Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy

Background Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation. Methods We assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed. Results Changes in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients. Conclusions Monitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation

Adsorption of Metal Clusters on Graphene and Their Effect on the Electrical Conductivity

When adsorbates are introduced in graphene, the electric conductivity is highly modified. This chapter discusses how to estimate the electrical conductivity of graphene sheets with adsorbates, using electronic structure calculations and some theoretical approaches. Also, we discussed how the clustering of adsorbates attached to the graphene can impact electrical conductivity. We will focus in using metallic clusters as adsorbates (Mn; M = Ag, Au, Pt, and Pd; n = 1, 2, 3, and 4). The electrical conductivity is found using theoretical approaches, which are summarized in this chapter. We compare these approaches between each other to determine which is the most appropriate for each system

Risk factors for hospitalization of children with diarrhea in Shahrekord, Iran

Background: Diarrheal infections are responsible for over a quarter of all childhood mortality worldwide. The present study was performed to establish risk factors for hospitalization of children with diarrhea in Shahrekord, Iran. Materials and methods: For this case-control study, cases were selected through children hospitalized due to acute diarrhea lasting less than 14 days and controls were compromised of children with a clinical diagnosis of acute diarrhea lasting for less than 14 days who did not require hospitalization. Controls were selected from out-patient department (OPD) or 3 primary health care centers. Results: The study population included 259 hospitalized children (cases), 245 OPD and 245 primary health centres controls. In total, bloody diarrhea, dehydration, breastfeeding for ≤6 months, history of hospitalization in the previous year, lack of access to safe water, keeping animals at home and the presence of watery stool were associated with an increased risk of hospitalization during univariate analysis. However, multivariate analysis revealed that bloody diarrhea, watery stool, vomiting, use of unsafe water, prior hospitalization, and the presence of rotavirus or salmonella in the stool were independent factors increasing the risk of hospitalization. Conclusion: Our results indicate that improving environmental sanitation, socio-economic status and establishing training programs for parents can reduce risk of hospitalization due to diarrhea in children

Comparison of Mycobacterium tuberculosis drug susceptibility using solid and liquid culture in Nigeria.

BACKGROUND: This study compares Mycobacterium tuberculosis culture isolation and drug sensitivity testing (DST) using solid (LJ) and liquid (BACTEC-MGIT-960) media in Nigeria. METHODS: This was a cross sectional survey of adults attending reference centres in Abuja, Ibadan and Nnewi with a new diagnosis of pulmonary tuberculosis (TB) or having failed the first-line TB treatment. Patients were requested to provide three sputum specimens for smear-microscopy and culture on LJ and BACTEC-MGIT-960. Positive cultures underwent DST for streptomycin, isoniazid, rifampicin and ethambutol. RESULTS: 527 specimens were cultured. 428 (81%) were positive with BACTEC-MGIT-960, 59 (11%) negative, 36 (7%) contaminated and 4 (1%) had non-tuberculosis mycobacteria (NTM). 411 (78%) LJ cultures were positive, 89 (17%) negative, 22 (4%) contaminated and 5 (1%) had NTM. The mean (SD) detection time was 11 (6) and 30 (11) days for BACTEC-MGIT-960 and LJ. DST patterns were compared in the 389 concordant positive BACTEC-MGIT-960 and LJ cultures. Rifampicin and isoniazid DST patterns were similar. Streptomycin resistance was detected more frequently with LJ than BACTEC-MGIT-960 and ethambutol resistance was detected more frequently with BACTEC-MGIT-960 than LJ, but differences were not statistically significant. MDR-TB was detected in 27 cases by LJ and 25 by BACTEC-MGIT-960 and using both methods detected 29 cases. CONCLUSIONS: There was a substantial degree of agreement between the two methods. However using the two in tandem increased the number of culture-positive patients and those with MDR-TB. The choice of culture method should depend on local availability, cost and test performance characteristics

Epidemiology of dengue fever in Guatemala

Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, but all serotypes caused epidemics. The largest outbreak occurred in 2010 with 1080 DENV2 cases reported. The incidence was higher among adults during epidemic years, with significant increases in 2005, 2007, and 2013 DENV1 outbreaks, the 2010 DENV2 and 2003 DENV3 outbreaks. Adults had a lower incidence immediately after epidemics, which is likely linked to increased immunity

Yield of Smear Microscopy and Radiological Findings of Male and Female Patients with Tuberculosis in Abuja, Nigeria

