Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Shukla H [original query] |
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FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea
Hiruy H , Bala S , Byrne JM , Roche KG , Jang SH , Kim P , Nambiar S , Rubin D , Yasinskaya Y , Bachmann LH , Bernstein K , Botgros R , Cammarata S , Chaves RL , Deal CD , Drusano GL , Duffy EM , Eakin AE , Gelone S , Hiltke T , Hook Iii EW , Jerse AE , McNeil CJ , Newman L , O'Brien S , Perry C , Reno HEL , Romaguera RA , Sato J , Unemo M , Wi TEC , Workowski K , O'May GA , Shukla SJ , Farley JJ . Clin Infect Dis 2024 There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop. |
Persistent transmission of circulating vaccine-derived poliovirus - Somalia, January 2017-March 2024
Mendes A , Mohamed GA , Derow M , Stehling-Ariza T , Mohamed A , Mengistu K , Bullard K , Akbar IE , Shukla H , Al Safadi M , Martinez M . MMWR Morb Mortal Wkly Rep 2024 73 (25) 575-580 Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission worldwide: global eradication of WPV types 2 and 3 were certified in 2015 and 2019, respectively, and endemic transmission of WPV type 1 continues only in Afghanistan and Pakistan. After the synchronized global withdrawal of all serotype 2 oral poliovirus vaccines (OPVs) in 2016, widespread outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2) have occurred, which are linked to areas with low population immunity to poliovirus. Officials in Somalia have detected ongoing cVDPV2 transmission since 2017. Polio vaccination coverage and surveillance data for Somalia were reviewed to assess this persistent transmission. During January 2017-March 2024, officials in Somalia detected 39 cVDPV2 cases in 14 of 20 regions, and transmission has spread to neighboring Ethiopia and Kenya. Since January 2021, 28 supplementary immunization activities (SIAs) targeting cVDPV2 were conducted in Somalia. Some parts of the country are security-compromised and inaccessible for vaccination campaigns. Among 1,921 children with nonpolio acute flaccid paralysis, 231 (12%) had not received OPV doses through routine immunization or SIAs, 95% of whom were from the South-Central region, and 60% of whom lived in inaccessible districts. Enhancing humanitarian negotiation measures in Somalia to enable vaccination of children in security-compromised areas and strengthening campaign quality in accessible areas will help interrupt cVDPV2 transmission. |
Persistent colonization of Candida auris among inpatients rescreened as part of a weekly surveillance program
Arenas SP , Persad PJ , Patel S , Parekh DJ , Ferreira TBD , Farinas M , Sexton DJ , Lyman M , Gershengorn HB , Shukla BS . Infect Control Hosp Epidemiol 2023 1-4 We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests. |
Considerations for endpoint titer determination in syphilis testing using newly marketed, automated rapid plasma reagin instruments
Shukla M , Pereira L , Sun Y , Fakile YF , Kersh EN , Cao W . Public Health Rep 2023 333549231176007 Syphilis is a sexually transmitted disease (STD) caused by the bacterium Treponema pallidum, subspecies pallidum (T. pallidum).1 The resurgence of syphilis in the last 2 decades is a major public health concern in the United States. In 2020, a total of 133 945 cases of all stages of syphilis were reported in the United States, an increase of more than 70% since 2015. The national rate of congenital syphilis has increased 254% since 2016. In 2020, a total of 2148 cases of congenital syphilis were reported, including 149 congenital syphilis–related stillbirths and infant deaths.2 However, syphilis diagnosis is still challenging, partially because of overlapping and ambiguous clinical presentation, particularly during early infection.3 For laboratory testing, darkfield microscopy examinations and direct molecular detection of T. pallidum from clinical specimens are definitive methods for diagnosing early syphilis, but both methods are currently not widely performed at local, reference, or public health laboratories and have challenges in identifying asymptomatic or early-stage infection without the presence of visible lesions for suitable specimen collection.4 Darkfield microscopy requires special equipment and experienced operators for reliable results.5 US Food and Drug Administration (FDA)–cleared molecular tests for syphilis are still not available, and laboratory-developed molecular tests are limited in availability. Therefore, serological tests that detect treponemal and nontreponemal antibodies remain the mainstay for routine laboratory diagnosis of active syphilis infection.6 |
Evaluation of three automated nontreponemal rapid plasma reagin (RPR) tests for the laboratory diagnosis of syphilis
Shukla MR , Pereira L , Gaynor AM , Sun Y , Edwards D , Simmons T , Andrews CW , Park IU , Hong J , Cao W , Kersh EN , Fakile Y . J Clin Microbiol 2023 61 (6) e0016823 Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations. |
Food and Drug Administration public workshop summary-development considerations of antifungal drugs to address unmet medical need
Yasinskaya Y , Bala S , Waack U , Dixon C , Higgins K , Moore JN , Jjingo CJ , O'Shaughnessy E , Colangelo P , Botgros R , Nambiar S , Angulo D , Dane A , Chiller T , Hodges MR , Sandison T , Hope W , Walsh TJ , Pappas P , Katragkou A , Kovanda L , Rex JH , Marr KA , Ostrosky-Zeichner L , Sekine S , Deshpande M , Shukla SJ , Farley J . Clin Infect Dis 2023 77 (3) 380-387 Pressing challenges in the treatment of invasive fungal infections (IFI) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics; clinical trial endpoints; prolonged trial duration; difficulties in patient recruitment, including subpopulations (e.g., pediatrics); and heterogeneity of the IFIs. On August 4, 2020, the U.S. Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This paper summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development. |
Defining the risk of SARS-CoV-2 variants on immune protection.
