“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.
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.
“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.
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.
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
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.
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.
A few friends sent me links to recent articles touting the development of a new class of drugs against malaria. Trials in mice have shown that a single dose of the medication can fully eliminate the parasite from the blood with little or no side effects.
I applaud the ongoing efforts of researchers to develop new malaria medications. Chloroquine has long been rendered useless in many parts of the world, and artemisinin based medications, while currently effective, might possibly go the way of chloroquine in the near future. We need more and a wider variety of drugs to fight the disease.
The optimism, however, may be misplaced. First, the researchers have only recently obtained approval for human trials. Until now, the drug has only been tested in mice, which are unable to contract the human strains of malaria. Second, the claims of few side effects are suspect. While serious side effects (like death) are quite obvious, mice have no effective means of communication with their keepers.
Third, what is magical today, may be useless in the future. Drugs are only as good as hosts as parasites allow them to be. Without true trials in the field, we can never know how quickly Plasmodium parasites will adapt to a new set of pressures. Experience to date indicates that they do rather well.
Fourth,before touting unsubstantiated successes in the popular press, the question of genetic compatibility must be addressed. Not all humans (and parasites) are created from the same mold. What works in Zambia might be useless in Cambodia.
I find overly optimistic predictions annoying, though unsurprising in the popular press. Scientists, however, should refrain from making rash predictions as to the success of their efforts. Certainly, this makes us appear wishy washy in the eyes of the public, but ’tis better to err on the side of caution lest we set ourselves up for ridicule and failure.
I just got word that one of the papers that I’ve been working on with the Clinton Foundation and the UM Business School has been officially published in Malaria Journal. We’ve been working on a project assessing the impact of supply side drug subsidies on the availability of malaria medications in Tanzania.
This is good!
Trends in availability and prices of subsidized ACT over the first year of the AMFm: evidence from remote regions of Tanzania
Prashant Yadav, Jessica L Cohen, Sarah Alphs, Jean Arkedis, Peter S. Larson, Julius Massaga and Oliver Sabot
Malaria Journal 2012, 11:299 doi:10.1186/1475-2875-11-299
Published: 28 August 2012
BackgroundThe Affordable Medicines Facility for malaria (AMFm) is a pilot supra-national subsidy program that aims to increase access and affordability of artemisinin combination therapy (ACT) in public sector clinics and private retail shops. It is unclear to what extent the AMFm model will translate into wide scale availability and price reductions in ACT, particularly for rural, remote areas where disparities in access to medicines often exist. This study is the first to rigorously examine the availability and price of subsidized ACT during the first year of the AMFm, measured through retail audits in remote regions of Tanzania.
Periodic retail audits of Accredited Drug Dispensing Outlets (ADDOs) were conducted in two remote regions of Tanzania (Mtwara and Rukwa). Temporal and spatial variation in ACT availability and pricing were explored. A composite measure of ADDO remoteness, using variables, such as distance to suppliers and towns, altitude and population density, was used to explore whether ACT availability and price vary systematically with remoteness.
Between February 2011 and January 2012, the fraction of ADDOs stocking AMFm-ACT increased from 25% to 88% in Mtwara and from 3% to 62% in Rukwa. Availability was widespread, though dispersion throughout the region was achieved more quickly in Mtwara. No significant relationship was found between ACT availability and remoteness. Adult doses of AMFm-ACT were much more widely available than any other age/weight band. Average prices fell from 1529 TZS (1.03 USD) to 1272 TZS (0.81 USD) over the study period, with significantly higher prices in Rukwa. The government recommended retail price for AMFm- ACT is 1,000 TZS ($0.64 USD). The median retail ACT price in the final round of data collection was 1,000 TZS.
The AMFm led to large increases in availability of low priced ACT in Tanzania, with no significant variation in availability based on remoteness. Availability did remain lower and prices remained higher in Rukwa, which is a more remote region overall. Low availability of child and adolescent ACT doses could be due in part to lower quantities of non-adult packs imported into Tanzania. Future research will explore whether increased availability and affordability persists and whether it translates into higher ACT use in Tanzania.
Malaria has been around a lot longer than that, but 115 years ago, on August 20, 1897, Dr. Ronald Ross definitely proved his hypothesis that Anopheles mosquitoes transmit malaria to humans.
