Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-20 (of 20 Records) |
Query Trace: Nolan M [original query] |
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Do Aedes triseriatus respect state boundaries?: A paucity of La Crosse Virus in the South Carolina Appalachian Mountains
Gual-Gonzalez L , Dye-Braumuller K , Warner A , Bunting T , Bryant D , Connelly R , Burkhalter K , Nolan MS . Vector Borne Zoonotic Dis 2023 Background: La Crosse virus is an important endemic public health concern in the North Carolina Appalachian Mountains; however, human incidence is not commonly noted in this region on the South Carolina side of the mountain range border. No relevant studies have been performed in South Carolina evaluating mosquito vector populations for La Crosse virus (LACV) infection; thus, a pilot mosquito surveillance study was executed in summer 2020. Material and Methods: Vector surveillance occurred at five South Carolina state parks bordering neighboring state endemic counties from May to August 2020. Collections were approved by the state park authority, as noted in Permit No. N-8-20. Results: All three competent mosquito vectors were collected during the study duration; however, these vectors were collected in low abundance: Aedes triseriatus (4.5% of all collected mosquitos); Aedes albopictus (2.0%); Aedes japonicus (1.4%). Principal mosquito vector specimens, Ae. triseriatus, were sent to Centers for Disease Control and Prevention for testing of LACV by real-time reverse transcription PCR-all were negative. Discussion: While entomologic evidence suggests low transmission risk for this arbovirus in the South Carolina Appalachian Mountain region, further eco-epidemiologic investigations are warranted to understand this endemicity variance within a relatively small geographic area. |
Association of radiology findings with etiology of community acquired pneumonia among children
Arnold SR , Jain S , Dansie D , Kan H , Williams DJ , Ampofo K , Anderson EJ , Grijalva CG , Bramley AM , Pavia AT , Edwards KM , Nolan VG , McCullers JA , Kaufman RA . J Pediatr 2023 261 113333 OBJECTIVE: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study. STUDY DESIGN: Hospitalized children <18 years of age with CAP enrolled in the Etiology of Pneumonia in the Community study at 3 children's hospitals between January 2010 and June 2012 were included. Testing of blood and respiratory specimens used multiple modalities to identify typical and atypical bacterial, or viral infection. Study radiologists classified chest radiographs (consolidation, other infiltrates [interstitial and/or alveolar], pleural effusion) using modified World Health Organization pneumonia criteria. Infiltrate patterns were compared according to etiology of CAP. RESULTS: Among 2212 children, there were 1302 (59%) with consolidation with or without other infiltrates, 910 (41%) with other infiltrates, and 296 (13%) with pleural effusion. In 1795 children, at least 1 pathogen was detected. Among these patients, consolidation (74%) was the most frequently observed pattern (74% in typical bacterial CAP, 58% in atypical bacterial CAP, and 54% in viral CAP). Positive and negative predictive values of consolidation for typical bacterial CAP were 12% (95% CI 10%-15%) and 96% (95% CI 95%-97%) respectively. In a multivariable model, typical bacterial CAP was associated with pleural effusion (OR 7.3, 95% CI 4.7-11.2) and white blood cell ≥15 000/mL (OR 3.2, 95% CI 2.2-4.9), and absence of wheeze (OR 0.5, 95% CI 0.3-0.8) or viral detection (OR 0.2, 95% CI 0.1-0.4). CONCLUSIONS: Consolidation predicted typical bacterial CAP poorly, but its absence made typical bacterial CAP unlikely. Pleural effusion was the best predictor of typical bacterial infection, but too uncommon to aid etiology prediction. |
Overcoming staffing challenges when implementing a birth defects surveillance system: a Ugandan experience
Namale-Matovu J , Barlow-Mosha L , Mumpe-Mwanja D , Kalibbala D , Serunjogi R , Nankunda J , Valencia D , Nabunya E , Byamugishat J , Birabwa-Male D , Okwero MA , Nolan M , Williamson D , Musoke P . J Glob Health Rep 2020 4 Every year, 3–6% of infants worldwide are born with a serious birth defect.1 Approximately 3.3 million children under 5 years die from birth defects, and among those who survive, 3.2 million suffer with disabilities for life.1 Over 94% of all birth defects and 95% of deaths due to the birth defects occur in developing countries.1 Comprehensive, reliable data on birth defects are not available for most developing countries2,3 because implementing and maintaining birth defects surveillance systems requires substantial resources including staffing. |
