For cholera, new tool buys time before an outbreak, but investment in water and sanitation wanes

10 Jun 2011

Patrick Adams

Source: TropIKA.net

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Cholera is easily cured. But when left untreated, it kills with speed. And in communities lacking clean water and sanitation, the disease can spread just as quickly.

The ability to predict when cholera outbreaks are likely to occur could allow governments and health officials to prepare in advance by mobilizing resources for vulnerable communities and responding early enough to contain outbreaks before they spread.

According to scientists at the International Vaccine Institute (IVI), that may soon be possible. Their analysis of climate records and cholera outbreaks between 1997 and 2006 in Zanzibar, Tanzania revealed that an increase of one degree Celsius in the average monthly minimum temperature was associated with a 2-fold increase in cholera cases within 4 months. An increase of 200 mm in rainfall presaged a 1.6-fold increase in cases within 2 months.(1)

Writing in the June issue of the American Journal of Tropical Medicine & Hygiene, the researchers report that “the interaction of temperature and rainfall yielded a significant association (P = 0.04) with cholera at a 1-month lag”—reassuring evidence that the two risk factors are “key drivers of cholera outbreak, consistent with results from other studies.” Those findings will inform the development of an early-warning system that lead author Rita Reyburn says could save lives and cut back on cases.

“We are getting very close to developing a reliable forecasting system that would monitor temperatures and rainfall patterns to trigger pre-emptive measures—like mobilizing public health teams or emergency vaccination efforts—to prepare for an outbreak before it arrives,” Reyburn said in a press release.

Although the model is still being refined—the researchers say more work is needed before it will be ready for routine use—the tool has been heralded as a major advance and one that could “transform medical care in impoverished tropical zones,” as the Guardian’s Ian Sample put it recently. “With a few months’ warning,” he added, “health services would stand a better chance of mobilizing pre-emptive measures, including vaccine programmes and the distribution of medication to vulnerable communities to combat the illness.”

Ironically, the most devastating cholera outbreak in recent years was not one that any weather forecast could have predicted. Rather, as a United Nations-appointed panel concluded last month, the past year’s cholera outbreak in Haiti was caused by fecal waste from UN peacekeeping troops that had been improperly disposed of, and was exacerbated by a number of different factors, including the salinity gradient of the Artibonite River, where the fecal waste was dumped, and the country’s “poor water and sanitation conditions.” (2)

As Haiti illustrates, an early-warning system that would allow for, among other pre-emptive interventions, vaccination of vulnerable communities can hardly be considered a panacea--and not only because cholera outbreaks can occur independently of changes in climate. Studies in Bangladesh and India have shown that oral cholera vaccines can now prevent many cases (3,4). However, Dukoral, currently the only cholera vaccine approved by the WHO, is, at roughly $40 per dose, far too costly for large-scale deployment in developing countries.

A second oral vaccine is already licensed and commercially available in India (as Shanchol) and in Vietnam (as mORCVAX). Developed by the IVI with support from the Bill & Melinda Gates Foundation (BMGF), the Government of Korea and the Swedish International Development Agency (SIDA), Shanchol is produced by Shantha Biotech, an Indian firm recently acquired by Sanofi-Aventis. The company is currently applying for WHO pre-qualification to produce Shanchol for international use and makes the vaccine available to developing countries at less than $2 a dose.

Still, vaccinating millions of people in a country as bereft of infrastructure, access to health care and education as Haiti would have been a daunting logistical challenge even before the January 2010 earthquake. For one, poor roads and a mountainous terrain make transportation in Haiti difficult. And then there’s the vaccine itself, which must be administered to patients on two separate occasions.

In October, 2010, the Haitian ministry of health (MPPP) and WHO rejected a proposal to vaccinate children under five living in two slums that had yet to report large outbreaks, citing the shortage of available vaccine as well as concerns that vaccination would lull people into a false sense of security, causing them to relax sanitary measures.(5)

Although the WHO has since changed its position on cholera vaccines in Haiti to potentially include such pre-emptive measures as those proposed in October, the decision to do so came only after “a growing clamor for ways to slow Haiti’s outbreak,” as New York Times medical correspondent Donald McNeil wrote.

