Bednets are failing

Undefeated (© IRD / M. Dukhan)

Bednets seemed the perfect malaria intervention: cheap, needing no doctors or needles but saving the lives of perhaps five children for every thousand covered. But unfurling hundreds of millions of mosquito-killing nets across Africa has provoked a wave of insecticide resistance. Resistant mosquitos pass through and bite instead of dying. Also, children eventually come out from under bednets when they are older which might be worse than having had no protection to begin with in areas with intense malaria transmission. Remarkably, the most recent and comprehensive research on malaria mortality shows weak or no evidence that bednets save the lives of children in Africa.

In 2000, health officials set a goal to protect 60 percent of the population at greatest risk of dying from malaria, children under five and pregnant women.  Compelling studies had shown that bednets dramatically reduced malaria and saved lives. In 2005, the World Health Assembly voted to hoist the target to 80 percent. Distribution of nets leapt to 47 million in 2006, up from 17 million the year before. In 2007, Melinda Gates called for the total global eradication of malaria. In 2008, the world spun up and delivered more than 60 million nets. Nets became a cause célèbre, with Ashton Kutcher leading the charge on Twitter in 2009. In 2010, more than 140 million nets were shipped to sub-Saharan Africa, where more than 750 million people are at risk for malaria.

Insecticide treated nets (ITNs) distributed to sub-Saharan Africa. WHO, World Malaria Report 2011

Scale-up drives resistance

But living organisms try to stay that way. And the immense selective pressure of mosquitocidal nets drove a proportionate resistance pushback. More nets, deployed for more time, select for a more resistant mosquito population. For example, in a large trial in Asembo, Kenya, as bed net coverage ascended, a key mutation conferring insecticide resistance expanded through the mosquito population. When bednet coverage reached 100 percent, the resistance mutation also neared 100 percent frequency.

Adapted from Mathias et al., “Spatial and temporal variation in the kdr allele L1014S in Anopheles gambiae s.s. and phenotypic variability in susceptibility to insecticides in Western Kenya,” DOI: 10.1186/1475-2875-10-10

Treated nets all use pyrethroids, a class of insecticides originally derived from chrysanthemums. Pyrethroids are enormously toxic to mosquitos but comparatively safe for humans. Pyrethroids act on nerve cells by binding to a receptor site on a sodium channel, inhibiting its deactivation. In susceptible mosquitos, pyrethroids trigger rapid paralysis or “knockdown,” then death.

Not all die, however. Mosquitos have evolved a number of defenses. Some are metabolic — insects rapidly detoxifying or sequestering poisons. In addition, researchers looking at mosquito feet with an electron microscope have even detected “cuticular thickening” which slows or blocks insecticide absorption when mosquitos touch down on nets. Mosquitos might be evolving their behavior as well to avoid bednets. A recent study of two villages in Benin found that mosquitos shifted their peak feeding time from the middle of the night, when nets protect people sleeping under them, toward dawn when villagers are waking up and exposed. 

More important, however, are mutations that reconfigure the sodium channel to prevent the short-circuiting effects of pyrethroids. A sufficient dose of pyrethroids kills up to 100 percent of susceptible mosquitos but in some “knockdown resistant” phenotypes, as many as 100 percent survive.

The frequency of resistance genes within a population ebbs and flows, and pyrethroids can still do serious damage even where resistance is present. Although the large number of nets drives selection for resistance, the insecticide onslaught also kills huge numbers of mosquitos, reducing transmission. Against susceptible mosquitos, bednets radically reduce bloodfeeding, by 90 percent or more. By contrast, bloodfeeding of knockdown-resistant mosquitos is essentially unaffected by the pyrethroids on bednets. And, by itself, the physical barrier presented by nets provides only very partial protection.

The search for alternatives

Venerable pyrethroids are now roughly half a century old. There are efforts to find new insecticides, but none are in sight. The Innovative Vector Control Consortium (IVCC), set up and funded by the Bill and Melinda Gates Foundation, has been working on the problem since 2005.  IVCC’s current portfolio shows no new chemicals entering into a development or registration for use phase. If there are any promising candidates further upstream, IVCC chief operating officer Tom McLean won’t talk about them. He fielded a question on status by saying: “At this early stage of the development process it is not appropriate to publish specific chemical structures of what is in the pipeline because it is essential to preserve the commercially competitive nature of these products.”

The Gates Foundation directly funded out-of-the-box projects like “click chemistry” in which two non-toxic chemicals bind together lethally inside mosquitos. But that clever idea did not pan out.

According to Helen Pate Jamet, senior scientist for bednet maker Vestergaard Frandsen, “ideally we need at least 2-3 new insecticides from completely different insecticide classes in order to have a real impact on resistance and have the ability to rotate/mix different classes.”

