Category Archives: Resistance

Preventing Malaria Drug Resistance in the African Setting …

and Dealing with it Should Resistance Occur

Professor Joseph Ana, Africa Centre for Clinical Governance Research & Patient Safety in Calabar, Nigeria shares his experiences and concerns in this blog.

Drug resistance is one of the biggest challenges facing health care systems in the world today. Around 25,000 people die each year from resistant viral and bacterial infections in Europe, but no new classes of antibiotics have come on the market for more than 25 years. The figures are difficult to obtain for Africa and other developing countries.

Medicine shops may sell inappropriate malaria medicines, thus contributing to resistance

Medicine shops may sell inappropriate malaria medicines, thus contributing to resistance

Drug resistance is considered important in the failure of control and treatment of diseases its consequences, and it is considered to be one of the causes of emergence of new strains of infective organisms and re-emergence of once-controlled diseases. The occurrence and impact of the phenomenon is worse in Africa and parts of Asia for malaria according to WHO and the US CDC. Viral and bacterial diseases are also affected in this region.

Therefore, there is urgent need for global sustained action to prevent drug resistance from happening, and to control it, if it happens. The causes of Drug resistance are varied including lack of or poor implementation of the control of access to drugs, population migration and movement, misdiagnosis, under-treatment and irrational drug prescription and use.

Global Report malaria drug resistanceTo prevent drug resistance, countries need to legislate and implement adequate control of access to drugs, sustain public education on the dangers of drug resistance, educate health workers on and enforce rational drug prescribing and use. Effective monitoring of treatment outcomes is also important to know when drug resistance is occurring. With the global and country by country best efforts drug resistance may still occur because of mutation and adaptation of infective organisms.

For diseases like Malaria for which resistance to the most effective drug today, artemisinin-combination drugs, is being reported from Southeast Asia, the development of new drugs alongside vector control is essential by all countries, particularly in Africa.


Professor Joseph Ana – BM.BCh (UNN), FRCSEd, FRSPH, JtCertRCGP-UK, DFFP (RCOG)-UK, DipUrology-UK, Cert.ClinGov.UK; Lead Consultant Trainer / CEO; joseph ana <jneana@yahoo.co.uk>; Contact: Africa Centre for Clinical Governance Research & Patient Safety; @Health Resources International (HRI WA); Consultants in Clinical Governance & Patient Safety (MDCN Accredited CPD Provider); 8 Amaku Street State Housing  (& 20 Eta Agbor Road UNICAL Road),  Calabar, Nigeria.

Visit Website: www.hriwestafrica.com; email: hriwestafrica@gmail.com    Tel: +2348063600642

Does Malaria Meet the Criteria for Eradication?

World Malaria Report 2015 CoverWhat it is that makes a disease “eradicable,” or more correctly what makes it possible to eliminate malaria in each country leading to the total eradication world-wide. Bruce Aylward and colleagues identified three main sets of factors by drawing on lessons of four previous attempts to eradicate diseases (including the first effort at malaria eradication in the 1950s and ‘60s).[1]

  1. biological and technical feasibility
  2. costs and benefits, and
  3. societal and political considerations

So far smallpox is the only success because as Aylward et al. pointed out biologically, humans were the only reservoir and on the technical side a very effective vaccine was developed. The eradication campaign was promoted in clear terms of economic and related benefits. While the early malaria eradication efforts started with political will and recognition of the potential economic benefits of malaria eradication, the will was not sustained over two decades. On the technical side at that time there was only one main tool again malaria, indoor residual insecticide spraying, and mosquitoes quickly developed resistance to the chemicals. Are we better able to meet the three eradication criteria today?

Today’s technical challenges are embodied in intervention coverage problems. The World Malaria Report of 2015[2] (WMR2015) explains that the problem is most pronounced in the 15 highest burden countries, and consequently these showed the slowest declines in morbidity and mortality over the past 15 years. Use of insecticide treated nets and intermittent preventive treatment for pregnant women hovers around 50%, while appropriate case management of malaria lags well below 20%, a far cry from the goals of universal coverage. A further explanation of the technical challenges as outlined in the WMR2015 lies in “weaknesses in health systems in countries with the greatest malaria burden.”

