Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 ...in two cohorts.
Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality.
Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%).
Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B.
Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27–49) VS. 66 (46–70) years, whereas in cohort B 37 (27–46) VS. 48 (47–60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26–19.2%) natives; p-value: 0.005).
The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.
A point-of-care (POC) device is reported for highly sensitive and selective detection of Plasmodium falciparum lactate dehydrogenase (Pf-LDH), a biomarker of malaria infection, based on a single-step ...magneto-immunoassay, a single-use microfluidic paper device and a customized hand-held fluorescence reader. The single-step magneto-immunoassay consists in a single 5-min incubation of immuno-modified magnetic particles (c-MAb-MPs), biotinylated detection antibody (bd-MAb), and an enzymatic signal amplifier (Poly-HRP). After on-chip MP concentration and washing, signal generation is achieved by adding a fluorescent enzymatic substrate (QuantaRed). Fluorescence signal is measured using a low-cost customized, portable, and sensible fluorescent detector. The POC affords quantitative Pf-LDH detection in <20 min, with a detection limit of 0.92 ng mL−1 (equivalent to 4.6 parasites μL−1). Furthermore, Pf-LDH quantitation in clinical samples correlates with that provided by the reference ELISA, is more sensitive than a commercial rapid diagnostic test (RDT) and entails little user intervention. These results show that fluorescent paper-based microfluidic devices can be exploited to simplify magneto-immunoassay handling, taking this type of test closer to the requirements of POC testing.
Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.
The purpose of ...this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers.
A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.
Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.
Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole POS in the Treatment of Asymptomatic Chronic Chagas Disease P05267 STOP CHAGAS: NCT01377480).
Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the ...adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 76%) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.
Rapid diagnostic tests (RDTs) for point-of-care (POC) testing of infectious diseases are popular because they are easy to use. However, RDTs have limitations such as low sensitivity and qualitative ...responses that rely on subjective visual interpretation. Additionally, RDTs are made using paper-bound reagents, which leads to batch-to-batch variability, limited storage stability and detection of only the analytes they were designed for. This work presents the development of a versatile technology, based on short magneto-assays and inexpensive paper-based microfluidic electro-analytical devices (PMEDs). PMEDs were produced locally using low-cost equipment, they were stable at room temperature, easy to use, and provided quantitative and objective results. The devices served to detect alternatively a variety of magneto-assays, granting quantitation of streptavidin-HRP, biotinylated HRP and Pasmodium falciparum lactate dehydrogenase (Pf-LDH) in less than 25 min, using either commercial or customized screen-printed electrodes and measurement equipment. Furthermore, Pf-LDH detection in diluted lysed whole blood displayed a linear response between 3 and 25 ng mL
, detection and quantification limits ranging between 1 and 3 ng mL
and 6-12 ng mL
, respectively, and provided results that correlated with those of the reference ELISA. In short, this technology is versatile, simple, and highly cost-effective, making it perfect for POC testing.
According to the WHO, chronic Chagas disease (CD) diagnosis is based on two serological techniques. To establish a definitive diagnosis, the results must be concordant. In cases of discordances, the ...WHO proposes repeating serology in a new sample, and if results remain inconclusive, a confirmatory test should be performed. This study, conducted at two Tropical Medicine Units in Europe over 4 years, aims to assess the diagnostic yield of TESA- (trypomastigote excreted–secreted antigens) blot as a confirmatory technique in patients with inconclusive and discordant results. Of 4939 individuals screened, 1124 (22.7%) obtained positive results and 165 (3.3%) discordant results. Serology was repeated in 88/165 sera and discrepancies were solved in 25/88 (28.4%) cases. Patients without a definitive diagnosis were classified in two different groups: Group 1, including patients with inconclusive results despite retesting (n = 63), and Group 2, including patients with discordant results not retested (n = 77). TESA-blot was performed for all of Group 1 and 39/77 of Group 2 and was positive for 33/63 (52.4%) and 21/39 (53.8%), respectively. Analysis of Group 1 results showed a moderate agreement between results of the ELISA based on native antigen and TESA-blot (κ 0.53). In contrast, a clear disagreement was observed between the ELISA based on recombinant antigens and TESA-blot (κ <0). A sizeable proportion of patients are suspected to have CD with inconclusive results or in whom re-testing is not feasible. TESA-blot was positive in half of these patients, highlighting the need for a confirmatory assay in European centres caring for exposed individuals.
Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and ...meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.
Multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) are global concerns, with stagnant treatment success rates of roughly 54% and 30%, respectively. Despite adverse events ...associated with several DR-TB drugs, newly developed drugs and shorter regimens are
bringing hope; recent concern has focused on drugs that prolong the corrected QT interval (QTc). QTc prolongation is a risk factor for torsades de pointe (TdP), a potentially lethal cardiac arrhythmia. While QTc prolongation is used in research as a surrogate marker for drug safety, the correlation
between QTc and TdP is not perfect and depends on additional risk factors. The electrocardiogram (ECG) monitoring that has been recommended when new drugs are used has created alarm among clinicians and National Tuberculosis Programmes (NTPs). ECG monitoring is often challenging in high-burden
settings where treatment alternatives are limited. According to a review of studies, the prevalence of sudden death directly attributable to TdP by QTc-prolonging DR-TB drugs is likely less than 1%. The risk of death from an ineffective MDR-TB/XDR-TB regimen thus far exceeds the risk of death
from arrhythmia. In patients with QTc prolongation who develop cardiac events, other significant risk factors in addition to the drugs themselves are nearly always present. Clinicians and NTPs should be aware of and manage all possible circumstances that may trigger an arrhythmia (hypopotassaemia
and human immunodeficiency virus infection are probably the most frequent in DR-TB patients). We present the limited but growing evidence on QTc prolongation and DR-TB management and propose a clinical approach to achieve an optimal balance between access to life-saving drugs and patient safety.
Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine ...detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively AUC > 0.938). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.
Chagas disease has been increasingly diagnosed in non-endemic countries. This is a prospective observational study performed at the Tropical Medicine Units of the International Health Program of the ...Catalan Health Institute, Barcelona (PROgrama de Salud Internacional del Instituto Catalán de la Salud, PROSICS Barcelona, Spain), that includes all patients with Chagas disease who attended from June 2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274 patients were included, the mean age of the patients was 37.7 years, 67.5% were women and 97% came from Bolivia. Thirteen patients had immunosuppressive conditions. The prevalence of cardiac involvement was 16.9%, lower than in previous studies performed in endemic areas (20–60%). Cardiac alterations were found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence of digestive involvement was 14.8%. The rate of digestive involvement is very different among previous studies because of different diagnostic tools and strategies used. Barium enema alterations were found in 21.4% of symptomatic and 10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies, Chagas disease in non-endemic countries affects younger patients and has lower morbidity.
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