Meanwhile, Vestergaard Frandsen is testing nets impregnated with chlorfenapyr which comes from a new class of insecticides called pyrroles. Unfortunately, they aren’t as good as pyrethroids. Chlorfenapyr is less toxic to mosquitos and more harmful to humans than pyrethroids. Chlorfenapyr is a "prodrug" that has to be broken down before starting the chain of events that, in time, kills the mosquito. Consequently, chlorfenapyr-treated nets provide little to no personal protection from malaria. Mosquitos still bite, only dying later. “Any inhibition of blood feeding associated with the insecticide treatment was not statistically significant,” according to one study of chlorfenapyr–laced bednets. To work, much of the community must also sleep under a net, thereby reducing the mosquito population. The direct life-saving benefit of pyrethroid bednets is lost.

Geographic extent and implications

Pyrethroid resistance has been found all over the African continent. Mosquitos have developed resistance to other insecticides, but according to WHO's most recent report, "Resistance to pyrethroids seems to be the most widespread." And it's worsening. Previously there were pockets of resistance; now there are pockets of susceptibility. 

Adapted from:  Ranson, et al., “Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?” DOI: 10.1016/j.pt.2010.08.004 and WHO, “Global Plan for Insecticide Resistance Management in Malaria Vectors”

Yet remarkably there is debate about whether insecticide resistance impacts malaria control. “[T]here is broad consensus that the degree of resistance that has developed and its likely trajectory are a cause for serious concern,” according to Scott Filler, senior advisor at the Global Fund for Aids, TB and Malaria. The trajectory, Filler says is toward “widespread control failure,” but “the pace of this process and the degree of reduction in malaria control effectiveness remains unknown.” The Global Fund purchases the majority of the world’s bednets, some 56 million in 2010.

Janet Hemingway, director of the Liverpool School of Tropical Medicine concurs that there is “undoubtedly a rapid increase” in pyrethroid resistance in Africa and that “at some point we will get failure.”

However, according to Christian Lengeler, it is “probably right” that “we have already now some detrimental effect...” because of pyrethroid resistance. Lengeler is director of the health interventions unit at the Swiss Tropical and Public Health Institute. Together with WHO, Lengeler advocated for bednets in the mid-1990s. He also authored the influential meta-analysis of bednet trials in 2004 showing 5.5 lives could be saved for each 1,000 children covered by nets.

Uncertainty principle

Getting a grip on the actual effects of bednets is difficult. The Global Fund’s Filler gave a mixed message on whether a decline in effectiveness can be measured. “No – no such [study] design exists,” said Filler. But he then added: “This can be accomplished in carefully designed trials but these are complex, expensive and need a high level of epidemiological expertise to conduct….”

A study of bednets in the village of Dielmo in Senegal published last year showed nets rapidly reduced malaria when first introduced, consistent with many previous studies. However, within two years, 48 percent of mosquitos had a mutation for pyrethroid knockdown resistance, up from 8 percent at the beginning of the study. Cases of malaria rebounded to just below pre-bednet levels.

Controversy ensued. “This paper is bad,” Lengeler said of the Dielmo study. The study, Lengeler continued, “has no credit whatsoever in the malaria community.” A commentary accompanying the Dielmo study applauded the rigor of the research but cautioned against extrapolating its conclusions to the rest of Africa.

However, the authors of the commentary themselves produced a study just a few months earlier which appeared to show bednet failure. In Luangwa, Zambia, bednet use rose dramatically in two years from about half the population to 86 percent. However, malaria infections went up. Although the paper seemed to demonstrate some kind of failure, one of the authors, Thomas Eisele, wrote in email: "That is not accurate.” Eisele, of the Tulane University School of Public Health and Tropical Medicine, did not reply to subsequent requests to elaborate. He pointed instead to research from the Institute for Health Metrics & Evaluation (IHME) showing more favorable results.

Claims on nets overstretching evidence

The IHME study found that bednets were associated with a statistically significant reduction of mortality from any cause of 23%. However, the study did not examine the effect of insecticide treated nets (ITNs) on death from malaria. As the study authors pointed out, "we were only able to examine the relationship between ITNs and all-cause mortality as the surveys we used do not include information on cause-specific mortality." 

However, a press release from IHME about the study used less cautious language, claiming: "researchers found clear evidence that bed nets reduce the number of child deaths from malaria." That statement did not appear in the peer-reviewed paper and is not supported by evidence in the paper.

IHME recently published a more comprehensive, exhaustive malaria mortality study. It made global headlines, reporting a higher death toll for malaria than previous estimates. Part of the difference came from a much larger estimate of deaths among adults. However, the study found that bednets did not reduce adult deaths from malaria in Africa: "coverage of insecticide-treated bednets," read the report, "was not a statistically significant predictor of African adult malaria mortality." But on the even larger question of whether bednets save children in Africa, the study is silent.

