Category Archives: Mosquitoes

Ivermectin against malaria: novel idea, but can it be scaled

Several news sources have picked up on a new article in the American Journal of Tropical Medicine and Hygiene that reported when communities take annual ivermectin doses for controlling onchocerciasis and lymphatic filariasis, they may also be protecting themselves or their neighbors from malaria. Specifically the researcheds reported that ivermectin Mass Drug Administration (DA) “reduced the proportion of Plasmodium falciparum infectious Anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern Senegal.”

The process works the same way that ivermectin treats head lice in that when insects take a bloodmeal from someone who has swallowed the drug, the medicine kills the insect. Sarah Boseley points out that some of the attractions of ivermectin are that it has been safely used in humans for 30 years and that it is inexpensive.

The Merck company has been supplying ivermectin (under its brand name Mectizan) free through the Mectizan Donation Program (MDP) to the African Program for Onchocerciasis Control for 16 years.  Over time coverage has reached over 100,000 villages in 18 African countries. Annual distribution in Africa contrasts with more frequent distribution in the smaller focal transmission points in Latin America where the diseases has almost been completely eliminated.

MDP reports that, “Currently, more than 70 million treatments are approved for onchocerciasis in Africa and Latin America and 80 million for lymphatic filariasis in Africa and Yemen each year.” That is a lot of free medicine and one of the largest and far reaching corporate social responsibility programs known.

Back to Senegal – the researchers found that the effect of ivermectin on mosquitoes lasted up to two weeks. They also raise the question of whether more frequent ivermectin distribution in onchocerciasis or filariasis MDA communities during the main malaria transmission season would be feasible.  Possibly a small scale operations research proposal could be submitted to the Mectizan Expert Committee.

cdi_report_08.jpgOf importance is the fact that the Community Directed Treatment with Ivermectin (CDTI) approach utilized by APOC projects has been tested and found quite accommodating to the addition of other Community Directed Interventions (CDI) such as community case management of malaria, ITN delivery and use monitoring and Vitamin A distribution among other basic health services.

The availability of tens of millions of exra ivermectin doese in communities where MDA is already occurring is unknown at present, let alone the feasibility of starting free ivermectin in malarious areas that have no onchocerciasis or filariasis.  In addition, for onchocerciasis, the idea time for distribution is before the rainy season so that microfilariae loads are seriously reduced before the black fly vectors emerge. This timing may not benefit malaria control fully.

Regardless of the unknowns, it is encouraging that people are thinking of synergistic ways to control the various endemic diseases that inflict suffering on poor communities.

Mosquito Mis-Match

dscn3027sm.jpgVisiting a clinic in Binji Local Government Area of Sokoto State Nigeria today we saw the attached poster.  In fact there were three copies posted on walls in the public waiting areas. It was not clear whether this poster was intended as a job aid (reminder) for the health staff or a public education poster. If the latter, there is too much happening on the poster for it to be a good BCC material.

The main concern about this poster is that it implies that all mosquitoes are responsible for malaria. The pictures in fact implicate other mosquitoes such as the culicine species and Aedes aegypti.  Covering pots and getting rid of old cans and bottles will prevent mosquito breeding, but more than likely will prevent yellow fever, not malaria.

Clearing dirty gutters can prevent breeding of culex and the various viral diseases they carry, but not malaria. Yes, we want people to prevent mosquito breeding generally, as there appear to be no ‘good’ mosquitoes, but promising that preventing breeding of non-anophelene species will prevent malaria is misinformation.

We can be straightforward with the public and say there are many types of mosquitoes, and they carry many different diseases. It helps to prevent the breeding of all, but as different ones breed in different places, we can not expect every action will result in the prevention of malaria. We also need to stress that not all fevers are malaria, and we need testing to ensure the right medicine is given, not ACTs for dengue or west nile virus (which are carried by the other mosquitoes – adding to the public’s confusion).
At present there are two major vector control measures recommended by the RBM community – insecticide treated bednets and indoor residual spraying.  A few places have been successful with limited larviciding, but since breeding sites are ubiquitous, this is an almost never ending activity.  Lets focus on what is feasible.

