Background
Malaria continues to cause unacceptably high levels of disease and death, as documented in successive editions of the World malaria report [3]; according to the latest report, there were an estimated 229 000 cases and 409 000 deaths globally in 2019. Malaria is preventable and treatable, and the global priority is to reduce the burden of disease and death while retaining the long-term vision of malaria eradication. Here we present the WHO Guidelines for malaria developed by the WHO Global Malaria Programme as a comprehensive and inclusive resource for advice on malaria.
The Global technical strategy for malaria 2016–2030 [4] (GTS) provides an overarching framework to guide malaria control and elimination efforts. Adopted by the World Health Assembly in May 2015, the strategy defines goals, milestones and targets on the path to a world free of malaria (). The goals focus attention both on the need to reduce morbidity and mortality, as well as to progressively eliminate malaria from countries that had malaria transmission in 2015. The GTS presents a framework through which the goals can be achieved ().
Goals, milestones and targets for the Global technical strategy for malaria 2016–2030.
The Global technical strategy for malaria 2016 - 2030 [4] states that it is essential for malaria programmes to ‘ensure access to malaria prevention, diagnosis and treatment as part of universal health coverage’ (Pillar 1). Universal health coverage (UHC) means that all individuals and communities receive the health services they need without suffering financial hardship. It includes the full spectrum of essential, quality health services, from health promotion to prevention, treatment, rehabilitation and palliative care. For malaria, WHO has recommended a range of interventions - namely vector control, chemoprevention, diagnostic testing and treatment - to reduce transmission and prevent morbidity and mortality. A UHC approach means ensuring that individuals and communitieis are covered by the appropriate mix of these interventions, based on local context, to control and ultimately, eliminate malaria.
The principal objective of national malaria programmes is to combine a selection of these interventions into packages that are tailored to achieve sustainable and equitable impact in a given setting. To decide upon the appropriate intervention package and allocation of resources that will achieve this objective and contribute to UHC, programmes should use a process that combines the analysis of impact and value for money with extensive stakeholder engagement and discussion. The process should be informed by past and current malaria transmission intensity and incidence data; contextual vulnerability related to the human host, parasites, vectors and past and present intervention coverage; acceptability; and equality of access and use (including analysis of financial barriers and how to address them). When the objective is elimination, a similar process is undertaken although the types of interventions and value for money analysis will be different than in high burden settings.
Global technical strategy for malaria 2016 - 2030: framework, pillars and supporting elements.
Following progressive reductions in malaria burden between 2000 and 2015, progress stalled. By 2017 the world was off track to achieve the malaria morbidity and mortality reduction targets. In response, a revitalization effort, called “High burden to high impact”, was launched in 2018 [5]. This approach focuses attention on how to get back on track: garnering political will to reduce the toll of malaria; using strategic information to drive impact; developing better guidance, policies and strategies; and improving coordination of support for national malaria responses. Although the impetus for articulating these key activities was the need to get back on track to achieve the GTS morbidity and mortality targets, these activities apply equally well to all malaria endemic countries and to ensuring continued progress with the GTS elimination goals.
Objectives
These consolidated WHO Guidelines for malaria aim to provide the latest evidence-based recommendations in one reference to support countries in their efforts to reduce and ultimately eliminate malaria. The objectives of the Guidelines are:
To provide evidence-based recommendations on the appropriate choice(s) for malaria prevention (vector control and chemotherapies) and case management (diagnosis and treatment) across all transmission settings;
To support the development by WHO Member States of evidence-based national malaria policies for prevention and case management across all transmission settings;
To encourage the use of local data to inform subnational stratification to maximize the impact of available resources; and
To inform the research agenda to enable updates to the Guidelines by identifying gaps in evidence that constrain the development of guidance or weaken current recommendations.
Target audience
The primary audience for these guidelines is the policy makers in ministries of health and the managers of national malaria control programmes in endemic countries. The Guidelines may also be of interest to health care practitioners, environmental health service professionals, procurement agencies, the private sector, and civil society groups. The Guidelines are also intended for use by international development partners, donors and funding agencies in order to support decision-making on allocation of resources in support of interventions and procurement of appropriate malaria control products. They are also intended to guide researchers, research funders and those interested in the outcomes of research to address the evidence gaps that are constraining the development of guidance or weakening current recommendations.
Scope
The consolidated WHO Guidelines for malaria bring together all recommendations for malaria, including prevention using vector control and preventive chemotherapy, diagnosis, treatment and elimination strategies. The Guidelines also provide links to other resources including guidance and information on: strategic use of information to drive impact; surveillance, monitoring and evaluation; operational manuals handbooks, and frameworks; and a glossary of terms and definitions.
