Diagnostics to support mycetoma management-Development of two target product profiles.

OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different microorganisms and identified by the WHO as one of the high-priority diseases for developing diagnostic tests. To ensure the production of diagnostic assays for use by clinical staff in endemic regions, target product profiles (TPPs) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another that would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a 1-month online public consultation on 25 October 2021, and the final TPP was posted online on 5 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them.

Glucose and leukocyte esterase levels are possible biomarkers for bacterial septic arthritis.

OBJECTIVE: The objective of the study was to determine the added value of synovial fluid (SF) glucose levels and other biochemical parameters as possible biomarkers of bacterial septic arthritis (SA). MATERIALS AND METHODS: We prospectively examined adult patients with SA. As a control group, adults with uninfected joints were enrolled. SF samples were obtained, and microbiological analyses were made. SF glucose levels, pH, and leukocyte esterase were measured using a glucometer and colorimetric test strips. Blood samples were collected from both groups to determine glucose levels. RESULTS: We included eight subjects with knee ligaments lesions, six with meniscus lesions, and five with osteoarthritis as the control group, as well as 20 patients with SA. SF culture was positive in 60%. SF glucose levels from patients were lower than the controls (p = 0.0018) with the lowest concentration in patients with a positive culture (p = 0.0004). Blood and SF glucose concentration from the positive culture patients were compared (p < 0.0001). Leukocyte esterase presented the highest values in patients with a positive culture (p < 0.0001) and a more acidic pH was found compared to the control group (p < 0.0001). CONCLUSION: These biochemical parameters might be a quick and inexpensive added value for distinguishing between infective and non-infective joint disease.

OBJETIVO: Evaluar el valor añadido de los niveles de glucosa en el líquido sinovial (LS) y otros parámetros bioquímicos en el diagnostico de artritis séptica (AS). MATERIAL Y MÉTODOS: Análisis prospectivo de pacientes adultos con AS. Pacientes con articulaciones no infectadas fueron incluidos como grupo control. Se tomaron muestras de LS y sangre para la realización de análisis microbiológicos y bioquímicos en los pacientes y controles. RESULTADOS: Incluimos 8 sujetos con lesión ligamentosa de rodilla, 6 con lesiones meniscales y 5 con osteoartritis como grupo control, así como 20 pacientes con AS. El cultivo de LS fue positivo en 60%. Los niveles de glucosa en LS de pacientes con AS fueron más bajos que los controles (P = 0.0018) con la concentración más baja en pacientes con cultivo positivo (p = 0.0004). La relación de glucosa en sangre y LS de pacientes con cultivo positivo se vio afectada (p < 0.0001). La esterasa leucocitaria presentó valores más altos en pacientes con cultivo positivo (p < 0.0001); se encontró un pH más ácido en comparación con el grupo control (p < 0.0001). CONCLUSIÓN: Estos parámetros bioquímicos podrían ser un valor agregado útil, rápido y económico para distinguir entre enfermedad articular infecciosa y no infecciosa.

Systemic and Local Cytokines Profile Determine Severity and Prognosis in Human Septic Arthritis.

BACKGROUND: Septic arthritis (SA) is a medical emergency. The most common etiological agents are bacteria, which activate the local immune response coordinated by cytokines; however, little is known about the cytokine profile in human SA. AIM: To determine the association of local and systemic cytokine profiles with the severity and prognosis of patients with SA. METHODS: Patients with clinical and laboratory diagnosed SA were enrolled as well as a control group. Serum and synovial fluid (SF) samples were obtained for determining cytokines and glucose levels; SF samples were used for histological analysis. Osteochondral damage and general health status and quality of life (SF-36) were evaluated during recruitment day. WOMAC osteoarthritis index score and SF-36 questionnaire were used a year after recruitment day as a follow up. RESULTS: A systemic and local proinflammatory cytokine profile was found in patients compared to the control group (p <0.05). IL-6 was 28 and 525 times higher than controls in sera and SF, respectively (p <0.0001). Systemic IL-6 correlated negatively with general mental health score (p = 0.0184) and was associated with a higher osteoarthritis index after one year follow-up in the patients (p = 0.0352). HMGB1 in SF was found higher in patients with SA (p <0.0001), and it was associated with osteochondral damage (p = 0.0042). TNF-α in SF correlated negatively with SF-36 questionnaire one year after patients' recruitment in role limitation score (p = 0.0318), body pain score (p = 0.0315), and general mental health score (p = 0.0197). CONCLUSION: Serum and SF cytokine signatures are associated with disease severity and prognosis in patients with SA.