DeGrace MM , Ghedin E , Frieman MB , Krammer F , Grifoni A , Alisoltani A , Alter G , Amara RR , Baric RS , Barouch DH , Bloom JD , Bloyet LM , Bonenfant G , Boon ACM , Boritz EA , Bratt DL , Bricker TL , Brown L , Buchser WJ , Carreo JM , Cohen-Lavi L , Darling TL , Davis-Gardner ME , Dearlove BL , Di H , Dittmann M , Doria-Rose NA , Douek DC , Drosten C , Edara VV , Ellebedy A , Fabrizio TP , Ferrari G , Florence WC , Fouchier RAM , Franks J , Garca-Sastre A , Godzik A , Gonzalez-Reiche AS , Gordon A , Haagmans BL , Halfmann PJ , Ho DD , Holbrook MR , Huang Y , James SL , Jaroszewski L , Jeevan T , Johnson RM , Jones TC , Joshi A , Kawaoka Y , Kercher L , Koopmans MPG , Korber B , Koren E , Koup RA , LeGresley EB , Lemieux JE , Liebeskind MJ , Liu Z , Livingston B , Logue JP , Luo Y , McDermott AB , McElrath MJ , Meliopoulos VA , Menachery VD , Montefiori DC , Mhlemann B , Munster VJ , Munt JE , Nair MS , Netzl A , Niewiadomska AM , O'Dell S , Pekosz A , Perlman S , Pontelli MC , Rockx B , Rolland M , Rothlauf PW , Sacharen S , Scheuermann RH , Schmidt SD , Schotsaert M , Schultz-Cherry S , Seder RA , Sedova M , Sette A , Shabman RS , Shen X , Shi PY , Shukla M , Simon V , Stumpf S , Sullivan NJ , Thackray LB , Theiler J , Thomas PG , Trifkovic S , Treli S , Turner SA , Vakaki MA , vanBakel H , VanBlargan LA , Vincent LR , Wallace ZS , Wang L , Wang M , Wang P , Wang W , Weaver SC , Webby RJ , Weiss CD , Wentworth DE , Weston SM , Whelan SPJ , Whitener BM , Wilks SH , Xie X , Ying B , Yoon H , Zhou B , Hertz T , Smith DJ , Diamond MS , Post DJ , Suthar MS . Nature 2022 605 (7911) 640-652 The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced following infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH) established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines, and therapeutics and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity, and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models, and pivotal findings facilitated by this collaborative approach and identify future challenges. This program serves as a template for the response against rapidly evolving pandemic pathogens by monitoring viral evolution in the human population to identify variants that could erode the effectiveness of countermeasures. |
Progress toward poliomyelitis eradication - Afghanistan, January 2020-November 2021
Sadigh KS , Akbar IE , Wadood MZ , Shukla H , Jorba J , Chaudhury S , Martinez M . MMWR Morb Mortal Wkly Rep 2022 71 (3) 85-89 Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected only in Afghanistan and Pakistan. In 2020, these countries reported their highest number of WPV1 cases since 2014 and experienced outbreaks of type 2 circulating vaccine-derived poliovirus (cVDPV2)* (1); in Afghanistan, the number of WPV1 cases reported increased 93%, from 29 in 2019 to 56 in 2020, with 308 cVDPV2 cases reported. This report describes the activities and progress toward polio eradication in Afghanistan during January 2020-November 2021 and updates previous reports (2-4). Despite restrictions imposed by antigovernment elements since 2018, disruption of polio eradication efforts by the COVID-19 pandemic, and civil and political instability, eradication activities have resumed. During January-November 2021, four WPV1 cases and 43 cVDPV2 cases were detected, representing decreases of 93% from 56 and 85% from 281, respectively, during the same period in 2020. After the assumption of nationwide control by the current de facto government of Afghanistan during August 2021, health officials committed to oral poliovirus vaccine (OPV) campaigns nationwide, with the potential to vaccinate approximately 2.5 million children against poliovirus who were previously not accessible for ≥2 years. Although challenges remain, vigorous, sustained polio eradication efforts in Afghanistan could result in substantial progress toward eradication during 2022-2023. |
Evaluation of the effect of extended refrigerated storage of serum and plasma specimens on syphilis serologic test results
Sun Y , Shukla MR , Deutsch J , Cao W , Fakile Y , Kersh EN , Pereira LE . Diagn Microbiol Infect Dis 2022 102 (2) 115588 The effect of extended refrigerated storage of 14 serum and plasma specimens on 5 syphilis serologic tests was evaluated for 16 weeks. Higher stability of nontreponemal and treponemal antibodies in serum was recorded compared to plasma. Described work may provide insights on refrigerated specimens' stability and suitability for syphilis tests. |
At-home Specimen Self-Collection and Self-Testing for STI Screening Demand Accelerated by the COVID-19 Pandemic - A Review of Laboratory Implementation Issues.
