Monday, March 19, 2007

The HIV trial in Libya, part 4: How the infection must have occurred

This is continued from part 3 - the previous post (http://mayas-corner.blogspot.com/2007/03/hiv-trial-in-libya-part-3-tale-of-two.html). Here, I'll try to keep my writing as short as possible and to use instead citations from people who know better. Two important terms, used below, are iatrogenic - caused by medical procedures, and nosocomial - acquired in a hospital; both terms refer to health damage, usually an infection.
Let's begin from the beginning: decades earlier and thousands of miles away from the Libyan "crime scene", a virus found a new host. The following citation is from http://main.uab.edu/show.asp?durki=8535.
"Origin of HIV-1 Discovered
...Scientists at the University of Alabama at Birmingham (UAB) have discovered the origin of Human Immunodeficiency Virus Type 1 (HIV-1)...The researchers identified a subspecies of chimpanzee (Pan troglodytes troglodytes) native to West-Central Africa as the natural reservoir for HIV-1...The final piece of the puzzle was put in place when the researchers realized that the natural habitat for Pan troglodytes troglodytes overlaps precisely with the region in West-Central Africa where all three groups of HIV-1(M, N, and O) were first recognized. Based on these findings, Hahn and her colleagues concluded that Pan troglodytes troglodytes is the origin of HIV-1 and has been the source of at least three independent cross-species transmission events...While the origin of the AIDS epidemic has been clarified, an explanation for why the epidemic arose in the mid-20th century, and not before, remains a matter of speculation."Chimpanzees are frequently hunted for food, especially in West-Central Africa, and we believe that HIV-1 was introduced into the human population through exposure to blood during hunting and field dressing of these animals," says Hahn. She further believes that while incidental transmissions of chimpanzee viruses to humans may have occurred throughout history, it was the socio-economic changes in post-World War II Africa that provided the particular circumstances leading to the spread of HIV-1 and the development of the AIDS epidemic. "Increasing urbanization, breakdown of traditional lifestyles, population movements, civil unrest, and sexual promiscuity are all known to increase the rates of sexually transmitted diseases and thus likely triggered the AIDS pandemic," adds Hahn."
Dr. Hahn omitted one very important factor for spreading HIV: the health care system, which was practically not present in Africa until the 20th century. You think I am stretching my thesis too much? First, please read the following translation from the book "Sanu, bature" by Bulgarian zoologist Peter Beron. He describes his experience in Nigeria in 1976:
"Before returning to Bulgaria, we had to be immunized against cholera. There was a special immunization center in the town. However, before we went there, Dr. Malyavko (a Russian physician - M.M.) gave me three sealed disposable syringes and told me to insist that the local doctor uses them. I was hesitating - the doctor could be offended by such lack of trust. I went to the center with Kinka and Vladko (the author's wife and son, respectively - M.M.). In the street, there was an endless line. The doctor was sitting in front of the door and immunizing everybody with one and the same needle. These were prospective hajjis. They were preparing to travel to Mecca and the local Asclepius evidently thought that Allah wouldn't let any hepatitis creep into such pious Muslims. At that time, nobody knew about AIDS. Seeing us, the Asclepius called us and offered to immunize us immediately. I told him I had had polyo before and for that reason had to use a separate syringe. Vladko had been in contact with a person with hepatitis etc. The doctor showed full understanding. He unsealed the first syringe, injected Vladko, then injected Kinka with the second syringe and me with the third one. Then he, with my needle, continued injecting the long line of the candidate hajjis."
The case of the infected more than 400 Libyan children would be tragic even if it were exceptional, but unfortunately it isn't. We shall never know the exact number of AIDS victims throughout Africa and elsewhere whom medicine, instead of helping, failed, betrayed and doomed. The following citation (as well as others which I'll indicate by their PubMed identification numbers) is obtained from PubMed, a database of biomedical literature. PubMed abstracts and some full text articles can be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed.
Gisselquist D. et al. (2003). Let it be sexual: how health care transmission of AIDS in Africa was ignored. PMID: 12665437
"The consensus among influential AIDS experts that heterosexual transmission accounts for 90% of HIV infections in African adults emerged no later than 1988. We examine evidence available through 1988, including risk measures associating HIV with sexual behaviour, health care, and socioeconomic variables, HIV in children, and risks for HIV in prostitutes and STD patients. Evidence permits the interpretation that health care exposures caused more HIV than sexual transmission... Preconceptions about African sexuality and a desire to maintain public trust in health care may have encouraged discounting of evidence."
Another work: Brewer D.D. et al. (2003). Mounting anomalies in the epidemiology of HIV in Africa: cry the beloved paradigm. PMID: 12665436. The citation is from http://www.cirp.org/library/disease/HIV/brewer1/, where the full text of the article is given.
"A number of these observations raise the question of an alternative route of transmission, for which medical care and the use of injections are prime candidates17,19-22. Prostitutes, for example, are often recruited for studies from STI clinics, where treatment is frequently given by injection, where non-sterile equipment is used with high frequency, and wherein the underlying prevalence of HIV is high7. Many studies that have assessed the impact of sexual activity on HIV transmission -notably those in Mwanza and Rakai, whose discordant results are still a subject of debate23-failed to consider the potential confounding effects of medical care in the propagation of HIV24.
Rapid HIV transmission in Africa has often occurred in countries with good access to medical care, like Botswana, Zimbabwe, and South Africa. For example, high rates in rural South Africa have paralleled aggressive efforts to deliver health care to rural populations. It is difficult to understand how improved access to health care, with its offers of public health messages, free condoms, and preventive services, would be associated with increased HIV transmission. Similarly, HIV prevalence is often higher in cities and among persons of high socioeconomic attainment than in rural areas or among less fortunate persons. Favourable access to health care is one of the differences that distinguishes between these groups."

