Elizabeth Fair

Intussusception among Infants Given an Oral Rotavirus Vaccine

BACKGROUND Intussusception is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Our investigation began on May 27, 1999, after nine cases of infants who had intussusception after receiving the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) were reported to the Vaccine Adverse Event Reporting System. METHODS In 19 states, we assessed the potential association between RRV-TV and intussusception among infants at least 1 but less than 12 months old. Infants hospitalized between November 1, 1998, and June 30, 1999, were identified by systematic reviews of medical and radiologic records. Each infant with intussusception was matched according to age with four healthy control infants who had been born at the same hospital as the infant with intussusception. Information on vaccinations was verified by the provider. RESULTS Data were analyzed for 429 infants with intussusception and 1763 matched controls in a case-control analysis as well as for 432 infants with intussusception in a case-series analysis. Seventy-four of the 429 infants with intussusception (17.2 percent) and 226 of the 1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case-control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). In the case-series analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. Assuming full implementation of a national program of vaccination with RRV-TV, we estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. CONCLUSIONS The strong association between vaccination with RRV-TV and intussusception among otherwise healthy infants supports the existence of a causal relation. Rotavirus vaccines with an improved safety profile are urgently needed.

Younger Age at Vaccination May Increase Risk of Varicella Vaccine Failure

To determine vaccine effectiveness (VE), a varicella outbreak in a highly vaccinated day-care center (DCC) population in Pennsylvania was investigated. In Pennsylvania, proof of immunity is required for children >or=12 months old for DCC enrollment. Questionnaires were administered to parents of children who had attended the DCC continuously during the study period (1 November 1999-9 April 2000) to determine history of varicella disease or vaccination and for information about any recent rash illnesses. VE was calculated for children >or=12 months old without a history of varicella. There were 41 cases of varicella among 131 attendees, with 14 cases (34%) among vaccinated children. VE was 79% against all varicella and 95% against moderate or severe varicella. Vaccination at <14 months was associated with an increased risk of breakthrough disease (relative risk, 3.0; 95% confidence interval, 0.9-9.9). Despite varicella vaccination coverage of 80%, a sizeable outbreak occurred. Early age at vaccination may increase the risk of vaccine failure.

International Standards for Tuberculosis Care: revisiting the cornerstones of tuberculosis care and control

Tuberculosis (TB) remains an enormous global health problem. There are 8–9 million new cases and 2 million deaths from TB annually. Despite the overwhelming burden of disease, the basic principles of care for persons with, or suspected of having, TB are the same worldwide: a diagnosis should be established promptly and accurately, standardized treatment regimens of proven efficacy should be used together with appropriate treatment support and supervision, the response to treatment should be monitored, and the essential public health responsibilities must be carried out. As an approach to improving the care of patients with TB, an evidence-based document, the International Standards for Tuberculosis Care (ISTC) was developed and has been endorsed by more than 30 international and national agencies. This special report introduces the ISTC and discusses the fact that accurate diagnosis and effective treatment are not only essential for good patient care, they are the key elements in the public health response to TB and are the cornerstone of TB control. With the recent emergence of extensively drug-resistant TB, there is an urgent need to ensure globally that standards of TB care are based on rigorous scientific findings, are clear and well understood, and are accessible to and applied by all types of healthcare providers in all corners of the world.

Updating the International Standards for Tuberculosis Care. Entering the Era of Molecular Diagnostics