The economic benefits criteria should be most pronounced in the high burden countries, but these are also generally ones with low personal income. Ironically, the WMR2015 points out that it is the high costs of malaria care and the malaria burden that further weaken health systems. More investment is needed in order to see more economic benefits.

Biological challenges to elimination are also identified in the WMR2015. Examples of existing and arising biological difficulties include –

  • Plasmodium vivax malaria which requires a more complicated regimen to affect a cure.
  • “Since 2010, of 78 countries reporting (insecticide resistance) monitoring data, 60 reported resistance to at least one insecticide in one vector population.
  • “P. falciparum resistance to artemisinins has now been detected in five countries in the Greater Mekong subregion.” Historically chloroquine and sulfadoxine-pyrimethamine resistance spread from this area and now artemisinin resistance marks a ‘Third Wave” of resistance emanating from the region.[3]
  • “Human cases of malaria due to P. knowlesi have been recorded – this species causes malaria among monkeys in certain forested areas of South-East Asia,” and so far human-to- human transmission has not been documented.

On the positive side greater political support to elimination efforts has been expressed by the African Leaders Malaria Alliance (ALMA) who met at the African Union Leaders Summit in Addis Abba early in 2015 and resolved to eliminate malaria by 2030.[4] This call to action was backed up with an expansion of ALMA’s quarterly scorecard rating system of African countries’ performance to include elimination indicators.[5]

In conclusion, political will exists, but needs to be backed with greater financial investment in order to produce economic benefits. Time is of the essence in taking action because biological and technical forces are pressing against elimination. 2030 seems far, but we cannot wait another 15 years to take action against these challenges to malaria elimination.

[1] Aylward B, Hennessey KA, Zagaria N, Olivé J, Cochi S. When Is a Disease Eradicable? 100 Years of Lessons Learned. American Journal of Public Health, 2000; 90(10): 1515-20.

[2] World Health Organization. World Malaria Report 2015. WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland, 2015.

[3] IRIN (news service of the UN Office for the Coordination of Humanitarian Affairs). “Third wave” of malaria resistance lurks on Thai-Cambodia border. August 29, 2014. http://www.irinnews.org/report/100549/third-wave-of-malaria-resistance-lurks-on-thai-cambodia-border

[4] United Nations Secretary-General’s Special Envoy on MDGs. African Leaders Call for Elimination of Malaria by 2030. Feb. 3, 2015. http://www.mdghealthenvoy.org/african-leaders-call-for-elimination-of-malaria-by-2030/

[5] African Malaria Leaders Alliance. ALMA 2030 Scorecard Towards Malaria Elimination, December 2014. http://alma2030.org/sites/default/files/sadc-elimination-scorecard/alma_scorecards_poster_english.pdf

Epidemiology of Resurgent Malaria in Eastern Zimbabwe: Risk Factors, Spatio-Temporal Patterns and Prospects for Regaining Malaria Control

Mufaro Kanyangarara and her PhD thesis adviser, Luke Mullany, of the Johns Hopkins Bloomberg School of Public Health Department of International Health, have been looking into the challenges of controlling and eventually eliminating malaria in a multi-country context in southern Africa. We are sharing abstracts from her pioneering work. The first seen below provides an overview of the three components of the study.

Incidence 2012Despite recent reductions in malaria morbidity and mortality due to the scale up of malaria interventions, malaria remains a public health problem in sub-Saharan Africa, especially among children under five years of age, pregnant women and people living with HIV/AIDS. A recent resurgence in malaria, in areas where malaria control was previously successful, has brought to the forefront the importance of research to understand the epidemiology of malaria and the effectiveness of malaria control efforts in resurgent settings. Using cross-sectional surveys, routine data from health-facility based surveillance and freely available remotely sensed environmental data, this research examined the distribution of malaria and the impact of vector control in Mutasa, a rural district in Zimbabwe characterized by resurgent malaria.

