Archive
Needless Drug Shortages Threaten the Lives of TB Patients
Several drugs to treat Tuberculosis have made it to the FDA’s drug shortage list. (I recommend a quick glance at the list. Big government (thankfully) at work!)
A friend/acquaintance of mine posted that the following medications are presently in short supply, or unavailable: Isoniazid, Rifampin, Ethambutol, Amikacin, Streptomycin, Tubersol and Aplisol.
Now, I’m not going to pretend to be an expert on TB, though I do know enough about the condition to know that TB is most common among the poorest and most marginalized members of society. In Malawi, I’ve seen active and advanced cases of TB. It’s an awful sight.
People who live in substandard housing in urban areas, prisoners, alcoholics and homeless people are at particular risk for infection. It’s particularly common in Africa, and a problem that seem to be getting worse, rather than better. Coinfections with HIV are common.
Japan, specifically the Airin area of Osaka, where homeless men and day laborers congregate in substandard and densely occupied housing units, is well known to have one of the highest incidence rates of TB in the developed world. Russian prisons are also famous for TB transmission, as the work of Paul Farmer has shown.
According to the FDA list, many of the drugs are in short supply due to “Demand increase for the drug.” I find the claim to be somewhat dubious. Drug companies have long been known to be sleeping at the wheel when it comes to development of new drugs for TB. Most of the drugs that are currently used were developed in the early the mid 20th century, with one very recent exception (Bedaquiline).
I find it highly unlikely that demand for the drugs went by unnoticed to drug companies. I suspect that there simply isn’t enough profit in the drugs to warrant ramping up manufacturing.
The implications are, of course, immense. If drugs to treat TB are unavailable, opportunities to transmit TB will persist. Given the nature of the populations which are at risk for the disease, we can expect a resurgence in cases. Worse yet, the longer a patient has the disease, the more likely it is that the infection will become resistant to all medications, making treatment nearly impossible.
HIV “Cure” Found in Mississippi: Nothing to be proud of
Dubious reports have surfaced that an allegedly HIV positive infant born prematurely in rural Mississippi to an HIV infected mother has been cleared of the virus due to a non-standard administration of HIV drugs. Naturally, I am extremely skeptical.
I wonder if the child ever truly had HIV in the first place. Given that the child was born prematurely, I also wonder how generalizable the strategy would be, assuming that the child did, in fact, have HIV.
The world, however, seems to believe that this is a “cure” for HIV. Optimistically, I would call this a case of prophylaxis.
Most frustrating for me, is the surge of pride from Mississippians. Having grown up there, I don’t think that this is anything to be proud of. The profile of HIV in Mississippi (see my paper draft) is overwhelmingly rural, poor and, most salient, black (See my lit review on HIV in Mississippi).
The simple reason that this so-called “cure” was “found” in Mississippi, as opposed to say, Vermont, is Mississippi’s crushing level of endemic poverty, entrenched racism, and institutionalized marginalization and exclusion. Mississippi’s backward politics and racist history are what caused this epidemic in the first place. Nothing to be proud of.
Equally frustrating are the absurd comments to the effect that “God has come and given us this cure” likely stemming from the heart wrenching involvement of an infant. Assuming that such a deity exists, we should probably fault God with creating the disease in the first place, and allowing babies to be infected through no fault of their own. It seems silly to me to praise a despot for delivering services after he’s made a mess of the place.
Mississippi is sixth in the nation for new cases of HIV. The social dynamics which determine transmission are different in rural and urban areas. Dividing states into clases of rural HIV and urban HIV, Mississippi would come in number 3 just behind Georgia and Louisiana. In fact, though, I would argue that Mississippi’s rate of new HIV cases (25 per 100,000) is actually an underestimate. Health delivery in Mississippi’s HIV hotspots is so inadequate and health care utilization so low, that many new cases are undetected.
I will wait and see if the optimistic reports are true. My feeling is that this is a case of hopeful overstatement. Until then, I will remain skeptical.
“Crowded” Vaccine Schedule Deemed Safe….
as one would expect. The Institute of Medicine within the National Academies of Sciences recently produced a 230 page report addressing the concerns of parents that the current recommended vaccine schedule is too “crowded” and thus puts children at excessive risk.