The International Standards for Tuberculosis Care, first published in 2006 (Lancet Infect Dis 2006;6:710-725.) with a second edition in 2009 ( www.currytbcenter.ucsf.edu/international/istc_report ), was produced by an international coalition of organizations funded by the United States Agency for International Development. Development of the document was led jointly by the World Health Organization and the American Thoracic Society, with the aim of promoting engagement of all care providers, especially those in the private sector in low- and middle-income countries, in delivering high-quality services for tuberculosis. In keeping with World Health Organization recommendations regarding rapid molecular testing, as well as other pertinent new recommendations, the third edition of the Standards has been developed. After decades of dormancy, the technology available for tuberculosis care and control is now rapidly evolving. In particular, rapid molecular testing, using devices with excellent performance characteristics for detecting Mycobacterium tuberculosis and rifampin resistance, and that are practical and affordable for use in decentralized facilities in low-resource settings, is being widely deployed globally. Used appropriately, both within tuberculosis control programs and in private laboratories, these devices have the potential to revolutionize tuberculosis care and control, providing a confirmed diagnosis and a determination of rifampin resistance within a few hours, enabling appropriate treatment to be initiated promptly. Major changes have been made in the standards for diagnosis. Additional important changes include: emphasis on the recognition of groups at increased risk of tuberculosis; updating the standard on antiretroviral treatment in persons with tuberculosis and human immunodeficiency virus infection; and revising the standard on treating multiple drug-resistant tuberculosis.

Microevolution of the Direct Repeat Locus of Mycobacterium tuberculosis in a Strain Prevalent in San Francisco

ABSTRACT We describe a microevolutionary event of a prevalent strain of Mycobacterium tuberculosis that caused two outbreaks in San Francisco. During the second outbreak, a direct variable repeat was lost. We discuss the mechanisms of this change and the implications of analyzing multiple genetic loci in this context.

Tuberculosis contact investigation in low- and middle-income countries: standardized definitions and indicators.

There is a need for better utilization of program data for global tuberculosis (TB) control. Significant information could be gained from data collected by TB programs that could supplement traditional sources of evidence and contribute to policy development. For this operational information to be useful, it must be collected in a uniform manner, using standardized definitions and approaches to evaluation. As an example of an approach to uniformity in generating useful program data, we present recommendations for the standardization of definitions and indicators for the investigation of contacts of persons with infectious TB in low- and middle-income countries.

Identifying barriers to and facilitators of tuberculosis contact investigation in Kampala, Uganda: a behavioral approach

BackgroundThe World Health Organization recommends routine household tuberculosis contact investigation in high-burden countries but adoption has been limited. We sought to identify barriers to and facilitators of TB contact investigation during its introduction in Kampala, Uganda.MethodsWe collected cross-sectional qualitative data through focus group discussions and interviews with stakeholders, addressing three core activities of contact investigation: arranging household screening visits through index TB patients, visiting households to screen contacts and refer them to clinics, and evaluating at-risk contacts coming to clinics. We analyzed the data using a validated theory of behavior change, the Capability, Opportunity, and Motivation determine Behavior (COM-B) model, and sought to identify targeted interventions using the related Behavior Change Wheel implementation framework.ResultsWe led seven focus-group discussions with 61 health-care workers, two with 21 lay health workers (LHWs), and one with four household contacts of newly diagnosed TB patients. We, in addition, performed 32 interviews with household contacts from 14 households of newly diagnosed TB patients. Commonly noted barriers included stigma, limited knowledge about TB among contacts, insufficient time and space in clinics for counselling, mistrust of health-center staff among index patients and contacts, and high travel costs for LHWs and contacts. The most important facilitators identified were the personalized and enabling services provided by LHWs. We identified education, persuasion, enablement, modeling of health-positive behaviors, incentivization, and restructuring of the service environment as relevant intervention functions with potential to alleviate barriers to and enhance facilitators of TB contact investigation.ConclusionsThe use of a behavioral theory and a validated implementation framework provided a comprehensive approach for systematically identifying barriers to and facilitators of TB contact investigation. The behavioral determinants identified here may be useful in tailoring interventions to improve implementation of contact investigation in Kampala and other similar urban settings.

Drop-out from the tuberculosis contact investigation cascade in a routine public health setting in urban Uganda: A prospective, multi-center study.