Ross himself called the day “Mosquito Day,” an anniversary international health professionals (particularly the London School of Tropical Medicine and Hygiene) continue to celebrate. Certainly, if Dr. Ross had not found parasites during his dissection of mosquitoes, someone else would have. Dr. Ross, though, can be credited with speeding up the process of malaria elimination efforts, perhaps saving the lives of billions of children.
Though the discovery of Plasmodium parasites in the gut of Anopheline mosquitoes was vastly important, Dr. Ross most important contribution was his word on mathematical models of infectious disease transmission, which continue to push research to this day.
Though malaria was eventually eliminated from the US, Europe, Japan and a host of other countries following World War II, it continues to kill children throughout most of the developing world. Nearly half the world’s population, 3.3 billion people, lives at some risk for malaria and nearly one million people die from the disease every year.
We still have much work to do, even 115 years later.
An amazing excerpt from his 1923 notebook where he recalls that very important day:
“…The 20 August 1897—the anniversary of which I always call Mosquito Day – was, I think, a cloudy, dull, hot day. I went to hospital at 7am, examined my patients and attended to official correspondence… After a hurried breakfast at the Mess I returned to dissect the cadaver (Mosquito 36) but found nothing new in it… At about 1pm I determined to sacrifice the seventh Anopheles (A. stephensi) of the batch fed on the 16th, Mosquito 38, although my eyesight was already fatigued. Only one more of the batch remained.
The dissection was excellent and I went carefully through the tissues, now so familiar to me, searching every micron with the same passion and care as one would search some vast palace for a little hidden treasure. Nothing. No, these new mosquitoes also were going to be a failure: there was something wrong with the theory. But the stomach tissue still remained to be examined – lying there, empty and flaccid, before me on the glass slide, a great white expanse of cells like a large courtyard of flagstones, each one of which must be scrutinised—half an hour’s labour at least. I was tired and what was the use? But the Angel of Fate fortunately laid his hand on my head; and I had scarcely commenced the search again when I saw a clear and almost perfectly circular outline before me of about 12 microns in diameter. The outline was much too sharp, the cell too small to be an ordinary stomach- cell of a mosquito. I looked a little further. Here was another, and another exactly similar cell.
The afternoon was very hot and overcast; and I remember opening the diaphragm of the sub-stage condenser of the microscope to admit more light and then changing the focus. In each of these cells there was a cluster of small granules, black as jet and exactly like the black pigment granules of the Plasmodium crescents… I laughed, and shouted for the Hospital Assistant – he was away having his siesta… Then I made rough drawings of nine of the cells on page 107 of my notebook, scribbled my notes, sealed my specimens, went home to tea (about 3 p.m.) and slept solidly for an hour…”
Like other islands, the people make their living almost entirely through fishing. Small scale fisherman capture Nile Perch, Tilapia and catfish, bring them back to community fishing boards, which then sell them to larger brokers, which then take them to the notorious (and mysterious) “factory.” The “factory” then filets the fish and sells them to European and American dealers. The welfare of this tiny island depends entirely on the whims of hungry Europeans. The global economy starts on islands like Sucru.
In contrast with the other islands, however, the locals appear to eat some of what they catch. In fact, I assume that the majority of what they eat comes straight from the water. I could see absolutely no evidence of agriculture of any kind on this tiny island. The result is that the residents of the island appear quite well fed, some are even fat, but clearly lack essential vitamins due to their monotonous diet.
Housing conditions are miserable, and, like many islands here, sanitation is quite poor. About twenty years ago, a group came and installed a septic and well system to try to keep the locals from openly defecating and drinking their own sewage, but the system appears to have never been used. Like most areas around Lake Victoria, people prefer to crap in the bushes over a formal toilet. The result is that diarrheal disease is constant, and children live in states of vastly poor health.
Though only having a handful of residents, malaria is endemic to the island. Black mambas (considered the most dangerous snake in the world) are also native and live in plentiful numbers. We found a freshly killed one on a rock.
Safari ants are also plentiful. A few crawled up my pant leg and drew blood. I can be seen in one of the pictures picking them off myself. I think everyone had their pants off at some point picking off ants.
Despite all the challenges, the locals are incredibly kind (like many people around the lake), appear quite happy and don’t mind being photographed. They laugh hysterically at my rudimentary (though improving) command of the Luo language.