In my recent post, I argued that sexually transmitted diseases shouldn't be regarded as God's punishment because they infect the innocent as well as the "guilty". In fact, it is worse - they infect first and foremost the innocent. Just read the following citation:
Gisselquist D. et al. (2004). HIV transmission during paediatric health care in sub-Saharan Africa--risks and evidence. PMID: 15034989
"Health care systems in sub-Saharan Africa are challenged not only to improve care for the increasing number of HIV-infected children, but also to prevent transmission of HIV to other children and health care workers through contaminated medical procedures and needlestick accidents. HIV-infected children aged to 1 year typically have high viral loads, making them dangerous reservoirs for iatrogenic transmission... This leads to high HIV prevalence among inpatient and outpatient children... Investigations of large iatrogenic outbreaks in Russia, Romania, and Libya demonstrate efficient HIV transmission through paediatric health care... In addition, several studies have reported much higher HIV prevalence in children 5-14 years old than could be expected from mother-to-child transmission alone."
So we are coming to the Libyan scene. The following citation, I think, illustrates well how the Libyan health care system initially reacted to the crisis - it focused efforts not on controlling the infection but on attempting to cover it up:
Kovac C, Khandjiev R. (2001). Doctors face murder charges in Libya. PMID: 11157524
"Nine Libyans, including the director of the Al-Fateh Hospital and the undersecretary of Benghazi's Department of Health, are charged with exposing 19 of the mothers of the infected children to HIV. They "hid the fact that the children were already infected" and failed to take prophylactic measures to protect the mothers... Ironically, according to a UNAIDS report, Libya has not supplied any information on AIDS cases in that country for 1998-2000."
In the same year, doctors in Switzerland analyzed the blood of infected children:
Yerly S. et al. (2001). Nosocomial outbreak of multiple bloodborne viral infections. PMID: 11443566
"After a major outbreak of human immunodeficiency virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively... The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed."
The finding of other blood-borne viruses in such a high proportion of the HIV-infected children supports the poor hygiene hypothesis, not the intentional infection hypothesis which lies so close to the hearts of Libyan prosecutors. Mention also that some children visited the hospital several (up to 6) times, so it is possible that they after being infected became secondary sources of infection for other young patients.
The next report is by Italian scientists:
Visco-Comandini U. et al. (2002). Monophyletic HIV type 1 CRF02-AG in a nosocomial outbreak in Benghazi, Libya. PMID: 12167281
"A cluster of HIV-1 infection has been identified in Libya in 1999, involving 402 children admitted to "El-Fath" Children's Hospital in Benghazi (BCH) during 1998 and 19 of their mothers... Out of this group, 104 children and 19 adult women have been followed at the National Institute for Infectious Diseases L. Spallanzani in Rome during 1 year. At BCH, all children had received intravenous infusions but not blood or blood products. A single child receiving a blood transfusion in 1997 and the 17 infected mothers were never hospitalized in Benghazi. In addition, two nurses were diagnosed as HIV-1 infected... The phylogenetic analyses showed that a monophyletic recombinant HIV-1 form CRF02-AG was infecting all of the HIV-1-seropositive patients admitted at BCH... A different strain was found in the child infected by blood transfusion."
Please mention that a child was infected in 1997 by blood transfusion with a different strain of HIV. This fact alone seems to disprove the claims of many Libyans that before the accused medics introduced the virus in 1998, there had been no HIV in Libya. Rather, the virus had arrived but the Libyan health care officials weren't ready to confront the threat and preferred to bury their heads into the sands of wishful thinking - our people aren't promiscuous, so it won't happen here...
The other noteworthy detail in this report is that the HIV strain is described as "recombinant". This English term can mean "product of natural recombination process" (as above) or "product of recombinant DNA technology (gene engineering)". Bulgarian journalists reporting from the Libyan courtroom said that the term was translated to Arabic and interpreted by Libyans in its second meaning only, i.e. that it was not a natural HIV strain but one modified by gene engineering. Hence, the infection must have been intentional. I don't know whether this misinterpretation was due to deliberate framing of the accused or to incompetence of the Libyan "experts". Let's not be paranoic and prefer the second explanation. In fact, the incompetence of some of the experts seems to be a public secret in Libya. Defense lawyer Byzanti at one point, after hearing reports of such experts accusing his clients, exclaimed, "But what scientists are they?". (The judge didn't like the remark.) If we talk seriously, even if the infection was intentional, it wouldn't make sense to use modified virus. If you intend to use a common cold virus as a bioweapon, you of course first have to modify it quite a lot, because the original virus is almost harmless. But why modify a virus which is lethal as it is? Just to leave a smoking gun at the crime scene? Why don't people use their heads, why are they ready to believe every nonsense they hear?
The next citation is from one of the most prestigeous scientific journals, Nature.
