Evidence to date suggests that the AMFm was pushed forward too far, too fast and with too much money.

There is one important caveat here – IPTc is only “effective” where the transmission is quite high. In the communities in Burkina Faso and Mali where the study was conducted transmission was  very intense (3-13 infective mosquito bites per person per month). At medium and low levels of transmission (last two rows of the table) the strategy becomes rather untenable, expending a lot of drug (which wastes money and risks side effects and resistance), for preventing a single case. Caveat to my caveat – the interpretation of rates differences in number needed to treat calculations is not always straightforward though I believe valid in this case.

Table: Number need to treat (NNT) and post-intervention incidence rate across varying baseline transmission and IPTc efficacy

Interestingly, similar to the famous Garki project the reductions in incidence appear to be much greater than reductions in prevalence – likely due to the seasonal nature of the intervention against a high vectorial capacity and thus risk of exposure.  Since the focus here is burden reduction, and not transmission reduction as in Garki, it doesn’t matter though.

]]> http://topnaman.com/treatment/new-results-for-intermittant-preventative-therapy-in-children/feed/ 0 http://topnaman.com/treatment/act-subsidies-do-they-work/ http://topnaman.com/treatment/act-subsidies-do-they-work/#comments Sat, 16 Apr 2011 21:11:41 +0000 naman http://topnaman.com/?p=1091 No.

According to a recent report by the Evidence to Policy Initiative (funded by the Gates Foundation which in turn also supported the ACT subsidy idea) . The conclusions are no surprise (see here and here for previous discussions on the idea of selling subsidized artemisinin combination therapy in pharmacies). The summary points were:

• Pilots found a rapid rise in ACT availability in private outlets (pharmacies, drug stores, and other retail outlets), as did one national program. Subsidies were associated with reduced consumer prices (i.e., these subsidies were largely passed along the supply chain to the consumer)
• ACT market share increased rapidly in pilots, crowding out other anti-malarials (e.g., CQ, SP, artemisinin monotherapy), but market share did not increase rapidly in national programs
• Pilots found conflicting evidence on ACT use (one trial was positive, one was negative) and national programs found very little change in use
• The available evidence suggests that ACT price subsidies have less impact among poor, remote communities than among wealthier, urban communities

Notice the first two points arose from small pilots, while the latter deal with scaled programs and are more important to note. None of the evaluations addressed patient-facing outcomes, as a good friend would quickly point out, which are likely to be even worse. Thanks to Devi for the link.

First, are decreased private sector costs even passed on to buyers? It’s hard to say in any systematic way, especially past the small trial projects. Daily Nation media from Kenya reports that the first batches to hit drug stands all over the country are going for 1.25  to 6 times the recommended price of Sh40 (US$0.50). Expect similar reports from other countries.

Second, even if the strategy works to lower drug costs in pharmacies – will it have much public health benefit? Access issues will likely persist in rural areas, where the treatments are most needed, as pharmacies are concentrated in urban areas anyways. Among those with access, the majority of people with fever will not actually have malaria and that proportion is declining as control efforts are strengthened. The resultant overuse of drugs will be enormous, other etiologies of fever may go untreated, and increased drug pressure could quicken the spread of resistance. Adherence to the full course of drugs, which are dispensed without much counseling, may be poor. Coupling a system of diagnosis with the subsidized drugs  seems near impossible, and not doing so is irresponsible.

Finally, let’s remember this is not about providing a quality medical service and does nothing to strengthen a country’s health system. The essential strategy of AFMm is to enable people to continue to “self-medicate but now with better drugs”. It is a desperation move, a stop gap at best.

Pro-market groups, such as the Clinton and Gates foundations, who pushed AFMm are showing no signs of stopping – they’ve learned one trick (and not even well) and want to try it out everywhere. In an Indian editorial, Clinton Foundation blindly promotes the idea in a country where it possibly makes the least sense (in India less than 2% of fevers are due to malaria in most areas and the government is making large investments in improving primary care). While the private sector has a role to play in improving malaria care, we should not invest money or energy in risky and unproven approaches towards this end.

