These facility-based data stratified by age and transmission intensity reveal a series of important findings directly relevant for the revision of malaria diagnostic recommendations within the context of deployment of new ACT policies in Uganda.
First, the prevalence of malaria parasitaemia among most outpatient groups was lower than initially expected. Indeed, across different transmission settings, which are all traditionally viewed as high malaria transmission intensity areas, only 17–25% of patients above five years of age were parasitaemic. The prevalence rate of 44% was higher in children below five years of age; however, this rate did not exceed 54% even in the areas historically described as having the highest EIRs in the world with between 564 and 1,564 infective bytes per person per year [2
] and community-based childhood malaria prevalence rates as high as 79–91% [8
]. However, the comparisons between community and facility-based prevalence rates are not straightforward. Intuitively, prevalence rates among sick outpatients can be expected to be at least similar, if not higher, compared to those obtained from household surveys among healthy populations. The self-selection of populations presenting to facilities, who may have higher socio-economic status or different health-seeking behaviour may provide some explanation to this pattern [9
]. Nevertheless, the findings in this study suggest that in nearly all studied populations, the majority of patients present to outpatient facilities without malaria parasitaemia.
Second, given the low prevalence of malaria (24%), high frequency of fever among outpatients (79%), and health workers' practices largely reflecting recommendations promoting presumptive malaria diagnosis for all febrile patients, the current rates of outpatient malaria over-diagnosis in Uganda are massive, reaching as high as 79% for patients five years and older and remaining high even in the children below five years of age in the study areas of highest malaria transmission (47%). The over-diagnosis rates of routine practices were not much lower than 75% previously reported rates from an area of low and unstable malaria transmission in western Uganda [11
Yet, it was worrying to observe that despite the minimum overall deviations from national diagnosis recommendations, the current practices in very high transmission areas resulted in a large proportion (49%) of children below five years of age who are not diagnosed although parasitaemic and subsequently not treated for malaria. As observed repeatedly in many studies in the past two decades across Africa [12
], any deviation from the case definition equalizing fever with malaria increases the specificity of malaria diagnosis, however at the cost of substantially decreased sensitivity. This inevitably results in malaria under-diagnosis, the magnitude of which is dependent on the background prevalence of the disease. The under-diagnosis rates observed in this study present an unacceptable trade-off in children, the population most vulnerable to severe and potentially fatal malaria complications. Therefore, the only potential solution to circumvent problems of malaria misdiagnosis (both over- and under-diagnosis) in Uganda is the change of diagnostic policy from presumptive to parasitological diagnosis of malaria and systematic use of malaria tests for all febrile patients by performing reliable malaria microscopy and introducing rapid diagnostic tests (RDTs).
Finally, a shift from the current presumptive policy based on fever to an effective policy based on malaria diagnostics is unlikely to be trivial. The findings at facilities with functional microscopy in study districts suggest that: 1) febrile patients are not sufficiently tested regardless of whether testing is recommended (46%) or discouraged by guidelines (38%), and 2) there is an overwhelming tendency to ignore negative slide results and prescribe anti-malarial drugs (58%). The underuse of malaria microscopy and the prescription of anti-malarials for negative test results revealed in this study mirror well-described patterns of microscopy use and results interpretation reported in past studies in Kenya [17
], Zambia [18
] and Tanzania [20
]. With respect to the routine laboratory performance, the quality of routine malaria slide reading was poor (sensitivity and specificity below 60%) and characterized by substantial over-reporting of positive slides across all age groups (55–86%), however, most of the results routinely reported as negative were truly negative, more commonly in patients five years and older (93%) than in children below five years of age (71%). While 29% of false negative results might offer justification for the treatment of test negative children, the findings in patients five years and older are in obvious discordance with prescription practices where nearly all positive tests are routinely treated but also 47% of patients with negative tests. This irrational practice of overruling negative test results, and still performing malaria tests, may have multiple causes but an important one stems out from the decades of ambiguous recommendations translated into pre-service and in-service training programmes and routine practice where malaria microscopy has been seen as a tool to confirm clinical suspicion but rarely as a tool to rule out malaria diagnosis [22
]. Despite the problems of ensuring large-scale quality of routine microscopy-based malaria case-management across Africa, recent, smaller-scale studies suggest that intensive interventions including at least five days long, integrated in-service training for clinical and laboratory staff supported with supervision and strengthened surveillance may improve some aspects of microscopy-based malaria case-management [24
]. The challenge remains defining most cost-effective components of such interventions, their routine scale up and maintenance to ensure long-term performance at all facilities providing microscopy services.
The Ugandan Ministry of Health should be commended for the current revisions of malaria diagnostic policies to promote greater access to parasitological-based diagnosis. An important component of this is the introduction of malaria RDTs to complement microscopy specifically in health facilities without laboratory services. Malaria RDTs are accurate under controlled conditions, easy to use and interpret, provide rapid results, and can be performed with the minimum of training and equipment. Yet, the success of this diagnostic strategy encompassing RDTs will be critically dependent on ensuring high accuracy (in particular sensitivity) of RDTs under field conditions [11
], and ensuring a radical change of health workers current practices with emphasis on systematic screening of all fevers, respect of test negative results, and capacity building to manage non-malarial fevers. A quality assurance process at national and peripheral level; development, validation and distribution of clear clinical guidelines to address malaria and non-malaria fevers; health workers', preferably on-job training to introduce tests, initiate translation of guidelines into practice, but also to solve local obstacles to implement microscopy and RDTs; and frequent effective supervision to maintain good practices are the minimum pre-requisites for the success of such a strategy. Therefore, it is important that the introduction of RDTs is accompanied by similar activities to strengthen the quality of microscopy, either as a separate preliminary activity or as an activity integrated within the RDT implementation process [28
Finally, prior to the national policy change and scale-up, it would be wise that the implementation package introducing RDTs and strengthening malaria microscopy is piloted at district-level in areas of different malaria endemicity. Such pilots should include an operational research component which should monitor routine health workers' practices and real-world accuracy of both diagnostic tools, and evaluate cost and health benefits of a parasitological-based diagnostic strategy in particular compared with the presumptive treatment strategy in the most vulnerable groups such as children below five years of age. The lessons learned from these pilots should help policy makers to improve upon implementation delivery and take informed decisions if all age groups and transmission settings should be the targets of parasitological-based diagnosis for the national scale-up. Failing to approach the introduction of this new diagnostic tool in a careful and evidence-based manner will mean that no lessons have been learned from the experiences of implementing malaria microscopy.