Kersh EN , Shukla M , Raphael BH , Habel M , Park I . J Clin Microbiol 2021 59 (11) Jcm0264620 The idea of specimen self-collection or self-STI testing is not new. In 2019, the World Health Organization (WHO) published the "WHO Consolidated Guideline on Self-Care Interventions for Health" as a first installment in a planned series for various diseases (8). The first document focused on "Sexual and Reproductive Health and Rights". Self-care including self-testing has the readily apparent benefits of privacy, confidentiality, speed, convenience, and access if the price is affordable. It is "people-centered" (9) and enables active participation in one's own health. It is also a health system approach as it can reduce burden on stretched systems with world-wide shortages in medical personnel or other barriers to health care access. Potential risks include: low specimen return rates, uncertain follow-up (linkage to care including treatment, repeat testing including test of cure, partner notification, counseling on risk reduction), unintended/unnecessary use (resulting in false positives with their own set of associated problems), incorrect use, lack of understanding of window periods (resulting in false negatives), lack of surveillance data generation, among other issues (9). The WHO systematically reviewed evidence for self-testing or specimen self-collection for GC, CT and syphilis, including US studies, and published a meta-analysis of available evidence (9). Programs offering self-collection of samples increased overall uptake of STI testing services (RR: 2.941, 95% CI 1.188 to 7.281) and case finding (RR: 2.166, 95% CI1.043 to 4.498), prior to the pandemic (9). U. S. laboratory research on the equivalence and/or superiority of self-collected versus provider-collected specimens for test sensitivity was reported by Gaydos et al (summarized or referenced in (10)). Based on this evidence, WHO issued a new recommendation in 2019 "Self-collection of samples for Neisseria gonorrhoeae and Chlamydia trachomatis should be made available as an additional approach to deliver STI testing services for individuals using STI testing services" (8). In addition, WHO issued a new and conditional recommendation: "Self-collection of samples for Treponema pallidum (syphilis) and Trichomonas vaginalis may be considered as an additional approach to deliver STI testing services for Individuals using STI testing services" (8). Thus, even before the COVID-19 pandemic, substantial expert agreement existed concerning benefits of this approach. |
Progress Toward Poliomyelitis Eradication - Afghanistan, January 2019-July 2020.
Martinez M , Akbar IE , Wadood MZ , Shukla H , Jorba J , Ehrhardt D . MMWR Morb Mortal Wkly Rep 2020 69 (40) 1464-1468 Wild poliovirus type 1 (WPV1) transmission is ongoing only in Afghanistan and Pakistan (1). Following a decline in case numbers during 2013-2016, the number of cases in Afghanistan has increased each year during 2017-2020. This report describes polio eradication activities and progress toward polio eradication in Afghanistan during January 2019-July 2020 and updates previous reports (2,3). Since April 2018, insurgent groups have imposed bans on house-to-house vaccination. In September 2019, vaccination campaigns in areas under insurgency control were restarted only at health facilities. In addition, during March-June 2020, all campaigns were paused because of the coronavirus disease 2019 (COVID-19) pandemic. The number of WPV1 cases reported in Afghanistan increased from 21 in 2018 to 29 in 2019. During January-July 2020, 41 WPV1 cases were reported as of August 29, 2020 (compared with 15 during January-July 2019); in addition, 69 cases of circulating vaccine-derived poliovirus type 2 (cVDPV2), and one case of ambiguous vaccine-derived poliovirus type 2 (aVDPV2) (isolates with no evidence of person-to-person transmission or from persons with no known immunodeficiency) were detected. Dialogue with insurgency leaders through nongovernmental and international organizations is ongoing in an effort to recommence house-to-house campaigns, which are essential to stopping WPV1 transmission in Afghanistan. To increase community demand for polio vaccination, additional community health needs should be addressed, and polio vaccination should be integrated with humanitarian services. |
The traditional or reverse algorithm for diagnosis of syphilis: Pros and cons
