Storage of Sputum in Cetylpyridinium Chloride, OMNIgene.SPUTUM, and Ethanol Is Compatible with Molecular Tuberculosis Diagnostic Testing

YesWe compared cetylpyridinium chloride (CPC), ethanol (ETOH), and OMNIgene.SPUTUM (OMNI) for 28-day storage of sputum at ambient temperature before molecular tuberculosis diagnostics. Three sputum samples were collected from each of 133 smear-positive tuberculosis (TB) patients (399 sputum samples). Each patient's sputum was stored with either CPC, ETOH, or OMNI for 28 days at ambient temperature, with subsequent rpoB amplification targeting a short fragment (81 bp, GeneXpert MTB/RIF [Xpert]) or a long fragment (1,764 bp, in-house nested PCR). For 36 patients, Xpert was also performed at baseline on all 108 fresh sputum samples. After the 28-day storage (D28), Xpert positivity did not significantly differ between storage methods. In contrast, higher positivity for rpoB nested PCR was obtained with OMNI (n = 125, 94%) than with ETOH (n = 114, 85.7%; P = 0.001). Smears with scanty acid-fast bacilli (AFB) had lower rpoB PCR positivity with ETOH storage (n = 10, 41.7%) than with CPC (n = 16, 66.7%; difference, 25%; 95% confidence interval [CI], 3.5 to 46.5; P = 0.031) or OMNI (n = 16, 69.6%; difference, 26.1%; 95% CI, 3.8 to 48.4; P = 0.031), with no difference between CPC and OMNI. Poststorage, the threshold cycle (CT ) values significantly decreased compared to those prestorage with ETOH (difference, -1.1; 95% CI, -1.6 to -0.6; P = 0.0001) but not with CPC (P = 0.915) or OMNI (P = 0.33). For one patient's ETOH- and CPC-stored specimens with a CT of <10, Xpert gave results of rifampin false resistant at D28, which was resolved by repeating Xpert on a 1/100 diluted specimen. In conclusion, 28-day storage of sputum in OMNI, CPC, or ETOH at ambient temperature does not impact short-fragment PCR (Xpert), including for low smear grades. However, for long-fragment PCR, ETOH yielded a lower PCR positivity for low smear grades, while the performance of OMNI and CPC was excellent for all smear grades. (The study has been registered at ClinicalTrials.gov under registration number NCT02744469.).Directorate General for Development (DGD), Belgium (FA4 to C.N.S., B.C.D.J., D.A., and L.R.), and the European Research Council-INTERRUPTB starting grant (number 311725 to B.C.D.J., C.J.M., and L.R.

Ascertainment of childhood vaccination histories in northern Malawi

OBJECTIVE: To assess factors related to recorded vaccine uptake, which may confound the evaluation of vaccine impact.METHODS: Analysis of documented vaccination histories of children under 5 years and demographic and socio-economic characteristics collected by a demographic surveillance system in Karonga District, Malawi. Associations between deviations from the standard vaccination schedule and characteristics that are likely to be associated with increased mortality were determined by multivariate logistic regression.RESULTS: Approximately 78% of children aged 6-23 months had a vaccination document, declining to &lt;50% by 5 years of age. Living closer to an under-5 clinic, having a better educated father, and both parents being alive were associated with having a vaccination document. For a small percentage of children, vaccination records were incomplete and/or faulty. Vaccination uptake was high overall, but delayed among children living further from the nearest under-5 clinic or from poorer socio-economic backgrounds. Approximately 9% of children had received their last dose of DPT with or after measles vaccine. These children were from relatively less educated parents, and were more likely to have been born outside the health services.CONCLUSIONS: Though overall coverage in this community was high and variation in coverage according to child or parental characteristics small, there was strong evidence of more timely coverage among children from better socio-economic conditions and among those who lived closer to health facilities. These factors are likely to be strong confounders in the association of vaccinations with mortality, and may offer an alternative explanation for the non-specific mortality impact of vaccines described by other studies

Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study.

ABSTRACT: BACKGROUND: Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. METHODS: We did a prospective diagnostic study in a Medecins Sans Frontieres-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. RESULTS: Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear ([greater than or equal to]1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p=0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p=0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p=0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p=0.016), respectively. CONCLUSIONS: The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context

Guidelines for using HIV testing technologies in surveillance: selection, evaluation, and implementation

[UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance]."WHO/CDS/CSR/EDC/2001.16.""UNAIDS/01.22E.""Global surveillance of HIV/AIDS and sexually transmitted infections (STIs) is a joint effort of the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS). The UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance, initiated in November 1996, is the main coordination and implementation mechanism for UNAIDS and WHO to compile the best information available and to improve the quality of data needed for informed decision-making and planning at national, regional and global levels. ... The Centers for Disease Control and Prevention (CDC), Atlanta, USA, deserves special credit for having prepared these Guidelines. The key professional staff, Dr. Christopher Murrill and Dr. Rebecca Martin, should be congratulated for their efforts in producing this document, with editorial assistance from Ms. Sadhna Patel and Ms. Beatrice Divine." - p. iiAlso available via the World Wide Web.Includes bibliographical references (p. 37-38)

Hepatitis B and C Viruses and Hepatocellular Carcinoma

Chronic liver disease is responsible for over 1.4 million deaths annually  [1] and is characterized by permanent inflammatory processes that predispose to liver cancer and in particular hepatocellular carcinoma (HCC). In healthy liver, inflammatory processes stimulate growth and repair and restore normal liver architecture. However, if liver inflammation becomes chronic, the balance of damage versus regeneration in the liver is disrupted and can lead to the formation of excessive scar tissue, termed fibrosis. In the long-term, an exacerbation of fibrosis will lead to cirrhosis, which is characterized by abnormal liver architecture and function and is associated with a significant reduction in overall health and wellbeing. At cirrhotic stages, liver damage is often irreversible or difficult to treat. Cirrhosis leads frequently to death from liver failure or to HCC (Figure 1). Indeed, HCC is the first cause of death in cirrhotic patients [2], and is a tumor with poor prognosis, ranking third in terms of death by cancer. Furthermore, it is the fifth most prevalent cancer worldwide, with 800,000 new cases per year in the world [2,3]. [...