De Oliveira T. et al. (2006). Molecular epidemiology: HIV-1 and HCV sequences from Libyan outbreak. PMID: 17171825
"In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection were reported in children attending Al-Fateh Hospital in Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were already circulating and prevalent in this hospital and its environs before the arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a Palestinian doctor) who stand accused of transmitting the HIV strain to the children."
No comment needed, I think.
The last PubMed citation I'll give is an appeal by Sidaction (I don't know this organization but its name is evidently derived from SIDA - AIDS in French):
Fleutelot E. (2006). 'Libyan Trial': a verdict running counter to scientific evidence. PMID: 17192180
"Sidaction denounces this trial as a parody of justice, which cannot hide the total incapacity of the Libyan Government to promote an appropriate politics of prevention and take care of people who are ill secondary to HIV infection-adults and children-in an appropriate way. It is useful to recall that the majority of Libyan people living with AIDS who are in need of an antiretroviral treatment can still not afford it."
***
It is easy to violate safety rules when working with blood and other human material under inadequate funding and supervision. I admit I have done it myself.
In recent decades reusable syringes, needles and other items were largely replaced by disposable ones. This was meant to assure safety, because sterilization of reusable equipment can always fail for some technical reason. However, as a result medical workers lost their expertise in sterilization and the good habit to perform it. So, when they are short of disposable equipment, they are quite likely to reuse it without even attempting sterilization or at least disinfection. Simple boiling would kill HIV without damaging most types of disposable equipment; but there must be somebody to do the boiling.
What exactly happened in Benghazi? Of course I cannot know exactly, but this is how I imagine it. The hospital has too many patients and too few syringes and needles. So, a nurse or a sanitary worker at the end of the day collects the used ones, soaks them in water and then washes them. Just washing, no sterilization. The boss hasn't ordered sterilization or disinfection. Trapped in the "good-people-don't-get-STDs" mentality, he cannot even think that the hospital's patients, these little angels, may have AIDS. But one child has it, contracted somehow outside the hospital. He is injected and then, when his syringe and needle are soaked, the virus contaminates all the other soaked needles. So other children, possibly dozens of them at once, are infected. The remaining virus in the hospital eventually dies out, it cannot reproduce outside the human body, but then one of the infected children comes for a new shot...
I would wish to end my post here, but I remember something I read on Highlander's blog:
"Whilst I’m sure many of them (medics-guest workers in Libya) honoured their contracts I can tell you from personal experience that some of them could not care less, and even the fact that US sanctions resulted in the deterioration of Libyan hospitals and that probably some Libyan health workers were also unscrupulous does not give the right to foreign workers to treat the Libyan patients like 'shit'. I’ve seen it as some of them ruled unconditionally in the hospitals and clinics, and you don’t want to be on their bad side as they may not treat you or worse may give you the wrong treatment. So again I wanted to say that not all of them were angels and saviours" (http://lonehighlander.blogspot.com/2005/04/case-441999-story-of-bulgarian-medics.html).
Of course, among the health workers from any country some are not very good professionals, some are capable but not very polite, and even those who are both may have their bad days; besides, miscommunication because of language barrier can create impression of rudeness. This is not the point. The point, I think, is the implicit question behind the cited text: Was it a mere coincidence that the infection happened in a hospital with so many foreign workers? My answer: Maybe it wasn't. I must immediately state that this is not an admission that the defendants are guilty - there were dozens of other guest workers in the El Fateh hospital, while two of the accused had never worked there.
First, one of the most important factors pushing us to do good work is pressure from our clients. If we are health workers, this means that we shall work better if our relations, friends, neighbours or their children can become our patients any minute. If we are treating some completely unrelated people, we are more likely to take it easy. Remember, one of the other major iatrogenic AIDS outbreaks was among Romanian orphan children. The doctors and nurses immunizing them relaxed the safety rules because they knew their own children and their friends' children wouldn't be among the patients.
Second, a guest worker is unlikely to become a whistleblower. He'll prefer just to do what he is paid for and not risk trouble. Remember the Egyptian doctor who warned a Bulgarian nurse (in Part 2). However, he didn't warn the Libyan patients and the local community. The Bulgarian workers in fact couldn't do this even if they wanted, because they didn't speak Arabic. It was the journalists of the La magazine who first gave publicity of the outbreak, and they did get into trouble. They knew they were risking, but still wrote the article because they cared. They regarded it as their duty as citizens. So, before we all become true citizens of the world, it makes no harm to remember that only a citizen is likely to care.

