Tuesday, July 23, 2013

Perspectives on AIDS - Essays from AIDS course in Coursera

Here are some of the essays/write-ups I had written for the different assignments of the 'AIDS' course in 'Coursera'. The course was taken by Dr. Hagen of Emory University and several other guest lecturers joined for specific topics. Although AIDS is a huge topic, I have written about the aspects which appealed to me as a Biologist. The essays were written for specific questions and specific word limits (and in many cases, since I started at the last moment, very short time limits) and thus, may not have fully justified arguments. In any case, I think it has some interesting perspectives and I would like to share them. I have changed a few sentences to make it suitable for blogging as certain reference only makes sense for the participants of the course.

Short summary of five things which appealed me in the course

1) Immunosuppression makes common diseases more threatening :

It was a common knowledge that due to AIDS, a patient succumbs to many opportunistic infections. Many of these are rare infections, and some of these are common too. However, after Dr. Jeffrey Lennox's lecture, I realized that immunosuppression due to AIDS actually makes these common diseases much more threatening. It is therefore not only about suffering from diseases frequently, but also about suffering from much more atypical symptoms of diseases, for which probably not every clinic worldwide is ready to handle. According to Dr. Lennox's words, "HIV increases the chance that a person will develop  illness due to an unusual disease, or have atypical symptoms of a common disease."
This is probably because even when a disease overcomes the immune system in a non- immunosupressed person, the immune system atleast helps to combat so that the disease doesn't have a 'free-range' and only affects some aspects which are used as the major hallmarks of the disease. However, when the person is immunosuppressed, the disease freely expresses itself and reaches its fullest potential which makes things worse.

2) Anal sex and vaginal sex are not equivalent risk factors :

People are often unaware that anal sex is a much more riskier and is more efficient in spreading the infection. The initial few lectures and then a specific lecture by Dr. Patrick Sullivan made it clear that there is enough proof now that unprotected anal sex presents much more risk than unprotected vaginal sex. This, of course, doesn't mean that unprotected vaginal sex are safe, but it means the probability of an infected person spreading the infection via anal sex is more than vaginal sex. It seems the biological structure of the outer tissue in the anus is responsible for that. Probably the more wear and tear in the layer allows better uptake of the virus.
This also says why a lot of the initial cases were identified among MSMs (Men having Sex with Men) and was also used by some radical groups as an anti-gay agenda, evoking this as punishment from god. The fact is that this is dependent on the biology of the process and has nothing to do with homosexuality vs heterosexuality.

3) World wide initiatives and research :

Although I knew about the various initiatives for AIDS awareness and education, the number of examples I saw in the course was a surprise to me. Initiatives like 'Scenarios from Africa' is very impressive, these not only spread AIDS awareness, but also in general educate the masses in many other agendas like domestic violence, drug abuse, safe sex, women's rights. Also the kinds of detailed research shown in the course was impressive. HIV researchers can't use other animal models like Rabbits or mouse as the virus is specific to primates and that too only very specific primates. Still with all the difficulties, the kind of surveys and researches to uncover details of risk factors and medications is praiseworthy. 

4) HIV as a Lentivirus :

{This point is elaborated in another essay below}
HIV's role as a lentivirus makes it particularly threatening because once infected, the symptoms come very late, sometimes after many years. During this time the patient may spread it to many people via unprotected sex or other routes.

5) Zoonosis - Continuous risk of new diseases from wild populations :

{This point is elaborated in another essay below}
We need to realize that we are at a risk of getting infected from rare diseases from the wild populations. AIDS is one such disease, bird flu is another. But the microbial population in wild populations is huge and diverse and is a potential source of new and unknown diseases. This calls for a better management of wildlife and a better monitoring of man-animal interactions.