Firstly, individual- and household level factors independently associated with individual malaria risk were identified using multilevel logistic regression models based on data from cross-sectional surveys conducted between October 2012 and September 2014. Secondly, geostatistical methods and remotely sensed environmental data were used to model the spatial and seasonal distribution of household malaria risk; then develop seasonal malaria risk maps with corresponding maps of the prediction uncertainty. Lastly, an evaluation of the effect of introducing an organophosphate for indoor residual spraying was conducted using routine health facility data covering 24 months before and 6 months after the campaign.

The results of multilevel model suggested that malaria risk was significantly higher among individuals who were younger than 25 years, did not sleep under a bed net, and lived close to the Zimbabwe-Mozambique border. The spatial risk maps depicted relatively increased risk of finding a positive household in low-lying areas along the Mozambique border during the rainy season. Lastly, the introduction of organophosphates to this pyretheroid resistant area resulted in a significant reduction in malaria incidence following spraying. These findings elucidate the heterogeneous distribution of malaria, identify risk factors driving malaria transmission and assess the quantitative impact of switching insecticide classes on health outcomes. Collectively, the findings provide evidence to guide country-specific decision making for regaining malaria control and underscore the need for strong between-country initiatives to curb malaria in Mutasa District and elsewhere.

Drug-resistant malaria in Myanmar: A call for increased funding to prevent a global catastrophe

We are happy to re-post a blog by Alice Sowinski, Craigen Nes, and Diane Del Pozo in the SBFPHC Policy Advocacy Blog of the Social and Behavioral Foundations of Primary Health Care Course at the Johns Hopkins Bloomberg School of Public Health….

The CDC estimates there are 198 million cases of malaria that occur worldwide with more than 500,000 people dying from the disease every year. Although this disease has slowly declined in recent years, experts believe that certain endemic areas could still be at high risk for drug resistance. One such area includes Myanmar, a Southeast Asian region located on the border between India and China.

myanmar malaria map

Myanmar is a high-risk area for artemisinin resistant malaria

Over 76% of Myanmar’s population lives in regions stricken with poverty and poor health infrastructure that contribute to the mass spread of disease in areas where malaria is endemic. This area in particular is becoming resistant to artemisinin, the first line of defense. Experts suggest Myanmar is a priority region for the elimination of artemisinin resistant malaria (ARM) in order to avoid the international disaster that would result if ARM were to spread to India and Africa. Immediate and large-scale action along with substantial financial support from multiple stakeholders is needed to prevent further spread of ARM and avoid a looming malaria catastrophe.

The Burmese government estimates that it will need US$1.2 billion over the next 15 years or $80 million per annum. The proposed solution would strengthen surveillance, increase rapid diagnostic testing and create new drugs to combat ARM. However, recently the Australian government, one of the 3MDG Fund donors, the largest development fund in Myanmar, has decided to cancel its pledged sum of $42 million in aid to the country. The implications of this withdrawal are uncertain and untimely.

With the ability of the malaria parasite to thwart off once effective drugs, the fear of widespread resistance is now a reality. Scientists believe we have a small window of opportunity to support Myanmar’s national campaign to increase funding to prevent a global health disaster and achieve Myanmar’s 2030 malaria elimination goals.

Asia-Pacific: a region of contrasting hopes for eliminating malaria

The burden of malaria in the Asia-Pacific region, being much lower than that of Africa, has led to some neglect in the past when it comes to rolling back the disease. Two news reports today show why neglect is not an option is global country-by-country elimination os the disease is to be achieved.

eliminating-malaria-in-the-philippines-sm.jpgHope was expressed clearly by national Department of Health authorities in the Philippines who exclaimed that “THE Philippines could be malaria-free by 2020 as the number of cases declined by 80 percent in the recent years, the Department of Health (DOH) said on Friday.” The article in the Manila Sun-Star quoted Health Secretary Enrique Ona who said “The government has recorded 9,642 malaria cases in 2011 as compared to 43,441 in 2003.”