Ortiz DA , Shukla MR , Loeffelholz MJ . Clin Infect Dis 2020 71 S43-s51 We reviewed relevant syphilis diagnostic literature to address the question "What diagnostic considerations should be taken into account when screening for syphilis using the traditional or reverse algorithm?" Improved laboratory diagnosis of syphilis is an important element of the effort to reduce syphilis rates. Screening for syphilis is performed using either a nontreponemal or treponemal test (part of the traditional or reverse algorithm, respectively). Both syphilis algorithms are used by laboratories. However, there are limited data on the performance and cost-effectiveness of the algorithms. An expert panel generated "key questions" in the laboratory diagnosis of syphilis. This paper pertains to the key factors that should be considered when deciding whether to screen for syphilis using either the traditional or the reverse algorithm. A systematic literature review was performed, and tables of evidence were created to address this question. |
Development of a novel magnetic particle-based agglutination immunoassay for anticardiolipin antibody detection in syphilis
Shukla MR , Deutsch JW , Pereira LE , Kersh EN , Fakile YF . Sex Transm Infect 2020 96 (6) 411-416 OBJECTIVES: Serological tests of non-treponemal and treponemal types are the most frequently used for syphilis diagnosis. Treponemal tests are available in wide variety of assay formats; however, limited advances have been made for the improvement of conventional non-treponemal tests. The objective of this work was to develop a novel non-treponemal magnetic particle-based agglutination assay (NT-MAA) and evaluate its feasibility for syphilis testing. METHODS: Cardiolipin was modified and coupled to magnetic microbeads. Serum diluted in phosphate-buffered saline was mixed with cardiolipin-coupled beads and incubated in a round bottom microplate for 90-120 min followed by visual inspection. A panel of reported syphilis (n=127) and non-reactive (n=244) specimens was prepared to evaluate the NT-MAA performance in comparison to conventional rapid plasma reagin (RPR). Treponema pallidum particle agglutination (TP-PA) assay and enzyme immunoassay (EIA) were included. Analytical sensitivity and reproducibility of NT-MAA were also determined. RESULTS: The non-treponemal NT-MAA and RPR showed sensitivity of 90.6% and 88.2% and specificity of 96.7% and 100%, respectively. The treponemal TP-PA and EIA yielded sensitivity of 100% and 99.2%, respectively, and 100% specificity by both assays. The per cent agreement between NT-MAA and RPR was 97% (kappa=0.931, 95% CI 0.891 to 0.971). Analytical sensitivity determined with IgM anticardiolipin antibody (ACA) was 2.6 microg/mL for both NT-MAA and RPR, while IgG ACA yielded 0.9 microg/mL and 1.7 microg/mL for NT-MAA and RPR, respectively. Qualitative results of intra-assay and interassay reproducibility revealed 100% consistency for NT-MAA. CONCLUSION: Preliminary evaluation of the novel NT-MAA validated proof of concept using laboratory-characterised syphilis sera and demonstrated performance comparable to RPR. Further validation of NT-MAA using additional specimens with better clinical staging may broaden the scope of developed test for syphilis diagnosis. |
Development of a syphilis serum bank to support research, development, and evaluation of syphilis diagnostic tests in the United States
Shukla M , Sun Y , McCormick J , Hopkins A , Pereira L , Gaynor A , Kersh E , Fakile Y . Diagn Microbiol Infect Dis 2019 96 (1) 114913 The Centers for Disease Control and Prevention's (CDC) Division of STD Prevention, in collaboration with the Association of Public Health Laboratories (APHL), is developing a nationally available syphilis serum repository for research of Food and Drug Administration (FDA)-cleared or investigational syphilis diagnostic assays in the United States. State and local public health laboratories (PHL) submitted de-identified residual sera with information on collection date, volume, storage conditions, freeze-thaw cycles, PHL serology results, reported syphilis stage and demographic details if available. Previous test results were blinded and sera (N = 152 reported syphilis stage, N = 131 unknown status) were tested at CDC using five FDA-cleared and one investigational syphilis tests. Treponemal and nontreponemal test sensitivity ranged from 76.3-100% and 63.2-100%, respectively, among staged specimens. The conventional treponemal assays showed high concordance of 95.4%. By providing syphilis stage and comprehensive serological test data, developed repository may serve as a valuable resource for diagnostic test validation studies. |
Progress Toward Poliomyelitis Eradication - Afghanistan, January 2018-May 2019.
