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CSU 120/2010: TWO ON MALARIA PROGRAMME IMPACT

Thursday, 25th of November 2010

CSU 120/2010: TWO ON MALARIA PROGRAMME IMPACT

1) MALARIA IN AFRICA: PROGRESS AND PROSPECTS IN THE DECADE SINCE THE ABUJA DECLARATION

Also at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907486/pdf/ukmss-31458.pdf

Robert W Snow and Kevin Marsh

Kenya Medical Research Institute/Wellcome Trust Collaborative Programme, Centre for

Geographic Medicine, Nairobi and Kilifi, Kenya (Prof R W Snow FMedSci, Prof K Marsh

FMedSci); and Centre for Tropical Medicine, Nuffeld Department of Clinical Medicine, Centre for

Clinical Vaccinology and Tropical Medicine (CCVTM), University of Oxford, Oxford, UK, (R W

Snow, K Marsh)

Malaria is a global health problem but more than 70% of the total morbidity is in Africa.1 10 years ago, heads of state from across Africa signed a declaration in Abuja, Nigeria, to “halve the malaria mortality for Africa’s people by 2010”.2 This Viewpoint discusses how far we have come in this effort, what we can expect for the future, and what our priorities should be.

Not long after the launch of the Global Malaria Eradication Programme in 1955, it became apparent that elimination was not yet achievable in sub-Saharan Africa. In 1969, global malaria eradication changed from a time-limited campaign to a long-term goal. The strategy started to focus on control, but in practice this approach relied on treatment of febrile illness and during the 1970s and 1980s, malaria-specific mortality began to rise frighteningly as resistance to chloroquine spread.3

By the early 1990s, the failure of national and international institutions to control malaria was increasingly seen as a disaster. A meeting of the world’s health ministers in Amsterdam, Netherlands, in 1992 aimed to refocus attention on malaria by launching a global declaration on the control of the disease that gave special prominence to Africa and expressed the “urgent need for commitment to malaria control by all governments, all health and development workers, and the world community”.4 In 1995, the UN Secretary-General launched a special initiative for Africa that included malaria control as one of a limited number of specific goals. In 1998, the Director of WHO launched the Roll Back Malaria movement as a cabinet-level initiative. At the Abuja meeting in April, 2000, African leaders agreed to halve mortality from malaria in Africa by 2010 by implementing the strategies and actions of the Roll Back Malaria programme, ensuring that at least 60% of the continent’s at-risk population was protected or treated with appropriate methods.2 The Global Fund to Fight AIDS, Tuberculosis and Malaria was established in 20025 to make large-scale funding available for health-related Millennium Development Goals (MDGs).6 Roll Back Malaria, leading the resurgence of interest and implementation, had an explicit focus on countries with a high burden of disease, and for the first time Africa was at the centre of international attention for malaria.

Correspondence to: Prof Robert W Snow, Malaria Public Health and Epidemiology Group, Centre for Geographic Medicine, KEMRI–

University of Oxford–Wellcome Trust Collaborative Programme, Kenyatta National Hospital Grounds, PO Box 43640-00100,

Nairobi, Kenya, rsnow@nairobi.kemri-wellcome.org.

Contributors

RWS wrote and revised the report. KM contributed to intellectual content and helped to revise the report.

Conflicts of interest

We declare that we have no conflicts of interest.

UKPMC Funders Group

Author Manuscript

Lancet. Author manuscript; available in PMC 2010 July 21.

Published in final edited form as:

Lancet. 2010 July 10; 376(9735): 137–139. doi:10.1016/S0140-6736(10)60577-6.

UKPMC Funders Group Author Manuscript UKPMC Funders Group Author Manuscript

Despite a faltering start and substantial criticism, international advocacy has been

remarkably successful. In 1998, worldwide spending on malaria control was around US$100 million.7 By the end of 2009, the Global Fund had approved $5·3 billion for 191 malaria grants in 82 countries, almost 75% of all external financing for these countries.8 The new funds have been used to support a fairly consistent set of priority interventions across most African countries, including use of insecticide-treated nets, selective use of indoor residual house spraying, reduction of maternal and neonatal consequences of infection during pregnancy, replacement of failing drugs with artemisinin-based combination therapy (ACT), and improvement of diagnostic capacities at the point of care with rapid tests. Most of these interventions were not available during the time of the Global Malaria Eradication Programme and therefore provide a new opportunity for revised objectives for malaria in Africa. The scale of the increased funding for malaria control and prevention has led to an exponential rise in the importation of bednets and ACTs.9 Policies to support free massdistribution of insecticide-treated nets have been established in an increasing number of African countries,10 supported by WHO. More countries are adopting indoor residual spraying9 to augment use of insecticide-treated nets. In 2003, only four countries in Africa had adopted ACTs as first-line treatment; by 2010 ACTs were first-line treatment in every malaria-endemic country in Africa.

Against general long-term trends of changing epidemiology, economic development, and

population growth and mobility, more recent changes have included substantial reductions in malaria transmission and incidence of clinical malaria, reported from different locations across Africa.11-15 In some of these situations the changes have been striking. In our own experience on the coast of Kenya, we have seen the incidence of severe malaria fall by more than 90% in 5 years, changing it from a major cause of childhood illness and death to a relatively minor problem.14,15 Two points are important here. First, this reduction should not be assumed to be occurring everywhere in Africa; some areas even within a country show no change or continued increases in disease risks.14 Second, although these changes could be attributed to enhanced prevention and control activities, the truth is probably much more complex. Certainly, on the Kenyan coast there is evidence of a long-term reduction in malaria transmission going back over 15 years, with recent falls in clinical disease the result of a much longer-term process that is not well understood.15

The first effect that good malaria control might be expected to have is a reduction in cause specific malaria morbidity and mortality. Because malaria accounts for a large proportion of attendances at clinics and admissions to hospital, this reduction would be of major public health importance. However, many experts have argued that malaria has a major, although poorly defined, effect on increasing propensity to other diseases, particularly invasive bacterial disease.16 With the decline in malaria transmission on the Kenyan coast, we have seen a remarkable reduction in admissions to hospital for children with life-threatening invasive bacterial diseases, particularly those caused by gram-negative organisms. This trend has been paralleled by a halving in all-cause child mortality over 20 years.