One important aspect of AIDS

Lentiviruses - The hidden enemy

"HIV is a Lentivirus, which is more dangerous because Lentiviruses show their effects much later but can spread during the time of no apparent symptoms"
While going through the 'week - 1 lectures', we learnt HIV is a kind of virus known as Lentivirus [1][2]. I realized this is a very significant reason for the pattern of HIV's spread. Lentiviruses have long incubation period, during which they remain inactive [1]. This can take few years. Thus, the person carrying this virus, externally doesn't show much symptoms. However, being inactive doesn't mean that it won't transmit from one person to other, it keeps spreading without anyone realizing and only many years later the symptoms appear, by that time many would have been infected. This feature of HIV makes it even more threatening.
HIV has genes for establishing a latent state [3], which helps it to integrate into the host's cells in a way which enables them to remain undetected from the host's immune system.  In the meantime, the host might introduce the virus to different people for many years. The new recipients of the virus will also be unaware about the infection, will be new sources of infection and a chain reaction will start. Later when the symptoms appear and the outbreak happens, already huge  number of people are infected. Although a proper investigation on AIDS started only in 1980s, and some of the earlier cases were in late 50s, it is believed that HIV actually made the human jump around 1930s [4]. Just imagine, if AIDS was not a Lentivirus, then in 1930s people would have started showing the symptoms and a proper investigation would have been commissioned. Even if the cure had not have been discovered, atleast the basic precautions could have been taken and probably it won't have spread  so much. One can also compare the recent outbreaks of bird flu, which are also viral in origin. Although fatal, atleast these showed immediate symptoms, and thus, doctors could take immediate action to contain the spread of this virus. Unfortunately for us, HIV is a Lentivirus, which takes its time, remains hidden, a time bomb ticking inside and spreading.

Supporting Information :
[4] - http://www.pbs.org/wgbh/pages/frontline/aids/virus/origins.html

One important lesson from AIDS


Growing importance of Zoonotic disease management

It is more than 30 years since the first report of AIDS (not known as AIDS back then) has reported in 1981 [1]. AIDS is now understood from various aspects - its mechanism in the body, the origin of the virus, behavioral role of humans in spreading or containing the disease, drugs and treatments against the disease. However, one of the aspects of the AIDS pandemic which I would like to focus on is its Zoonotic origin [2] [3]. Zoonoses is are those pathogenic diseases where the pathogen from different animals transfer to humans [4]. AIDS research has made substantial progress, including the recent reports of success in an infant [5] and some hope of a drug [6]. One can only hope that in recent future we can device a vaccine or a concrete treatment and the recent results can only make us more optimistic. However, we need to remember the root of AIDS and how it spread within the human settlements. Transmittance of infectious disease from wild populations is a common occurrence and one estimate suggests that more than 60% of infectious diseases have a zoonotic origin [7]. Recent outbreak of fatal diseases like SARS and pandemic influenza are other examples of zoonotic diseases [8]. What makes these diseases more dangerous is that these are the first contract of the microbes with our body and thus, our immune system is not, in many times, equipped to handle these [12]. Furthermore, a new condition demands fresh research for medical science and thus, treatment is not always prompt. In cases like AIDS which occurs due to lentivirus, viruses which stay in the body for years before the patient shows symptoms [9], and during that time has spread to many more people, the difficulty increases manifold.
We can describe the microbial populations in the wild populations as some sort of reservoir of 'time bomb', waiting to unleash its venom upon human contact. It is high time we start preparing ourselves to combat zoonotic diseases at a much prior level, i.e, even before the infection. After all, prevention is better than cure. Otherwise, we will always have emergencies like AIDS, SARS and many more. For example we know now that HIV has infected humans not in a single episode but multiple times [3], some of which either didn't spread much or were not virulent enough. The HIV which is prevalent in human populations worldwide is the HIV-1 Group M, where others like HIV-1 Group N and O are locally spread [3]. It is proposed that consumption of bush meat from wild primates is the reason for the infection. So, even if we succesfully create a treatment or vaccine for current strains of HIV, and not stop the regular entry of HIV into human population, we are still living at a risk. If we encounter another kind of mutation in HIV which attacks our system in an alternative way then we would need to again look for its treatment and reinvent the wheel. Furthermore, its not only the question about HIV, potentially any virus, bacteria or other microbes can be the source of yet another fatal disease. Even now more and more examples of new zoonotic agents coming up regularly [10] [11] [14]. It is high time we learn from diseases like AIDS, SARS and device ways to address these larger issues.
The good news is that the scientific community is concerned about these issues and researchers are working to device policies to avoid the next pandemic zoonosis. Scientists are working on risk assessment models [8], which means that they are identifying of a set of parameters which will tell us which areas in the planet are most at risk and which animals and microbes are most likely to contract us with vulnerable microbes. Currently the 'global pandemic prevention strategy' is being revised using our knowledge from past outbreaks of pandemics, technological advances of pathogen detection and utilization of the communication technology of mobile phones and internet [8]. Scientists have tasted success when two new human viruses were identified very early in Saudi Arabia and central Africa [10] [11]. Even many web-based surveillance resources like ProMED, GPHIN, HealthMap and Biocaster have been established for better communication and spread of information [13]. However, very crucial would be to understand zoonotic diseases using an holistic approach where we take our understandings from seemingly unrelated fields like Ecology (important to understand the potential zoonotic sources), agricultural and livestock agencies (another source where pathogen outbreak can happen and subsequently spread), political network (managing policies to control infection, for example in case of HIV, a better control on bush meat trade etc.). Only a global cooperation can help us in decreasing the spread of pandemic zoonotic diseases and ensure that the tragedy of AIDS is not repeated again.