Martinez M , Shukla H , Nikulin J , Mbaeyi C , Jorba J , Ehrhardt D . MMWR Morb Mortal Wkly Rep 2019 68 (33) 729-733 Since October 2016, Afghanistan and Pakistan have been the only countries with reported cases of wild poliovirus type 1 (WPV1) (1). In Afghanistan, although the number of cases had declined during 2013-2016, the polio eradication program experienced challenges during 2017-2019. This report describes polio eradication activities and progress in Afghanistan during January 2018-May 2019 and updates previous reports (2,3). During May-December 2018, insurgent groups (antigovernment elements) banned house-to-house vaccination in most southern and southeastern provinces, leaving approximately 1 million children inaccessible to oral poliovirus vaccine (OPV) administration. During January-April 2019, vaccination targeting children at designated community sites (site-to-site vaccination) was permitted; however, at the end of April 2019, vaccination campaigns were banned nationally. During 2018, a total of 21 WPV1 cases were reported in Afghanistan, compared with 14 during 2017. During January-May 2019, 10 WPV1 cases were reported (as of May 31), compared with eight during January-May 2018. Sewage sample-testing takes place at 20 sites in the highest-risk areas for poliovirus circulation; 17 have detected WPV1 since January 2017, primarily in the southern and eastern provinces. Continued discussion with antigovernment elements to resume house-to-house campaigns is important to achieving polio eradication in Afghanistan. To increase community support for vaccination, collaboration among humanitarian service agencies to address other urgent health and basic needs is critical. |
Developing a model to predict unfavourable treatment outcomes in patients with tuberculosis and human immunodeficiency virus co-infection in Delhi, India
Madan C , Chopra KK , Satyanarayana S , Surie D , Chadha V , Sachdeva KS , Khanna A , Deshmukh R , Dutta L , Namdeo A , Shukla A , Sagili K , Chauhan LS . PLoS One 2018 13 (10) e0204982 BACKGROUND: Tuberculosis (TB) patients with human immunodeficiency virus (HIV) co-infection have worse TB treatment outcomes compared to patients with TB alone. The distribution of unfavourable treatment outcomes differs by socio-demographic and clinical characteristics, allowing for early identification of patients at risk. OBJECTIVE: To develop a statistical model that can provide individual probabilities of unfavourable outcomes based on demographic and clinical characteristics of TB-HIV co-infected patients. METHODOLOGY: We used data from all TB patients with known HIV-positive test results (aged >/=15 years) registered for first-line anti-TB treatment (ATT) in 2015 under the Revised National TB Control Programme (RNTCP) in Delhi, India. We included variables on demographics and pre-treatment clinical characteristics routinely recorded and reported to RNTCP and the National AIDS Control Organization. Binomial logistic regression was used to develop a statistical model to estimate probabilities of unfavourable TB treatment outcomes (i.e., death, loss to follow-up, treatment failure, transfer out of program, and a switch to drug-resistant regimen). RESULTS: Of 55,260 TB patients registered for ATT in 2015 in Delhi, 928 (2%) had known HIV-positive test results. Of these, 816 (88%) had drug-sensitive TB and were >/=15 years. Among 816 TB-HIV patients included, 157 (19%) had unfavourable TB treatment outcomes. We developed a model for predicting unfavourable outcomes using age, sex, disease classification (pulmonary versus extra-pulmonary), TB treatment category (new or previously treated case), sputum smear grade, known HIV status at TB diagnosis, antiretroviral treatment at TB diagnosis, and CD4 cell count at ATT initiation. The chi-square p-value for model calibration assessed using the Hosmer-Lemeshow test was 0.15. The model discrimination, measured as the area under the receiver operator characteristic (ROC) curve, was 0.78. CONCLUSION: The model had good internal validity, but should be validated with an independent cohort of TB-HIV co-infected patients to assess its performance before clinical or programmatic use. |
Longevity of adenovirus vector immunity in mice and its implications for vaccine efficacy
Sayedahmed EE , Kumari R , Shukla S , Hassan AO , Mohammed SI , York IA , Gangappa S , Sambhara S , Mittal SK . Vaccine 2018 36 (45) 6744-6751 There is a high incidence of adenovirus (AdV) infection in humans due to the presence of more than 60 types of human adenoviruses (HAdVs). The majority of individuals are exposed to one or more HAdV types early in their lives, leading to the development of AdV type-specific neutralizing antibodies. Similarly, immunization or gene therapy with AdV vectors leads to immune responses to the AdV vector. This 'vector immunity' is a concern for AdV vector-based applications for vaccines or gene therapy, especially when the repeated administration of a vector is required. The objective of this investigation was to establish whether AdV neutralizing antibody titers decline sufficiently in a year to permit annual vaccination with the same AdV vector. Naive or human adenoviral vector group C, type 5 (HAdV-C5)-primed mice were mock-inoculated (with PBS) or inoculated i.m. with 10(8)PFU of either HAd-GFP [HAdV-C5 vector expressing the green fluorescent protein (GFP)] to mimic the conditions for the first inoculation with an AdV vector-based vaccine. At 1, 3, 6, and 10months post-HAd-GFP inoculation, naive- or HAdV-primed animals were vaccinated i.m. with 10(8)PFU of HAd-H5HA [HAdV-C5 vector expressing hemagglutinin (HA) of H5N1 influenza virus]. There was a significant continual decrease in vector immunity titers with time, thereby leading to significant continual increases in the levels of HA-specific humoral and cell-mediated immune responses. In addition, significant improvement in protection efficacy against challenge with an antigenically heterologous H5N1 virus was observed in HAdV-primed animals at 6months and onwards. These results indicate that the annual immunization with the same AdV vector may be effective due to a significant decline in vector immunity. |
Progress toward poliomyelitis eradication - Afghanistan, January 2017-May 2018
Martinez M , Shukla H , Ahmadi M , Inulin J , Widodo MS , Ahmed J , Mbaeyi C , Jabra J , Gerhardt D . MMWR Morb Mortal Wkly Rep 2018 67 (30) 833-837 Afghanistan, Pakistan, and Nigeria remain the only countries where transmission of endemic wild poliovirus type 1 (WPV1) continues (1). This report describes polio eradication activities, progress, and challenges to eradication in Afghanistan during January 2017-May 2018 and updates previous reports (2, 3). Fourteen WPV1 cases were confirmed in Afghanistan in 2017, compared with 13 in 2016; during January-May 2018, eight WPV1 cases were reported, twice the number reported during January-May 2017. To supplement surveillance for acute flaccid paralysis (AFP) and laboratory testing of stool samples, environmental surveillance (testing of sewage samples) was initiated in 2013 and includes 20 sites, 15 of which have detected WPV1 circulation. The number of polio-affected districts increased from six in 2016 to 14 in 2017 (including WPV1 cases and positive environmental samples). Access to children for supplementary immunization activities (SIAs) (mass campaigns targeting children aged <5 years with oral poliovirus vaccine [OPV], regardless of vaccination history), which improved during 2016 to early 2018, worsened in May 2018 in security-challenged areas of the southern and eastern regions. To achieve WPV1 eradication, measures to maintain and regain access for SIAs in security-challenged areas, strengthen oversight of SIAs in accessible areas to reduce the number of missed children, and coordinate with authorities in Pakistan to track and vaccinate mobile populations at high risk in their shared transit corridors must continue. |
Laboratory evaluation of a commercially available rapid syphilis test
Pereira LE , McCormick J , Dorji T , Kang J , Sun Y , Shukla M , Hopkins A , Deutsch J , Kersh EN , Bernstein K , Fakile YF . J Clin Microbiol 2018 56 (10) Serological diagnosis of syphilis depends on assays that detect treponemal and non-treponemal antibodies. Laboratory certification and trained personnel are needed to perform most of these tests, while high costs and long turnaround time can hinder treatment initiation or linkage to care. A rapid treponemal syphilis test (RST) that is simple to perform, accessible and inexpensive would be ideal. The Syphilis Health Check (SHC) assay is the only Food and Drug Administration (FDA)-cleared and Clinical Laboratory Improvement Amendments (CLIA)-waived RST in the US. In this study, 1,406 archived human sera were tested using SHC and traditional treponemal and non-treponemal assays. Rapid test results were compared with treponemal data alone, and with a laboratory test panel consensus defined as being reactive by both treponemal and non-treponemal assays for a given specimen, or nonreactive by both types of assays. Sensitivity and specificity of SHC when compared with treponemal tests alone were 88.7% (86.2-90.0%) and 93.1% (90.0-94.9%), respectively, while comparison with the laboratory test panel consensus showed 95.7% (93.6-97.2%) sensitivity and 93.2% (91.0-95.1%) specificity. The data were further stratified based on age, sex, pregnancy and HIV status. Sensitivity and specificity of SHC ranged from 66.7% (46.0-83.5%) to 91.7% (87.7-94.7%) and 88% (68.8-97.5%) to 100% (47.8-100%), respectively, across groups when compared to traditional treponemal assays, generally increasing for all groups except the HIV+ population when factoring the laboratory test panel consensus. These data contribute to current knowledge of SHC performance for distinct populations and may guide use in various settings. |
Progress toward poliomyelitis eradication - Afghanistan, January 2016-June 2017
