Tropical Health Matters

Malaria Journal published a few days ago an article comparing the costs of treating children and adults for malaria at a Nigerian hospital based on clinical diagnosis versus treating only when microscopy was positive for parasites. Normally we would pass abstracts from such articles on to members of our listserve (see link at right), but comments from a colleague in Nigeria gave pause.

He rightly pointed out that normally any research that helps us consider the factors involved in proper malaria diagnosis and treatment is welcome as we move toward universal coverage and elimination. His concern was that the researchers, who conducted their study in 2009, had not followed national malaria treatment policy and guidelines, which had been promulgated in 2005 based on the alarming growth of resistance of malaria parasites to the common, though cheap, antimalarials such as chloroquine and sulphadoxine-pyrimethamine (SP).

First the cost findings from the team at Bowen University Teaching Hospital (aka Baptist Medical Center, Ogbomosho) –

• For children, testing all but treating only Giemsa positives was $6.04/child
• Empiric treatment of all children clinically diagnosed was $4.49/child
• For adults, treating only Giemsa positives was $4.84/adult for treatment option one and $4.97/adult for option two
• Empiric treatment for adults was $4.14/adult for option one and $4.63/adult for option 2

In spite of the cost findings, the researchers did point out the drawbacks of empirical or clinical diagnosis in terms of accuracy and potentials for promoting drug resistance and called for scale up of rapid diagnostic tests (RDTs) to address these concerns.

The treatment regimens in this study included …

• Pediatric patients: artesunate (6-9 tablets of 3 mg/kg on day one and 1.5 mg/kg for the next four days) plus amodiaquine (10 mg/kg on days one to two and 5 mg/kg on day three in suspension)
• Adult option one: four and one-half 50 mg artesunate tablets on day one and nine additional artesunate tablets over the next four days, plus three 500 mg sulphadoxine/25 mg pyrimethamine tablets
• Adult option two: four and one-half 50 mg artesunate tablets on day one and nine additional artesunate tablets for the next four days plus nine 200 mg tablets of amodiaquine at a dose of 10 mg/kg on day one to two and 5 mg/kg on day three

National treatment guidelines specifically stress use of artemisinin-based combination therapy (ACT) for basic, uncomplicated malaria treatment.These guidelines are undergoing further revision with a stronger emphasis on ACT use based on RDTs and microscopy where available and recognition of the dangers of monotherapy drugs like chloroquine, SP and even artesunate itself.

The researchers from Ogbomosho are rightly concerned about cost issues, and being a private/NGO university and hospital, they do witness the direct effects of medication costs on patients that health staff in the public sector may not see.

This is still no excuse for not following national treatment guidelines when these drugs were available for their procurement in 2009. Now with the advent of the Affordable Medicine Facility malaria (AMFm) in Nigeria all health facilities, especially NGO hospitals like Ogbomosho, have no reason not to buy and dispense the correct medicines.

To re-emphasize this point, a press release from November 2010 clearly states –

“The Federal Government has directed all medical doctors and other health officials in the country to henceforth start using Artemisinin-based Combined Therapy (ACT) for the treatment of malaria disease in the country. Minister of Health, Prof. Onyebuchi Chukwu, gave the directive yesterday in Abuja during the ministerial press briefing on Affordable Medicines Facility (AMF) for malaria programme. According to the minister, the spread of malaria had become so critical that everyone in the country was now involved.”

We hope health workers in all sectors get the word! Hopefully national authorities will step up their efforts to disseminate guidelines to all front line health workers whether in public, private or NGO sectors.

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“:

A 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.

This 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.

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.”

A 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.

On an almost daily basis new research studies about malaria are published. What happens to these studies? In particular how does such research affect policies and programs? Wellcome Trust has reported that, “Research funded by the Wellcome Trust has helped shaped international and national health policy for two of the world’s most important public health challenges: malaria and dengue fever.”

Wellcome points out that, “Research by Dr Noor from the Kenya Medical Research Institute-University of Oxford-Wellcome Trust Collaborative Programme has fed directly into the Kenyan government’s 10-year plan for the monitoring and evaluation of malaria,” which was launched in November 2009. This research contributed to a refined mapping of malaria in the country which will enable better targeted interventions.

The study by Noor et al. led to a “Model based geo-statistical methods (that) can be used to interpolate malaria risks in Kenya with precision … our model shows that the majority of Kenyans live in areas of very low P. falciparum risk. As malaria interventions go to scale effectively tracking epidemiological changes of risk demands a rigorous effort to document infection prevalence in time and space to remodel risks and redefine intervention priorities over the next 10-15 years.”

