Tropical Health Matters

The Malaria Society of Nigeria is planning a seminar to update members and those concerned about controlling malaria in the country on management of malaria. The event will take place at the Nigerian Institute for Medical Research in Yaba, Lagos, on 12 May 2010 at 10 a.m.

There are many aspects to managing malaria, but to take only one – case management – is a challenge in itself.  The National Malaria Control Program‘s 2010 annual workplan outlines five key activities that need to be accomplished in order to properly treat a person who has suspected malaria:

• Parasitological confirmation of malaria cases by rapid diagnostic tests (RDT) and scaling up of diagnosis by microscopy
• Treatment of uncomplicated malaria with an ACT within 24 hours of fever onset through all health care providers (public and private)
• Expansion of access to free ACTs to community level through local human resources
• Early recognition and improved management of severe malaria cases
• Drug efficacy and quality monitoring

To this we should add ‘counseling’ of those receiving ACTs to ensure adherence to the full course of treatment.  As a recent Malaria No More posting noted, “The only pill that works is the pill that’s swallowed.”

The current national malaria treatment policy, guidelines and training materials were adopted in 2005. While these are technically correct in terms of stressing ACTs, but there is still a reliance on clinical or symptomatic diagnosis. While parasitological diagnosis is addressed in the current workplan, it also needs to be disseminated in easy to read guidelines and training materials.

Much has changed in the five years since the last malaria treatment policy and guidelines were adopted including the pressing need to use rapid diagnostic tests in primary health care facilities, the huge multiplication of brands of ACTs on the market, the impending large scale roll out of home management of malaria through community volunteers and patent medicine vendors, and related to the latter, the award of a pilot Affordable Medicines Facility (malaria) grant.

These changes are built on an unsteady foundation as documented in the 2008 Demographic and Health Survey. Three years after the national treatment policy had been updated, ACTs were very rarely reported in malaria treatment, as seen in the chart.

An ACT Watch survey in December 2008 of 468 medicine outlets (public and private) found that only 16.7% had the national firstline ACT – artemether-lumefantrin.  In all cases, the most common antimalarials in stock were non-artemisinin drugs.

Increased malaria funding for Nigeria from the Global Fund, DfID, USAID and the World Bank Booster Program should make ACTs and RDTs more readily available if supply and distribution systems are strengthened. This will only be effective if health professionals understand the national malaria treatment policy and the case management implications of proper parasitological diagnosis. We hope that the Malaria Society’s upcoming seminar can contribute toward this goal.

The old saying goes, ‘don’t look a gift horse in the mouth.’ Equine experts can tell a lot about the age, health and travails of a horse by examining the teeth and mouth.  The admonition not to examine an animal that is a gift might arise from not wanting to embarrass the giver, and why worry anyway if you did not pay for the horse.

It may me another matter when the intended gift is to be swallowed.

News reports record that, “The Chinese government on Monday (18 January 2010) donated over 244,000 doses of anti-malarial drugs to the Uganda in a bid to fight the deadly disease that kills over 320 people daily in the East African country.” The donation includes 144,000 doses of Arco and 100,000 doses of Duo-Cotexin.

Supplies of the same two drugs were also donated by China in April 2009. The two medicines apparently are not yet included in the country’s essential medicine list or listed as firstline treatments in the national malaria strategy/policy. “The drugs are, however, still awaiting pre-qualification from the World Health Organisation (WHO).”

Duo-Cotexin is a dihydroartemisinin plus piperaquine product (of which other brands include Artekin, Artecom, CV8) and is “given in a four-dose regimen that has proved highly effective and well tolerated in South East Asian trials.” ARCO is a combination of two drugs – Artemisin and Naphthoquine Phosphate. At present the only two combinations that have WHO pre-qualified products are Artemether+Lumefantrine (AL) and Amodiaquine+Artesunate (AA).  AL is the firstline treatment used in Uganda.

The two donated drugs apparently do offer a more convenient regimen than AL, which is taken for 3 days. “For Arco, its dose is swallowed once while Duo-Cotexin the tablets are swallowed once a day as prescribed by a doctor.”

The main concern is that when there are many different types of drugs on the shelves with different regimens, as is the case here, health workers and patients can get confused. There may also be different formulations for different age groups.

