Surbhi Modi

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

Use of isoniazid preventive therapy for tuberculosis prophylaxis among people living with HIV/AIDS: a review of the literature.

Background:Tuberculosis (TB) is the leading preventable cause of death in persons living with HIV (PLHIV), accounting for over a quarter of all HIV-associated deaths in 2012. Isoniazid preventive therapy (IPT) has the potential to decrease TB-related cases and deaths in PLHIV; however, implementation of this has been slow in many high HIV- and TB-burden settings. Methodology:We performed an assessment of the evidence for the use of IPT in adults living with HIV based on a review of the literature published from 1995 to 2013. Eligible articles included data on mortality, morbidity, or retention in care related to the provision of IPT to adults with HIV in low- or middle-income countries. Cost-effectiveness information was also abstracted. Results:We identified 41 articles involving over 45,000 PLHIV. While there was little evidence to demonstrate that IPT reduced mortality in PLHIV, there was substantial evidence that IPT reduced TB incidence. While these findings were consistent irrespective of CD4 or antiretroviral therapy status, studies frequently demonstrated a greater benefit among patients with a positive TB skin test (TST). Duration of effectiveness and benefits of prolonged therapy varied across settings. Conclusions:This analysis supports World Health Organization recommendations for the provision of IPT to PLHIV to reduce TB-associated morbidity and serves to highlight the need to strengthen IPT implementation. While there appears to be a greater benefit of IPT among PLHIV who are TST positive, IPT should be provided to all PLHIV without presumptive TB when TST is not available.

PEPFAR scale-up of pediatric HIV services: Innovations, achievements, and challenges

Abstract: HIV/AIDS has had a profound impact on children around the world since the start of the epidemic. There are currently 3.4 million children under the age of 15 years living with HIV globally, and more than 450,000 children currently receiving lifesaving antiretroviral treatment. This article describes efforts supported by the Presidents Emergency Plan for AIDS Relief (PEPFAR) to expand access to treatment for children living with HIV in high-burden countries. The article also highlights a series of case studies that illustrate the impact that the PEPFAR initiative has had on the pediatric HIV epidemic. Through its support of host governments and partner organizations, the PEPFAR initiative has expanded HIV testing and treatment for pregnant women to reduce vertical transmission of HIV, increased access to early infant diagnosis for HIV-exposed infants, improved training and resources for clinicians who provide pediatric care and antiretroviral treatment, and, through public–private partnerships with pharmaceutical manufacturers, helped increase the number of medications available for the treatment of HIV-infected children in resource-limited settings.

Characteristics of multidrug-resistant tuberculosis in Namibia

BackgroundTo describe the epidemiology and possible risk factors for the development of multidrug-resistant tuberculosis (MDR-TB) in Namibia.MethodsUsing medical records and patient questionnaires, we conducted a case-control study among patients diagnosed with TB between January 2007 and March 2009. Cases were defined as patients with laboratory-confirmed MDR-TB; controls had laboratory-confirmed drug-susceptible TB or were being treated with WHO Category I or Category II treatment regimens.ResultsWe enrolled 117 MDR-TB cases and 251 TB controls, of which 100% and 2% were laboratory-confirmed, respectively. Among cases, 97% (113/117) had been treated for TB before the current episode compared with 46% (115/251) of controls (odds ratio [OR] 28.7, 95% confidence interval [CI] 10.3–80.5). Cases were significantly more likely to have been previously hospitalized (OR 1.9, 95% CI 1.1–3.5) and to have had a household member with MDR-TB (OR 5.1, 95% CI 2.1–12.5). These associations remained significant when separately controlled for being currently hospitalized or HIV-infection.ConclusionsMDR-TB was associated with previous treatment for TB, previous hospitalization, and having had a household member with MDR-TB, suggesting that TB control practices have been inadequate. Strengthening basic TB control practices, including expanding laboratory confirmation, directly observed therapy, and infection control, are critical to the prevention of MDR-TB.

Performance of Clinical Screening Algorithms for Tuberculosis Intensified Case Finding among People Living with HIV in Western Kenya.

Objective To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya. Design Prospective cohort study Methods PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and “Improving Diagnosis of TB in HIV-infected persons” (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey. Results Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9–12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1–82.2); MOH, 77.5% (95% CI, 68.6–84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9–81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9–46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3–86.4)] and men [77.2% (95% CI, 68.3–84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4–93.9) and 96.1% (95% CI, 94.4–97.3), respectively, among asymptomatic men and non-pregnant women. Conclusions Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.

TB screening among people living with HIV/AIDS in resource-limited settings.

Abstract:Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among people living with HIV (PLHIV), making improved prevention and treatment of HIV-associated TB critical to ensuring long-term survival of PLHIV. TB screening among PLHIV is central to implementation of the World Health Organizations 3 Is interventions for reducing the impact of the TB and HIV syndemics. Effective TB screening will result in the identification of PLHIV with presumptive TB disease (ie, those with a positive symptom screen who require appropriate evaluation, including the use of diagnostic tools such as the Xpert MTB/RIF assay) and those eligible for isoniazid preventive therapy (ie, those who have a negative clinical symptom screen or who have a positive screen but are found not to have TB disease). Identification of PLHIV with presumptive TB also facilitates implementation of basic administrative measures for TB infection control, including fast tracking of coughing patients and separation from noncoughing PLHIV to reduce TB transmission. By contributing to the early diagnosis of TB disease among PLHIV, TB screening is also critical to facilitate early initiation of antiretroviral treatment among PLHIV diagnosed with TB disease who might not otherwise be eligible for antiretroviral treatment based on CD4 count or clinical staging. TB screening thus serves as a gateway for multiple TB/HIV interventions and is an integral part of routine clinical services for PLHIV at each clinic visit.

