Sickle cell disease is a common, life-threatening genetic disorder that is best managed when diagnosed early by newborn screening. However, sickle cell disease is most prevalent in low-resource regions of the world where newborn screening is rare and diagnosis at the point-of-care is challenging. In many such regions, the majority of affected children die, undiagnosed, before the age of five years. A rapid and affordable point-of-care test for sickle cell disease is needed. The diagnostic accuracy of HemoTypeSC, a point-of-care immunoassay, for sickle cell disease was evaluated in individuals who had sickle cell disease, hemoglobin C disease, the related carrier (trait) states, or a normal hemoglobin phenotype. Children and adults participated in low-, medium- and high-resource environments [Ghana (n=383), Martinique (n=46), and USA (n=158)]. Paired blood specimens were obtained for HemoTypeSC and a reference diagnostic assay. HemoTypeSC testing was performed at the site of blood collection, and the reference test was performed in a laboratory at each site. In 587 participants, across all study sites, HemoTypeSC had an overall sensitivity of 99.5% and specificity of 99.9% across all hemoglobin phenotypes. The test had 100% sensitivity and specificity for sickle cell anemia. Sensitivity and specificity for detection of normal and trait states were >99%. HemoTypeSC is an inexpensive (<$2 per test), accurate, and rapid point-of-care test that can be used in resource-limited regions with a high prevalence of sickle cell disease to provide timely diagnosis and support newborn screening programs.

Summary Sickle cell disease (SCD) is a significant healthcare burden worldwide, but most affected individuals reside in low-resource areas where access to diagnostic testing may be limited. We developed and validated a rapid, inexpensive, disposable diagnostic test, the HemoTypeSC™, based on novel monoclonal antibodies (MAbs) that differentiate normal adult haemoglobin (Hb A), sickle haemoglobin (Hb S) and haemoglobin C (Hb C). In competitive enzyme-linked immunosorbent assays, each MAb bound only its target with <0.1% cross-reactivity. With the HemoTypeSC™ test procedure, the sensitivity for each variant was <5.0 g/l. The accuracy of HemoTypeSC™ was evaluated on 100 whole blood samples from individuals with common relevant haemoglobin phenotypes, including normal (Hb AA, N=20), carrier or trait (Hb AS, N=22; Hb AC, N=20), SCD (Hb SS, N=22; Hb SC, N=13), and Hb C disease (Hb CC, N=3). The correct haemoglobin phenotype was identified in 100% of these samples. The accuracy of the test was not affected by Hb F (0-94.8% of total Hb) or Hb A2 (0-5.6% of total Hb). HemoTypeSC™ requires <1 μl of whole blood and no instruments or power sources. The total time-to-result is <20 min. HemoTypeSC™ may be a practical solution for point-of-care testing for SCD and carrier status in low-resource settings.

Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls (P less than 0.001). TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the same in both groups. TLI was associated with significant radiation-related mortality, and nondiabetic TLI-treated rats weighed significantly less than controls. We conclude that TLI is effective in the prevention of BB rat diabetes. However, TLI fails to correct the subclinical immunologic abnormalities of the model and is associated with significant morbidity.

dUrinary tract infections (UTIs) are frequently encountered in clinical practice and most commonly caused by Escherichia coli and other Gram-negative uropathogens. We tested RapidBac, a rapid immunoassay for bacteriuria developed by Silver Lake Research Corporation (SLRC), compared with standard bacterial culture using 966 clean-catch urine specimens submitted to a clinical microbiology laboratory in an urban academic medical center. RapidBac was performed in accordance with instructions, providing a positive or negative result in 20 min. RapidBac identified as positive 245/285 (sensitivity 86%) samples with significant bacteriuria, defined as the presence of a Gram-negative uropathogen or Staphylococcus saprophyticus at >10 3 CFU/ml. The sensitivities for Gram-negative bacteriuria at >10 4 CFU/ml and >10 5 CFU/ml were 96% and 99%, respectively. The specificity of the test, detecting the absence of significant bacteriuria, was 94%. The sensitivity and specificity of RapidBac were similar on samples from inpatient and outpatient settings, from male and female patients, and across age groups from 18 to 89 years old, although specificity was higher in men (100%) compared with that in women (92%). The RapidBac test for bacteriuria may be effective as an aid in the point-of-care diagnosis of UTIs especially in emergency and primary care settings. Bacterial urinary tract infections (UTIs) are a common clinical problem across the age spectrum in both genders (1). Women and girls are disproportionately affected by UTIs, with the lifetime risk estimated at Ͼ60% (2). In the United States, the overall annual cost of diagnosis and treatment of UTIs is considerable, estimated at $2.3 billion in 2010 (1). Gram-negative bacteria are the causative agents in up to 95% of uncomplicated UTIs in women, with Escherichia coli responsible for 70% to 90% (1).Diagnosis of UTI remains problematic in certain settings. The presence of uropathogenic bacteria in urine is the hallmark of UTI, and urine culture is the gold standard method for determination of clinically relevant bacteriuria. However, the 24-to 48-h delay in obtaining urine culture results has presented a longstanding need for more rapid diagnostic methods. Currently available rapid methods for detection of bacteriuria, including microscopy and test strips for detecting nitrite, have been shown to have poor sensitivity (3-5). A meta-analysis of 34 studies evaluating the accuracy of nitrite test strips across settings and populations found a mean sensitivity of 48% (using a definition of 10 5 CFU/ml for significant bacteriuria) (6). Microscopic urinalysis and urine Gram staining, two relatively laborious methods, have been shown by several studies to lack sensitivity below 10 5 CFU/ml and to have poor specificity (4,5,7,8). Guidelines for UTI from the Infectious Disease Society of America (IDSA) do not recommend urine culture for most cases of acute uncomplicated cystitis, the most common UTI presentation, and do not address laboratory methods for diagnosing UTI (9).An accurate ...

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