Active case detection for malaria elimination: a survey among Asia Pacific countries

Over the last decade, major investments in malaria control have led to substantial decreases in the global burden of disease[1, 2]. Today, 99 countries are malaria free, with an additional 34 currently eliminating malaria[1, 3]. Malaria elimination is gaining global political support, and for many countries, national malaria elimination is no longer a question of if, but rather when it will occur[4].

The transition from malaria control to elimination is complex, requiring a shift in strategy and the introduction of new activities that must be tailored to a country’s individual context. A robust surveillance system for the detection of symptomatic and asymptomatic cases, in addition to notification, reporting and investigation of all malaria infections is crucial[1, 4‐6]. Detailed case investigations are particularly important, as they allow malaria control programmes to determine the origin (indigenous or imported) of a case, and conduct appropriate activities in response[7].

Traditionally, countries have used passive case detection (PCD) to capture cases, relying on symptomatic patients to present to a health facility for diagnosis and treatment[8]. It has been well documented, however, that asymptomatic and subclinical or sub-patent infections are common and contribute substantially to ongoing transmission[5, 8‐10]. These individuals do not have malaria symptoms, do not seek treatment, and remain infected for long periods and are, therefore, a source for onward transmission without their knowledge. A control programme may conduct active case detection (ACD) to seek out infection and residual parasite carriers, a strategy recommended by the World Health Organization (WHO) that can be particularly useful for capturing asymptomatic infections[7]. Malaria infections in all transmission settings tend to be clustered geographically in a focus, defined by WHO as a 'defined, circumscribed locality situated in a currently or former malarious area containing the epidemiological factors necessary for malaria transmission’[7]. At a finer resolution, infections cluster into microfoci or “hotspots”, which can be comprised of individuals, households or groups of households that maintain ongoing transmission in a community[11]. In some low transmission settings, malaria is clustered in demographic groups or specific high-risk populations, known as “hot” populations, or “hot-pops”, that may carry infection from their work place to their villages or may be at higher risk of infection because of behavioural factors[6]. If infections are clustered in hotspots, then geographically based active surveillance strategies may be effective at preventing further malaria transmission and reducing transmission towards zero.

ACD is defined by WHO as the 'detection by health workers of malaria infections at community and household level in population groups that are considered to be at high risk. ACD can be conducted as fever screening followed by parasitological examination of all febrile patients or as parasitological examination of the target population without prior screening’[7].

Countries engage in a wide variety of activities that they consider to fall within the scope of their ACD strategy, and may include proactive case detection (PACD) and reactive case detection (RACD)[12, 13]. PACD consists of targeted or mass screening to search for cases in the community, which may include screening to find cases that are symptomatic or asymptomatic without the trigger of passively detected cases[14, 15]. RACD is an active surveillance method that is triggered by passively detected cases and involves screening households or individuals within a specified area, typically a pre-determined radius around a locally acquired case, with the goal of preventing further malaria transmission by identifying additional infections, symptomatic or asymptomatic[8, 16]. Many countries have or are currently implementing PACD and/or RACD to achieve and maintain malaria elimination[8, 14, 15, 17]. Despite these efforts, there is a lack of guidance on how, when and where to employ ACD, and limited evidence exists on the effectiveness of ACD as a strategy to halt ongoing transmission[6, 17].

This study aims to describe and compare case investigation and ACD strategies and activities currently employed in partner countries of the Asia Pacific Malaria Elimination Network (APMEN), a group of 14 countries (Bhutan, Cambodia, China, Democratic People’s Republic of Korea, Indonesia, Malaysia, Nepal, Philippines, Republic of Korea, Solomon Islands, Sri Lanka, Thailand, Vanuatu, and Vietnam) in the Asia Pacific region. A major goal of APMEN is to provide a platform to gather and share national malaria control programme experiences and strategies employed for malaria elimination, such as ACD. For Solomon Islands and Vanuatu, the strategies and activities described in this study only reflect those undertaken in the elimination provinces, as the two countries presently have sub-national malaria elimination goals.

