[The epidemiological advantage of preferential targeting of tuberculosis control at the poor]. / La ventaja epidemiológica de la orientación preferencial del control de la tuberculosis hacia los pobres.

Tuberculosis (TB) remains disproportionately concentrated among the poor, yet known determinants of TB reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on TB disparities in India and the wealth distribution of known TB risk factors, we describe how social mixing patterns could be contributing to TB disparities. Wealth-assortative mixing, whereby individuals are more likely to be in contact with others from similar socio-economic backgrounds, amplifies smaller differences in risk of TB, resulting in large population-level disparities. As disparities and assortativeness increase, TB becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how TB control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted at those living below the poverty line than with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, TB control efforts would lead to a greater reduction in secondary TB cases per primary case diagnosed if they were preferentially targeted at the poor. We highlight the need to collect programmatic data on TB disparities and explicitly incorporate equity considerations into TB control plans.

Prevalence of pyrazinamide resistance and Wayne assay performance analysis in a tuberculosis cohort in Lima, Peru.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) regimens often contain pyrazinamide (PZA) even if susceptibility to the drug has not been confirmed. This gap is due to the limited availability and reliability of PZA susceptibility testing. OBJECTIVES: To estimate the prevalence of PZA resistance using the Wayne assay among TB patients in Lima, Peru, to describe characteristics associated with PZA resistance and to compare the performance of Wayne with that of BACTEC™ MGIT™ 960. METHODS: PZA susceptibility using the Wayne assay was tested in patients diagnosed with culture-positive pulmonary TB from September 2009 to August 2012. Factors associated with PZA resistance were evaluated. We compared the performance of the Wayne assay to that of MGIT 960 in a convenience sample. RESULTS: The prevalence of PZA resistance was 6.6% (95%CI 5.8-7.5) among 3277 patients, and 47.7% (95%CI 42.7-52.6) among a subset of 405 MDR-TB patients. In multivariable analysis, MDR-TB (OR 86.0, 95%CI 54.0-136.9) and Latin American-Mediterranean lineage (OR 3.40, 95%CI 2.33-4.96) were associated with PZA resistance. The Wayne assay was in agreement with MGIT 960 in 83.9% of samples (κ 0.66, 95%CI 0.56-0.76). CONCLUSION: PZA resistance was detected using the Wayne assay in nearly half of MDR-TB patients in Lima. This test can inform the selection and composition of regimens, especially those dependent on additional resistance.

Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients.

OBJECTIVE: To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa. DESIGN: Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance. RESULTS: MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB). CONCLUSION: An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.

Causes of death during tuberculosis treatment in Tomsk Oblast, Russia.

SETTING: Tuberculosis (TB) incidence and mortality in Russia have risen dramatically over the past 15 years. OBJECTIVE: To identify risk factors and causes of death among TB patients in Russia. DESIGN: A retrospective study conducted to determine the risk factors and causes of death in patients receiving TB therapy in Tomsk, Siberia. RESULTS: Of 1916 patients who initiated treatment between 1 January 2002 and 31 December 2003, 183 (9.6%) died during treatment, 38 (21%) in the first week of therapy. Twenty-five per cent of deaths were not directly attributable to TB. Risk factors for death included older age, previous treatment for TB, multidrug resistance and alcoholism. CONCLUSIONS: The high death rate during TB treatment observed in this cohort likely reflects an increased risk of dying not only from TB, but also from comorbid conditions, such as alcoholism and cardiovascular disease. Overall, alcoholism and late presentation both contributed substantially to the mortality in this cohort.

Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element.

Using a gel shift assay, we analyzed the binding of in vitro translated alpha- and beta-thyroid hormone (T3) receptors to a T3-response element (TRE) derived from the rat GH gene. No receptor-TRE complexes were observed when translated receptor alone was incubated with the TRE. However, addition of a nuclear extract from liver to the translational products resulted in the formation of two receptor-DNA complexes for both the alpha- and beta-receptors. These complexes were shown to contain translated receptor by comigration of 32P-labeled TRE and 35S-labeled receptor in the gel shift assay. A competition experiment demonstrated that formation of the complexes was sequence specific. Preincubation of the liver nuclear extract at 60 C abolished formation of both complexes indicating that receptor-TRE binding required a heat-labile nuclear factor. Phosphocellulose chromatography of the nuclear extract resulted in separation of the activities required for formation of the two complexes. Analysis of nuclear extracts from different tissues revealed that one complex formed in the presence of all extracts, whereas the second complex appeared predominantly with a nuclear extract from liver. Addition of T3 to the binding reaction had no effect on receptor-TRE complex formation. We suggest that nuclear factors interact with the T3 receptor to enhance hormone-independent binding to a TRE.