Upon reviewing stakeholder concerns and scientific literature regarding the entire childhood immunization schedule, the IOM committee finds no evidence that the schedule is unsafe. The committee’s review did not reveal an evidence base suggesting that the U.S. childhood immunization schedule is linked to autoimmune diseases, asthma, hypersensitivity, seizures, child developmental disorders, learning or developmental disorders, or attention deficit or disruptive disorders.
Existing mechanisms to detect safety signals — including three major surveillance systems of FDA-approved products maintained by the CDC and a supplemental vaccine safety monitoring initiative by the FDA—provide further confidence that the current childhood immunization schedule is safe.
It’s quite a tempting narrative. Small defenseless children are jabbed multiple times, allowing harmful foreign substances to enter the body, all with the nefarious intent of making profits for large pharma giants. However, children are assaulted by pathogens from the second they exit the birth canal, and continue to be throughout the course of their lives.
The inactivated versions of the pathogens they might otherwise come into contact with should present no extra burden to an immune system that already anticipates invasion. Of course, coming into contact with a dead version of a pathogen is far preferable to coming into contact with the live version. The assertion that the schedule is “crowded”, given daily attacks on the immune system, is completely absurd.
Moreover, the report found that States with loose vaccine policy, have higher incidence of disease, in this case Pertussis:
While parents generally worry about children’s health and well-being, and their concerns about immunization safety can be viewed in that context, delaying or declining vaccination has led to outbreaks of such vaccine-preventable diseases as measles and whooping cough that may jeopardize public health, particularly for people who are under-immunized or who were never immunized. States with policies that make it easy to exempt children from immunizations were associated with a 90 percent higher incidence of whooping cough in 2011.
Of course, we are experiencing record numbers of Pertussis cases. It must be noted, that like influenza, most cases of Pertussis are asymptomatic. In fact, it is estimated that 5 out of 6 cases of Pertussis come without symptoms, yet transmission occurs. (2 out of every 3 influenza cases are asymptomatic. Next time someone tells you they never get the flu, don’t believe them.) Unvaccinated people may still contract the disease, not experience symptoms, and still pass it one to an unvaccinated person, who, of course, could very well die.
Many of the diseases on the vaccine schedule are very much still in circulation. One excellent example is tetanus, a bacteria which lives happily in soil (not rust, as commonly believed). Tetanus passes through our digestive tract regularly through food, but when the bacteria enter the other parts of the body, particularly the low-oxygen environment of the muscles, the usual outcome is to suffer for months and often die a truly horrible death. Nearly all cases of tetanus in the US occur in unvaccinated individuals.
Given tetanus’ ubiquity in the environment, I often scratch my head when parents tell me they don’t vaccinate their children as the risks of the disease far outweigh the risks of the vaccine. Here, of course, it isn’t the vaccine that’s killing kids, but politics and self-serving conspiracy hacks.
WHO Stating the Absolute Obvious
From the WHO’s “Malaria Elimination: A Field Manual for Low and Moderate Endemic Countries“:
“Malaria transmission is particularly difficult to interrupt in areas with efficient mosquito vectors, a long or year-round transmission season, poor state of overall development, marginalized populations and weak health systems with inadequate coverage of health services, as well as in areas with civil unrest, illegal cross-border movement, or areas that border high-burden neighboring countries and experience intense cross-border population movement. Each of these factors will reduce the feasibility of malaria elimination”
Shouldn’t this be completely obvious? They are describing every place where malaria is, outside a few exceptional cases at this point. The WHO is stating clearly that malaria elimination in Sub-Saharan Africa is absolutely impossible.
Uganda Drops Death Penalty for Homosexuals
The Times reported this morning that the Ungandan lawmaker who originally introduced the now famous bill recommending the death penalty for homosexuals, has drop that particular portion. Instead, he favors imprisonment for homosexuals and people who advocate of behalf of them.
There’s no doubt that Sub-Saharan African countries have become a battleground for the debates of the United States, much as the DRC and Angola were de facto theaters of war for the US and the Soviet Union. However, as complicit as we are, the elephant in the room is that Uganda should spend more of its time figuring out how to lift its numerous poor out of poverty and how to protect the health of its children.