Asked that question in email, however, one of the paper’s authors, IHME’s Stephen Lim, replied that “ITNs [bednets] were a statistically significant predictor of African child mortality.” In other words, bednets worked to save the lives of the largest and most vulnerable group, children in Africa.

But the basis for this unpublished claim isn’t clear. The IHME study incorporates data from many smaller studies of particular geographic areas and then extrapolates as needed to country and continent levels using sophisticated, computationally-intensive modeling techniques. IHME actually generated many hundreds of models which were then averaged together into an ensemble to most closely approximate reality. However, Lim said IHME did not calculate an average hazard ratio for the effects of bednets. (A  hazard ratio is a number that indicates whether an intervention increases or decreases risk, in this case the risk of dying from malaria.) “Analytically,' said Lim in email, "we can calculate an ‘average’ hazard ratio but it is not something we have currently in place and would involve a considerable amount of work.” 

Not having a hazard ratio raises the question of how the statistical significance of bednets was assessed. IHME spokesperson William Heisel wrote in email that 131 models found bednet coverage to be a significant predictor of malaria mortality for children under five in Africa. However, at one point in the analysis, there are a total of 214 models for children under five in Africa. IHME did not reply to an email asking if this meant 131 models were and 83 models were not significant for bednets. 

A greater number of models does not necessarily mean the variable being tested is statistically significant because models are weighted differently. IHME had earlier cautioned against simply counting the models in their list: “This list by itself," wrote Lim, "is not easily interpretable as different individual models are given more weight in generating the ensemble model.”

Asked whether IHME had based their assessment of statistical significance on a count of models, Heisel replied that IHME would not answer any more questions in email, .

Possible mistake?

Although difficult to countenance, distributing bednets in high transmission areas—like much of sub-Saharan Africa—might have been a mistake.

Intensity of malaria transmission worldwide. Darkest color indicates very high (>40 percent) infection prevalence and high transmission.  Gething, et al., “A new world malaria map: Plasmodium falciparum endemicity in 2010” DOI: 10.1186/1475-2875-10-378

Where malaria is intense, being bitten is a kind of deadly hazing ritual with survival conferring a degree of immunity. In very young, non-immune children, malaria infection leads to fever—and possibly death. The fatality rate of malaria infections is, perhaps contrary to expectations, very low. Only an estimated 0.3 percent of infections globally cause death. But infections are so numerous that hundreds of thousands of children die each year. Children who survive, however, generally can better control infections later in life and even show no symptoms while carrying perhaps millions of parasites.

Research in the late 1990s concluded that “a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life…” Malaria, including cerebral malaria and severe malaria, declined as children got older. Risk for severe malaria was highest where transmission was less intense, likely because people don’t acquire immunity without exposure to considerable infective biting.

Such natural tolerance is a mystery. There is no definitive set of biomarkers for it. And it’s no free pass: immunity may wane without some amount of continued infective biting, making severe disease a possibility.

One of the authors of the study, Robert Snow, now head of the public health group at the Kenya Medical Research Institute/Wellcome Trust Program, said recently, “I remain convinced that a certain degree of parasite exposure is required to develop functional immune responses to reduce risks of death and severe disease from malaria.”

Nets were originally targeted at children under five because most deaths from malaria occurred in that age range. But where malaria is intense, infection is unavoidable, with bednets deferring it to a later age. The age range least likely to sleep under a net is age 5 to 19. The most protected become the least protected—with potentially more adverse health consequences. Studies have found a shift in disease burden to older age groups following introduction of bednets. Trape and colleagues found this in Dielmo, Senegal. Other researchers, in an earlier 2009 paper, showed that nets reduced malaria risk in younger but not older children, a finding “consistent with older children having used [bednets] when they were younger, and therefore having acquired less immunity.” Thus to the extent bednets have saved lives in high transmission settings, they may also have created a population with reduced natural immunity, possibly setting the stage for a rebound of malaria.

“The issue of rebound and building up a time-bomb of susceptibles is interesting and you will find people willing to argue either side,” said Simon Hay, of Oxford University where he heads the Malaria Atlas Project.

The Global Fund’s Scott Filler said rebound concerns were “one major progenitor to move from targeted distribution of [bednets] to children under five to the goal of achieving universal coverage…” WHO switched to recommending universal coverage in 2007. (As the graph above shows, however, bednets distributed actually declined in 2011.)

Gerry Killeen of the Ifakara Health Institute in Tanzania believes rebound “is highly implausible unless the interventions themselves fail (resistance) or are withdrawn.”  His parenthetical mention of resistance, however, could mean trouble. Azra Ghani, of Imperial College London, and colleagues concluded that “If the effectiveness of the intervention gradually wanes, the impact on immunity is likely to be minimal and the incidence of clinical disease will return to pre-intervention settings,” perhaps ten years later.

