Development of a rapid serological assay for the diagnosis of strongyloidiasis using a novel diffraction-based biosensor technology.

BACKGROUND: Strongyloidiasis is a persistent human parasitic infection caused by the intestinal nematode, Strongyloides stercoralis. The parasite has a world-wide distribution, particularly in tropical and subtropical regions with poor sanitary conditions. Since individuals with strongyloidiasis are typically asymptomatic, the infection can persist for decades without detection. Problems arise when individuals with unrecognized S. stercoralis infection are immunosuppressed, which can lead to hyper-infection syndrome and disseminated disease with an associated high mortality if untreated. Therefore a rapid, sensitive and easy to use method of diagnosing Strongyloides infection may improve the clinical management of this disease. METHODOLOGY/PRINCIPAL FINDINGS: An immunological assay for diagnosing strongyloidiasis was developed on a novel diffraction-based optical bionsensor technology. The test employs a 31-kDa recombinant antigen called NIE derived from Strongyloides stercoralis L3-stage larvae. Assay performance was tested using retrospectively collected sera from patients with parasitologically confirmed strongyloidiasis and control sera from healthy individuals or those with other parasitoses including schistosomiasis, trichinosis, echinococcosis or amebiasis who were seronegative using the NIE ELISA assay. If we consider the control group as the true negative group, the assay readily differentiated S. stercoralis-infected patients from controls detecting 96.3% of the positive cases, and with no cross reactivity observed in the control group These results were in excellent agreement (κ = 0.98) with results obtained by an NIE-based enzyme-linked immunosorbent assay (ELISA). A further 44 sera from patients with suspected S. stercoralis infection were analyzed and showed 91% agreement with the NIE ELISA. CONCLUSIONS/SIGNIFICANCE: In summary, this test provides high sensitivity detection of serum IgG against the NIE Strongyloides antigen. The assay is easy to perform and provides results in less than 30 minutes, making this platform amenable to rapid near-patient screening with minimal technical expertise

Rabies post-exposure prophylaxis started during or after travel: a GeoSentinel analysis

Background Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5–20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel. Methodology/Principal findings We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014–July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12–0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0–1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99–11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5–157.2; P = 0.01), were more likely to receive RIG in the country of exposure. Conclusions/Significance This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention

Area of exposure and treatment challenges of malaria in Eritrean migrants: a GeoSentinel analysis

Background: Recent reports highlight malaria as a frequent diagnosis in migrants who originate from Eritrea. A descriptive analysis of GeoSentinel cases of malaria in Eritrean migrants was done together with a literature review to elucidate key attributes of malaria in this group with a focus on possible areas of acquisition of malaria and treatment challenges.Results: A total of 146 cases were identified from the GeoSentinel database from 1999 through September 2017, with a marked increase in 2014 and 2015. All patients originated from Eritrea and the main reporting GeoSentinel sites were in Norway, Switzerland, Sweden, Israel and Germany. The majority of patients (young adult males) were diagnosed with malaria following arrival in the host country. All patients had a possible exposure in Eritrea, but may have been exposed in documented transit countries including Ethiopia, Sudan and possibly Libya in detention centres. Most infections were due to Plasmodium vivax (84.2%), followed by Plasmodium falciparum (8.2%). Two patients were pregnant, and both had P. vivax malaria. Some 31% of the migrants reported having had malaria while in transit. The median time to onset of malaria symptoms post arrival in the host country was 39days. Some 66% of patients were hospitalized and nine patients had severe malaria (according to WHO criteria), including five due to P. vivax.Conclusion: sThe 146 cases of mainly late onset, sometimes severe, P. vivax malaria in Eritrean migrants described in this multi-site, global analysis reflect the findings of single-centre analyses identified in the literature search. Host countries receiving asylum-seekers from Eritrea need to be prepared for large surges in vivax and, to a lesser extent, falciparum malaria, and need to be aware and prepared for glucose-6-phosphate dehydrogenase deficiency testing and primaquine treatment, which is difficult to procure and mainly unlicensed in Europe. There is an urgent need to explore the molecular epidemiology of P. vivax in Eritrean asylum-seekers, to investigate the area of acquisition of P. vivax along common transit routes and to determine whether there has been re-introduction of malaria in areas, such as Libya, where malaria is considered eliminated, but where capable vectors and Plasmodium co-circulate

