Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Khare M [original query] |
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Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen (preprint)
Bender NG , Khare P , Martinez J , Tweedell RE , Nyasembe VO , López-Gutiérrez B , Tripathi A , Miller D , Hamerly T , Vela EM , Howard RF , Nsango S , Cobb RR , Harbers M , Dinglasan RR . bioRxiv 2020 2020.11.29.402669 Malaria transmission-blocking vaccines (TBVs) are a critical tool for disease elimination. TBVs prevent completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen and structure-function studies have identified two Class II epitopes that induce potent transmission-blocking (T-B) antibodies. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ was immunogenic and immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity and establishing UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.Competing Interest StatementThe authors have declared no competing interest. |
SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse.
Konings F , Perkins MD , Kuhn JH , Pallen MJ , Alm EJ , Archer BN , Barakat A , Bedford T , Bhiman JN , Caly L , Carter LL , Cullinane A , de Oliveira T , Druce J , El Masry I , Evans R , Gao GF , Gorbalenya AE , Hamblion E , Herring BL , Hodcroft E , Holmes EC , Kakkar M , Khare S , Koopmans MPG , Korber B , Leite J , MacCannell D , Marklewitz M , Maurer-Stroh S , Rico JAM , Munster VJ , Neher R , Munnink BO , Pavlin BI , Peiris M , Poon L , Pybus O , Rambaut A , Resende P , Subissi L , Thiel V , Tong S , van der Werf S , von Gottberg A , Ziebuhr J , Van Kerkhove MD . Nat Microbiol 2021 6 (7) 821-823 A group convened and led by the Virus Evolution Working Group of the World Health Organization reports on its deliberations and announces a naming scheme that will enable clear communication about SARS-CoV-2 variants of interest and concern. | | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has a linear, unsegmented, positive-sense RNA genome. As with all viruses, SARS-CoV-2 continuously adapts to changing environments in real time via random genome mutations that are subject to natural selection. Most mutations are neutral or detrimental to the virus; however, a small number of mutations may provide a selective advantage, such as escape from the host immune system or resistance to antiviral drugs. Such mutations may also lead to increased fitness for transmissibility. As mutated forms of viruses or variants spread from person to person, they will eventually be detected at the population level. |
Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
Bender NG , Khare P , Martinez J , Tweedell RE , Nyasembe VO , López-Gutiérrez B , Tripathi A , Miller D , Hamerly T , Vela EM , Davis RR , Howard RF , Nsango S , Cobb RR , Harbers M , Dinglasan RR . NPJ Vaccines 2021 6 (1) 49 Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts. |
Japanese encephalitis virus as cause of acute encephalitis, Bhutan
Wangchuk S , Tamang TD , Darnal JB , Pelden S , Lhazeen K , Mynak ML , Letson GW , Khare S , Leader BT , Marfin AA , Hills SL . Emerg Infect Dis 2020 26 (9) 2239-2242 In 2011, Bhutan's Royal Centre for Disease Control began Japanese encephalitis (JE) surveillance at 5 sentinel hospitals throughout Bhutan. During 2011-2018, a total of 20 JE cases were detected, indicating JE virus causes encephalitis in Bhutan. Maintaining JE surveillance will help improve understanding of JE epidemiology in this country. |
Brucella exposure risk events in ten clinical laboratories, New York City, 2015 - 2017
Ackelsberg J , Liddicoat A , Burke T , Szymczak WA , Levi MH , Ostrowsky B , Hamula C , Patel G , Kopetz V , Saverimuttu J , Sordillo EM , D'Souza D , Mitchell EA , Lowe W , Khare R , Tang YW , Bianchi AL , Egan C , Perry MJ , Hughes S , Rakeman JL , Adams E , Kharod GA , Tiller R , Saile E , Lee S , Gonzalez E , Hoppe B , Leviton IM , Hacker S , Ni KF , Orsini RL , Jhaveri S , Mazariegos I , Dingle T , Koll B , Stoddard RA , Galloway R , Hoffmaster A , Fine A , Lee E , Dentinger C , Harrison E , Layton M . J Clin Microbiol 2019 58 (2) During 2015-2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events ("Brucella events") in 7 clinical laboratories (CLs). Most patients traveled to endemic countries and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as clinicians did not consider brucellosis until notified that bacteremia with Brucella was suspected.In 3 Brucella events, CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), with limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events that accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including procedures that could generate infectious aerosols. During 3 Brucella events, CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each, CLs had isolated Brucella previously.Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred.Laboratory assessments were conducted after Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF for identification until BTAs have been ruled out. |