Worse yet, the sill hypocrisy is evident. Anti-Gay proponents claim that homosexuality in Africa will undermine African family values. As near as I can tell, poverty, HIV and massive gender inequality have done more than their fair share of damage to African family values. Like the US, conservative voices are remarkably silent on these issues.
Politicians love to pick on the defenseless, particularly when they are in small numbers and especially when they can’t vote. David Bahati, the bigot (and member of the fundamentalist US Christian group The Family) who introduced the bill, no doubt receives political concessions and maybe even financial contributions from abroad.
Even if the bill does pass, enforcement will be laughable. Police in any Sub-Saharan country are noticeably absent, particularly in the rural areas. The trouble is that, where police are not present, mob violence is. In Kenya, a petty thief at a rural market can expect to be horribly beaten and publicly burned to death without trial. The Ugandan Parliament merely fans the flames of this type of sickening violence by codifying hatred into law.
Malaria in the News: 1858-Present
Malaria in the South 1925-1935
A search for all articles with “malaria” in the text yields an amazing 33,800 results. Browsing through the headlines is like reading a brief history of the disease as seen through an American lens.
The oldest article is from 1889, a report on a malaria outbreak on the upper Hudson in New York: “An epidemic of a malarial nature is reported from towns along the upper Hudson, one physician in Newburg reporting more than seventy cases under his care. Newburg is famous for its breakneck streets.”
The article is notable because in 1889, very little was known about the disease. Of course, in 2012, we know much, much more, but the challenges (problems in diagnosis, complex and often contradictory observations on ecological factors and socio-economic infection gradients) are the same now as they were then.
From 1925:
“30 INSANE PARETICS CURED BY MALARIA; Long Island College Hospital Reports Marked Success With New Treatment. Thirty patients regarded as hopelessly insane are back at work and leading normal lives after being artificially inoculated with malaria, allowed to suffer chills and fever for two weeks or so and then treated with drugs, according to an announcement yesterday by the Long Island College Hospital.”
I don’t think that anyone really knew what the “paretics” were suffering from, but it was likely syphilis. Malaria was used briefly to treat a variety of neurological disorders caused by infectious agents, with varying degrees of success and failure.
There are a few other shockers. Prisoners were used to test malaria drugs until halted in 1974, a practice that no IRB would ever approve now.
Vaccines have long been “just around the corner,” only to die in sad failure. The most overly optimistic claim came in 1984 from then head of USAID, M. Peter McPherson (who later became President of Michigan State University):
M. Peter McPherson, administrator of the Agency for International Development, said he expected that a vaccine would be ready for trial in humans within 12 to 18 months and widely available throughout the world within five years. ”We think this is a practical schedule,” he told a news conference at the State Department today.
A classic case of overstatement, I’m sure that he regrets this event to this day. No wonder scientists have to be wishy washy with their predictions. Statement like this live in sad perpetuity. We still don’t have a vaccine, and the outlook for having one any time soon hasn’t gotten much better now than in 1984.
Selected highlights:
1889 North River Malaria
1925 30 INSANE PARETICS CURED BY MALARIA
1925 WAR ON MALARIA BEGUN BY LEAGUE
1938 MALARIA SCOURGE FOUGHT BY THE TYA
1943 Malaria Problem; Our Knowledge Is Still in an Unsatisfactory State
1944 us HEALTH SERVICE COMBATS MALARIA
1945 New Drugs to Combat Malaria Are Tested in Prisons for Army
1946 CURE FOR MALARIA BARED BY CHEMISTS
1948 NEW DRUGS TO END MALARIA SCOURGE
1951 Army Tests Drug as Malaria Cure; Doses Given Troops
1952 un GAINS GROUND AGAINST MALARIA
1957 World-Wide Battle On Malaria Mapped
1961 New Malaria Threat Is Studied At Infectious Diseases Center
1965 A ‘NEW’ MALARIA RAGES IN VIETNAM
1966 Leprosy Drug Reduces Malaria Among gi’s
1970 Malaria Up Sharply in Nation; Most Cases Traced to Vietnam
1971 Drug Users Spur Malaria Revival
1974 Prison Official in Illinois Halts Malaria Research on Inmates
1977 Malaria Spreading in Central America as Resistance to Sprays Grows
1984 MALARIA VACCINE IS NEAR, U.S. HEALTH OFFICIALS SAY
1987 Drug Combinations Offer New Hope in Fighting Malaria
1988 Scientists Report Advances In Vaccine Against Malaria
1991 Outwitted by Malaria, Desperate Doctors Seek New Remedies
1991 Hope of Human Malaria Vaccine Is Offered
1993 Mefloquine Is Found Best Against Malaria
1994 Vaccine Cuts Malaria Cases In Africa Test
1995 Vaccine for Malaria Failed in New Test
1996 Tests of Malaria Drug From China Bring Hope and Cautionary Tales
Sometimes, when Good Ideas Die, Kids Die (from Malaria)
The Affordable Medicines Facility – Malaria (AMFm), an innovative subsidy program designed to increase access to life saving malaria medications in poor countries, died last week.
