <http://www.bbc.co.uk/news/world-africa-21783076>.
Temple, Bliss. Schistosoma Haematobium (blood Flukes). Schistosomiasis Haematobium (blood Flukes). Stanford University, May 2004. Web. 10 June 2013. <http://www.stanford.edu/class/humbio103/ParaSites2004/Schisto/website.html>.

Nothing could be worse than watching your seven-year-old lying in a hospital bed fighting for his life after being diagnosed with hemolytic uremic syndrome. Unfortunately, Mary McGonigle-Martin experienced it first hand as her son, Chris, fought for his life after being poisoned by E. coli 0157:H7 found in contaminated raw milk. Like many mothers, Mary was coerced into believing the inaccurate “facts” given to her by the farm she purchased raw milk from. Too often across the US, parents are given incorrect information about the safety of the milk they drink and unfortunately, it is often children that pay the price.

Few people today know of a time when they didn’t have the choice to drink anything but raw milk. Now there is an overwhelming argument that pasteurization is decreasing the nutritional value and safety of the milk. During the 1800s, Louis Pasteur developed the germ theory which claimed that germs outside the body, like those found in raw milk, have the ability to cause infection. As a result, he developed the process of pasteurization which is used in many foods we consume today, including milk, to kill bacteria. In the past couple decades, many consumers have decided that they would rather consume more natural and organic foods rather than those that were produced by more modern methods. It is frequently believed that these natural foods, such as raw milk, are healthier which is not the case.

Pasteurizing milk has had many benefits through history. One of its major contributions is the massive reduction in human tuberculosis cases as the bacteria that causes bovine tuberculosis can also infect humans. Bovine tuberculosis can be spread to humans through contact with an infected animal but most commonly through ingestion of raw milk. Although the prevalence of tuberculosis in humans in the US has significantly reduced since pasteurization began, there are still a number of other zoonotic pathogens that can be transmissible from milk to humans including salmonella, campylobacter, listeria, and E. coli 0157:H7, all of which can have dangerous or unpleasant consequences or even potentially be fatal. E. coli is possibly the most dangerous since it only needs less than 100 organisms to cause infection. It can lead to a dangerous condition called hemolytic uremic syndrome (HUS) which may cause kidney failure. According to the CDC, there have been 148 dairy product-associated outbreaks from 1998 – 2011 that were a result of consumption of raw milk or cheese which resulted in 2,384 illnesses, 284 hospitalizations, and 2 deaths. Today, milk is heated to 161°F for 15 seconds to destroy the bacteria. This is called high temp, short time pasteurization. Another form of pasteurization is low temp, long time, 145°F for 30 minutes.

Proponents of raw milk often argue it has a greater nutritional value than pasteurized milk. There have been numerous studies that have de-bunked this myth according to the CDC. Many factors are involved when determining the nutritional value of a product. One thing that is analyzed is how readily a body breaks down and utilizes a nutrient. If a mineral or vitamin is passed through the body quickly, any loss would be irrelevant. A second analysis would be the percent contribution of the nutrient to the recommended daily intake. If people don’t rely on a certain product as the main source of an essential nutrient, the loss of the nutrient is almost negligible. It is true that some nutrients or enzymes are slightly reduced during pasteurization. For example, lysine is the most relevant essential amino acid found in milk. After heating the milk, only 1-4% loss of the amino acid was observed^1,5,7. But like what was previously alluded to, reduction of nutrients like vitamin C is not considered a significant concern as milk is not a major source of vitamin C. It would take 20 liters of milk to consume the daily requirement of vitamin C, regardless if it was raw or pasteurized milk³. The availability of nutritionally relevant vitamins such as B2 or B12 were found to be affected minimally or not at all by most common heat treatments^2,5. Finally, while milk is a significant source of calcium and phosphorus, neither were affected by heating the milk³.

