Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 45 Records) |
Query Trace: Verma S[original query] |
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Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine
Bhatla N , Muwonge R , Malvi SG , Joshi S , Poli URR , Lucas E , Esmy PO , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Vashist S , Mishra G , Jadhav R , Siddiqi M , Anantharaman D , Panicker G , Butt J , Sankaran S , Kannan Tpra , Varghese R , Kartha P , Pillai MR , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Hum Vaccin Immunother 2023 19 (3) 2289242 Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier. |
Range of the perfluorooctanoate (PFOA) safe dose for human health: An international collaboration
Burgoon LD , Clewell HJ , Cox T , Dekant W , Dell LD , Deyo JA , Dourson ML , Gadagbui BK , Goodrum P , Green LC , Vijayavel K , Kline TR , House-Knight T , Luster MI , Manning T , Nathanail P , Pagone F , Richardson K , Severo-Peixe T , Sharma A , Smith JS , Verma N , Wright J . Regul Toxicol Pharmacol 2023 145 Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different. This sort of discrepancy invites scrutiny and explanation. Otherwise what is the lay public to make of this disparity? The Steering Committee of the Alliance for Risk Assessment (2022) called for scientists interested in attempting to understand and narrow these disparities. An advisory committee of nine scientists from four countries was selected from nominations received, and a subsequent invitation to scientists internationally led to the formation of three technical teams (for a total of 24 scientists from 8 countries). The teams reviewed relevant information and independently developed ranges for estimated PFOA safe doses. All three teams determined that the available epidemiologic information could not form a reliable basis for a PFOA safe dose-assessment in the absence of mechanistic data that are relevant for humans at serum concentrations seen in the general population. Based instead on dose-response data from five studies of PFOA-exposed laboratory animals, we estimated that PFOA dose-rates 10–70 ng/kg-day are protective of human health. © 2023 Elsevier Inc. |
Persistence of immunity following a single dose of inactivated poliovirus vaccine: a phase 4, open label, non-randomised clinical trial
Sharma AK , Verma H , Estivariz CF , Bajracharaya L , Rai G , Shah G , Sherchand J , Jones KAV , Mainou BA , Chavan S , Jeyaseelan V , Sutter RW , Shrestha LP . Lancet Microbe 2023 4 (11) e923-e930 BACKGROUND: The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. METHODS: In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ(2) to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. FINDINGS: From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. INTERPRETATION: A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. FUNDING: WHO and Rotary International. |
A new WHO bottle bioassay method to assess the susceptibility of mosquito vectors to public health insecticides: results from a WHO-coordinated multi-centre study
Corbel V , Kont MD , Ahumada ML , Andréo L , Bayili B , Bayili K , Brooke B , Pinto Caballero JA , Lambert B , Churcher TS , Duchon S , Etang J , Flores AE , Gunasekaran K , Juntarajumnong W , Kirby M , Davies R , Lees RS , Lenhart A , Lima JBP , Martins AJ , Müller P , N'Guessan R , Ngufor C , Praulins G , Quinones M , Raghavendra K , Verma V , Rus AC , Samuel M , Ying KS , Sungvornyothin S , Uragayala S , Velayudhan R , Yadav RS . Parasit Vectors 2023 16 (1) 21 BACKGROUND: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both. METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC(50) and LC(99), respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI(50) and OI(99)), to measure mortality and the sterilizing effect, respectively. RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC(50)/LC(99) or OI(50)/OI(99) values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were < 10% for most mosquito species-insecticide combinations. CONCLUSION: Our findings, based on the largest susceptibility dataset ever produced on mosquitoes, showed that the new WHO bottle bioassay is adequate for evaluating mosquito susceptibility to new and promising public health insecticides currently deployed for vector control. The datasets presented in this study have been used recently by the WHO to establish 17 new insecticide discriminating concentrations (DCs) for either Aedes spp. or Anopheles spp. The bottle bioassay and DCs can now be widely used to monitor baseline insecticide susceptibility of wild populations of vectors of malaria and Aedes-borne diseases worldwide. |
Community-based survey to assess seroprevalence of poliovirus antibodies in far-north Cameroon in 2020
ClaireEndegue M , Sein C , LopezCavestany R , Jeyaseelan V , Palmer T , NorbertSoke G , Diaha A , Jafri B , Mainou BA , Verma H , Mach O . Vaccine X 2022 12 100244 BACKGROUND: This study assessed seroprevalence of poliovirus antibodies in children from selected poliovirus high-risk areas of the Far North region of Cameroon which serves to monitor polio immunization program. METHODS: This was a community-based cross-sectional seroprevalence survey involving collection of dried blood specimens (DBS) among children aged 12-59months (n=401). Multi-stage cluster sampling using GIS was applied to select the study sample. Collected DBS were analysed with microneutralization assays for poliovirus neutralizing antibody levels. RESULTS: The overall seroprevalence of types 1, 2 and 3 neutralizing antibodies were 86.8% (95% confidence interval [CI]: 83.1-89.8), 74.6% (95% CI: 70.1-78.6) and 79.3% (95% CI: 75.1-83.0), respectively. Median titers (log(2) scale) for type 1, 2 and 3 were 7.17 (6.5-7.5), 5.17 (4.83-5.5), and 6.17 (5.5-6.5), respectively. There was an increasing trend in median titers and seroprevalence with age, statistically significant between the youngest and oldest age groups (p<0.001). CONCLUSION: Though there were several opportunities for vaccination through supplementary immunization activities (SIA) and routine immunization (RI), seroprevalence levels were low for all three serotypes, particularly for type 2. This highlights the need to strengthen RI and SIA quality coverage. Low population immunity makes Cameroon vulnerable to new importations and spread of polioviruses. |
Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination
Joshi S , Anantharaman D , Muwonge R , Bhatla N , Panicker G , Butt J , Rani Reddy Poli U , Malvi SG , Esmy PO , Lucas E , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Divate U , Vashist S , Mishra G , Jadhav R , Siddiqi M , Sankaran S , Pillai Rameshwari Ammal Kannan T , Kartha P , Shastri SS , Sauvaget C , Radhakrishna Pillai M , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Vaccine 2022 41 (1) 236-245 BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination. |
Utility of the lateral flow urine lipoarabinomannan tuberculosis assay in patients with advanced HIV disease at antiretroviral therapy centres in Mumbai, India
Acharya S , Deshpande P , Asirvatham ES , Palkar A , Sarman CJ , Laxmeshwar C , Setia MS , Rathod D , Koli S , Dale J , Yeldandi V , Allam R , Agarwal R , Verma S , Upadhyaya S , Nyendak M . PLoS One 2022 17 (9) e0273970 BACKGROUND: People with Advanced HIV Disease (AHD) are at higher risk of TB coinfection and mortality. However, there are challenges in TB diagnosis with the currently recommended diagnostic tools. WHO recommends lateral flow urine lipoarabinomannan (LF-LAM) assay to assist TB diagnosis among AHD patients. We assessed the utility and acceptability of using urine LF-LAM assay for TB diagnosis among patients at public Antiretroviral Therapy (ART) Centres in Mumbai. METHODS: The cross-sectional study was conducted among adult AHD patients accessing care from 17 ART centres during November,2020-June, 2021. Urine LF-LAM was offered as routine care for eligible patients in combination with standard diagnostic tests. We calculated the proportion of positive LF-LAM results by CD4 categories and TB symptoms and performed multivariable logistic regression to determine the factors associated with LF-LAM positivity. RESULTS: Among 2,390 patients, the majority (74.5%) had CD4 between 101-200 cells/mm3. The mean age was 43.7 years (SD:10.6), 68.6% were male, 8.4% had TB symptoms and 88.0% were on ART. The overall proportion of patients with urine LF-LAM positive results was 6.4%. Among PLHIV with CD4≤100 cells/mm3, the positivity was 43.0% and 7.7% in symptomatic and asymptomatic patients, respectively. Among PLHIV with a CD4>100 cells/mm3, the positivity was 26.7% and 2.7% in symptomatic and asymptomatic patients respectively. Urine LF-LAM positivity was higher among inpatients, ART naïve, patients on treatment for <6 months, symptomatic and in WHO clinical stage III/IV of HIV disease as compared to the reference categories. We detected an additional 131 TB cases with urine LF-LAM in combination with the standard diagnostic tests. CONCLUSION: The study demonstrated the utility of urine LF-LAM for TB diagnosis among AHD patients and the simple, user-friendly test was acceptable as part of routine care. Inclusion of urine LF-LAM test in the current diagnostic algorithm may facilitate early TB diagnosis among AHD patients. |
Seroprevalence of AAV neutralizing antibodies in males with Duchenne muscular dystrophy.
Verma S , Nwosu SN , Razdan R , Upadhyayula SR , Phan HC , Koroma AA , Leguizamo I , Correa NS , Kuipa M , Lee D , Vanderford TH , Gardner MR . Hum Gene Ther 2022 34 430-438 Adeno-associated virus (AAV) based gene therapies are emerging strategies in Duchenne muscular dystrophy (DMD) treatment. Exposure to wild-type AAV can lead to development of neutralizing antibodies (NAb) and block AAV transduction, thereby limiting the delivery of AAV vector-based gene therapy. Therefore, it is imperative to check for the presence of AAV NAbs in a patient who is a candidate for gene therapy. We prospectively enrolled 101 genetically confirmed males with DMD (median age 11 years, 48% ambulatory, 59% on steroids) and performed AAV neutralization assays against AAV2, AAV8, AAV9, and AAVrh74 serotypes. Serotype analysis showed AAV9 (36%) and AAVrh74 (32%) seroprevalence was lower compared to AAV2 (56%) and AAV8 (47%). Interestingly, age was not correlated with NAb titer for any of the capsids. NAb responses were observed at a higher frequency in African American participants and at a lower frequency for Caucasian participants for all four serotypes. Further analysis showed no significant differences in NAb titers depending, regardless of serotype, on whether participants were taking steroids. Finally, we observed higher AAV8, AAV9, and AAVrh74 seroprevalence and significantly higher AAV2 and AAV8 NAb titers in participants that were ambulatory compared to the non-ambulatory participants. Overall, these data identify AAV9 and AAVrh74 as the two serotypes with lower preexisting NAbs in this study's cohort of 101 males with DMD, possibly showing their utility for future gene therapy applications to treat this cohort men with DMD. |
Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study
Mathur P , Malpiedi P , Walia K , Srikantiah P , Gupta S , Lohiya A , Chakrabarti A , Ray P , Biswal M , Taneja N , Rupali P , Balaji V , Rodrigues C , Lakshmi Nag V , Tak V , Venkatesh V , Mukhopadhyay C , Deotale V , Padmaja K , Wattal C , Bhattacharya S , Karuna T , Behera B , Singh S , Nath R , Ray R , Baveja S , Fomda BA , Sulochana Devi K , Das P , Khandelwal N , Verma P , Bhattacharyya P , Gaind R , Kapoor L , Gupta N , Sharma A , VanderEnde D , Siromany V , Laserson K , Guleria R . Lancet Glob Health 2022 10 (9) e1317-e1325 BACKGROUND: Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available. METHODS: A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis. FINDINGS: 26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp. INTERPRETATION: The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies. FUNDING: US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section. |