A close accounting of the 58 provinces that are considered endemic in the Philippines found that nine have had no cases in the past three years, and forty have been reporting less than 1 case per 1000. While definitely being optimistic about the prospects of overall elimination from the country, the Health Secretary is realistic as quoted by the Sun-Times: “The journey towards elimination status is more difficult than working for a reduction in cases and we will need more commitments and resolutions of the different sectors to be consolidated into a singular, comprehensive initiative so that the whole country, not just the 58 endemic provinces, will be declared malaria-free by 2020.”

The situation in another regional partner is more dire. VOA reports that the problem of malaria drug resistance is “more severe in Cambodia than anywhere else in the world.” The National malaria Center in Cambodia found that, “About 17 percent of all cases in the Cambodian-Thai border area of Pailin were drug-resistant in 2011, up from 10 percent the year before.”

On the positive side, even though the proportion of drug-resistant cases in increasing, the total number of cases continues to decrease. Still, there is concern about ramification of the situation “beyond borders.” Travel and migration among the Mekong region countries means that resistance may not stay put in Pailin. A comprehensive control program, not just reliance on treatment, needs to be in place throughout the region.

Fortunately there are groups like the Asia Pacific Malaria Elimination Network (APMEN) that brings countries in the region together to address common and cross-border challenges. APMEN recognizes that, “Elimination requires a different strategy than sustained control,” and is thus, in am important position to help the rest of the world learn innovative approaches to put paid to malaria.

Scale-up Meets Resistance

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

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

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

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

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

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

Mumbai – is transmission season increasing?

The Times of India reports that, “Malaria is no longer restricted to just monsoon months as in the past. Spurred on by widespread construction activity and the resulting poor sanitation, the disease has becomes a round-the-year feature in Mumbai, killing less people but afflicting more.”

An increase was noted: “In all, 76,755 contracted the ailment in 2010, 74% more than the 2009’s figure of 44,035,” but with fewer deaths (better case management?), but it is not clear whether these cases were parasitologically diagnosed.

A member of the medical association attributes the increase, especially the off-season rise, to human activity – construction projects. The official stated that, “Construction sites have puddles of water in which mosquitoes breed. Since construction work goes on throughout the year, so does the breeding. This obviously increases the incidence of malaria.”

Worry was also expressed about, “resistance developed by the Anopheles albimanus mosquito that the civic body’s insecticide fumigation has no effect on it.” This has led the city to consider using “bacillus thuringiensis variety israelensis” for control.

Ironically, in pointing out that, “Another reason for the spread of malaria, which is caused by a parasite called plasmodium, during non-monsoon months is that plasmodium can stay in the body for a long period,” the article raises the possibility that the upswing may not be fully due to new transmission.

asia-in-wmr-2008.gifAside from these possible limitations on the validity of the data,  the potential for increased transmission is worrisome, especially in a part of the world that has received less (but increasing) attention from the Roll Back Malaria Partnership. The map from the 2008 World Malaria Report shows the extent of the problem in Asia.

India has a double problem with malaria, hosting both P. vivax and P falciparum.  A recently published article reports that while the national control program has introduced artemisinin-based combination therapy for P. falciparum as a first-line treatment, the older drugs, chloroquine (CQ) and Sulphadoxine-Pyrimethamine (SP) are still available. Unfortunately Shrabanee Mullic and colleagues found that, “In Jalpaiguri District the overall failure rate of CQ was 61% and of SP 14%, which was well above the WHO recommended cut-off threshold level (10%) for change of drug policy.”