Another raw milk marketing tool some farmers use is to claim that their cattle are grass fed. When cattle were first domesticated, they were raised on a grass diet. As the understanding of animal nutrition grew, farmers discovered that cattle would gain weight faster if they fed them grain which is economically beneficial. Proponents of grass fed cattle argue that grain is not their natural food and the growth at a faster than normal rate is unhealthy. A grass-fed animal does not mean the animal is healthier. Nutritionally speaking, it was hypothesized that grass fed cattle have a lower milk fat content. The amount of grain does play some role in the fat development but energy and dietary protein intake and the current state of pasture the cattle are being grazed on must also be accounted for. In addition, milk fat content is also determined by the genetics of the individual animal, whether or not it currently has or had infections in her udder, and her stage of lactation³.

In addition, grass-fed cattle don’t necessarily carry a lower bacterial load. Even at the most sanitary facilities, milk is often contaminated by fecal material carrying pathogens during the milking process. According to Dr. Jim Kazmierczak, a Public Health Veterinarian with the Wisconsin Department of Health Services, there have been numerous studies that proved grass-fed cattle shed E. coli 0157:H7 in the feces longer than grain-fed cattle⁴ and that “cattle fed a forage diet were 0157:H7 culture-positive longer and with higher numbers of bacteria in their feces than cattle fed a grain diet.⁶” This means that E. coli 0157:H7 remained alive in their feces longer than grain-fed cattle.  In addition to being found in fecal material, E. coli 0157:H7 can be found where cattle are grazing, can live on different environmental reservoirs for many months, such as gates, walkways, or water troughs, and is found more frequently during the summer.

We are blessed in the US to have a relatively safe food supply. Sure there will be occasional food-borne illness outbreaks but we are fortunate to have the technology, sanitary methods, and capabilities to keep the food we consume free from diseases to the best of our abilities. The invention of pasteurization reduced the number of illnesses and deaths caused by contaminated dairy products while maintaining the integrity and nutritional value of the milk. But there is a misconception of pasteurized milk across the country that has led to people making deadly decisions. Mary McGonigle-Martin would have never given her child raw milk had she known that it had the potential to harm or kill him. The risks are high when consuming raw milk and people need to be properly informed before their put their families and themselves in unnecessary danger.

1. Andersson, I., and Öste, R. (1995). Nutritional quality of heat processed liquid milk. In P. F. Fox (Ed.), Heat-induced changes in milk (2nd ed.) (pp. 279e307). Brussels: International Dairy Federation.

2. Burton, H. (1984). Reviews of the progress of dairy science: the bacteriological, chemical, biochemical and physical changes that occur in milk at temperatures of 100e150 _C. Journal of Dairy Research, 51, 341e363.

3. Claeys, W. L., et. Al (2013). Raw or heated cow milk consumption: Review of risks and benefits.

4. Hovde, C. J., et al. (1999). Effect of cattle diet on Escherichia coli O157:H7 acid resistance. Appl Environ Microbiol 65:3233–32

5. Schaafsma, G. (1989). Effects of heat treatment on the nutritional value of milk. Bulletin of the International Dairy Federation, 238, 68e70.

6. Van Baale, M. J., at al. (2004). Effect of Forage or Grain Diets with or without Monensin on Ruminal Persistence and Fecal Escherichia coli O157:H7 in Cattle. Appl Envir Microbiol 70:5336-5342.

7. Walstra, P., and Jeness, R. (1984). Dairy chemistry and physics (p. 467). New York: John Wiley & Sons.

Although we can never know, there are estimates in the range of 15,000 displaced pets in the wake of 2005 Hurricane Katrina.  Many of the dogs found their way to shelters and homes in our community around the Monterey Bay in California.  As a local veterinarian the most notable observation I saw was how it “seemed” that so many were heartworm positive.  Six years later we have a published study finding a 48.8% prevalence of heartworm in these dogs.