The epidemiological advantage of preferential targeting of tuberculosis control at the poor.

Tuberculosis (TB) remains disproportionately concentrated among the poor, yet known determinants of TB reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on TB disparities in India and the wealth distribution of known TB risk factors, we describe how social mixing patterns could be contributing to TB disparities. Wealth-assortative mixing, whereby individuals are more likely to be in contact with others from similar socio-economic backgrounds, amplifies smaller differences in risk of TB, resulting in large population-level disparities. As disparities and assortativeness increase, TB becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how TB control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted at those living below the poverty line than with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, TB control efforts would lead to a greater reduction in secondary TB cases per primary case diagnosed if they were preferentially targeted at the poor. We highlight the need to collect programmatic data on TB disparities and explicitly incorporate equity considerations into TB control plans.

Diet and cerebral malaria: the effect of famine and refeeding.

In an outbreak of Plasmodium falciparum malaria following refeeding after famine cerebral malaria was restricted to children eating grain. Nomad children consuming a predominantly milk diet were free of this complication despite an equivalent incidence of uncomplicated malaria. Freedom of nomads from cerebral complications may be due to inhibition by the milk diet of rapid division of the parasite combined with delayed recovery after famine of T cell function.

Parotid enlargement, forehead edema, and suppression of malaria as nutritional consequences of ascariasis.

Bilateral painless enlargement of the parotids, a curiously localized edema of the forehead and relative freedom from malaria were striking findings in children of Anjouan but not of Grande Comore, two neighboring islands of the Comorro group in the Indian Ocean. Compared with those of Grande Comore, Anjouan children were heavily infested with Ascaris lumbricoides. We suggest that the clinical findings may be the nutritional consequence of severe ascariasis and that the low incidence of malaria in Anjouan children may be an example of the delicate ecological balance between the host, the Ascaris, and the plasmoidum.

Quantification of frost damage in plant tissues by rates of electrolyte leakage.

A method for assessing frost hardiness of plant tissues [using shoots of Picea rubens Sarg. syn P. rubra (Du Roi) Link] has been developed based upon the rate of electrolyte leakage from shoots immersed in distilled water after exposure to a range of freezing treatments. The relationship between conductivity (the electrolyte concentration in solution) and time has been shown to follow an asymptotic curve, which may be represented by a first-order equation: Ct -Co = Cauto -Co - C-kt ) where C1 is the conductivity at time t, Co is the initial conductivity, Cauto is the conductivity after autoclaving and k is the first-order rate constant (units time-1 ). The rate of electrolyte leakage (k) varies directly with the extent of tissue damage. In P. rebens a rate of 0-4%, h-1 distinguished between shoots which eventually died, and shoots which remained alive. A minimum of 3 conductivity measurements (after 1 day, 5 days and after autoclaving) is required for a reliable estimate of k. This objective, quantitative method of assessing frost hardiness may therefore be used directly to estimate LT50 values within a population.

The influence of acid mists on growth, dry matter partitioning, nutrient concentrations and mycorrhizal fruiting bodies in red spruce seedlings.

Two-year-old spruce (Picea rubens Sarg.) seedlings were exposed to acid mists containing equimolar ammonium sulphate and nitric acid giving treatments of pH 2.5, 3.0 and 5.0. Acid mist treatments were applied twice weekly from late July until early October, 1987, when the plants were harvested. There were no significant differences in biomass accumulation or in height growth between treatments, but marked differences in root morphology were found. Significantly larger amounts of coarse roots were produced in the pH 5.0 acid mist treatment and plants in the pH 3.0 treatment produced significantly greater amounts of fine roots. Plants receiving acid mists of pH 3.0 or less had a greater frequency of fine root branches along their coarse roots. Production of mycorrhizal fruiting bodies of Thelephora terrestris Ehrenb.: Fr. was significantly greater (P < 0.001) at pH 5.0 than in the other treatments. Plants in the pH 2.5 and 3.0 treatments contained larger concentrations of N, 1.54 and 1.12% and S, 0.52 and 0.28% respectively, than those receiving acid mist at pH 5.0, i.e. 1.00 and 0.21% respectively. However, the between treatment differences of tissue nutrient concentrations were small relative to the differences in inputs between treatments. Foliar S exceeded concentrations recommended for nursery stock by 50 and 150% at pH 3.0 and 2.5 respectively.