Diaphanous nets and ghosts of the past

Bednets were hoped to be a precise, stealthy intervention beneath the notice of mosquitos. But protecting even a portion of the population appears to have engaged their evolutionary attention.  The switch to universal coverage also shifted the strategy: the purpose of the nets has become to kill mosquitos. “In order for their full potential to be realized,” reads the WHO position statement, bednets “should be deployed as a vector control intervention.”

However, if the goal was to knock transmission into an unrecoverable tailspin, it hasn’t worked. Transmission in high intensity areas dropped, but the force of infection still “needs a bit more help get it over a hump of stability that will impact on disease burden in the longer term,” said Robert Snow. The question is how because, continued Snow, the “expectation that [bednets] alone were to be the panacea in high transmission areas was misplaced.”

Resistance to DDT caused the technical failure of the mid-20th century effort to eradicate malaria. Nonetheless, over time, bednet policy has taken on a worrying semblance to this unsuccessful strategy. The previous effort didn’t even attempt to take on the heartland of malaria in sub-Saharan Africa, with some researchers arguing success was impossible using DDT. Also, planners of the oft-maligned effort actually knew resistance would be a problem where DDT was used and consequently they set a blitzkrieg timeline for achieving victory in a few years before resistance rose up. In comparison, the bednet strategy seems ad hoc and improvisational.

The coverage targets, initally 60 percent and then 80 percent, “were moved because we weren't going to meet them on time,” said David Smith of the University of Florida. “Instead of admitting nothing was happening, the intervention coverage target was increased and the date moved back—seeming to have some thought behind it, but mostly just saving face.”

Pyrethroid resistance was not part of the agenda at the Gates World Malaria Forum last October nor was it mentioned in congressional hearings on malaria last December. That omission may come from a concern, expressed by Killeen, “that doom-and-gloom stories will kill public enthusiasm for things that have saved many lives,” which he estimates to be half a million in Tanzania over the last five years. Scaling up such interventions “took a long time to get in place.” He concludes, “I am the father of two under fives and I live in a part of rural Tanzania where over 80 percent of people use [bednets] so this is a very real issue for me.”

Malaria is horrific, nature unsentimental. Sustainably reducing or ridding the disease from the world is unquestionably desirable. “But as we are now seeing,” say other researchers, controlling mosquitos with chemical killing agents comes at a price, “and the price is resistance.”

The long struggle: vaccines versus malaria

Photo: Caitlin Kleiboer 

"After clean water, vaccines may have saved more lives than any other public health intervention. Eradication of malaria, a disease that may have killed more humans than any other single cause, likely requires a malaria vaccine. However, after nearly a century of research, today’s only candidate might not pack enough immunological punch to win deployment. Sadly, there are no obvious successors. Goals for vaccines set in 2006 are now approaching, but may not be possible to meet."

Read the rest @ Ars Technica

Third in my series on malaria.

1) Drug resistant malaria takes new ground, raising fears of global spread

2) After artemisinin: searching for the next front-line malaria drug

Polio almost crushed in Africa—except Nigeria

In anticipation of future performance: Rotary recognized Nigerian president Jonathan Goodluck in April for his vision of a polio free Nigeria. (Photo: Nigeria PolioPlus Committee)

Polio cases across Africa are near zero, with the exception of Nigeria where they are surging, jeopardizing a continent that is close to polio-free after decades of effort. Nigeria and international agencies are taking measures to halt the recrudescence and prevent spread outside the country, but the amount of disease and mobility of populations gives the virus a fighting chance to kindle outbreaks elsewhere on the continent.

With India having rid itself of polio, Nigeria now is the main front in the effort to eradicate the virus. Nigeria is the only African country which has never interrupted transmission of the disease, making it a supplier of poliovirus to its neighbors and the rest of the continent. Nigeria made huge strides, bringing cases down to 21 cases in 2010.  But then public health lost out to politics. Elections in early 2011 turned attention away from polio and cases bounced back to 65 for the year. Already in 2012 there are 35, even though it is the low season for cases. The only other country in Africa to report cases this year is Chad with three.

Vaccination rounds have been scheduled in countries neighboring Nigeria, but polio’s renewed momentum could carry it to any number of places in Africa where population immunity is low. “That’s the big question,” says the Gates Foundation’s Apoorva Mallya concerning the possibility of export. “We are trying a lot of new strategies, but it is definitely a tough challenge,” he said. Outbreaks could go undetected in remote areas, becoming larger and even seeding secondary outbreaks, undoing at least part of the work in getting rid of polio.  At the same time, the Global Polio Eradication Initiative has become adept at swiftly extinguishing outbreaks. And the initiative has returned to the some of the same countries several times already to stamp out recurrences of polio.