Setting Seven public tuberculosis (TB) units in Kampala, Uganda, where Uganda’s national TB program recently introduced household contact investigation, as recommended by 2012 guidelines from WHO. Objective To apply a cascade analysis to implementation of household contact investigation in a programmatic setting. Design Prospective, multi-center observational study. Methods We constructed a cascade for household contact investigation to describe the proportions of: 1) index patient households recruited; 2) index patient households visited; 3) contacts screened for TB; and 4) contacts completing evaluation for, and diagnosed with, active TB. Results 338 (33%) of 1022 consecutive index TB patients were eligible for contact investigation. Lay health workers scheduled home visits for 207 (61%) index patients and completed 104 (50%). Among 287 eligible contacts, they screened 256 (89%) for symptoms or risk factors for TB. 131 (51%) had an indication for further TB evaluation. These included 59 (45%) with symptoms alone, 58 (44%) children <5, and 14 (11%) with HIV. Among 131 contacts found to be symptomatic or at risk, 26 (20%) contacts completed evaluation, including five (19%) diagnosed with and treated for active TB, for an overall yield of 1.7%. The cumulative conditional probability of completing the entire cascade was 5%. Conclusion Major opportunities exist for improving the effectiveness and yield of TB contact investigation by increasing the proportion of index households completing screening visits by lay health workers and the proportion of at-risk contacts completing TB evaluation.

‘It makes the patient's spirit weaker': tuberculosis stigma and gender interaction in Dar es Salaam, Tanzania

SETTING Dar es Salaam, Tanzania. OBJECTIVES To describe tuberculosis (TB) related stigma and to understand how it interacts with gender to affect access to care. DESIGN Eight focus group discussions were held among 48 TB patients and their household members, and a thematic content analysis was carried out. RESULTS The main components of stigma were fear, self-isolation, ostracization, loss of status in the community, and discrimination by providers. Participants described the cultural context in which stigma operated as characterized by a general lack of health knowledge, cultural beliefs about TB, and engendered beliefs about disease in general. Both genders described some similar effects of stigma, including relationship difficulties and specifically challenges forming new relationships, but many effects of stigma were distinct by gender: women described challenges including assumptions about promiscuity and infidelity, as well as rejection by partners, while men described survival challenges. Stigma acted as a barrier to care through a cyclical pattern of stigma and fear, leading to health-seeking delays, with resulting continued transmission and poor health outcomes that further reinforced stigma. CONCLUSION TB-related stigma is prevalent in this setting and operates differently for men and women. Interventions designed to increase case detection must address stigma and its interaction with gender.

Linking private, for-profit providers to public sector services for HIV and tuberculosis co-infected patients: A systematic review

Background Tuberculosis (TB) is the leading cause of infectious disease deaths worldwide and is the leading cause of death among people with HIV. The World Health Organization (WHO) has called for collaboration between public and private healthcare providers to maximize integration of TB/HIV services and minimize costs. We systematically reviewed published models of public-private sector diagnostic and referral services for TB/HIV co-infected patients. Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, Google Scholar, Science Direct, CINAHL and Web of Science. We included studies that discussed programs that linked private and public providers for TB/HIV concurrent diagnostic and referral services and used Review Manager (Version 5.3, 2015) for meta-analysis. Results We found 1,218 unduplicated potentially relevant articles and abstracts; three met our eligibility criteria. All three described public-private TB/HIV diagnostic/referral services with varying degrees of integration. In Kenya private practitioners were able to test for both TB and HIV and offer state-subsidized TB medication, but they could not provide state-subsidized antiretroviral therapy (ART) to co-infected patients. In India private practitioners not contractually engaged with the public sector offered TB/HIV services inconsistently and on a subjective basis. Those partnered with the state, however, could test for both TB and HIV and offer state-subsidized medications. In Nigeria some private providers had access to both state-subsidized medications and diagnostic tests; others required patients to pay out-of-pocket for testing and/or treatment. In a meta-analysis of the two quantitative reports, TB patients who sought care in the public sector were almost twice as likely to have been tested for HIV than TB patients who sought care in the private sector (risk ratio [RR] 1.98, 95% confidence interval [CI] 1.88–2.08). However, HIV-infected TB patients who sought care in the public sector were marginally less likely to initiate ART than TB patients who sought care from private providers (RR 0.89, 95% CI 0.78–1.03). Conclusion These three studies are examples of public-private TB/HIV service delivery and can potentially serve as models for integrated TB/HIV care systems. Successful public-private diagnostic and treatment services can both improve outcomes and decrease costs for patients co-infected with HIV and TB.