Visible foliar injury of red spruce seedlings subjected to simulated acid mist.

Two-year-old red spruce seedlings [Picea rubens Sarg. syn. P. rubra (Du Roi) Link] were subjected to 6 simulated acid mist treatments (pH 2.5, 2.7, 3.0, 3.5, 4.0, 5.0) in a replicated experiment using open-top chambers. Acid mist solutions containing equimolar (NH4 )2 SO4 , and HNO3 were applied twice weekly for 22 weeks, each application being equivalent to 2 mm of precipitation. Visible symptoms of foliar damage were observed on the 3 most acidic mist treatments (pH 2.5, 2.7, 3.0). The inputs of nitrogen, sulphur and acidity in the most acidic treatment were 55, 42, 1,3 kg ha-1 , respectively, over a 10 week period. The plants subjected to the pH 2.5 treatment were found to be most severely damaged with approximately 40% foliar necrosis after 10 weeks of treatment. On approximately 80% of seedlings, necrosis was confined to current year needles only. These damaged needles were initially light brown or light orange in colour turning a deeper red 3 to 5 weeks after initial necrosis. Percentage foliar damage was linearly related to concentration (of NH4 + , NO3 - , SO4 2- and H+ ) with 62% foliar damage in the pH 2.5 treatment after a 22-week period. Spray application stopped in December 1987. Observations during the following spring showed that the pH 2.5 and pH 3 treatments induced earlier Hushing, requiring 60 day °C less thermal time than the pH 5-0 treatment. In 1988, this decrease in thermal requirement was equivalent to flushing 11 days earlier. There was no evidence of acid mist treatments inducing bud mortality.

Effects of acid mist on the frost hardiness of red spruce seedlings.

Seedlings of red spruce [Picea rubens Sarg. syn. P. rubra (Du Roi) Link] were exposed to mists containing equimolar (NH4 , SO4 and HNO3 at pHs of 2.5, 2.7, 3.0, 35, 4.0 or 5.0. The mists were applied twice each week, amounting to 2 mm precipitation equivalent on each occasion, between July and December, to open-top chambers supplied with charcoal-filtered air. Frost hardiness of shoots excised from seedlings was determined on 6 occasions starting on 21 September, and was found to be strongly influenced by acid mist treatments, seedlings subject to the most acidic mists being the least frost hardy. On 21 September when the first sample was taken the lethal temperature for killing 50% of shoots (LT50 ) was - 11 °C for the least acidic (pH 5.0) mist and - 7 °C for the most acidic (pH 2.5). By 19 October, the LT50 s of pH 5.0 and pH 2.5 mists were -27 and -15 °C respectively. All intermediate treatments ranked according to treatment concentration, with the smaller concentrations causing lower LT.50 values. The treatment at pH 30 provided S and N inputs to the seedlings similar to those experienced by red spruce at elevations of about 1000 m in the southern Appalachians. At pH 3.0, the frost hardiness LT10 during October was typically 8 °C higher than the pH 5.0 treatment, leading to a significant increase in the probability of frost damage at the LT10 level in an average October. The proximity of minimum night temperatures during September to December to the LT10 temperatures of red spruce shoots receiving large inputs of SO4 2- , NO3 - , NH4 + and H+ suggests that decreases in frost hardiness caused by intercepted cloud water containing large concentrations of these ions may play a significant part in the observed decline at mountain-top locations.

Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine.

Lignification in beech (Fagus sylvatica) grown at elevated CO2 concentrations: interaction with nutrient availability and leaf maturation.

Beech (Fagus sylvatica L.) seedlings were grown in an ambient or elevated CO2 concentration ([CO2]) either in small stands in microcosms for three to four seasons or individually in pots fertilized at different nutrient supply rates. Leaves at different stages of development, as well as stems and roots at the end of the growing season, were used for analysis of structural biomass and lignin. In elevated [CO2], lignification of leaves was slightly retarded compared with structural biomass production and showed a strong correlation with the activities of ionically, cell-wall-bound peroxidases but not with total soluble peroxidases or covalently wall-bound peroxidases. The effect of elevated [CO2] on lignin concentration of mature tissues was dependent on nutrient supply rate. In leaves and roots, elevated [CO2] increased the lignin concentration in dry mass in N-limited plants. In seedlings grown with high nutrient supply, the lignin concentration in dry mass was unaffected or diminished by elevated [CO2]. Because elevated [CO2] enhanced seedling growth in the high nutrient supply treatments, the total amount of lignin produced per seedling was higher in these treatments. We predict that long-term sequestration of carbon will increase as long as biomass production is stimulated by elevated [CO2] and that tissue quality will change depending on developmental stage and nutrient availability.

