Local production of nitric oxide in patients with tuberculosis.

Nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is important in host defence against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. We investigated iNOS and nitrotyrosine (Ntyr) expression in pleural (n = 7), pulmonary (n = 5) and lymph node biopsies (n = 5) from untreated, newly diagnosed tuberculosis patients. Many iNOS and Ntyr reactive macrophages were observed in granulomas, including Langhans giant cells, indicating high-output NO production at the primary site of disease in tuberculosis.     

Diagnosis of tuberculous lymphadenitis in Butajira,rural Ethiopia

Tuberculous lymphadenitis (TBLN) is a diagnostic challenge in sub-Saharan Africa, where there is a high rate of human immunodeficiency virus (HIV) infection. This study aimed to find ways to improve the diagnosis in Butajira, rural Ethiopia, where TBLN constitutes 40% of the total tuberculosis (TB) diagnosis. Among 147 clinically suspected cases, 107 (72.8%) were confirmed as TBLN by fine-needle aspiration (FNA) cytology and acid-fast bacillus (AFB) smear examination. Of the remaining 40 cases, denoted non-tuberculous lymphadenitis (NTBLN) after this smear examination, 37 (92.5%) showed a cytological pattern with neutrophil aggregates. The clinical manifestations were similar and cervical lymph nodes were the most affected in these 2 groups. 24 of the 107 TBLN cases (22.4%) and 9 (22.5%) of the other cases were seropositive for HIV infection (p > 0.5). FNA cytology combined with AFB smear examination is a good alternative to histology in rural Ethiopia where the expertise in taking biopsies is very limited. Polymerase chain reaction for Mycobacterium tuberculosis complex DNA was positive in 15 of 23 cases tested with NTBLN cytology, showing that an additional independent criterion for the presence of M. tuberculosis is needed for diagnosis in lymphadenitis cases of this kind. These findings could help to strengthen the diagnostic algorithm suggested by the National TB Control Program.     

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial

Purpose

The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA?≥?0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA?≥?0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89.

Methods

Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA?≥?0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline.

Results

At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P?=?0.047]. When unadjusted for baseline variables, P?=?0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P?=?0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (??0.5, 19.5) vs. 4 mmHg (??4.0, 11) P?=?0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P?=?0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P?=?0.005]. The median EAA change in the population was ??12.9% (range: increase 49.2%–reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P?=?0.08.

Conclusions

These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA?≥?0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality.

Trial registration

Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

     

The water footprint of humanity

This study quantifies and maps the water footprint (WF) of humanity at a high spatial resolution. It reports on consumptive use of rainwater (green WF) and ground and surface water (blue WF) and volumes of water polluted (gray WF). Water footprints are estimated per nation from both a production and consumption perspective. International virtual water flows are estimated based on trade in agricultural and industrial commodities. The global annual average WF in the period 1996–2005 was 9,087 Gm³/y (74% green, 11% blue, 15% gray). Agricultural production contributes 92%. About one-fifth of the global WF relates to production for export. The total volume of international virtual water flows related to trade in agricultural and industrial products was 2,320 Gm³/y (68% green, 13% blue, 19% gray). The WF of the global average consumer was 1,385 m³/y. The average consumer in the United States has a WF of 2,842 m³/y, whereas the average citizens in China and India have WFs of 1,071 and 1,089 m³/y, respectively. Consumption of cereal products gives the largest contribution to the WF of the average consumer (27%), followed by meat (22%) and milk products (7%). The volume and pattern of consumption and the WF per ton of product of the products consumed are the main factors determining the WF of a consumer. The study illustrates the global dimension of water consumption and pollution by showing that several countries heavily rely on foreign water resources and that many countries have significant impacts on water consumption and pollution elsewhere.     

Transmission of herpes simplex virus Type 2 among factory workers in Ethiopia

The herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) epidemics are believed to fuel each other, especially in sub-Saharan countries. In Ethiopia during 1997-2002, a retrospective study was conducted to examine risk factors for infection and transmission of HSV-2, in a cohort of 1612 factory workers. Prevalence of HSV-2 seropositivity at enrollment was 40.9%, and incidence of seroconversion was 1.8 seroconversions/100 person-years (PY), which decreased over time. Independent risk factors for seropositivity were having an HSV-2-seropositive partner, female sex, HIV antibodies, positive Treponema pallidum particle agglutination assay result, older age, low education level, and orthodox religion. These same factors were independent risk factors for HSV-2 seroconversion, with the exception of the latter 3. Most HSV-2-infected persons did not report symptoms. Among 41 monogamous HSV-2-serodiscordant heterosexual couples, incidence of HSV-2 seroconversion was 20.75 seroconversions/100 PY for women and 4.93 seroconversions/100 PY for men. The high burden of both HSV-2 and HIV infection in Ethiopia warrants stringent control measures.     

Risk factors for multidrug resistant tuberculosis patients in Amhara National Regional State

Background

Multidrug resistant tuberculosis(MDR-TB) is becoming a major threat to tuberculosis control programs in Ethiopia.

Objectives

To determine risk factors of MDR-TB patients in Amhara National Regional State, Ethiopia.

Methods

Case-control study was conducted from May 2013 to January 2014. Resistance to rifampicin and isoniazid were done molecularly using line probe assay. TB patients infected with MDR-M.tuberculosis and non MDR-M.tuberculosis strain were considered as cases and controls, respectively. Data was collected using structured questionnaire with face to face interview. Patients'' clinical record review was also done.Multivariate analysis was computed to determine the risk factors of MDR-TB.

Results

A total of 153 MDR-TB and equal number of non MDR-TB patients'' participated in the study. Patients who had TB treatment failure (AOR=13.5,CI=2.69–70), cavitations on chest x-ray (AOR=1.9,CI=1.1–3.38) and contact with MDR-TB patients (AOR=1.4,CI=0.19–0.39) were more likely to be MDR-TB patients. Low monthly income (AOR=1.1,CI=0.34–0.47),alcohol consumption (AOR=1.5,CI=0.2–0.98) and young age (AOR=2.9,CI=1.07–7.68) were the other risk factors of MDR-TB.

Conclusions

TB treatment failure, cavitation on chest X-ray, contact with MDR-TB patients and low socioeconomic status were important risk factors for development of MDR-TB. Therefore, strict adherence to directly observed therapy, appropriate management of TB patients and advice on the value of nutrients are helpful to control the spreading of MDR-TB.