Mass testing and treatment for malaria in low transmission areas in Amhara Region, Ethiopia

More than 63 million people live in areas at risk of malaria in Ethiopia and more than 3 million presumed and confirmed cases of malaria were reported in 2013 [1]. Amhara National Regional State is the second-most populous region in Ethiopia and accounts for 31 % of the national malaria burden [2]. Malaria parasite prevalence in this region was estimated at 2 % in 2011 [3] and malaria accounted for 22 % of outpatient visits, 24 % of hospital admissions, and 10 % of health facility deaths in 2012 [4]. While the proportion of outpatient visits, hospital admissions and health facility deaths attributed to malaria has fallen to 7, 2 and 1 %, respectively, since 2012, malaria remains an important source of morbidity and mortality in the region [5, 6].

The Ethiopian Federal Ministry of Health is striving to achieve substantial progress toward malaria elimination in low transmission areas by 2020 [7]. Current malaria control strategies in Ethiopia include long-lasting insecticide-treated bed nets (LLINs), indoor residual spraying (IRS), case management and epidemic detection and response where appropriate [8]. To move toward malaria elimination, new strategies will need to be employed to address the large proportion of infections that remain asymptomatic or minimally symptomatic and never present for testing and treatment [9, 10].

Population-wide or mass approaches that target infected individuals for treatment with anti-malarial drugs regardless of whether they are symptomatic or present-to-care are a means to clear malaria parasites and reduce malaria transmission in this context [11]. Mass testing and treatment (MTAT) is the testing of an entire population with a point-of-care test and administration of treatment to individuals with a positive test result. Currently, rapid diagnostic tests (RDTs) are the only programme-relevant option available. In Ethiopia, the current first-line anti-malarial drug for Plasmodium falciparum and mixed (P. falciparum and P. vivax) malaria is artemether-lumefantrine with a regimen of six doses over 3 days, with multiple pills in each dose depending on weight or age [8]. Adherence to a six-dose regimen of artemether-lumefantrine has been found to be low in some settings [12, 13]. Given this context, MTAT with artemether-lumefantrine and RDTs, with attention to treatment adherence, might be a reasonable approach for parasite clearance in Ethiopia.

Published literature has reported on MTAT approaches to malaria parasite clearance in Burkina Faso, Zambia and Zanzibar [14‐16], but no literature has described the implementation of a mass approach to clear malaria parasites from populations in Ethiopia. An MTAT campaign to clear malaria parasites from the population in low transmission areas in Amhara Region was conducted to evaluate its feasibility, impact and costs to inform the Government of Ethiopia’s strategy for malaria elimination. This paper presents the results of the operational feasibility and describes the profile of the targeted population and the risk factors associated with RDT-positivity.

The Ethiopian Federal Ministry of Health is striving to achieve substantial progress toward malaria elimination by 2020 [7]. As new malaria parasite clearance strategies are being considered to supplement current vector control and case management strategies, information from the implementation of a mass parasite clearance approach can help guide decision-making. This MTAT provided the first in-country experience to inform the Ministry of Health’s decision-making about mass malaria parasite clearance strategies and the findings have several implications for malaria elimination planning and programme implementation in Ethiopia.

The results show that it is feasible to implement a mass malaria parasite clearance intervention in a large geographic area over a short period of time. However, it is also resource intensive and the two-person field teams required additional people and training above and beyond existing human resources within the health system. The coverage of households (percentage of total households in the population that participated) and the coverage of individuals within households (percentage of individuals in visited households that were included) was high (87 % for both). The main reason for not including 13 % of the households in the area was that households were not visited (81 %), with refusals (4 %) and absent households (15 %) representing a much lower percentage. In the households that were visited, the main reason for not including 13 % of the members was that they were absent (84 %), while the rest were refusals (7 %) and exclusions based on age (infants younger than 6 months, 9 %). This resulted in an effective coverage of 75.5 % of all individuals in the targeted geographic areas, which was lower than desired. Thus greater efforts should be made to improve both the households’ and individuals’ coverage, that is visit every single household in the targeted areas and, for households that are visited but have absent members, try to track those individuals when they come back. These coverage estimates are comparable to published estimates of coverage for MTAT interventions implemented elsewhere. During an MTAT campaign in Zanzibar with two rounds of testing and treatment, 64 % of the population was reached during one or both rounds [16]. During an MTAT campaign in Zambia with three rounds of testing and treatment, 88 % of the population was reached in one or more rounds [15]. It is likely that a higher proportion of the targeted population (both households and individuals) would have been reached if multiple MTAT rounds had been implemented. While little information (age and sex) was collected about the individuals that were not reached during the MTAT implementation, these individuals differed from individuals who were reached, with more adults and a higher proportion of males, who are at higher risk of malaria infection. This suggests that a mass malaria parasite clearance approach with a door-to-door campaign may systematically miss important segments of the population if no efforts are made to reach individuals who are not at home at the time of the campaign. Additional mechanisms would be needed to increase the coverage, either by increasing the number of visits conducted to households with absent individuals and/or through strategies that specifically target mobile populations upon their return.