Granted, Uganda has not often had the luxury of too many malaria drugs, and shortages have been common. Thus, there may be the tendency not to look this gift horse (or medicine) in the mouth. Uganda, like most endemic countries, is definitely under pressure to scale up for impact this year.

We can only encourage the malaria partners in Uganda to practice pharmaco-vigilance with these donations and ensure thorough in-service education for health staff and patient education to promote adherence among clients.

BBC’s Focus on Africa has identified Africa as the dumping ground for counterfeit goods. Some are cheap knock-offs of branded luxury goods that consumers know are not the real deal. Electronics are another area where the customer should beware. Others camouflage as the original product with packaging that is indistinguishable from the authentic item.

Toothpaste is a good example where the fake, which retailers call ‘Chinese’ contains a poison known as diethylene glycol which is used in anti-freeze.  The retailers sell both products for about the same price, but the incentive for pushing the fakes is profit.

On the genuine product he has made a 13% mark-up, on the counterfeit an impressive 50%. Fair play to him, some might say – after all it is only toothpaste.

But one cannot say ‘it is only medicine’ when drugs are fake. BBC notes that, “According to the World Health Organization (WHO), 30% of medicines sold in developing countries are fakes, and a major problem is that high numbers of government-owned drugs are being illegally obtained and then sold on for profit in the private sector.” BBC worries that …

… with the rising number of direct trade routes between Africa and China, together with porous border controls, outdated legislation and weak enforcement mechanisms, the continent has become fair game for counterfeiters – and the recession has made it worse.

Furthermore, “A UN report published in July 2009 reveals that revenues gained from 45 million counterfeit anti-malarial medicines were worth $438m – more than the annual gross domestic product of Guinea-Bissau.”

SafeMedicines.org keeps an update of fake medicine reports. For example in Ghana, “A citizen brought suspect antimalarial medication to a sentinel site set up by the U.S. Agency for International Development (USAID)’s Drug Quality Information Program (DQI).” This was reported July 22, 2009, and involved a fake of Novartis Pharmaceuticals’ malaria product Coartem.

Researchers at Georgia Tech University shared information on the magnitude of the problem. “The percentage of over-the-counter counterfeit artesunate tablets containing no artesunate apparently increased from 38 to 53 percent in southeast Asia between 1999 and 2004.”

Fake drugs kill directly with dangerous ingredients or indirectly when inadequate or no active ingredients are present. They also may drive legitimate manufacturers out of business.  The threat is real and widespread in its impact.

The new funding program, Affordable Medicines Facility malaria (AMFm) aims to enable countries to place quality low-cost antimalarials into the private sector at prices that will supposedly compete favorably with inappropriate and fake medicines. Careful monitoring will be needed to see if this really happens.

Considering the profit margins mentioned above, the fake drugs may still out-compete the subsidized ones.  In short, nothing can replace a vigorous drug regulatory system and donors need to strengthen technical assistance to countries to regulatory capabilities actually work.

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.

In Guyana Stabroek News reports that, “Minister of Health Dr Leslie Ramsammy has thrown down the gauntlet to pharmacies to desist from selling the single dose artemisinin malaria drug by the end of this year or he would instruct officers from the Food & Drugs Department to size the drug from their shelves.” Guyana has been promoting ACTs since 2004.

In Guyana, the coastal areas are considered to be malaria free while the interior areas are considered to be high-risk malaria areas. Guyana therefore, may not me among the most endemic countries for malaria, but all endemic countries need to take the disease seriously, like Guyana’s Minister of Health, in order for global elimination to succeed.

Guyana has seen success in promoting malaria control. In endemic areas bednet use by children under 5 years of age increased from 7% to 70% between 2000 and 2006, according to the Multiple Indicator Cluster Survey.

Guyana’s Round 7 Global Fund proposal also aims to decrease malaria incidence by 70%. Included in the strategies are diagnosis and treatment with the intention that all health facilities (including the private sector) would be appropriately trained and equipped with microscopes and have adequate amounts of drugs and rapid tests. This is why the need for appropriate treatment with ACTs, not monotherapy drugs is being stressed.

As we have mentioned before, Guyana’s malaria control efforts are complicated by migrant miner populations in the endemic areas. It is such populations that may help drive the demand for cheaper, though inappropriate malaria medicines like artemisinin monotherapies.

