Archive for the 'Delivery' Category

Malaria hotspots and targeting

Heterogeneity exists in the risk of malaria – both between different areas and between individuals in the same area. The old maxim states “malaria is a local and focal disease”. Targeting malaria control interventions (nets, spraying, etc) is thus, a time-honored activity. Countries which undertook malaria eradication efforts have stratified populations at-risk for intervention delivery since  in the 1950s-60s.

In recent years a spate of papers (here, here, and a policy piece here) have emerged on the idea of hotspots and ‘hitting them’ for high-impact control. What do these papers add? These studies quantified the heterogeneity in risk at the individual and household levels and their change with time. Another innovation in measuring the concentration of transmission was the use of serological in addition to parasitological data – although the two studies conflicted on which serological measurement was better. Finally, the papers recommend individual or household-level targeting of certain control interventions (vaccines, mass drug administration, specific vector control activities) at certain times based on annual surveys. What do these studies miss? First, as with many studies, particularly those conducted or focused in sub-Saharan Africa (all of the above), they suffer from a lack of historical perspective. Enamored with the idea of novelty, the authors fail to acknowledge decades of experience in ‘hitting hotspots’ using different data and different units of selection elsewhere in the world. Second, these studies do not assess, deductively or empirically, the direct and indirect costs of targeting. What are the training, delivery, coverage gaps and leakage implications of using serological data compared to parasitological data or of using household level stratification compared to village or area stratification? Without the comparative and programme perspectives such key questions remain unasked.

Using and improving targeting is an important area of work in malaria control. But the detection of these hotspots therefore, does not necessarily lead to their use in control work. Long-standing, sophisticated malaria control programmes face considerable difficulty in targeting activities using much coarser criteria. Conclusions and recommendations should follow from study results. This is a basic principle of scientific writing, and possibly, the most violated due to well-meaning intentions to ‘do something’ along with the less noble imperative to overstate one’s work. Academic research and publication will always favor the new over the credible, future possibilities over present realities. This is not necessarily a bad thing. We need to aim high and we need to look ahead. Programme managers and other practical consumers of the literature should be prudent in the promotion of such work. What worries me is the academic-donor nexus which prevents this caution and brings in varying degrees of distraction.

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More on the not-so-Affordable Medicines Facility for malaria

The evidence just keeps piling up with this new report from Africa Fighting Malaria and a series of papers in Malaria Journal (1, 2, and 3). Not only is the availability and cost falling short of goals as we’ve discussed (here, here, here and here), the patient-centered outcomes which actually matter, are likely far worse. In addition to flaws in the logic of the program and its operations, the report adds a previously undocumented dimension of AFMm failure – leadership. The leaked minutes from its board meeting display an unflattering preoccupation with “reputational risk” for the Global Fund and its donors and a disregard for data that suggests the program may not be working as planned. The report concludes:

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

New results for intermittent preventative therapy in children

Truly beautiful studies – well designed, well thought, even examined cost and service delivery – were recently conducted for regular, presumptive antimalarial treatment (using SP and amodiaquine) of children in Mali and Burkina Faso in settings where treated bed-nets are already in use (PLoS Medicine – open access!). The intervention was effective at reducing clinical burden – from malaria incidence, the primary target, to secondary endpoints such as anemia, all-cause mortality, and stunting.

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

IPTc Efficacy

85%

75%

65%

Baseline*

Rate

NNT

Rate

NNT

Rate

NNT

1000.0

150.0

0.1

250.0

0.1

350.0

0.2

100.0

15.0

1.2

25.0

1.3

35.0

1.5

10.0

1.5

11.8

2.5

13.3

3.5

15.4

1.0

0.2

117.6

0.3

133.3

0.4

153.8

0.1

0.0

1176.5

0.0

1333.3

0.0

1538.5

*Baseline transmission and rates with the intervention are expressed per 100 persons per season

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.

ACT subsidies: do they work?

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.

Millions of malaria drugs and dollars down the drain

The Affordable Medicines Facility for malaria (AMFm, previously introduced here) may go down as one of the largest failures in public health history. Subsidizing effective antimalarials (namely artemisinin-combination therapies) for sale through private vendors (largely the wide-spread pharmacy/drug kiosk) is an untested idea for increasing access – yet is backed by more than $225 million in funding at a time when the successful Global Fund is struggling to finance existing commitments.

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

Directly observed therapy for anti-relapse primaquine treatment

It worked. Really well.

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.

Low-tech coolers for storing malaria rapid diagnostic tests in remote areas

Rapid diagnostic tests for malaria (and other diseases) can extend diagnosis to remote areas. This is sorely needed. Beyond benefits against the disease at hand, the introduction of diagnostics along with associated systems of quality assurance can strengthen the overall health system (previously discussed here). A major barrier for expanding the use of rapid tests is a short-shelf life under field conditions. Tropical temperature and humidity degrade such diagnostics, which use delicate reagents like antibodies, in a matter of months. The short shelf life can necessitate restocking at a frequency which may not be logistically feasible. Thus, routine operation in many countries leads to the use of compromised, or a complete wastage of, tests.

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.


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