Finally we need to recall that when we talk to local people about mosquito breeding, they may not understand what we mean by mosquito larvae.  Among the Yoruba, for example, these larvae are called tanwiji and are thought to be a different animal from actual mosquitoes themselves.  People have been confused by attempts at BCC on larval control thinking that health workers are saying that swallowing the tanwiji causes malaria.

Again, for now lets make headway with our treated nets and appropriately targeted IRS.  If we can achieve those coverage targets, the 2015 Millennium Development Goals will be achievable.

Mosquitoes also do not want to be infected

When the small copepod or cyclops swallows a guinea worm larva, seeing it as food, several things may happen as the larva develops – either someone swallows the cyclops when drinking the pond water, continuing the guinea worm cycle, or the larva grows so large that the cyclops is destroyed. Control measures have included putting temephos in ponds to kill the cyclops. All of these mean death for the cyclops. None of these alternatives bode well for the cyclops.

dscn0333-sm.jpgIt is not surprising to learn, as reported in PLoS Biology that disease vectors or intermediate hosts themselves are not very ‘happy’ to get infected with disease organizms that are later passed to humans. In essence Anophleles gambiae mosquitoes have genes that encode ‘essential components of the mosquito immune defense against malaria parasites.’

Furthermore, these genes are not static. Rottschaefer and colleagues report that, “Our data indicate that functionally variable APL1 alleles are evolutionarily maintained to combat diverse pathogens, perhaps including but probably not restricted to Plasmodium species.”

Most malaria control measures to date that involve the vector are aimed at killing, repelling or sterilizing.  These range from the newest, a toxic sugar bait, to the widely used instecticide treated bednets. There is exploration into a human vaccine that would prevent the parasite from developing in the mosquito.

While mosquitoes are certainly a nuissance in their own right, they are not necessarily the main enemy in the fight against malaria. We should certainly continue using bednets and indoor spraying and in appropriate cases larviciding, as major gains have been made from these. It would be hard though to completely eliminate the vectors.  Therefore continued research is needed on vaccines and genetic modifications that make mosquitoes a hostile host to plasmodium species.

The great outdoors … for mosquitoes

The press has had a field day over the publication of data in Science that identifies a new population subgroup of the African malaria vector Anopheles gambiae. The mosquito variant in adult form is hard to catch and in the laboratory, very susceptible to malaria infection.

The authors clearly point out that there is no evidence yet that the GOUNDRY mosquito, named after a village in Burkina Faso where the researchers worked, is highly attracted to humans. The press has rounded up experts like William Black, a medical entomologist at Colorado State University to speculate on the matter. Black was quoted in the LA Times thus …

“We’ve got egg on our face. We’ve been working with this mosquito for so long … and right under our noses, here’s this other form of mosquito,” he said — one that could force researchers “to start thinking about what’s going on outside of those huts.”

Again Science itself accurately headlines an editorial on the article by saying that these findings could have ‘unexpected’ results.

Because the new mosquitoes were found in the same larval pool collections and were genetically indistinguishable from indoor-resting adult mosquitoes, the options for control point to larviciding should ‘Goundry’ prove a threat to humans.  This is a challenging control measure as not all larval pools are easily visible and in fact may be multitudinous. Of course prompt and appropriate treatment and IPTp have to be part of the mix, despite health systems weaknesses in delivering medicines that may be more of a threat right now than the mosquitoes.

The key lesson is not that an immediate, previously unknown threat lurks outside our huts, but that nature and malaria can continue to surprise us.  We have surveillance in Southeast Asia for parasite resistance and the growing potential for human-primate malaria transmission, to name a few of the upcoming challenges to eliminating this ancient disease. Vigilence is the key.

Two for One – ivermectin and mosquitoes

Suppose that when mosquitoes bit you, they died. The possibility that a human blood meal can kill mosquitoes sounds far fetched, but has been observed as a by-product of mass community mass drug administration (MDA) of ivermectin for lymphatic filariasis in Senegal.

Researchers in Senegal compared villages where MDA was performed with a control set of villages and concluded that, “Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages.”

This is not the only time links have been made between malaria and lymphatic filariasis. A good example was community distribution of insecticide treated nets were provided in Nigeria, which curtailed the mosquitoes that carried both diseases.