An interesting irony is that WHO lists Guyana among the 16 countries that have never registered artemisinin monotherapy drugs. This implies that the availability of such medicines in Guyana is truly against the law and also shows how slippery the pharmaceutical import business can be.

WHO as of 16 November 2009, lists 33 endemic countries as not taking adequate steps to stop the sales of monotherapy artemisinin drugs.  Another 29 have “taken regulatory measures to withdraw the marketing authorization of oral artemisinin-based monotherapies after implementing ACT policy.” The approach of these 29 does not mean the immediate withdrawal of monotherapies, as some like Nigeria are simply letting the current registration of these drugs run out – meaning they may be on the market for another 2-3 years.

Unless all endemic countries take action like that proposed in Guyana, we may not be proceeding along the pathway to elimination, but down the road to drug resistance.

ICCM was the theme of a symposium at the MIM 5th Pan-African Malaria Conference last week. The organizers defined ICCM as a ‘strategy that delivers to the most vulnerable groups anti-malarials, antibiotics and a combination of oral rehydration therapy and zinc at the community level by trained community health workers.’ during the course of discussion CHWs were defined as people not only from the community, but also working in the community.

A little leeway has been taken with the latter definition in an ICCM study from Ghana where RDTs, ACTs, Amoxicillin and Paracetamol were availble for use by Community Health Officers posted in village health services known as Community Health Planning (CHPs) compounds.  Having both the RDTs and alternative treatment for pneumonia in the case of negative tests resulted in less overall drug use in the 8 intervention CHPs compounds compared with the 8 controls. Integration can only happen when health workers have all the materials they need to do appropriate case management.

Documentation of ICCM policy and program implementation for 68 countries was reported to the symposium. Only 55% of countries had a CCM policy for malaria, 50% for diarrhea, 30% for pneumonia and none for neonatal infections. Some countries were implementing without policies. Less than half had integration of three diseases – malaria, diarrhea and poneumonia.

Even with policies, not all countries implement CCM on a national basis, though there were examples of implementation across many or just a few pilot districts.

Potential barriers to CCM policy and implementation were identified through interviews with Ministry of Health officials from the selected countries. Common concerns were the ability to guarantee quality of care, incentives, supplies, monitoring and evaluation, training and supervision.

Ethical concerns were raised as to whether CCM really provides quality care to the poor.  In contrast, presenters working in post-conflict areas found that these situations provided opportunities for creative thinking on how to reach disenfranchised communities.

The session did not have time to get into the role of the informal private sector – especially patent medicine vendors – in CCM.  Also the focus on individual CHWs tended to divert attention away from the word ‘community.’ It is hoped that CCM can take a leaf from the Community Directed Interventions process and focus on strengthening community leadership and systems to take charge of health matters, and not rely solely on an individual CHW who may be here today and gone tomorrow.

NOTE: ICCM training materials and job aids are being consolidated by WHO/Unicef. The CORE Group also has a set of CCM training materials under development.

The ACT Consortium is in the process of addressing four key issues in ACT delivery through research projects in 9 countries with around 21 partner institutions according to a symposium Thursday at the MIM 5th Pan-African Malaria Conference. The Consortium had a long gestation period with the idea being floated around 2001 and final funding securred in 2007.

During that gestation period millions of doses of ACTs have been delivered, and is universal coverage is to be achieved in 2010, millions more doses will have to be provided next year and beyond. Research results from the consortium may not come online for a few more years, and we hope that the findings will be relevant for sustaining treatment during the crucial years between scale-up and pre-elimination.

The four key areas for research into how to improve access to appropriate, high quality medicines are as follows:

1. Access – including equity issues
2. Targeting – with a focus on improved diagnostics, cost-effectiveness and supply management
3. Safety – drugs are licensed after trials on only 6,000 people, so surveillance for rare adverse events is needed as well as interactions with other medications (e.g. for HIV)
4. Quality – addressing substandard, fake/counterfeit, and degraded (through transport, storage) medicines

Panelists shared their research plans which included, for example, the possible effects of RDT use on rational prescribing. There is also interest in finding out what prescribers do when RDT results are negative, which depends on having treatment for alternative causes of fever.

