Poor performance of universal sample processing method for diagnosis of pulmonary tuberculosis by smear microscopy and culture in Uganda.

Laboratory methods to improve smear microscopy are an urgent priority for global tuberculosis control. The novel universal sample processing (USP) method has been reported to improve conventional diagnostic testing for tuberculosis while also providing inhibitor-free specimens for molecular assays. However, no studies evaluating the method in the field have been conducted. In this study, we compared the performance of the USP method to that of the standard N-acetyl-L-cysteine-NaOH (NALC) method for conventional diagnosis of tuberculosis in 252 adults admitted to Mulago Hospital in Kampala, Uganda, with a clinical suspicion of pneumonia. A single early-morning sputum specimen collected from each patient was divided into two aliquots, each of which was assigned a random identification number. One randomly numbered specimen was processed by the USP method and the other by the NALC method. Mycobacterial cultures were more frequently negative in USP compared to NALC specimen aliquots (58% versus 43%; P < 0.001). There was no difference in the proportion of contaminated mycobacterial cultures (12% versus 11%; P = 0.87). The sensitivity and specificity of smear microscopy for the USP method were 52% and 86%, respectively, and were not significantly different from those for the NALC method (56% and 86%, respectively) using mycobacterial culture results as a reference standard. These results suggest that the USP method did not provide any significant advantage over the standard NALC method for conventional diagnosis of tuberculosis in our setting and illustrate the importance of well-designed, field-level evaluations of novel diagnostic techniques.

Examining Intervention Design: Lessons from the Development of Eight Related Malaria Health Care Intervention Studies.

Abstract-Rigorous evidence of "what works" to improve health care is in demand, but methods for the development of interventions have not been scrutinized in the same ways as methods for evaluation. This article presents and examines intervention development processes of eight malaria health care interventions in East and West Africa. A case study approach was used to draw out experiences and insights from multidisciplinary teams who undertook to design and evaluate these studies. Four steps appeared necessary for intervention design: (1) definition of scope, with reference to evaluation possibilities; (2) research to inform design, including evidence and theory reviews and empirical formative research; (3) intervention design, including consideration and selection of approaches and development of activities and materials; and (4) refining and finalizing the intervention, incorporating piloting and pretesting. Alongside these steps, projects produced theories, explicitly or implicitly, about (1) intended pathways of change and (2) how their intervention would be implemented.The work required to design interventions that meet and contribute to current standards of evidence should not be underestimated. Furthermore, the process should be recognized not only as technical but as the result of micro and macro social, political, and economic contexts, which should be acknowledged and documented in order to infer generalizability. Reporting of interventions should go beyond descriptions of final intervention components or techniques to encompass the development process. The role that evaluation possibilities play in intervention design should be brought to the fore in debates over health care improvement.

Behind the scenes of the PRIME intervention: designing a complex intervention to improve malaria care at public health centres in Uganda.

BACKGROUND: In Uganda, health system challenges limit access to good quality healthcare and contribute to slow progress on malaria control. We developed a complex intervention (PRIME), which was designed to improve quality of care for malaria at public health centres. OBJECTIVE: Responding to calls for increased transparency, we describe the PRIME intervention's design process, rationale, and final content and reflect on the choices and challenges encountered during the design of this complex intervention. DESIGN: To develop the intervention, we followed a multistep approach, including the following: 1) formative research to identify intervention target areas and objectives; 2) prioritization of intervention components; 3) review of relevant evidence; 4) development of intervention components; 5) piloting and refinement of workshop modules; and 6) consolidation of the PRIME intervention theories of change to articulate why and how the intervention was hypothesized to produce desired outcomes. We aimed to develop an intervention that was evidence-based, grounded in theory, and appropriate for the study context; could be evaluated within a randomized controlled trial; and had the potential to be scaled up sustainably. RESULTS: The process of developing the PRIME intervention package was lengthy and dynamic. The final intervention package consisted of four components: 1) training in fever case management and use of rapid diagnostic tests for malaria (mRDTs); 2) workshops in health centre management; 3) workshops in patient-centred services; and 4) provision of mRDTs and antimalarials when stocks ran low. CONCLUSIONS: The slow and iterative process of intervention design contrasted with the continually shifting study context. We highlight the considerations and choices made at each design stage, discussing elements we included and why, as well as those that were ultimately excluded. Reflection on and reporting of 'behind the scenes' accounts of intervention design may improve the design, assessment, and generalizability of complex interventions and their evaluations.

The PRIME trial protocol: evaluating the impact of an intervention implemented in public health centres on management of malaria and health outcomes of children using a cluster-randomised design in Tororo, Uganda.

BACKGROUND: In Africa, inadequate health services contribute to the lack of progress on malaria control. Evidence of the impact of interventions to improve health services on population-level malaria indicators is needed. We are conducting a cluster-randomised trial to assess whether a complex intervention delivered at public health centres in Uganda improves health outcomes of children and treatment of malaria, as compared to the current standard of care. METHODS/DESIGN: Twenty public health centres (level II and III) in Tororo district will be included; 10 will be randomly assigned to the intervention and 10 to control. Clusters will include households located within 2 km of health centres. The trial statistician will generate the random allocation sequence and assign clusters. Health centres will be stratified by level, and restricted randomisation will be employed to ensure balance on cluster location and size. Allocation will not be blinded. The intervention includes training in health centre management, fever case management with use of rapid diagnostic tests (RDTs) for malaria, and patient-centered services, and provision of artemether-lumefantrine (AL) and RDTs when stocks run low. The impact of the intervention on population-level health indicators will be assessed through community surveys conducted at baseline in randomly selected children from each cluster, and repeated annually for two years. The impact on individuals over time will be assessed in a cohort study of children recruited from households randomly selected per cluster. The impact on health centres will be assessed using patient exit interviews, monthly surveillance, and assessment of health worker knowledge and skills. The primary outcome is the prevalence of anaemia (haemoglobin <11.0 g/dL) in individual children under five measured in the annual community surveys. The primary analysis will be based on the cluster-level results. DISCUSSION: The PRIME trial findings will be supplemented by the PROCESS study, an evaluation of the process, context, and wider impact of the PRIME intervention which will be conducted alongside the main trial, together providing evidence of the health impact of a public sector intervention in Uganda. TRIAL REGISTRATION AND FUNDING: This trial is registered at Clinicaltrials.gov (NCT01024426) and is supported by the ACT Consortium.