This story is an example of a few important lessons.  First, how things seemed to me, in my clinical practice turned out to be 48.8% of the dogs, not all.  (Of course in our area we may have had a different subset of positive dogs, but I thought, in general, they were nearly all heartworm positive). Secondly, how long it takes for a study to be done and published.  In this case the study I referenced has a six year interval between the event and publication of data examining an aspect of concern.

Now, let’s step into the present.  I’m currently taking courses for a Masters in Public Health at the University of Iowa to branch out from my basic training in veterinary medicine.

Yesterday, in a course I’m taking we had a lecture on a group of zoonotic diseases, Trypanosomes.  This group of little single celled organisms, protozoans, causes problems all over the world.   In Africa it causes, Sleeping Sickness, in Latin America, Chagas’ disease.  We don’t hear a lot about it here in North America.

What came to my attention was a disease described in dogs, here, in the U.S. caused by one in this group called Leishmania.  Dogs are a known reservoir in areas where these diseases are endemic but these U.S. reports starting in the late 1990’s were in two breeds with whopping over representation, specifically Foxhounds¹ and Neapolitan Mastiffs.

That’s weird, I thought.  I’ve been a small animal veterinarian for a long time and those are not two very common breeds.  What’s up?

The first two things you need to know have to do with our basic understanding of where this parasite lives and how it infects mammals.  It has been traditionally thought a mammal becomes infected from the bite of an insect vector (tsetse fly in Africa or sand fly in South America), which is carrying the protozoa.  Also, although this occurs more rarely, you can become infected by direct contact with the blood of an infected animal into your tissue, read blood-to-blood transmission.  This second bit of information will be important later.

As well from studying these outbreaks in Foxhounds, one research group received a donated pregnant bitch they new was infected which allowed them to examine the puppies and look to see if they were also infected.  They found Leishmania in the puppies.  This lends evidence of transmission of the organism from mother to puppies in utero. Their thought is the Leishmania protozoan circulates in the mother’s blood and crosses over the placenta to infect the developing fetuses.

An important point here is the novel idea that transmission of the infection can be vertical and DOES NOT REQUIRE A VECTOR.  This would mean you could sustain the parasite in a mammal population where it has never lived before and would not normally be expected to be able to live.

This disease is endemic in parts of Europe and these two breeds, although fairly rare here in the U.S., often are imported from Leishmania endemic areas to be incorporated into U.S. breeding stock lines.   These imported dogs are very valuable and key to their breeding programs.

The work done showing vertical transmission from mother to pup suggests we can establish the infectious agent in a host indefinitely.  So far we are lucky and the areas where these dogs live don’t have vector insects readily available.  I wouldn’t count on that lasting too long.  Between global travel and climate change alone, and if historical record of disease spread with so many other zoonotic infectious agents is any guide, it’s really, likely, just a matter of time.

So a final concern, more immediate, goes back to that second route of traditional transmission I described above, the direct contact, blood-to-blood infection.   Here’s the thing.  These dogs, the Foxhounds and Neapolitan Mastiff’s that are infected are breeding dogs.  Breeding dogs, by definition, are sexually intact.  Dogs that have their “parts” can more often get into scrapes (read: fights).  When dogs fight they really can tear each other up.  The fighting often occurs around the head, neck and ears.  All fight wounds bleed, a lot.  Ears especially bleed like stuck pigs.

People try to break up the fighting dogs.  People get bitten all the time doing this.  (Read: Do not try to break up fighting dogs yourself, but that’s another essay of it’s own).  The dog blood that is all over the dogs is now all over you.  You have an open bite wound.  The dog’s blood now is mingling with your tissue and blood.  You now have Leishmania.  This is the problem.

The good news is if you are immune-competent you should mount a good response to this insult and have a very good likelihood of clearing the infection.  It will require a significant effort calling upon both arms of your immune systems, the cellular and the humoral.  Unfortunately you will not be immune to reinfection should another exposure event occur.  The bad news is if you are in anyway immune compromised, not so good.  You are likely to get clinical illness.