The World Health Assembly voted last week to make polio a global health emergency, raising the profile of the issue and perhaps attracting additional funding for a project continuously declaring funding shortfalls. The emergency declaration could also mean travel restrictions for countries that fail to bring polio under control, Nigeria being the obvious candidate. Leaving the country might come to require proof of vaccination.

Polio also continues to roam freely in parts of Pakistan and Afghanistan. That locus is considered a lesser threat for exporting the disease, although polio did cross from Pakistan into China before being quickly smothered.

Nigeria, hard pressed today, is perhaps at best several years away from putting an end to polio. President Jonathan Goodluck has set 2015 as his target, and global health authorities believe Nigerian leadership is sincere in its efforts. As in India, the tactics or “micro plans” for vaccination are changing to emphasize mobile and remote populations which have been consistently missed, perhaps since eradication efforts began decades ago. India shows eradication can be done and, in many ways how, but also the enormity of the effort required.

Drug resistant malaria takes new ground, raising fears of global spread

Photo: Robert Semeniuk

In Southeast Asia, drug-resistant falciparum malaria may have evolved resistance to another frontline therapy and established itself in new territory in western Thailand, according to the World Health Organization. The new area in Thailand joins previous hot spots in Cambodia, Vietnam, and Myanmar, with the latter being badly equipped to stanch further spread. Despite containment efforts, the possibility this strain may spread to Africa, which has the most significant malaria burden, remains very real.

From my article in Ars Technica, first in a series on malaria.

Read the full story

Robert Semeniuk's stirring photo shows a man from Myanmar with severe malaria who walked with his wife for four days to cross the border into Thailand, coming to the Mao Tao clinic in the village of Mae Sot. A forthcoming Lancet paper will describe the detection of artemisinin resistance arising in that region of Thailand. http://www.robertsemeniuk.com

India triumphs over polio

A two-woman vaccination team in Firozabad, Uttar Pradesh, (Photo: UNICEF)

From my article on Ars Technica:

In the year since January 13, 2011, India has had zero cases of polio. Previously, India led the world, accumulating over 5,000 cases since 2000. Polio's last victim in India was 18 month-old Rukhsar, a girl in West Bengal who began showing signs of paralysis on this day in 2011. Now, epic immunization efforts have brought global eradication of the disease a giant step closer. Outside India, however, backsliding Pakistan and Nigeria and splotches of polio across Africa have blocked the final stamping out of the disease worldwide...

 

 

 

