Cost-effectiveness of malaria diagnosis using rapid diagnostic tests compared to microscopy or clinical symptoms alone in Afghanistan

Background Improving access to parasitological diagnosis of malaria is a central strategy for control and elimination of the disease. Malaria rapid diagnostic tests (RDTs) are relatively easy to perform and could be used in primary level clinics to increase coverage of diagnostics and improve treatment of malaria.<p></p> Methods A cost-effectiveness analysis was undertaken of RDT-based diagnosis in public health sector facilities in Afghanistan comparing the societal and health sector costs of RDTs versus microscopy and RDTs versus clinical diagnosis in low and moderate transmission areas. The effect measure was ‘appropriate treatment for malaria’ defined using a reference diagnosis. Effects were obtained from a recent trial of RDTs in 22 public health centres with cost data collected directly from health centres and from patients enrolled in the trial. Decision models were used to compare the cost of RDT diagnosis versus the current diagnostic method in use at the clinic per appropriately treated case (incremental cost-effectiveness ratio, ICER).<p></p> Results RDT diagnosis of Plasmodium vivax and Plasmodium falciparum malaria in patients with uncomplicated febrile illness had higher effectiveness and lower cost compared to microscopy and was cost-effective across the moderate and low transmission settings. RDTs remained cost-effective when microscopy was used for other clinical purposes. In the low transmission setting, RDTs were much more effective than clinical diagnosis (65.2% (212/325) vs 12.5% (40/321)) but at an additional cost (ICER) of US$4.5 per appropriately treated patient including a health sector cost (ICER) of US$2.5 and household cost of US$2.0. Sensitivity analysis, which varied drug costs, indicated that RDTs would remain cost-effective if artemisinin combination therapy was used for treating both P. vivax and P. falciparum. Cost-effectiveness of microscopy relative to RDT is further reduced if the former is used exclusively for malaria diagnosis. In the health service setting of Afghanistan, RDTs are a cost-effective intervention compared to microscopy.<p></p> Conclusions RDTs remain cost-effective across a range of drug costs and if microscopy is used for a range of diagnostic services. RDTs have significant advantages over clinical diagnosis with minor increases in the cost of service provision.<p></p&gt

UK vaccines network:Mapping priority pathogens of epidemic potential and vaccine pipeline developments

During the 2013–2016 Ebola outbreak in West Africa an expert panel was established on the instructions of the UK Prime Minister to identify priority pathogens for outbreak diseases that had the potential to cause future epidemics. A total of 13 priority pathogens were identified, which led to the prioritisation of spending in emerging diseases vaccine research and development from the UK. This meeting report summarises the process used to develop the UK pathogen priority list, compares it to lists generated by other organisations (World Health Organisation, National Institutes of Allergy and Infectious Diseases) and summarises clinical progress towards the development of vaccines against priority diseases. There is clear technical progress towards the development of vaccines. However, the availability of these vaccines will be dependent on sustained funding for clinical trials and the preparation of clinically acceptable manufactured material during inter-epidemic periods

The Impact of Delayed Treatment of Uncomplicated \u3ci\u3eP. falciparum\u3c/i\u3e Malaria on Progression to Severe Malaria: A Systematic Review and a Pooled Multicentre Individual-Patient Meta-Analysis

BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as \u27test-and-treat\u27 policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as \u27Good\u27, scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged \u3c15 years) SM patients and 5,780 (79.6% aged \u3c15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of \u3e24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p \u3c 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p \u3c 0.001) for a delay of \u3e7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] \u3e3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment

Motivation, money and respect: A mixed-method study of Tanzanian non-physician clinicians

Poor quality of care is a major concern in low-income countries, and is in part attributed to low motivation of healthcare workers. Non-physician clinicians (mid-level cadre healthworkers) are central to healthcare delivery in half of the countries in Africa, but while much is expected from these clinicians, little is known about their expectations and motivation to perform well. Understanding what motivates these healthworkers in their work is essential to provide an empirical base for policy decisions to improve quality of healthcare. In 2006-2007, we conducted a mixed-method study to evaluate factors affecting motivation, including reasons for varying levels of motivation, amongst these clinicians in Tanzania. Using a conceptual framework of 'internal' and 'environmental' domains known to influence healthworker motivation in low-income countries, developed from existing literature, we observed over 2000 hospital consultations, interviewed clinicians to evaluate job satisfaction and morale, then designed and implemented a survey instrument to measure work motivation in clinical settings. Thematic analysis (34 interviews, one focus group) identified social status expectations as fundamental to dissatisfaction with financial remuneration, working environments and relationships between different clinical cadres. The survey included all clinicians working in routine patient care at 13 hospitals in the area; 150 returned sufficiently complete data for psychometric analysis. In regression, higher salary was associated with 'internal' motivation; amongst higher earners, motivation was also associated with higher qualification and salary enhancements. Salary was thus a clear prerequisite for motivation. Our results are consistent with the hypothesis that non-salary motivators will only have an effect where salary requirements are satisfied. As well as improvements to organisational management, we put forward the case for the professionalisation of non-physician clinicians.Tanzania Motivation Clinical officer Non-physician clinician Financial incentives Mixed-methods Salary

Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization. RESULTS: A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27). CONCLUSIONS: Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499 [controlled-trials.com].)

Socioeconomic and environmental factors important for acquiring non-severe malaria in children in Yemen: a case-control study.

Little is known about the relative importance of environmental and socioeconomic factors for acquiring malaria in Yemen. A case-control study was conducted to determine the importance of these factors for acquiring malaria among children in Yemen. Cases of non-severe malaria were recruited from health centres; community controls were from the neighbourhood of the cases. Data were collected by personal interview and direct inspection during home visits. In total, 320 cases and 308 controls were recruited. In the multivariate analysis, environmental factors (living near streams and freshwater marshes), earth roofs of houses and history of travel were all significantly and positively associated with the occurrence of malaria, whilst regular spraying with insecticides at home was a protective factor. There was no association with socioeconomic factors, including crowding, education and occupation of parents, and ownership of house assets. An index created based on a number of indicators of wealth showed a significant association with malaria in the univariate analysis but was not significant in the multivariate analysis. Control activities can be targeted on identifiable environmental factors such as stream and freshwater marshes, although this needs further investigation. Extra protective measures may be needed by all those who travel in Yemen