Background
There is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.
Methods
We performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.
Findings
Two hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73–0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79–0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0–69·0%) than CRP (28·1%, 95% CI: 20·2–41·8%) (
p
= 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2–98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3–99·9%) was higher.
Interpretation
For active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.
Funding
National Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).
The aim of this study will be to analyze the effects of microwave diathermy (MWD) and transcutaneous electrical nerve stimulation (TENS) on primary dysmenorrhea. Eighty eight women, age range 18-44 years, with no previous pregnancy, no practice physical activities, a BMI of ≤29.9 kg/m, a regular menstrual cycle and a diagnosis of primary dysmenorrhea, with menstrual pain ranging from mild to severe, will be selected. The participants will be randomized into four groups: MWD and TENS, MWD and placebo TENS, placebo MWD and TENS, and placebo MWD and placebo TENS. Pain will be measured using the visual numeric scale and the McGill Pain Questionnaire; the pressure pain threshold using a digital algometer and conditioned pain modulation using the cold pressor test. Brazilian Clinical Trials Registry (RBR-5QKCK4. Registered on 16 March 2016).
We found no statistically significant differences in serological response to treatment with doxycycline or benzathine penicillin among HIV-infected patients with early, late latent or latent syphilis of unknown duration. Our findings suggest that doxycycline is an acceptable treatment to HIV-infected patients with nontertiary stages of syphilis.
Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.
Background
Although systematic tuberculosis screening in high-risk groups is recommended by WHO, implementation in prisons has been limited due to resource constraints. Whether Xpert Ultra sputum pooling could be a sensitive and efficient approach to mass screening in prisons is unknown.
Methods
1,280 sputum samples were collected from inmates in Brazil during mass screening and tested using Xpert G4. We selected samples for mixing in pools of 4, 8, 12, and 16, which were then tested using Ultra. In each pool, a single positive sample of differing Xpert mycobacterial loads was used. Additionally, 10 pools of 16 negative samples each were analyzed as controls. We then simulated tuberculosis screening at prevalences of 0.5-5% and calculated the cost per tuberculosis case detected at different sputum pooling sizes.
Results
The sensitivity and specificity of sputum pooling were high (sensitivity: 94%; 95% CI: 88–98; specificity: 100%, 95% CI: 84–100). Sensitivity was greater in pools in which the positive sample had a high mycobacterial load compared to those that were very low (100% vs 88%). In settings with a higher tuberculosis prevalence, pools of 4 and 8 were more efficient than larger pool sizes. Larger pools decreased the costs by 87% at low prevalences whereas smaller pools fitted greater at higher prevalences (57%).
Conclusions
Sputum pooling using Ultra was a sensitive strategy for tuberculosis screening. This approach was more efficient than individual testing across a broad range of simulated tuberculosis prevalence settings and could enable active case finding to be scaled while containing costs.
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