Category Archives: Research

Involving ‘Alumni’ in Strengthening the Tropical Disease Research Program

TDR PresentationsmThe Special Programme for Research and Training in Tropical Diseases (TDR – Unicef/UNDP/World Bank/WHO) seized the opportunity of the Multilateral Initiative on Malaria (MIM) 6th Pan-African Conference on Malaria in Durban 6?11 October to touch base with its ‘alumni’ who have received research and training grants over the almost 40 years since its inception.  A workshop was held discuss a new TDR alumni network platform and seek input on ideas for what that platform might look like and accomplish.

TDR has trained and supported thousands of researchers across the globe. We would like to assess how we can continue to support our alumni and their connections to people and institutions. This is a major new initiative that TDR will develop in 2014, and it wanted people who are familiar with TDR to provide feedback to initial plans for a new platform that will allow for better tracking of career progression and promotion, and to get ideas on how to increase opportunities for collaborations with other researchers and funders.

The idea of an alumni network was received enthusiastically by the more than 40 participants at the session, many of whom attested to the crucial role TDR played in their scientific careers either by supporting their doctoral studies or providing them grants that resulted in published work that help promote their careers.

Participants discussed various web based options where alumni profiles could be maintained and opportunities to share skills and solicit collaboration on research and training activities.  Other suggestions included an alumni newsletter and regular alumni meetings to coincide with international conferences that address the diseases of poverty.

TDR Director John Reeder said the organization was enthusiastic about receiving alumni input.  This participation will hopefully reinvigorate an organization that had been in a quiet transition over the past few years. The network will provide a good opportunity to learn how TDR investment in individuals and small teams has spawned further discoveries and disease control innovations.

On a personal basis, I can say that TDR grants to our team at the University of Ibadan beginning in 1981, helped us refine the concepts and capacities of volunteer community health workers (CHW) in tropical disease control including a contribution to guinea worm elimination in Nigeria, dissemination of pre-packaged anti-malarial drugs and refining the concept of the community directed distributor of ivermectin for onchocerciasis control and elimination.

These CHW principles have been worked into a new offering on Coursera, “Training and Learning Programs for Community Health Workers,” so that others can benefit from the lessons engendered through TDR support. Hopefully other alumni can use the network to share the benefits they have gained from TDR.

Research on Universal Coverage: the malaria examples

whr-2013-sm.jpgThe World Health Report 2013 entitled Research for Universal Health Coverage has been released. Since universal coverage has been a central Roll Back Malaria target since 2009, we have included below some of the mentions of studies and activities around malaria service provision and scaling-up.

The case for investing in research is made, in part, by demonstrating that scientific investigations really do produce results that can be translated into accessible and affordable health services that provide benefits for health… In one (example) a systematic review of survey data from 22 African countries showed how the use of insecticide-treated mosquito nets was associated with fewer malaria infections and lower mortality in young children. This evidence underlines the value of scaling up and maintaining coverage of insecticide-treated nets in malaria-endemic areas. (page xiv)

(Environmental risk factors) also contribute to the transmission of vector-borne diseases: malaria is associated with policies and practices on land use, deforestation, water resource management, settlement siting and house design. (Page 41).

By killing or repelling mosquitoes, insecticide-treated bed nets protect the individuals sleeping under them from malaria. By killing mosquitoes, they should also reduce malaria transmission in the community. Randomized controlled trials conducted in sub-Saharan Africa in a range of malaria endemic settings have provided robust evidence of the efficacy of ITNs in reducing malaria parasite prevalence and incidence and all-cause child mortality. Such trials showed that ITNs can reduce Plasmodium falciparum prevalence among children younger than five years of age by 13% and malaria deaths by 18%. (page 61)

(More research is needed because) In contrast with the findings of controlled trials, ITNs may be less effective in routine use because the insecticidal effect wears off, or nets may be used inappropriately or become damaged. The impact of ITNs, as used routinely, on malaria and childhood mortality is therefore uncertain.  (page 62)

As we can see from the World Health Report, malaria research has made a major contribution to our understanding of factors and effects of scaling up programs to try to achieve universal coverage.  As WHO recommends, more funding for health service coverage is needed, and malaria countries countries themselves need to contribute their own share in supporting their own research institutions.