The Guidelines provide:
evidence-based recommendations pertaining to vector control tools, technologies and approaches that are currently available for malaria prevention and control, and for which sufficient evidence on their efficacy is available to support systematic reviews. The Guidelines are intended to provide an underlying framework for the design of effective, evidence-based national vector control strategies and their adaptation to local disease epidemiology and vector bionomics;
evidence-based recommendations on the use of antimalarial medicines as preventive chemotherapy in people living in malaria-endemic areas who are at risk of malaria morbidity and mortality. These approaches include intermittent preventive treatment (IPT) in pregnancy (IPTp), IPT in infants (IPTi) and seasonal malaria chemoprevention (SMC);
evidence-based recommendations on the treatment of uncomplicated and severe malaria in all age groups and situations, including in young children and pregnant women; and
guidance on strategies for elimination settings (recommendations are in development).
No guidance is given on the use of antimalarial agents to prevent malaria in people travelling from non-endemic settings to areas of malaria transmission. This is available in the WHO International travel and health guidance [6].
Structure of the Guidelines
The guidelines are organized around the major interventions available for malaria: prevention (vector control and preventive chemotherapies), case management (diagnosis and treatment), and strategies to be used in elimination settings. Although guidance on surveillance, monitoring and evaluation is not generated using the same methodology as other recommendations, it is an important source of information on approaches to optimize implementation and can be accessed through links for ease of reference. The Guidelines are structured as follows:
Section 4. Prevention: recommendations and practice statements for prevention strategies including vector control and preventive chemotherapies.
Section 5. Case Management: recommendations and practice statements for diagnosing malaria; treating uncomplicated malaria; treating special risk groups; treating uncomplicated malaria caused by
P. vivax, P. ovale, P. malariae or
P. knowlesi; and treating severe malaria. Also included is information for treating malaria in special situations (e.g. epidemics and humanitarian emergencies and elimination settings) and other considerations in treating malaria.
Section 6. Elimination: recommendations and practice statements for implementation in elimination settings (currently in development and anticipated to be published in 2021. Also includes links to the framework for malaria elimination
Section 7. Surveillance: high level overview on surveillance and presents information on the strategic use of information for subnational stratification to drive impact and links to further resources.
Section 8. Methods: describes the methods used to develop the recommendations and practice statements.
Section 9. Glossary: defines commonly used terms for malaria control and elimination and links to the WHO publication on malaria terminology.
Section 10. Contributors and interests: presents the many contributors to the development of this guideline and their declared interests.
Etiology
Malaria is a life-threatening disease caused by the infection of red blood cells with protozoan parasites of the genus Plasmodium that are transmitted to people through the bites of infected female Anopheles mosquitoes. Four species of Plasmodium (P. falciparum, P. vivax, P. malariae and P. ovale) most commonly infect humans. P. falciparum and P. vivax are the most prevalent species and P. falciparum is the most dangerous. A fifth species, P. knowlesi (a species of Plasmodium that primarily infects non-human primates) is increasingly being reported in humans inhabiting forested regions of some countries of South-East Asia and the Western Pacific regions, and in particular on the island of Borneo.
Malaria transmission, acquisition of immunity, and clinical manifestations of disease
The intensity of transmission depends on factors related to the parasite, the vector, the human host and the environment. Transmission tends to be more intense in places where the mosquito lifespan is longer and where the females prefer to bite humans rather than other animals. The survival and longevity of female mosquitoes is of critical importance in malaria transmission, as the malaria parasite generally requires a period of 7–10 days to develop inside the mosquito into a form that is infective to humans. Female mosquito longevity is dependent on intrinsic, genetic factors, as well as on environmental factors including temperature and humidity. The strong human biting habit of the African vector species is one of the reasons why approximately 90% of the world’s malaria cases occur in Africa.
Transmission intensity is usually assessed as the incidence of cases or the prevalence of infection. Most countries have information on the annual parasite incidence (number of new parasitologically confirmed malaria cases per 1000 population per year) from routine surveillance and/or on the parasite prevalence from surveys, often conducted during or just after periods of peak transmission [7].
The following categories of transmission intensity are indicative and meant to provide an adaptable framework in which each country can conduct a stratification exercise to classify geographical units according to local malaria transmission.
Areas of high transmission are characterized by an annual parasite incidence of about 450 or more cases per 1000 population and a P. falciparum prevalence rate of ≥35%.
Moderate transmission areas have an annual parasite incidence of 250–450 cases per 1000 population and a prevalence of P. falciparum/P. vivax malaria of 10–35%.
Areas of low transmission have an annual parasite incidence of 100–250 cases per 1000 population and a prevalence of
P. falciparum/P. vivax of 1–10%. It should be noted that the incidence of cases or infections is a more useful measure in geographical units in which the prevalence is low, given the difficulty of measuring prevalence accurately at low levels [
8].
