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Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Objective To investigate a method of using patient-held records to collect contraception data in Malawi, that could be used to explore contraceptive discontinuation and method switching. Methods In 2012, all 7393 women aged 15 to 49 years living in the area covered by the Karonga demographic surveillance site were offered a family planning card, which was attached to the woman's health passport--a patient-held medical record. Health-care providers were trained to use the cards to record details of contraception given to women. During the study, providers underwent refresher training sessions and received motivational text messages to improve data completeness. After one year, the family planning cards were collected for analysis. Findings Of the 7393 eligible women, 6861 (92.8%) received a family planning card and 4678 (63.3%) returned it after one year. Details of 87.3% (2725/3122) of contacts between health-care providers and the women had been recorded by health-care providers on either family planning cards or health passports. Lower-level health-care providers were more diligent at recording data on the family planning cards than higher-level providers. Conclusion The use of family planning cards was an effective way of recording details of contraception provided by family planning providers. The Involvement of health-care providers was key to the success of this approach. Data collected in this way should prove helpful in producing accurate estimates of method switching and the continuity of contraceptive use by women. [TEXT NOT REPRODUCIBLE IN ASCII] Objectif Examiner une methode consistant a utiliser les dossiers tenus par les patients pour recueillir des donnees sur la contraception au Malawi qui pourraient permettre d'analyser les interruptions et les changements de methodes de contraception. Methodes En 2012, l'ensemble des 7393 femmes agees de 15 a 49 ans de la region couverte par le systeme de surveillance demographique de Karonga s'est vu proposer une carte de planification familiale, attachee a leur carnet de sante--un dossier medical tenu par les patients. Les professionnels de sante ont ete formes a utiliser ces cartes pour noter les renseignements sur la contraception prescrite aux femmes. Au cours de l'etude, ils ont assiste a des seances de remise a niveau et ont recu des SMS d'incitation en vue d'ameliorer l'exhaustivite des renseignements inscrits. Au bout d'un an, les cartes de planification familiale ont ete recueillies pour analyse. Resultats Sur les 7393 femmes eligibles, 6861 (92,8%) ont recu une carte de planification familiale et 4678 (63,3%) l'ont restituee au bout d'un an. Des renseignements sur 87,3% (2725/3122) des contacts entre les professionnels de sante et les femmes avalent ete consignes par les professionnels de sante sur les cartes de planification familiale ou les carnets de sante. Les professionnels de sante de niveau Inferieur etaient plus appliques a inscrire les renseignements sur les cartes de planification familiale que ceux de niveau plus eleve. Conclusion L'utilisation de cartes de planification familiale s'est revelee un moyen efficace de consigner les renseignements sur la contraception prescrite par les prestataires de services de planification familiale. L'implication des professionnels de sante etait indispensable a la reussite de cette demarche. Les donnees recueillies de cette maniere devraient permettre de faire des estimations precises des changements de methodes et de la continuite du recours aux contraceptifs par les femmes. [TEXT NOT REPRODUCIBLE IN ASCII] Objetivo Investigar un metodo para hacer uso de las historias clinicas de los pacientes para recopilar datos sobre los anticonceptivos en Malawi, los cuales podrian utilizarse para estudiar la eliminacion de los anticonceptivos y los cambios de metodos. Metodos En 2012, se ofrecio a todas las 7.393 mujeres de entre 15 y 49 anos que vivian en la zona cubierta por los puestos de vigilancia demografica de Karonga una cartilla de planificacion familiar, que se adjuntaba a su pasaporte sanitario (la historia clinica del paciente). -Se enseno a los profesionales sanitarios a hacer uso de las historias para documentar detalles sobre los anticonceptivos administrados a las mujeres. A lo largo del estudio, los profesionales se sometieron a sesiones formativas de actualizacion y recibieron mensajes de texto motivacionales para mejorar el cumplimiento total de los datos. Despues de un ano, se recogieron las cartillas de planificacion familiar para analizarlas. Resultados De las 7.393 mujeres que cumplian los requisitos, 6.861 (92,8%) recibieron una cartilla de planificacion familiar y 4.678 (63,3%) la devolvieron al cabo de un ano. Los detalles del 87,3% (2.725/3.122) de las visitas entre los profesionales sanitarios y las mujeres fueron documentados por los primeros en las cartillas de planificacion familiar o bien en los pasaportes sanitarios. Los proveedores de atencion sanitaria de bajo rango fueron mas minuciosos a la hora de documentar los datos en las cartillas de planificacion familiar que los de alto rango. Conclusion El uso de las cartillas de planificacion familiarfue una forma efectiva de registrar los detalles de los anticonceptivos administrados por los proveedores de planificacion familiar. La implicacion de los proveedores de atencion sanitaria fue clave para el exito de este enfoque. La informacion recopilada de esta forma debera ser de ayuda a la hora de producir estimaciones rigurosas sobre si existen cambios de metodos y continuidad en el uso de anticonceptivos por parte de las mujeres., Introduction Access to contraceptive services is important, not only because of the direct effect on reproductive health, but also because contraceptive use may lead to indirect improvements in general health [...]