A survey on ACD activities was developed in collaboration with national malaria control programmes and partner organizations of APMEN. The survey aimed to gather information on strategies employed by national malaria control programmes to investigate and detect malaria cases, specifically related to index case investigation and RACD. Questions pertained to: standard operating procedures (SOPs), classification of cases as local or imported, RACD methods, screening measures used in response to local and/or imported cases, monitoring and supervision of programme staff, and additional measures (e g, vector control and entomological surveillance) conducted in response to cases. Countries were also asked to provide national level SOPs or other available materials to supplement survey responses.

Definitions of case investigation, active and reactive case detection were provided to survey respondents as part of the survey form. The definitions of case investigation and active case detection were adapted from the definition provided by WHO[18]. Case investigation was defined as 'gathering enough information to allow classification of a malaria case by origin of infection. It includes, but is not limited to, administration of a standardized questionnaire to a person diagnosed with malaria infection’. Active case detection was defined as 'the operation carried out by surveillance agents who visit every locality in a defined area at regular intervals (usually monthly during the transmission season), in order to enquire for fever cases through individual house visits, and to test for malaria (and treat if positive) each suspected person so discovered’. Of note, a revised WHO definition of active case detection was issued while the survey was underway, from involving screening symptomatic individuals only to including screening both asymptomatic and symptomatic individuals[7]. The definition used in the survey for reactive case detection was adapted from Moonen et al.[16], and was described as 'triggered whenever a case is identified by passive case detection…and will involve visiting the household of the locally acquired case, screening family members, and screening neighbors within a defined radius’.

The survey was piloted in November 2011 with three APMEN collaborating country partners and one partner organization. Revisions were made according to the results of the pilot survey. In December 2011, the survey was distributed to country representatives of each APMEN country partner, of which there were 11 at the time. The survey was then distributed to the three new APMEN country partners in October 2012. Follow-up, including questions on missing or unclear text answers, was conducted in May 2013.

Quantitative and qualitative data were entered into an Excel database, and a descriptive analysis of quantitative survey questions was conducted in STATA IC, version 12. Qualitative data were analysed in Excel.

The national malaria control programmes of 14 APMEN countries were invited to participate in the ACD survey, of which 13 responded to the survey. Some countries responded to all questions and some failed to respond to certain questions or entire components of the survey.

Table 1 describes the participating countries and their respective nationally reported cases from 2010 and the country’s total population[19‐21]. Each country’s annual parasite index (API), or the number of reported malaria cases per 1,000 risk population per year, was reported by country programmes in the survey. Most respondent programmes (eight of ten) in the survey described case investigation and RACD practices that programmes aim to conduct universally throughout the country. Two respondents, Solomon Islands and Vanuatu, reported that they conduct the activities described in the survey only in designated malaria elimination provinces. The Solomon Islands has a goal of eliminating malaria from Temotu and Isabel Provinces by 2014[13]. Tafea Province in Vanuatu is targeted for elimination by 2014[22].

Survey results indicate that systems and procedures for case investigation and RACD are widely in place in the malaria elimination programmes of the APMEN partner countries. Thirteen out of the 14 partner countries responded to the survey and all of the respondent countries carried out case investigation, while 12 reported using RACD. Across respondents, the strategies employed varied, especially in regard to RACD, with different people screened (symptomatic versus asymptomatic) and the number of people screened (household only versus the whole village or a 2.5 km radius). Which of these RACD approaches is effective at preventing and reducing transmission is not known. Better understanding of which strategy is most effective is critical as they are human resource intensive.

Index case investigation practices varied, including the proportion of cases for which case investigation occurred. Most respondents (seven) reported following WHO guidelines to conduct case investigation within one to two days of a case being detected[7]. Many countries also reported collecting broad demographic data during case investigation, most of which are recommended by the WHO, such as: current address, length of time at that address, occupation and place of work, recent travel history, and recent contact with known malaria cases[7]. Although most respondents reported following case investigation data collection guidelines, there is an array of parameters that each programme chooses to assess, and likely reflect tailoring of investigations to local conditions and programme capacity. In some countries, supervision and management of case investigation occurs regularly, also likely related to programme capacity.