Martinez M , Shukla H , Nikulin J , Wadood MZ , Hadler S , Mbaeyi C , Tangermann R , Jorba J , Ehrhardt D . MMWR Morb Mortal Wkly Rep 2017 66 (32) 854-858 Afghanistan, Pakistan, and Nigeria remain the only countries where the transmission of endemic wild poliovirus type 1 (WPV1) continues (1). This report describes polio eradication activities, progress, and challenges in Afghanistan during January 2016-June 2017 and updates previous reports (2,3). Thirteen WPV1 cases were confirmed in Afghanistan in 2016, a decrease of seven from the 20 cases reported in 2015. From January to June 2017, five WPV1 cases were reported, compared with six during the same period in 2016. The number of affected districts declined from 23 (including WPV1-positive acute flaccid paralysis [AFP] cases and positive environmental sewage samples) in 2015 to six in 2016. To achieve WPV1 eradication, it is important that Afghanistan's polio program continue to collaborate with that of neighboring Pakistan to track and vaccinate groups of high-risk mobile populations and strengthen efforts to reach children in security-compromised areas. |
Progress toward poliomyelitis eradication - Afghanistan, January 2015-August 2016
Mbaeyi C , Shukla H , Smith P , Tangermann RH , Martinez M , Jorba JC , Hadler S , Ehrhardt D . MMWR Morb Mortal Wkly Rep 2016 65 (43) 1195-1199 Only 74 cases of wild poliovirus (WPV) were reported globally in 2015, the lowest number of cases ever reported worldwide (1,2). All of the reported cases were WPV type 1 (WPV1), the only known WPV type still circulating; WPV type 2 has been eradicated, and WPV type 3 has not been detected since November 2012 (1). In 2015 in Afghanistan, WPV detection also declined from 2014, and trends observed in 2016 suggest that circulation of the virus is limited to a few localized areas. Despite the progress, there are concerns about the ability of the country's Polio Eradication Initiative (PEI) to meet the goal of interrupting endemic WPV transmission by the end of 2016 (3). The deteriorating security situation in the Eastern and Northeastern regions of the country considerably limits the ability to reach and vaccinate children in these regions. Furthermore, because of frequent population movements to and from Pakistan, cross-border transmission of WPV1 continues (4). Although the national PEI has taken steps to improve the quality of supplementary immunization activities (SIAs),* significant numbers of children living in accessible areas are still being missed during SIAs, and routine immunization services remain suboptimal in many parts of the country. This report describes polio eradication activities and progress in Afghanistan during January 2015August 2016 and updates previous reports (5,6). During 2015, a total of 20 WPV1 cases were reported in Afghanistan, compared with 28 cases in 2014; eight cases were reported during JanuaryAugust 2016, compared with nine cases reported during the same period in 2015. To achieve interruption of poliovirus transmission in Afghanistan, it is important that the 2016-2017 National Emergency Action Plandagger for polio eradication be systematically implemented, including 1) improving the quality of SIAs and routine immunization services, 2) ensuring ongoing dialogue between PEI leaders and local authorities, 3) adopting innovative strategies for reaching children in security-compromised and inaccessible areas, and 4) strengthening cross-border coordination of polio vaccination and surveillance activities with Pakistan. |
Current research and opportunities to address environmental asbestos exposures
Carlin DJ , Larson TC , Pfau JC , Gavett SH , Shukla A , Miller A , Hines R . Environ Health Perspect 2015 123 (8) A194-7 Asbestos-related diseases continue to result in approximately 120,000 deaths every year in the United States and worldwide. Although extensive research has been conducted on health effects of occupational exposures to asbestos, many issues related to environmental asbestos exposures remain unresolved. For example, environmental asbestos exposures associated with a former mine in Libby, Montana, have resulted in high rates of nonoccupational asbestos-related disease. Additionally, other areas with naturally occurring asbestos deposits near communities in the United States and overseas are undergoing investigations to assess exposures and potential health risks. Some of the latest public health, epidemiological, and basic research findings were presented at a workshop on asbestos at the 2014 annual meeting of the Society of Toxicology in Phoenix, Arizona. The following focus areas were discussed: a) mechanisms resulting in fibrosis and/or tumor development; b) relative toxicity of different forms of asbestos and other hazardous elongated mineral particles (EMPs); c) proper dose metrics (e.g., mass, fiber number, or surface area of fibers) when interpreting asbestos toxicity; d) asbestos exposure to susceptible populations; and e) using toxicological findings for risk assessment and remediation efforts. The workshop also featured asbestos research supported by the National Institute of Environmental Health Sciences, the Agency for Toxic Substances and Disease Registry, and the U.S. Environmental Protection Agency. Better protection of individuals from asbestos-related health effects will require stimulation of new multidisciplinary research to further our understanding of what constitutes hazardous exposures and risk factors associated with toxicity of asbestos and other hazardous EMPs (e.g., nanomaterials). |
Field evaluation of a real-time fluorescence loop-mediated isothermal amplification assay, RealAmp, for the diagnosis of malaria in Thailand and India