TB setbacks: lessons for malaria control

Tuberculosis is one of the big three receiving Global Fund support, and like HIV and malaria control efforts, the emphasis is on multiple interventions to ensure ultimate success. Compared to the other diseases, TB’s interventions have been mainly limited to immunization and directly observed treatment. Both of these interventions have recently met some major challenges that have also plagued the other big diseases.

Roger Bate and colleagues, who have focused on the problems of fake and substandard malaria drugs have turned their attention to TB. (see ). Their investigation at pharmacies in 19 Asian and African countries found around 9% of TB drugs were substandard/poor quality. The rate of fake medicines was 16% in Africa and 10% in Asia.

Governments in these countries were encouraged to give these issues greater attention including better regulation and collaboration with international policing efforts.

The need for new vaccines is a necessary development to maintain a strong disease control arsenal. For TB, “A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG.” (as reported in The Lancet )

As the BBC report on this study pointed out, “BCG is only partially effective against the bacterium that causes TB, which is why several international teams are working on new vaccines.” (see BBC at )

While the new vaccine “… was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration.” Fortunately research on other vaccine candidates is underway.

Continued control and eventual elimination of malaria and TB will require research that is both basic (vaccines) and applied (drug quality) in order to develop, maintain and implement effective strategies. Disease research budgets should not be compromised in the ever changing world of pathogen/parasite evolution.

Dr Agomo – Congratulations on a Productive Career in Malaria Research

The Nigerian Institute for Medical Research (NIMR) in Yaba, Lagos has been a major player in generating knowledge about malaria for national and international policy makers. Just a few days ago, one of its distinguished researchers Dr. P.U. Agomo (BSc Hons, MSc, PhD, AIMLS) retired after 32 years of service. He had attained the post of Director  of Research  (Biochemistry  and Nutrition) at NIMR. Below is the citation provided by NIMR on the occasion of his send-off party, 13 August 2012.

agomo2.jpgDr Philip Agomo was born in August, 1947. He graduated from Greenwich University, London,  UK with  a BSc (Hons)  in  Biochemistry  (1973),  MSc in Applied Immunology from Brunel University, Uxbridge, Middlesex, England, UK (1977) and PhD from University of London, UK (1980).

Dr Agomo joined NIMR in 1980 as a research Fellow II and rose through the ranks of leadership to become the Director of Research (Biochemistry and Nutrition)  in 2008 and acting Director General of NIMR  from  July 2008 to May, 2010. Dr Agomo has also served the World health Organization (WHO) as an adviser on Antimalarial drug packaging for home management of malaria, appropriateness of childhood fever treatment in Africa, Health Sector Reform for Capacity Strengthening  and Malaria control in Africa and implementation  of community based management of Acute respiratory  infection  (ARI)  in Africa.

At the regional level, Dr. Agomo served West African Health Organization (WAHO) as an adviser on Health Research System Strengthening in the West African region. He also served as the Chairman of the Monitoring and evaluation sub-Committee of the National Malaria Control Committee (transformed  to NMCP in 2005) from 2001 to date.

Dr Agomo has also participated in many malaria control programmes at international,  regional, national and state levels as a Principal Investigator winning many  academic awards and research grants. Notable among these is the placement of NIMR as a training sub-recipient in the implementation  of global fund round 4 phase 2 (2008)  and round 8 (2010),  funded with about N150m Naira.

Dr. Agomo is well recognized not only for scholastic, administrative  and leadership qualities but also as a mentor of students and junior research scientists at NIMR, in Nigerian universities and outside the country. He has produced more than 10 PhD holders as a co-supervisor  in Malaria research (Pharmacokinetics,  Drug Resistance and Immunology),  Nutritional  Biochemistry  and Toxicology.  Dr. Agomo has to his credit over 80 scientific publications in peer-reviewed journals. He is happily married and blessed with two children. He is also a grandfather. 

