Category Archives: Eradication

The Tail End of Eradication, an Elusive Goal

We are nowhere near eradicating malaria with hundreds of thousands of cases annually throughout the world.  It reappears in Greece, and in subclinical form stymies surveillance efforts in the Solomon Islands. But eventually we will close in on this parasite. What can we learn from eradication efforts of another scourge, polio?

Recently the Express Tribune published an article that provided some shock not only in Pakistan, where the issue was detected, but throughout the polio eradication community. “The Prime Minister’s polio cell, the World Health Organisation (WHO), and the United Nations Children’s Fund (UNICEF) confirmed … a newly-found strain of the polio virus.”

The technical reason for the new stain was explained by the international health agencies: cVDPV cases that cause type 2 poliovirus mutate and attain a form that can cause paralysis after passing through multiple children in environments with substandard sanitation. Fortunately polio associated with vaccines is extremely rare, but a more damning administrative explanation of why this may have happened in Pakistan is “poor routine immunization coverage” that enabled these mutations to occur.

Administrative problems include poor scheduling of the current immunization round during a sacred religious period resulted in four districts not participating, but on top of this was a more pressing problem,  “the global shortage of the oral polio vaccines especially as anti-polio campaigns are increasing .” This calls into question the upcoming second round of immunization in December. The problem is persistent since it was reported earlier this year that,  “Polio coverage (in Pakistan) remained sub-optimal during the past year in Islamabad, as revealed by an independent evaluation report on the post-polio campaign conducted by the World Health Organization.”

polio-cases-as-of-mid-november-in-2011-sm.jpgFour endemic countries remain as seen in the graph, and Pakistan’s performance to date is actually better than some of the others, but the situation is volatile, as is the civil/political situation in the remaining affected countries. Interestingly, another eradication-targeted disease, Guinea Worm, was down to 1058 cases in 2011 and remains in only 4 countries, but this is 17 years after the initial date set for its eradication.

Polio and Guinea Worm offer malaria some lessons for the present in countries approaching pre-elimination now and those who will hopefully join them over the next decade (if global funding levels are maintained). One lessons is that surveillance is an active part of current polio eradication efforts, otherwise these reports on progress and its challenges would not be published. But the key lesson is that regardless of the effectiveness of the technical intervention (e.g. a vaccine), deployment of the technical intervention is subject to human, administrative, managerial and social complications.

Polio focuses on a vaccine; malaria has treatment medicines, preventive medicines, insecticide sprays, treated bednets, diagnostic tests, and maybe also one day an effective vaccine.  It is not too early to plan on how to coordinate all this into achieving effective disease elimination, nationally, regionally and globally.

Reactive Malaria Case Detection – Tools for Elimination

Kelly M. Searle, ScM and her advisor at the Johns Hopkins Bloomberg School of Public Health, William J. Moss, MD MPH share the findings from her masters thesis: “Evaluation of Reactive Case Finding to Target Focal Malaria Transmission in Two Different Settings in Macha, Zambia.” They offer ideas on how we can move toward the challenging target of malaria elimination…

figure-1-rdt-zambia-sm.jpgWith malaria elimination in the minds of many, new methods of identifying and treating asymptomatic parasite carriers are being investigated. The current study evaluated reactive case detection as a malaria transmission intervention. Reactive case detection is the result of a malaria case being identified in a clinic by passive case detection, testing and treating that individual and their household contacts, and surrounding neighbors.

Survey sample data from different areas of Macha, Zambia in 2007 and 2008 were used to determine proportions of malaria infected individuals caught passively and reactively. Simulations were done to extrapolate this data to non-sampled households. Radii surrounding identified positive households (index households) were examined to determine the proportion of positive households in each radius.