Globe-spanning effort tightens vise on polio; eyes on Angola

Statistics at left, tragedy at right
Closer to victory than ever, polio eradication efforts have intensified, with 2011 bringing new initiatives and funding to most every front in the global war on the virus. The encirclement extends from presidential palaces to the streets of Luanda, Angola to tent villages on the Kosi River in India. “[T]he reach is incredible,” said Ellyn Ogden, USAID’s polio eradication coordinator, “to the doorstep of every child in the developing world, multiple times… It is an extraordinary human achievement that is hard for most people imaging in a peace-time program.”
In India, for example, an army of 2.5 million vaccinator visited 68 million homes and immunized 172 million children; the president of India kicked off the January campaign. Cumulative efforts have driven cases in India to historic lows, just 42 cases last year versus 741 in 2009.
In Africa, 15 African countries launched a synchronized immunization campaign late last year with 290,000 vaccinators targeting 72 million children. But a similar campaign took place the year before—and the year before that. Yet despite these huge efforts, polio keeps coming back. Some countries like Burkina Faso have gotten rid of polio three times.
Nigeria once exported the most polio in Africa, but record-setting progress has occurred there. However, polio has developed a new stronghold—in Angola, which has fed explosive cross-border outbreaks. This year Angola will likely be the source of one third of the world’s polios cases. Continued transmission there has caused the Global Polio Eradication Initiative (GPEI) initiative to miss a major end-2010 milestone. “Angola now is almost the most important front in the global war on polio, and the whole world is watching to see how we do here," said UNICEF Executive Director Anthony Lake. Lake visited Angola with Tachi Yamada, president of global health at the Bill & Melinda Gates Foundation, in January.
Angola freed itself of polio in 2002 only to suffer re-importation—from India. Since then, 33 vaccination campaigns over half a decade have failed to stamp out the disease. Lack of political commitment explains these failures, according to multiple sources within the eradication initiative. Angola’s vaccination rounds have been staffed to a large extent by children. Inadequate supervision has meant just a few hours of vaccinating a day, with efforts dropping off further over the course of three-day campaigns.
Political commitment now appears solidly locked in. Visiting Angola, Lake and Yamada met with President José Eduardo dos Santos. “ ‘I’ll lead the campaign,’ ” Yamada said the president told him. The following day, Angop, the state-run news agency, ran the headline “Head of State committed to eradication of polio.” Subsequent news releases showed a domino effect down the political chain of command from the vice-president, to governors, to administrators of individual districts. One release identified a district manager by name and as acknowledging “the availability of the necessary conditions for vaccinators to reach all areas of the district,” likely coded language for placing direct responsibility on the manager for ensuring vaccination of the 156,000 children under five in that district.
The World Health Organization (WHO) places equal emphasis on community involvement in its formula for effective immunization campaigns. In the past, vaccination plans have been centrally created and handed down for execution. WHO finds that the best “microplans,” which map out block-by-block strategies and awareness efforts, are developed by the communities involved. In this way, “communities hold themselves accountable,” as Tim Petersen, a program
officer at the Bill & Melinda Gates Foundation, puts it.
Angola conducted a three-day polio vaccination campaign, February 23-25, across five high-risk areas of the country. A WHO spokesperson said the new decentralized planning led to some “hiccups” in execution. A report from independent monitors, expected in about a week, will reveal the quality of the campaigns which aim to immunize 90% of children under five.
[Note: I attempted to travel to Angola to cover the vaccination campaigns but was not granted a visa. The Angolan consulate in New York informed me four days before my flight that the signature page of my application was “missing,” that my letter from WHO did not meet requirements for documentation related to the purpose of travel and, still less plausibly, that the consulate had been trying unsuccessfully to reach me concerning these problems.]
High risk areas will be covered twice more in upcoming nation-wide vaccination campaigns. However, “It is clear that Angola has a tough few months ahead,” says Sona Bari, communications officer for polio at WHO. But Angola has beaten polio before. Today cases are relatively few, at about 30 a year, certainly in comparison with 1999 which saw more than 1,000. Also, the intensity of transmission is much lower in Angola than that faced by, say, India.
While political commitment seems to be in place, stability might be an issue. Some political tremors from Tunisia and Egypt have reached Angola, such as a call for public protest on March 7. (Recently Angola was without internet access for about two days which state media attributed to a cut cable.) Prior to the 7th, US State Department spokesperson Hilary Renner said she was not aware of “significant demonstrations in Angola.” The Associate Press report on turn out and reaction on the 7th suggests revolutionary force so far is not strong.
Rest of the World: Key Fronts
The eradication initiative must close out the major global sources of polio, India and Nigeria. India is closer to the goal and mostly needs to sustain its exertions. Nigeria trails but has made enormous progress; there are risks but today the country is essentially on track. If Angola too has turned in the right direction, Pakistan becomes the next focus.
Pakistan presents almost all possible obstacles to polio eradication. Like India, the oral polio vaccine in Pakistan fails to immunize among a significant number of children, usually under conditions of very low health and hygiene. Some parents in Pakistan refuse to allow their children to be immunized, a problem also once seen among Muslims in Nigeria who feared the vaccine had been purposefully tainted.
Much of Pakistan’s polio burden falls on border states with Afghanistan where security issues prevent vaccination teams from operating. The virus travels to more secure areas of the country where poorly run, corruption-riven vaccination campaigns fail to stamp it out. Even the house of a former minister of health was bypassed—twice—by polio vaccinators. “I had to call them to get my kids vaccinated,” reported the former minister.
Pakistan’s political stability is low. Natural disasters—huge flooding—have made a difficult situation worse. Last year saw a jump to 144 cases, up from 89. And so far in 2011, cases are accumulating more rapidly. Fortunately, the Pakistan/Afghanistan polio complex has not exported the virus to the rest of the world—so far.
Pakistan figured prominently in the careful eradication orchestrations of early 2011. Bill Gates met with President Asif Ali Zardari on January 15th. On January 25th, an emergency plan to immunize 32 million children was announced. The same day brought a joint announcement of $100 million in funding from the Gates Foundation and Mohammed bin Zayed Al Nahyan, crown prince of Abu Dhabi, to support vaccination efforts, with $34 million earmarked for polio immunization in Pakistan and Afghanistan.
Afghanistan offers ample challenges, including security problems. However the absolute number of cases, about 30 per year, is not extreme. Described as a “pretty strong program” by the Gates Foundation’s Tim Petersen, the Afghan polio eradication team appears to already enjoy the confidence of the members of the global eradication initiative.

The least controlled polio rampage is taking place in the Democratic Republic of Congo (DRC). Cases last year exploded to 100 versus three in 2009. The DRC and its northeastern neighbor, Angola, comprise an epidemiological block like Afghanistan and Pakistan. There is “huge cross-border traffic” between Angola and the DRC, according to Apoorva Mallya, a program officer at the Bill & Melinda Gates Foundation. A lack of roads and transportation infrastructure greatly complicate operations. For example, biological samples from possible polio victims sometimes must be floated down the Congo River en route to a lab for analysis.