In MDA programs for filariasis control “The goal is to treat 80% of the eligible, at risk population yearly, for at least 5 years, in order to interrupt transmission and prevent children from becoming infected.” The window of opportunity for collaboration between MDA and malaria control programs is therefor, very focused.

A smaller scale study reported in July of this year found that, “In mosquitoes feeding on volunteers given ivermectin the previous day, mean survival was 2.3 days, compared with 5.5 days in the control group (P < .001, by log-lank test). Mosquito mortality was 73%, 84%, and 89% on days 2, 3, and 4 in the ivermectin group." Since ivermectin started as a drug for veterinary parasites, it is useful to note that similar results on mosquitoes were found after cattle were given ivermectin. Researchers from Michigan State University* reported that, "Most (90%) of the An. gambiae s.s. that fed on the ivermectin-treated cattle within 2 weeks of treatment failed to survive more than 10 days post-bloodmeal. No eggs were deposited by An. gambiae s.s. that fed on ivermectin-treated cattle within 10 days of treatment." The authors concluded that, "Treatment of cattle with ivermectin could be used, as part of an integrated control programme, to reduce the zoophilic vector populations that contribute to the transmission of the parasites responsible for human malaria." community-ivermectin-distribution-in-buea-cameroon.jpgIvermectin distribution of course has been the major strategy of the the African Program for Onchocerciasis Control (APOC) for the past 15 years.  APOC’s efforts will continue much longer than those of lymphatic filariasis in over 100,000 communities throughout the continent.

More attention to joint planning and coordinating of malaria and other disease control efforts should be synergistic and mutually beneficial for the populations, who according to APOC, live beyond the end of the road.

*http://www.ingentaconnect.com/content/maney/atmp/2009/00000103/00000006

Update on Malaria Research in Mozambique

Arsenio Manhice, a journalist from Mozambique, provides us an update on malaria research at a leading institute in his country. A version of this report appeared in Portuguese in the newspaper “notícias“:

cism_logo.gifA series of scientific initiatives are underway at the Center for Research in Health Manhica (CISM) aiming to provide solutions to tackle the problem of resistance to drugs and insecticides used against malaria.

According to Eusébio Macete, Director of the biomedical research institute, among other initiatives, scientists are collecting mosquitoes that transmit the malaria parasite. The exercise includes an analysis of the different episodes of illness in people who arrive at clinics in the district of Manhica.

“We hope to have a block of information that can monitor the trend of malaria in its most complex context. That is why we consider the clinical aspects and impact of various measures are being introduced to control the disease as spraying, use of mosquito nets and medication,” the Director said.

For the purpose of study and possible solutions, the researchers began to distribute mosquito nets in the province of Sofala. Districts were chosen Inhaminga, Mwanza, Nhamatanda and Gorongosa.

dscn8015-sm.JPGThis is a joint initiative between the Centre for Health Research Manhiça, US President’s Malaria Initiative (PMI) of the United States, PSI and the National Malaria Control Program. PSI is involved in the local distribution of mosquito nets.

In Manhica CISM will monitor the transmission of malaria to know how it varies. “We do what are called cross-sectional studies that look at aspects such as the number of people who were infected and number of mosquito nets, houses fumigated and malaria cases registered in hospitals,” the Director said. It is an annual activity.

Studying malaria in pregnant women is another component of research that is being seen by scientists. This arises because one of the guidelines of the National Malaria Control is using intermittent preventive treatment with sulphadoxine-pyrimethamine (SP).

Due to the resistance of parasites to SP in other countries, the CISM is preparing a new alternative to save pregnant women. The initiative is from Mozambique and four other African countries. Having started in March 2009, the study ends in the middle of next year. “The goal is to see if mefloquine might have the same effect as SP in terms of preventing malaria in pregnancy.”

New solutions are not enough. Macete encourages people to use the tools to combat malaria are available. “Certainly there is a complexity that is the durability of the nets during the rainy season. The technicians who do the spraying must find the balance needed for example to do more patrols and use insecticides that last longer,” the Director stressed.

For now, the scientist believes that much work must be done to adjust the conditions of the country versus the available financial resources, characteristics of transmitters and type of insecticides available in the market.