In the 2007 transmission setting, screening 500 meters surrounding index households would have identified 89% of all households with an RDT positive resident and 90% of all RDT positive individuals. Screening 1 kilometer surrounding index households would have identified 95% of all households with an RDT positive resident and 94% of all RDT positive individuals (Figure 1). In the 2008 transmission setting, screening 500-meters surrounding index households would have identified 77% of all households with an RDT positive resident and 76% of all RDT positive individuals. Screening 1 kilometer surrounding index households would have identified 89% of all households with an RDT positive resident and 89% of all RDT positive individuals (Figure 2).

figure-2-rdt-zambia-sm.jpgReactive case detection has the potential to be an effective malaria intervention for populations of both moderate transmission settings and transmission settings transitioning (or that have recently transitioned) from moderate to low. With reactive case detection, a large proportion of malaria-infected individuals are accounted for using screening radius of 500 meters. A greater proportion of total households would have to be screened in the lower transmission setting, likely due to the overall lower numbers of cases existing. For reactive case finding to be most effective, it should be targeted at malaria foci and hotspots where transmission is greater than the overall area.

Scale-up Meets Resistance

News this week from The Lancet confirming suspicions of malaria parasite resistance to artemisinin-based drugs deals a double blow to malaria control efforts coming just a few months after announcements by Global Fund to cancel Round 11 funding.  Pressure on malaria drugs is nothing new, especially since the same problem has arisen in the same region of the world for two previous and cheaper mainstays of malaria case management.

In all our hopes for rolling back malaria over the past 14 years, did we tell ourselves that such resistance was this time not inevitable?   Unlike in previous waves of resistance, this time we should have been better prepared with effective anti-vector measures. BUT this assumes that we have met our RBM targets and are happily progressing toward 2015 expecting no more malaria deaths.

We get reports that scale-up and case reduction are occurring, such as a recent newspaper article from Jigawa State in Nigeria, but basically we have not achieved our 2010 scale-up targets – so what will come first – 2015 success or the wave of parasite resistance spreading out from Southeast Asia?

The hopes of the current RBM effort were based on the fact that by 2000 we had 3-4 effective anti-malaria interventions, unlike the reliance on mainly one during the first stab at eradication.  Unfortunately the question is still the same as it was in the 1950s-60s – are our health systems strong enough to deliver the goods? More effective interventions that do not reach people will not present a strong bulwark against spreading drug resistance.

mali-net-given-to-community-health-agent-2.jpgFrustration may mount even more when we realize that all the insecticide treated nets distributed over the prolonged period of campaigns from 2009-2012 will need to be replaced, mostly well before 2015.  Our coverage to date has not been adequate, our funding is threatened – what guarantees that we can keep up with adequately containing malaria before the resistant strains of the parasite reach Africa where the bulk of cases and deaths occur?

Some of our ‘easy’ eradication targets like guinea worm and polio are still flaunting their capacity to harm.  These like other previous efforts are at risk from donor fatigue.  Malaria, which is more complex than those two diseases, is at even greater risk. The RBM Partnership needs to develop a serious and workable strategy to get well ahead to the resistance wave NOW.

Closing in on Malaria Elimination in the Asia Pacific Region

malaria-distribution-in-asia-pacific-region-sm.jpgThe Asia Pacific Malaria Elimination Network (APMEN) is starting a workshop entitled ‘Building Competence in Connnunity Engagement for Malaria Elimination,’ tomorrow (22 November) in Chiang Mai, Thailand. APMEN includes 11 countries that are making clear progress to malaria elimination in the region.

The meeting will feature discussions on topics such as …

  • Lessons from 60 years of community participation in communicable disease control and elimination
  • Going to scale with community engagement for malaria elimination (models for equitable access and sustainability)
  • Experiences and challenges in achieving synchronous cross‐border community engagement for malaria elimination
  • Embedding community engagement for malaria elimination in comprehensive Primary Health Care delivery: A systems strengthening approach

Country case studies will be shared by Bhutan, China, Indonesia, Malaysia, Philippines, Republic of Korea, Solomon Islands, Sri Lanka, Thailand and Vanuatu. Discussions will focus on identifying intervention, training and research strategies to support elimination efforts.  Reports on the meeting will begin tomorrow.

How important are target dates?

If target dates were realistic, there would have been no more guinea worm in the world as of 1995. As it stands today

“Ghana appears to have broken Guinea worm transmission! With 7 consecutive months of zero cases reported since May 2010, and 14 months after reporting its last known uncontained case in October 2009, Ghana might have conquered Guinea worm disease! Surveillance continues while the Guinea Worm Eradication Program waits and watches. Currently, only four countries continue to report cases of Guinea worm disease: Southern Sudan, Mali, Ethiopia, and Chad.”