Changes in malaria, invasive bacterial disease, and all-cause mortality occurring in parallel over many years might simply suggest broader changes in society and access to health care.

The experience of the island of Bioko, Equatorial Guinea, is therefore important. In 2003, a programme of integrated malaria control began on the island. An assessment of progress over the first 4 years showed major reductions in entomological indices of transmission and encouraging declines in rates of parasitaemia and anaemia. By far the most important result was a two-thirds reduction in mortality in children under 5 years of age.13 Even more astonishing was the fact that this change took place over a short period, corresponding to the year in which malaria transmission was substantially reduced by an indoor residual spraying paign. In effect, Bioko achieved its MDG for childhood mortality in a single year by a single intervention. Although Bioko has a fairly small population, why shouldn’t the same sort of effect on childhood mortality be achievable in larger populations and in all malaria endemic countries?

Such successes have brought a sense of optimism to the malaria community. In October,

2007, a meeting was held in Seattle, WA, USA, that transformed the framework of global malaria control. Unexpectedly, the central idea was that malaria eradication was not only possible, but should be the only goal.17 Many articles flooded the scientific and popular press and previously cautious malariologists, released from a 40-year collective depression after the perceived failure of the global eradication campaign, have been invigorated by the notion of elimination. Roll Back Malaria and WHO’s targets moved quickly from carefully designed plans to support the MDGs to supporting a “universal roadmap to ensure nationwide malaria control, elimination, and eventual eradication”.18 Several African ministries of health announced plans for eliminating malaria within the next 7–10 years.

Increased advocacy and international funding have had an effect on disease in some areas of Africa and this success must be applauded. However, progress has been, on a continental scale, modest at best. Even though the public health effects of insecticide-treated nets had been reported for more than 15 years, in 2002 the proportion of African children sleeping under insecticide-treated nets was only 1·8%. With the rise in funding and changing methods of delivery, this proportion rose to 18·5% by 2007.10 Although this increase is encouraging, tens of millions of children remain unprotected9,10 and 33 countries had coverage of less than 40% in 2007.9,10,15 Treatment of all clinical cases of malaria with an ACT has so far proven to be the most challenging target to meet. Despite the overwhelming evidence that ACTs are preferable to existing monotherapies, and the substantial and important investment in discovering new products, these drugs still reach only a small proportion of people who

need them.9 Poor planning, tendering, and drug supply continue to result in shortages of new effective medicines to treat malaria in the public sector. When ACTs are available they are often dispensed presumptively, without accurate diagnosis.

There has been an unprecedented increase in international funding for malaria control.

However, in 2007 only three countries had more than $4 per head at risk to undertake an

integrated package of control: Djibouti, Sao Tome and Principe, and Equatorial Guinea.

Average funding per head for 20 countries in Africa was less than $1.19 There remains a substantial funding gap. Full, effective coverage of an effcacious intervention strategy

consisting of prevention, disease management, and health promotion has been estimated to cost $4·46 per person in Africa per year,20 or $2·9 billion for populations living under conditions of stable Plasmodium falciparum risk in Africa in 2007.19 Although this cost is high, the experience of the past 10 years has shown that it is not an inconceivable target; indeed, continued pressure on donors is needed to reach and maintain this level of funding.

There is an obvious euphoric sense that elimination might be possible when low levels of transmission have been reached. However, the move from low prevalence to no transmission is not simply a matter of “more of the same” and a final push. A fundamentally different approach is needed, with a completely different set of activities involving surveillance of communities and travellers, and massive investment at a time when the public health consequences of malaria infection are negligible. A recent analysis of the feasibility of malaria elimination in Zanzibar, an island that has reached a position of low parasite prevalence and subsequent substantial declines in disease incidence,11 suggests that active detection of all new cases would be diffcult and would not be cost effective over the next 25 years; overall elimination would be 65% more expensive than maintaining sustained control.

UKPMC Funders Group Author Manuscript UKPMC Funders Group Author Manuscript

The problem of maintaining investment in control once the disease is of minor importance is often emphasised. However, this is not fundamentally different from the case with control of childhood diseases by vaccines in the Expanded Programme on Immunization and no one is seriously suggesting that we should stop funding measles vaccination. Nonetheless, the consequences of donor fatigue are very real and the effects could be worse than simply losing ground and slowly migrating backwards up the mortality curve—rebound is something potentially far more devastating. Reducing present amounts of malaria funding that are providing effective intervention coverage in some countries would be disastrous.

Some of the Abuja targets for 2010 can be reached for some but not all countries in Africa, and we need to focus on a bigger picture of funding universal coverage at a continental scale if we are to reproduce the successes of areas where scaled intervention and effect has been reported. Eradication is the dream of all public health professionals, whether they work on tuberculosis, measles, or malaria. However, in the short to medium term, by which we mean 10–20 years, emphasis on elimination or eradication in strategic plans for most African countries is at best irrelevant and at worst counterproductive if it results in a deviation of resources from previously set goals and raises expectations that cannot be met.