Evidence of likely autochthonous Chagas disease in the southwestern United States: A case series of Trypanosoma cruzi seropositive blood donors
Lynn MK , Dye-Braumuller KC , Beatty NL , Dorn PL , Klotz SA , Stramer SL , Townsend RL , Kamel H , Vannoy JM , Sadler P , Montgomery SP , Rivera HN , Nolan MS . Transfusion 2022 62 (9) 1808-1817 BACKGROUND: Chagas disease is a parasitic infection that can insidiously cause non-ischemic cardiomyopathy. Given the largely silent nature of this progressive disease, asymptomatic blood donors pose potential blood transfusion risk. Blood donation screening has become an unintentional form of Chagas disease surveillance, with thousands of new cases identified since national surveillance was initiated in 2007. STUDY DESIGN AND METHODS: We recruited T. cruzi-positive blood donors identified from California and Arizona blood centers for confirmatory blood screening and assessment of lifetime infection risk. RESULTS: Among eight suspected cases, we identified four confirmed US autochthonous infections. The current manuscript details the transmission sources, healthcare-seeking behaviors post-blood donation resulting, and clinical course of disease among persons without any history of travel to endemic Latin American countries. DISCUSSION: This manuscript presents four additional US-acquired Chagas disease cases and identifies an opportunity for blood centers to assist in confronting barriers surrounding Chagas disease in the US. |
Needs assessment of Southeastern United States vector control agencies: Capacity improvement is greatly needed to prevent the next vector-borne disease outbreak
Dye-Braumuller KC , Gordon JR , Johnson D , Morrissey J , McCoy K , Dinglasan RR , Nolan MS . Trop Med Infect Dis 2022 7 (5) A national 2017 vector control capacity survey was conducted to assess the United States' (U.S.'s) ability to prevent emerging vector-borne disease. Since that survey, the southeastern U.S. has experienced continued autochthonous exotic vector-borne disease transmission and establishment of invasive vector species. To understand the current gaps in control programs and establish a baseline to evaluate future vector control efforts for this vulnerable region, a focused needs assessment survey was conducted in early 2020. The southeastern U.S. region was targeted, as this region has a high probability of novel vector-borne disease introduction. Paper copies delivered in handwritten envelopes and electronic copies of the survey were delivered to 386 unique contacts, and 150 returned surveys were received, corresponding to a 39% response rate. Overall, the survey found vector control programs serving areas with over 100,000 residents and those affiliated with public health departments had more core capabilities compared to smaller programs and those not affiliated with public health departments. Furthermore, the majority of vector control programs in this region do not routinely monitor for pesticide resistance. Taken as a whole, these results suggest that the majority of the southeastern U.S. is vulnerable to vector-borne disease outbreaks. Results from this survey raise attention to the critical need of providing increased resources to bring all vector control programs to a competent level, ensuring that public health is protected from the threat of vector-borne disease. |
Trypanosoma cruzi in Nonischemic Cardiomyopathy Patients, Houston, Texas, USA
Nolan MS , Aguilar D , Misra A , Gunter SM , Erickson T , Gorchakov R , Rivera H , Montgomery SP , Murray KO . Emerg Infect Dis 2021 27 (7) 1958-1960 To investigate possible cardiac manifestations of Chagas disease, we tested 97 Latinx patients with nonischemic cardiomyopathy in Houston, Texas, USA, for Trypanosoma cruzi infection. We noted a high prevalence of underdiagnosed infection and discrepant results in clinical diagnostic assays. Latinx cardiac patients in the United States would benefit from laboratory screening for T. cruzi infection. |