[1] - First Report of AIDS - http://www.cdc.gov/mmwr/pdf/wk/mm5021.pdf
[6] - Hope for AIDS drugs - http://www.bbc.co.uk/news/health-21783945
[8] - Other Zoonotic diseases and risk management - http://www.ncbi.nlm.nih.gov/pubmed/23200504
[10] - Early identification of Virus outbreak in Saudi Arabia -http://www.ncbi.nlm.nih.gov/pubmed/23075143
[11] - Early identification of Virus outbreak in Central Africa -http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002924
[12] - Zoonotic agents as the 'unknown' for immune system - http://ncbeingprepared.blogspot.com.es/2011/09/new-virtual-immune-system.html
[13] - Web based resources info - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427560/
[14] - An emerging zoonotic agent -  http://www.ncbi.nlm.nih.gov/pubmed/22710318

Countering the HIV origin myth

Countering the myth : HIV invaded human population because some man in Africa had sex with a Chimpanzee

{The following was required to be written as a real conversation}

[Scene: In a train two guys were discussing about AIDS]

Me - "Hi, I just heard you guys mentioning HIV came from chimps as a result of a rather odd sounding sexual encounter. I daresay, this is misleading information.
Guy-1 - "Well, even scientists have also proved this. HIV comes from Chimps."
Me - "Ofcourse scientists have proved that primates like Chimps and Gorillas, among others, are indeed the source of HIV [1], although technically you can't call their version as HIV, but anyways for our purpose just call them HIV. But there is no proof that it transmitted to humans via sexual activity. In fact, this is widely accepted as one of the myths about HIV/AIDS [2]."
Guy-2 - "How else would HIV have spread to humans then?"
Me - "Surely you still don't believe sexual engagement is the only route of HIV transfer?"
2 - "I know the facts. It can also spread from mother to child through breast milk or during child birth, or to one person to another via blood transfusion. However, all these are not possible between a chimp and a man and thus, sexual engagement is the only explanation.
Me - "True! But blood transfusion is not the only way of blood contact. Eating wild animals is prevalent in many communities even today and we have evidences that wild meat trade, called Bush meat trade, many times includes large primates like Chimps. Scientists have made predictions that bush meat trade is most likely to have spread this virus to humans [1]. Think about it, bush meat trade includes handling of raw flesh and blood and then consuming the meat, conditions ripe for spreading the virus.
1 - "I agree the 'bush meat' theory can be a likely explanation. But sexual encounter can also do the same, so both are possible. You can't prove any of them. You need to believe that such incidences do occur."
Me - "Yes, they do occur. Human - animal sexual encounters are not common but do happen and is known as bestiality, and is well documented [3]. However, there are various indirect evidences to indicate that this has not been the case here. Firstly, behaviorally wild Chimps don't like hanging around humans [1], thus, an intimate contact seems unlikely. Secondly, even if such encounters had happened, one can imagine them to happen very less frequently, and not regularly. Do you agree to that?
1 - "Yes, seems reasonable.  But what's the point?"
Me - "In general HIV virus to transmit and spread in a single sexual encounter is not a very likely event [4]. On average, it requires repeated sexual exposure. All I can say is that, although no one can prove this with a clinching evidence, the factors 'bush meat trade', behavioral differences, requirement of repeated sexual encounters makes your assumption very unlikely. Anyways, my station has come. Goodbye!"