We believe the priorities are clear. We have made substantial progress in international and national advocacy and investment in malaria control. There is convincing evidence that, with currently available methods, malaria can be reduced from a major public health priority to a fairly minor burden on already stretched health systems. Additionally, the secondary benefits of good malaria control are so great that many countries could go a long way to achieving their MDGs for reducing childhood mortality by immediately focusing and intensifying their effort on malaria control. The situation that will deliver this success can be characterised as low endemic control. This goal is admittedly less attractive than elimination or eradication, but it is achievable, its financing requirements are predictable, and its effects

are measurable. Achieving this public health benefit across Africa within the next 10–20 years would leave a legacy that the global community could be proud of in 2030.

Acknowledgments

RWS is supported by the Wellcome Trust as Principal Research Fellow (#079080) and KM is supported by the

Wellcome Trust (#077092). The authors acknowledge the support of the Kenyan Medical Research Institute

(KEMRI) and this report is published with the permission of the director of KEMRI.

References

1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum. Nature 2005;434:214–17. [PubMed: 15759000]

2. WHO. The Abuja Declaration and the Plan of Action. [accessed March 14, 2010]. Apr 252000 An extract from the African Summit on Roll Back Malaria, Abuja(WHO/CDS/RBM/2000.17).

http://www.rollbackmalaria.org/docs/abuja_declaration_final.htm

3. White NJ, Nosten F, Looareesuwan S, et al. Averting a malaria disaster. Lancet 1999;353:1965–67.

[PubMed: 10371589]

4. Kidson C. Global malaria challenge: the Amsterdam summit. Southeast Asian J Trop Med Public Health 1992;23:635–40. [PubMed: 1298069]

5. Feachem RGA, Sabot OJ. An examination of the Global Fund at 5 years. Lancet 2006;368:537–40.

[PubMed: 16890842]

6. Sachs JD, McArthur JW. The Millennium Project: a plan for meeting the Millennium Development Goals. Lancet 2005;365:347–53. [PubMed: 15664232]

7. Narasimhan V, Attaran A. Roll Back Malaria? The scarcity of international aid for malaria control. Malar J 2003;2:8. [PubMed: 12787469]

Lancet. Author manuscript; available in PMC 2010 July 21.

UKPMC Funders Group Author Manuscript UKPMC Funders Group Author Manuscript

8. Global Fund to Fight AIDS, Tuberculosis and Malaria. Commitments and disbursements. [accessed March 14, 2010]. 2009 http://www.theglobalfund.org/en/commitmentsdisbursements/

9. WHO. World malaria report 2009. [accessed March 14, 2010].

http://www.who.int/malaria/world_malaria_report_2009/en/index.html

10. Noor AM, Mutheu JJ, Tatem AJ, Hay SI, Snow RW. Insecticide treated net coverage in Africa: mapping progress in 2000–07. Lancet 2009;373:58–67. [PubMed: 19019422]

11. Zanzibar Malaria Control Program. Malaria elimination in Zanzibar: a feasibility assessment. Mar 14. 2010 October, 2009.

http://www.malariaeliminationgroup.org/sites/default/files/MalariaEliminationZanzibar.pdf

12. Ceesay SJ, Casals-Pascual C, Erskine J, et al. Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis. Lancet 2008;372:1545–54. [PubMed: 18984187]

13. Kleinschmidt I, Schwabe C, Benavente L, et al. Marked increase in child survival after four years of intensive malaria control. Am J Trop Med Hyg 2009;80:882–88. [PubMed: 19478243]

14. Okiro EA, Alegana VA, Noor AM, Mutheu JJ, Juma E, Snow RW. Malaria hospitalization between 1999 and 2008 across Kenya. BMC Med 2009;7:75. [PubMed: 20003178]

15. O’Meara WP, Bejon P, Mwangi TW, et al. Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet 2008;372:1555–62. [PubMed: 18984188]

16. Molineaux L. Malaria and mortality: some epidemiological considerations. Ann Trop Med Parasitol 1996;91:811–25. [PubMed: 9625938]

17. Roberts L, Enserink M. Did they really say…eradication? Science 2007;318:1544–45. [PubMed: 18063766]

18. Roll Back Malaria. Global Malaria Action Plan for a malaria-free world. 2008 http://www.rollbackmalaria.org/gmap/toc.html.

19. Snow RW, Guerra CA, Mutheu JJ, Hay SI. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission. PLoS Med 2008;7:e142. [PubMed: 18651785]

20. Teklehaimanot A, McCord GC, Sachs JD. Scaling up malaria control in Africa: an economic and epidemiological assessment. Am J Trop Med Hyg 2007;77:138–44. [PubMed: 18165486]

2) IMPACT OF NATIONAL MALARIA CONTROL SCALE-UP PROGRAMMES IN AFRICA

‘Several factors potentially have contributed to recent health improvement in African countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality.’

Full text, with figures, is at http://www.malariajournal.com/content/9/1/299

Malaria Journal 2010, 9:299 doi:10.1186/1475-2875-9-299

Richard W Steketee (rsteketee@path.org)

Carlos C Campbell (cccampbell@path.org)

ISSN 1475-2875

Article type Research

Submission date 1 July 2010

Acceptance date 27 October 2010

Publication date 27 October 2010

Article URL http://www.malariajournal.com/content/9/1/299

Malaria Journal

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Impact of national malaria control scale-up programmes in Africa: magnitude and

attribution of effects

Richard W Steketee*, Carlos C Campbell

Malaria Control and Evaluation Partnership in Africa (MACEPA), PATH

2201 Westlake Avenue, Suite 200

Seattle, WA 98121 USA

Email addresses:

Richard Steketee: rsteketee@path.org (*corresponding author)

Carlos Campbell: cccampbell@path.org

Abstract

Background

Since 2005, malaria control scale-up has progressed in many African countries. Controlled

studies of insecticide-treated mosquito nets (ITNs), indoor residual spraying (IRS),

intermittent preventive treatment during pregnancy (IPTp) and malaria case management

suggested that when incorporated into national programmes a dramatic health impact, likely

more than a 20% decrease in all-cause childhood mortality, was possible. To assess the

extent to which national malaria programmes are achieving impact the authors reviewed

African country programme data available through 2009.