There is a history of WHO and the Tropical Disease Research Program conducting and using research to update malaria guidelines and policies. The 2004 document, “Scaling up home-based management of malaria: From research to implementation” explains that …

Large-scale research studies and pilot studies have shown that scaling up home-based management of malaria is both feasible and effective – and is already being implemented on a limited scale in some African countries. Research experience and demonstration projects have provided guidance on how home-based management of malaria can be scaled up to reach the majority of populations.

In developing malaria treatment guidelines in 2006 WHO explained that, “Wherever possible, systematic reviews of randomized trials that directly compare two or more treatment alternatives in large populations were identified and used as the basis for recommendations.”

The dissemination and adoption of research at the country level may be slow. The value of Artemisinin-based Combination Therapy (ACT) was proven by the time Roll Back Malaria was launched over ten years ago, but it took five or more years before some countries adopted this medicine as first-line treatment. Even after a new treatment policy was promulgated, the actual practice of ACT use by practitioners in the field lagged another 2-4 years.

Researchers themselves often need to learn how to become advocates for their own findings. The Future Health Systems Consortium has stressed the need for the research community to learn about “influencing health policy at various levels, either as a direct or indirect outcome of the proposed (research).”  FHS stresses the “need for systematic analysis of strategies to promote integration of research into policy processes.”

Research will definitely be a crucial component for progress along the pathway to malaria elimination. Vaccine research continues, new drugs must be discovered, and better net distribution mechanisms should be tested. We must always facilitate communication between researchers and policy makers to ensure progress along that pathway.

Researchers from the Indian Institute of Health Management Research launched a report on the health situation of communities in the Sundarbans of West Bengal State yesterday. The According to the IIHRM team, led by Dr Barun Kanjilal, Sundarbans are a unique bioshpere of islands of mangrove forests in the river delta just south of Kolkata in West Bengal State, India.

The study conducted as part of the Future Health Systems Consortium examined the health and health care situation of the over 4 million people living on 54 of the 102 islands in the Sundarbans. Some of the key findings on health status include –

• General morbidity rate is higher that the state average
• There is a mixed burden of communicable (e.g. diarrhoea) and non-communicable diseases (e.g. coronary health disease) and injury (e.g. snake bite)
• Mental health problems are higher than expected
• Half of the children <5 years of age are malnourished
• Women have a higher burden of disease than men

These health issues must be viewed in light of the findings on health systems –

• Most care is delivered by informal providers known as rural medical practitioners (RMPs)
• Utilization of maternal health care is low
• Child immunization rates are lower than the state average
• There are serious shortages of public health facilities and trained human resources

These conditions were worsened by the effects of Cyclone Aila.

The team recommends developing what they are calling Basic Health Guard Units (BHGU) at the village level, which includes improving the skills of RMPs who were frequently found to prescribe inappropriate and even harmful medicines. In particular the BHGU should provide appropriate and timely treatment for common communicable diseases such as diarrheal diseases, respiratory infections, kala-azar and malaria.

India generally and West Bengal specifically are not highly endemic for malaria, which is usually seasonal.  Malaria deaths may be decreasing but continue to occur. Outbreaks result “from weaknesses in malaria control measures and a combination of factors, including vector breeding, low implementation of personal protection and weak case detection.”

Even in low endemic areas vigilance is needed to prevent, detect and treat malaria if elimination is going to happen.  If these proposed BHGUs bring better malaria diagnosis and treatment to the grassroots – or in this case the mangrove roots – West Bengal will be closer to eliminating malaria.

The Navrongo Research Center located in the Upper East Region of Ghana is observing its 20th anniversary. The Minister for that Region pointed out some of the important knowledge that had been generated at the Navrongo Health Center including, “the administration of Vitamin A to infants, the use of impregnated bed nets in the control of malaria, the Community-based Health Planning System (CHPS) compounds where health delivery and family planning services are made accessible to community members.”

According to Navrongo’s Director, much of current research including “an Artesunate trial, Intermittent Preventive Treatment (ITP) of Malaria in Pregnancy, Distribution channel for Schistosomiasis drugs on trial, the Bolgatanga-Urban Malaria Project, Malaria gene study, Use of Rapid Diagnostic Tests and Adolescent Sexual and Reproductive Health Project,” relate to malaria control.

Navrongo’s mission is as follows: “The NHRC is set up to conduct research into major national and international health problems with the aim of informing policy for the improvement of health. This will be achieved by focusing primarily on assessing the impact of interventions through community and clinical trials,social and demographic research, and human resource development.”

The Regional Minister lamented that this mission may be threatened. While Navrongo had contributed to “national development it was confronted with challenges including inadequate funds to support research work, its inability to attract and retain scientists and under developed infrastructure.”