The Global Fund to Fight AIDS, Tuberculosis and Malaria's investments in harm reduction through the rounds-based funding model (2002-2014)

Background: Harm reduction is an evidence-based, effective response to HIV transmission and other harms faced by people who inject drugs, and is explicitly supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria. In spite of this, people who inject drugs continue to have poor and inequitable access to these services and face widespread stigma and discrimination. In 2013, the Global Fund launched a new funding model-signalling the end of the previous rounds-based model that had operated since its founding in 2002. This study updates previous analyses to assess Global Fund investments in harm reduction interventions for the duration of the rounds-based model, from 2002 to 2014. Methods: Global Fund HIV and TB/HIV grant documents from 2002 to 2014 were reviewed to identify grants that contained activities for people who inject drugs. Data were collected from detailed grant budgets, and relevant budget lines were recorded and analysed to determine the resources allocated to different interventions that were specifically targeted at people who inject drugs. Results: 151 grants for 58 countries, plus one regional proposal, contained activities targeting people who inject drugs-for a total investment of US 620. million. Two-thirds of this budgeted amount was for interventions in th

Percent Fat Mass Increases with Recovery, But Does Not Vary According to Dietary Therapy in Young Malian Children Treated for Moderate Acute Malnutrition.

BackgroundModerate acute malnutrition (MAM) affects 34.1 million children globally. Treatment effectiveness is generally determined by the amount and rate of weight gain. Body composition (BC) assessment provides more detailed information on nutritional stores and the type of tissue accrual than traditional weight measurements alone.ObjectiveThe aim of this study was to compare the change in percentage fat mass (%FM) and other BC parameters among young Malian children with MAM according to receipt of 1 of 4 dietary supplements, and recovery status at the end of the 12-wk intervention period.MethodsBC was assessed using the deuterium oxide dilution method in a subgroup of 286 children aged 6-35 mo who participated in a 12-wk community-based, cluster-randomized effectiveness trial of 4 dietary supplements for the treatment of MAM: 1) lipid-based, ready-to-use supplementary food (RUSF); 2) special corn-soy blend "plus plus" (CSB++); 3) locally processed, fortified flour (MI); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). Multivariate linear regression modeling was used to evaluate change in BC parameters by treatment group and recovery status.ResultsMean&nbsp;±&nbsp;SD %FM at baseline was 28.6%&nbsp;±&nbsp;5.32%. Change in %FM did not vary between groups. Children who received RUSF vs. MI gained more (mean; 95% CI) weight (1.43; 1.13, 1.74 kg compared with 0.84; 0.66, 1.03 kg; P&nbsp;=&nbsp;0.02), FM (0.70; 0.45, 0.96 kg compared with 0.20; 0.05, 0.36 kg; P&nbsp;=&nbsp;0.01), and weight-for-length z score (1.23; 0.79, 1.54 compared with 0.49; 0.34, 0.71; P&nbsp;=&nbsp;0.03). Children who recovered from MAM exhibited greater increases in all BC parameters, including %FM, than children who did not recover.ConclusionsIn this study population, children had higher than expected %FM at baseline. There were no differences in %FM change between groups. International BC reference data are needed to assess the utility of BC assessment in community-based management of acute malnutrition programs. This trial was registered at clinicaltrials.gov as NCT01015950

The Psychiatrization of Poverty: Rethinking the Mental Health-Poverty Nexus

The positive association between ‘mental illness’ and poverty is one of the most well established in psychiatric epidemiology. Yet, there is little conclusive evidence about the nature of this relationship. Generally, explanations revolve around the idea of a vicious cycle, where poverty may cause mental ill health, and mental ill health may lead to poverty. Problematically, much of the literature overlooks the historical, social, political, and cultural trajectories of constructions of both poverty and ‘mental illness’. Laudable attempts to explore the social determinants of mental health sometimes take recourse to using and reifying psychiatric diagnostic categories that individualize distress and work to psychiatrically reconfigure ‘symptoms’ of oppression, poverty, and inequality as ‘symptoms’ of ‘mental illness’. This raises the paradoxical issue that the very tools that are used to research the relationship between poverty and mental health may prevent recognition of the complexity of that relationship. Looking at the mental health–poverty nexus through a lens of psychiatrization (intersecting with medicalization, pathologization, and psychologization), this paper recognizes the need for radically different tools to trace the messiness of the multiple relationships between poverty and distress. It also implies radically different interventions into mental health and poverty that recognize the landscapes in which lived realities of poverty are embedded, the political economy of psychiatric diagnostic and prescribing practices, and ultimately to address the systemic causes of poverty and inequality

Challenges for clinical practice and research in family medicine in reducing the risk of chronic diseases. Notes on the EGPRN Spring Conference 2017 in Riga

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