Methods

National survey data, published literature, and organization or country reports produced

during 2000–2009 were reviewed to assess available malaria financing, intervention delivery, household or target population coverage, and reported health benefits including infection, illness, severe anaemia, and death.

Results

By the end of 2009, reports were available for ITN household ownership (n=34) and

use (n= 27) in malaria-endemic countries in Africa, with at least two estimates (pre-2005 and post-2005 intervals). Information linking IRS and case management coverage to impact were more limited. There was generally at least a three-fold increase in household ITN ownership across these countries between pre-2005 (median of 2.4% of households with at least one ITN) and post-2005 (median of 32.5% of households with at least one ITN). Ten countries had temporal data to assess programme impact, and all reported progress on at least one impact indicator (typically on mortality); in under-five year mortality rates most observed a decline of more than 20%. The causal relationship between malaria programme scale-up and reduced child illness and mortality rates is supported by biologic plausibility including mortality declines consistent with experience from intervention efficacy trials, consistency of ndings across multiple countries and different epidemiologic settings, and temporal

congruity where morbidity and mortality declines have been documented in the 18 to 36

months following intervention scale-up.

Conclusions

Several factors potentially have contributed to recent health improvement in African

countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality. The documented impact provides the evidence required to support a global commitment to the expansion and long-term investment in malaria control to sustain and increase the health impact that malaria control is producing in Africa.

Background

The Roll Back Malaria (RBM) Partnership endorsed “Scale Up for Impact” (SUFI) as the approach to rapidly increase access to and use of malaria control interventions (as referenced in its Global Malaria Action Plan [1]). SUFI is predicated on the rapid deployment of a package of proven malaria interventions to high levels of coverage to quickly achieve the optimal health effects based on evidence from controlled trials (see Figure 1). Programme impact accrues from multiple intervention effects and, when scaled to high coverage nationwide, is expected to have greater impact than any one intervention alone.

Experience in national programme scale-up has identified key determinants of achieving

impact by assuring that policies and mechanisms are in place to deploy the full package of proven malaria interventions. The preventive interventions—insecticide-treated nets (ITNs) [2-5], indoor residual spraying (IRS) [6-9], and prevention in pregnancy with intermittent preventive treatment (IPTp) and ITNs [10-12]—all have documented efficacy from controlled trials. Malaria case management is clearly assumed to be effective as an intervention, but cannot be tested in placebo-controlled trials because not giving treatment to a malaria-infected person is unacceptable; as a consequence, efficacy estimates for this intervention are not based on clinical trials. Further, the only data available are either summarized expert opinion [13] or time-sequence data from health facilities to provide estimates of protective efficacy for case management with mortality as the outcome [14-17].

These efficacy estimates have been recently reviewed and calibrated for use in models that can estimate the expected benefit in lives saved based on intervention coverage achieved [18].

From 2005 through 2009, a number of countries have scaled up programme coverage,

particularly with prevention interventions, to levels that have achieved measureable impact.

Similarly, data were available from large-scale, but sub-national, malaria control scale-up efforts where impact was documented [19]. In analysing the results of these national and large sub-national programmes, it is important to critically assess the causal relationships across a range of national estimates and programming contexts. This report summarizes recent progress in sub-Saharan African countries and makes the case for attributing health impact to the malaria programme interventions.

Methods

Information was reviewed from national household population-based surveys—including Demographic and Health Surveys (DHS) [20], Multiple Indicator Cluster Surveys (MICS) [21], Malaria Indicator Surveys (MIS) [22], and AIDS Indicator Surveys (AIS) [23]—as well as published literature and a variety of organization reports examining changes from 2000 through 2009 (with emphasis on the interval from 2004 through 2009) in reported delivery of malaria prevention and control products (ITNs, IRS, drugs for prevention and treatment), changes in intervention coverage rates, and reported health benefits (infection, illness, and death). Because malaria is largely a disease of the rural poor and because inequities in intervention delivery have historically resulted in rural and poor populations being underserved [24], the authors focused on estimates of intervention coverage in rural areas of the countries as reported in standard surveys. Standard outcome and impact measures have been set through an iterative review process managed by the RBM Monitoring and Evaluation Reference Group (MERG) [25-27]. The core health impact measures are: 1) all ause

mortality of children younger than five years (in Africa and similar high-endemic

settings); 2) parasite prevalence within age groups (0–59 months or 6–59 months); 3)

anaemia (Hb<8.0gm/dl) rates in young children (6–59 or 6–36 months of age); 4) outpatient case rates preferably with laboratory confirmation; 5) in-patient admission rates preferably with laboratory confirmation; and 6) case fatality rates preferably with laboratory confirmation of parasitaemia. Because rural populations are typically at highest risk of ria and have historically benefited the least by disease control programme scale up, an analysis for rural areas is provided where it was available; “rural” was defined by each country using their national office of statistics’ definitions for population-based surveys.

