Impact of home-based management of malaria on health outcomes in Africa: a systematic review of the evidence

Malaria remains one of the major public health problems worldwide, and of the estimated 400 to 900 million episodes of fever occurring yearly in African children, probably about half are due to malaria, resulting in over one million deaths [1‐3]. However, the proportion of deaths due to malaria varies widely with malaria transmission [4, 5]. Prompt treatment with effective antimalarial therapy is essential and African leaders have committed to ensuring that 80% of malaria episodes are adequately treated within 24 hours of onset of symptoms by 2010 [6]. However, treatment of malaria is challenged by inadequate health-care infrastructure in many parts of Africa [7, 8]. Health facilities are often resource-limited, and access to care may be limited by distance, fees, inadequate staffing, and lack of essential medicines [9‐11]. The direct and especially indirect costs of seeking health care from formal facilities may be substantial, providing a major barrier for many households [12]. Thus, febrile illnesses are commonly treated at home, frequently with drugs purchased from shops [13]. It is estimated that fewer than 20% of children with malaria in endemic areas are treated in formal health-care settings [1].

To improve access to antimalarials, the World Health Organization (WHO) is promoting home-based management of malaria (HMM) as a major strategy for Africa [14]. HMM involves presumptively treating febrile children at or near home with antimalarial drugs distributed by trained members of the community [14, 15]. Community distributors provide medications and educate primary caregivers about treatment of malaria, administration of antimalarial drugs, and recognition of severe illness. Emphasis on prompt treatment and distribution of pre-packaged antimalarials are strengths of the HMM strategy [16, 17]. However, there are potential downsides to presumptive treatment at home. Use of antimalarials to treat all febrile episodes, even if administered correctly, may delay treatment of other illnesses [18]. In addition, unnecessary over-treatment with antimalarials could promote drug resistance [19, 20] and is likely to have substantial economic consequences [21].

Recently, antimalarial treatment policies in Africa have undergone a major transition; most countries have adopted artemisinin combination therapies (ACTs) as first-line treatment for uncomplicated malaria [22]. Whether ACTs can be successfully incorporated into HMM and used safely and effectively at home is a critical question [23, 24]. The cost of implementing ACTs in sub-Saharan Africa according to current prescribing practices has been estimated at US$ 1.6 – 3.4 billion per year, and the cost-effectiveness of deploying ACTs in HMM remains uncertain [21, 23]. Quoted data supporting HMM policy are limited, and the impact of HMM on malaria-associated morbidity and mortality has not been fully established in most settings. The ideal regimen for use in HMM programmes is also not clear, and may vary by setting. This paper presents a review of published studies evaluating the health impact of community- and home-based treatment for malaria in Africa. The aim of this review is to summarize the current evidence base for HMM, and to identify areas where further research could guide implementation of HMM in Africa.

A search of PubMed was conducted on 10 June 2007 using the keyword strategy in Table 1. All abstracts identified in the search were reviewed for potential relevance; if abstracts appeared to satisfy the stated criteria, the full text was obtained. Bibliographies of relevant publications and studies referred to in the gray literature (WHO and national reports) were also reviewed. Inclusion criteria for studies reviewed were as follows: 1) the intervention evaluated consisted of antimalarial treatment administered presumptively for febrile illness; 2) the treatment was administered by local community members who had no formal education in health care; 3) measured outcomes included specific health indicators such as malaria morbidity (incidence, severity) and/or mortality, and/or malariometric indices including parasite rates, hemoglobin or packed cell volume (PCV), and spleen rates; and 4) the study was conducted in Africa.

One thousand sixty-nine (1,069) potentially relevant articles were identified, most of which were not related to community-based diagnosis or treatment of malaria. Of the remainder, the following were excluded: a study that evaluated treatment in schools [25], as well as studies that measured only process indicators [26‐28], assessed only changes in care-seeking and referral patterns [18, 28], or evaluated only feasibility and acceptability [29‐32]. A study from Niger, published in 1985, reported differences in malaria morbidity between villages with and without village health workers who provided both chemoprophylaxis and presumptive treatment with chloroquine (CQ), but there were no data distinguishing the effects of treatment from those of chemoprophylaxis [33]. Only one study, also published in 1985, was excluded on the basis of being conducted outside Africa; this study reported on the health impact of a village-based programme for presumptive antimalarial treatment of fever in Papua New Guinea [34]. Six studies that met all inclusion criteria were identified (Figure 1).