I guess our best hope at this point in time is to help breeders see the need and importance of choosing disease free dogs.  Encourage them to buy and bring only dogs that they have tested and know are free of Leishmania into the U.S.  I know breeding for phenotype and working characteristics and abilities is the holy grail of breeders, but can’t we do it looking at the bigger picture, the greater good?

¹Monti, Dean (June 2000). “Hunters hounded as leishmaniasis is diagnosed in Foxhounds”. J Am Vet Med Assoc 216 (12): 1887, 1890.

After successfully completing a job interview I had the opportunity to take the next step in my employment process: taking a Tuberculosis or TB test.  I have received the test before but never really understood the point of testing for a disease no one ever sees in my community. I always thought, “Why not focus all this effort and money on more prevalent infectious agents such as Ebola or HIV?” You know, focus on something important.  So, as the nurse called me in from the waiting room I began to curse that hard little bubble that would soon be forming under my skin, and the inconvenience it would be to have to come back to this same clinic to have it read.

This same type of experience is known throughout the United States and other developed countries.  However, many people like myself, do not know the importance of this test.  They might not know that this test is a crucial part of the much larger goal of eradicating a deadly and common worldwide disease.

What is tuberculosis and why is it even important?

Tuberculosis is a contagious disease that is found in both animals and humans. The human form of the disease is caused by a group of three bacteria: Mycobacterium bovis, Mycobacterium avium, and Mycobacterium tuberculosis.  This disease can come in two forms: latent and active.  The active form of tuberculosis causes pockets of pus called granulomatous lesions in lungs and has a death rate around 50%. It is estimated that TB infects around one third of the human population on earth and is the second leading cause of death by infectious disease, behind HIV, killing around million people annually, according to the Center for Disease Control and Prevention; CDC (4).  The greatest prevalence of TB occurs in developing countries and their low socioeconomic populations.  This is likely due to the limited availability of health care, poor nutrition, and overcrowding conditions these people face on a daily basis.  Immunosuppressed individuals, such as people infected with HIV, are also more likely to contract tuberculosis.  TB is also very hard to treat and many forms of the disease are resistant to antibiotics.

Another reason TB is so dangerous is the threat of Mycobacterium bovis. M. bovis is another strain of tuberculosis that mainly infects cattle, cervids (deer like animals), elephants, bison, etc (7,10). What makes this bacterium interesting is its been known to infect people through the consumption of raw (unpasteurized) milk or products that were made from that raw milk (1,5,7,10). This zoonotic microorganism is responsible for two percent of all new cases of TB in the US (7) with an even a greater percentage worldwide (6).  The zoonotic nature of M. Bovis allows for it to hide in wildlife populations which act as a reservoir for the disease (6,9). The good news is a campaign to eradicate M. Bovis from the US food supply began in 1993(5). The bad news is that TB remains endemic in wildlife and agricultural animal populations worldwide. The program in the United States has been a success and most of the United States is considered Bovine Tuberculosis free.  However some states, such as Michigan, still find M. bovis in their wild deer herds making the continual threat of reemergence a reality.

So what have we done about this problem?

The United States government has taken a leading role in the fight against TB. It formed the Advisory Council for the Elimination of Tuberculosis to address the growing resurgence of TB in the 1980’s (5). It also passed legislation like the Comprehensive Tuberculosis Elimination Act which called for the increase of federal funding, education, and international collaboration in the fight against TB.  Other non-governmental advancements have taken place over the years too.  A vaccine was created and is now available throughout the world.  Known as BCG, this vaccine is good at protecting children against the disease, however, it loses its effectiveness as children grow older and has not shown promising results in adults (8).  This, coupled with the increasing amount of antibiotic resistant cases (known as Multi Drug Resistant Tuberculosis or MDR TB) once again proves the fight to eradication or even control might be more of an uphill battle then we once thought.