Understanding the contribution of common childhood illnesses and opportunistic infections to morbidity and mortality in children living with HIV in resource-limited settings

Objective:Although antiretroviral treatment (ART) has reduced the incidence of HIV-related opportunistic infections among children living with HIV, access to ART remains limited for children, especially in resource-limited settings. This paper reviews current knowledge on the contribution of opportunistic infections and common childhood illnesses to morbidity and mortality in children living with HIV, highlights interventions known to improve the health of children, and identifies research gaps for further exploration. Design and Methods:Literature review of peer-reviewed articles and abstracts combined with expert opinion and operational experience. Results:Morbidity and mortality due to opportunistic infections has decreased in both developed and resource-limited countries. However, the burden of HIV-related infections remains high, especially in sub-Saharan Africa, where the majority of HIV-infected children live. Limitations in diagnostic capacity in resource-limited settings have resulted in a relative paucity of data on opportunistic infections in children. Additionally, the reliance on clinical diagnosis means that opportunistic infections are often confused with common childhood illnesseswhich also contribute to excess morbidity and mortality in these children. Although several preventive interventions have been shown to decrease opportunistic infection-related mortality, implementation of many of these interventions remains inconsistent. Conclusions:In order to reduce opportunistic infection-related mortality, early ART must be expanded, training for front-line clinicians must be improved, and additional research is needed to improve screening and diagnostic algorithms.

Comparative Yield of Different Diagnostic Tests for Tuberculosis among People Living with HIV in Western Kenya

Background Diagnosis followed by effective treatment of tuberculosis (TB) reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum smear microscopy is widely used for diagnosis, despite limited sensitivity in PLHIV. Evidence is needed to determine the optimal diagnostic approach for these patients. Methods From May 2011 through June 2012, we recruited PLHIV from 15 HIV treatment centers in western Kenya. We collected up to three sputum specimens for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF (Xpert), and culture, regardless of symptoms. We calculated the incremental yield of each test, stratifying results by CD4 cell count and specimen type; data were analyzed to account for complex sampling. Results From 778 enrolled patients, we identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified 25 (33.6%); Xpert identified those plus an additional 18 (incremental yield = 24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases; whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/μL and 30/45 (67.0%) of cases with CD4 counts ≥100 cells/μl. Conclusions In PLHIV, Xpert substantially increased diagnostic yield compared to smear microscopy and had the highest yield when used to test morning specimens and specimens from PLHIV with CD4 count <100 cells/μL. TB programs unable to replace smear microscopy with Xpert for all symptomatic PLHIV should consider targeted replacement and using morning specimens.

Reporting Patterns and Characteristics of Tuberculosis among International Travelers, United States, June 2006 to May 2008

BACKGROUND As part of efforts to prevent the introduction of communicable diseases into the United States, the Centers for Disease Control and Prevention (CDC) conducts surveillance for selected diseases in international travelers. One of these diseases, tuberculosis (TB), received substantial attention in May 2007 when the CDC issued travel restrictions and a federal isolation order for a person with drug-resistant TB who traveled internationally against public health recommendations. METHODS Reports of TB in international travelers in the CDCs Quarantine Activity Reporting System (QARS) from 1 June 2006 through 31 May 2007 (year 1) were compared with reports from 1 June 2007 through 31 May 2008 (year 2). These reports were classified using the CDC and American Thoracic Society guidelines and analyzed for epidemiologic characteristics and trends. RESULTS Among QARS reports, 4.6% were classified as active TB disease and 1.7% as no TB disease. Active TB disease reports increased from 2.5% of QARS reports in year 1 to 6.4% in year 2 (p < .001). The proportion of active TB disease reports leading to a federal travel restriction increased from 6.8% in year 1 to 15.4% in year 2 (p = .08). CONCLUSIONS The significant increase in reports of international travelers with TB disease likely represents more attention to and a higher index of suspicion for TB. The increased use of federal travel restrictions was associated with the development of new procedures to limit travel for public health reasons. Continued efforts are needed to decrease the number of persons with TB who travel while potentially contagious.

Overcoming Health System Challenges for Women and Children Living With HIV Through the Global Plan

Abstract: To meet the ambitious targets set by the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), the initial 22 priority countries quickly developed innovative approaches for overcoming long-standing health systems challenges and providing HIV testing and treatment to pregnant and breastfeeding women and their infants. The Global Plan spurred programs for prevention of mother-to-child HIV transmission to integrate HIV-related care and treatment into broader maternal, newborn, and child health services; expand the effectiveness of the health workforce through task sharing; extend health services into communities; strengthen supply chain and commodity management systems; reduce diagnostic and laboratory hurdles; and strengthen strategic supervision and mentorship. The article reviews the ongoing challenges for prevention of mother-to-child HIV transmission programs as they continue to strive for elimination of vertical transmission of HIV infection in the post-Global Plan era. Although progress has been rapid, health systems still face important challenges, particularly follow-up and diagnosis of HIV-exposed infants, continuity of care, and the promotion of services that are respectful and client centered.