Next-generation vaccines for tropical infectious diseases.

Tropical infectious diseases inflict an unacceptable burden of disease on humans living in developing countries. Although anti-pathogenic drugs have been widely used, they carry a constant threat of selecting for resistance. Vaccines offer a promising means by which to enhance the global control of tropical infectious diseases; however, these have been difficult to develop, mostly because of the complex nature of the pathogen lifecycles. Here, we present recently developed vaccine candidates for five tropical infectious diseases in the form of a catalog that have either entered clinical trials or have been licensed for use. We deliberate on recently licensed dengue vaccines, provide evidence why combination vaccination could have a synergistic impact on schistosomiasis, critically appraise the value of typhoid conjugate vaccines, and discuss the potential of vaccines in the efforts to eliminate vivax malaria and hookworms.

Urinary nephrin-a potential marker of early glomerular injury: a systematic review and meta-analysis.

BACKGROUND: Both early recognition of glomerular injury and diagnosis of renal injury remain important problems in clinical settings, and current diagnostic biomarkers have limitations. The aim of this review was to determine the diagnostic accuracy of urinary nephrin for detecting early glomerular injury. METHODS: A search was conducted through electronic databases for all relevant studies published until January 31, 2022. The methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled sensitivity, specificity, and other estimates of diagnostic accuracy were determined using a random effect model. The Summary Receiver Operating Characteristics (SROC) was used to pool the data and to estimate the area under the curve (AUC). RESULTS: The meta-analysis included 15 studies involving 1587 participants. Overall, the pooled sensitivity of urinary nephrin for detecting glomerular injury was 0.86 (95% CI 0.83-0.89) and specificity was 0.73 (95% CI 0.70-0.76). The AUC-SROC to summarise the diagnostic accuracy was 0.90. As a predictor of preeclampsia, urinary nephrin showed a sensitivity of 0.78 (95% CI 0.71-0.84) and specificity of 0.79 (95% CI 0.75-0.82), and as a predictor of nephropathy the sensitivity was 0.90 (95% CI 0.87-0.93), and specificity was 0.62 (95% CI 0.56-0.67). A subgroup analysis using ELISA as a method of diagnosis showed a sensitivity of 0.89 (95% CI 0.86-0.92), and a specificity of 0.72 (95% CI 0.69-0.75). CONCLUSION: Urinary nephrin may be a promising marker for the detection of early glomerular injury. ELISA assays appear to provide reasonable sensitivity and specificity. Once translated into clinical practice, urinary nephrin could provide an important addition to a panel of novel markers to help in the detection of acute and chronic renal injury.

A practical guide to the stereological assessment of glomerular number, size, and cellular composition.

The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), ß-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.