To assess the strength of the evidence for a causal link between the scale-up of malaria

control interventions and reductions in child morbidity and mortality, considered established criteria for causal association were considered [28]. Several country experiences were reviewed in detail for Tanzania [29-33] and Zanzibar [34], Zambia [35-38], and Bioko Island (Equatorial Guinea) [39-41] to further address aspects of causal association.

Results

Malaria prevention programme scale-up in Africa

Many countries across sub-Saharan Africa have rapidly increased their malaria prevention coverage, particularly with ITNs, but also with IRS in targetedareas and with IPTp and ITNs in pregnant women. Figure 2 demonstrates the substantial progress since 2005 in scaling up rogrammes; it shows national estimates for rural areas (where most of the malaria transmission occurs) in ITN household ownership in 33 countries in sub-Saharan Africa with 29 of these countries having at least two national estimates during the pre-2005 and 2005 through 2009 time interval. Prior to 2005, most countries recorded less than 5% of households having at least one ITN (median of 2.4% ownership). While only three countries exceeded 60% of households with at least one ITN in rural areas from 2005 through 2009, 10

exceeded 40% and 17 exceeded 25% of rural households with at least one ITN (median of ownership for the post-2005 surveys). Figure 3 shows the progress in use of IPTp

and/or ITNs in pregnant women in 28 countries; while nine countries have exceeded 25% use

of IPTp or ITNs in rural pregnant women, 19 have coverage levels below 20%. Figure 4 shows ITN ownership estimates across the African continent by pre-2005 and 2005 through 2009 intervals to provide a profile of the geographic distribution of the scale-up. In general, this increase in coverage coincides with dramatic growth in external committed financing for malaria control from approximately US$100 million in 2003 to US$1.7 billion in 2009 [42].

The scale-up timing lags by approximately one year after the funding becomes available due to the time required for commodity procurement and distribution.

Evidence for programme impact

Based both on country reports and those published in peer-reviewed journals [19], there is consistent temporal evidence for impact (e.g., morbidity and mortality reduction) as malaria programme coverage has increased in countries in the Africa region. Information from 2000–2008 on malaria control progress was reviewed from countries where data were available in the published literature. Some countries and sub-national regions (South Africa, Swaziland, southern Mozambique and Eritrea; see references 57-63 and 45,46 respectively) reported

progress from 2000 through 2004. The majority of countries (Benin, Burundi [43,44],

Ethiopia [47-50], Equitorial Guinea [39-41], Gambia [51, 52], Kenya [53-56], Rwanda [64], Senegal [67], United Republic of Tanzania [29-34], and Zambia [35-38]) had demonstrable progress from 2005 through 2009. Four countries (Cameroon [68]; Congo [69]; Madagascar [70]; and Sudan [71]) had early reports of little or no progress and three countries (Burkina Faso [72], Nigeria [73] and Zimbabwe [74]) had early reports of worsening malaria; more recent information on improved funding and scale-up for malaria control has been reported from these countries but is not yet adequately documented.

Countries and areas with published data on national intervention scale-up and impact include:

Equatorial Guinea-Bioko Island, Eritrea, Ethiopia, Gambia, Kenya, Rwanda, São Tomé and Príncipe, South Africa-Swaziland-Mozambique in the Lubombo Spatial Development Initiative (LSDI) Project, Tanzania (mainland and Zanzibar), and Zambia. Figure 5 shows percentage point increases in coverage for malaria prevention interventions during the past decade for these 10 settings. Marked increases in IRS coverage were documented in the LSDI area and on the islands of Bioko, São Tomé and Príncipe, and Zanzibar; most countries relied predominately on ITN scale-up with some use of IRS and IPTp. Figure 6 shows the temporal reduction in childhood morbidity and mortality.

Country vignette: Mainland Tanzania and Zanzibar

Malaria control scale-up has progressed on both mainland Tanzania [29-33] and on Zanzibar [34]. Mainland Tanzania with its large geographic area and population has yet to achieve full scale-up across all districts, but has increased household ownership of ITNs in both urban and rural areas. In 1999, the Tanzania DHS reported that while 20% of children under five years of age reportedly slept under a mosquito net, only 10% of these nets were treated with insecticide—thus there was an estimated 2% use of ITNs in 1999. By the 2007–2008 DHS, 39% (59% in urban and 33% in rural areas) of houses owned at least one ITN; and the use of IPTp in pregnant women had risen to 30% nationwide. Between 2006 and 2008, malaria parasite prevalence in children under five years of age declined by nearly 30% from 20% to 14%; and in some areas with higher household ITN ownership, the decline was more dramatic [33].

In contrast to the gradual improvement on mainland Tanzania, rapid deployment and high coverage of IRS and ITNs was achieved on Zanzibar, as has the use of diagnostics and artemisinin-based combination therapy (ACT). Zanzibar’s dramatic scale-up of IRS and of ACT began in the 2003 through 2004 time interval and increasing household ownership of ITNs occurred between 2005 and 2006; increasing use of diagnostics began in the 2006 through 2007 interval. This scale-up coincided with documented reductions in child morbidity and mortality; this includes a 68% reduction in outpatient malaria diagnoses, a 75% reduction in malaria hospital admission, a 63% reduction in blood transfusion, and a 72% reduction in overall malaria-attributed mortality [34].

Country vignette: Zambia

From 2004 through 2008, Zambia increased household ITN ownership and use and IPTp coverage nation-wide; IRS was initially targeted to urban and peri-urban areas of 12 districts, eventually expanding to 36 of the 72 districts. ACT was initiated in 2004, but coverage of ACT for clinical or confirmed malaria cases has not experienced the same dramatic increase as that seen as a result of scale-up of prevention intervention coverage. Figure 7 shows this scale-up of coverage from 2001 through 2008: households owning at least one ITN (40% increase), households owning two or more ITNs (64% increase), households with IRS in the last 12 months (58% increase), and children and pregnant women sleeping under an ITN (80% and 85% increase, respectively).