The eradication initiative is looking at “local, local solutions,” according to Mallya. At the same time it seeks high level political commitment, just as in Angola and indeed all countries. WHO Director-General Margaret Chan travelled to the DRC in February to meet with President Laurent Kabila. UNICEF’s Anthony Lake then visited in in the first week of March and called for “an absolute commitment” to vaccinate every child.

New Trends in Media Coverage
The front in the polio war has been discouragingly broad and variable. Countries have been won and lost—some more than once. Low numbers or even single cases perpetually spatter the map. Gabon just reported a case, its first in more than ten years. Seemingly safe areas like Tajikistan and Congo have recently seen blowout epidemics. Transmission has become fully re-established in four African countries, not only Angola but also, for instance, Chad. Total cases globally have rarely dipped under a thousand a year over the last decade, giving rise to the view that this “last one percent,” like Jell-O, will squish somewhere else no matter how hard it is squeezed.
But the polio eradication initiative has focused on choking off the sources, following the strategy of von Clausewitz, who in, On War, recommended subduing the enemy “center of gravity.” In polio, that’s India and Nigeria. No other countries come close in polio burden. It’s not over, but India is astonishingly near to eliminating polio. The states of Bihar and Uttar Pradesh, where polio has been worst in India, haven’t seen a single case in six months. Among much else, this required tracking and immunizing enormous mobile populations. As many as six million people are on the move each day, according to a WHO estimate, with accessibility complicated by flooding of the Kosi River in Bihar. In addition, India’s eradication effort has overcome vaccine failure by achieving very high levels of population immunity: the virus basically can’t penetrate the thicket of immune people to access the vulnerable, those children in which the vaccine didn’t take.
The Associated Press recently recognized these developments in "India brings hope to stalled fight against polio."  ABC News posted a story in which progress in India provides hope for polio becoming “just the second disease to be wiped off the planet since smallpox.” (ABC News received $1.5 million from the Gates Foundation to support a television series on global health, making the representativeness of their current coverage more difficult to ascertain.)
Most recently, The Globe and Mail ran a polio package driving off successes in India, saying “Polio is all but gone from India…” (I have written to similar effect in Scientific American.) One article is entitled: “Anti-polio battle on verge of victory.”
No country has been as difficult as India. The obstacles in the countries of the rest of the world are largely different combinations of known problems which have been surmounted somewhere already. Polio has been expunged from anarchic, conflict-ridden states like Somalia. Rejection of vaccine by parents on cultural or religious grounds has been overcome in Nigeria. The quality and coverage of vaccination campaigns has been lifted even amidst rife corruption. Clearly, however, past performance doesn’t guarantee future results. Completely novel problems could arise. Failure on one or more of the numerous fronts in eradication is likely; compound failures could wreck the broader enterprise.
However, while feasibility remains an issue, coverage appears to be shifting—to whether the polio “endgame” can be won. The wild poliovirus is not the only threat to eradication. Very rarely, the oral polio vaccine, which uses a live attenuated virus, mutates into virulent form. Thus, in a sense, the eradication effort is fighting fire with fire, as a recent op-ed piece in the Los Angeles Times points out in “The Polio Virus Fights Back.” Not long after, Myanmar reported just such a case of vaccine-derived poliovirus. These mutants can—and have—spread. So far no related cases have been reported because the vaccine protects against it. And in Myanmar, “Immunization demand is high and the country conducts good quality campaigns,” according to WHO’s Sona Bari. In India, where oral polio vaccine dosing has been most intense, 2010 saw only one case of vaccine-derived virus. Rightly, however, the subject will likely gain in prominence in media coverage.
Not only has the nature of feasibility questioning changed, shifting to whether the next phase can be won, the position of arch critic of eradication now appears to be open. Donald Henderson played a key role in smallpox eradication but has long been skeptical of polio eradication. According to a January Seattle Times article, however, Henderson changed his mind six months ago and now believes polio could be eliminated. But not long after, The New York Times cited Henderson as a vehement critic of eradication. In mid-February, however, they ran a different story, Can Polio Be Eradicated? A Skeptic Now Thinks So, which (re-)disclosed that Henderson had changed his mind. The title of the earlier article in which Henderson was a critic also appears to have been changed online from “Critics Say Gates’s Anti-Polio Push Is Misdirected” to “Gates Calls for a Final Push to Eradicate Polio.”
At present, this leaves only the desirability of polio eradication in question. While no one argues for polio, there are other diseases which are more widespread, taking more lives and causing greater suffering. According to The New York Times, Richard Horton, editor-in-chief of The Lancet tweeted that:
“Bill Gates’s obsession with polio is distorting priorities in other critical [Bill &Melinda Gates Foundation} areas. Global health does not depend on polio eradication.”
The Gates Foundation, however, embraces the accusation. “We are overemphasizing polio,” says the foundation’s Tachi Yamada. Polio became the foundation’s number one priority late last year. And it’s not just Bill Gates or his foundation. In 2008, WHO Director-General Margaret Chan said “I am putting the full operational power of the World Health Organization into the job of finishing polio eradication… I am making polio eradication the Organization’s top operational priority on a most urgent, if not an emergency basis.”
But the emphasis on polio is indeed disproportionate. Both the Gates Foundation and WHO recognize that eradication would not just rid the world of a horrific disease: it would be a giant symbolic victory for global health. Chan, in her 2008 speech, also said “We have to prove the power of public health,” a goal which eradication would achieve. Similarly, Gates Foundation’s Yamada doesn’t want to give “fuel to cynics” by having eradication fail but instead to demonstrate that “this is what development assistance can do.”
Returning to the matter of eradication critics, The New York Times also quoted bioethicist Arthur L. Caplan, a professor at the University of Pennsylvania as saying “We ought to admit that the best we can achieve is control.” In June, 2009, Caplan wrote an opinion piece in The Lancet entitled, “Is Disease Eradication Ethical?” Caplan wondered if eradication was possible since it hadn’t worked after more than two decades of effort. The financial cost was high and diverted resources from better, more life-saving uses.
Caplan declined to comment for this article. However, questioning eradication as a strategy in global health, as polio demonstrates, is a worthwhile endeavor. And if polio resurges, so will skepticism of eradication.
Space Race to Human Race
The upcoming retirement of the Space Shuttle likely will attract enormous coverage. The Shuttle is not being replaced, however. And there are currently no plans for even a single human to permanently leave the planet. Still, the expectation of a spacefaring humanity persists although the 1960s might remain the golden age of manned space exploration.
In other words, the world has missed that the next giant step for humankind will take place on planet earth. The polio eradication effort might actually be larger than the Apollo program. Already in India, the number of cases can be counted down to zero; other countries might follow.
It’s a good story.