Breweries should become malaria partners

PLoS One has just published a study from Burkina Faso entitled, “Beer Consumption Increases Human Attractiveness to Malaria Mosquitoes.” Beer and water consumers were compared and “Water consumption had no effect on human attractiveness to An. gambiae mosquitoes, but beer consumption increased volunteer attractiveness.”

african-beers-sm.jpgSpecifically, “Body odours of volunteers who consumed beer increased mosquito activation (proportion of mosquitoes engaging in take-off and up-wind flight) and orientation (proportion of mosquitoes flying towards volunteers’ odours).”  The authors therefore concluded that, “beer consumption is a risk factor for malaria and needs to be integrated into public health policies for the design of control measures.”

This is not the first study to look at what attracts mosquitoes to human beings. For example in 2003 Mukabana and colleagues found that “… mosquitoes preferred certain individuals despite being presented with emanations of three persons simultaneously.”

A year later BBC reported on another study the found that, “A key chemical found in
sweat is what draws the mosquito that spreads malaria in Africa to bite its human victims.” The researchers from Yale and Vanderbilt indicated that, “The chemical, or odorant, in sweat responsible for this attraction is called 4-methylphenol.”

Researchers from the University of Florida also explained that, “… the process of attraction begins long before the landing. Mosquitoes can smell their dinner from an impressive distance of up to 50 meters … This doesn’t bode well for people who emit large quantities of carbon dioxide.”

So back to beer drinking – the smells and chemical attractants emitted by the beer drinkers put them at risk. What can be done?  During these days of counting malaria out we need all the partners we can get.  We ask whether breweries are contributing their fair share to protecting their customers and the customers’ families from mosquitoes? Shouldn’t breweries contribute a certain portion of the price of each bottle to the national malaria control program or an appropriate NGO?

Breweries are known for having contests and give aways at local pubs in order to increase sales – instead of giving away caps and t-shirts with the beer logos, maybe they should now give out insecticide treated bednets with their logos.  The role for corporate responsibility by the breweries could not be more clear.

Research continues to target mosquitoes

If mosquitoes could read, they would know from two recent announcements that their way of life is threatened. Neither of the innovations is ready to go to scale, but both demonstrate the need for continuing research and new tools if malaria is eventually to be eliminated.

The attention grabber among these two tools is a laser gun that shoots down mosquitoes. At the annual TED Conference “Former Microsoft CTO Nathan Myhrvold says his company, Intellectual Ventures, can assemble electronic parts from readily available devices — printers, digital cameras, projectors — to make ground-to-air lasers that can take out mosquitoes.”

According to the New York Times, “Mr. Myhrvold said the software detects the speed and size of the image before deciding whether to shoot. It would reject a butterfly or a human, for example, and more powerful laser blasts could be used for locusts. In regions afflicted by malaria, the lasers could be used to create protective fences around clinics, homes, or even agricultural fields as a substitute for pesticides.”

laser-kills-mosquito-sm.jpgA video shows the laser in action shearing off the wings of mosquitoes. SmartPlanet.com reports that, “Altogether, the device could cost as little as $50, depending on volume. For now, it’s merely a proof-of-concept device.”  In addition to bring down the price, the inventors must ensure a battery operated model is available in endemic rural communities.

A second innovation is “A new insecticide against malaria mosquitoes has proved safe and effective as an alternative to DDT in an experimental trial in Benin, West Africa.” The chemical is the long-lasting insecticide, chlorpyrifos-methyl. N’Geussan and colleagues found that this insecticide, “killed 95% of An. gambiae that entered the hut as compared to 31% with lambdacyhalothrin and 50% with DDT.”

The challenge with chlorpyrifos-methyl was that it did not have the repellent power of the other insecticides and therefore may allow resistance to develop faster.  Still, this compound might be used in combination with other insecticides for greater effect.

The important lesson to come out of the insecticide research is that, “The remarkable residual activity indicates that cost-effective alternatives to DDT are feasible through modern formulation technology.”