Confirmation by 16S rRNA PCR of the COBAS AMPLICOR CT/NG Test for Diagnosis of Neisseria gonorrhoeae Infection in a Low-Prevalence Population

The COBAS AMPLICOR CT/NG test is widely used for the diagnosis of Neisseria gonorrhoeae infection using genital swabs or urine samples. Although highly specific, cross-reactivity occurs with some nonpathogenic strains of Neisseria and Lactobacillus species. In low-prevalence populations, even highly specific assays may require confirmatory testing of positive results. We assessed the positive predictive value (PPV) of this test in a low-prevalence (0.5%) setting. Genital and urine specimens testing positive using the COBAS AMPLICOR NG test were retested using an investigational 16S rRNA PCR assay. Additionally, 737 specimens were tested in parallel by both culture and the above PCR protocol. Of 9,772 specimens tested in-house, 168 were positive by the AMPLICOR test; in addition, 62 AMPLICOR-positive specimens were referred to our laboratory for confirmatory testing, yielding 230 positive specimens. Of these, 72 were confirmed positive by 16S rRNA PCR, yielding a specificity of 98.7% and a PPV of 31.3%. Specificity was similar for all specimen types, whereas PPV varied with prevalence: specimens from males, females, urine specimens, and genital swabs had PPVs of 70.8, 13.3, 51.9, and 20.1%, respectively. The PPV was higher when the initial AMPLICOR optical density (OD) was ≥3.5 versus initial and repeat OD readings in an equivocal zone of ≥0.2 to <3.5 (65.1 versus 10.1%; P < 0.001). On repeat testing of specimens with ODs in the equivocal zone, 54 gave ODs of ≥0.2 and <2.0, 35 gave ODs of ≥2.0 and <3.5, and 12 gave ODs of ≥3.5, with 3.7, 20, and 33.3% confirmed positive, respectively (P = 0.004). Comparing PCR to culture as the “gold standard,” specificity increased from 96.8 to 99.9% when 16S rRNA PCR was performed on specimens positive by the COBAS AMPLICOR NG test. Confirmatory testing with a more specific method such as 16S rRNA PCR should be considered in low-prevalence populations, especially for specimens with an OD in the equivocal zone

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada

Randomized Trials Comparing Inactivated Vaccine After Medium- or High-titer Measles Vaccine With Standard Titer Measles Vaccine After Inactivated Vaccine: A Meta-analysis.

BACKGROUND: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated vaccines [after medium-titer MV (MTMV) or high-titer MV (HTMV)] and a live standard titer MV (after an initial inactivated vaccine). METHODS: The trials were conducted in Sudan, Senegal, The Gambia and Guinea-Bissau. The intervention group received live MTMV or HTMV from 4 to 5 months and then an inactivated vaccine from 9 to 10 months of age; the control children received inactivated vaccine/placebo from 4 to 5 months and standard titer MV from 9 to 10 months of age. We compared mortality from 9 months until end of study at 3 to 5 years of age for children who received inactivated vaccine (after MTMV or HTMV) and standard titer MV (after inactivated vaccine), respectively. The original datasets were analyzed using a Cox proportional hazards model stratified by trial. RESULTS: The mortality rate ratio (MRR) was 1.38 (95% confidence interval: 1.05-1.83) after an inactivated vaccine (after MTMV or HTMV) compared with a standard titer MV (after inactivated vaccine). Girls had a MRR of 1.89 (1.27-2.80), whereas there was no effect for boys, the sex-differential effect being significant (P = 0.02). Excluding measles cases did not alter these conclusions, the MRR after inactivated vaccines (after MTMV or HTMV) being 1.40 (1.06-1.86) higher overall and 1.92 (1.29-2.86) for girls. Control for variations in national immunization schedules for other vaccines did not modify these results. CONCLUSIONS: After 9 months of age, all children had been immunized against measles, and mortality in girls was higher when they had received inactivated vaccines (after MTMV or HTMV) rather than live standard titer MV (after an inactivated vaccine)

Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report.

Background : Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. Methods : This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. Results : New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. Conclusions : Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea