Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active ...infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4-16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4+ and CD8+ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4+ and CD8+T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to increased susceptibility and severity to infectious diseases.
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•This is the first known randomised trial assessing the impact of deworming on active tuberculosis (TB).•Deworming did not show a significant change in TB score.•Albendazole treatment ...showed a significant decline in IL-10 and eosinophils.•Deworming leads a trend towards significant weight gain.
Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3months. In an exploratory analysis after 12weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5kg versus 8.2±8.7kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.
SETTING: Ethiopia has a high prevalence of tuberculosis (TB) and is one of the countries with the highest burden of multidrug-resistant TB (MDR-TB).OBJECTIVE: To understand the costs that patients ...incur in obtaining diagnosis and treatment for MDR-TB.DESIGN: In March 2013, interviews
were conducted with 169 MDR-TB patients at three hospitals in Ethiopia to identify the cost to patients and the impact on employment and family income.RESULTS: The average MDR-TB patient incurred a total cost of US$1378, which represented 25 months of a mid-treatment household income
of US$54. The impact on the patient's employment and on overall patient and family income was generally catastrophic: 74% of all respondents reported losing their jobs, 66% of patients lost household income, and household income was reduced by 38%. To help cover the costs, 38% of patients
sold some type of property, while 7% leased out property and 41% took out loans, any of which could jeopardize their future financial situation even further.CONCLUSION: Despite services being officially free of charge, most patients incurred catastrophic costs and suffered significant
income loss as a result of obtaining diagnosis and treatment for MDR-TB.
To assess the performance of the GenoType MTBDR
v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment ...Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.
Direct sputum MTBDR
results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.
Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDR
and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDR
result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDR
results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDR
results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDR
inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDR
. The majority of inconclusive MTBDR
results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (
< 0.001).
MTBDR
can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.
OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in ...pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of
patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification
according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR
(adjusted OR aOR 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P
= 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers
needs to be verified in prospective studies.
To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote regions in which the disease is endemic, a simple cheap sampling method is required for ...miltefosine quantification. The aims of this study were to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spot (DBS) samples and to validate its use with Ethiopian patients with visceral leishmaniasis (VL). Since hematocrit (Ht) levels are typically severely decreased in VL patients, returning to normal during treatment, the method was evaluated over a range of clinically relevant Ht values. Miltefosine was extracted from DBS samples using a simple method of pretreatment with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10 to 2,000 ng/ml, and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at the lower limit of quantification), respectively. The method was accurate and precise for blood spot volumes between 10 and 30 μl and for Ht levels of 20 to 35%, although a linear effect of Ht levels on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C. Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS/plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson'sr= 0.946). Correcting for patient-specific Ht levels did not further improve the concordance between the sampling methods. This successfully validated method to quantify miltefosine in DBS samples was demonstrated to be a valid and practical alternative to venous blood sampling that can be applied in future miltefosine pharmacokinetic studies with leishmaniasis patients, without Ht correction.
Objective: To evaluate serum concentrations of trace elements in tuberculosis (TB) patients with or with out human immunodeficiency virus (HIV) coinfection before and after anti-TB chemotherapy. ...Subjects: A total of 155 TB patients, 74 of which were coinfected with HIV, and 31 healthy controls from Gondar, Ethiopia. Methods: Serum levels of copper, zinc, selenium and iron were determined using an inductively coupled plasma mass spectrometer from all subjects at baseline and from 44 TB patients (22 with HIV coinfection) at the end of an intensive phase of anti-TB chemotherapy. Results: Compared with the control group, the concentrations of iron, zinc and selenium were significantly lower (P<0.05) while that of copper and copper/zinc ratio was significantly higher (P<0.05) in the serum of TB patients. TB patients with HIV coinfection had significantly lower serum zinc and selenium concentrations and significantly higher copper/zinc ratio compared to that in TB patients without HIV coinfection (P<0.05). The serum concentration of zinc had significantly increased at the end of intensive phase of anti-TB chemotherapy in patients without HIV coinfection (P<0.05). An increase in serum selenium level was observed in TB patients with or without HIV coinfection after therapy. On the contrary, serum copper concentration and copper/zinc ratio declined significantly after anti-TB chemotherapy irrespective of HIV serostatus (P<0.05). Conclusions: The results indicate that TB patients have altered profile of trace elements in their sera. This warrants the need for further investigations so that strategies for trace elements supplementation can be planned in addition to their potential as diagnostic parameters in monitoring responses to anti-TB chemotherapy.
A key objective of the Nephrology Sister Centre Programme between the renal units in Cardiff and Addis Ababa, sponsored by the International Society of Nephrology, is to facilitate development of the ...local clinical service in Ethiopia specifically focused on the management of acute kidney injury (AKI).
To examine the relationship between AKI risk factor recognition and monitoring of renal function in three hospitals in Ethiopia.
Cross-sectional data were gathered regarding renal function monitoring, recording the presence of AKI risk-associated comorbidities and prescription of nephrotoxic medications across the disciplines of medicine, surgery, obstetrics and gynaecology. Results. Patients were more likely to have their renal function checked at the hospital with specialist services. Across all centres, the highest proportion of patients who had renal function measurements were those admitted to a medical ward. There was a positive relationship between documented comorbidities and the measurement of renal function but not between the prescription of nephrotoxic drugs and measurement of renal function.
There was great variability in the extent to which doctors recognised the presence of risk factors for the development of AKI. Failure to identify these risk factors represents a lost opportunity to identify patients at high risk of developing renal injury who would benefit from renal function monitoring.
Summary In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine ...could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia ( n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69–3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p < 0.01). A low baseline eNO (<10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies. ClinicalTrials.gov identifier: NCT00857402 ( www.clinicaltrials.gov )
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