One full or two fractional doses of inactivated poliovirus vaccine for catch-up vaccination in older infants: A randomized clinical trial in Bangladesh
Aziz AB , Verma H , Jeyaseelan V , Md Y , Nowrin S , Moore DD , Mainou BA , Mach O , Sutter RW , Zaman K . J Infect Dis 2022 226 (8) 1319-1326 BACKGROUND: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine and introduction of bivalent (types 1&3) OPV (bOPV) and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. METHODS: We conducted an open-label randomized clinical trial assessing two interventions, full or fractional-dose IPV (fIPV, 1/5 of IPV), administered at age 9-13 months with a second dose given two-months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. RESULTS: A single fIPV dose at age 9-13 months yielded 75% (95%CI:68-82) seroconversion against type 2, whereas two fIPV doses resulted in 100% seroconversion compared with 94% (95%CI: 89-97) after a single full dose (p < 0.001). Two doses of IPV resulted in 100% seroconversion. CONCLUSIONS: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either one full dose of IPV or two doses of fIPV could be used to vaccinate missed cohorts, two fIPV doses being antigen-sparing and more immunogenic. CLINICAL TRIAL REGISTRY: This trial was registered with ClinicalTrials.gov, number NCT03890497. |
Intradermal administration of fractional doses of the inactivated poliovirus vaccine in a campaign: a pragmatic, open-label, non-inferiority trial in The Gambia
Bashorun AO , Badjie Hydara M , Adigweme I , Umesi A , Danso B , Johnson N , Sambou NA , Fofana S , Kanu FJ , Jeyaseelan V , Verma H , Weldon WC , Oberste MS , Sutter RW , Jeffries D , Wathuo M , Mach O , Clarke E . Lancet Glob Health 2022 10 (2) e257-e268 BACKGROUND: A rapid increase in circulating vaccine-derived poliovirus type 2 outbreaks, and the need to reserve inactivated poliovirus vaccine (IPV) for routine immunisation, has increased the value of fractional dose IPV (fIPV) as a measure to prevent acute flaccid paralysis. However, the intradermal route of administration has been viewed as prohibitive to outbreak response campaigns. We aimed to establish the immunogenicity and safety of administering intradermal fIPV with a disposable syringe jet injector (DSJI) or an intradermal adaptor (IDA) compared with standard administration with a BCG needle and syringe (N&S). METHODS: This pragmatic, non-inferiority trial was undertaken in a campaign setting in communities in The Gambia. Children aged 4-59 months without contraindication to vaccination were eligible. Children were not individually randomly assigned; instead, the vaccination teams were randomly assigned (1:1:1) to one of three administration methods. Parents and the field team were not masked, but laboratory personnel were masked. Baseline demographic and anthropometric data were collected from the participants. Public health officers experienced at intradermal immunisation, and nurses without experience, had 2 h of training on each of the administration methods before the campaign. Participants were vaccinated using the administration method in use by the vaccination team in their community. Poliovirus serum neutralising antibodies (SNA) were measured in children aged 24-59 months before and 4 weeks after vaccination. Adverse events and data on injection quality were collected from all participants. The primary outcome was the type 2 immune response rate (seroconversion in seronegative [SNA titre <8] children plus a 4-fold titre rise in seropositive children). Adjusted differences in the immune response between the DSJI or IDA group versus the N&S group were calculated with 97·5% CIs. A margin of -10% was used to define the non-inferiority of DSJI or IDA compared to N&S. Immunogenicity analysis was done per protocol. The trial is registered with ClinicalTrials.govNCT02967783 and has been completed. FINDINGS: Between Oct 28 and Dec 29, 2016, 3189 children aged 4-59 months were recruited, of whom 3170 were eligible. Over 3 days, 2720 children were vaccinated (N&S, 917; IDA, 874; and DSJI, 929). Among 992 children aged 25-59 months with a baseline SNA available, 90·1% (95% CI 86·1-92·9; 281/312) of those vaccinated using the DSJI had an immune response to type 2 compared with 93·8% (90·6-95·8; 331/353) of those vaccinated with N&S and 96·6% (94·0-98·0; 316/327) of those vaccinated with IDA. All (53/53) type 2 seronegative children seroconverted. For polio type 2, non-inferiority was shown for both the IDA (adjusted difference 0·7% [97·5% CI -3·3 to 4·7], unadjusted difference 2·9% [-0·9 to 6·8]) and DSJI (adjusted difference -3·3% [-8·3 to 1·5], unadjusted difference -3·7% [-8·7 to 1·1]) compared with N&S. Non-inferiority was shown for type 1 and 3 for the IDA and DSJI. Neither injection quality nor the training and experience of the vaccinators had an effect on immune response. No safety concerns were reported. INTERPRETATION: In a campaign, intradermal fIPV is safe and generates consistent immune responses that are not dependent on vaccinator experience or injection quality when administered using an N&S, DSJI, or IDA. Countries facing vaccine-derived poliovirus type 2 outbreaks should consider fIPV campaigns to boost population immunity and prevent cases of acute flaccid paralysis. FUNDING: World Health Organization and the Medical Research Council. |
Challenges of and Solutions for Developing Tailored Video Interventions That Integrate Multiple Digital Assets to Promote Engagement and Improve Health Outcomes: Tutorial.
