topnaman | Malaria blog

Below is a comment, on the PMI clarification, from one of the authors of the WHO Bulletin article.

In regard to the Director’s response to criticisms about the PMI program in Angola, I would like to make a few comments, having written the article in English, with the approval of my two colleagues, especially Martinho Somandjinga, the first author and an experienced and highly competent malaria control official.

The primary fault in the whole story was the use of administrative reports on malaria, based on clinical diagnoses of malaria, which in fact were simply diagnoses of fever and headache.  No blood slides were taken to confirm these administrative reports.  Therein lies the problem.

The secondary problem we pointed out is that WHO, in their global planning and analysis, uses the same faulty administrative reports of fevers, instead of making lab diagnoses for the malaria parasite.

Thirdly, although Mr. Somandjinga and I worked out and recommended to PMI a monitoring plan complete with labs, blood slide collections, and microscopic diagnoses, PMI has continued to ignore the need for this more precise process for monitoring and evaluating their effort in Angola and in the rest of Africa.

The First Law for attacking malaria in Africa is that it is like building a huge cathedral or mosque, it will take generations.  So evaluation and monitoring is essential if we are to make progress over the next several decades.  You cannot control malaria in Africa with public relations, it is a tough disease.

A really good sign however, is the increased role of epidemiologists from CDC in PMI and in Geneva.  These folks know the score.  Some have run studies showing that the false positivity rate of these clinical diagnoses is erratic and can be very high, like 50%!  And a recent study in Khartoum showed a false positive rate of 90%.  So the administrative data is useless, and I trust Robert Newman and Larry Slutsker will work towards establishment of microscopic diagnoses on appropriate sentinel populations.  Then we will know what the problem really is, and where to put our efforts.

It will take a while, but we can do it.  And now is a wonderful time to capture the popular enthusiasm for malaria control in Africa.

Bill Jobin
Cortez, Colorado

The title of this post is a bit sensational for my tastes but honest in regards to the charges levied by Somandjinga et al in the Bulletin of the WHO. The history of malaria control is replete with stories of gaffes small and large. However, the “policy and practice” article contains frank and detailed criticism, which rarely ever appear in print, about USAID/PMI (previously introduced here) operations in Angola. Before summarizing the alleged mistakes, it should be stressed that all human efforts will be imperfect. Seems obvious but we often fail to recognize the difficulties faced in executing programs. This does not excuse lapses in critical thinking – rather it is to stress the importance of process. That the ability to acknowledge errors, learn from them, and iterate efforts may be more important than our propensity to commit mistakes.

Here are the USAID/PMI mistakes as stated, sometimes directly and at other times in between the lines, by the authors:

- Failure to gain demonstrated national commitment (in the form of increased malaria staff or local funds) prior to beginning the program

- Rush to implement the program

- Poor understanding and use of routine data

- Selection of a single control measure

- No pretreatment evaluation

- Disregard for objections from the authors (one of whom is the regional public health manager)

- False assurances regarding CDC support and data collection

- Communication barriers from a lack of language proficiency (Portuguese)

- All of which culminated in the spraying of the homes of 500,000 people in an area without adult mosquitoes or breeding sites, i.e. likely no to minimal malaria transmission

- Overall, inexperience of PMI-Angola leadership in malaria control

Does PMI accept these critiques? Have they learned from their mistakes? I emailed PMI asking if there was a public response to the article or if they wished to provide another perspective on this post. I was pleased to receive a kind and prompt reply which is posted below in its entirety. Readers can draw their own conclusions.

PMI Clarification:

Dear Mr. Naman Shah,

Thank you for your query sent to “Ask the Malaria Coordinator” regarding the recent World Health Organization Bulletin article authored by Somandjinga et al., which critiques some aspects of the President’s Malaria Initiative’s (PMI) work in Angola in 2005/2006.  The indoor residual spraying (IRS) program referred to in the article was the very first round of IRS supported by the PMI in any country.  Although important lessons were undoubtedly learned during implementation of this first spray round in Angola, the implementation of this campaign was considered a success with a 90% acceptance rate among householders in the communities targeted for spraying, more than 590,000 people residing in houses sprayed were protected from malaria, and with no outbreaks of malaria detected in these areas following the spraying campaign.

There are several statements found within the article that are factually incorrect.  It is inaccurate to state that PMI failed to secure national commitment prior to beginning the spray program.  Angola was selected as one of the first three PMI countries.  The process for country selection for the President’s Malaria Initiative has always included high level consultation between US Ambassadors and the host country leadership including Ministries of Health, and Angola was no exception.  The first annual operational plan for PMI support in Angola including support for the aforementioned IRS campaign, as with subsequent annual plans, was prepared in consultation and collaboration with the Angola National Malaria Control Program (NMCP).