7 comments:

Julius said...

of course your language has future! all languages has their own beauty. :) i think your language is nice. Is is like Russian? thanks for the posts. :) i love it.

AngloLibyan said...

maya, I just started reading your excellent posts on this tragedy, im finding your articles very educational and do make a lot of sense, as you probably know I am concentrating more on the children's plight because they have been ignored and mainly by the Libyan government. I do hope that the nurses & doctor are innocent, I just cant see why they would do such a crime plus I grew up in Libya where we had many decent Bulgarian guest workers, some were our neighbours. I know that the only solution for this is for Libya to set up an international court, it has taken 8 years so far, most of us are not convinced with the Libyan findings, there is more to it and I pray that the truth comes out soon.

programmer craig said...

Excellent series of posts, Maya :)

Julius said...

its just now that i have read all the content of this post. really nice to know info about AIDS

Maya M said...

Thanks for your comments.
AngloLibyan, I have deliberately written about the children in short and calm words in order to avoid distraction from the main subject - and also suspicions in hypocrisy. But advocacy for the children and their families is of course much needed and I only regret that this cause has been almost completely hijacked by the forces of evil.
Julius, Bulgarian is indeed similar to Russian. However, "Sanu, Bature" is not a sample of Bulgarian, as a reader of this post may think. It means "Hello, European" in Hausa, a West African language. So the local people greeted Beron while he was working in Nigeria.

Kyle D said...

My questions about the HIV trial have not be satisfied by this blog. I was hoping for something more scientific. Instead, all I read was biased, political invective.

Here are my questions concerning this case:

1) All 418 children were infected with the same monophylitic strain of HIV-1. This is confirmed even in the 2006 Nature study which purports a nosocomical conclusion. What is the likelihood that this same exact strain of HIV-1 could be passed to all 418 children in this one section of the hospital without any mutations between infections? Keep in mind that HIV mutates as it gets passed from patient to patient, unless all patients were infected with the same exact batch of infected blood, which is extremely unlikely in a nosomcomical scenario.