The increased coverage rate of malaria prevention interventions from 2001 through 2008 coincided with reductions in child parasitaemia rates, which fell 53%, with most of the decline in rural areas, and child anaemia rates, which fell 68%, (see Figure 8). All-cause child mortality rates decreased between the DHS of 2001–02 and 2007 (reductions for 0–5 ear age group, 1–11 month age group, and 1–4 year age group were 29%, 38%, and 36%, respectively). Specific analysis of the 2006 MIS data comparing households with ITNs versus households without ITNs showed that after adjusting for other known associations (including child age, urban-rural status, socio-economic status, and use of IRS), children living in houses with ITNs had significant reductions in morbidity in the two year interval:

28% fewer fever episodes in the previous two weeks, 39% lower rates of P. falciparum infection, and 28% less severe anaemia (Hb<8gm/dl). Households owning two or more ITNs had the best results in morbidity reduction. Reported paediatric hospital admissions, hospital deaths attributed to malaria (not all parasitologically confirmed), and paediatric outpatient visits for suspected malaria have similarly decreased, particularly in the 2006 through 2008 interval [37].

Potential contributing factors to the decline in all-cause infant and child mortality were

examined (Figure 9). Most health indicators reflected no or only modest improvement

during the 2001 through 2008 interval; there were no changes in immunization coverage

rates or treatment coverage rates for diarrheal or respiratory diseases during this interval.

DHS and MIS survey data comparisons identified a nearly 50% reduction in the frequency of underweight children (from 28% to 15%) and a substantial increase in the rate of exclusive breastfeeding in infants less than six months of age (from 15% to 35%) from 2005 through 2007. While better breastfeeding practices may have contributed to improved child survival, this alone would not be expected to account for the observed large reductions in child mortality. The improvement in underweight children less than five years of age may have been due to a variety of factors including reduced malaria infections in the population (there were no changes in stunting and wasting). The largest change in intervention coverage that could have positively impacted child survival during this time interval and at this magnitude was the scale-up of malaria control interventions.

Country vignette: Bioko Island, Equatorial Guinea

A substantial effort in Bioko Island started in 2004 with rapid, large-scale increases in twice yearly

IRS coverage, introduction of diagnostics, ACT, and use of IPTp; this was followed

with ITN introduction in 2007. Figure 10 shows the immediate and steep reduction in allcause child mortality (a 69% reduction, from a pre-intervention interval average of 152 to a post-intervention interval average of 55 per 1000 live births) associated with this malaria control scale-up. There were concomitant reductions in vector populations (over 90% reduced), mosquito sporozoite prevalence rates (over 90% reduced), parasite prevalence rates in children under five years of age (68% reduced), fever rates (89% reduced), and severe anaemia rates (Hb <8gm/dl; 87% reduced) [41].

Discussion

The past five years have witnessed the adoption of SUFI by many malaria-endemic African countries, deploying efficacious interventions and collecting comparable indicators that permit assessment of trends in child survival and malaria morbidity. There is remarkable consistency in impact across a diverse range of countries. Among the settings describing marked progress, three are islands (Bioko, São Tomé and Príncipe, and Zanzibar with a combined population of approximately 1.5 million), there is a three-country partnership (LSDI working with some districts in each of Mozambique, South Africa, and Swaziland); three are small countries (Eritrea, Gambia, and Rwanda with a combined population of approximately 16 million), and three are larger countries (Ethiopia, Tanzania, and Zambia with a combined population of more than 100 million). The epidemiologic and demographic breadth of these settings cannot yet be claimed to be representative of the diversity of malaria in Africa. But additional countries are progressing with malaria programme scale-up, and while it is understood that there is an inherent interval between programme scale-up and

documenting programme outcomes, it is clear that a broad and representative profile of

programme impact is emerging.

Attribution of malaria control to the documented improvement in child survival

With the increasing documentation of geographic expansion of malaria programme scale-up in the Africa region, it is important to assess whether the observed health benefits are simply associations in time and place, or if convincing evidence exists to assert a causal relationship between the malaria control interventions and the dramatic documented health improvements.

Based on B.A. Hill’s 1965 epidemiologic framework for causal inference [28], eight criteria need to be considered: 1) experimental evidence; 2) plausibility; 3) strength of association; 4) specificity of the association; 5) temporal congruity [or lack of temporal ambiguity]; 6) biologic gradient; 7) consistency of findings; and 8) coherence of the evidence. For the alaria control interventions, the first two criteria are addressed by the existing scientific studies that document the efficacy of interventions in controlled trials—that is, the interventions have been proven to reduce morbidity and mortality and it is fully plausible that their use in national settings can achieve the comparable results. The country data on intervention coverage scale-up and impact measures largely address criteria 3 through 8. For the strength and specificity of association and the temporal congruity (criteria 3, 4 and 5), a programme assessment may lack the most stringent criteria, however in the examples of Bioko Island, Zambia and Zanzibar, the association and time link between malaria control scale up and reductions in malaria morbidity and mortality is strong; and efforts to examine alternative explanations did not demonstrate substantial weaknesses with the associations.

The timing of the intervention application and the benefit achieved is closely sequenced. The Bioko Island experience shows a dramatic and almost immediate drop in child mortality following the application of the malaria prevention and treatment package [41]. Similarly, the experience in Zanzibar showed a dramatic response to a combination of IRS, ITNs, and aggressive diagnosis and treatment [34]. Regarding biologic-gradient or dose-response, the sum of the multi-country information may not yet fully establish the dose-response effect where higher coverage is directly linked to higher impact. However, it is quite clear that low coverage of malaria interventions remains linked to limited improvements in child survival.