We’ve started our visits to drug shops in this region of Tanzania, which mostly entails sitting alongside interviews in Swahili and waiting long hours for customers to show up. It’s a national holiday so everyone must be busy attending to children at home, cause noone seems to be interested in buying pharmaceuticals today.
This village sits on the outskirts of Sumbwanga town in Rukwa Region. The local economy is based on agricultural trade and local buying and selling of goods available anywhere in Sub Saharan Africa. The market consists of the usual fare, soap, haircuts, soft drinks and beer, but sports a variety of dried fishes and local fruits. I pass on the dried fish as delectable as it looks. The omelet with French fries is also out, sad to say. The oranges, no problem.
Like most places in Africa, people are very kind and will repeatedly thank you making the long journey to their very small and mostly unknown village. Here, so close to friendly and peaceful hotspots like Malawi and Zambia, extreme kindness is a given.
The only business here is small business. Like everywhere in Africa, businesses are informal, sole proprietorships. The drug shops are no exception. I spoke with two shop owners today, both were trained as nurses, but left public service to open or work at small drug shops.
The relationship of drug shops with the public system is worth noting. As the public system in Tanzania relies completely on government revenue and donor aid to function, drugs are often unavailable. In theory, this opens a market opportunity for private shops but in reality it appears that public employees are funneling drugs to shops they have a stake in, as a recent scandal has unveiled.
I spoke with a gentleman today who may be considered exceptional, but likely isn’t. 20 year old Charles, living in an extremely remote town worked burning charcoal for pennies, saved his earnings and opened a small shop, debt free. Now he sells soap, cooking oil and single cigarettes from a small storefront adjacent to one of the drug shops we visited. He would like to save his money and open a shop which sells lights, generators and electrical goods aimed at other shops.
One common misconception about Africa is that Africans lack an entrepreneurial spirit. Far from it, what they actually lack is capital.
All Africans are entrepreneurs. Americans on the other hand mostly just draw paychecks.
The Lancet recently published the results of a longitudinal study examining resistance by malaria parasite to the latest and most effective treatment for the disease, Artemisinin Combination Therapy (ACT) along the Thai-Myanmar border.
Parasite clearance rates increased from a mean half life of 2.7 hours in 2001 to 3.6 hours in 2010, indicating that resistance is growing. Resistance was originally observed on the western side of Cambodia, but has now either spread geographically to western Thailand or emerged on its own. The latter scenario is actually the more frightening possibility. If resistant strains emerge in Sub-Saharan Africa, it could be a major setback.
Though research to develop new drugs is ongoing, ACTs are presently the most effective treatment and a major part of the arsenal with which to stop transmission and prevent early childhood death. Past treatment strategies are now largely ineffective.
Vaccines are also in development (most notably the RTSS vaccine), though I have little confidence that it will be of much use for long. It is a long series of shots and difficult to deliver in areas where medical delivery is poor or non-existent and efficacy is strain and context specific. Malaria vaccines are nice in the popular press, but impractical on the ground.
That resistance is growing in this particular end of the world, is in itself significant. Both regions are notable for poor health delivery, sporadic armed conflicts and marginalized populations. Efforts to contain the spread of resistance are likely futile. Even in the best of times, adequate delivery of care and prevention strategies are near impossible. Displacement of people due to conflict always provide ample opportunities for infectious agents, poor health and death. Tens of thousands of people languish in refugee camps along the border.
The subject of resistance in this region comes up often in meetings of malaria researchers, though I am always struck at the absence of discussion of social factors and conflict and how they create conditions favorable for the spread of resistant pathogens. It is no accident that malaria occurs in the places it does, and no accident that resistant strains of Plasmodium are able to fester and evade efforts to reign it in. It is almost as if the malaria research world believes that genetic adaptation happens at random, which it does not.
Discussion of malaria eradication cannot proceed without discussion of how to eradicate worldwide conflict, entrenched poverty and proper delivery and access to basic health care and the global forces which create these conditions. Yet it does.
Medications, vaccines and preventative interventions cannot work if there is no way to delivery them, and people cannot access them unless there is a local economy with which to support such a system. Malaria research has to address this fundamental issue or we’re just talking in the wind.