Below are listed some of the more recent articles eminating from research in and around Navrongo. These demonstrate the wide variety of medical, social and biological research that such a field based research center can produce.  If we are to achieve malaria elimination, more and better funded research centers such as Navrongo are needed in endemic communities to ensure relevant answers are developed for the special challenges in each environment.

• Insecticide resistance profiles for malaria vectors in the Kassena-Nankana district of Ghana. Anto F, Asoala V, Anyorigiya T, Oduro A, Adjuik M, Owusu-Agyei S, Dery D, Bimi L, Hodgson A. Malar J. 2009 Apr 23;8:81.
• A randomized, comparative study of supervised and unsupervised artesunate-amodiaquine, for the treatment of uncomplicated malaria in Ghana. Oduro AR, Anyorigiya T, Anto F, Amenga-Etego L, Ansah NA, Atobrah P, Ansah P, Koram K, Hodgson A. Ann Trop Med Parasitol. 2008 Oct;102(7):565-76.
• A randomized, controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine, amodiaquine, or the combination in pregnant women in Ghana. Clerk CA, Bruce J, Affipunguh PK, Mensah N, Hodgson A, Greenwood B, Chandramohan D. J Infect Dis. 2008 Oct 15;198(8):1202-11.
• Understanding and retention of the informed consent process among parents in rural northern Ghana. Oduro AR, Aborigo RA, Amugsi D, Anto F, Anyorigiya T, Atuguba F, Hodgson A, Koram KA. BMC Med Ethics. 2008 Jun 19;9:12.
• Duration of protection against malaria and anaemia provided by intermittent preventive treatment in infants in Navrongo, Ghana. Cairns M, Carneiro I, Milligan P, Owusu-Agyei S, Awine T, Gosling R, Greenwood B, Chandramohan D. PLoS One. 2008 May 21;3(5):e2227.
• Amodiaquine in future combination treatment of malaria in Ghana. Oduro AR, Anyorigiya T, Koram K, Anto F, Atobrah P, Hodgson A. Trop Doct. 2007 Jul;37(3):154-6.
• Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana. Oduro AR, Koram KA, Rogers W, Atuguba F, Ansah P, Anyorigiya T, Ansah A, Anto F, Mensah N, Hodgson A, Nkrumah F. Malar J. 2007 Jul 27;6:96.
• Mutations in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance genes, and treatment outcomes in Ghanaian children with uncomplicated malaria. Duah NO, Wilson MD, Ghansah A, Abuaku B, Edoh D, Quashie NB, Koram KA. J Trop Pediatr. 2007 Feb;53(1):27-31. Epub 2006 Dec 10.

Two presentations today at the MIM 5th Pan-African Malaria Conference shared experiences with the use of mixed media channels to promote socially marketed malaria interventions as well as vouchers. Both speakers, Christopher Mshana and Hadji Mponda, are associated with the Ifakara Health Institute in Tanzania.

In both projects a mix of communication channels were employed such as road show/drama, poster, radio, newspaper, health worker talks, cinema, branded vehicle, and free cap/T-shirt.

The social marketing communication project found some important age and gender differences in perceived exposure with younger males more likely to have reporting greater contact with the interventions such as road shows, caps/T-shirts, the branded vehicle and cinemas.  It was surmised that women may not have the time to attend such events.Another challenge was that even among those who were exposed to the communication activities, olnly 60% mentioned a malaria prevention method like nets, and 19% recalled the need to get prompt treatment for children at the health center. Messages on caps/T-shirts seemed to be recalled better than those from other sources.

The project observed an increase in care seeking after the communication efforts, but their inquiry was not designed to directly attribute this to the media interventions. Overall only 35% of 3632 people interviewed reported contact with the program’s media efforts.

Costs of the communication efforts were not reported, but it certainly seems to have been an expensive way to learn which channels reach whom with what messages. One wonders if more targeted media and messages could have been developed through formative research prior to the intervention.

The project that examined mixed communication methods used in promoting the net vouchers interviewed 6260 households. They did look at people’s normal media use behaviors, and found that for media like radio, newspapers and posters there was increase perception of health messaging from these sources with increasing socio-economic status.  The did not observe gender differences.

Only 23% overall had seen messages on the Tanzania Voucher Scheme. The main media source for information was the radio (60% of those who had heard).

Communications is seen as a main component of malaria control interventions.  These two project reports show the need to design such interventions in a way that not only allows attribution to behavior change, but also compares the relative effectiveness and cost of different media channels in achieving desired program ends.

Wen Kilama of the African Malaria Network Trust brought a challenging idea to the malaria researchers gathered at MIM’s 5th Pan-African Malaria Conference on Tuesday. He explained that while we have a strong tradition of biomedical ethics that protect the individual from harm in research trials, we do not have a clear code of ethical processes, not the mechanism to oversee and regulate these for public or population health research.