I would argue that malaria is the most important health issue in the world. This ancient disease kills the young, debilitates the living, and universally strikes the weakest of the weak and the poorest of the poor. Malaria’s complex biology doesn’t lend itself to the easy creation of vaccines, and its deep relationship with poverty makes it nearly impossible to eradicate. The only way to successfully eradicate malaria will be to eradicate poverty itself, not an easy task.
We have been able to create drugs which successfully treat malaria, but the parasite quickly finds and exploits weaknesses in the drugs. After time, the drugs become utterly useless. Right now, our last hope is medical cocktail based on artemisinin, a ancient plant grown in China, Artemisinin Combination Therapies (ACTs). The drugs are effective, and the cocktail based nature of the drug means that the parasite has difficulty developing a resistance to it.
Despite ACTs being effective, most people in parts of the world where malaria is most common have no access to it. ACTs are expensive, delivery difficult and developing country health systems poor and ineffective. In the public sector, stockouts are common making them an unreliable source. Distance from facilities is also a barrier. In Sub-Saharan Africa, for example, most people (often the poorest) live too far away from a facility to justify the trip.
This is where the AMFm comes in. The AMFm takes money from the Global Fund to Fight TB, Malaria and HIV and pays it directly to manufacturers for ACTs. Private wholesalers in participating countries are then able to procure ACTs at low prices. Wholesalers then pass this discount on to small private drug retailers, who are able to sell ACTs at a price equivalent to less effective (and cheap) anti-malarial medications. As private drug retailers exist just about everywhere, cheap ACTs become widely available to the poorest and most remote of populations at a price they can afford. The private sector, with profit as a motivator will maintain consistent stocks and older, ineffective medications are crowded out of the market.
At least, this was the hope. A meeting of the Global Fund last week effectively killed the AMFm.
The program was first proposed in 2002, has been piloted in 8 countries (7 in Africa and 1 in South East Asia), and has been under review for the past few years. Full disclosure, I was a part of a review of the AMFm as part of a a group affiliated with the UM Business School.
We found that under the AMFm, availability of ACTs increased, stocks were more consistent and prices fell. Our results agreed with other evaluations. Granted, problems in equity of access still existed, but, given the challenges of drug delivery in Sub-Saharan African countries, the AMFm was a rounding success, and potentially a more effective method of increasing access to meds than strategies which exclusively rely on the public sector.
The AMFm, despite all the indications that the program was going to bring (and has brought) life saving meds to populations that would normally go without, faced intense criticism. The critics most notably came from within the United States. The Presidents Malaria Initiative (PMI), a program started under George W. Bush to fight malaria was the most vocal. Some critics worried about diversion to non-AMFm countries. The same critic, with almost no data, (right wingers) even claimed that the AMFm supported organized crime.
PMI claims that the AMFm haphazardly doled out ACTs to people who did not need them, wasting resources and potentially inducing parasite resistance to the drug, rendering it ineffective. They claim that the AMFm undermined the public sector’s ability to provide services. They claim that ACTs under the AMFm disproportionately went to areas which had low levels of malaria transmission, such as the nearly malaria-free island of Zanzibar. The problem isn’t that these claims are false. They are all based on an independent evaluation of the AMFm sponsored by the Global Fund. The problem is in how the results were spun.