Indeed, only weeks earlier, John Andrus, deputy director of the Pan-American Health Organization (PAHO) and a vaccine specialist, told reporters that “measures to prevent and treat [cholera] are so effective…that we don’t vaccinate our own staff on the ground or staff we’re sending there.” In January, after talks about how to proceed with a large-scale vaccination campaign had already begun, Andrus told Nature that the vaccination effort “won’t have a major public-health impact.”

In a joint statement on cholera prevention and care published last week in the open-access journal PLoS NTDs, a group of 44 leading medical and public health researchers, policymakers and practitioners made the case for a “comprehensive, integrated cholera response in Haiti.” Led by Paul Farmer, co-founder of Partners in Health (PIH) and United Nations Special Envoy to Haiti, they identified three principal goals: aggressive case finding and scale-up of all treatment efforts; strengthening Haiti’s water and sanitation infrastructure; and linking prevention to care by bolstering surveillance, education campaigns, and water, sanitation and hygiene (WASH) efforts.(7)

“Prevention must also include advocacy for scaled-up production of cholera vaccine and the development of a vaccine strategy for Haiti,” they add. “A vaccination campaign should be implemented if adequate vaccine and resources can be mobilized without undermining efforts to treat acutely ill patients or strengthen water and sanitation infrastructure.”

While the authors acknowledge that “past epidemics have been curbed without vaccines,” they believe that vaccination, “a pillar of prevention,” has a “significant role to play in Haiti given the vulnerability of the post-earthquake health, water and sanitation systems and the observed virulence of the El Tor strain.” The MSPP, they add, “has called for nothing less than a universal vaccination campaign—an end goal this document endorses.”

But why the ambiguity? An article about the joint statement in Science Daily states that the group regards vaccination as “essential to ending the crisis.” However, nothing in the document seems to support this claim; “significant” is not “essential.” In fact, the only thing the document describes as “essential” is the distribution of free water in the internally-displaced persons (IDP) camps, where cases have been relatively rare. Presumably, if Farmer et al felt the same about vaccination, they would have said so. Yet on the contrary, they allow that “the current epidemic could be curbed before [a sufficient vaccine] supply becomes available.”

Meanwhile, the media has largely ignored assertions about the primacy of effective water, sanitation and health delivery infrastructure. A vaccination campaign that undermines efforts to strengthen these services, the authors make clear, would not be acceptable.
“The lack of modern sanitation is a principal cause of fecal-oral bacterial transmission,” they write. Yet to date, “few substantial sanitation projects have been launched in Haiti.” And this despite the fact that as early as February 2010, health officials were calling attention to the fact that waste accumulation was creating the conditions for major disease outbreaks, including cholera.

“It has been decades since the basic human needs of water, sanitation and hygiene were explicitly addressed by the [World Health] Assembly,” wrote Yael Velleman, health policy analyst for the non-profit organization WaterAid, in an op-ed for the Guardian. “This is incredible given that the WHO estimates 10 percent of global disease could be prevented with safe water, sanitation and hygiene.”

Velleman reminded readers that the WHO has repeatedly stated that efforts to address cholera should focus on improving water and sanitation. However, she added, “We are now hearing more and more about vaccines in relation to cholera and other diseases”--including in the opening address to the World Health Assembly by WHO director general Margaret Chan, who noted that “new, powerful, more affordable vaccines are among the most important health developments of the year.”

“There is no doubt that vaccines have a role to play in ridding the world of many of its worst diseases,” Velleman added. “But they should not be a substitute for existing preventive measures.” If the results of a 2007 poll by the British Medical Journal are any guide, the scientific community agrees; the so-called “sanitary revolution” was voted the greatest medical advance in the past 150 years, beating out 15 other milestones.