As for coherence of the evidence, it is critical to examine alternative explanations. Factors that could offer alternative explanations for the suggested link between malaria control scaleup and malaria morbidity and mortality reductions might include: 1) variations in rainfall and temperature; 2) broad socio-economic change; 3) changing HIV conditions; 4) other child health interventions discussed previously that might account for the differences; and/or 5) biologic changes in the malaria-vector-human cycle that is making malaria infection and illness less virulent. Many of the studies address and account for rainfall and temperature patterns and demonstrate that these are not plausible explanations of marked reductions in malaria during this time interval in most African countries. In Ethiopia, weather patterns are thought to have contributed to a substantial malaria epidemic from 2003 through 2005, so some of the findings there may be accounted for by this earlier period with high malaria as a

comparison time for more recent scale-up and impact; however, this is not the case for

country settings. Some socio-economic change certainly occurred in Bioko Island with the growth of the oil industry, and improved copper prices in the 2005 through 2008 interval may have contributed indirectly in Zambia—but again, such socio-economic improvements occur in many countries but are not likely to explain the dramatic reduction in childhood mortality documented in the setting of SUFI. HIV rates have not dropped consistently across these countries, but improved treatment with anti-retroviral drugs may have contributed partially to the improved child survival and reductions in fever and malaria incidence and prevalence.

There are numerous challenges in a multi-country review of programme scale-up and its

consequences. Largely, the study relied on national population-based survey data, which typically come from DHS, MICS and MIS, which have been repeatedly compared and updated to assure common wording and sequence of questions and standard reporting procedures; thus it is not expected that these different surveys introduced substantial bias in comparisons. For some questions, the timing of the survey is important. For example ITN use may vary substantially between the high transmission season and the hotter and dryer seasons when few or no mosquitoes prompt people to use their ITNs less; this would generally bias any results to being underestimates of actual ITN use in the peak transmission season. For counting malaria cases, however, a substantial variability is expected between and within countries as the introduction and expansion of diagnostics has increasingly excluded non-malarial fevers over time; unfortunately this leads to over-reporting of progress in reducing malaria cases and it is not possible to fully account for this in this summary review. In addition, child survival may well have been improving in some of these countries prior to intervention scale-up. The health systems must be reasonably robust to deliver the spectrum of malaria interventions through child health services, maternal health services, and

community outreach and campaign distributions. These systems likely have been delivering other services (e.g., immunizations, vitamin A, and treatment of other illnesses) that improve child survival. While a clear majority alternative explanation for the improved health in these countries was not observed, each of these (and possibly additional factors) should be considered carefully by programmes examining the benefit of their malaria control scale-up.

Some of the observed measures of impact are at higher programme effectiveness levels than were predicted based on the coverage levels achieved and the known intervention efficacy data. This should not be surprising for several reasons. First, programmes are typically using ultiple interventions simultaneously (ITNs, IRS, IPTp, and case management), not just one intervention that might have been tested in a controlled trial. Second, the controlled trials likely improved the services for both the intervention and comparison groups, thus making the efficacy estimate a conservative one. In contrast, programmes are being compared historically to times when much less was being done overall for malaria and possibly for other child health interventions, thus their observed gains appear large.

No single intervention can be credited with these dramatic improvements in the many

countries; IRS may be credited in one country, ITNs in another, and effective drugs for case management in a third country. In fact, it is more likely that the composite package of preventive interventions (ITNs, IRS, IPTp) and treatment interventions (changing to highly effective drugs and using quality diagnostics) is responsible for the level of mortality reduction in individual countries. In some settings the benefit has been attributed to a specific intervention but this may be because countries have not clearly accounted for the role of the other interventions. For example, in most countries with marked improvement of case management, it is likely that the use of good diagnostics is responsible for much of the decline in reported malaria cases – by leading to the exclusion of non-malaria fevers from that case count. While scale-up of case management may have been the weakest of the efforts to date, recent emphasis on diagnostics may help further address this in the coming years. Of

note, the overall effect of malaria control has been generated largely through the reduction of malaria transmission—both vector control and aggressive diagnosis and treatment in places like Zanzibar have contributed substantially to reduced transmission. It is inevitable that programme orientation to sustain the current gains will require an intense focus on transmission reduction.

Conclusion

Coincident with the dramatic increase in funding over the past five years, African

governments and their partners have documented the health impact that malaria control can produce by a coordinated national scale-up of the package of malaria control interventions.

The important observation is that the evolving malaria control approach, SUFI, is robust in terms of predictably producing health impact and this can be led by national governments with partners. It can be confidently stated that national malaria programme scale-up has achieved substantial impact across a growing array of African countries. The reductions in child mortality are consistent with or even greater than the estimated 20% reduction in allcause child mortality predicted from the controlled trials of ITNs. In 2010, hundreds of thousands of African children will not die of malaria because of recent national investments.

This represents an impressive health impact across the region achieved through nationalscale implementation of effective prevention and treatment measures. Malaria control with the current array of interventions represents a compelling investment that predictably prevents childhood deaths. But malaria control currently requires daily attention, the ITN must be hung tomorrow just as it was last night, and it must be replaced when it loses efficacy. The global malaria community now understands that malaria control is indeed the best buy currently in terms of child survival in Africa; and much still remains to be done in many countries including countries with large populations and persistent high malaria burdens. Malaria control cannot be sustained as an open-ended recurrent cost for donors and governments. The critical test will be developing the country experience with programming

for incremental elimination of transmission to sustain the benefits of malaria control for

future generations of African children.