The reality, that PMI (and others) seem to ignore, is that nothing is perfect in Sub-Saharan African countries. In a world where the extent of poverty and human suffering is so great, a less than perfect result might be better than anything that was there before. Even if people are being misdiagnosed, the truth is that a number of people who do have the disease and did not have access before, now have access to drugs. Even if the public sector is being crowded out, the truth is that public sector health delivery in SSA is frought with problems. In survey after survey, people state that the private sector is their first choice for medical treatment. Bolstering health delivery through the private sector is an obvious solution.
In the end, the AMFm was held to a standard that was impossible to reach. I can think of no program in the past decade which has been held to this level of scrutiny. The AMFm, in this regard, was doomed to fail from the start.
Malaria metrics are often elusive. Information on malaria mortality exists, but only for people who show up and die at a formal facility. Estimates of infection prevalence exist, but asymptomatic cases and the difficulty of reaching remote and very poor populations reduces confidence. We know that malaria cases are down everywhere, but determining the exact causes of this decline are difficult. it is admittedly difficult to know how many kids the AFMm saved. We do know, however, that untreated symptomatic malaria in children is dangerous and that drugs are hard to get.
The odd thing to me, is that PMI, being a American group started by a free-market Republican would disparage an effort to bolster private sector health delivery. In essence, PMI is suggesting that a top down, government centered form of health delivery is optimal, which is entirely backwards from the stated philosophy of the Republican Party. Domestically, we know the attitude to be quite different. Personally, I think this smacks of paternalism. Private sector health care in the US is lauded, but Africans can’t be trusted with the same models.
I admit, before I became involved with this project, I was also skeptical of private health care delivery in developing countries. While regulation and certification programs are key to optimizing efficiency and insuring that standards of effective delivery are met, the results of the AMFm evaluations indicate that the private sector can be very effective. Really, it took me going to these areas and visiting these shops to realize how effective it can be. I wonder if the administrators of PMI ever took the time to visit.
Improving access to medications saves lives. Now that the AMFm is dead, I worry that kids will die, simply because a few people didn’t take the time to put their feet on the ground.
“Health Care Plans of the Candidates”: Burying Our Heads in the Sand
A short op-ed in the NYT yesterday had this to say:
“Mitt Romney’s health care plan offers 15 guiding principles, but appropriately leaves to Congress the resolution of most details. Obamacare’s 2,400 pages were never understood even before passage, push all risk to taxpayers and promise economic disaster.”
This is, of course, either, at best, a demonstration of complete ignorance of the facts, or at worst, another example of conservative revisionism. When the Obama admin came into office, they also presented only some general guidelines. The crafting of the Affordable Care Act was left almost entirely to the Congress. In fact, the Obama admin was repeatedly criticized for not taking a more forceful role in the bill’s creation. This isn’t ancient history. It was in 2009.
On the surface, Romney’s claims of repealing the Affordable Care Act are patently fantastical. It took decades to get comprehensive health care reform in the country. When the political will finally surfaced, it was a fight to the death. Romney must recognize this, carefully choosing his words stating “I will act to repeal Obamacare on my first day.” “Acting to” is very different from “doing.” This nuance, I am afraid, is lost on the electorate. What he plans to do, is another mystery. The discussion is bordering on infantile.
More frustrating for me, is the constant call for “market solutions” to our problems of health care delivery. We have given the market a chance. The market has had free reign to do as it likes for decades. We have seen this market approach to health fail miserably. Why? Simply because health markets don’t work like hardware stores.
People who have insurance really have no clue what the lives of people without insurance are like. Similarly, the wealthy have little concept of the lives of the poor. Clearly, Romney is both.
Romney and the Return of the Global Gag Rule
Sadly, I have been pondering the possibility of a Romney win in November. It hadn’t occurred to me, but Romney looks poised to reinstate the “global gag rule.” That is, international groups receiving funds from the United States will be barred from discussing abortion with patients, or risk losing funding.
The past three Republican Presidencies have all used the global gag rule, and Romney promises to bring it back on his first day in office.