Estimation tools for reducing the impact of sampling and nonresponse errors in dual-frame RDD telephone surveys
Wolter KM , Ganesh N , Copeland KR , Singleton JA , Khare M . Stat Med 2019 38 (23) 4718-4732 We discuss alternative estimators of the population total given a dual-frame random-digit-dial (RDD) telephone survey in which samples are selected from landline and cell phone sampling frames. The estimators are subject to sampling and nonsampling errors. To reduce sampling variability when an optimum balance of landline and cell phone samples is not feasible, we develop an application of shrinkage estimation. We demonstrate the implications for survey weighting of a differential nonresponse mechanism by telephone status. We illustrate these ideas using data from the National Immunization Survey-Child, a large dual-frame RDD telephone survey sponsored by the Centers for Disease Control and Prevention and conducted to measure the vaccination status of American children aged 19 to 35 months. |
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Shrivastava A , Kumar A , Thomas JD , Laserson KF , Bhushan G , Carter MD , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Isenberg SL , Johnson R , Pirkle JL , Sharer JD , Hall PL , Yadav R , Velayudhan A , Papanna M , Singh P , Somashekar D , Pradhan A , Goel K , Pandey R , Kumar M , Kumar S , Chakrabarti A , Sivaperumal P , Kumar AR , Schier JG , Chang A , Graham LA , Mathews TP , Johnson D , Valentin L , Caldwell KL , Jarrett JM , Harden LA , Takeoka GR , Tong S , Queen K , Paden C , Whitney A , Haberling DL , Singh R , Singh RS , Earhart KC , Dhariwal AC , Chauhan LS , Venkatesh S , Srikantiah P . Lancet Glob Health 2017 5 (4) e458-e466 BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9.6 [95% CI 3.6 - 24]) and absence of an evening meal (2.2 [1.2-4.3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7.8 [95% CI 3.3-18.8], without evening meal; OR 3.6 [1.1-11.1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12.4 mug/g to 152.0 mug/g and MCPG ranged from 44.9 mug/g to 220.0 mug/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention. |
Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014
Shrivastava A , Srikantiah P , Kumar A , Bhushan G , Goel K , Kumar S , Kumar T , Mohankumar R , Pandey R , Pathan P , Pappanna M , Pasi A , Pradhan A , Singh P , Somashekar D , Velayudhan A , Yadav R , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Laserson K , Earhart KC , Sivaperumal P , Kumar AR , Chakrabarti A , Thomas J , Schier J , Singh R , Singh RS , Dhariwal AC , Chauhan LS . MMWR Morb Mortal Wkly Rep 2015 64 (3) 49-53 Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children. |
Quantifying bias in a health survey: modeling total survey error in the national immunization survey.
Molinari NM , Wolter KM , Skalland B , Montgomery R , Khare M , Smith PJ , Barron ML , Copeland K , Santos K , Singleton JA . Stat Med 2011 30 (5) 505-14 Random-digit-dial telephone surveys are experiencing both declining response rates and increasing under-coverage due to the prevalence of households that substitute a wireless telephone for their residential landline telephone. These changes increase the potential for bias in survey estimates and heighten the need for survey researchers to evaluate the sources and magnitudes of potential bias. We apply a Monte Carlo simulation-based approach to assess bias in the NIS, a land-line telephone survey of 19-35 month-old children used to obtain national vaccination coverage estimates. We develop a model describing the survey stages at which component nonsampling error may be introduced due to nonresponse and under-coverage. We use that model and components of error estimated in special studies to quantify the extent to which noncoverage and nonresponse may bias the vaccination coverage estimates obtained from the NIS and present a distribution of the total survey error. Results indicated that the total error followed a normal distribution with mean of 1.72 per cent (95 per cent CI: 1.71, 1.74 per cent) and final adjusted survey weights corrected for this error. Although small, the largest contributor to error in terms of magnitude was nonresponse of immunization providers. The total error was most sensitive to declines in coverage due to cell phone only households. These results indicate that, while response rates and coverage may be declining, total survey error is quite small. Since response rates have historically been used to proxy for total survey error, the finding that these rates do not accurately reflect bias is important for evaluation of survey data. Published in 2011 by John Wiley & Sons, Ltd. |
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