Archive for the 'Drug resistance' Category

A flood of artemisinin resistance

Articles that is. The spread of resistance to artemisinin drugs, the main-stay of modern Plasmodium falciparum (and even P. vivax in some places) malaria therapy, would endanger control programs globally (previously discussed here, here, here, and here). Last week saw a series of high-profile publications which received an impressive amount of coverage in the general media, here’s the list:

  • Evidence for a genetic basis for much of the observed resistance – are molecular markers in sight?
  • Another combination therapy trial with prolonged clearance in both treatment arms among patients from Western Cambodia
  • Longer clearance half-lives among patients with a high parasite load treated with just artemisinin on the Thai-Burma border, it’s already spread
  • An accessible narrative providing a glimpse of the operations of the Thai-Cambodia containment program (thanks Matt)
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A needed review on parasite clearance

The parasite clearance curve and, the more commonly used, parasite clearance time is a measure of the reduction of parasite density over time or the time until the patient is parasite free, after beginning treatment. Interest in parasite clearance has peaked as a means to gauge artemisinin resistance (previously discussed here and here) as combination therapies often have few outright failures and other tools to detect early resistance such as in vitro tests and molecular markers are not useful or possible at this time.

Professor Nick White, one of the world’s foremost experts in treating malaria, just published a fantastic review (Malaria Journal – open access!) on the topic. The article presents a great discussion of  measurement issues and common limitations, analyzing by density reduction or time until clearance, the kinetics and trend of results, connections with stage-specific action, and much more. As we’re in the midst of analyzing two years of artesunate+sulphadoxine-pyrimethamine trial data from India’s National Antimalarial Therapeutic Efficacy Monitoring Network, we’re fortunate for the release of the article since examining the parasite clearance in our patients is one of the key concerns.

Antimalarial drug resistance in India 1978-2007

Probably the largest, longest running, drug efficacy monitoring effort in the malaria world yet little appreciated and recognized. I hope our analysis and publication of thirty years of data (sorry, not open access – email me for the PDF) helps amend that. And something I do not say often enough: I am so grateful for my colleagues and mentors in India, with whom I have learned, and continue to learn, the difficult task of improving public health.

WWARN data explorer: visualizing drug resistance

WWARN (previously introduced here) has released their interactive data viewer. It is fantastic to see and use.

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Viewing the tabulated data for any study (as opposed to just summary data) is a bit tricky: > click on the study icon on the map > look to the bottom left of the pop-up > click investigate study and a new pop-up will appear.

While there are few (clinical) studies in the database thus far, WWARN should be commended for the extent of raw data they make available for each, including:

  • Location map
  • Study profile
  • Patient age range
  • Recurrent parasitemias
  • WHO treatment outcomes
  • PCR-Adjusted cure-rate chart
  • Unadjusted cure-rate chart
  • Cure-rate table

Blog for the artemisinin resistance containment project

We’ve talked about the looming threat of artemisinin-resistant malaria and its spread before (here and here). Well the Gates Foundation funded containment project for the P. falciparum strains along the Thai-Cambodia border has a blog. And it looks terrific – from vivid photos, an interview with Dr Wichai Satimai (director of the Thai Bureau of Vector-Borne Diseases), and a close look at the neat Cambodian cooler boxes, the writers have been busy since starting in September. I will be following with great interest.

Has WHO eliminated artemisinin resistant parasites?

Possibly, but probably not, and certainly too early to tell. Though some would have you believe it already. The World Health Organization press release makes two claims: 1) artemisinin-resistant malaria (previously discussed here and here) has almost disappeared from areas tested in a pilot project managed by WHO and 2) the overall incidence of malaria has reduced significantly in the zone targeted by the project.

For the first claim no citation, efficacy or parasite clearance time data, or evidence of any sort are mentioned including who these researchers might be. The (presented) basis for the second claim lies in the screening of just 2,782 persons (it is unclear if this was a mass survey or several months of active case detection) in which only 2 P. falciparum cases were found. I realize this is not a scientific paper, but the ‘screening’ of a few thousand people in a border population of millions before the main malaria transmission season over the upcoming months seems little to be excited about. What was the need for this? The project just began in 2009. Why not wait another two years before making any public pronouncements? Alternatively, only provide regular updates through a somber and detailed format such as an annual project summary.

I believe in WHO. First, WHO has an unique mandate for supranational coordination. Second, WHO operates by consensus which, while time-consuming and difficult at times, allows countries large and small to have a voice at the table. And finally (related to the previous point), they maintain the trust of ministries of health in a way no other organization does – at least for now… They are losing their reputation by continuing to release shoddy statements backed by limited or poor quality data.

I’ve already complained about science and public health by press release. I understand it though from NGOs but I do not understand this trend from an organization which prides itself as a leader in developing quality health recommendations and soliciting technical excellence.

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WWARN – The world-wide antimalarial resistance network

The world-wide antimalarial resistance network (WWARN) is a great idea. The concept is simple: drug-resistant strains spread and a bigger picture is needed – consolidate data from existing monitoring efforts and standardize protocols to ensure comparability. A series of articles in 2009, published in Malaria Journal, outlined the rationale and a plan for creating a global network. The supplement further details each of the four technical components which comprise drug resistance monitoring: clinical efficacy, in vitro testing, clinical pharmacology, and molecular markers. Results deposited into WWARN, about 28,000 patients thus far, are promised to be open and transparent (hopefully the data will be liberated in the coming months).

A few questions and comments:

The Tropika team reports on the recent WWARN presentation at the MIM conference.

Why is WWARN based at Oxford? A lot of expenses could be saved if the group was hosted, in say New Delhi, where the cost of living is lower and expertise in both malaria and information technology is abundant.

WWARN seems to involve mostly academic researchers. One concern about the viability of any common database is the hesitance of many researchers to share data. Also, much of drug resistance monitoring is conducted directly by national control programs. Will a network of international researchers be able to build credibility with and engage program managers?

Traditionally, the World Health Organization has served to coordinate activities at the supranational level (such as WWARN). WHO is better placed to present itself as a neutral body to promote standardization as well as to request and collate national data. They also have a better relationship with control programs, which would help translate the data into action. Yet, here we seem to have another deliberate effort to bypass them. This is a disturbing trend for the world’s foremost health agency.


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