Anti-carbamylated protein antibodies positivity and disease activity in Hispanic patients with established rheumatoid arthritis: An observational study.

OBJECTIVES: We aimed to determine the prevalence of anti-carbamylated protein (anti-CarP) antibodies in Mexican Hispanics with established rheumatoid arthritis (RA) and to assess their relationship with disease activity. METHODS: A cohort study was conducted in 278 patients with established RA during an 18-month follow-up. We measured IgG/IgM/IgA rheumatoid factor (RF), IgG anticitrullinated protein antibodies (ACPA) and IgG/IgM/IgA anti-CarP antibodies using enzyme-linked immunosorbent assay (ELISA). For disease activity, we performed the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR). Repeated measures one-way ANOVA was used to test the association between anti-CarP IgG antibody status and longitudinal DAS28-ESR scores. Patients were evaluated at baseline and at 6, 12, and 18 months during follow-up. RESULTS: Anti-CarP IgG antibodies were positive in 47.8% of patients and, accounting for all isotypes, in 9.5% of patients with negative RF and ACPA. Triple antibody positivity was present in 42.6% of patients in our sample. Anti-CarP IgG antibody positivity did not show statistically significant differences in mean DAS28-ESR when compared to anti-CarP IgG antibody negative patients at baseline, 6, 12 or 18 months. CONCLUSION: Anti-CarP IgG antibodies are not associated to a higher disease activity in Hispanic patients with established RA. Our findings suggest that the clinical value of measuring anti-CarP antibodies in RA diminishes over time.

Human Eosinophils Reduce Viral Titer, Secrete IL-8, and Increase RIG-I Expression in Response to Influenza A H1N1 pdm09.

Eosinophils participate in the immune response against many pathogens, including viruses. Since mouse eosinophils are susceptible to influenza A virus infection and possess antiviral activity, we evaluated the expression of sialic acid residues in human eosinophils and their response against influenza virus in vitro. We demonstrated that human eosinophils express α2,6- and α2,3-linked sialic acid, and drastically reduced influenza virus titer. After influenza virus exposure, eosinophils upregulated retinoic acid-inducible gene I (RIG-I) mRNA expression, but no other pattern recognition receptors. Finally, high concentrations of interleukin-8 (IL-8) were found in influenza virus-exposed eosinophil cultures. These data suggest that human eosinophils possess antiviral activity and may play a role in the innate immune response to influenza virus.

Immunosuppression by UVB radiation exacerbates Leishmania mexicana skin lesions in mice.

Cutaneous leishmaniasis is the most common form of leishmaniasis in humans. The disease is caused by several species, such as Leishmania mexicana, a protozoa parasite. Several major risk factors are associated with this disease, including poverty, poor housing, inadequate domestic hygiene, malnutrition, mobility, and occupational exposure. Solar radiation (UVB) has not been considered a risk factor because there is no scientific evidence demonstrating a correlation with increased susceptibility to cutaneous leishmaniasis. In this study, the shaved skin of the back of C57BL/6 mice was irradiated with 24.2 mJ/cm2 of UVB. A delayed-type hypersensitivity (DTH) reaction was used to assess UV-induced immune suppression. Skin lesions were quantitated, and parasite burden and the presence of anti-Leishmania mexicana antibodies in serum and germinal centers in draining lymph nodes were determined. We found an increased in the lesion size and parasitic load in UVB-irradiated mice compared to the WT mice and B lymphocyte activation in draining lymph nodes and increased IgG1 production. Our results show an important role of UVB-induced suppression in cutaneous leishmaniasis through local production of IL-10 and systemic IgG1antibodies. This is the first study that demonstrates the effects of UVB radiation on cutaneous leishmaniasis by Leishmania mexicana.

Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice.

Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with N. brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6 and IL-10 expression were similar and TNF-α was lower.

Cortisol and perceived stress are associated with cytokines levels in patients infected with influenza B virus.

Influenza B virus (IBV) causes respiratory infectious disease. Cytokines are important immune mediators during infectious diseases. Cortisol and stress have been related to respiratory infection susceptibility and cytokine regulation. Little is known about systemic cytokines, cortisol, and perceived stress in the early stages of IBV infection. We researched the systemic cytokines and cortisol, as well as the perceived stress and blood cell count in patients infected with IBV. The diagnosis was established using the Luminex xTAG RVP kit and confirmed with qRT-PCR for IBV viral load. The perceived stress was evaluated using the perceived stress scale (PSS-10). Twenty-five plasma cytokines were determined using multiplex immunoassay and cortisol by ELISA. The leukocyte differential count was measured with a standard laboratory protocol. Th1, Th17, and IL-10 cytokines were higher in IBV infected patients (P < 0.05). Leukocytes and neutrophil count negatively correlated with viral load (P < 0.05). Perceived stress had a negative effect on monocyte and systemic cytokines in IBV infected patients (P < 0.05). Cortisol was higher in patients infected with IBV and correlated positively with CCL20 (P < 0.05). Cortisol showed a positive effect on most of the systemic cytokines (P < 0.05). In conclusion, a cytokine pattern was found in IBV infected patients, as well as the possible role of leukocyte counts in the control of IBV. Our results suggest the importance of cortisol and perceived stress on systemic cytokines in patients infected with IBV, but more studies are needed to understand their role in cytokine production in respiratory infectious disease.

Immune response to Leishmania mexicana: the host-parasite relationship.

Leishmaniosis is currently considered a serious public health problem and it is listed as a neglected tropical disease by World Health Organization (WHO). Despite the efforts of the scientific community, it has not been possible to develop an effective vaccine. Current treatment consists of antimonials that is expensive and can cause adverse effects. It is essential to fully understand the immunopathogenesis of the disease to develop new strategies to prevent, treat and eradicate the disease. Studies on animal models have shown a new paradigm in the resolution or establishment of infection by Leishmania mexicana where a wide range of cytokines, antibodies and cells are involved. In recent years, the possibility of a new therapy with monoclonal antibodies has been considered, where isotype, specificity and concentration are critical for effective therapy. Would be better to create/generate a vaccine to induce host protection or produce passive immunization with engineering monoclonal antibodies to a defined antigen? This review provides an overview that includes the current known information on the immune response that are involved in the complex host-parasite relationship infection caused by L. mexicana.

Inducible nitric oxide synthase blockade with aminoguanidine, protects mice infected with Nocardia brasiliensis from actinomycetoma development.

Mycetoma is a chronic infectious disease that can be caused by fungi or bacteria, Madurella mycetomatis and Nocardia brasiliensis are frequent etiologic agents of this disease. Mycetoma produced by bacteria is known as actinomycetoma. In mycetoma produced by fungi (eumycetoma) and actinomycetoma, diagnosis of the disease is based on clinical findings: severe inflammation, with deformities of affected tissues, abscesses, fistulae, sinuses and discharge of purulent material that contains micro colonies of the etiologic agent. Microscopic examination of infected tissue is similar regardless of the offending microbe; hallmark of infected tissue is severe inflammation with abundant neutrophils around micro colonies and granuloma formation with macrophages, lymphocytes, dendritic and foamy cells. Even though medical treatment is available for mycetoma patients, amputation, or surgical intervention is frequently needed. The pathogenesis of actinomycetoma is little known, most information was obtained from experimental animal models infected with bacteria. In other experimental mice infections with different microbes, it was demonstrated that nitric oxide is responsible for the intracellular killing of Mycobacterium tuberculosis by activated macrophages. Nitric oxide is a free radical with potent stimulatory and suppressive effects in innate and adaptive immunity. The unstable nitric oxide molecule is produced by action of nitric oxide synthases on L-arginine. There are three nitric oxide synthases expressed in different cells and tissues, two are constitutively expressed one in neurons, and the other in endothelial cells and one that is inducible in macrophages. Aminoguanidine is a competitive inhibitor of inducible nitric oxide synthase. Its administration in experimental animals may favor or harm them. We used aminoguanidine in mice infected with Nocardia brasiliensis, and demonstrated that all treated animals were protected from actinomycetoma development. Anti N. brasiliensis antibodies and T cell proliferation were not affected, but inflammation was reduced.