Six studies that involved presumptive administration of antimalarial treatment at or near the household level and that met the search criteria were identified (Table 2 and Figure 2) [35‐42]. One project in Kenya [35, 36] and another in The Gambia [37, 38] were described in multiple papers.

Prompt treatment with effective antimalarials is a cornerstone of malaria control in Africa. HMM has the potential to improve treatment delivery and decrease malaria-associated morbidity and mortality. However, the HMM strategy is a major undertaking, and its implementation should be based on sound evidence of public health benefit. To assess the current evidence base for HMM, a review was conducted of published studies that evaluated the health impact of community- and home-based treatment for malaria in Africa. The six studies identified were conducted in diverse epidemiological settings in five countries over a span of 18 years. Heterogeneity of the evaluations, including variability in study design, precluded meta-analysis. All studies were conducted in rural areas, and most were done in settings with seasonal malaria transmission. Of the two trials conducted in perennial transmission areas, one in Kenya showed no obvious effect of the intervention [35, 36], while the other in the Democratic Republic of Congo showed a decrease in malaria morbidity but no impact on mortality [39]. All studies evaluated presumptive treatment with CQ, and only two studies (both in Burkina Faso) reported using pre-packaged drugs, a key element of the HMM strategy; critically, no data are available on use of ACTs or other alternative therapies [45]. Of the four studies that included mortality endpoints, only one showed a benefit [41]. Data showing an impact of community-based programmes on malaria morbidity are also relatively sparse with only one study showing a decrease in malaria prevalence and incidence [39], and one demonstrating a decreased risk of progression to severe (essentially cerebral) malaria [42]. Thus, current evidence demonstrating the health benefit of home- and community-based presumptive treatment of fever with antimalarials is limited, and does not necessarily support widespread implementation of HMM.

The WHO has advocated scaling up home-based programmes in malaria-endemic countries, supported by the positive results of the two most recent studies [14, 41, 42]. As of 2004, three countries in Africa (Eritrea, Ethiopia and Uganda) were implementing the full HMM strategy with a non-ACT regimen, while other countries were incorporating some components of the strategy [15]. In Uganda, HMM was initiated with pre-packaged CQ + sulfadoxine-pyrimethamine (Homapak), but artemether-lumefantrine (AL) has recently been introduced in the HMM programme in northern districts, and widespread introduction of AL is expected in the future. Although there are plans to evaluate use of AL in HMM in Uganda, and a community-based trial of AL is currently on-going in Burkina Faso (Sirima, personal communication), currently there are no published data on use of ACTs in HMM programmes.

Provision of ACTs in HMM could have substantial economic and public health implications. Implementation of home- or community-based programmes based on non-ACT regimens (CQ or CQ plus sulfadoxine-pyrimethamine) have been shown to be relatively affordable [40, 46], and a cost-effectiveness model found that provider training, community education and pre-packaging of CQ compared favorably with other malaria control measures [47]. The system costs of implementing HMM are expected to be similar regardless of which regimen is used; however, the cost of deploying ACTs in HMM will certainly be higher than that of CQ. Although the effectiveness of HMM with ACTs is likely to be greater than with CQ, this has not been demonstrated. In addition, further evaluation of the cost-effectiveness of HMM, particularly using ACTs, would be instructive. Deployment of ACTs just within the public health sector already poses a significant challenge to many countries due both to cost and to limitations in the global supplies of artemisinin compounds [48‐50], and the costs and benefits of further deployment of ACTs in HMM programmes should be assessed.