Of course, this is fine for domestic right wingers, many of whom have never been to the countries affected by the rule. Romney gets his votes and Christians can go home and sleep happily, knowing that their will, God’s will, has been successfully imposed on hapless poor people in Africa.
Deaths from abortion, often provided untrained individuals under deplorable conditions, are common in Sub Saharan Africa. There were nearly 3,000,000 abortions performed in East Africa in 2008. 36% of these were performed under unsafe conditions. It is estimated that 18% of all maternal deaths in East Africa are due to unsafe abortion practices.
The evidence for wider access to abortion services and reductions in maternal deaths in sub Saharan Africa is out there. South Africa reduced its abortion related mortality rate by 91% following full legalization and the expansion of safe and available abortion providers. Abortion still remains illegal in most sub-Saharan African countries though the extent of the laws vary by country. In some areas with strict laws, governments are known to turn a blind eye to certain NGOs providing services.
While right wingers in the US can smugly claim that their efforts are saving babies, the truth is that women faced with an unwanted pregnancy in Sub Saharan Africa will seek an abortion if they want one. Romney’s vision would leave even victims of rape in conflict ridden areas such as the DRC with no option but obtain a home abortion. Granted, women in these areas have little access to medical care at all, but this restrictive policy only serves to make a bad situation even worse.
The Cure for Malaria is Development: A Controversial Notion?
I think not. I’ve just returned from a meeting of malaria researchers in Basel, Switzerland. The meetings were excellent. It is rare to have such a wide showing of malaria experts in one place, talking about nothing but malaria.
The meeting was notable for what was included, namely excellent presentations on vaccine development, subsidies to increase access to medications, malaria elimination programs in less than talked about parts of the globe (Bhutan, Turkmenistan, PNG), and the paucity of research on Plasmodium vivax.
The meeting was also notable for what it did not include, namely global economic determinants of malaria.
To me, malaria is 100% a disease of poverty. Where poverty is low, malaria is low. This is true globally, as well as within still malarious countries. The graph to the right shows the relationship of country level GDP with the estimated number of malaria cases per 100,000 in 2006. Though accurate data on the true number of cases is difficult to obtain for developing countries for a host of reasons, the trend should be clear. More money equals less malaria.
Is this because on better funding for malaria programs? After all, wealthier countries are able to put more resources into prevention, mosquito control, and treatment. Sure, I think this is partially the case. It has to be said, however, that malaria was eliminated from the United States without modern medicines and insecticide treated bednets, cornerstones of current malaria control strategies. Though DDT was instrumental in helping to control malaria transmitting mosquitoes in the US, the truth is, the bugs are still here.
Malaria deaths around the world are down. It is also the case that worldwide development is up. The economies of developing countries are improving, record numbers of people are moving out of entrenched poverty and, while within country inequality is increasing, global inequality is decreasing. Personally, I think the relationship between development and malaria is no accident at all.
What strikes me, is that this topic was hardly mentioned last week. I brought it up a couple of times, but, unfortunately, scientists are hesitant to move out of their comfort zone, and wish to give it little thought. Talk of politics or economics produces blank looks in scientists trained in microbiology or entomology. I’m sure its the same on the other end. Certainly, the current research is important, helpful, relevant and should be continued. However, I don’t think that we, as scientists, should stick our heads in the sand and willfully ignore the bigger picture.
Malaria will be eliminated not through fancy pharmaceuticals and ever improved bednets, but through the increase in access to employment, market economies and remunerative opportunities. Malaria will be eliminated through the elimination of entrenched poverty, the expansion of free education, reductions in gender inequities and improved nutrition. In my opinion, these were the true factors which led to the elimination of malaria from the US, Europe, Japan. Granted, there are climatic differences between those countries and sub-Saharan Africa, but P. vivax, a cold weather malaria, was also fully eliminated.
People I spoke with sort of waved their hands and acted as if there is nothing we can do about these global and economic problems. I disagree, of course. Policy makers look to scientists for answers (though they make ignore what they don’t like). Endless bednet trials that only marginally expand on previous research do not do much to ameliorate the structural factors which keep people in poverty. Research which explores those big picture factors, however, could have vast benefits.