Sixteen years after the supposed eradication date approximatelt 376 cases were documented in the first four months of 2011.

Even the famous smallpox eradication effort could not achieve its targets until a paradigm shift occurred that changed intervention approaches from from maintaining high vaccine coverage to case containment that focused on outbreaks – vaccinating in a radius around cases until the disease disappeared.

Another set of goals – 80% coverage with key malaria interventions by the end of 2010 – has come and gone. The country with the largest burden of disease, Nigeria, was able to achieve around 67% of its insecticide treated bednet distribution target by 31 December 2011, let alone actual use by 80% of the population.  Nigeria is not alone in this situation.

The website, Global Atlanta, headlines that “U.S. Works to End Malaria by 2015”. While not technically true, the headline is followed by the actual goal – “The U.S. government is leading the way in ending malaria-related deaths by 2015, the head of the President’s Malaria Initiative said at a youth leadership conference organized by Usher’s New Look Foundation.”

nigeria-mdg5.jpgThe 2015 date refers to the Millennium Development Goals. Many countries find themselves lagging in in the interrelated MDGs (see picture). Our ability to reduce malaria mortality (if not morbidity) depends so much on health systems issues – procurement, supply, distribution, access, and use.

We have to be careful with public goal statements lest we create and then deflate expectations, with the unwanted side-effect of scaring away donors and national financial commitment.  Goals are a public relations tool – just be careful that they are realistic and don’t backfire.

Net coverage; how much is enough?

We are unlikely to eliminate mosquitoes, according to Tanya Russell and colleagues, but she notes that this should not stop us from implementing all available interventions. Specifically their study of malaria vectors in Tanzania found that the at reduced densities of mosquito populations, they try to reproduce more, meaning we may never get below 10% mosquito elimination.

Instead, a member of the National Malaria Control Program in Tanzania says our goal “should be to reduce, and eventually halt, transmission of the parasite, rather than eliminating the vector.” If we can achieve no more than 90% elimination of mosquitoes, what is a realistic coverage figure for malaria interventions?

Applications of net and case management strategies in Rwanda and Ethiopia have definitely shown that major drops in malaria incidence are possible.  But the RBM targets of 80% coverage (85% for the US President’s Malaria Initiative) are elusive.  Demographic and malaria surveys from Senegal, Liberia and Nigeria show that even in homes that own nets, net use among people at most risk, does not reach this target.

Are we really sure that 80% is the right target?

Fred Binka was one of the first to demonstrate that people living in homes without nets can be protected by their neighbors’ nets, which kill mosquitoes in the community. ITNs “provided very good personal protection to children using them, and also protected nonusers in nearby compounds. Among nonusers, the mortality risk increased by 6.7% with each additional shift of 100 m away from the nearest compound” with nets. This led the researchers to speculate on the need to study whether the “mass effect from a small number of highly dispersed nets would provide equivalent protection to complete coverage.”

A few years later William Hawley and co-researchers reported that, “protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels.”

As part of the move toward universal coverage, Killeen and colleagues examined the importance of considering all household members, not just the ‘vulnerable.’ The group condluded that …

Using field-parameterized malaria transmission models, we show that high (80% use) but exclusively targeted coverage of young children and pregnant women (20% of the population) will deliver limited protection and equity for these vulnerable groups. In contrast, relatively modest coverage (35%–65% use, with this threshold depending on ecological scenario and net quality) of all adults and children, rather than just vulnerable groups, can achieve equitable community-wide benefits equivalent to or greater than personal protection.

Barat has called for ‘data driven decision making‘ in the effort to eliminate malaria. Using data in models as done by Killeen is a further important step. The onchocerciasis control community has been working with such models for over 15 years now. New data are fed into the Onchosim model based on program progress such that it is possible to forecast that onchocerciasis could be eliminated from areas with high initial prevalence if 65% coverage of ivermectin treatment were maintained for at least 25 years.