Supporting Information :

Why is the conspiracy theorist, AIDS denialist's arguments are flawed?

On his website the American scientist Peter Duesberg asserts that “… the various American/European AIDS diseases are brought on by the long-term consumption of recreational drugs and/or [the anti-retroviral drug] AZT itself, which is prescribed to prevent or treat AIDS.” What evidence do we have that Dr. Duesberg’s argument is flawed?

Dr. Peter Duesberg has been one of the most influential of the 'HIV dissenters' who maintain that HIV is not the cause of AIDS [1]. Dr. Duesberg, in 1987, published a provocative paper where he proposed that AIDS virus is just a latent non pathogenic infection which results from the other symptoms of AIDS [2]. Thus, he envisions HIV infection as the consequence of AIDS rather than the cause. He later proposed that the long-term consumption of recreational drugs and prescriptions of anti-HIV drugs cause all AIDS diseases in America and Europe [3]. Thus, contrary to scientific and popular belief, his 'drug hypothesis' predicts that AIDS is non-contagious [3].
Although Dr. Duesberg have earned accolades for his prior scientific work [4], his 'drug hypothesis' was widely criticized by the scientific community [1]. To start with, the studies in Haemophilia patients has been an important point in learning about AIDS causality. Many of the Haemophilia patients had been diagnosed with  AIDS in 1980s [5], and according to Dr. Duesberg that is due to increased use of 'factor VIII' [6]. However, scientists have shown in studies that there is no correlation between higher dosage of factor VIII with higher mortality in HIV+  Haemophilics, the HIV+ Haemophilics have a similar death rate for different dosage of factor VIII, whereas the HIV- Haemophilics have not been affected by different dosage of factor VIII [6]. If indeed factor VIII had a role, then higher dosage of factor VIII would have caused more deaths in HIV+ and HIV- patients due to AIDS. However, Dr. Duesberg, uses the problems of monitoring medical history of these patients throughout to argue that proper studies have not been made regarding this [6]. Further correlation studies in Thailand shows that a huge increase in AIDS patient has been correlated with a huge increase in HIV+ people in the local population [7].
Dr. Duesberg's theory about AZT or other anti-HIV drugs as the cause of HIV was also proven invalid after three laboratory workers contracted HIV virus, started showing symptoms after 68 months and severe AIDS defining immunological problems after 83 months, all these time not receiving AZT or any anti-HIV drugs [8].
A much more recent study show that recreational drug usage don't correlate with CD4 population [9], immune cells which show dramatic reduction in AIDS patients and is a standard symptom of AIDS victims, when goes down beyond a threshold. The scientific study [9], claims that there is no association between use of drugs like Marijuana, Cocaine, Poppers, or Amphetamines and CD4 and CD8 cell parameters such as total count, percentages or rates of changes, in either HIV+ or HIV- homosexual men. In yet another study [10], it was shown that illicit drug ('Hard drug') usage, although has implications in a range of infectious diseases, do not associate with changes in AIDS related parameters like CD4 cell percentage, HIV RNA levels or mortality.
Conclusion :
Dr. Duesberg's theories are provocative and has gained some mileage as the 'lone scientist standing against authority', but in proper scientific studies it was been proven beyond much doubt that HIV is the cause of AIDS. Recreational drugs, although harmful, are not involved in creating AIDS. The focus of the AIDS debate should shift to its strategies of cure and prevention rather than the causative agent.

