the correlation between the two responses on the same flock. The main risk factor that was 2 identified was rearing flocks in cages compared to barns and free-range systems. The results 3 also showed a significant higher risk for Salmonella for a one week increase in flocks' age as 4 well as with a unit increase in the size of the flock. 5 6
SummaryBackgroundCross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV.MethodsWe did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samples for all patients obtained every 12–16 weeks. This trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and ClinicalTrials.gov (number NCT00988039).FindingsBaseline genotypes were available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group. 176 (89%) of 198 patients prescribed a protease inhibitor with no predicted-active NRTIs had viral suppression (viral load <400 copies per mL) at week 144, compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0·02) and 233 (61%) of 280 patients in the protease inhibitor monotherapy group at week 96 (p<0·0001). Compared with results with no active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral suppression (p=0·3) and 20 (77%) of 26 patients with two or three active NRTIs had viral suppression (p=0·08). Over all follow-up, greater predicted NRTI activity was associated with worse viral load suppression (global p=0·0004).InterpretationGenotypic resistance testing might not accurately predict NRTI activity in protease inhibitor-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.FundingEuropean and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Institito de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.
BackgroundIn sub-Saharan Africa antiretroviral therapy (ART) is being decentralized from tertiary/secondary care facilities to primary care. The Lablite project supports effective decentralization in 3 countries. It began with a cross-sectional survey to describe HIV and ART services.Methods81 purposively sampled health facilities in Malawi, Uganda and Zimbabwe were surveyed.ResultsThe lowest level primary health centres comprised 16/20, 21/39 and 16/22 facilities included in Malawi, Uganda and Zimbabwe respectively. In Malawi and Uganda most primary health facilities had at least 1 medical assistant/clinical officer, with average 2.5 and 4 nurses/midwives for median catchment populations of 29,275 and 9,000 respectively. Primary health facilities in Zimbabwe were run by nurses/midwives, with average 6 for a median catchment population of 8,616. All primary health facilities provided HIV testing and counselling, 50/53 (94%) cotrimoxazole preventive therapy (CPT), 52/53 (98%) prevention of mother-to-child transmission of HIV (PMTCT) and 30/53 (57%) ART management (1/30 post ART-initiation follow-up only). All secondary and tertiary-level facilities provided HIV and ART services. In total, 58/81 had ART provision. Stock-outs during the 3 months prior to survey occurred across facility levels for HIV test-kits in 55%, 26% and 9% facilities in Malawi, Uganda and Zimbabwe respectively; for CPT in 58%, 32% and 9% and for PMTCT drugs in 26%, 10% and 0% of facilities (excluding facilities where patients were referred out for either drug). Across all countries, in facilities with ART stored on-site, adult ART stock-outs were reported in 3/44 (7%) facilities compared with 10/43 (23%) facility stock-outs of paediatric ART. Laboratory services at primary health facilities were limited: CD4 was used for ART initiation in 4/9, 5/6 and 13/14 in Malawi, Uganda and Zimbabwe respectively, but frequently only in selected patients. Routine viral load monitoring was not used; 6/58 (10%) facilities with ART provision accessed centralised viral loads for selected patients.ConclusionsAlthough coverage of HIV testing, PMTCT and cotrimoxazole prophylaxis was high in all countries, decentralization of ART services was variable and incomplete. Challenges of staffing and stock management were evident. Laboratory testing for toxicity and treatment effectiveness monitoring was not available in most primary level facilities.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6963-14-352) contains supplementary material, which is available to authorized users.
According to the European Food Safety Authority, salmonellosis is still one of the main causes of infectious foodborne gastroenteritis in humans. Broilers are an important source of salmonellosis after eggs and pork. Between 1987 and 1999 the trend of human salmonellosis incidence in Belgium increased constantly. However, from 2000 until 2005 a decrease in human cases was observed, probably following the sanitary measures implemented in the poultry breeder and laying sector. In order to decrease human infections it is essential to tackle the problem at the farm level to minimize cross contamination from farm to fork. This paper seeks to answer two questions (i) given the Salmonella status of the farm at a certain occasion (equal to the sampling time of the flock), what are the risk factors that the farm will be Salmonella positive at a following occasion? And (ii) what are the risk factors for a farm to be persistently positive for two consecutive flocks? We used surveillance data on 6,824 broiler flocks studied for Salmonella infectivity from 2005 to 2006 in Belgium. The farms were tested regularly (three weeks before slaughter of each broiler flock) for the presence of Salmonella based on multiple faecal samples per flock on a farm yielding clustered data. Generalized estimating equations, alternating logistic regression models, and randomintercept logistic regression models were employed to analyze these correlated binary data. Our results indicated that there are many factors that influence Salmonella risk in broiler flocks, and that they interact. Accounting for interactions between risk factors leads to an improved determination of those risk factors that increase infection with Salmonella. For the conditional analysis, the risk factors found to increase the risk of Salmonella infection on a farm at a current occasion given the previous Salmonella status included: Salmonella infection of day-old chicks (of the current flock); a previously infected flock even though the farm was equipped with a hygiene place to change clothes prior to entering the broiler house; having temporary workmen when there was a separation between birds of different species; and separating birds of different species in the Walloon region relative to the Flanders region. Sanitary measures such as a cleaning and disinfecting procedure conducted by an external cleaning firm, applying the all-in all-out procedure, and hand washing decreased the risk despite their interaction with other factors. From the joint analysis, the most important factors identified for increased risk for persistent Salmonella on a farm involved the interaction between having temporary workmen when there were poultry or farmers in contact with foreign poultry or persons, and the interaction between having temporary workmen when there were poultry or farmers in contact with external poultry or persons.
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