2) The mortality rate of the children was extraordinarily high, around 10%, which indicates high viremia. What is the probability that medical negligence would have given all 418 children a heavy infection? No amount of shared needles will result in a high viremia infection. Shared blood catheters maybe, but all reports state there were no blood catheters being used on site among all 418 patients.

3)Time is a huge factor here. If the infection was accidental, then infections must have occurred over a period of time as it passed on from patient to patient. Given an infection span of months or years, do you really think it's likely that it would be the same monophylitic strain of HIV-1 in all the patients? Bear in mind, mutations occur all the time in HIV, which is one of the reasons why it's so difficult to treat.

4) The numbers simply don't pan out. We are talking about a near 100% infection rate among these patients in a short period of time. That simply does not happen in a nosocomical scenario.

5) The only real support for a nosocomical scenario come from scientists who either
a) Had no hard empirical data (Montagnier/Colizzi report)
b) Used improper Bayesian modelling which even an amateur in the field would be able to notice
To the latter point, the 2006 Nature study didn't factor in the recombinant factor in HIV when estimating its age, instead only relying on point-substitution, a far rarer phenomenon. Thus, their estimates of the age of the strain in question appear to be much older than it actually is-- of course it would be when you don't factor in the most important way that HIV mutates.

I don't think this case is as clear-cut and dry as you make it sound. There is a lot of room for skepticism, especially since the Nature 2006 article doesn't even prove a nosocomical theory, only that epidemiologically, the particular strain of HIV originated before the workers got there. That doesn't rule out foul play since said workers could have used HIV laden blood that was already present within the hospital and deliberately infected those patients.

None of the international reports address fundamental problems with the case involving transmission methods. They all seem to focus in on time as being the primary factor, ignoring all the holes in their theory insofar as transmission is concerned.

Maya M said...

Kyle,
You expect a person who could easily be in the defendants' situation to be unbiased? You expect a blogger to have no political motivation? Please don't make me laugh!
As for the "more scientific" expectations, you have raised the bar too high to be ever satisfied - even the Nature journal isn't scientific enough for you!
To your questions:

1) Being monophyletic doesn't exclude accumulation of mutations. The Nature study talks of a "cluster" and, more importantly, of finding "the most recent common ancestor of each cluster" by molecular clock methodology, which clearly shows that there WERE mutations between infections:
http://www.nature.com/nature/journal/v444/n7121/extref/444836a-s1.pdf
You mention it yourself in your question No. 5!

2) I think the high mortality could also be due to delay in diagnosis and treatment and to the presence of other infections, such as hepatitis B and C.

3) Keeping in mind that children, as not active sexually and not using drugs, are a LOW risk population for HIV, I find it very probable for the HIV infection to be monophyletic. I am sure that in many hospitals with similar level of hygiene across Libya and Africa, luck alone saved the young patients from being HIV-infected. About the mutations - see my answer to question (1).

4) My knowledge and experience with nosocomial infection is with staphylococcal and streptococcal ones, for which the infection rate is close to 100%. I presume that the situation is likely to be different for HIV, but I do not know the "standard" infection rate, and I do not know where the infection rate among the Al-Fateh patients was indeed near 100%. I think that for the both pieces of data, the burden of proof is on you.

5) I do not feel competent enough to question the methodology of the Nature study, and I can only suggest that you write a letter (or, possibly, a full-length article) to the journal. And again, I find it a bit unfair of you to hold a blogger like me to standards that even scientists publishing in Nature cannot meet. Being an amateur in the HIV science, I still ask - if the viruses are monophyletic, how could recombination between themselves increase their mutation rate?

I would be glad if you report how, to your opinion, researchers could "prove" nosocomial (or any other) theory. Your statement that the Nature study did not prove it strongly reminds me of the statements of antivaxers that no study has so far proved that autism is not due to vaccines. These people simply will reject any evidence contradicting their pet theory.

And your pet theory - of foul play and deliberate infection, is, to my opinion, insane. It explains pretty well why no amount of scientific evidence is enough to you to vindicate the Bulgarian medics. I am glad that, after the revolution against Qaddafi broke out, I have not seen or heard any Libyan expressing support for this theory.