Although the article points out that the target areas for the first spray round were areas later found to have low levels of malaria transmission, PMI selected the areas targeted for spraying with the support of the Ministry of Health of Angola and with direct guidance from the Angola National Malaria Control Program Director.  It is important to note that this first spray round was part of a multi-donor effort in the southern provinces of Angola, with PMI support complementing the IRS program supported by WHO in an adjacent province.   Furthermore, the spraying of these malaria-epidemic prone areas was consistent with current WHO guidance for selecting areas appropriate for IRS and the success of the first IRS campaign in Angola carried out in these low transmission areas provided the experience and confidence to enable successful targeting of IRS in higher transmission areas in future spray rounds.

Finally, PMI, working in direct collaboration with NMCPs in the 15 PMI countries and together with other donors and partners, has demonstrated significant progress in scaling-up malaria prevention and control interventions, with clear evidence of reductions in malaria burden in many of the PMI countries.  Specifically related to IRS, since 2005/2006 PMI has been leading efforts to incorporate IRS as a major component of malaria control programs in Africa.  PMI-supported IRS programs work in close collaboration with national and district government counterparts and have expanded emphasis on building local capacity to implement quality IRS activities, including placing significant attention to environmental issues and best practices surrounding the intervention.  Prior to the launch of PMI, IRS was only being implemented by NMCPs in a few southern African countries and in Ethiopia and Eritrea, in addition to limited private sector investments in a handful of African countries.  PMI has played a key role in re-introducing IRS as an effective malaria control tool in Africa.  Currently many African countries that are not among the 15 PMI countries, have begun or are planning implementation of IRS programs after having learned from the successful experience demonstrated by their neighboring NMCPs in collaboration with PMI.

It is important to note that two of the three authors of this article were former contract employees of the PMI IRS implementing partner.

Two events prompted this post. First, several people have asked me if the malaria vaccine they heard about in the news will eliminate malaria. Second, the GSK CEO Andrew Witty discussed pricing strategies (5% profit above the yet unknown production costs) for this vaccine, called RTS,S, at a recent talk. Wait – pricing? We don’t even know how well the vaccine works! The press touts RTS,S as the world’s most advanced malaria vaccine. This is true in someways, it is in phase III trials which is the stage immediately preceding licensure and market sales. In and of itself this is a terrific achievement. However, advanced does not equal effective, and effective does not equal useful. Concerns about vaccine storage, dosing, delivery, and cost still remain.

The available RTS,S phase II results (previously discussed here) were far from spectacular, but efficacy was not the main endpoint of these trials. At that stage the investigators were focused on other aspects of a vaccine such as safety, dose finding, and immune response. The larger phase III study should answer the question of efficacy, but which efficacy are we talking about? Is it the efficacy in reducing all clinical malaria vs severe manifestations vs parasitemia or in children vs adults or for the first vs the fifth year after the receipt of the vaccine? Likely several different endpoints will be presented, and there will be disagreements about which one is meaningful for a particular country. If I were a betting man my guess is poor efficacy and low utility for public health, but I hope I’m wrong.

On a related note – will GSK receive a priority review voucher if RTS,S is licensed? The priority review voucher program was created in 2007 as an market-based incentive for companies to develop drugs and vaccines for neglected diseases. It allows a company to decrease the standard FDA review time, by 6-12 months, for another treatment of their choice. The economic value from the accelerated approval of a blockbuster drug is estimated at $100-500 million. Could the prospect of a voucher influence GSK’s decision to seek FDA approval? There is also the issue of the GSK-owned novel adjuvant (an immune response booster) used with RTS,S. What is the licensing process for adjuvants? I suspect that if an adjuvant has been used in a licensed vaccine, it can then be sold for use in any existing or new vaccine. Or at the least other companies would be more likely to risk using that adjuvant during vaccine development. If so, GSK may have another incentive to license RTS,S. From the talk of their CEO they already seem certain that a vaccine of any form will be pushed through the FDA.

PS GSK’s contribution and committment to the malaria vaccine began in 1987 and is commendable. Other contributors should also be noted. The Walter Reed Research Institute (run by the US Army) conducted much of the key early research. The Gates Foundation, through their Malaria Vaccine Initiative, has funded much of the vaccine’s development costs since 2001.

PPS The first voucher granted under the priority review program was for malaria. Novartis received one for its antimalarial drug Co-artem (artemether+lumefantrine). In this case the drug was not novel, available for almost a decade now, but was only recently licensed in the US making it eligible.

As a follow-up to the previous post on the Calcutta School of Tropical Medicine is a remarkable piece of history on its origins written by Helen Power. The subtitle “institutionalizing medical research in the periphery” summarizes the article and the insights one can expect from reviewing such a process. How are institutions forged? Who decides and why? A recurring theme (in the stories of institutions) I find amusing is the extent to which matters of whim and expediency, as opposed to deliberate intent, influenced history. Amidst our everyday work it is a rare oppurtunity to step back and reflect upon the broader forces (foreign strategy, national politics, financial competition) or petty conflicts (disciplinary divides, ego clashes) which shaped our present, regardless of where we may be.