Corrigendum to "CD206+ Cell Number Differentiates Influenza A (H1N1)pdm09 from Seasonal Influenza A Virus in Fatal Cases".

[This corrects the article DOI: 10.1155/2014/921054.].

Eosinophils and Respiratory Viruses.

Eosinophils have been mainly associated with parasitic infection and pathologies such as asthma. Some patients with asthma present a high number of eosinophils in their airways. Since respiratory viruses are associated with asthma exacerbations, several studies have evaluated the role of eosinophils against respiratory viruses. Eosinophils contain and produce molecules with antiviral activity, including RNases and reactive nitrogen species. They can also participate in adaptive immunity, serving as antigen-presenting cells. Eosinophil antiviral response has been demonstrated against some respiratory viruses in vitro and in vivo, including respiratory syncytial virus and influenza. Given the implication of respiratory viruses in asthma, the eosinophil antiviral role might be an important factor to consider in this pathology.

Impaired Cerebral Vasomotor Reactivity in Alzheimer's Disease.

BACKGROUND: Recent studies have shown that cerebral vascularity may be impaired in Alzheimer's disease. Cerebral vasomotor reactivity could be an important biomarker for this pathology. AIMS: The aim of this study was to investigate the alterations in cerebral vascular motor reactivity in Alzheimer's disease subjects and to associate these changes with their cognitive scores. METHODS: We recruited subjects with a diagnosis of Alzheimer's disease and healthy controls. Demographic, clinical, imaging, and cognitive test were obtained. Then all participants performed a cerebral vascular motor reactivity test with 7% CO2 and cerebral blood flow velocities (CBFV) were recorded with transcranial doppler ultrasound before and after the test. RESULTS: We recruited 45 subjects, 26 (21 female) Alzheimer's disease participants and 19 (15 female) healthy controls. There were no differences in baseline cerebral blood flow velocities between the groups. After the cerebral vasomotor reactivity test, absolute mean difference in mean CBFV (ΔCBFV-m) was 8.70±4.14 versus 4.81±6.96 (p<0.01), respectively. Calculated percentage of change (%CVMR) was lower in the AD group 7.45±18.25 versus 23.29±17.48, and there was a positive but weak correlation with mini-mental scores (ρ=0.337, p=0.023). CONCLUSIONS: In this study, Alzheimer's disease subjects showed significant changes in all absolute cerebral blood flow velocities after the cerebral vasomotor reactivity test with CO2, but only diastolic phase responses were statistically significant. There was a positive but weak correlation between cerebral vasomotor reactivity and cognitive scores. Further studies are needed to investigate these effects in larger Latin-American samples.

Inflammatory and Anti-inflammatory Responses Co-exist Inside Lung Granuloma of Fatal Cases of Coccidioidomycosis: A Pilot Report.