Unlike onchocerciasis control, malaria elimination rests on multiple interventions.  This makes modeling much more urgent, as outlined by malERA’s research agenda for eradication. Since universal coverage unfortunately does not mean universal usage, we need to seek valid data and models to help us plan for distribution of malaria interventions more strategically in ways that are affordable and can be maintained and at the same time can achieve maximum reductions in morbidity and mortality.

thoughts on elimination

Sarah Boseley of the Guardian has opined that, “not to say that elimination should no longer be contemplated. It’s just more possible in some countries than in others.” Some comments we added to her blog follow:

When Melinda Gates used the ‘E’ word, she did add the caveat that eradication would not be in the immediate future, and as we have learned, the Gates Foundation has invested a lot in vaccine research.  Even with the addition of a vaccine, malaria elimination will continue to require multiple tools adapted and adopted according to the epidemiological situation of the area. Surveillance will continue to be the foundation tool for any effort to eliminate a disease.

The overall question of when can we start seriously talking about elimination requires a quick look back in history. Medical News Today in reviewing Feachem’s recent Lancet article, notes that, “Up to 1945, about 178 nations had endemic malaria. Since then 79 countries have eradicated the disease.” (Technically they have eliminated malaria since eradication only occurs when elimination country-by-country has occurred worldwide).  So 44% achievement in elimination over 65 years means _____ (your guess – fill in the blank).
There has been massive scale-up of malaria control activities over the past 5 years, but even with this, ensuring that an insecticide treated nets are inside a household does not guarantee that people will use them according to recent Demographic and Health Surveys and Malaria Indicator Surveys.

The danger of targeting a specific year is that once that year passes, donors and the public lose interest.  This is why it might be logical in the near term to ensure that appropriate malaria control and elimination activities are integrated into basic and universal primary health care services – which hopefully will not go out of style.

Is eradication really forever?

Spain has reported a case of indigenously transmitted malariaP. vivax. Although there are up to 500 ‘imported’ cases annually, it is believed that the local vector, Anopheles atroparvus, was responsible.

The last such case in Spain occurred in 1961. “Malaria was officially declared eradicated in Spain in 1964,” according to the Examiner. Technically the term for removing malaria from one country is elimination, while eradication is reserved for worldwide cessation of transmission, but whatever one calls it, the situation in Spain shows that we cannot be complacent once we think malaria might be gone from a country.

A similar experience occurred in Virginia in the USA in 2002. “Two cases of Plasmodium vivax malaria near the US capital seem to have been acquired locally from indigenous malaria carrying mosquitoes breeding in the area, not from malaria carrying mosquitoes escaping from Dulles international airport.”

Malaria shows a penchant for moving with its human hosts. In observance of the 400th anniversary of the settlement of Jamestown in the USA, National Geographic Magazine (2007) made the claim that, “Colonists carried the plasmodium (vivax) parasite to Virginia in their blood. Mosquitoes along the Chesapeake were ‘infected’ by the settlers and spread the parasite to other humans.”

botdistributiongrad.jpgMany countries on the frontline of malaria elimination such as Botswana and Namibia should be concerned. First more attention is being paid to high burden countries than those close to elimination. Secondly, opportunities to learn how to achieve elimination are not receiving donor attention. This attention needs to include strategies for keeping malaria out once elimination has been declared.

For example, in its Roadmap to universal coverage Botswana documents …

  • No specific govt allocation towards LLINS
  • National requirement for universal coverage is 400,000
  • Need to re-orient the program towards pre-elimination
  • Inadequate resources for malaria focal persons

Malaria is a moving target. Are we ready to keep up the chase?

Monkey Business – sharing disease

Humans and monkeys have shared and competed in the same environments, though not always to the benefit of monkeys.  In an interesting form of retribution for killing and eating monkeys, humans may have acquired the simian immunodeficiency virus (SIV) which mutated into HIV.

Although the earliest evidence of HIV was traced to about 60 years ago, a new study in Science as reported by the New York Times, suggests that monkeys may have harbored SIV for over 30,000 years. The Times notes that scientists have questioned …

What happened in Africa in the early 20th century that let a mild monkey disease move into humans, mutate to become highly transmissible and then explode into one of history’s great killers, one that has claimed 25 million lives so far? Among the theories different researchers have put forward are the growth of African cities and the proliferation of cheap syringes.

HIV is not the only health problem humans and monkeys share. Erma Sulistyaningsih and colleagues are among the most recent to address the problem of Plasmodium knowlesi, acquired from monkeys when tourists among others visit forests as a possible fifth form of human malaria in southeastern Asia including Indonesia, Malaysia, Vietnam,  the Philippines and recently in Myanmar.

There is also … “the theory of P. vivax originating in macaques in Southeast Asia and the close relationship to other primate malaria parasites.” Studies in Brazil also show that monkeys could serve as reservoirs for P vivax.

Researchers have also been exploring the “co-speciation hypothesis” in the relationship between P. reichenowi in chimpanzees and P. falciparum in humans. Hughes and Verra concluded that, “The available data are thus most consistent with the hypothesis that P. reichenowi (in the strict sense) and P. falciparum co-speciated with their hosts about 5–7 million years ago.”

Then last year Medical News Today reported that, “Researchers based in Gabon and France report the discovery of a new malaria agent infecting chimpanzees in Central Africa. This new species, named Plasmodium gaboni, is a close relative of the most virulent human agent P. falciparum.”

The authors of the Gabon study warn that, “The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria.” Similarly other researchers have expressed concern that, “Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria.”

Hence we see the lesson. In all our efforts to eliminate malaria, we do not want to monkey around with other possible reservoirs of infection.  Capacity to monitor our simian cousins is a key element in eventually ridding humans of the malaria parasite.

Does future eradication means lives lost now?

rbm-progress-report-3.jpgFirst the good news. Roll Back Malaria’s “Saving Lives with Malaria Control: Counting Down to the Millennium Development Goals” report provides encouragement when one reads that, “it is estimated that in the past 10 years, scaling up malaria prevention has saved the lives of nearly three quarters of a million children in 34 malaria-endemic African countries, 85% of these in the past 5 years alone.”

This is the latest report in RBM’s Progress Series and indicates that, “the results suggest that if current scale-up trends are maintained until 2015, another 1.14 million African children’s lives will be saved between 2011 and 2015.”

On the other hand, RBM warns that, “if funding were to cease in 2010 and prevention efforts were to fall, an estimated 476 000 additional children would die in that same period.” Is it possible that a greater focus on future eradication of malaria could distract from saving lives now and reaching the 2015 Millennium Development Goals?

The New York Times reported three years ago that, “challenging global health orthodoxy, Bill and Melinda Gates called for the eradication of malaria.” According to the Times, the Gateses labeled this call to action ‘audacious,’ while some partners called it ‘inspirational,’ ‘noble but quixotic’ and even ‘harmful.’

Now the Seattle Times reports that Bill and Melinda Gates are, “revamping the scientific agenda with their eyes on the controversial goal they set three years ago: driving malaria to extinction”

Justifying the focus, the Seattle Times indicated that, “Although total eradication of the disease may be as much as forty years away, it’s important to start work on drugs and vaccines that could take a decade or more to bring to the field, David Brandling-Bennett, leader of the Gates Foundation’s malaria programs.”

The implications of “The increased focus on the future means the Gates Foundation is ending its support for some efforts to lessen the disease’s current toll. Those include research to improve treatment of the severe infections that strike children and pregnant women, and that are responsible for most of the estimated 850,000 annual deaths from malaria,” according to the Seattle Times. Fears have arisen that this change by Gates, due to its financial influence, may pull resources away from other malaria research and program implementation efforts.

pledges-to-global-fund-august-2009.jpgOn the programming side, Gates has pledged 3% of the total Global Fund pledges as of August 2009, which is three-quarters of the funds pledged by all non-governmental organizations (foundations, corporations, etc.). While this is important, it is unlikely that even if Gates does not continue its support for programming, the bigger threat to major malaria funding sources – i.e. governments – is the current weak global economic environment.

We can all agree that Bill and Melinda Gates have influence. Currently they are using it to advocate to other wealthy individuals, corporations and foundations to contribute more toward charitable pursuits. In the area of malaria, they can also advocate with governments – both donor and endemic – to maintain and increase their financial support for malaria control and elimination. By then the new malaria tools deriving from Gates-supported research may be ready to carry elimination into eradication world-wide.