Tom Wingfield

Chronic norovirus infection in an HIV-positive patient with persistent diarrhoea: A novel cause

The Monsall Unit, Infectious Diseases and Tropical Medicine Department, North Manchester General Hospital, Manchester, UK Enteric Virus Unit, Virus Reference Department, Centre for Infections, Health Protection Agency, Colindale, London, UK Central Manchester Foundation Trust, Department of Virology, Manchester, UK Molecular Diagnostics Department, Health Protection Agency North West, Manchester Royal Infirmary, Manchester, UK

The Seasonality of Tuberculosis, Sunlight, Vitamin D, and Household Crowding

Background. Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years. Methods. Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained. Results. Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001). Conclusions. The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis.

Autoimmune encephalitis: a case series and comprehensive review of the literature

Encephalitic syndromes are a common medical emergency. The importance of early diagnosis and appropriate treatment is paramount. If initial investigations for infectious agents prove negative, other diagnoses must be considered promptly. Autoimmune encephalitides are being increasingly recognized as important (and potentially reversible) non-infectious causes of an encephalitic syndrome. We describe four patients with autoimmune encephalitis--3 auto-antibody positive, 1 auto-antibody negative--treated during the last 18 months. A comprehensive review of the literature in this expanding area will be of interest to the infectious diseases, general medical and neurology community.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study

BACKGROUND Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

Designing and implementing a socioeconomic intervention to enhance TB control: operational evidence from the CRESIPT project in Peru

BackgroundCash transfers are key interventions in the World Health Organisation’s post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.MethodsNewly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings).To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders.ResultsOver 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally.Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering.Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to the initial bank-provider being limited; and conditions requiring participation of all TB-affected household members (e.g. community meetings) being hard to achieve.Refinements were made to improve project acceptability and future impact: the initial bank-provider was changed; conditional and unconditional cash transfers were combined; cash transfer sums were increased to a locally-appropriate, evidence-based amount; and cash transfer size varied according to patient household size to maximally reduce mitigation of TB-related costs and be more responsive to household needs.ConclusionsA novel TB-specific socioeconomic intervention including conditional cash transfers has been designed, implemented, refined and is ready for impact assessment, including by the CRESIPT project. The lessons learnt during this research will inform policy-makers and decision-makers for future implementation of related interventions.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

Abstract Objective To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. Methods A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru’s national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. Findings Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1–4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0–2.6). These improvements were equitable, being independent of household poverty. Conclusion A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Cryptococcal meningitis in an HIV-negative patient with rheumatoid arthritis treated with rituximab

Judith Payet, Raphaèle Seror, Julien Hanss, Didier Clerc, Corinne Miceli, Stéphan Pavy, Christine Le Pajolec and Xavier Mariette Department of Rheumatology, Assistance Publique Hopitaux de Paris, Hôpital Bicêtre, INSERM U802, Department of Rheumatology, Université Paris-Sud 11, Le Kremlin Bicêtre and Department of Oto-rhino-laryngology, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Université ParisSud 11, Le Kremlin Bicêtre, France. Accepted 15 April 2011 Correspondence to: Raphaèle Seror, Department of Rheumatology, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France. E-mail: raphaele.seror@bct.aphp.fr

Towards cash transfer interventions for tuberculosis prevention, care and control: key operational challenges and research priorities

BackgroundCash transfer interventions are forms of social protection based on the provision of cash to vulnerable households with the aim of reduce risk, vulnerability, chronic poverty and improve human capital. Such interventions are already an integral part of the response to HIV/AIDS in some settings and have recently been identified as a core element of World Health Organization’s End TB Strategy. However, limited impact evaluations and operational evidence are currently available to inform this policy transition.DiscussionThis paper aims to assist national tuberculosis (TB) programs with this new policy direction by providing them with an overview of concepts and definitions used in the social protection sector and by reviewing some of the most critical operational aspects associated with the implementation of cash transfer interventions. These include: 1) the various implementation models that can be used depending on the context and the public health goal of the intervention; 2) the main challenges associated with the use of conditionalities and how they influence the impact of cash transfer interventions on health-related outcomes; 3) the implication of targeting diseases-affected households and or individuals versus the general population; and 4) the financial sustainability of including health-related objectives within existing cash transfer programmes. We aimed to appraise these issues in the light of TB epidemiology, care and prevention. For our appraisal we draw extensively from the literature on cash transfers and build upon the lessons learnt so far from other health outcomes and mainly HIV/AIDS.ConclusionsThe implementation of cash transfer interventions in the context of TB is still hampered by important knowledge gaps. Initial directions can be certainly derived from the literature on cash transfers schemes and other public health challenges such as HIV/AIDS. However, the development of a solid research agenda to address persisting unknowns on the impact of cash transfers on TB epidemiology and control is vital to inform and support the adoption of the post-2015 End TB strategy.

Health, Healthcare Access, and Use of Traditional Versus Modern Medicine in Remote Peruvian Amazon Communities: A Descriptive Study of Knowledge, Attitudes, and Practices

There is an urgent need for healthcare research, funding, and infrastructure in the Peruvian Amazon. We performed a descriptive study of health, health knowledge and practice, and healthcare access of 13 remote communities of the Manatí and Amazon Rivers in northeastern Peru. Eighty-five adults attending a medical boat service were interviewed to collect data on socioeconomic position, health, diagnosed illnesses, pain, healthcare access, and traditional versus modern medicine use. In this setting, poverty and gender inequality were prevalent, and healthcare access was limited by long distances to the health post and long waiting times. There was a high burden of reported pain (mainly head and musculoskeletal) and chronic non-communicable diseases, such as hypertension (19%). Nearly all participants felt that they did not completely understand their diagnosed illnesses and wanted to know more. Participants preferred modern over traditional medicine, predominantly because of mistrust or lack of belief in traditional medicine. Our findings provide novel evidence concerning transitional health beliefs, hidden pain, and chronic non-communicable disease prevalence in marginalized communities of the Peruvian Amazon. Healthcare provision was limited by a breach between health education, knowledge, and access. Additional participatory research with similar rural populations is required to inform regional healthcare policy and decision-making.

Extreme elevation of ferritin and creatine kinase in primary infection with HIV-1

The diagnosis of primary HIV-1 infection can be challenging, especially in the absence of reported risks or when presenting features are unusual and uncommon. We report an atypical case of primary HIV-1 infection with HIV-1 subtype C in a 61-year old Caucasian man who presented with extreme hyperferritinaemia without iron overload and marked elevation of serum creatine kinase without rhabdomyolysis. In view of his symptomatic seroconversion and low baseline CD4+ T-lymphocyte count, the patient was treated promptly with combination antiretroviral therapy. Subsequently, he made good clinical improvement on treatment and no opportunistic infections were diagnosed at presentation or as part of a later immune reconstitution syndrome. This novel case highlights the importance of clinical suspicion of HIV and suggests that primary HIV-1 infection should be considered in patients presenting with severe hyperferritinaemia or markedly elevated creatine kinase levels. Further studies are required to explain the causative biological mechanisms underlying this rare presentation.