List of abbreviations

Abbreviations used in this report include: ACT = Artemisinin-based combination therapy;

AIS = AIDS indicator survey; DHS = Demographic and Health Survey; Hb = Hemoglobin;

HIV = Human immunodeficiency virus; IPTp = Intermittent preventive treatment during

pregnancy; IRS = Indoor residual spraying;

ITN = Insecticide-treated mosquito net; LSDI = Lubombo Spatial Development Imitative;

MERG = RBM Monitoring and Evaluation Reference Group;

MICS = Multiple indicator cluster survey; MIS = Malaria indicator survey;

RBM = Roll Back Malaria; SUFI = Scale up for impact.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors’ contributions

RWS and CCC both contributed to overall design, assembly of information, writing of the report and reviewing of the final manuscript.

Acknowledgements

We would like to acknowledge the many dedicated individuals, organizations and national ministries of health who collected, assembled, and initially reported the information that is summarized here. Their hard work is very much appreciated. Cristina Herdman provided valuable editorial assistance and Manny Lewis proofread the manuscript.

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Figure legends

Figure 1. Malaria programme scale-up: relationship between coverage and expected

burden reduction.

Note: Programme scale-up showing gradual incremental coverage increases (in red)

versus rapid and accelerated coverage increases (in blue); the expected concomitant

burden reduction suggests that the rapid and accelerated approach leads to an

increased burden reduction and added benefit (in gray) from accelerated scale-up.

This graphic assumes a direct relationship between population-based intervention

coverage and programme impact; it also suggests a time lag between achieving high

coverage and having the population experience the intervention benefit (perhaps

across a malaria transmission season).

Figure 2. Percent coverage in rural areas of countries where households own at least one insecticide-treated net (ITN): pre-2005 coverage level (blue) and post-2005 increase in coverage levels (red) from national survey data.

Source: Demographic and Health Surveys (MACRO, www.measuredhs.org); Multiple

Indicator Cluster Surveys (UNICEF, www.childinfo.org); and Malaria Indicator Surveys

(RBM, www.rollbackmalaria.org).

Figure 3. Percent coverage in rural areas of the countries using prevention in pregnant women—either repeated use of intermittent preventive treatment during pregnancy (IPTp) or ITN use.

* These estimates were not specified as two or more doses of sulphadoxine-pyrimethamine

received at antenatal clinic visit.

~These estimates reflect pregnant women sleeping under an ITN the night before the survey;

all others are IPTp received among women giving birth in the past two years.

Source: Demographic and Health Surveys (MACRO, www.measuredhs.com), Multiple

Indicator Cluster Surveys (UNICEF, www.childinfo.org), and Malaria Indicator Surveys

(RBM, www.rollbackmalaria.org).

Figure 4. Geographic distribution in Africa of household ownership of at least one

insecticide-treated net (ITN) from national surveys in the intervals of 1999–2004 and 2005–2009.

Source: Demographic and Health Surveys (MACRO, www.measuredhs.org), Multiple

Indicator Cluster Surveys (UNICEF, www.childinfo.org), and Malaria Indicator Surveys

(RBM, www.rollbackmalaria.org).

Figure 5. Percentage point increases in core malaria interventions in 10 countries

reporting substantial improvement with malaria intervention scale-up.

Source: Demographic and Health Surveys (MACRO, www.measuredhs.org), Multiple

Indicator Cluster Surveys (UNICEF, www.childinfo.org), Malaria Indicator Surveys (RBM,

www.rollbackmalaria.org), and country reports.

Figure 6. Percent changes in key malaria indicators in countries with substantial

malaria control programme scale-up.

Source: Impact of national malaria control scale-up programs in Africa: magnitude and

attribution of effects. Report for the Malaria Control and Evaluation Partnership in Africa

(MACEPA)/PATH, Seattle, USA citing the following articles: Zambia [38], Zanzibar [34],

Rwanda and Ethiopia [48].

Figure 7. Malaria intervention coverage rates from national surveys (2001–2008), and parasitaemia and anaemia rates from Malaria Indicator Surveys (2006 and 2008) in Zambia.

Note: National survey data is available for 2001–2002, 2004, 2006, 2007, and 2008; interim

annual estimates are linear extrapolations between known data points. HH: households;

IPTp: intermittent preventive treatment in pregnancy; IRS: indoor residual spraying; ITN:

insecticide-treated net; anaemia = Hb <8gm/dl.

Figure 8. Malaria intervention coverage rates per national surveys (2001–2008) and infant and child mortality rates (DHS 2001-2002 and 2007)in Zambia.

Note: National survey data is available for 2001–2002, 2004, 2006, 2007, and 2008; interim

annual estimates are linear extrapolations between known data points. IPTp: intermittent

preventive treatment in pregnancy; IRS: indoor residual spraying; ITN: insecticide-treated

net.

Figure 9. Changes in intervention coverage, malaria morbidity and mortality, and

other child health intervention coverage in Zambia between 2001 and 2008.

Source: Demographic and Health Surveys (DHS) in 2001–2 and 2007; Malaria Indicator

Surveys (MIS) in 2006 and 2008.

Figure 10. Rates of all-cause under-five mortality on Bioko Island, Equatorial Guinea: pre- and post-malaria control interventions (IRS, ITNs, case management).

Source: Data taken directly from Table four in Kleinschmidt et al [41]. Malaria interventions

included indoor residual spraying (IRS) and malaria case management with diagnosis and

artemisinin-based combination therapy; increased household ownership of insecticidetreated

mosquito nets (ITNs) was added in 2007.

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