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. These fungi are endemic in the southern USA and northern Mexico. Immunocompromised patients are susceptible to develop severe forms of this fungal infection. Cytokines play an important role in controlling the fungal infection, but little is known about the predominant immunological environment in human lung tissue from fatal cases. Our aim was to analyze the pro-inflammatory and anti-inflammatory cytokines and monocyte/macrophages markers (CD14 and CD206) in the granulomas of six fatal cases of coccidioidomycosis. Cytokines and surface markers were higher in coccidioidomycosis cases when compared to control (P < 0.05). CD14 positive cells were increased inside the coccidioidal granuloma when compared to the outside (P < 0.05). No differences were found in the number of CD206+ cells inside the granuloma when compared to the outer population (P > 0.05). Interestingly, an analysis of stain intensity signals showed an increased signaling of CD14, CD206, IL-10 and TNFα inside the granuloma when compared to the outside (P < 0.05). iNOS and IL-12 gene expression were not detected in coccidioidomycosis cases, while IL-10, IL-6 and TGFß gene expression were detected, but the differences when compared to healthy lungs were not significant (P > 0.05). TNFα gene expression was lower in coccidioidomycosis cases when compared to healthy lung (P = 0.05). In conclusion, pro- and anti-inflammatory responses co-exist inside of the granulomas of fatal cases of coccidioidomycosis and the absent of iNOS and IL-12 gene expression may be related with patient's outcome.

Disseminated actinomycetoma due to Nocardia wallacei.

BACKGROUND: Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge. AIMS: Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma. MATERIALS AND METHODS: We evaluated the medical management of an 18-year-old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique. RESULTS: The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found. DISCUSSION: Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma. CONCLUSION: Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei.

Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study

Abstract Background l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2-4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study.

BACKGROUND: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. METHODS: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. RESULTS: Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value=0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2-4), compared to none of the nine children who relapsed who had positive skin tests (p-value<0.001). CONCLUSION: Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

The esperanza window trap reduces the human biting rate of Simulium ochraceum s.l. in formerly onchocerciasis endemic foci in Southern Mexico.

BACKGROUND: The Esperanza Window Trap (EWT) baited with CO2 and human sweat compounds is attractive to Simulium ochraceum s.l., the primary vector of Onchocerca volvulus in the historically largest endemic foci in México and Guatemala. METHODOLOGY/PRINCIPAL FINDINGS: The ability of the EWT to locally reduce numbers of questing S. ochraceum s.l. was evaluated in two formerly onchocerciasis endemic communities in Southern México. At each community, two EWTs were placed in or near a school or household and flies were collected sequentially for a total of 10 days. Black fly collections were then carried out for an additional 10 days in the absence of the EWTs. Flies were also collected outside the dwellings to control for variations in the local fly populations. When the EWTs were present, there was a significant reduction in the human biting rate at both the household and school locations at collection sites, with a greater effect observed in the schools. CONCLUSIONS/SIGNIFICANCE: These results indicate that the EWTs not only have potential as a black fly monitoring tool but may be used for reducing personal exposure to fly bites in Mesoamerica.

Possible association of rare polymorphism in the ABCB1 gene with rifampin and ethambutol drug-resistant tuberculosis.

Human P-glycoprotein (P-gp) is a membrane transporter encoded by ABCB1 (also known as MDR1) that plays a critical role in pharmacokinetics of many unrelated drugs. Rifampin (RMP) and ethambutol (ETB), two anti-tubercular agents, are substrates of P-gp. Single nucleotide polymorphisms (SNPs) in ABCB1 have been associated with resistance to several drugs; however, their association with RMP and ETB resistance in tuberculosis patients has not yet been studied. Genotype/allele frequencies in C1236T, G2677T/A and C3435T SNPs of ABCB1 were obtained from 99 tuberculosis patients susceptible or resistant to RMP and ETB (NoRER or RER). 2677G>A allele prevalence was found to be significantly higher in the RER group compared to NoRER (5 resistant vs 2 non-resistant patients, P < 0.01; OR, 11.0; 95% CI, 2.00-56.00). No differences were found in genotype/allele frequencies in C1236T and C3435T SNPs of ABCB1 and resistance to RMP and ETB in tuberculosis patients (P > 0.05). The present study suggests the 2677G>A allele of ABCB1 could be associated with simultaneous resistance to RMP and ETB in pulmonary tuberculosis patients. Further studies with larger sample sizes are needed to confirm this association and explore its nature.

TGF-ß Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia.

There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca(++), Cl(-), prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (p<0.05). IL-6 levels were significantly elevated in influenza A (H1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (p<0.05). TGF-ß serum levels discern between healthy controls, influenza A (H1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-ß levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-ß levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis.