Performance and utility of more highly sensitive malaria rapid diagnostic tests.

BACKGROUND: A new more highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum malaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now called NxTek™ Eliminate Malaria Ag Pf) was launched in 2017. The test has already been used in many research studies in a wide range of geographies and use cases. METHODS: In this study, we collate all published and available unpublished studies that use the HS-RDT and assess its performance in (i) prevalence surveys, (ii) clinical diagnosis, (iii) screening pregnant women, and (iv) active case detection. Two individual-level data sets from asymptomatic populations are used to fit logistic regression models to estimate the probability of HS-RDT positivity based on histidine-rich protein 2 (HRP2) concentration and parasite density. The performance of the HS-RDT in prevalence surveys is estimated by calculating the sensitivity and positive proportion in comparison to polymerase chain reaction (PCR) and conventional malaria RDTs. RESULTS: We find that across 18 studies, in prevalence surveys, the mean sensitivity of the HS-RDT is estimated to be 56.1% (95% confidence interval [CI] 46.9-65.4%) compared to 44.3% (95% CI 32.6-56.0%) for a conventional RDT (co-RDT) when using nucleic acid amplification techniques as the reference standard. In studies where prevalence was estimated using both the HS-RDT and a co-RDT, we found that prevalence was on average 46% higher using a HS-RDT compared to a co-RDT. For use in clinical diagnosis and screening pregnant women, the HS-RDT was not significantly more sensitive than a co-RDT. CONCLUSIONS: Overall, the evidence presented here suggests that the HS-RDT is more sensitive in asymptomatic populations and could provide a marginal improvement in clinical diagnosis and screening pregnant women. Although the HS-RDT has limited temperature stability and shelf-life claims compared to co-RDTs, there is no evidence to suggest, given this test has the same cost as current RDTs, it would have any negative impacts in terms of malaria misdiagnosis if it were widely used in all four population groups explored here.

Exploring Shigella vaccine priorities and preferences: Results from a mixed-methods study in low- and middle-income settings.

Background: Shigella is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed Shigella vaccines currently exist but several promising candidates are in development and could be available in the next five years. Despite Shigella being a well-known public health target of the World Health Organization for decades, given current burden estimates and competing preventable disease priorities in low-income settings, whether the availability of an effective Shigella vaccine will lead to its prioritization and widespread introduction among countries at highest risk is unknown. Methods: We conducted a mixed-methods study of national stakeholders and healthcare providers in five countries in Asia and Africa and regional stakeholders in the Pan American Health Organization to identify preferences and priorities for forthcoming Shigella vaccines. Results: In our study of 89 individuals, diarrhea was the most frequently mentioned serious health concern for children under five years. Antimicrobial resistance (AMR) was more often considered very concerning than diarrhea or stunting. Shigella awareness was high but not considered a serious health concern by most stakeholders. Most participants were willing to consider adding a new vaccine to the routine immunization schedule but expressed reservations about a Shigella vaccine because of lower perceived burden relative to other preventable diseases and an already crowded schedule; interest was highest among national stakeholders in countries receiving more financial support for immunization. The priority of a Shigella vaccine rose when participants considered vaccine impacts on reducing stunting and AMR. Participants strongly preferred oral and combination vaccines compared to injectable and a single-antigen presentations, citing greater perceived community acceptability. Conclusions: This study provides a critical opportunity to hear directly from country and regional stakeholders about health priorities and preferences around new vaccines. These findings should inform ongoing Shigella vaccine development efforts and eventual vaccine introduction and implementation planning.

Evaluation of a protein-to-creatinine dipstick diagnostic test for proteinuria screening in selected antenatal care clinics in three Districts in the Bono-East Region of Ghana.

BACKGROUND: Preeclampsia and eclampsia contribute significantly to maternal and newborn deaths worldwide. Early and accurate identification of pregnant women at risk can avert these deaths, but the necessary diagnostics are not widely available. A protein and creatinine ratio, rather than a measurement of protein alone, may provide better identification of proteinuria. The objective of this study was to assess the operational and performance characteristics of the LifeAssay Diagnostics (LAD) Test-it™ protein-to-creatinine ratio (PrCr) urinalysis dipstick test in a representative antenatal care setting (ANC). METHODS: Mixed methods were used to assess the operational and performance characteristics of the PrCr test, including a usability study with 25 participants, a prospective cross-sectional diagnostic accuracy study (N = 1483), and a targeted reassessment of discordant frozen samples (N = 200). Several other commonly used proteinuria tests were included for comparison. RESULTS: The test demonstrated improved clinical performance for detection of proteinuria over the current standard-of-care tests widely used in Ghana. The LAD PrCr test showed a sensitivity of 50.7% and specificity of 69.2% when run at the point of care. In contrast, the standard-of-care Accu-Tell® protein dipstick test was found to have a sensitivity of 32.4% and a specificity of 82.2%. The LAD test shows minor improvement over the tests currently used in Ghana to detect proteinuria. CONCLUSIONS: The PrCr test offers the potential for improved detection of proteinuria over the standard-of-care tests used in ANC. However, this test and the others evaluated for this study demonstrate limited performance, particularly among samples with a low level of proteinuria. Additional exploration in other clinical use cases, such as triage among high-risk populations, is warranted. The LAD test can also be considered a transition product, as health systems consider adopting next-generation biomarker tests when more readily available.