Malaria infection prevalence as measured by RDTs was low overall (1.4 %) and varied widely by kebele, ranging from 0.3 to 5.1 %. However, malaria prevalence was probably underestimated due to an imperfect RDT sensitivity. While RDTs generally have a high sensitivity in clinical settings, their detection limit in the field is around 100 parasites per µl [18]. Evidence indicates that sub-microscopic infections may be common in low prevalence settings and the intervention may have missed a substantial proportion of individuals with malaria infection [19]. In a recent MTAT campaign in Zanzibar, RDT sensitivity was estimated to be only 5.6 % for infections with any parasite density and 47.6 % for infections with parasite densities greater than 100 parasites per µl [16]. Thus without more sensitive point-of-care tests for malaria, a substantial proportion of malaria infections may remain undetected and untreated when using an MTAT approach for mass malaria parasite clearance. Mass drug administration is an alternative for clearing infections that would not otherwise be detected.

Several risk factors were associated with significantly higher odds of being RDT-positive. However, only 59 % to 71 % (in under ten and over 10 years of age respectively) of RDT-positive individuals had at least one of those risk factors. While information on the presence of these risk factors could be used to target populations at highest risk of malaria infection, screening for these risk factors would leave many infections undetected. These results also confirm that, even in low transmission areas, more than half (60.6 %) of RDT-positive individuals were asymptomatic. Interventions that are based on fever screening will miss many infections in such a setting [20]. Further, these results indicate that population movement is a driver of malaria transmission for individuals 10 years of age or older. An important income source for many families in the area is the seasonal agricultural work that young males do in other areas of Amhara with higher malaria transmission. Most leave for the farming season and come back home between September and December [21]. Thus the higher RDT-positivity among young adult males is probably a reflection of the large percentage of individuals in this age group who are returning migrant workers. Previous studies in Ethiopia have also found travel history to be a risk factor for malaria [22, 23], suggesting the importance of strategies that target migrant workers and other mobile populations to prevent the importation of malaria into their home communities. Also, given that intra-household transmission is a driver for individuals of all ages, mosquito net coverage and usage and IRS coverage need to be improved.

Across all kebeles, the field teams tested 73 RDT-negative individuals for every RDT-positive individual identified. This ratio ranged from 20 to 401 depending on kebele, suggesting that the efficiency of a mass malaria parasite clearance approach varies widely by geography, even within areas with consistently low rates of malaria. Focal malaria parasite clearance approaches that target specific sub-sets of the population based on proximity to passively detected malaria cases may be an efficient alternative to mass malaria parasite clearance approaches in areas with less malaria transmission [11]. The frequency of passively detected malaria cases can be used to determine which areas to target with population-wide versus focal approaches. However, as the risk factor analysis showed, any focal strategy that selects the sub-population to test based on specific characteristics will leave infections undetected in the population.

Only 52.7 % of RDT-positive individuals were infected by P. falciparum alone; 47.3 % had P. vivax or mixed malaria. Mass and focal malaria parasite clearance approaches that target P. falciparum alone will leave many transmissible P. vivax infections untreated. For Ethiopia to move to malaria elimination, strategies for malaria parasite clearance will require drugs that effectively clear both P. falciparum and P. vivax infections, including clearance of the persistent liver stages in P. vivax-infected individuals.

With population-wide treatment approaches using a multi-day and multi-dose drug, adherence to the full course of treatment is important. Low self-reported and observed treatment completion rates were found among individuals who received the six-dose regimen of artemether-lumefantrine and who were followed up more than 3 days after administration of their first dose. This is consistent with findings from a recent prospective observational study in Ethiopia that found only 38.7 % of patients to be ‘probably adherent’ to artemether-lumefantrine following administration of the drug in a routine care setting [12]. Additionally, field teams did not always directly observe the intake of the first dose as per protocol, with only 88.5 % of participants reporting to have taken the first dose. Poor adherence to artemether-lumefantrine will limit the impact of a mass malaria parasite clearance approach and attention to adherence is critical. New drugs are now available that require fewer doses (e.g., dihydroartemisinin-piperaquine) and these may provide important advantages for population-wide malaria clearance efforts.

The study had some limitations. First, the six intervention kebeles were purposively selected to represent variation in malaria transmission intensity, altitude, accessibility, and population mobility within Amhara Region. While results from a mass malaria parasite clearance approach in these kebeles provides insight into potential expansion into other parts of Ethiopia, these kebeles are not necessarily representative of Amhara Region or Ethiopia as a whole. Second, the effective coverage was lower than desired, with an estimated 24.5 % of the targeted population not reached, which indicates that greater efforts would be needed to target the hard-to-reach subgroups. Third, household enumeration was done for this study both prior to and during the intervention. The household enumeration was not validated using satellite images or other means and it is possible that some households were enumerated more than once and that some households were never enumerated. Thus the coverage estimates should be interpreted with caution.