Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis.

To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response

EFFECT OF FEED SUPPLEMENTATION ON MILK YIED IN SELECTED LAMAS FOR MEAT PRODUCTION

Se utilizó 20 llamas gestantes del Centro de Investigaciones IVITA-Maranganí, Cusco, a las que se midió el área de grupa, volumen del muslo, peso corporal y perímetro torácico del rebaño. Se utilizó un diseño factorial 2 x 2, donde A = Suplemento (a1: con heno; a2: sin heno) y B = Medidas biométricas (b1: altas; b2: bajas). La cantidad de heno de alfalfa fue de 1 kg/animal/día. Se midió el efecto de las medidas biométricas y la suplementación sobre la producción de leche y tasa de crecimiento de las crías durante las primeras siete semanas de lactación. Se registró semanalmente el peso de la madre y la cría y se estimó la producción de leche (producción de 12 horas luego del uso de un protector de ubre que impide el amamantamiento). Las llamas que recibieron suplemento tuvieron una mayor producción de leche (0.05>p<0.01) entre la 3ra a la 7ma semana de lactancia. El pico de la producción de leche ocurrió a la 2da (a2) y 3ra (a1) semana. Las crías de las llamas suplementadas y de aquellas con medidas biométricas altas tuvieron las mayores ganancias de peso (p<0.05). No hubo interacción significativa entre los efectos de los tratamientos en el peso de las crías; no obstante, se observó una mayor tasa de crecimiento en las crías de madres suplementadas con medidas biométricas altas. La correlación entre la producción de leche con el peso de las crías por efecto del suplemento y de las medidas biométricas de las madres fueron significativas a partir de la cuarta semana de lactación. El efecto de la suplementación con heno y las medidas biométricas, así como la interacción entre las dos variables, no afectó significativamente el peso de las madres durante las primeras siete semanas de lactación, aunque se pudo observar una ligera disminución de peso corporal entre la 1ra y 3ra semana de lactancia. El peso promedio al parto y en la 7ma semana de lactación fue de 96.9 ± 8.4 y 95.3 ± 9.1 kg, respectivamente. Se concluye que hubo efecto significativo de las medidas biométricas y de la suplementación de las madres sobre la producción de leche y crecimiento de las crías.Twenty pregnant lamas from the IVITA Research Center, Maranganí, Cusco, were selected, and the rump area, thigh volume, body weight and thoracic perimeter were measured. A 2 x 2 factorial design was used, where A = Supplement (a1: with hay; a2: without hay) and B = Biometric measures (b1: high values; b 2: low values). The amount of supplemented hay was 1 kg/animal/day. The effect of biometric measures and feed supplementation on dam milk production and calf growth during the first seven weeks of lactation was evaluated. Body weight of both dams and calves was weekly recorded. Milk production was estimated (milking after 12 hours of wearing an udder protector to avoid suckling). Supplemented lamas showed higher milk yield (0.05>p<0.01) between the3rd and 7th week of lactation. The peak of milk production occurred at the 2nd (a2) and 3rd (a1) week. Calves of supplemented lamas and those with higher biometric measures had the highest body weight gain (p<0.05). No significant interaction was found between treated groups on calf weight; however, there was a higher growth rate in calves of supplemented lamas with high biometric measures. Correlations between milk yield with calf body weight due to the effect of feed supplementation and biometric measures were significant from the 4th week onwards. The effect of feed supplementation and biometric measures, and the interaction between them did no significantly affect dams body weight during the first weeks of lactation, however, there was a slight reduction of body weight between the 1st and the 3rd week of lactation. The average body weight at parturition and on the 7th week of lactation was 96.9 ± 8.4 and 95.3 ± 9.1 kg respectively. The results showed a significant effect of feed supplementation and biometric measures on milk production and calf body weight

EFFECT OF TOLTRAZURIL AND THE COMBINATION OF SULFADOXINE AND PIRIMETAMINE IN THE TREATMENT OF CANINE SARCOCYSTIOSIS DURING THE PREPATENT PERIOD