Below are a few of Dr Agomo’s malaria-related publications that span his 30-year career:

  • Prevalence of malaria in pregnant women in Lagos, South-West Nigeria. Agomo CO, Oyibo WA, Anorlu RI, Agomo PU. Korean J Parasitol. 2009 Jun;47(2):179-83. Epub 2009 May 27.
  • Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria. Agomo PU, Meremikwu MM, Watila IM, Omalu IJ, Odey FA, Oguche S, Ezeiru VI, Aina OO. Malar J. 2008 Sep 9;7:172.
  • Treatment of childhood fevers and other illnesses in three rural Nigerian communities. Salako LA, Brieger WR, Afolabi BM, Umeh RE, Agomo PU, Asa S, Adeneye AK, Nwankwo BO, Akinlade CO. J Trop Pediatr. 2001 Aug;47(4):230-8.
  • Analysis of human antibodies to erythrocyte binding antigen 175 of Plasmodium falciparum. Okenu DM, Riley EM, Bickle QD, Agomo PU, Barbosa A, Daugherty JR, Lanar DE, Conway DJ. Infect Immun. 2000 Oct;68(10):5559-66.
  • Effect of chlorpheniramine on the pharmacokinetics of and response to chloroquine of Nigerian children with falciparum malaria. Okonkwo CA, Coker HA, Agomo PU, Ogunbanwo JA, Mafe AG, Agomo CO, Afolabi BM. Trans R Soc Trop Med Hyg. 1999 May-Jun;93(3):306-11.
  • “Antimalarial” medicinal plants and their impact on cell populations in various organs of mice. Agomo PU, Idigo JC, Afolabi BM. Afr J Med Med Sci. 1992 Dec;21(2):39-46.
  • Cell-mediated immunity in the liver of mice vaccinated against malaria. Playfair JH, De Souza JB, Dockrell HM, Agomo PU, Taverne J. Nature. 1979 Dec 13;282(5740):731-4.
  • Development and suppression of a population of late-adhering macrophages in mouse malaria. Lelchuk R, Taverne J, Agomo PU, Playfair JH. Parasite Immunol. 1979 Spring;1(1):61-78.

Lesson on World AIDS Day – don’t forget human behavior

This morning’s Washington Post featured a story concerning another setback in HIV/AIDS prevention research. The article stated that, “The abrupt closure last week of one part of a complicated study called VOICE marked the third time in eight months that anti­retroviral drugs did not prevent infection in those assigned to use them.” Ironically, the interventions had proven effective in smaller scale trials.  What happened during scale up?

logo-wad.jpgThe two research interventions focused on either having women insert a vaginal gel daily or people taking pills. One explanation offered for the failure the second time around was as follows:

The answers may lie in subtle differences between the groups being studied and the designs of the experiments. For example, the volunteers in Partners PrEP (pre-exposure prophylaxis study) were long-term couples in which one person was infected and the other not. It’s possible they may have been more motivated to take the pills every day. In CAPRISA (the South African PrEP study), the women inserted the vaginal gel before and after sexual intercourse rather than every day — a targeted approach that may have helped them stick to the program.

Such differences in the social and behavioral context of research make all the difference – basic research on drug effectiveness cannot be divorced from the people who receive the medications. The Post contacted experts who offered the following opinions about why there were problems.

  • The daily regimen just probably was not acceptable; if the gel were being used according to instructions some differences between groups should have emerged.
  • Other studies of vaginal microb­icides and pre-exposure prophylaxis have shown that few people use prevention tools as regularly as they say they do, but the more “adherent” people are, the more protection they get.
  • What we have to face up to is that everything in HIV prevention is based in human behavior.

The article concluded by saying, “What seems clear is that this strategy, once viewed as the easiest and most certain, is going to require a lot of fine-tuning even if it works.”

With malaria interventions, similar lessons apply. ACTs do not protect is people do not adhere to the 3-day regimen. LLINs do not protect if people use them to cover their vegetable gardens. IPTp is not effective unless pregnant women attend antenatal care regularly. Rapid diagnostic tests are wasted if health workers do not believe in their efficacy.

Often we wait until problems of non- or inappropriate utilization of health interventions occur before we start looking at social and behavioral factors. The Post quoted one epidemiologist who said, “People are upset. It’s a big head-scratcher as to why it didn’t work.” Researchers should be embarrassed to admit such, as this means they did not do adequate formative research in advance to understand the social and cultural context into which they were introducing their innovations.

Certainly similar mistakes have been made in malaria research and intervention, but now with international donor funding severely threatened, we cannot waste resources pushing interventions that are not socially and culturally acceptable.