So how is the fight to end TB going?

Over the past few decades we have made progress and in 2011, the World Health Organization reported “The absolute number to TB cases has been falling since 2006”. However, in that same report, the WHO also stated, even though TB cases had dropped, “In 2009 there were almost 10 million children who were orphans as a result of parental deaths caused by TB” (12,13).  As long as there TB is left to reside in our low income populations and in animal reservoirs it will continue to plague millions worldwide.

So where do we go from here?

The continuation and strengthening of surveillance and research projects worldwide is the key to combat tuberculosis.  The more we know about the disease and its ecology the better prepared we will be to face the challenges we may encounter during its eradication process.  Will we ever get to total world eradication of tuberculosis?  This writer thinks so but to quote the great Robert Frost it seems that “we have miles to go before we can sleep”.

1)      http://www.aphis.usda.gov/animal_health/animal_diseases/tuberculosis/

2)      http://www.cdc.gov/tb/publications/factsheets/general/mbovis.htm

3)      http://www.cdcnpin.org/scripts/tb/eliminate.asp

4)      http://www.cdc.gov/tb/statistics/default.htm

5)      http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5412a1.htm

6)      http://wwwnc.cdc.gov/eid/article/19/6/12-0543_article.htm

7)      http://www.cfsph.iastate.edu/Factsheets/pdfs/bovine_tuberculosis.pdf

8)      http://www.chop.edu/service/vaccine-education-center/a-look-at-each-vaccine/tuberculosis-vaccine.html

9)      http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION=tests-and-diagnosis

10)  http://www.lung.org/lung-disease/tuberculosis/factsheets/multidrug-resistant.html

11)  http://www.ncbi.nlm.nih.gov/pubmed/20819249

12)  http://www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf

13)  http://www.who.int/mediacentre/factsheets/fs104/en/index.html

14)  http://en.wikisource.org/wiki/Comprehensive_Tuberculosis_Elimination_Act_of_2008

15)  http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis

16)  http://en.wikipedia.org/wiki/Mycobacterium_avium-intracellulare_infection

17)  http://en.wikipedia.org/wiki/Tuberculosis

Of the many health problems that everyone is bound to have at some point, influenza, or just “the flu,” is one of the most prominent. In fact, we call the time during which it is most prevalent the “flu season”. It has now become a regular occurrence in the U.S. to just get a shot before the flu season hits, and be free of it for the rest of the year. In some cases, like me, people just decide not to get the vaccine at all. I say to myself all the time: “It is just the flu. If I do get it, I’ll just take a nap, and I’ll be fine.” However, there are serious complications with influenza if the individual is afflicted with certain diseases, making the vaccine a necessity. Even in the general population, influenza infections could lead to serious health problems, at a lower rate, that could complicate the daily lives of individuals.

Influenza is a generic description of a variety of strains of influenza viruses, including influenza A (H1N1, H3N2), and influenza B. It is a widespread virus, and can infect both human and animals, albeit with different strains. (1) The influenza virus is difficult to completely control since it constantly undergoes different changes through antigenic drifts and shifts, small and abrupt changes in the virus constructs, respectively. (2) It causes fever, coughs, sore throat, runny nose, and a host of other symptoms that target different parts of the body. In extreme, severe cases, it may cause the death of the infected individuals. It can spread from person to person up to 6 feet away through coughing and sneezing, spraying droplets containing infectious particles into the air. The droplets either lands in the other individual’s mouth, or is inhaled into the lung. Influenza is very contagious, due to the fact that it can infect others prior to the development of symptoms, as well as a period after. In addition, there exist asymptomatic carriers that can infect others without knowing. There are vaccines provided every year prior to the start of the “flu season:” a period of time in which the population is most likely to acquire the disease. Once the symptoms develop, it can be treated with antiviral medicine, such as Tamiflu (oseltamivir) and Relenza (zanamivir).