Presumptive treatment of all childhood fevers in Africa would greatly increase ACT demand and drug pressure, even if just a proportion of fevers were actually treated. A number of studies suggest that increased antimalarial use speeds the emergence and spread of parasite resistance [20, 51‐53]. Instead of deploying a single ACT regimen as first-line treatment in both health facilities and HMM, use of different regimens in different settings may be an alternative approach. Early modeling work suggests that using more than one ACT in a region, e.g. administering different ACTs in facilities and in HMM, may slow development of resistance, although this theory requires further investigation [54]. Poor patient adherence to treatment is also likely to contribute to the development of parasite resistance, through exposure of parasites to subtherapeutic drug levels [55, 56]. Use of pre-packaged drugs, as promoted for HMM, has been shown to improve adherence [16, 17] which may deter parasite resistance. The impact of widespread presumptive use of ACTs in HMM programmes on the development of drug resistance requires further study.

Considering the available literature, how can future research address the gaps in evidence, especially in the era of ACTs? Evaluation of the impact of community-based treatment on malaria-associated morbidity and mortality in different epidemiologic settings, particularly areas with perennial malaria transmission, would be useful to help support wide-scale implementation of HMM. Additional questions exist regarding the optimal regimen for HMM, method of drug distribution and maintenance of supplies, use of incentives, programme design in different social settings (e.g. rural vs urban), safety risks, sustainability, and cost-effectiveness. A recent WHO document provides a detailed review of the implementation processes of HMM studies conducted in Burkina Faso, Ghana, Nigeria and Uganda, identifying "lessons learned" and challenges for future programme planning [45]. Observations summarized in this document can help to identify opportunities to improve existing HMM programmes and directions for further research. In countries that plan to implement HMM with ACTs, research could be closely linked to implementation, for example by randomizing communities to HMM with ACTs in a phased design with a robust impact assessment data collection system. Further, it will be important to evaluate the impact of different models of delivery of ACTs. For example, what is the added value of HMM with ACTs in a setting where formal health care is strengthened, minimizing medicine stock-outs and motivating staff?

The question of payment of CHWs is an important issue: financial compensation may provide incentive for CHWs to provide consistent service, but payment may also disrupt existing social patterns of reciprocity, and contribute unnecessarily to the cost of the programme [57]. The WHO recommends that CHW incentives and remuneration should be agreed upon with the communities where programmes are implemented [45]. The impact of CHWs, and different compensation approaches, on local socioeconomic structures may be an interesting area for further research. An additional challenge for community-based programmes is the shift in social structures and malaria epidemiology brought on by rapid urbanization in sub-Saharan Africa [58, 59]. Community health interventions in rural areas may be more successful than in urban areas with looser social ties. This effect has already been seen with community-directed treatment for lymphatic filariasis in Ghana, where the programme in urban areas was affected by the "lack of closely knit community structure and ... intense migration" [60]. Consideration of social networks in urban areas will be necessary if successful community-based health programmes are to be implemented in cities, where an increasingly large percentage of the African population lives.

Use of diagnostics to target therapy versus presumptive treatment of fever is another important question. Empiric treatment of fever with antimalarials is widely advocated and practiced in Africa, although presumptive diagnosis has been demonstrated in many settings to be highly inaccurate [61‐64]. Field evaluations of commercially available rapid diagnostic tests (RDTs) for malaria have shown that personnel with no formal training are able to satisfactorily prepare and interpret these tests [65, 66]. RDTs may prove useful in targeting treatment to patients most likely to be suffering from malaria, and their adoption in African HMM programmes should be studied. However, the successful use of RDTs will require a significant cultural shift in the way health workers deal with negative test results [67, 68].

Ideally, all children with malaria in Africa should be treated promptly with effective antimalarials. Presumptive treatment of febrile children with pre-packaged antimalarials in HMM programmes is likely to increase delivery of effective drugs, and improve the timing, adherence, and dosing of treatment. Results from evaluations of community acceptability and feasibility are encouraging, but further study of health outcomes, including the impact on morbidity and mortality, will provide stronger evidence to support sustained implementation of community-based interventions. Introduction of ACTs into HMM will require substantial investment, and may divert funds from other public health programmes and investment in health facilities. Malaria epidemiology, drug resistance patterns, health infrastructure, and societal structures vary widely across Africa. The approach to drug delivery and treatment will likely need to be tailored to local conditions. Further evaluations of HMM and community-based delivery of antimalarials will help to optimize treatment strategies and maximize health benefits.