Harshbarger C , Burrus O , Rangarajan S , Bollenbacher J , Zulkiewicz B , Verma R , Galindo CA , Lewis MA . JMIR Mhealth Uhealth 2021 9 (3) e21128 BACKGROUND: Video is a versatile and popular medium for digital health interventions. As mobile device and app technology advances, it is likely that video-based interventions will become increasingly common. Although clinic waiting rooms are complex and busy environments, they offer the opportunity to facilitate engagement with video-based digital interventions as patients wait to see their providers. However, to increase efficiency in public health, leverage the scalability and low cost of implementing digital interventions, and keep up with rapidly advancing technology and user needs, more design and development guidance is needed for video-based tailored interventions. OBJECTIVE: We provide a tutorial for digital intervention researchers and developers to efficiently design and develop video-based tailored digital health interventions. We describe the challenges and solutions encountered with Positive Health Check (PHC), a hybrid app used to deliver a brief, interactive, individually tailored video-based HIV behavioral counseling intervention. PHC uses video clips and multimedia digital assets to deliver intervention content, including interactive tailored messages and graphics, a repurposed animated video, and patient and provider handouts generated in real time by PHC. METHODS: We chronicle multiple challenges and solutions for the following: (1) using video as a medium to enhance user engagement, (2) navigating the complexity of linking a database of video clips with other digital assets, and (3) identifying the main steps involved in building an app that will seamlessly deliver to users individually tailored messages, graphics, and handouts. RESULTS: We leveraged video to enhance user engagement by featuring "video doctors," full-screen video, storyboards, and streamlined scripts. We developed an approach to link the database of video clips with other digital assets through script coding and flow diagrams of algorithms to deliver a tailored user experience. We identified the steps to app development by using keyframes to design the integration of video and digital assets, using agile development methods to gather iterative feedback from multidisciplinary teams, and creating an intelligent data-driven back-end solution to tailor message delivery to individual users. CONCLUSIONS: Video-based digital health interventions will continue to play an important role in the future of HIV prevention and treatment, as well as other clinical health practices. However, facilitating the adoption of an HIV video intervention in HIV clinical settings is a work in progress. Our experience in designing and developing PHC presented unique challenges due to the extensive use of a large database of videos tailored individually to each user. Although PHC focuses on promoting the health and well-being of persons with HIV, the challenges and solutions presented in this tutorial are transferable to the design and development of video-based digital health interventions focused on other areas of health. |
Randomized controlled clinical trial of bivalent oral poliovirus vaccine and inactivated poliovirus vaccine in Nigerian children
Tagbo BN , Verma H , Mahmud ZM , Ernest K , Nnani RO , Chukwubike C , Craig KT , Hamisu A , Weldon WC , Oberste SM , Jeyaseelan V , Braka F , Mkanda P , Esangbedo D , Olowu A , Nwaze E , Sutter RW . J Infect Dis 2020 226 (2) 299-307 BACKGROUND: We conducted a trial in Nigeria to assess the immunogenicity of the new bOPV + IPV immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016-March 2017 period, well past the tOPV-bOPV switch in April 2016. METHODS: This was an open-label, two-arm, non-inferiority, multi-center, randomized controlled trial. We enrolled 572 infants of age ≤14 days and randomized them into two arms. Arm A received bOPV at birth, 6 and 10 weeks, bOPV+IPV at week 14 and IPV at week 18. Arm B received IPV each at 6, 10, 14 weeks and bOPV at 18 weeks of age. RESULTS: Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95%CI:96.7-99.8) and 98.1% (95%CI:88.2-94.8) in Arm A, and 89.6% (95%CI:85.4-93.0) and 98.5% (95%CI:96.3-99.6) in Arm B. Type 2 seroconversion with one dose IPV in Arm A was 72.0% (95%CI:66.2-77.3), which increased significantly with addition of second dose to 95.9% (95%CI:92.8-97.9). CONCLUSION: This first trial on the new EPI schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3, and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV respectively. |
Immunogenicity of reduced-dose monovalent type 2 oral poliovirus vaccine in Mocuba, Mozambique
de Deus N , Capitine IPU , Bauhofer AFL , Marques S , Cassocera M , Chissaque A , Bero DM , Langa JP , Padama FM , Jeyaseelan V , Oberste MS , Estivariz CF , Verma H , Jani I , Mach O , Sutter RW . J Infect Dis 2020 226 (2) 292-298 BACKGROUND: Monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: one-drop instead of two-drops. METHODS: We conducted a randomized, controlled, open-label, non-inferiority trial (10% margin) to compared immunogenicity following administration of one versus two-drops of mOPV2. We enrolled 9-22-months old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in sera collected before and one month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (>1:8) after vaccination or boosting titers by >4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (number ACTRN12619000184178p). RESULTS: We enrolled 378 children and 262 (69%) completed per-protocol requirements. Immune response of mOPV2 was 53.6% (95% confidence interval [CI]: 44.9%-62.1%) and 60.6% (95% CI: 52.2%-68.4%) in 1-drop and 2-drops recipients, respectively. The non-inferiority margin of the 10% was not reached (difference=7.0%; 95%CI= -5.0-19.0). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the non-inferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization, recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further. |
Potent in vitro activity of beta-D-4'-chloromethyl-2'-deoxy-2'-fluorocytidine against Nipah virus