In addition to the problems that a regular influenza infection can cause, in individuals with certain diseases, complications could develop from the interaction between the influenza virus and the disease currently affecting the patient. In asthma patients, the attacks are often triggered by respiratory virus infection, whether by the virus particle itself or the inflammation resulting from the influenza symptoms. Also, the influenza viruses could augment natural responses to allergenic particles resulting in a more severe than normal attack; influenza patients with asthma are often hospitalized as the result. (3) In patients with cardiovascular disease, influenza infections represent a high level risk. The infection could destabilize existing plaques (blocks in the artery) in atherosclerotic patients. In addition to the acute responses from the destabilization, influenza infections could also induce chronic inflammation in the body, as well as reduced clotting ability. (4) For patients with diabetes, infection with influenza represents a high risk of hospitalization and death. In diabetics, the immune system is weakened, making it difficult to fight of the disease. In addition, the infection can cause fluctuation in the level of blood sugar in the patients, through natural immune responses, or lack of desire to eat due to the effects of the influenza symptoms. There is also an increased risk of acquiring pneumonia as a complication of the infection. (5) As in the case with diabetics, patients with cancer and HIV/AIDS are also likely to have complications due to weakened immune systems from both treatment and disease.

From the variety of complications that could result from influenza infections, one can now see that it is extremely important for an individual to receive the vaccines when available. In some places, vaccines are often offered free of charge, especially in workplaces that have high exposure risks, such as hospitals and research facilities. In addition to reducing the likelihood of being affected by influenza, flu vaccines have shown to have reduced the development and progression of other diseases such as chronic obstructive pulmonary disease (COPD). (6) For individuals with HIV/AIDS, vaccines are especially important since they are more vulnerable to infections. In addition, they must be aware of the type of vaccines they are using, since certain vaccines do not work sufficiently in people with immune-deficient issues. However, there exist other treatments for the prevention of the disease, such as chemoprophylaxis, that would allow these individuals to be properly protected against possibilities of infection. (7) With the prevalence of the influenza virus in both the U.S. and globally, it is important that an individual keep up with the most current vaccines, as they are designed to combat the most common forms that would appear that flu season, since the strains changes every year.

References:

1. CDC. Seasonal Influenza (Flu). http://www.cdc.gov/flu/index.htm
2. CDC. How the Flu Virus Can Change. http://www.cdc.gov/flu/about/viruses/change.htm
3. Glezen, W. Paul. Asthma, influenza, and vaccination. Journal of Allergy and Clinical Immunology 188(6): 1199-1206.
4. Madjid M, Nagahvi M, Litovsky S, Casscells SW, Influenza and Cardiovascular Disease. Circulation 108:2730-2736.
5. CDC. Flu and People with Diabetes. http://www.cdc.gov/flu/diabetes/index.htm
6. Poole PJ, Chacko E, Wood-Baker RWB, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews.
7. CDC. HIV/AIDS and the Flu. http://www.cdc.gov/flu/protect/hiv-flu.htm

If you are anything like me, you have been told countless reasons over the years why we must watch what we eat, keep our cholesterol intake down, and try to work out. It shouldn’t really come as a surprise then that I, since I am a public health student after all, aim to convince you of yet another reason why a healthy diet and exercise are valuable. What is this huge reason to avoid Big Macs and think about taking the stairs instead of the elevator you ask? Well, it may help you to prevent gall bladder cancer, is all.