There is a strong social science component that will explore provider and user perceptions and the determinants of the decisions they make to prescribe medicines and use them.  In Ghana the studies will have important economic implications for their national health insurance scheme.

In Tanzania where ACT access among children was said to be only 14% at present, the research is addressing the private sector and may tie in with the greatly anticipated AMFm grant. Tanzania is trying to scale up efforts at improving the quality of private sector medicine shops through training and franchising in Accredited Drug Dispensing Outlets – the ADDO shops. A Herculean effort to bring 10,000 new shops on board will be aided by research in at least 3 provinces.

Answers to many ACT access questions are needed now. We happily await the results of the ACT Consortium’s efforts. In the meantime countries should also use the operation research funding available through their Global Fund and soon to be deployed AMFm grants to answer more immediate delivery and bottleneck questions. Basic procurement, supply and use monitoring will also go a long way to inform our efforts to guarantee appropriate universal coverage of ACTs.

The potential demise of presumptive treatment for malaria was the topic of a ‘Controversies’ session at the 5th MIM Pan-African Malaria Conference on Monday.  One view was expressed by Ambrose Talisuna from Uganda Ministry of Health that as we move into the phases of sustained control toward elimination, there will be a greater need for parasitological diagnosis of malaria and more rational provision of ACTs.  Since the process of policy formulation to full implementation may take 2-4 years, Ambrose Talisuna thought it would not hurt to get started on efforts to update malaria treatment guidelines to emphasize a parasitological diagnostic component as a requirement for prescribing ACTs

Another perspective expressed by Mike English from Kenya Medical Research Institute was that it may be very difficult to change case management norms away from presumptive treatment until we can increase the confidence of clinicians in parasitological diagnostic methods by guaranteeing quality. Also there is concern that at least half of children in endemic areas live in high burden countries where presumptive treatment is still be a rational choice.

An interesting viewpoint came from Franco Pagnoni from TDR who said all treatment is presumptive. Even with parasitological diagnosis there are presumptions based on perceived quality of the diagnostic procedures and their interpretation.

There was a general sense that some Rapid Diagnostic Tests are clearly effective under research conditions, but have not been thoroughly tested in real life clinical conditions.  Another RDT challenge includes the general procurement and supply management difficulties facing all malaria commodities. There are cost issues too – will AMFm or a similar effort guarantee affordable malaria tests?  Another challenge of malaria treatment is the private sector, especially the informal component, and the community/home – how far will RDTs be distributed, and how can quality be maintained under such conditions?

As with all our efforts to move toward elimination we must recognize that different countries and different regions within countries are at different epidemiological stages.  We need development of flexible and appropriate case management and diagnostic guidelines. These must be disseminated in a way that builds diagnostic capacity at all levels – from the research lab to the community – with back-up to ensure 1) RDT and microscopy quality and 2) training that builds clinicians’ and treatment providers’ confidence in the tests and their own ability to use the tests correctly.

In a relatively short period, 2003 – 2007, all malaria endemic countries in Africa adopted artemisinin-based combination therapy (ACT) drugs as their nationally approved first line treatment.  Unfortunately the uptake of ACTs in actually treating children remains extremely low. The Press Center at the Multilateral Initiative for Malaria 5th Pan-African Malaria Conference hosted a press conference to highlight efforts to promote and keep track of ACT use.

Suprotik Basu, Advisor to the UN Special Envoy for Malaria, moderated the panel and explained that the United Nations is promoting universal coverage of correct and prompt malaria treatment by the end of 2010 with a goal of ending malaria deaths by 2015. This is a huge challenge starting from a baseline in 2006 of only 3% of children who received any malaria treatment getting ACTs.

While there are efforts underway to ensure that more ACTs will be available at prices people can afford, including the new ‘experimental’ program Affordable Medicines Facility – malaria (AMFm), it is also important to have a mechanism in place to track what is happening with ACTs.

Des Chavasse, PSI’s Vice President for Malaria Control and Child Survival, is also heading up the ACT Watch project, funded by the Bill and Melinda Gates Foundation. ACT Watch is monitoring malaria medicine outlets – public and private – in 7 countries in Africa and Southeast Asia and conducting community surveys to achieve this goal of ACT tracking.