Immunologic timeline of Ebola virus disease and recovery in humans
McElroy AK , Akondy RS , McLlwain DR , Chen H , Bjornson-Hooper Z , Mukherjee N , Mehta AK , Nolan G , Nichol ST , Spiropoulou CF . JCI Insight 2020 5 (10) A complete understanding of human immune responses to Ebola virus infection is limited by the availability of specimens and the requirement for biosafety level 4 (BSL-4) containment. In an effort to bridge this gap, we evaluated cryopreserved PBMCs from 4 patients who survived Ebola virus disease (EVD) using an established mass cytometry antibody panel to characterize various cell populations during both the acute and convalescent phases. Acute loss of nonclassical monocytes and myeloid DCs, especially CD1c+ DCs, was noted. Classical monocyte proliferation and CD38 upregulation on plasmacytoid DCs coincided with declining viral load. Unsupervised analysis of cell abundance demonstrated acute declines in monocytic, NK, and T cell populations, but some populations, many of myeloid origin, increased in abundance during the acute phase, suggesting emergency hematopoiesis. Despite cell losses during the acute phase, upregulation of Ki-67 correlated with recovery of cell populations over time. These data provide insights into the human immune response during EVD. |
The etiology and impact of co-infections in children hospitalized with community-acquired pneumonia
Nolan VG , Arnold SR , Bramley AM , Ampofo K , Williams DJ , Grijalva CG , Self WH , Anderson EJ , Wunderink RG , Edwards KM , Pavia AT , Jain S , McCullers JA . J Infect Dis 2017 218 (2) 179-188 Background: Recognition that co-infections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. Methods: We analyzed data from 2219 children hospitalized with CAP and compared demographics, clinical characteristics, and outcomes between groups with viruses alone, bacteria alone, or co-infections. We also assessed the frequency of selected pairings of co-detected pathogens and their clinical characteristics. Results: 576 (26%) of the children studied had a co-infection. Children with only virus detection were younger and more likely to be black and have co-morbidities such as asthma compared to those with bacteria alone. Children with virus-bacteria co-infections had a higher frequency of leukocytosis, consolidation on chest X-ray, increased length of stay, and more frequent parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation when compared to viruses alone. Virus-virus co-infections were generally comparable to single virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. Conclusions: Co-infections occurred in 26% of children hospitalized for CAP. Children with bacterial infections, alone or complicated by a virus, have worse outcomes than children infected with a virus alone. |
Methylprednisolone acetate induces, and Delta7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice
Patton JB , Bonne-Annee S , Deckman J , Hess JA , Torigian A , Nolan TJ , Wang Z , Kliewer SA , Durham AC , Lee JJ , Eberhard ML , Mangelsdorf DJ , Lok JB , Abraham D . Proc Natl Acad Sci U S A 2017 115 (1) 204-209 Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Delta7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection. |
Estimating the high-arsenic domestic-well population in the conterminous United States
Ayotte JD , Medalie L , Qi SL , Backer LC , Nolan BT . Environ Sci Technol 2017 51 (21) 12443-12454 Arsenic concentrations from 20450 domestic wells in the U.S. were used to develop a logistic regression model of the probability of having arsenic >10 mug/L ("high arsenic"), which is presented at the county, state, and national scales. Variables representing geologic sources, geochemical, hydrologic, and physical features were among the significant predictors of high arsenic. For U.S. Census blocks, the mean probability of arsenic >10 mug/L was multiplied by the population using domestic wells to estimate the potential high-arsenic domestic-well population. Approximately 44.1 M people in the U.S. use water from domestic wells. The population in the conterminous U.S. using water from domestic wells with predicted arsenic concentration >10 mug/L is 2.1 M people (95% CI is 1.5 to 2.9 M). Although areas of the U.S. were underrepresented with arsenic data, predictive variables available in national data sets were used to estimate high arsenic in unsampled areas. Additionally, by predicting to all of the conterminous U.S., we identify areas of high and low potential exposure in areas of limited arsenic data. These areas may be viewed as potential areas to investigate further or to compare to more detailed local information. Linking predictive modeling to private well use information nationally, despite the uncertainty, is beneficial for broad screening of the population at risk from elevated arsenic in drinking water from private wells. |