Very low transmission areas have an annual parasite incidence of < 100 cases per 1000 population and a prevalence of P. falciparum/P. vivax malaria > 0 but < 1%.
The relation between parasite incidence, parasite prevalence and the number of cases presenting to a health facility per week can be estimated in models [9]. Differences in transmission from one area to another may be due to geographical characteristics, such as altitude, temperature and humidity, rainfall patterns, proximity to water bodies, land use, vector species and distribution, socio-demographic characteristics, access to antimalarial treatment, and coverage with vector control. In most endemic areas, seasonal patterns of transmission are seen, with high transmission during part of the year. Both the intensity and timing of transmission are important considerations in designing elimination strategies.
The manifestation of clinical disease depends strongly on the background level of acquired protective immunity, which is a consequence of the pattern and intensity of malaria transmission in the area of residence. In areas of moderate to high transmission, partial immunity to clinical disease and a reduced risk of developing severe malaria are acquired in early childhood. The pattern of acquired immunity is similar across the Sahel subregion, where malaria transmission is intense only during the 3- or 4-month rainy season and low at other times. In both these situations, clinical disease is confined mainly to young children, who may develop high parasite densities that can progress rapidly to severe malaria. In contrast, in these settings adolescents and adults are partially immune and suffer clinical disease much less frequently, although they often are infected with low blood-parasite densities. Immunity is modified in pregnancy, and gradually lost, at least partially, when individuals move out of the endemic areas for prolonged periods (e.g. a year or more).
In areas of low and very low transmission, as found in much of Asia, Latin America and other malaria endemic areas, the transmission fluctuates widely by season, year, and over relatively small distances. P. vivax is an important cause of malaria in these regions. This generally low transmission delays acquisition of immunity, so that adults and children alike suffer from acute clinical malaria, with a significant risk for progression to severe malaria if left untreated. Epidemics may occur in these low or very low transmission areas when the inoculation rate increases rapidly because of a sudden increase in vectorial capacity. Epidemics may result in a very high incidence across all age groups which can overwhelm health services.
In moderate and high transmission areas, with sustained high coverage of vector control and access to treatment, reduced exposure to malaria infection may change the population structure of acquired immunity to reflect that found in low or very low transmission areas, resulting in a corresponding change in the clinical epidemiology of malaria and an increasing risk of epidemics if control measures are not sustained.
Strategic information to tailor programmatic response and selection of interventions
As malaria control improves, malaria transmission and risk become increasingly heterogeneous, both between and within countries. Thus, a “one size fits all” approach to program decisions about intervention selection becomes inefficient. The situation requires stratification of the country at subnational levels according to past, present and future malaria risk, the structure and function of the health system, and other contextual factors. Stratification provides a rational basis to identify context-specific packages of interventions to target specific populations in the different subnational strata. Local data are essential to complete stratification and to inform the selection of the optimal mixes of interventions to maximize impact. Given that resource constraints usually limit the implementation of all desirable interventions in all areas of malaria risk, a prioritization exercise must also be conducted to ensure resource allocation also optimizes intervention mixes and resultant impact. Guidance on these activities is available in Section 7 (Surveillance).
The choice of interventions in each stratum should be informed by WHO’s recommendations. However, given the complexities of malaria, with heterogeneity of risk and the unique contexts which every program has to consider, global guidance is not intended and should not be used to provide prescriptive guidance on what should be done in every situation. These Guidelines signal a paradigm shift towards a problem-solving approach using local data to identify recommendations that are relevant at a country level, and based on local context, that define strata-specific packages of interventions that optimize impact and are prioritized for resource allocation. This shift moves away from overly prescriptive recommendations and will clearly distinguish evidence-informed recommendations from contextual considerations. The contextual considerations at national and subnational levels will inform how recommendations should be applied and strategies that may increase access for the target population.
Accurate stratification of malaria transmission intensity is essential for effective targeting of interventions. As countries progress towards elimination, finer scale mapping is required, and stratification should be more specific, ideally at the level of localities or health facility catchment areas [10][11]. As transmission intensity is progressively reduced, stratification needs to include vulnerability and receptivity to malaria, i.e. the risk for importation of malaria cases and the inherent potential of the vector-human ecosystem to transmit malaria.
Conclusion
These Guidelines therefore provide a framework within which national malaria programmes and their implementing partners may adopt and adapt the recommendations for use. Good quality surveillance data can also feed into this process by providing the granular local information needed to inform and evaluate national program decisions (see Section 7. Surveillance). Where the boundaries of current knowledge are pushed, it is particularly important to ensure adequate attention to monitoring and evaluation. The information generated can then feed into updated guidance.