PS: Medecins Sans Frontieres commentary about quality concerns with AFMm

Vivax malaria can relapse from liver stages (hypnozoites) adding to patient burden and further transmission. In tropical settings, upwards of 50-80% of patients may relapse within 1-3 months of the primary infection. Treating the dormant liver stages, which are unaffected by standard therapies, requires 14 days of treatment with primaquine. Adherence to therapy is generally regarded as poor – patients already feel better from the main therapy, primaquine has a number of side effects, and daily dosing for two weeks is a long regimen. Explaining the rationale for the therapy is important to ensure adherence but many health workers have little training or time for counseling and, in my experience, often altogether skip it.

Directly observed therapy (DOT) is exactly what it sounds like. It can be resource intensive but is a proven strategy for ensuring complete and effective treatment (particularly in tuberculosis control efforts). The powerhouse Mahidol University tropical diseases group conducted a randomized study of DOT primaquine in Thailand and followed the patients closely over the next three months to look for new infections.

Among those receiving DOT with primaquine the incidence rate of vivax malaria during follow-up was 3.4 cases / 10,000 person-days while in the self-administered group the rate of vivax was 13.5 cases / 10,000 person-days. No serious adverse events were reported. A quick number needed to treat calculation (with some assumptions about risks) reveals that in this setting the use of DOT primaquine in just 11 cases prevented 1 additional case over three months. The authors note the (already impressive) effect of DOT on subsequent P. vivax appearance is likely an underestimate. The self-administered adherence is inflated compared to the real world. Patients are more compliant under trial conditions (they know they are being studied) and a study follow-up visit at day 7 serves as a convenient reminder halfway through the treatment.

Takeuchi et al. also examined risk factors for vivax malaria reappearance and unfortunately devoted the entire discussion to these findings. I think more conversation about the DOT strategy itself – around questions of when, where, and how to use it in program settings – is the true point of interest in this work.

Cambodia has a solution. The National Malaria Program designed ‘cooler boxes’ using the simple technology of evaporative cooling.They tested the boxes and their ability to maintain temperature, humidity, and extend the usability of malaria tests. RDTs in ambient conditions tested negative on control blood at 210 days while RDTs kept in the cooler box provided positive results up to 360 days. I love this story. First, it tackles a small but immediate need in current operations. Second, the cooler boxes were developed by Cambodia for use in their own programs. Third, they rigorously tested it – with the help of some WHO support (David Bell has been relentlessly working to advance all things rapid diagnosis). It is a judicious use of aid reminiscent of a past WHO where more funds were spent on research, small victories, and demonstration projects.

The article suggests that “For a poor farmer in Cameroon or a poor market woman in Ghana, the difference between 20 cents and $8 is huge” which is true but fails to mention that in many countries ACTs are available free of charge through public and private health facilities. ACTs are already subsidized through national control programs though the extent of their reach could be expanded. I must admit I have my doubts about this plan. First, as Dr. Bernard Nahlen notes in the Times article, there’s scant evidence for a scale-up of this approach. The deputy director of the President’s Malaria Initiative (a solid CDC EIS alumnus – random aside I think CDC involvement is a key reason for PMI’s to date success) is justified in his skepticism. The bulk of data are basic case studies from a few Clinton Foundation pilot projects. Second, even if more rigorous evaluations demonstrate some impact, is it really a desirable way forward?

We need more delivery channels and increasing the availability of ACTs is critical, but it should be done as a component of improving overall case management. The idea of encouraging  indiscriminate pill-popping (even if it is the current scenario) with better drugs probably does not align with most countries health priorities. Additionally, there are also the inherent risks of missing other etiologies of fever and increasing drug pressure. On the other hand, cheap ACTs in drug kiosks may be able to provide quick wins in areas which have seen little progress, but countries should think carefully before embarking on this road. It may be an OK stop gap to stave off some morbidity and mortality in places with non-existent health systems but could sabotage development in the long run.

A follow-up comment I posted on Science magazine’s blog which I think adds some more information:

Going the private route is not new. Global Fund drugs get distributed through private channels in many countries whether it is NGOs or partnerships with industries that have medical facilities. What is newer is the use of drug kiosks but even Cambodia for a few years has been marketing ACTs through private shops – with questionable impact. We’ll see how this effort progresses but it is not likely to help build health systems.