Adverse weather conditions and fatal motor vehicle crashes in the United States, 1994-2012
Saha S , Schramm P , Nolan A , Hess J . Environ Health 2016 15 (1) 104 BACKGROUND: Motor vehicle crashes are a leading cause of injury mortality. Adverse weather and road conditions have the potential to affect the likelihood of motor vehicle fatalities through several pathways. However, there remains a dearth of assessments associating adverse weather conditions to fatal crashes in the United States. We assessed trends in motor vehicle fatalities associated with adverse weather and present spatial variation in fatality rates by state. METHODS: We analyzed the Fatality Analysis Reporting System (FARS) datasets from 1994 to 2012 produced by the National Highway Traffic Safety Administration (NHTSA) that contains reported weather information for each fatal crash. For each year, we estimated the fatal crashes that were associated with adverse weather conditions. We stratified these fatalities by months to examine seasonal patterns. We calculated state-specific rates using annual vehicle miles traveled data for all fatalities and for those related to adverse weather to examine spatial variations in fatality rates. To investigate the role of adverse weather as an independent risk factor for fatal crashes, we calculated odds ratios for known risk factors (e.g., alcohol and drug use, no restraint use, poor driving records, poor light conditions, highway driving) to be reported along with adverse weather. RESULTS: Total and adverse weather-related fatalities decreased over 1994-2012. Adverse weather-related fatalities constituted about 16 % of total fatalities on average over the study period. On average, 65 % of adverse weather-related fatalities happened between November and April, with rain/wet conditions more frequently reported than snow/icy conditions. The spatial distribution of fatalities associated with adverse weather by state was different than the distribution of total fatalities. Involvement of alcohol or drugs, no restraint use, and speeding were less likely to co-occur with fatalities during adverse weather conditions. CONCLUSIONS: While adverse weather is reported for a large number of motor vehicle fatalities for the US, the type of adverse weather and the rate of associated fatality vary geographically. These fatalities may be addressed and potentially prevented by modifying speed limits during inclement weather, improving road surfacing, ice and snow removal, and providing transit alternatives, but the impact of potential interventions requires further research. |
Dietary nitrate and the epidemiology of cardiovascular disease: report from a National Heart, Lung, and Blood Institute Workshop
Ahluwalia A , Gladwin M , Coleman GD , Hord N , Howard G , Kim-Shapiro DB , Lajous M , Larsen FJ , Lefer DJ , McClure LA , Nolan BT , Pluta R , Schechter A , Wang CY , Ward MH , Harman JL . J Am Heart Assoc 2016 5 (7) In view of continuing unanswered questions regarding the geographical and demographic distribution of cardiovascular disease, and recent discoveries about the effects of dietary nitrate on cardiovascular physiology, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop to identify approaches to address how best to incorporate the study of nitrate exposures into ongoing studies of cardiovascular epidemiology. The NHLBI invited speakers who had made recent contributions to the study of the functions of nitrate on the cardiovascular system, on the occurrence of nitrate in foods and drinking water, or who had expert knowledge of cardiovascular surveys with wide geographical variability and therefore the greatest potential variability in dietary and drinking water nitrate. Because of the history of research on the possible carcinogenicity of nitrite, an expert in this field was also invited. The following document is a synthesis of the material presented and discussed and of literature cited at the workshop. The workshop from which this article is derived was funded and convened by the NHLBI. |