All of this begins with gallstone formation. Gallstones are hard deposits, usually of cholesterol, that become lodged in your gallbladder over time. Your gallbladder is an organ that helps to aid in digestion through the storage and release of bile which helps to break down fats in your small intestine. The gallbladder is located on the right side of the body attached to the liver. The process of gallstone formation is called cholelithiasis. In this process, cholesterol, which is not very soluble, becomes clustered together in droplets in the bile called micelles. This cholesterol droplet then hardens into the crystals that make up a gallstone. Obesity causes bile to transit the gallbladder less rapidly and increased cholesterol in the diet means there is more cholesterol available to form stones. It does not require and active imagination then, to understand how obesity and high cholesterol intake contribute to stone formation, but how does this all tie into cancer you ask? http://www.umm.edu/patiented/articles/what_gallstones_gallbladder_disease_000010_1.htm

It all comes down to infection with a bacterium known as Salmonella typhi. Yes, this is the same bacterium that causes Typhoid fever and was the malady that afflicted the famous Typhoid Mary. While many people may become infected with S. typhi over the course of their lives, those individuals with gallstones are 6-15 times more likely to become carriers of S. typhi in the gallbladder. This is important because those people with a chronic infection of S. typhi have been shown to have 3-200 times higher risk of developing gallbladder cancer then non-carriers. Furthermore, chronic carriers have a 1-6% lifetime risk of developing gallbladder cancer. In fact, gallbladder cancer is so linked to S. typhi infection that gallbladder removal, called cholecystectomy, is recommended for those people with gallstone disease who live in high risk areas. Where is a high risk area? Most developing countries of the world are high risk areas for S. typhi, especially countries in Asia, Africa, and Latin America. This means that travelers from the USA and other developed countries to these regions are at risk for developing the infection. However, even at home in the USA, low risk doesn’t mean no risk, and we should be vigilant against emergence of this bacterium.  

In conclusion for all my gallbladder-containing friends out there (I make this distinction because I, myself, am no longer at risk for gallbladder cancer since I had mine removed in 2006 after a bout with gallstone disease) stay aware of your cholesterol levels and pay attention to making sure you have a healthy diet because, like every health care professional will tell you, it might just save your life….perhaps in a way you don’t expect!

References:

1. University of Maryland Medical Center. Gallstones and gallbladder disease. Online http://www.umm.edu/patiented/articles/what_gallstones_gallbladder_disease_000010_1.htm
2. Ferreccio, Catterina. Salmonella typhi and Gallbladder Cancer. http://link.springer.com/chapter/10.1007/978-94-007-2585-0_5#page-1

Center for Disease Control online source. http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever/

The Human Immunodeficiency Virus (HIV) infection is one of the most significant global health challenges of this 21^st century. Since the isolation of the virus in 1983, it has infected 70 million people among whom 35 million have died of Acquired Immunodeficiency Syndrome (AIDS).¹ Although important progresses have been made in slowing down the pandemic and reducing the morbidity and mortality related to HIV/AIDS with the highly active antiretroviral therapy (HAART) drugs, there are still difficulties in stopping the dissemination of the infection. It is estimated that for every person gaining access to HART, there are two new others infected by the virus.² An effective and safe vaccine is therefore needed to prevent HIV from spreading, but the development of the vaccine has been proven to be an enormous scientific challenge.

HIV presents particularities that make it very difficult for researchers to find a vaccine. It is a lentivirus from the Retroviridae family, slowly progressive using an enzyme (called reverse transcriptase) for the transformation of its genome or genetic material (RNA in this case) into a new one (proviral DNA) integrated in that of the human host using another enzyme known as integrase. One of the most fascinating characteristics of the virus is its genetic variability in both an infected individual and geographically. In a same person, new mutations can be introduced in almost every new copy, creating up to millions of new particles every day. One antibody could then neutralize one virion, but not another.3 Additionally, super-infection in an individual already HIV infected results in new recombinants increasing further viral genetic diversity. The virus also presents two different types, HIV-1 worldwide and HIV-2 confined to West Africa. HIV-1 is further subdivided into subtypes or clades differently distributed on the globe and further diversified within each clade. Moreover, by integrating proviral DNA in the genome of memory cells of the immune system (CD4+ T cells) the HIV can escape the immune surveillance. To complicate the development of an effective vaccine, the virus envelope is able to hide receptor site to antibody that could potentially inhibit its effect (neutralizing antibodies). This explained the inefficiency of antibodies generated by vaccines targeting the glycoprotein 120 (gp120) located on the surface of virus developed in early vaccine trials.4