Lo MK , Amblard F , Flint M , Chatterjee P , Kasthuri M , Li C , Russell O , Verma K , Bassit L , Schinazi RF , Nichol ST , Spiropoulou CF . Antiviral Res 2020 175 104712 Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that continues to cause outbreaks in humans characterized by high mortality and significant clinical sequelae in survivors. Currently, no therapeutics are approved for use in humans against NiV infection. Here, we report that 4'-chloromethyl-2'-deoxy-2'-fluorocytidine (ALS-8112) inhibits NiV. ALS-8112 is the parent nucleoside of lumicitabine, which has been evaluated in phase I and II clinical trials to treat pediatric and adult respiratory syncytial virus infection. In this study, we tested ALS-8112 against NiV and other major human respiratory pneumo- and paramyxoviruses in 2 human lung epithelial cell lines, and demonstrated the ability of ALS-8112 to reduce infectious wild-type NiV yield by over 6 orders of magnitude with no apparent cytotoxicity. However, further cytotoxicity testing in primary cells and bone marrow progenitor cells indicated cytotoxicity at higher concentrations of ALS-8112. Our results warrant the evaluation of lumicitabine against NiV infection in relevant animal models. |
Low prevalence of viable Toxoplasma gondii in fresh, unfrozen, American pasture-raised pork and lamb from retail meat stores in the United States
Dubey JP , Hill DE , Fournet V , Hawkins-Cooper D , Cerqueira-Cézar CK , Murata FHA , Verma SK , Kwok OCH , Rani S , Fredericks J , Adams B , Jones JL , Wiegand RE , Ying Y , Guo M , Su C , Pradhan AK . Food Control 2020 109 In a national survey of fresh, unfrozen, American pasture-raised lamb and pork, the prevalence of viable Toxoplasma gondii was determined in 1500 samples selected by random multistage sampling (750 pork, 750 lamb) obtained from 250 retail meat stores from 10 major geographic areas in the USA. Each sample consisted of a minimum of 500 g of meat purchased from the retail meat case. To detect viable T. gondii, 50 g meat samples of each of 1500 samples were bioassayed in mice. Viable T. gondii was isolated from 2 of 750 lamb samples (unweighted: 0.19%, 0.00–0.46%; weighted: 0.04%, 0.00–0.11%) and 1 of 750 pork samples (unweighted: 0.12%, 0.00–0.37%; weighted: 0.18%, 0.00–0.53%). Overall, the prevalence of viable T. gondii in these retail meats was very low. Nevertheless, consumers, especially pregnant women, should be aware that they can acquire T. gondii infection from ingestion of undercooked meat. |
Review of acellular assays of ambient particulate matter oxidative potential: Methods and relationships with composition, sources, and health effects
Bates JT , Fang T , Verma V , Zeng L , Weber RJ , Tolbert PE , Abrams JY , Sarnat SE , Klein M , Mulholland JA , Russell AG . Environ Sci Technol 2019 53 (8) 4003-4019 Oxidative stress is a potential mechanism of action for particulate matter (PM) toxicity and can occur when the body's antioxidant capacity cannot counteract or detoxify harmful effects of reactive oxygen species (ROS) due to an excess presence of ROS. ROS are introduced to the body via inhalation of PM with these species present on and/or within the particles (particle-bound ROS) and/or through catalytic generation of ROS in vivo after inhaling redox-active PM species (oxidative potential, OP). The recent development of acellular OP measurement techniques has led to a surge in research across the globe. In this review, particle-bound ROS techniques are discussed briefly while OP measurements are the focus due to an increasing number of epidemiologic studies using OP measurements showing associations with adverse health effects in some studies. The most common OP measurement techniques, including the dithiothreitol assay, glutathione assay, and ascorbic acid assay, are discussed along with evidence for utility of OP measurements in epidemiologic studies and PM characteristics that drive different responses between assay types (such as species composition, emission source, and photochemistry). Overall, most OP assays respond to metals like copper than can be found in emission sources like vehicles. Some OP assays respond to organics, especially photochemically aged organics, from sources like biomass burning. Select OP measurements have significant associations with certain cardiorespiratory end points, such as asthma, congestive heart disease, and lung cancer. In fact, multiple studies have found that exposure to OP measured using the dithiothreitol and glutathione assays drives higher risk ratios for certain cardiorespiratory outcomes than PM mass, suggesting OP measurements may be integrating the health-relevant fraction of PM and will be useful tools for future health analyses. The compositional impacts, including species and emission sources, on OP could have serious implications for health-relevant PM exposure. Though more work is needed, OP assays show promise for health studies as they integrate the impacts of PM species and properties on catalytic redox reactions into one measurement, and current work highlights the importance of metals, organic carbon, vehicles, and biomass burning emissions to PM exposures that could impact health. |
Immune priming and long-term persistence of memory B cells after inactivated poliovirus vaccine in macaque models: Support for at least 2 doses
Bhaumik SK , Kulkarni RR , Weldon WC , Silveira ELV , Ahmed H , Gunisetty S , Chandele A , Antia R , Verma H , Sutter R , Pallansch MA , Oberste MS , Villinger F , Orenstein W , Murali-Krishna K . Clin Infect Dis 2018 67 S66-s77 Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells. |
Trends in poliovirus seroprevalence in Kano State, Northern Nigeria
Verma H , Iliyasu Z , Craig KT , Molodecky NA , Urua U , Jibir BW , Gwarzo GD , Gajida AU , McDonald S , Weldon WC , Oberste MS , Braka F , Mkanda P , Sutter RW . Clin Infect Dis 2018 67 S103-s109 Background: Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods: It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results: Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained <90% across serotypes. Seroprevalence to serotypes 1 and 3 in 2015 was similar to 2014; however, for serotype 2 there was a significant improvement. IPV received in supplemental immunization activities was found to be a significant predictor of seropositivity among 6-9-month-old infants for serotypes 1 and 2. Conclusions: Seroprevalence for serotypes 1 and 3 remains low (<80%) in 6-9-month-olds. This poses a significant risk for poliovirus spread if reintroduced into the population. Efforts to strengthen immunization coverage are imperative to secure and sustain high population immunity. |