Identify a part of our population unusually affected by AIDS and suggest ways to counter them.

Photo by: John Isaac / World Bank

Unfortunate Wives of adulterous men in India

The first reported cases of AIDS in India occurred 27 years ago in 1986 [1]. Then onwards, following the global trend, the cases of AIDS in India continued to rise. According to estimates in 2012, there are about 2.40 million Indians with HIV  [2]. One of the important factors of the spread of AIDS in India, among others, is sexual transmission, which accounts for more than 87% of reported HIV cases [2]. Most of these cases are resultant of male behavior. This seems to be a common theme in Asia. According to the commission of AIDS in Asia, "...in asia the HIV epidemic is mainly driven by men who go for paid sex".[3].
What the above reports and numbers tell us is that promiscuity by men is not only transmitting the virus from one host to another but also infecting the non-promiscuous sex partners, the wives. Adulterous men who visit brothels for paid sex are at a huge risk of getting the infection. This is mainly due to the fact that sex and AIDS education has not been adequate, atleast in the past, especially among the lower economic strata of the society who are also the least educated due to poverty. Thus, unprotected sex with sex workers, who form a huge risk group due to unprotected sex with multiple clients, transmits HIV to these men. Now when these men engage in sexual activities with their wife they transmit the virus. Given the fact that a husband is likely to have repeated sexual intercourse with the wife, makes it almost a surety that the wife will get infected. Thus, the non-promiscuous and monogamous wives have to suffer from the wrath of this infection. Moreover, child born from such unions are also at a high risk of getting the infection unless the proper medications and precautions have been taken.
The sufferings of these women don't end here. In many cases, they are not taken care of by her husbands' family. There are examples of such women being thrown out of the house for 'bringing AIDS to the family' [1]. In a patriarchal society, things can be even worse. There are reports that the family blames such women for 'not satisfying the husband' and thus, responsible for husbands' adultery![4]. In smaller towns and villages, the hospitals are also unwilling to deliver the baby from HIV infected women, because of misconceptions and lack of know-how on how to tackle such cases [4].
Thus, these women form an unfortunate group of HIV victims, who suffer from the medical complications, social alienation and personal humiliation.

How can we help them?

There are essentially two ways to look into this. 1) Firstly, to stop them getting infected. 2) Secondly, to have a support system for those who are already affected. The first part depends on husbands' activities and awareness, since if they are infected, it is very likely HIV will transmit to their married partner, unless the husband is aware and takes necessary steps and protections. Thus, I will focus on the second part and more particularly the need of awareness in the society which enables them to lead a normal and respectable life.
So, what are we dealing with here? A patriarchal society, mostly the lower economic groups with very low education and misconceptions. The mistreatment of the HIV infected women roots from the fears of the misunderstood 'evil', HIV. Any awareness program must be targeted to the basic misunderstandings in a feasible way. Grown ups normally have highly reinforced misconceptions and stereotypes and thus, it is not an easy task to raise an awareness at a level which can create a significant impact. One of the best tools in these contexts are audio-visual media like short cinemas. The cinemas need to be beyond the documentary styled preachy videos but need to be entertaining as well as educative, much like the 'Scenarios from Africa' initiative [1]. 'Scenarios from Africa' makes short films related to social issues of AIDS/HIV. The films apart from being educative are also entertaining and made by some of the top filmmakers of Africa. Having role models in such films, like a local celebrity - filmstar, sportsperson, politician - making an appearance can also make a great impact. Involvement of religious institutions can also be of much use. Religious figures like priests can be made aware of the facts and findings, who can educate the masses in their own way. Awareness programs might need to consider distribution of gifts/food for attracting people to attend them. Couples' counseling can be yet another way to promote the right perspectives on HIV/AIDS.
However, ultimately its the men who have to take responsibility. Those who have transmitted the virus to their wives, now atleast need to support them from the wrath of the society and take control of the situation and 'be a man' in the most positive sense.

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