Paraspinal Abscess Secondary to Tuberculous Spondylitis Diagnosed by Xpert MTB/RIF Assay in Rural Tanzania.

A 31-year-old HIV-negative man presented to our clinic with a 6-month history of back pain and a swelling at the back. Radiological studies revealed lumbar vertebral destruction. Ultrasound of the mass showed a septated cystic mass with turbid fluid. Diagnostic aspiration revealed thick pus and smear microscopy detected acid-fast bacilli. Xpert MTB/RIF assay detected Mycobacterium tuberculosis with no rifampicin resistance

Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV-1 infected individuals in vivo.

The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNγ). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27(-) phenotype was associated with active TB in HIV(-) (p = 0.0003) and HIV(+) (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV(-) subjects, MTB-specific CD4 T cell populations from HIV(+) TB-asymptomatic subjects were often dominated by CD27(-) cells. These data indicate that down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease. Furthermore, these data are consistent with the hypothesis that late, chronic HIV infection is frequently associated with increased mycobacterial activity in vivo. The analysis of T cell maturation and activation markers might thus be a useful tool to monitor TB disease progression

miRNA Signatures in Sera of Patients with Active Pulmonary Tuberculosis.

Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to discriminate between PTB and LTBI, but also among the other categories

Preservation of sputum samples with cetylpyridinium chloride (CPC) for tuberculosis cultures and Xpert MTB/RIF in a low-income country

Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on culture results and performance of Xpert MTB/RIF.; Consecutive sputum samples from microscopy smear-positive TB patients were collected. Two-hundred samples were equally split in two aliquots, one aliquot was treated with CPC and stored at ambient temperature for 7 days. The second aliquot was immediately processed. Samples were decontaminated for 20, 15 or 10 min, and subsequently cultured on Löwenstein-Jensen medium. Furthermore, 50 samples were stored for 7, 14 and 21 days, and 100 CPC-pretreated samples tested by Xpert MTB/RIF.; CPC pretreated samples showed a higher culture yield compared to non-treated sputum samples across all decontamination times: 94% vs. 73% at 10 min (p = 0.01), 94% vs. 64% at 15 min (p = 0.004), and 90% vs. 52% at 20 min (p < 0.001). The quantitative culture grading was consistently higher in CPC treated compared to non-CPC treated samples. The proportion of contaminated cultures was lower in CPC pretreated samples across all decontamination times (range 2-6%) compared to non-CPC treated samples (15-16%). For storage times of CPC treated samples of 7, 14, and 21 days, 84, 86, and 84% of the respective cultures were positive. Of 91 CPC treated samples with a positive culture, 90 were also Xpert MTB/RIF positive.; CPC increases culture yield, decreases the proportion of contamination, and does not alter the performance of Xpert MTB/RIF

Assessment of diabetes and prediabetes prevalence and predictors by HbA1c in a population from sub-Saharan Africa with a high proportion of anemia: a prospective cross-sectional study

Epidemiological data about diabetes mellitus (DM) for sub-Saharan Africa (SSA) are scarce and the utility of glycated hemoglobin (HbA1c) to diagnose DM is uncertain in African populations with a high proportion of anemia.; In a cross-sectional study, age-adjusted prevalence rates and predictors for DM and pre-DM were prospectively assessed by HbA1c in a semirural walk-in population of Tanzania (n=992). Predictors for DM were calculated by logistic regression. Correlations between HbA1c, hemoglobin, and blood glucose levels were done by Pearson's correlation.; Overall, DM and pre-DM prevalence rates were 6.8% (95% CI 5.3 to 8.5) and 25% (95% CI 22.8 to 28.3), respectively. There was an increase in DM prevalence in patients 50-59 (14.9%; 95% CI 9.1 to 22.5), ≥60 years old (18.5%; 95% CI 12.2 to 26.2) and in patients with overweight (9.3%; 95% CI 5.9 to 13.7), obesity (10.9%; 95% CI 6.9 to 16) compared with patients 18-29 years old (2.2%; 95% CI 0.9 to 4.4) (p<0.001) and to normal-weight patients (3.6%; 95% CI 2.1 to 5.6) (p<0.01), respectively. Age (OR 1.08, 95% CI 1.05 to 1.12; p<0.001), body mass index (BMI) (OR 1.10, 95% CI 1.04 to 1.16; p<0.001), and acute infection (OR 3.46, 95% CI 1.02 to 10.8; p=0.038) were predictors for DM. Comparing patients with a BMI of 20 kg/m; 2; and a BMI of 35 kg/m; 2; , the relative risk for DM increases in average by 2.12-fold (range 1.91-2.24) across the age groups. Comparing patients 20 years old with patients 70 years old, the relative risk for DM increases in average 9.7-fold (range 8.9-10.4) across the BMI groups. Overall, 333 patients (36%) suffered from anemia. Pearson's correlation coefficients (r) between HbA1c and hemoglobin was -0.009 (p=0.779), and between HbA1c and fasting blood glucose and random blood glucose, it was 0.775 and 0.622, respectively (p<0.001).; We observed a high prevalence of DM and pre-DM, mainly triggered by increasing age and BMI, and provide evidence that HbA1c is suitable to assess DM also in populations of SSA with high proportions of anemia.; NCT03458338

Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants

ABSTRACT: BACKGROUND: Intermittent preventive treatment in infants with sulphadoxine-pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%. Potentially, however, this intervention may compromise the acquisition of immunity, including the tolerance towards multiple infections with Plasmodium falciparum. METHODS: Plasmodium falciparum isolates were obtained from children participating in two Ghanaian IPTi-SP trials (Tamale, Afigya Sekyere) at 15 months of age, i.e., six months after they had received the second dose of IPTi-SP or placebo. By typing the polymorphic merozoite surface protein 1 (msp1) and msp2 genes, multiplicity of infection (MOI) was assessed in 389 isolates. A total of additional 133 samples were collected in Tamale at 3, 6, 9, and 12 months of age. Comparisons of MOI between groups were done by non-parametric statistical tests. RESULTS: The number of distinguishable P. falciparum clones (MOI) ranged between one and six. Mean MOI in Tamale was stable at 2.13 - 2.17 during the first year of life, and increased to 2.57 at age 15 months (P = 0.01). At no age did MOI differ between the IPTi-SP and placebo groups (each, P [greater than or equal to] 0.5). At 15 months of age, i.e., six months after the second dose, MOI was very similar for children who had received IPTi or placebo (means, 2.25 vs. 2.33; P = 0.55) as was the proportion of polyclonal infections (69.6% vs. 69.7%; P = 0.99). Adjusting for study site, current and prior malaria, parasite density, and season did not change this finding. CONCLUSIONS: IPTi-SP appears to have no impact on the multiplicity of infection during infancy and thereafter. This suggests that tolerance of multiple infections, a component of protective immunity in highly endemic areas, is not affected by this interventio

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.; Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB.; A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88-1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03-4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38-5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12-1.16, p = 0.088).; S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB. Treatment of helminths should be considered in clinical management of TB and TB control programs

Increased and Expedited Case Detection by Xpert MTB/RIF Assay in Childhood Tuberculosis: A Prospective Cohort Study

The Xpert MTB/RIF assay is a quick and accurate tuberculosis diagnostic tool in children. Compared with microscopy, 3-fold more tuberculosis cases were detected with a similar turnaround time, resulting in a potentially shortened time to tuberculosis diagnosi