The impact of constituent ions of acid mist on assimilation and stomatal conductance of Norway spruce prior and post mid-winter freezing.

Norway spruce seedlings were sprayed twice weekly with one of a range of artificial mists at either pH 2.5, 3.0 or 5.6, for three months. The mists consisted of either (NH4)2SO4 (pH 5.6), NH4NO3 (pH 5.6), water (pH 5.6), HNO3 (pH 2.5), H2SO4 (pH 2.5). In late December 1988 and early January 1989 the light response of assimilation and stomatal conductance were assessed in the laboratory following a 4-day equilibration period at 12 degrees C. The intact trees were then subjected to a mild (-10 degrees C), brief (3 h) frost in the dark and the recovery of light saturated assimilation (Amax) was followed during the subsequent light period. The same trees were then subjected to a second 3 h (-18 degrees C) frost. The recovery of Amax during the next day was followed. All ion-containing mists stimulated Amax and apparent quantum yield relative to control trees, irrespective of pH. The mists containing SO4 made stomatal conductance unresponsive to light flux density and caused the stomata to lock open. Frosts of -10 degrees C and -18 degrees C did not inhibit the Amax of control trees for longer than 200 min into the light period. In contrast, the ion-containing mists exerted a significant inhibitory effect upon the recovery of Amax. Nitric acid inhibited Amax to 35% of the pre-frost value, whilst the remaining treatments inhibited Amax between 15% and 40% of the pre-frost value. It is concluded that SO4 causes increased mid-winter frost sensitivity and NO3 ameliortes this effect. The results are discussed in relation to forest decline.

Leadership attributes identified by practicing occupational health nurses.

This study examined which theoretical approaches to leadership occupational health nurses perceive as most desirable. The trait approach dominates in North American research literature, with occupational health nurses favoring the more traditional leadership attributes of "visionary," "intellectually creative," and "strong linguistic ability." Australian occupational health nurses identified the managerial character traits of "being well informed," "good communication skills," and "objective decision maker" as most appropriate traits of good leaders. Occupational health nurses need to develop alternative leadership approaches to acquire effective political and organizational strategies in today's competitive environment.

Use of fluoroquinolone antibiotics leads to tuberculosis treatment delay in a South African gold mining community.

BACKGROUND: Empiric use of fluoroquinolone (FQ) antibiotics could delay tuberculosis (TB) treatment and lead to FQ-resistant TB. METHODS: We examined the impact of FQ use on TB outcomes, including smear status, treatment delay and FQ resistance, through a retrospective cohort study of 440 FQ-exposed and 511 non-exposed patients in a gold mining community in South Africa. We considered both recent (≤ 100 days before sputum collection) and distant exposure (≤ 1 year). We examined 201 and 180 isolates from FQ-exposed and non-exposed individuals for the presence of gyrA mutations. RESULTS: Patients recently exposed to ≥ 5 days of FQ were less likely to be smear-positive (OR 0.27, 95%CI 0.11-0.63), with an increased time to treatment (time ratio 2.02, 95%CI 1.19-3.44). The strength of association decreased when we considered distant exposure. Adjusting for smear status nullified the effect of FQ exposure on treatment delay. We detected a gyrA mutation in one isolate (0.5%) taken from an individual exposed to FQ for 8 days. CONCLUSION: FQ exposure is associated with treatment delay, mediated by negative smear status. Short exposures to FQ do not routinely lead to resistance encoded by gyrA mutations. We recommend prudent use of FQ in settings with a high burden of human immunodeficiency virus and TB.

The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis.