Future of human Chlamydia vaccine: Potential of self-adjuvanting biodegradable nanoparticles as safe vaccine delivery vehicles
Sahu R , Verma R , Dixit S , Igietseme JU , Black CM , Duncan S , Singh SR , Dennis VA . Expert Rev Vaccines 2018 17 (3) 217-227 INTRODUCTION: There is a persisting global burden and considerable public health challenge by the plethora of ocular, genital and respiratory diseases caused by members of the Gram-negative bacteria of the genus Chlamydia. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and interstitial pneumonia. The failures in screening and other prevention programs led to the current medical opinion that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, there is no human Chlamydia vaccine despite successful veterinary vaccines. A major challenge has been the effective delivery of vaccine antigens to induce safe and effective immune effectors to confer long-term protective immunity. The dawn of the era of biodegradable polymeric nanoparticles and the adjuvanted derivatives may accelerate the realization of the dream of human vaccine in the foreseeable future. Areas covered: This review focuses on the current status of human chlamydial vaccine research, specifically the potential of biodegradable polymeric nanovaccines to provide efficacious Chlamydia vaccines in the near future. Expert commentary: The safety of biodegradable polymeric nanoparticles-based experimental vaccines with or without adjuvants and the array of available chlamydial vaccine candidates would suggest that clinical trials in humans may be imminent. Also, the promising results from vaccine testing in animal models could lead to human vaccines against trachoma and reproductive disease simultaneously. |
Sustained progress, but no room for complacency: Results of 2015 HIV estimations in India
Pandey A , Dhingra N , Kumar P , Sahu D , Reddy DCS , Narayan P , Raj Y , Sangal B , Chandra N , Nair S , Singh J , Chavan L , Srivastava DJ , Jha UM , Verma V , Kant S , Bhattacharya M , Swain P , Haldar P , Singh L , Bakkali T , Stover J , Ammassari S . Indian J Med Res 2017 146 (1) 83-96 BACKGROUND & OBJECTIVES: Evidence-based planning has been the cornerstone of India's response to HIV/AIDS. Here we describe the process, method and tools used for generating the 2015 HIV estimates and provide a summary of the main results. METHODS: Spectrum software supported by the UNAIDS was used to produce HIV estimates for India as a whole and its States/Union Territories. This tool takes into consideration the size and HIV prevalence of defined population groups and programme data to estimate HIV prevalence, incidence and mortality over time as well as treatment needs. RESULTS: India's national adult prevalence of HIV was 0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV infections were an estimated 86,000 in 2015, reflecting a decline by around 32 per cent from 2007. The declining trend in incidence was mirrored in most States, though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh, Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were variations in the rate and trend of decline across India for this indicator also. INTERPRETATION & CONCLUSIONS: While key indicators measured through Spectrum modelling confirm success of the National AIDS Control Programme, there is no room for complacency as rising incidence trends in some geographical areas and population pockets remain the cause of concern. Progress achieved so far in responding to HIV/AIDS needs to be sustained to end the HIV epidemic. |
Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern Nigeria
Gofama MM , Verma H , Abdullahi H , Molodecky NA , Craig KT , Urua UA , Garba MA , Alhaji MA , Weldon WC , Oberste MS , Braka F , Muhammad AJG , Sutter RW . PLoS One 2017 12 (9) e0185284 BACKGROUND: Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV) on antibody seroprevalence. METHODS AND FINDINGS: We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child's health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%), 86% (79-91%), and 72% (65-79%) in Borno State, and 75% (67-81%), 74% (66-81%) and 69% (61-76%) in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%)]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and anti-polio neutralizing antibodies among 6-9-month-old infants for serotypes 1 and 3, but demonstrated a non-significant positive association for serotype 2. Children receiving IPV through SIAs demonstrated significantly higher anti-polio neutralizing antibodies for serotypes 1 and 3. CONCLUSIONS: The seroprevalence to poliovirus remains suboptimal in both Borno and Yobe States in Nigeria. The low seroprevalence facilitated the continued transmission of both wild serotype 1 and serotype 2 circulating vaccine-derived poliovirus detected in Borno State in 2016. Further efforts are necessary to improve the immunity status of these populations to ensure sufficient population immunity to interrupt transmission. |
Breastfeeding and breast cancer risk reduction: Implications for black mothers