Objective. To describe the yield of smear-microscopy and radiological findings by male and female patients with symptoms of tuberculosis in Abuja, Nigeria. Methods. Patients ≥15 years old with cough for >3 weeks submitted 3 sputum samples for smear microscopy. One specimen was cultured using MGIT-960. All patients had lung X-rays and screened for HIV. Results. were more likely to be smear-positive than females (262/774 [34%] and 137/547 [25%], P < .01), but similar proportions of males and females were culture-positive (437/691 [63%] and 294/495 [59%], P = .09). 317/626 (50.6%) males and 249/419 (59.4%) females were HIV-positive (P < .005). Among culture-positives patients, HIV-infected males were less likely to have positive smears than HIV-negative males (49.2% versus 66%, P = .001). Among females, smear positivity did not vary with HIV (46.4% for HIV-positive and 52.9% for HIV-negative, P = .38). Of 274 culture-confirmed TB cases, 226 (82.5%) had cavities, and 271 (99%) had ≥1 lung areas affected. HIV-positive males were more likely to have lung cavities than HIV-positive females (85% versus 69%, P < .04) and to have ≥3 lung areas affected (P = .03). Conclusion. Differences in the yield of smear-microscopy, culture and X-rays on presentation are due to several factors including HIV coinfection and gender

Risk for Tuberculosis among Children

Risk among children is underestimated in countries with a high incidence of this disease

Molecular detection of mycobacterium tuberculosis in oral mucosa from patients with presumptive tuberculosis

Funding: This research was funded by a Strategic Award grant from the European and Developing Countries Clinical Trials Partnership (grant DRIA2014-309) and its cofounders, the Medical Research Council UK, and Institutode Salud Carlos III (ISCIII), Spain (PI116/01912); and from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement no. 823854 (INNOVA4TB).Tuberculosis (TB) diagnosis is increasingly based on the detection of Mycobacterium tuberculosis complex (MTBC) DNA in sputum using molecular diagnostic tests as the first test for diagnosis. However, sputum can be difficult to obtain in children, patients without productive cough, and the elderly and approaches testing non-sputum samples are needed. We evaluated whether TB can be detected from the oral mucosa of patients with TB. Adults with presumptive TB were examined using culture, Xpert MTB/RIF, smear microscopy and X-Rays. Oral mucosa swabs collected on PrimeStore-MTM, stored at room temperature if tested within 30 days or at −20 °C if examined at a later time. RT-PCR was performed to detect M. tuberculosis DNA. Eighty patients had bacteriologically-confirmed TB, 34 had bacteriologically-negative TB (negative tests but abnormal X-rays) and 152 were considered not to have TB (not TB). Oral swabs RT-PCR were positive in 29/80 (36.3%) bacteriologically-confirmed, 9/34 (26.5%) bacteriologically-negative and 29/152 (19.1%) not TB. The yield varied among samples stored for less and more than 30 days (p = 0.013) from 61% (11/18) and 29% (18/62) among bacteriologically confirmed, and 30.8% (4/13) and 23.8% (5/21) among bacteriologically-negative participants. Among not TB patients, the specificity was 80.9% (123/152), being 78.3% (18/23) among samples stored less than 30 days and 81.4% (105/129) among samples stored for more than 30 days (p = 0.46). The detection of M. tuberculosis in oral mucosa samples is feasible, but storage conditions may affect the yield.Publisher PDFPeer reviewe

FluoroType MTB system for the detection of pulmonary tuberculosis

Altres ajuts: The authors would like to acknowledge Hain Lifescience (Germany) for their provision of a FluoroCycler and sufficient FluoroType MTB assays to carry out the study. Hain Lifescience had no influence on the study design, data analysis or preparation of the manuscript. Funding information for this article has been deposited with the Crossref Funder RegistryDiagnosis continues to be a major barrier for the control of tuberculosis (TB), especially in low- and middle-income countries (LMIC) [1]. The number of platforms for the molecular diagnosis of TB have increased in recent years and they can provide test results more rapidly than culture. Molecular assays are increasingly being used as alternative or adjunct methods to culture and smear microscopy, and modern systems seek to partially or fully automate the DNA extraction and amplification steps, increasing their suitability for resource-limited laboratories. One of these platforms, the GeneXpert MTB/RIF (Cepheid, USA), has a sensitivity of roughly 85% compared to culture [2] and has seen significant uptake in developing countries [3]. However, as a fully closed system, the DNA extracted during the process cannot be used for further downstream drug susceptibility testing (DST), which is crucial for patients with suspected drug-resistant TB. FluoroType MTB is a sensitive test for TB but specificity is low compared with fully integrated molecular system