Abstract Background Decentralised health services form a key part of chronic care strategies in resource-limited settings by reducing the distance between patient and clinic and thereby the time and costs involved in travelling. However, few tools exist to evaluate the impact of decentralisation on patient travel time or what proportion of patients attend their nearest clinic. Here we develop methods to monitor changes in travel time, using data from the antiretroviral therapy (ART) roll-out in a rural district in North Malawi. Methods Clinic position was combined with GPS information on the home village of patients accessing ART services in Karonga District (North Malawi) between July 2005 and July 2009. Potential travel time was estimated as the travel time for an individual attending their nearest clinic, and estimated actual travel time as the time to the clinic attended. This allowed us to calculate changes in potential and actual travel time as new clinics opened and track the proportion and origin of patients not accessing their nearest clinic. Results The model showed how the opening of further ART clinics in Karonga District reduced median potential travel time from 83 to 43 minutes, and median actual travel time fell from 83 to 47 minutes. The proportion of patients not attending their nearest clinic increased from 6% when two clinics were open, to 12% with four open. Discussion Integrating GPS information with patient data shows the impact of decentralisation on travel time and clinic choice to inform policy and research questions. In our case study, travel time decreased, accompanied by an increased uptake of services. However, the model also identified an increasing proportion of ART patients did not attend their nearest clinic.

Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development.

Objective: To evaluate the degree of interference that administration of hemoglobin glutamer-200 (Hb-200) caused for complete blood counts (CBC), biochemical profiles, cooximetry, and point of care (POC) testing in healthy dogs. Design: Prospective, longitudinal experimental study. Setting: Veterinary medical teaching hospital. Animals: Six purpose-bred research hounds. Interventions: Dogs were administered FDA-approved hemoglobin-based oxygen carrier (Hb-200) intravenously at 7.5 mL/kg over 2 hours. Arterial and venous blood samples were obtained before administration (Time 0) and at 3, 8, 14, 26, 50, 74, 98, 122, and 146 hours following administration. Measurements and main results: No adverse health effects were observed in any of the dogs. Characteristic mucous membrane, serum, and plasma color changes occurred following administration of Hb-200. Laboratory values that were significantly lower than baseline included packed cell volume, red blood cell count, hemoglobin, hematocrit, creatinine, cholesterol, alanine aminotransferase, and alkaline phosphatase. Laboratory values that were significantly greater than baseline included mean corpuscular hemoglobin concentration, arterial pH, arterial total carbon dioxide, arterial bicarbonate, amylase, albumin, total protein, globulin, calcium, phosphorous, total bilirubin, carboxyhemoglobin, and methemoglobin. All values returned to baseline by the completion of the 146-hour monitoring period. Conclusions: In normal dogs, administration of Hb-200 resulted in statistically significant changes in multiple laboratory parameters; however, these changes are not likely to be clinically significant in the care of critically ill dogs. [ABSTRACT FROM AUTHOR]

Objective--To compare the amount of air leakage into the thoracic cavity associated with each of 4 thoracostomy tube placement techniques in canine cadavers. Sample Population--28 canine cadavers. Procedures--Thoracostomy tube placement techniques (7 cadavers/technique) included subcutaneous tunneling with a silicone tube by use of Carmalt forceps or with a polyvinyl chloride tube by use of a trocar (SC-CARM and SC-TRO, respectively) and tunneling under the latissimus dorsi muscle with similar tube-instrument techniques (LD-CARM and LD-TRO, respectively). Differences in intrapleural pressures (IPPs) measured before and after tube placement and before and after tube removal were calculated; duration of air leak-age around the tubes was assessed by use of a 3-chamber thoracic drainage system. Results--Tunneling method and depth had no interaction effect on the difference in IPP measured before and after tube placement; the IPP difference for both forceps technique groups was significantly greater than findings for both trocar technique groups. Tunneling method and depth had an interaction effect on the difference in IPP measured before and after tube removal; compared with SC-TRO and LD-CARM group differences, the SC-CARM group difference was significantly greater, but the LD-TRO group difference was similar. More intermittent air leakage was associated with the 2 forceps techniques than with the 2 trocar techniques. Conclusions and Clinical Relevance--Trocar-implemented thoracostomy tube placement in canine cadavers resulted in less air leakage than the forceps method. Air leakage upon tube removal was less pronounced for the LD-CARM technique than the SC-CARM technique. The LD-TRO technique is recommended to prevent iatrogenic pneumothorax in dogs. [ABSTRACT FROM AUTHOR]