Anstey EH , Shoemaker ML , Barrera CM , O'Neil ME , Verma AB , Holman DM . Am J Prev Med 2017 53 S40-s46 Breast cancer is the most commonly diagnosed cancer and a leading cause of death from cancer among U.S. women. Studies have suggested that breastfeeding reduces breast cancer risk among parous women, and there is mounting evidence that this association may differ by subtype such that breastfeeding may be more protective of some invasive breast cancer types. The purpose of this review is to discuss breast cancer disparities in the context of breastfeeding and the implications for black mothers. Black women in the U.S. have lower rates of breastfeeding and nearly twice the rates of triple-negative breast cancer (an aggressive subtype) compared with white women. In addition to individual challenges to breastfeeding, black women may also differentially face contextual barriers such as a lack of social and cultural acceptance in their communities, inadequate support from the healthcare community, and unsupportive work environments. More work is needed to improve the social factors and policies that influence breastfeeding rates at a population level. Such efforts should give special consideration to the needs of black mothers to adequately address disparities in breastfeeding among this group and possibly help reduce breast cancer risk. Interventions such as peer counseling, hospital policy changes, breastfeeding-specific clinic appointments, group prenatal education, and enhanced breastfeeding programs have been shown to be effective in communities of color. A comprehensive approach that integrates interventions across multiple levels and settings may be most successful in helping mothers reach their breastfeeding goals and reducing disparities in breastfeeding and potentially breast cancer incidence. |
Ambient size distributions and lung deposition of aerosol dithiothreitol-measured oxidative potential: Contrast between soluble and insoluble particles
Fang T , Zeng L , Gao D , Verma V , Stefaniak AB , Weber RJ . Environ Sci Technol 2017 51 (12) 6802-6811 Ambient particulate matter may upset redox homeostasis, leading to oxidative stress and adverse health effects. Size distributions of water-insoluble and water-soluble OPDTT(dithiothreitol assay, measure of oxidative potential per air volume) are reported for a roadside site and an urban site. The average water-insoluble fractions were 23% and 51%, and 37% and 39%, for fine and coarse modes at the roadside and urban sites, respectively, measured during different periods. Water-soluble OPDTTwas unimodal, peaked near 1-2.5 m due to contributions from fine-mode organic components plus coarse-mode transition metal ions. In contrast, water-insoluble OPDTTwas bimodal, with both fine and coarse modes. The main chemical components that drive both fractions appear to be the same, except that for water-insoluble OPDTTthe compounds were absorbed on surfaces of soot and non-tailpipe traffic dust. They were largely externally mixed and deposited in different regions in the respiratory system, transition metal ions predominately in the upper regions and organic species, such as quinones, deeper in the lung. Although OPDTTper mass (toxicity) was highest for ultrafine particles, estimated lung deposition was mainly from accumulation and coarse particles. Contrasts in the phases of these forms of OPDTTdeposited in the respiratory system may have differing health impacts. 2017 American Chemical Society. |
Poliovirus seroprevalence before and after interruption of poliovirus transmission in Kano state, Nigeria
Iliyasu Z , Verma H , Craig KT , Nwaze E , Ahmad-Shehu A , Jibir BW , Gwarzo GD , Gajida AU , Weldon WC , Oberste SM , Takane M , Mkanda P , Muhammad AJ , Sutter RW . Vaccine 2016 34 (42) 5125-5131 INTRODUCTION: In September 2015, Nigeria was removed from the list of polio-endemic countries after more than 12months had passed since the detection of last wild poliovirus case in the country on 24 July 2014. We are presenting here a report of two polio seroprevalence surveys conducted in September 2013 and October 2014, respectively, in the Kano state of northern Nigeria. METHODS: Health facility based seroprevalence surveys were undertaken at Murtala Mohammad Specialist Hospital, Kano. Parents or guardians of children aged 6-9months, 36-47months, 5-9years and 10-14years in 2013 and 6-9months and 19-22months (corresponding to 6-9months range at the time of 2013 survey) in 2014 presenting to the outpatient department, were approached for participation, screened for eligibility and asked to provide informed consent. A questionnaire was administered and a blood sample collected for polio neutralization assay. RESULTS: Among subjects aged 6-9months in the 2013 survey, seroprevalence was 58% (95% confidence interval [CI] 51-66%) to poliovirus type 1, 42% (95% CI 34-50%) to poliovirus type 2, and 52% (95% CI 44-60%) to poliovirus type 3. Among children 36-47months and older, seroprevalence was 85% or higher for all three serotypes. In 2014, seroprevalence in 6-9month infants was 72% (95% CI 65-79%) for type 1, 59% (95% CI 52-66%) for type 2, and 65% (95% CI 57-72%) for type 3 and in 19-22months, 80% (95% CI 74-85%), 57% (49-63%) and 78% (71-83%) respectively. Seroprevalence was positively associated with history of increasing oral poliovirus vaccine doses. CONCLUSIONS: There was significant improvement in seroprevalence in 2014 over the 2013 levels indicating a positive impact of recent programmatic interventions. However the continued low seroprevalence in 6-9month age is a concern and calls for improved immunization efforts to sustain the polio-free Nigeria. |
Fractional-dose inactivated poliovirus vaccine immunization campaign - Telangana state, India, June 2016
Bahl S , Verma H , Bhatnagar P , Haldar P , Satapathy A , Kumar KN , Horton J , Estivariz CF , Anand A , Sutter R . MMWR Morb Mortal Wkly Rep 2016 65 (33) 859-863 Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. |
Screening difficult-to-reach populations for tuberculosis using a mobile medical unit, Punjab India
Binepal G , Agarwal P , Kaur N , Singh B , Bhagat V , Verma RP , Satyanarayana S , Oeltmann JE , Moonan PK . Public Health Action 2015 5 (4) 241-245 BACKGROUND: In India, the National Health Mission has provided one mobile medical unit (MMU) per district in the state of Punjab to provide primary health care services for difficult-to-reach populations. OBJECTIVES: To determine the number of patients with presumptive tuberculosis (TB) and the number of TB cases detected and treated among patients who used the MMU services from May to December 2012 in Mohali district, Punjab, India. METHODS: A cross-sectional study was conducted and registers of the out-patient, laboratory, radiology, and TB departments of the MMU were reviewed to determine the number of persons presumed to have TB and the number of persons diagnosed with TB. Results: Of 8346 patients who attended the MMUs, 663 (8%) had symptoms suggestive of TB. Among those with TB symptoms, 540 (81%) were evaluated for pulmonary TB using sputum examination or chest X-ray. In total, 58 (11%) patients had clinical or laboratory evidence of pulmonary TB, of whom 21 (36%) started anti-tuberculosis treatment. CONCLUSION: As MMUs are an integral part of the general public health system, these units have the potential to detect TB cases among difficult-to-reach populations. Additional research is required to optimise the diagnosis of TB at MMUs and to increase rates of TB treatment initiation. |