Patel JC , Lucchi NW , Srivastava P , Lin JT , Sug-Aram R , Aruncharus S , Bharti PK , Shukla MM , Congpuong K , Satimai W , Singh N , Udhayakumar V , Meshnick SR . J Infect Dis 2014 210 (8) 1180-7 BACKGROUND: To eliminate malaria, surveillance for submicroscopic infections is needed. Molecular methods can detect submicroscopic infections but have not hitherto been amenable to implementation in surveillance programs. A portable loop-mediated isothermal amplification assay called RealAmp was assessed in 2 areas of low malaria transmission. METHODS: RealAmp was evaluated in 141 patients from health clinics in India (passive surveillance) and in 127 asymptomatic persons in Thailand (active surveillance). The diagnostic validity, precision, and predictive value of RealAmp were determined using polymerase chain reaction (PCR) as the reference method. A pilot study of RealAmp was also performed on samples from patients presenting at a Thai health center. RESULTS: A total of 96 and 7 positive cases were detected in India and Thailand, respectively, via PCR. In comparison with nested PCR, the sensitivity and specificity of RealAmp in India were 94.8% (95% confidence interval [CI], 88.3%-98.3%) and 100% (95% CI, 92.1%-100%), respectively, with correct identification of all 5 Plasmodium vivax cases. In Thailand, compared with pooled real-time PCR, RealAmp demonstrated 100% sensitivity (95% CI, 59.0%-100%) and 96.7% specificity (95% CI, 91.7%-99.1%). Testing at the health center demonstrated RealAmp's potential to serve as a point-of-care test with results available in 30-75 minutes. CONCLUSION: RealAmp was comparable to PCR in detecting malaria parasites and shows promise as a tool to detect submicroscopic infections in malaria control and elimination programs worldwide. |
Cross-sectional serologic assessment of immunity to poliovirus infection in high-risk areas of northern India
Bahl S , Estivariz CF , Sutter RW , Sarkar BK , Verma H , Jain V , Agrawal A , Rathee M , Shukla H , Pathyarch SK , Sethi R , Wannemuehler KA , Jafari H , Deshpande JM . J Infect Dis 2014 210 Suppl 1 S243-51 INTRODUCTION: The objectives of this survey were to assess the seroprevalence of antibodies to poliovirus types 1 and 3 and the impact of bivalent (types 1 and 3) oral poliovirus vaccine (bOPV) use in immunization campaigns in northern India. METHODS: In August 2010, a 2-stage stratified cluster sampling method identified infants aged 6-7 months in high-risk blocks for wild poliovirus infection. Vaccination history, weight and length, and serum were collected to test for neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS: Seroprevalences of antibodies to poliovirus types 1, 2, and 3 were 98% (95% confidence interval [CI], 97%-99%), 66% (95% CI, 62%-69%), and 77% (95% CI, 75%-79%), respectively, among 664 infants from Bihar and 616 infants from Uttar Pradesh. Infants had received a median of 3 bOPV doses and 2 monovalent type 1 OPV (mOPV1) doses through campaigns and 3 trivalent OPV (tOPV) doses through routine immunization. Among subjects with 0 tOPV doses, the seroprevalences of antibodies to type 3 were 50%, 77%, and 82% after 2, 3, and 4 bOPV doses, respectively. In multivariable analysis, malnutrition was associated with a lower seroprevalence of type 3 antibodies. CONCLUSIONS: This study confirmed that replacing mOPV1 with bOPV in campaigns was successful in maintaining very high population immunity to type 1 poliovirus and substantially decreasing the immunity gap to type 3 poliovirus. |
Effectiveness of oral polio vaccination against paralytic poliomyelitis: a matched case-control study in Somalia
Mahamud A , Kamadjeu R , Webeck J , Mbaeyi C , Baranyikwa MT , Birungi J , Nurbile Y , Ehrhardt D , Shukla H , Chatterjee A , Mulugeta A . J Infect Dis 2014 210 Suppl 1 S187-93 BACKGROUND: After the last case of type 1 wild poliovirus (WPV1) was reported in 2007, Somalia experienced another outbreak of WPV1 (189 cases) in 2013. METHODS: We conducted a retrospective, matched case-control study to evaluate the vaccine effectiveness (VE) of oral polio vaccine (OPV). We retrieved information from the Somalia Surveillance Database. A case was defined as any case of acute flaccid paralysis (AFP) with virological confirmation of WPV1. We selected two groups of controls for each case: non-polio AFP cases ("NPAFP controls") matched to WPV1 cases by age, date of onset of paralysis and region; and asymptomatic "neighborhood controls," matched by age. Using conditional logistic regression, we estimated the VE of OPV as (1- odds ratio) x100. RESULT: We matched 99 WPV cases with 99 NPAFP controls and 134 WPV1 cases with 268 neighborhood controls. Using NPAFP controls, the overall VE was 70% (95% confidence interval [CI], 37-86), 59% (2-83) among 1-3 dose recipients, 77% (95% CI, 46-91) among ≥4 dose recipients. In neighborhood controls, the overall VE was 95% (95% CI, 84-98), 92% (72-98) among 1-3 dose recipients, and 97% (89-99) among ≥4 dose recipients. When the analysis was limited to cases and controls ≤24 months old, the overall VE in NPAFP and neighborhood controls was 95% (95% CI, 65-99) and 97% (95% CI, 76-100), respectively. CONCLUSIONS: Among individuals who were fully vaccinated with OPV, vaccination was effective at preventing WPV1 in Somalia. |
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