However, despite these challenges, encouraging progresses in the development of an effective HIV vaccine have been made. The first HIV vaccine trial was opened at the National Institutes of Health (NIH) Clinical Center in 1987, including 138 healthy volunteers. Other large scale trials included participants from North America and The Netherlands (1998), then Africa and Asia (1999).5 Three main approaches have been used in the development of an HIV vaccine: 1) the induction of neutralizing antibodies against HIV using the virus envelope proteins (gp120 or 140), 2) the use of viral vectors to stimulate responses form killer cells (CD8 T-cells or T cell that would recognize antigens on virus surface of the virus-infected cell, binds to it, and kill it), and 3) the optimization of cellular immunity (activation of killer cells) and humoral immunity (production of antibody) with prime-boosts (administration of one type of vaccine, such as a live-vector vaccine, followed by or together with a second type of vaccine, usually a recombinant).6 Also, to cope with the genetic variability of the virus, multiple strategies are explored, such as mixing envelope immunogens from several HIV subtypes or clades. Unfortunately, most of the tested vaccine models did not significantly reduce HIV infection in participants, except an envelope-based subunits’ vaccine tested in Thailand which showed significant decline by about 30% in HIV infection in 2009.⁷ Though modest, the results clearly show that HIV/AIDS is a vaccine preventable disease. More recently in 2012, a Spanish study showed promising results in the development of a therapeutic HIV vaccine effective in reducing the viral load by 90% after 12 weeks of therapy, awkwardly the vaccine lost effectiveness within a year.⁸ Just a few days ago, the Duke Human Vaccine Institute team published an important study, in which it has been able for the first time to map the co-evolutions of antibodies and virus in an infected individual, whose immune system launched a broad attack against the pathogen, using new technologies. They also identified the viral surface glycoprotein, which initiated the neutralizing antibody development.⁹

Despite two decades of disappointing results on HIV vaccine research, we now have started to see encouraging advances. For the first time a candidate vaccine was successful in significantly reducing the HIV infection. Furthermore, an important progress has been made very recently in identifying neutralizing antibodies initialization and mapping. The study provides crucial insights for the development of a vaccine that could mimic the actual antibody development and elicit non-strain specific antibodies. Progress towards finding an effective vaccine is slow, but we can optimistically say that the future is promising.

References

[1] World Health Organization (WHO), Global Health Observatory (GHO). HIV/AIDS, Global situation and trends. 2012. http://www.who.int/gho/hiv/en/

2 Letvin, Norman L. “Progress and obstacles in the development of an AIDS vaccine.” Nature Reviews Immunology 6.12 (2006): 930-939.

³Letvin NL. Progress Toward an HIV Vaccine. Annu. Rev. Med. 2005. 56:213–23

4Marc GP, OsmanovSK, Kieny MP. “A review of vaccine research and development: the human immunodeficiency virus (HIV).” Vaccine 24.19 (2006): 4062-4081.

5 National Institute of Allergy and Infectious Diseases (NIAID). History of HIV Vaccine Research. 2012. http://www.niaid.nih.gov/topics/hivaids/research/vaccines/Pages/history.aspx

6 Ross, Anna Laura, et al. “Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.” The Lancet infectious diseases 10.5 (2010): 305-316.

⁷ Rerks-Ngarm, Supachai, et al. “Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.” New England Journal of Medicine 361.23 (2009): 2209-2220.

⁸ García, Felipe, et al. “A Dendritic Cell–Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication.” Science translational medicine 5.166 (2013): 166ra2-166ra2.

⁹ Liao HX et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 2013. Epub April 3, 2013