His thoughts are also expounded in a current article in a supplement to Acta Tropica and ask us to consider difficult questions such as weighing individual protection and public benefit of an intervention beijng tested.  Examples of these have included immunization regimens, water fluoridation and iodization of salt. In malaria research we also must consider individual freedoms and choices balanced against the community protective effects of indoor residual spraying or wide coverage long lasting insecticide treated net (LLIN) campaigns.

Dr Kilama raised an interesting ethics about the distribution of two different types of LLINs.  One is a polyester multifiber net with insecticide coated yarn has received only Phase 2 approval from WHOPES, which approves insecticides for human safety. The other is a polyethylene monofilament net with insecticide incorporated into the yard. This has received Phase 3 WHOPES approval.  Ironically three times as many of the former were made available to the public than the later in recent years. Is this ethical?

Dr Kilama also raised an equity issue – how can we justify testing health interventions like LLINs on rural poor people who bear the greatest malaria burden when at the start of most programs, it is better off urban people who can afford the nets?

Corporate social responsibility also plays a role after research and testing for regulatory approval have been done. The manufacturers of the monofilament polyethylene nets have made provision for royalty free transfer and have already set up operations in one African country and are ready to move into others.  Their first African factory employs 6,000 people locally and has a positive economic impact on at least 30,000 in the community.

Ethical considerations in a population/public based research like vector control is complex. Community awareness and consent processes come at the start, but then effort must be made to enlist the informed participation of households and individuals.  Ghana’s Navrongo community research facility was mentioned as an example of an institution that has a codified community ethics process.

Dr Kilama called on the public health research community, and especially community malaria researchers, to develop consensus ethical procedures for community studies.

The first Plenary session of the Multilateral Initiative for Malaria’s 5th Pan African Malaria Conference in Nairobi started with Awa Coll-Seck, the Executive Director of Roll Back Malaria, emphasizing the role of malaria research in the Global Malaria Action Plan (GMAP).  She explained that the GMAP drew on malaria programming experiences over recent years to outline six main needs and directions for malaria research that will guide us from current control efforts into the future. These needs include –

• continuous research at each stage along the pathway, as well as continuous training of malaria researchers and all levels of malaria programming staff
• knowledge to help focus interventions locally and the burden of disease is changing and varies within and among countries
• how to achieve sustainability that reduces cases, reduces deaths and leads to eradication
• continuous advocacy for research and programming funds to see us through 2040 and beyond and based on evidence generated by program research and evaluation
• greater attention to social and cultural aspects of malaria control including community ownership and community systems strengthening
• maintaining a strong malaria partnership of diverse members including the research community

The importance of operations research (OR) in this process was stressed by Dr Robert Newman, the Director of WHO’s Global Malaria Program. Tying in with Dr Coll-Seck’s call for generating local research, Dr Newman noted the importance of enhancing the local decision making about program choices by using locally generated data.

A major concern expressed during the session was not just the need for more research funds designated specifically for malaria OR.  Very few countries use the availability of up to 10% of funds in their Global Fund Grants to conduct program relevant OR.

In contrast, Dr Newman reported that programs involved with Neglected Tropical Diseases use between 9-20% of their funds on OR.  He saw OR as a was to protect the investment of funds in disease control.

Today’s plenary session emphasized that research in malaria is not just an academic exercise. It generates new tools and helps us overcome program implementation bottlenecks.

Jambo

The Permanent Secretary of the Ministry of Public Health and Sanitation (MPHS), Mark Bor livened up the opening ceremony of the 5th MIM Pan African Malaria Conference in Kenya by encouraging the participants to greet each other in Kiswahili. He then introduced the Honorable Minister of MPHS, Beth Mugo.

The Minister stress key points in a malaria research agenda for the future and the importance of adequate investment in scaling up current and new malaria interventions so that eradication can one day be achieved.  She stressed research needs for …

• better diagnostic tools
• effective and affordable medicines
• vaccine development AND deployment
• community level vector control
• health systems strengthening including human resource capacity development

The Minister reminded the participants of the substantial increases in malaria funding over the past 10 years and the results that are becoming visible such as a 40% reduction in child mortality from malaria in Kenya.  Without sustaining this funding for research and intervention, she noted, we could see a backlash that made the resurgence of malaria after the failed eradication efforts of the 1950s and ‘60s look tame by comparison. Interventions must not only be sustained, but also improved, hence the need for continued research.

A regional approach is needed, the Minister stressed, since ‘mosquitoes don’t know boundaries.’ The Minister called on the malaria community to guarantee equal access of all countries to malaria resources as one country that lacks funds needed for control could help reintroduce malaria to its neighbors.  A regional approach to both funding and research is needed.

Karibu

see MIM Press Center here