Need to stay up to date on malaria research? MalariaWorld is a site which consolidates and summarizes recent papers. They also have a blog and a useful list of malaria related job openings and graduate research positions.

Chloroquine was discovered in Germany in 1934 (as Resochin) but was originally considered too toxic for human use. After American trials of the drug in World War 2 chloroquine became a mainstay of malaria treatment. In recent decades with the advent of worldwide drug resistance its use has declined. With perhaps the exception of Mesoamerica, the use of chloroquine for falciparum malaria is (or should be) minimal. The drug remains vital for vivax malaria, and other than Papua New Guinea, only a few stray case reports of treatment failure exist.

What’s fascinating about the drug is its potential application in other fields. Reported to have anti-viral, anti-inflammatory, and immunosuppressive properties chloroquine has been considered for many uses. Before the days of metronidazole it was a mainstay in the treatment of amoebiasis,  and I believe was used by the famous Dr. Ben Kean in his book M.D. during a fascinating attempt to dislodge the scolex (head) of a tapeworm from the patient’s intestinal wall. In India chloroquine is still used in primary health centers for the treatment of gout and in patients with suspected chikungunya during the recent outbreaks. Let’s see where it goes next.

The mosquito vector, and by extension local ecology, drives malaria transmission. So understanding vector biology is important to malaria control. Classical studies of mosquito flight range, feeding preferences, and resting habits were crucial in the development and application of control strategies. Modern vector biology research, dominated by molecular studies, has produced new tools for monitoring insecticide resistance in mosquitoes as well as identifying Anopheles sibling species among whom the potential for transmitting malaria can broadly vary.

Recently, I browsed through a malaria journal article (open access!) whose potential I have difficulty understanding. Can someone explain to me how research on variation in chromosomal inversions and their relationship with stress responses will improve malaria control? Looking carefully through the manuscript, the sole rationale that I could find was:

Polymorphism for the 2La inversion creates heterogeneity in the stress response within A.gambiae, which could directly or indirectly reduce the efficacy of vector control measures, and influence the reaction of vector populations to environmental variation including climate change.

I find this single sentence advanced by the authors both incomplete and unsatisfying. It tells you very little. So let’s think through the rationale ourselves. Understanding the ability of a vector to exploit different habitats is certainly useful – we could predict how mosquito ranges and other characteristics may change with the climate. Understanding the molecular basis of that ability might further help – if the molecular changes had a clear association with a phenotype of interest (i.e. real world characteristics of the mosquito) and were such that they could easily be monitored. Understanding polymorphisms in those molecular mechanisms and their relationship to stress response variation however is not intuitively valuable (perhaps for modelling purposes?). To be clear, my aim is not cast the research as meaningless (though it may be). Sometimes the impact of basic science take years or decades to be realized. Rather, I’m surprised the authors, and especially the reviewers, did not seek to clearly convey the value of the work. If the purpose of public health research is to improve health, then the communication of such research should describe its relevance in explicit and detailed language.

The Multilateral Initiative on Malaria conference is the largest scientific gathering for malaria with more than 2,000 attendees. The conference has a blog for the press but Tropika is the site to watch with initiatives like researcher interviews and day by day coverage. Actually, this is the first time I have seen scientific event reporting that is  accessible to the general public and innovative in its content. The usual fare consists of “advertisement” press releases  echoed around the web and in print by an uncritical press corps. More to come as news emerges.  (Thanks to Kanya)

I get a lot of emails about malaria and other global health events. Here’s a recent one that may be of some interest to those living near Washington, DC:

Malaria in the America Forum 2009:
“Counting Malaria Out” towards the 2010 targets and the UN Millennium Development Goals.

Friday, November 6, 2009
1:00pm – 4:30pm
Room B, Pan American Health Organization
525 Twenty-Third Street, NW
Washington D.C.

The Pan American Health Organization, the Pan American Health and Education Foundation and the Center for Global Health at the George Washington University in the 2009 commemoration forum for Malaria Day in the Americas on November 6, 2009 (Friday). We welcome you to take part in an engaging discussion which will highlight the progress of efforts towards achieving global goals and national targets on malaria prevention and control, the challenges of malaria elimination, and resolving various issues on malaria work with mobile populations.

Another reason this caught my eye  is I have an old malaria day of the America’s shirt from Guyana. The motto is quite a mouthful! Speaking of mobile populations and Guyana, Bill Brieger at Malaria Free Future has excellently covered both recently.

I’ve covered the Gates grand challenge exploration grants before, but some of the winners from the most recent round may take the “this just sounds crazy” cake – chewing gum for a saliva based diagnostic, and chocolate compounds as potential treatments!