El objetivo del estudio fue evaluar la eficacia del toltrazuril (2.5%) y de la combinación de sulfadoxina y pirimetamina (500/25 mg) en el tratamiento de la sarcocistiosis canina. El estudio se realizó durante los meses de octubre del 2005 a marzo del 2006, en la Estación Experimental del Centro de Investigaciones IVITA, Maranganí, Cusco, perteneciente a la Facultad de Medicina Veterinaria, UNMSM. Se utilizó 15 cachorros cruzados de ambos sexos, de 2-3 meses de edad, previamente desparasitados y alimentados solo con concentrado. Todos ellos fueron infectados con aproximadamente 9,000-10,000 quistes de Sarcocystis lamacanis, presentes en 4-5 g de tejido cardiaco de alpaca. Las heces se analizaron diariamente hasta observar la presencia de esporoquistes u ooquistes de Sarcocystis sp. Posteriormente fueron distribuidos en tres grupos de 5 animales c/u. Un grupo control no tratado y dos grupos tratados diariamente por 10 días, uno con toltrazuril (2.5%) en dosis de 15 mg/kpv y otro grupo con la combinación de sulfadoxina y pirimetamina (500/25 mg) en dosis de 20 y 1 mg/kgpv, respectivamente. Muestras fecales fueron recolectadas diariamente y se analizaron por el método de coproparasitologico de flotación con solución de Sheather para determinar la presencia de ooquistes o esporoquistes de Sarcocystis sp., y las muestras positivas se cuantificaron por el método de Stoll modificado, para determinar su número por gramo de heces. Los resultados muestran que el toltrazuril alcanzó una eficacia en el control de la sarcocistiosis del 94.7 % al tercer día de tratamiento y un 100% al sexto día, mientras que la combinación de sulfadoxina y pirimetamina no logró controlarla, llegando a mostrar una moderada eficacia al segundo día post tratamiento (88.1%).The objective of this study was to evaluate the efficacy of toltrazuril (2.5)% and the combination of sulfadoxine and pirimetamine (500-25 mg) on the treatment of canine sarcocystiosis. The study was conducted from October 2005 until March 2006 in the Experimental Station of the IVITA Research Center, Maranganí, Cusco. A total of 15 crossbred puppies, both sexes, 2-4 months of age, that were dewormed and fed with a diet extent of meat were used. Puppies were infected with approximately 9,000- 10,000 cysts of Sarcosystis lamacanis present in 4-5 g of alpaca heart. Feces were daily collected and analyzed to observe the presence of sporocysts or oocysts. Then, were distributed in three groups of 5 animals each. One group remained untreated (as control) and the other two groups were daily treated during 10 days with 15 mg/kg of toltrazuril (2.5%) or the combination of sulfadoxine and pirimetamine (500-25 mg) in a dose of 20 and 1 mg/kg respectively. Fecal samples were daily collected and analyzed by the flotation method using the Sheather solution to determine the presence of sporocysts or oocysts and the modified Stoll method to quantify the number of eggs per gram of feces. The results showed that the efficacy of toltrazuril in the control of sarcosystiosis was 94.7% at the 3rd day of treatment and 100% at day 6, whereas the combination of sulfadoxine and pirimetamine did not control it, and only a moderate efficacy (88.1%) was observed in the 2nd day

RELATIONSHIP BETWEEN THE SIZE OF MACROCYSTS OF SARCOCYSISTIS AUCHENIAE AND ITS VIABILITY IN CANIS FAMILIARIS

El objetivo del estudio fue determinar si el tamaño de los macroquistes de Sarcocystis aucheniae afectan la viabilidad y potencial biótico en los caninos domésticos. Se utilizaron 24 cachorros cruzados de 2.5 meses de edad, con pesos promedio de 2.6 kg., debidamente desparasitados y alimentados con una dieta casera exenta de carnes. Se obtuvo macrosquistes de S. aucheniae del cuello de alpacas y llamas en un camal local, clasificándolos en macroquistes grandes (>5 mm) y pequeños (1-3 mm). Diez cachorros fueron oralmente infectados con 500 macroquistes grandes (MG) y 12 cachorros con 500 macroquistes pequeños (MP), en ambos casos por dos días consecutivos. Además, 6 perros quedaron sin infectar como grupo control. Se recolectó diariamente muestras fecales a partir del 8º día post-infección y por un periodo de 22 días. Las muestras se analizaron por el método de flotación con solución de Sheather para determinar la presencia de ooquistes o esporoquistes de Sarcocystis sp. y el método de Stoll modificado para cuantificar su número por gramo de heces. Los resultados mostraron que animales infectados con MP presentaron una carga de esporoquistes 3.6 veces superior que aquellos infectados con MG; así mismo, el periodo prepatente promedio fue de 16.5 y 11.5 para los MG y MP, respectivamente.The objective of the study was to determine weather the size of Sarcocystis aucheniae macrocysts affect its viability and biotic potential in domestic canines. A total of 26 crossbred puppies, 2.5 month of age, 2.6 kg of body weight, were used. Puppies were dewormed and fed with a diet extent of meat. Macrocysts of S. aucheniae were obtained from alpaca and llama´s neck in the local slaughterhouse. Cysts were classified according to size in large (>5 mm) and small (1-3 mm) cysts. Ten puppies were orally infected with 500 large macrocysts (MG) and 12 puppies with 500 small macrocysts (MP), for 2 consecutive days, whereas 6 puppies were kept as controls. Fecal samples were daily collected and analyzed by the flotation method using the Sheather solution to determine the presence of oocysts and sporocysts of Sarcocystis sp. and the modified Stoll method to quantify the number of sporocysts per gram of feces. The results showed that the burden of sporocysts was 3.6 times more in puppies infected with MP than in those infected with MG. Furthermore, the average prepatent period was 16.5 and 11.5 days for MG and MP respectively