How programmes determine the origin of a case also differed across the respondent countries. Although “imported” cases are typically defined as a case originating in another endemic country, several respondents – including those with sub-national elimination strategies as those with national elimination strategies – reported defining cases as imported if they originate from another endemic district or province within the country itself. Programmes seem to prioritize local context when defining importation.

RACD in Asia Pacific countries involves screening households within a specified area, typically a pre-determined radius, around a locally acquired case with the goal of identifying other infections that might be symptomatic or asymptomatic. This process is similar to that found in other countries[14, 17, 23]. However, there is diversity in the strategies and activities used for RACD. Survey results from the Asia Pacific countries show that RACD can be triggered with one case or a defined threshold of multiple index cases, depending on local incidence and malaria control programme resources. Several countries reported screening symptomatic members of the index case household, while others screen all residents of the household. Recent evidence regarding the importance and frequency of asymptomatic infection in low transmission settings suggests that screening symptomatic people alone will not effectively and rapidly reduce malaria transmission[5, 10]. More evidence on the degree of clustering in the settings of APMEN partner countries is needed to support decision-making on how far to screen around an index household. Some countries reported screening all households within a specific administrative unit (e g, village) or a certain radius around the index case, a maximum of 2.5 km. The decision on how wide to screen is based on the theoretical dispersal of vectors and the operational capacity of the programme. However, it should be noted that it is operationally challenging to screen large numbers of households[24], as the radius around the index household increases the area to be covered increases by the square of the radius.

Most programmes collect a range of information from those screened, including information on residence, occupation, travel history, contact with travellers or immigrants, and other details. Different diagnostic methods (clinical diagnosis, microscopy, RDT, PCR, serology) are used to screen during RACD. There are particular challenges in diagnosing cases in areas with a high proportion of sub-patent or sub-microscopic cases[25]. Several countries are now using PCR confirmation in addition to other diagnostic methods, however, it is not known how routinely it is used in these countries and little evidence exists regarding which diagnostic methods are most effective in the setting of the Asia Pacific[17]. The response to a case or an outbreak should be well coordinated and include vector control and public health messaging components. This was reflected in the survey, as many countries include additional vector control, entomological surveillance and/or health education activities[13]. Although the results of this study show widespread use of RACD, there is a dearth of evidence to guide countries on the effectiveness of these activities.

The variation in case investigation and RACD practices across Asia Pacific countries illustrates the need for further research and informed guidance. In particular, the variation in triggers used for RACD and disparate target areas for screening - either the number of households or a radius - indicate that there remain gaps in knowledge to support optimal identification of malaria infections in the community and to identify the most effective and efficient way to capture them. A starting point to address these gaps would be the collection of standard data on both case investigation and RACD activities. Important metrics to assess are case investigation and RACD coverage rates, number of people screened and completeness of geographical coverage during RACD as well as timeliness of these activities. The survey showed that many programmes do not systematically collect robust data on these activities. Thus there is a need to establish these standardized metrics to monitor and evaluate programme effectiveness. The actual choice of metrics should be established through country programme and stakeholder consultation and integrated into routine surveillance data collection, taking into account the varying contexts in which programmes operate, namely funding constraints, epidemiology, geography and others.

As countries progress towards national or sub-national elimination, malaria programmes should devote staff time to investigating cases and conducting reactive surveillance activities to seek out remaining reservoirs of infection. It is critical for programmes to achieve high coverage of the population, ultimately reaching every case to determine the origin of the infection and if the infection has spread, and mount a response when necessary. Knowing the origin of each case is a critical component of an elimination campaign; it allows a programme to identify pockets or specific populations that contribute to ongoing transmission, and preserves programme resources by avoiding RACD work in areas where it may be unnecessary. Where RACD is necessary, it should be carried out in the most effective way.

Currently there are no standard metrics in use by country programmes for case investigation and RACD. The development and use of common metrics for these activities will allow the programmes to assess performance and results of resource-intensive surveillance measures and may benefit countries that considering implementing these activities in other parts of the world. There is much to learn from countries that are well on the way towards malaria elimination. This APMEN survey is a small step in distilling and disseminating this information.