Other research in India examined vector control with positive effects. “A study was conducted to evaluate the preventive efficacy of insecticide-treated mosquito nets (ITMNs) and mosquito repellent (MR) in a malaria-endemic foothill area of Assam, India, with forest ecosystem.” The researchers found that, “The total vector population in the three intervention sectors decreased significantly compared with that of the non-intervention one.”

Overall, malaria in India is a complex phenomenon with different forms of the parasite, different ecological settings and different levels of government involved. More attention is needed to address this complex situation is malaria is ever to be eliminated.

Resistance – a barrier to malaria elimination

whd2011_230x60_en.gifThe World Health Organization reminds us today that, “Antimicrobial resistance is not a new problem but one that is becoming more dangerous; urgent and consolidated efforts are needed to avoid regressing to the pre-antibiotic era.”  It is not just antibiotics that are in trouble, but other microbial agents including malaria drugs.

In the malaria community we are also worried about insecticide resistance.  Growing resistance to DDT was one of the reasons that earlier efforts to eradicate the disease were not globally successful.

WHO explains clearly that human behavior (patients, providers, health service managers and drug manufacturers) plays a big role in developing antimicrobial resistance:

Antimicrobial resistance is facilitated by the inappropriate use of medicines, for example, when taking substandard doses or not finishing a prescribed course of treatment. Low-quality medicines, wrong prescriptions and poor infection control also encourage the development and spread of drug resistance. Lack of government commitment to address these issues, poor surveillance and a diminishing arsenal of tools to diagnose, treat and prevent also hinder the control of drug resistance.

Scientific American this month has two timely articles on antibiotic resistance that also highlight how human behavior exacerbates the problem.  Agricultural use of antibiotics is one major problem. Another revolves around infection prevention procedures (or the lack thereof) in hospitals.

The use of combination drug treatments was expected to slow or prevent the emergence of resistance to another class of anti-malaria drugs, but prior and continued use of monotherapy artesunate drugs in Southeast Asia has raised the specter of resistance developing there and spreading throughout the world following the patterns of chloroquine and sulphadoxine-pyrimethamine. The following steps are designed to help:

  • Treatment only with combination therapies where there is no demonstrable resistance for either component of the combination
  • Treatment based only on positive results of parasitological tests thus avoiding indiscriminant use of malaria drugs
  • Regular/frequent drug efficacy testing using WHO protocols
  • Pharmacovigilence/Surveillance

Donors and National Malaria Control Programs must recognize and fund surveillance activities as one of the central interventions in efforts to eliminate malaria. As this year’s World Health Day theme clearly states: no action today, no cure tomorrow.

Keeping up with Malaria – 4 years and 500 postings

This month marks the 4th year for Malaria Matters and our 500th posting. Two of our first postings we examined what happens to chloroquine when it is no longer used as a first line drug,and how malaria proposals fare at the Global Fund.

Chloroquine was valued because it was inexpensive and therefore justifiably used for presumptive treatment. Resistance showed not only that the presumptive treatment approach was likely flawed, but that single drug or mono-therapy treatments were not appropriate. Research today continues to document the spread of chloroquine resistance for example, in vivax and falciparum malaria in Indonesia.

What our 2006 posting addresses was the fact that chloroquine resistance did reduce after the drug is withdrawn as the front line treatment in Malawi. These findings were backed up by a study from Kenya published last year. The Kenya researchers reported “a reduction in resistance to CQ following official withdrawal in 1999 was found, but unlike Malawi, the decline of resistance to CQ in Kilifi was much slower,”ultimately taking twice as long as it did in Malawi – assuming use remains at a low level.

dscn9149-sm.JPGThe practical research question moving into the future toward malaria elimination is whether an inexpensive drug like chloroquine can ever again find a place in the pharmacological arsenal against malaria. The experiences of both increasing and reducing drug efficacy also stress the importance of maintaining strong pharmaco-vigilence as part of any national malaria control effort.

