Thin-Layer-Agar-Based Direct Phenotypic Drug Susceptibility Testing on Sputum in Eswatini Rapidly Detects Mycobacterium tuberculosis Growth and Rifampicin Resistance Otherwise Missed by WHO-Endorsed Diagnostic Tests.

Xpert MTB/RIF rapidly detects resistance to rifampicin (RR); however, this test misses I491F-RR conferring rpoB mutation, common in southern Africa. In addition, Xpert MTB/RIF does not distinguish between viable and dead Mycobacterium tuberculosis (MTB). We aimed to investigate the ability of thin-layer agar (TLA) direct drug-susceptibility testing (DST) to detect MTB and its drug-resistance profiles in field conditions in Eswatini. Consecutive samples were tested in parallel with Xpert MTB/RIF and TLA for rifampicin (1.0 µg/ml) and ofloxacin (2.0 µg/ml). TLA results were compared at the Reference Laboratory in Antwerp with indirect-DST on Löwenstein-Jensen or 7H11 solid media and additional phenotypic and genotypic testing to resolve discordance. TLA showed a positivity rate for MTB detection of 7.1% versus 10.0% for Xpert MTB/RIF. Of a total of 4,547 samples included in the study, 200 isolates were available for comparison to the composite reference. Within a median of 18.4 days, TLA detected RR with 93.0% sensitivity (95% confidence interval [CI], 77.4 to 98.0) and 99.4% specificity (95% CI, 96.7 to 99.9) versus 62.5% (95% CI, 42.7 to 78.8) and 99.3% (95% CI, 96.2 to 99.9) for Xpert MTB/RIF. Eight isolates, 28.6% of all RR-confirmed isolates, carried the I491F mutation, all detected by TLA. TLA also correctly identified 183 of the 184 ofloxacin-susceptible isolates (99.5% specificity; 95% CI, 97.0 to 99.9). In field conditions, TLA rapidly detects RR, and in this specific setting, it contributed to detection of additional RR patients over Xpert MTB/RIF, mainly but not exclusively due to I491F. TLA also accurately excluded fluoroquinolone resistance.

Alternative observational designs to estimate the effectiveness of one dose of oral cholera vaccine in Lusaka, Zambia.

We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7-97.8) in the MCC study, 80.2% (95% CI: 16.9-95.3) in the TNCC design and 89.4% (95% CI: 64.6-96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.

Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

BACKGROUND: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. METHODS: We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. FINDINGS: Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). INTERPRETATION: PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. FUNDING: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.

Fly ash-derived strontium as an index to monitor deposition from coal-fired power plants.

The combustion of western U.S. coals releases significant amounts of strontium, which is relatively enriched in the fine particles of fly ash. Fly ash-derived strontium is readily absorbed by agronomic and native plant species when incorporated in soil. The strontium-87 to strontium-86 ratios of fly ash and soils were significantly different, but similar ratios were found in fly ash and plants treated with fly ash. A technique for measuring and monitoring deposition from coal-fired power plants is inferred from the enhanced plant uptake of fly ash strontium and the similarity in the isotopic ratios of fly ash and treated plants.

Routine use of Xpert® MTB/RIF in areas with different prevalences of HIV and drug-resistant tuberculosis.

SETTING: Despite the widespread introduction of Xpert(®) MTB/RIF in developing countries, reports of its use and value in routine conditions remain limited. OBJECTIVE: To describe Xpert results in relation to microscopy, treatment initiation, cost and workload under routine conditions at four sites in Cambodia, Georgia, Kenya and Swaziland. DESIGN: Laboratory and clinical information on presumed TB patients were obtained from routine registers over a period of at least 6 months between March and November 2012. RESULTS: Among the 6086 presumed TB patients included in the analysis, Xpert testing increased the number of biologically confirmed cases by 15% to 67% compared to microscopy. Up to 12% of the initial Xpert results were inconclusive. Between 56% and 83% of patients were started on treatment based on microscopy and/or Xpert results, with median delays of 1-16 days. Rifampicin resistance was detected in 3-19% of Xpert-positive patients. CONCLUSION: Despite the additional numbers of cases detected by Xpert compared to microscopy, large proportions of patients are still started on treatment empirically in routine practice. Patient and specimen flow should be optimised to reduce delays in treatment initiation. Simple, non-sputum-based point-of-care tests with high sensitivity are needed to improve TB diagnosis and management.

An assay for human chorionic gonadotrophin using the capillary fill immunosensor.

Recently there has been much research effort directed towards the development of immunosensors. Optical technologies are currently proving very attractive for the construction of such sensors. The fluorescence capillary fill device (FCFD) has been designed to fulfil these needs. The development of an assay for human chorionic gonadotrophin (hCG) in the FCFD for a variety of body fluids (whole blood, serum, urine and saliva) demonstrates the versatility and assay performance of the device.

Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China.

Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.