So while neither of these innovations is ready for prime time, they represent a much needed inquiry into multiple ways that malaria can be controlled.  A recurrent theme at last year’s 5th MIM Pan-African Malaria Conference was advocacy for continued and increased malaria research support.  This is the only way to guarantee appropriate and effective malaria control tools are available when needed.

It takes a village to understand malaria transmission

Malaria researchers in Niger have been observing malaria transmission and mosquito populations in two villages over two years and discovered major differences even though the settlements are only 30 km apart. Finding a 10-fold difference in mosquito density, the authors conclude that, “The highly focal nature of malaria in the Sahel makes detailed representation necessary to evaluate village-level risks associated with hydrology-related vector population variability.”

kwaciri10.JPGOther factors affecting transmission differentials include seasonal availability of nutrients and predators. Ultimately the authors recommend, “Topography, vegetation, soil type differences as well as shallow groundwater behaviour must all be incorporated at appropriate scales in order to accurately evaluate malaria transmission at the village scale using coarse resolution climate models.” These issues should inform ‘malaria early warning systems’ at a more focused level, the village.

The researchers were concerned about, “The sudden appearance of widespread but temporary water pools gives rise to a rapid increase in mosquito populations clustered around human habitation, resulting in the highly focal malaria transmission that is a characteristic of Sahel villages.”  While these local variations are known, the problem arises when computer models lump together areas of tens to hundreds of kilometers in size together, missing the local differences that imply different control strategies.While the overall climate and vector behavior were not different, local hydrology was. The researchers specifically modeled differences in “local topography, distributed land cover type, and subsurface hydrology environment.”

Such differences in transmission dynamics have also been reported for urban malaria. For example, in Luanda, Angola transmission was more than four times greater in areas 15 km or more beyond the city core, compared with the central areas.  In Dakar, Senegal transmission was highly focal, and “no mean figures for transmission would provide a comprehensive picture of the situation; risk evaluations should be conducted on a local scale,” even for areas only a few kilometers apart. Urban agriculture provides another example of very focal transmission.

A the present moment when countries are focusing on large efforts to ‘scale up for impact’ the small scale or focal differences might be ignored. As we move along the pathway toward elimination, more focal surveillance and intervention will be essential for mopping up transmission and monitoring against reinfestation. Now is the time to build those surveillance systems so that countries and communities will not be caught unaware when malaria attempts to make a comeback some years hence.

When spraying may not hit malaria

The Ghanaian Chronicle has reported on a good example of public-private partnership, in this case between the Ministry of Health and a Waste Management fiim. “ZOOMLION Ghana Limited, the country’s waste management experts, in collaboration with the Ministry of Health, has begun a mass mosquito spraying exercise in the Western Region, which would cover all the 17 districts.”

The question arises as to whether this will really have any effect on malaria.  According to an official from the company, “This is part of a nationwide routine spraying exercise, which targets public toilets, urinal sites, container sites, refuse evacuated sites, drains and ditches, stagnant water, market places and finally, disposal sites, which we intend to spray to be able to control diseases and vectors.”

The sites listed above may serve as breeding grounds for Culex, Aedes and Anopheles mosquitoes – and in fact the operation is dubbed the “Nationwide Mosquito Control Programme (NAMCOP).”  Anopheles like clean, usually sunlit and stagnant (i.e. not moving) sources of water for breeding, and this being the rainy season, such places may be found among those listed.

dscn2552a.JPGSince the program is aimed at larviciding, it will is challenged in the case of anopheles by the multitude of tiny water puddles over wide expanses of territory.  These may not even be stable with the heavy rains being experienced now. It is unlikely in 33 days during this season that all mosquito breeding in the region will come to a halt. The article notes the valuable employment opportunities offered by the exercise as jobs will be available on the 420 spray teams, but these teams might be better employed distributing insecticide treated bednets throughout the region to guarantee universal coverage.

In the long term there are important lessons to learn from Aedes control in Latin America. Communies have played a major role in reducing the breeding of Aedes aegypti mosquitoes and dengue fever in Cuba, Argentina and Honduras, for example. Communities can maintain efforts over time, which is needed for sustained vector control.

While there are more resources for malaria control today than ever, they are not enough to achive elimination.  We should focus our efforts for now on the few key interventions that are known to work.