Concerning the Global Fund we expressed disappointment in 2006 that malaria grants performed so poorly in Round 6 allocations in terms of relative proportion of total grants as well as proportion of submitted grants approved. Since that time the Roll Back Malaria Harmonization Working Group has mobilized human resources to strengthen the grant writing process. Since that time malaria grants have been gaining a greater share of total resources and have had better success in being approved.

According to AIDSPAN, this year’s Round 10 allocations may be a mixed bag for malaria. While 79% of submitted malaria proposals were recommended for approval (better than the 50% overall approval rate), only a small number of proposals were submitted (24) and ultimately approved (19) of the 89 from all sources.

This low ‘turnout’ may reflect the economic constraints at the Global Fund where there had even been some doubt earlier that a Round 10 would be issued, but it reflects poorly on the need to scale up and sustain malaria interventions into 2015 and beyond. This also does not reflect changes in Global Fund approaches such as the rolling continuation credit and the potential move toward funding based on national strategy, all of which are changes at the GFATM since 2006.

Overall once can see that in four short years the funding and technical landscape surrounding the control and elimination of malaria are changing quickly. We are closer now to a vaccine, WHO has updated its malaria treatment guidelines, long awaited rapid diagnostics tests are rolling out in larger quantities, and countries, such as those in southern Africa, that need to develop pre-elimination strategies are being identified. We intend that Malaria Matters will help you keep up with these vital changes.

If Myanmar cannot control malaria, what of Burma?

Myanmar has operated only three Global Fund Grants in its history. The Round 3 Malaria grant was terminated at Phase 1 in 2007. Two million dollars was disbursed, but no results were found in the progress report at the Global Fund website. No explanatory notes were offered.

In the meantime, malaria continues unabated. Reports from a remote rural area observe that, “About half of the villagers in this remote corner of Kachin State are suffering from the mosquito-borne disease, but medical supplies provided by the Kachin Baptist Convention (KBC), a Christian group, ran out two weeks ago.”

The website explains that villagers are reluctant to complain because, “In military-ruled Myanmar, saying anything seen as critical of the authorities can have serious consequences.” Instead villagers wait as they lack money needed to reach clinics and thus, resort to indigenous treatments.

Reports from the KBC indicate that they only had the resources to assist about five percent of the Kachin population in the fight against malaria. The mission group complained that, “There are many people we can’t reach, and it’s getting worse. It’s linked to poverty. Most of them can’t even afford mosquito nets.”

Myanmar does have an unsigned Round 9 malaria Global Fund grant pending. One wonders whether performance would be any better than Round 3.

Myanmar is part of the broader Mekong area where fears of malaria drug resistance are a constant concern. IRIN reports that, “Mekong countries of Cambodia, China, Lao PDR, Myanmar, Thailand and Vietnam, show (malaria drug) tolerance … with the drug proving less effective and taking longer than previously to kill the parasite.”

IRIN noted that, “… studies in Myanmar had shown that parasites were still detected in some cases after treatment, taking more than a benchmark three days to be cleared …  This is an indication that there is resistance .” Furthermore, “only around 500,000 ACT courses are available annually – a fraction of what is needed to treat an estimated 8.5 million malaria cases.”
wikimedia-commons-myanmar.jpgAccess to malaria treatment and prevention is not a unique problem. IRIN reminds us that in the wake of a major tropical cyclone in 2008 the Myanmar population in affected areas was threatened with malnutrition and diseases due to lack of adequate access to food and medicine. This health neglect is endemic.

Will new elections help? BBC reports that a group of 15 nations, “known as the Friends of Burma, called for inclusive, participatory and transparent elections. Afterwards the secretary general said he had expressed concern that conditions in Burma do not measure up to what is needed for an inclusive political process.”

Without an inclusive political culture can the political will and accountability exist to control and eventually eliminate malaria? This is not just an issue for the poor and suffering within Myanmar since practices there enhance malaria drug resistance in the region and ultimately the world.  If Myanmar cannot control malaria, one wonders if Burma could.