Training and Research needs to support community engagement in malaria elimination

gawrie.jpgGawrie Galappaththy guided a session at the Asia Pacific Malaria Elimination Network’s Community Engagement for Malaria Elimination Workshop that helped participants summarize their group work on training and research to support community participation in malaria elimination.  Her report follows:

All the participants were agreed and thought that following training areas are necessary for effective community engagement for malaria elimination.  Thoughts about training included key topics and target groups as seen below.

  • Advocacy – Advocacy  is needed for all level including central, district, village level for all the category of staff
  • Partnership with other sectors- specially with the public sector as more than 50% of patients in most of the countries seek treatment from the public sector
  • Skills on communication methods – As most of the health personnel is not very much familiar with communication, methods it is important to train all the trainers on communication methods eg -COMBI, materials, participatory approach)
  • Resource mobilization- funds as well as personals
  • Integration with other diseases – community engagement as an integral part of the health (health package)
  • Training for community – training of community on every aspects of malaria
  • Strategy developments – most of the malaria programmes in their strategic plans not mentions the involvement of community in malaria elimination. It is important to include this aspect along with key activities
  • Skills on Monitoring & Evaluation – most of the countries engaged community for malaria control but lack M&E component. It is important to include M&E as an integral part of the elimination statergy
  • Empowerment of community for sustainability of community engagement in malaria elimination

Many research areas were identified by the participants, but need to priority areas depending on funds availability.  Examples of priority research issues included …

  • Cost effectiveness of engagement of community in malaria elimination
  • Improvement of drug compliance specially among migrant workers
  • Case studies or documentation of success stories
  • Promote treatment seeking behaviour specially in   malaria elimination countries
  • KAP studies on malaria especially since perceptions may change as we progress toward elimination
  • Role of community in malaria elimination
  • Effectiveness of village malaria posts/brigade in malaria elimination
  • Role of NGOs/FBOs in malaria using community engagement
  • Development and testing of Training modules
  • Research on new mechanisms of community  engagement for mobile population
  • Understand community structure and to identify the mechanism to sustain motivationAchieving synchronous cross boarder community engagement for malaria elimination

thai-cambodia-border.jpgOf particular interest in the region are the training and research needs to identify and test strategies for community engagement between countries – cross-border areas present a special challenge in terms of mobile populations and malaria medicine resistance. APMEN therefore, has to play a major role in advocacy as it is important to increase awareness among politicians, decision makers regarding cross border problems between countries. APMEN can raise a voice in international bodies such as SAARC, ASEAN, BIMSTEC etc.

Regular meetings in cross-border areas are essential at district/state level between countries eg  Bhutan and ASSAM, Bhutan and West Bengal.  There is need to address the issue of communication methods between countries taking into consideration ethnicity, language, cultural background etc

Priority Research and training needs for cross-border areas include descriptive studies to understand the migrant pattern, behavior, and risk groups. We also require needs assessment studies including assessments of existing facilities among border populations.

On the final day of the workshop, participants refined and prioritized these research and training topics for follow-up action back home.

New Journal: Malaria Chemotherapy, Control & Elimination

John Costa of Ashdin Publishing has written to let us know about a new open access journal on malaria: Malaria Chemotherapy, Control & Elimination.

mcce-final-web.jpgJohn Costa explains that, the new journal, MCCE, has been recently launched by Ashdin Publishing. The journal aims to bridge basic and applied malaria research in tropical and other settings.

MCCE will provide contributors with a forum for publication of research findings, in the form of basic science, clinical studies, case reports, and focused or general reviews of science or policy. MCCE is published using an open access publication model, meaning that all interested readers will be able to access  the journal freely online without the need for a subscription.

Although Editorial Board positions have not yet all been been filled, there is a significant contribution from the London School of Tropical Medicine and Hygiene (LSHTM) and alumni as well as other distinguished workers. The publishers hope to see the journal accepted as an essential forum in the coming years.

Of note, the journal will be affiliated with the Malaria Center at the London School of Hygiene and Tropical Medicine, which houses the largest number of malaria researchers, students and support staff in Europe. The Center is unique in its size and breadth and draws together the diverse research and teaching activities carried out at the School.

Malaria Treatment Guidelines – are health workers aware?

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.

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.

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. 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.