At its start, ACT Watch has documented that more than half of parents access malaria medicines for their children in private outlets, and where ACTs are available in these shops, a rare occurrence, they can cost 10 to 20 times more than the (ineffective) common treatments available. Many parents are not aware of ACTs as the new approved malaria medicine, but those who do are four times more likely to get ACTs at a private outlet.

While efforts are underway to promote and track ACTs, ACT Watch is also tracking the distribution of other antimalarials.  Peter Olumese who focuses on malaria case management at WHO’s Global Malaria Program, explained that due to cost and communication challenges, monotherapy artesunate drugs are often sold in the private sector. This will exacerbate the development of resistance of malaria parasites to artemisinin-based drugs. The availability of effective and cheap ACTs through programs like AMFm will hopefully drive the ineffective or dangerous antimalarials from the market.

Oliver Sabot from the Clinton Foundation shared that although US$ 180 million was now available annually to buy ACTs, but in the best situation only about 25% of children who receive malaria treatment get ACTs.  There needs to be a dramatic scale-up if even 80% coverage is to be achieved by the end of 2010. AMFm may make a dent if ACTs can actually reach the consumer at only 5% of current retail costs.

The most exciting aspect of the press briefing was a report by Ambrose Talisuna who represents Medicines for Malaria Venture in Uganda. Uganda has been experimenting with with subsidized ACTs in the private sector. Child doses are only 10 US cents and 40 cents for adults in contrast to $US 6-10 generally.  ACT market share has increased from below 1% to 50-60%, and consumers seem to like ACTs. At the same time share of ‘obsolete’ malaria medicines in the market has dropped by 50%.

AMFm will not be a magic bullet to achieve universal coverage since the first few pilot countries will not receive funding until 2010 at the earliest. AMFm will also operate for only 2 years until an evaluation will guide further work. In the meantime more efforts like those in Uganda are needed – nothing stops countries using their existing GFATM grants to subsidize ACT costs in the private sector as Nigeria is doing.

A consensus has evolved that as malaria interventions become more widespread and successful, the need for Artemisinin-based Combination Therapy (ACT) medicines will decrease in endemic countries.  As a case in point, The RBM Needs Assessment produced by Burkina Faso in 2008 and used as a base for planning the Round 8 GFATM proposal projected a decline in the number of P. falciparum malaria cases and hence, a decrease in the need for ACT supplies.

While the attached chart shows a projected decrease in malaria cases starting in 2009, there is little evidence that LLIN distribution and use are adequate enough at present to produce such a drop.  Burkina Faso’s RBM Road Map shows that the most recent coverage is LLINs is 24% for children below 5 years of age and 28% for pregnant women.

Furthermore, the major distribution campaign to achieve universal coverage of LLINs in Burkina Faso is not slated to take off until July 2010 at the earliest.

Specifically, the Global Fund reports that, “The Global Fund has shown that where distribution of insecticide-treated bed nets (ITNs), spraying and treatment are scaled up to national population coverage, malaria cases and child mortality can be reduced by up to 50 percent.” It appears that in the countries cited, less than 80% coverage was able to achieve up to 50% reduction in cases over a couple years.

The major challenge though is how to ensure coverage/use after a big campaign, since actual use if often much less than proportions of households possessing nets. Then too, there is the challenge of promoting continued use. Lea Pare Toe and colleagues recently reported research findings on decreased motivation to use ITNs in Burkina Faso. Factors included –

• Acceptance was moderated by the fact that mosquitoes not seen as only cause of malaria
• Use of ITNs adversely affected by functional organization of the houses: e.g. if also cook in sleeping areas, see nets as fire hazard
• Bednets not used when perceived benefits of reduction in mosquito nuisance and of malaria were considered not to be worth the inconvenience of daily use

Universal coverage is not a one-time event. It must be maintained for many years. There must be continuous supplies of nets for new people and to replace old nets.  If after 3-4 years coverage falls, severe cases and mortality will rise as populations would have lost immunity.

And finally, any reduction in ACT need and use depends on use and acceptance of RDTs.  As the chart above shows, we will have no shortage of fever illness episodes even as malaria reduces.  Unless we couple diagnosis AND treatment, ACTs will be wasted and shortages will arise, especially if we reduce our orders of ACTs before we are sure that universal net coverage effects have really begun.