Decrease in rate of opioid analgesic overdose deaths - Staten Island, New York City, 2011-2013
Paone D , Tuazon E , Kattan J , Nolan ML , O'Brien DB , Dowell D , Farley TA , Kunins HV . MMWR Morb Mortal Wkly Rep 2015 64 (18) 491-4 From 2000 to 2011, the rate of unintentional drug poisoning (overdose) deaths involving opioid analgesics increased 435% in Staten Island, from 2.0 to 10.7 per 100,000 residents. During 2005-2011, disparities widened between Staten Island and the other four New York City (NYC) boroughs (Bronx, Brooklyn, Manhattan, and Queens); in 2011, the rate in Staten Island was 3.0-4.5 times higher than in the other boroughs. In response, the NYC Department of Health and Mental Hygiene (DOHMH) implemented a comprehensive five-part public health strategy, with both citywide and Staten Island-targeted efforts: 1) citywide opioid prescribing guidelines, 2) a data brief for local media highlighting Staten Island mortality and prescribing data, 3) Staten Island town hall meetings convened by the NYC commissioner of health and meetings with Staten Island stakeholders, 4) a Staten Island campaign to promote prescribing guidelines, and 5) citywide airing of public service announcements with additional airing in Staten Island. Concurrently, the New York state legislature enacted the Internet System for Tracking Over-Prescribing (I-STOP), a law requiring prescribers to review the state prescription monitoring system before prescribing controlled substances. This report describes a 29% decline in the opioid analgesic-involved overdose death rate in Staten Island from 2011 to 2013, while the rate did not change in the other four NYC boroughs, and compares opioid analgesic prescribing data for Staten Island with data for the other boroughs. Targeted public health interventions might be effective in lowering opioid analgesic-involved overdose mortality rates. |
Revisiting Pneumatic Nail Gun Trigger Recommendations
Albers J , Lowe BD , Lipscomb H , Hudock SD , Dement J , Evanoff B , Fullen M , Gillen M , Kaskutas V , Nolan J , Patterson D , Platner J , Pompeii L , Schoenfisch A . Prof Saf 2015 60 (3) 30-33 Pneumatic framing nail gun use is ubiquitous throughout the modern homebuilding industry. This tool has a safety device at the end of the gun muzzle that must be depressed before the fastener can be discharged. Generally, these devices have two types of trigger systems that then define how the nail gun fires in response to a trigger press: 1. The sequential actuation trigger requires that each nail can only be discharged when the safety tip is first depressed and, while held depressed, the trigger is squeezed. 2. The contact actuation trigger allows the operator to first squeeze the trigger and, while holding the trigger squeezed, repeatedly bump the safety tip on the workpiece to shoot multiple nails. In the authors' view, however, an unintended consequence of the recommendations published in (Baggs, et al, 1999) and (2001) has been the creation of the appearance of competing risks with nail gun trigger systems. |
Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes.
Neafsey DE , Waterhouse RM , Abai MR , Aganezov SS , Alekseyev MA , Allen JE , Amon J , Arca B , Arensburger P , Artemov G , Assour LA , Basseri H , Berlin A , Birren BW , Blandin SA , Brockman AI , Burkot TR , Burt A , Chan CS , Chauve C , Chiu JC , Christensen M , Costantini C , Davidson VL , Deligianni E , Dottorini T , Dritsou V , Gabriel SB , Guelbeogo WM , Hall AB , Han MV , Hlaing T , Hughes DS , Jenkins AM , Jiang X , Jungreis I , Kakani EG , Kamali M , Kemppainen P , Kennedy RC , Kirmitzoglou IK , Koekemoer LL , Laban N , Langridge N , Lawniczak MK , Lirakis M , Lobo NF , Lowy E , MacCallum RM , Mao C , Maslen G , Mbogo C , McCarthy J , Michel K , Mitchell SN , Moore W , Murphy KA , Naumenko AN , Nolan T , Novoa EM , O'Loughlin S , Oringanje C , Oshaghi MA , Pakpour N , Papathanos PA , Peery AN , Povelones M , Prakash A , Price DP , Rajaraman A , Reimer LJ , Rinker DC , Rokas A , Russell TL , Sagnon N , Sharakhova MV , Shea T , Simao FA , Simard F , Slotman MA , Somboon P , Stegniy V , Struchiner CJ , Thomas GW , Tojo M , Topalis P , Tubio JM , Unger MF , Vontas J , Walton C , Wilding CS , Willis JH , Wu YC , Yan G , Zdobnov EM , Zhou X , Catteruccia F , Christophides GK , Collins FH , Cornman RS , Crisanti A , Donnelly MJ , Emrich SJ , Fontaine MC , Gelbart W , Hahn MW , Hansen IA , Howell PI , Kafatos FC , Kellis M , Lawson D , Louis C , Luckhart S , Muskavitch MA , Ribeiro JM , Riehle MA , Sharakhov IV , Tu Z , Zwiebel LJ , Besansky NJ . Science 2015 347 (6217) 1258522 Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts. |
Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013
Ridpath A , Driver CR , Nolan ML , Karpati A , Kass D , Paone D , Jakubowski A , Hoffman RS , Nelson LS , Kunins HV . MMWR Morb Mortal Wkly Rep 2014 63 (50) 1195-8 Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs. |
Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda
Palaia JM , McConnell M , Achenbach JE , Gustafson CE , Stoermer KA , Nolan M , Guay LA , Leitner TK , Matovu F , Taylor AW , Fowler MG , Janoff EN . J Infect 2014 68 (3) 264-72 OBJECTIVES: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. METHODS: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. RESULTS: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 +/- 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. CONCLUSIONS: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers. |
Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single dose nevirapine
Aizire J , McConnell MS , Mudiope P , Mubiru M , Matovu F , Parsons TL , Elbireer A , Nolan M , Janoff EN , Fowler MG . J Acquir Immune Defic Syndr 2012 60 (5) 483-8 OBJECTIVE: To determine kinetics after single dose nevirapine (sdNVP) and the impact on HIV RNA (viral load: VL) in maternal plasma and breast milk (BM). METHODS: Cohort of 120 HIV-1 infected pregnant Ugandan women received perinatal sdNVP alone and followed with their infants through 24 weeks post-delivery.We assessed the relationship of nevirapine concentration (tandem mass-spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, v1.5) in maternal plasma and BM over time. RESULTS: At week 1 postpartum, NVP (≥10ng/ml) was detected in all 53 plasma and 47/51(92.2%) BM samples with median (interquartile ranges: IQR) of, respectively, 171(78-214) ng/ml and 112(64-158) ng/ml, p=0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery: R=0.71, p<0.001 and week1: R=0.69, p<0.001 but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma: R=0.39, p=0.004 and BM: R=0.48, p=0.013. There was a VL rebound in both compartments which peaked at week 4 to levels greater than at week 1, (significantly in plasma (p<0.001) but not in BM) and remained stable thereafter. Median VL was consistently greater (11-50 fold) in plasma than BM at all time points (all p<0.001). CONCLUSION: After sdNVP, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer "tail" (>1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces. |
High redundancy draft sequencing of 15 clinical and environmental Burkholderia strains
Mukhopadhyay S , Thomason MP , Lentz S , Nolan N , Willner K , Gee JE , Glass MB , Inglis TJ , Merritt A , Levy A , Sozhamannan S , Mateczun A , Read TD . J Bacteriol 2010 192 (23) 6313-4 The Gram negative Burkholderia genus includes several species of intracellular bacterial pathogens that pose substantial risk to humans. In this study we have generated draft genome sequences of 15 strains of B. oklahomensis, B. pseudomallei, B. thailandensis and B. ubonensis to an average sequence read coverage of 25-40 fold. |
Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration
Hudelson SE , McConnell MS , Bagenda D , Piwowar-Manning E , Parsons TL , Nolan ML , Bakaki PM , Thigpen MC , Mubiru M , Fowler MG , Eshleman SH . AIDS 2010 24 (4) 557-61 OBJECTIVE: Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women. METHODS: Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy. RESULTS: HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a nonsignificant trend between detection of NVP resistance in breast milk and plasma (P = 0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype, or concentration of NVP in breast milk or plasma. CONCLUSION: NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance. |
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