NYT Mistaken on Polio Eradication Feasibility

Whether polio eradication should be pursued or whether it is central to global health are questions that should be and are asked by The New York Times in “Critics Say Gates’s Anti-Polio Push Is Misdirected.” However, the Times also contends that “Victory may have been closest in 2006…” when victory may be closer now than ever before. And the latest blast of polio funding and initiatives, described by the Times, comes not because the eradication effort is on its heels but because it’s going for the kill.

Eradication hinges less on the number of countries suffering polio cases than on knocking out the sources—or “reservoirs”—of the disease. The two largest such reservoirs are India and Nigeria. Today, both countries have historic, record low cases. The Times describes this as “doing much better.” Perhaps also underappreciated by the article, wiping out the reservoirs of polio will stop outbreaks. The Times mentions outbreaks in Nepal, Kazakhstan, Tajikistan, Turkmenistan and Russia. All originated from India.

Further, the case of India seems to demonstrate that there are no scientific or technological barriers to eliminating polio. In particular, the Indian states of Bihar and Uttar Pradesh once were the most impregnable redoubts for the poliovirus anywhere on the planet. Yet, because of the huge expense and exertions described by The New York Times, Bihar and Uttar Pradesh saw nearly zero cases even during the “high season” for polio. (See my Polio in Retreat: New Cases Nearly Eliminated Where Virus Once Flourished.)

In Africa, Nigeria has been the most intractable polio problem. No sooner is eradication on track in that nation, than new sources—Angola, Chad, Congo and Sudan—arose to continue infecting the continent. Indeed, Angola and Sudan have even reverted back into polio reservoirs, the disease spreading within and across borders. The Times properly draws attention to this indisputable, highly problematic regress. But the obstacles to eliminating polio in Angola do not compare with those of India where the degree of difficulty approached near impossibility. And Angola has gotten rid of polio before. How did it come back? Cases imported from India, a reservoir now drawn down to historic lows.

The New York Times represents a crucial exception to the influence of the Gates Foundation on global health coverage. It is important to question whether, in retrospect, polio eradication ought to have been undertaken, given all the costs. Also, whether today polio ought to be treated as the number one priority in global health is likewise a valid inquiry. And the Times is right that the Bill & Melinda Gates Foundation has doubled down on polio eradication several times before in the aftermath of setbacks to the program. However, the recent slew of polio announcements and initiatives is not in response to setbacks. It’s to unload a knock-out punch while the opponent is staggered. It might work.