FREQUENCY OF SARCOCYSTIS SP. IN SHEEPDOGS FROM ALPACA ASSOCIATION BREEDERS, MARANGANÍ, CUSCO

El objetivo del estudio fue determinar la frecuencia de Sarcocystis sp. en perros pastores de asociaciones alpaqueras del distrito de Maranganí, Cusco, durante las dos épocas del año (seca y lluviosa). El trabajo se realizó entre abril de 2005 y febrero de 2006. Se colectaron 211 muestras fecales de perros pastores de los productores alpaqueros de la zona. Las heces fueron analizadas mediante el método de flotación con solución de Sheather para determinar la presencia de ooquistes o esporoquistes de Sarcocystis sp. Se encontró una frecuencia de 42.3 ± 9.2% (47/111) y 72.0 ± 8.8% (72/100) en la época seca y lluviosa, respectivamente. Los resultados muestran una asociación significativa entre la tasa de infección y la época del año (p<0.05). El mes de noviembre presentó la mayor tasa (77.8 ± 12.1%, 35/49) y en mayo se obtuvo la menor tasa (17.6 ± 12.8%, 6/34). Además, se encontró diferencias significativas entre grupos etáreos (p<0.05).The aim of the study was to determine the frequency of Sarcocystis spp. in sheepdogs of alpaca farm associations at Maranganí, Cusco, during the dry and rainy season (April 2005 until February 2006). Fecal samples (n = 211) were collected and evaluated using the method of flotation with Sheather solution to observe sporocysts of Sarcocystis spp. The frequency during the dry and rainy season was 42.3 ± 9.2% (47/111) and 72.0 ± 8.8% (72/100) respectively. The results showed an association between the rate of infection and the time of the year (p<0.05), where November had the highest rate (77.8 ± 12.1%, 35/ 45) and March had the lowest (17.6 ± 12.8%, 6/34). In addition, significant difference was found due to age of the dog (p<0.05)

PRESENCIA DE Neospora caninum EN LLAMAS DE UNA EMPRESA GANADERA DE LA SIERRA CENTRAL

El Neospora caninum es un protozoo implicado como agente causal de abortos y muerte neonatal, principalmente en el ganado bovino. El presente estudio se llevó a cabo para determinar la seroprevalencia a Neospora caninum en llamas de la zona central del país. Se evaluaron 175 sueros de llamas hembras en edad reproductiva, pertenecientes a la empresa Sociedad Agraria de Interés Social (SAIS) Pachacútec, del departamento de Junín, mediante la técnica de inmunofluorescencia indirecta (IFI). Los resultados confirman la presencia del Neospora caninum en llamas de la sierra central, aunque con una seroprevalencia reducida (2.9 ± 2.5%).The Neospora caninum is a protozoan that causes abortion, especially in cattle. Thepresent study was carried out to determine the seroprevalence to Neospora caninum inllamas of the central zone of the country. A total of 175 serum samples of breeding femalellamas of the Agrarian Cooperative Pachacútec were analyzed by the immunofluorescentantibody test (IFAT). The results confirmed the presence of Neospora caninum in llamasof the Central Sierra, but the seroprevalence was low (2.9 ± 2.5 %)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security