How Do Patients Who Fail First-Line TB Treatment but Who Are Not Placed on an MDR-TB Regimen Fare in South India?

Setting

Seven districts in Andhra Pradesh, South India

Objectives

To a) determine treatment outcomes of patients who fail first line anti-TB treatment and are not placed on an multi-drug resistant TB (MDR-TB) regimen, and b) relate the treatment outcomes to culture and drug susceptibility patterns (C&DST).

Design

Retrospective cohort study using routine programme data and Mycobacterium TB Culture C&DST between July 2008 and December 2009.

Results

There were 202 individuals given a re-treatment regimen and included in the study. Overall treatment outcomes were: 68 (34%) with treatment success, 84 (42%) failed, 36 (18%) died, 13 (6.5%) defaulted and 1 transferred out. Treatment success for category I and II failures was low at 37%. In those with positive cultures, 81 had pan-sensitive strains with 31 (38%) showing treatment success, while 61 had drug-resistance strains with 9 (15%) showing treatment success. In 58 patients with negative cultures, 28 (48%) showed treatment success.

Conclusion

Treatment outcomes of patients who fail a first-line anti-TB treatment and who are not placed on an MDR-TB regimen are unacceptably poor. The worst outcomes are seen among category II failures and those with negative cultures or drug-resistance. There are important programmatic implications which need to be addressed.     

Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance.     

Anticancer activities of novel chalcone and bis-chalcone derivatives

A series of novel chalcones and bis-chalcones containing boronic acid moieties has been synthesized and evaluated for antitumor activity against the human breast cancer MDA-MB-231 (estrogen receptor-negative) and MCF7 (estrogen receptor-positive) cell lines and against two normal breast epithelial cell lines, MCF-10A and MCF-12A. These molecules inhibited the growth of the human breast cancer cell lines at low micromolar to nanomolar concentrations, with five of them (1-4, 9) showing preferential inhibition of the human breast cancer cell lines. Furthermore, bis-chalcone 8 exhibited a more potent inhibition of colon cancer cells expressing wild-type p53 than of an isogenic cell line that was p53-null.     

Derivation of scenario-specific water quality guidelines for acid mine drainage in South Africa,using a risk-based approach

Acid mine drainage (AMD) continues to threaten water quality in many mining regions globally. Data paucity renders it challenging to inform appropriate water quality management strategies for a succinct scientific understanding of the effects of AMD on freshwater ecosystems. The current study investigated the effects of AMD collected from a defunct coalmine in Mpumalanga, South Africa, on freshwater ecosystems using a risk-based approach on five indigenous species, Adenophlebia auriculata, Burnupia stenochorias, Caridina nilotica, Pseudokirchneriella subcapitata and Oreochromis mossambicus in 2016. Species responded differently to AMD after 96 hours and 240 hours of exposure in static experimental test designs. Burnupia stenochorias was more sensitive to AMD after 96 and 240 hours of exposure, whereas O. mossambicus was tolerant during short-term exposure, but became more sensitive after 240 hours of exposure than the other species tested. The availability of metals in AMD was directly associated with dilution rate. Scenario-specific water quality guidelines for AMD have been derived as 0.122% for short-term and 0.014% for long-term exposure. These may form important indicative dilutions for other AMDs that do not match the scenarios of this study. The toxicity of AMD to a wide range of aquatic species, including field validations, requires further investigation.     

Cycloartanes from the Gum Resin of Gardenia gummifera L.f.

The gum resin exuding from the leaf buds of Gardenia gummifera was investigated. Eight new cycloartane triterpenes, 1 – 6, 8 , and 10 , together with two known triterpenes, 25‐hydroxycycloart‐23‐en‐3‐one ( 7 ) and cycloartenone ( 9 ), were isolated and identified by extensive NMR spectroscopy. For cycloartenone ( 9 ), full NMR assignments are given as these data were not available in the literature. Eight compounds possess a C(3)?O group, two are 3,4‐secocycloartanes bearing a free C(3)OOH group; in one of the cycloartanes, gummiferartane‐9 ( 10 ), ring A occurs as a seven‐membered lactone.     

Tuberculosis Management Practices by Private Practitioners in Andhra Pradesh,India

Setting

Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India.

Objectives

To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC.

Design

Cross- sectional survey using semi-structured interviews.

Results

Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine.

Conclusion

Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.