Endoscopic retrograde cholangiopancreatography-associated AmpC Escherichia coli outbreak
Wendorf KA , Kay M , Baliga C , Weissman SJ , Gluck M , Verma P , D'Angeli M , Swoveland J , Kang MG , Eckmann K , Ross AS , Duchin J . Infect Control Hosp Epidemiol 2015 36 (6) 1-9 BACKGROUND: We identified an outbreak of AmpC-producing Escherichia coli infections resistant to third-generation cephalosporins and carbapenems (CR) among 7 patients who had undergone endoscopic retrograde cholangiopancreatography at hospital A during November 2012-August 2013. Gene sequencing revealed a shared novel mutation in a bla CMY gene and a distinctive fumC/ fimH typing profile. OBJECTIVE: To determine the extent and epidemiologic characteristics of the outbreak, identify potential sources of transmission, design and implement infection control measures, and determine the association between the CR E. coli and AmpC E. coli circulating at hospital A. METHODS: We reviewed laboratory, medical, and endoscopy reports, and endoscope reprocessing procedures. We obtained cultures from endoscopes after reprocessing as well as environmental samples and conducted pulsed-field gel electrophoresis and gene sequencing on phenotypic AmpC isolates from patients and endoscopes. Cases were those infected with phenotypic AmpC isolates (both carbapenem-susceptible and CR) and identical bla CMY-2, fumC, and fimH alleles or related pulsed-field gel electrophoresis patterns. RESULTS: Thirty-five of 49 AmpC E. coli tested met the case definition, including all CR isolates. All cases had complicated biliary disease and had undergone at least 1 endoscopic retrograde cholangiopancreatography at hospital A. Mortality at 30 days was 16% for all patients and 56% for CR patients. Two of 8 reprocessed endoscopic retrograde cholangiopancreatography scopes harbored AmpC that matched case isolates by pulsed-field gel electrophoresis. Environmental cultures were negative. No breaches in infection control were identified. Endoscopic reprocessing exceeded manufacturer's recommended cleaning guidelines. CONCLUSION: Recommended reprocessing guidelines are not sufficient. |
Epigenetic research in cancer epidemiology: trends, opportunities, and challenges.
Verma M , Rogers S , Divi RL , Schully SD , Nelson S , Joseph Su L , Ross SA , Pilch S , Winn DM , Khoury MJ . Cancer Epidemiol Biomarkers Prev 2014 23 (2) 223-33 Epigenetics is emerging as an important field in cancer epidemiology that promises to provide insights into gene regulation and facilitate cancer control throughout the cancer care continuum. Increasingly, investigators are incorporating epigenetic analysis into the studies of etiology and outcomes. To understand current progress and trends in the inclusion of epigenetics in cancer epidemiology, we evaluated the published literature and the National Cancer Institute (NCI)-supported research grant awards in this field to identify trends in epigenetics research. We present a summary of the epidemiologic studies in NCI's grant portfolio (from January 2005 through December 2012) and in the scientific literature published during the same period, irrespective of support from the NCI. Blood cells and tumor tissue were the most commonly used biospecimens in these studies, although buccal cells, cervical cells, sputum, and stool samples were also used. DNA methylation profiling was the focus of the majority of studies, but several studies also measured microRNA profiles. We illustrate here the current status of epidemiologic studies that are evaluating epigenetic changes in large populations. The incorporation of epigenomic assessments in cancer epidemiology studies has and is likely to continue to provide important insights into the field of cancer research. |
Prevalence of asymptomatic poliovirus infection in older children and adults in northern India: analysis of contact and enhanced community surveillance, 2009
Mach O , Verma H , Khandait DW , Sutter RW , O'Connor PM , Pallansch MA , Cochi SL , Linkins RW , Chu SY , Wolff C , Jafari HS . J Infect Dis 2014 210 Suppl 1 S252-8 BACKGROUND: In 2009, enhanced poliovirus surveillance was established in polio-endemic areas of Uttar Pradesh and Bihar, India, to assess poliovirus infection in older individuals. METHODS: In Uttar Pradesh, stool specimens from asymptomatic household and neighborhood contacts of patients with laboratory-confirmed polio were tested for polioviruses. In Bihar, in community-based surveillance, children and adults from 250 randomly selected households in the Kosi River area provided stool and pharyngeal swab samples that were tested for polioviruses. A descriptive analysis of surveillance data was performed. RESULTS: In Uttar Pradesh, 89 of 1842 healthy contacts of case patients with polio (4.8%) were shedding wild poliovirus (WPV); 54 of 85 (63.5%) were ≥5 years of age. Shedding was significantly higher in index households than in neighborhood households (P < .05). In Bihar, 11 of 451 healthy persons (2.4%) were shedding WPV in their stool; 6 of 11 (54.5%) were ≥5 years of age. Mean viral titer was similar in older and younger children. CONCLUSIONS: A high proportion of persons ≥5 years of age were asymptomatically shedding polioviruses. These findings provide indirect evidence that older individuals could have contributed to community transmission of WPV in India. Polio vaccination campaigns generally target children <5 years of age. Expanding this target age group in polio-endemic areas could accelerate polio eradication. |
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