The prevalence of diabetes mellitus is increasing at a dramatic rate, and countries in Asia, particularly India and China, will bear the brunt of this epidemic. Persons with diabetes have a significantly increased risk of active tuberculosis (TB), which is two to three times higher than in persons without diabetes. In this article, we argue that the epidemiological interactions and the effects on clinical presentation and treatment resulting from the interaction between diabetes and TB are similar to those observed for human immunodeficiency virus (HIV) and TB. The lessons learned from approaches to reduce the dual burden of HIV and TB, and especially the modes of screening for the two diseases, can be adapted and applied to the screening, diagnosis, treatment and prevention of diabetes and TB. The new World Health Organization (WHO) and The Union Collaborative Framework for care and control of TB and diabetes has many similarities to the WHO Policy on Collaborative Activities to reduce the dual burden of TB and HIV, and aims to guide policy makers and implementers on how to move forward and combat this looming dual epidemic. The response to the growing HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated, despite clearly articulated warnings about the scale of the forthcoming problem. We must not make the same mistake with diabetes and TB. The Framework provides a template for action, and it is now up to donors, policy makers and implementers to apply the recommendations in the field and to 'learn by doing'.

La ventaja epidemiológica de la orientación preferencial del control de la tuberculosis hacia los pobres / The epidemiological advantage of preferential targeting of tuberculosis control at the poor

La tuberculosis (TB) continúa concentrada de manera desproporcionada entre los pobres, pero los determinantes conocidos de reactivación de la TB pueden no explicar las desigualdades observadas en las tasas de enfermedad según la riqueza. En el presente estudio, mediante la revisión de datos sobre desigualdades en TB en la India y la distribución de factores de riesgo de TB conocidos según riqueza, se describe cómo los patrones de mezcla social pueden estar contribuyendo a las desigualdades en TB. La mezcla social por afinidad selectiva según la riqueza, por la cual es más probable que las personas entren en contacto con otras personas de orígenes socioeconómicos similares, amplifica las pequeñas diferencias en el riesgo de TB y genera grandes desigualdades a nivel poblacional. A medida que las desigualdades y la asortatividad (o afinidad selectiva) aumentan, se hace más difícil controlar la TB; este efecto queda enmascarado cuando se examinan solamente promedios poblacionales de parámetros epidemiológicos, tales como las tasas de detección de casos. El estudio ilustra cómo los esfuerzos de control de TB pueden beneficiarse a partir de una orientación preferencial hacia los pobres. En la India, una intervención a escala equivalente podría tener un impacto sustancialmente mayor si se orientara a quienes viven por debajo de la línea de pobreza que el de una estrategia a toda la población. Además de las eficiencias potenciales de focalizar en poblaciones en más alto riesgo, los esfuerzos de control de la TB podrían llevar a una mayor reducción en el número de casos secundarios de TB por cada caso primario diagnosticado si es que tales esfuerzos fuesen preferencialmente orientados hacia los pobres. El estudio destaca la necesidad de recolectar datos programáticos sobre las desigualdades en TB e incorporar de manera explícita consideraciones de equidad en los planes de control de la TB.

Tuberculosis (TB) remains disproportionately concentrated among the poor, yet known determinants of TB reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on TB disparities in India and the wealth distribution of known TB risk factors, we describe how social mixing patterns could be contributing to TB disparities. Wealth-assortative mixing, whereby individuals are more likely to be in contact with others from similar socio-economic backgrounds, amplifies smaller differences in risk of TB, resulting in large population-level disparities. As disparities and assortativeness increase, TB becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how TB control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted at those living below the poverty line than with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, TB control efforts would lead to a greater reduction in secondary TB cases per primary case diagnosed if they were preferentially targeted at the poor. We highlight the need to collect programmatic data on TB disparities and explicitly incorporate equity considerations into TB control plans.

Consultation meeting on tuberculosis and diabetes mellitus: meeting summary and recommendations.

The steadily growing epidemic of diabetes mellitus (DM) poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between DM and TB. However, these studies have limitations: very few were carried out in low-income countries, and none in Africa, raising uncertainty about the strength of the DM-TB association in these settings, and many critical questions remain unanswered. As a result of these questions and uncertainties, the International Union Against Tuberculosis and Lung Disease (The Union), the World Diabetes Foundation and the World Health Organization Stop TB Department undertook a series of consultations as of January 2009. A systematic review and meta-analysis was undertaken by the Department of Epidemiology, Harvard School of Public Health between May and August 2009, and a consultation meeting involving the experts who reviewed the report took place at The Union Headquarters in Paris on 6 and 7 November 2009. This paper constitutes a summary report of the findings, the research gaps and prioritised areas of research, and the recommendations from that meeting.