“If past is prologue,” write Farmer et al, “there is little reason to believe that the ‘Haitian’ cholera epidemic will remain strictly Haitian for long…Cases traceable to the Haitian outbreak have already been reported in the Dominican Republic, Venezuela, Florida, and Massachusetts”—and now New York. These introductions, they write, are not expected to lead to disease outbreaks in areas with adequate water and sanitation systems. But for countries in the Caribbean and Latin America that lack these systems, they write, the threat of an epidemic is real.

The ability to predict outbreaks of cholera by monitoring trends in climate and rainfall represents a major advance likely to assist communities in averting thousands of deaths. And it may well transform medical care in vulnerable countries. But the development should not detract from efforts to improve the poor water and sanitation conditions that made Haiti’s cholera outbreak all but inevitable once the organism was introduced.

If the Haiti earthquake was a wake-up call for disaster response, the Haiti cholera epidemic may serve as a cautionary tale for neglecting to make the necessary investments in water, hygiene and sanitation. According to an OECD report released on World Water Day last March, funding from governments and the international community to meet water and sanitation infrastructure goals implied by the MDGs lags by $10-30 billion annually. And yet, as OECD Secretary-General Angel Gurria pointed out, “basic water supply and sanitation services are a good investment, with the savings outstripping costs by 7-fold.”

Indeed, a study by the World Bank-funded Disease Control Priorities Project demonstrated that promoting hygiene costs $3 per DALY, making it the most cost-effective of all major disease interventions, while sanitation costs just over $10 per DALY, putting it in the top ten. Still, the sector remains severely underfunded, and sanitation in particular is one of the most “off-track” MDGs.(8)

With regard to drinking water access, the WHO judges the world to be “on track.” However, according to Bartram and Cairncross, “the MDGs themselves are modest.” Writing in PLoS last year, they argued that even if the sanitation target is met, “1.6 billion people will still lack even a simple improved latrine at home.” The MDGs also ignore the need for sanitation and water in schools, workplaces and public areas. And though the drinking water target may well be reached in 2015, “800 million people will still live in homes where water is collected from distant or unprotected sources.”

Furthermore, they write, population growth is changing the picture: “Even if the target is met and the proportion of the unserved proportion is halved, neither the number of people unserved nor the global burden of disease will be halved.”

Headline indicators may be compelling in their simplicity, they add, but when the international community adopts a new set of goals for the sector after 2015, it should encourage progress improvement in both levels, quality of service and comprehensive access: “From the perspective of health, universal access to piped water and sanitation at home, school, and workplace must be the ultimate goal.”

References

Reyburn R, et al. (2011) Climate variability and the outbreaks of cholera in Zanzibar: a time-series analysis. Am. J. Trop. Med. Hyg. 84(6):862-869. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21633020
Final report of the independent panel of experts on the cholera outbreak in Haiti
WHO: Cholera page http://www.who.int/mediacentre/factsheets/fs107/en/
Clemens, Sack, & Harris et al. (1990) Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet 335: 270-273. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1967730
Sur D, Lopez AL, Kanungo S, et al. (2009) Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 374: 1694-1702. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19819004
Cyranoski D. (2011). Cholera vaccine plan splits experts. Nature. 470(7333): 175. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21248807
Farmer P, et al. (2011) Meeting Cholera's Challenge to Haiti and the World: A Joint Statement on Cholera Prevention and Care. PLoS Negl Trop Dis 5(5): e1145. Available from: http://www.plosntds.org/article/related/info%3Adoi%2F10.1371%2Fjournal.pntd.0001145;jsessionid=11981FFA5DA215318BCCDF304C5F722F.ambra02
WHO and UNICEF (2010) Progress on Sanitation and Drinking Water; 2010 update. Joint Monitoring Programme for Water Supply and Sanitation. Available from: http://www.who.int/water_sanitation_health/publications/9789241563956/en/index.html
Bartram J, Cairncross S (2010) Hygiene, Sanitation, and Water: Forgotten Foundations of Health. PLoS Med. 7(11): e1000367. Available from: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000367