Philip Bulterys

All Publications

• Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy. The New England journal of medicine Hamilton, M. P., Sugio, T., Noordenbos, T., Shi, S., Bulterys, P. L., Liu, C. L., Kang, X., Olsen, M. N., Good, Z., Dahiya, S., Frank, M. J., Sahaf, B., Mackall, C. L., Gratzinger, D., Diehn, M., Alizadeh, A. A., Miklos, D. B. 2024; 390 (22): 2047-2060

  Abstract

  The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).

  View details for DOI 10.1056/NEJMoa2401361

  View details for PubMedID 38865660

• The Histopathologic Features of Early COVID Pneumonia in a Pediatric Patient: New Insight into the Role of Macrophages INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY Bulterys, P. L., Xu, G., Pinsky, B. A., Troxell, M. L., Menke, J. R., Berry, G. J., Fernandez-Pol, S., Hazard, F. K. 2024

  View details for DOI 10.1177/10668969241236704

  View details for Web of Science ID 001196092100001

• Postpandemic Effects of COVID-19 Shelter-in-Place Orders on the Gastrointestinal Pathogen Landscape. Journal of clinical microbiology Bulterys, P. L., Leung, N. Y., Saleem, A., Budvytiene, I., Pinsky, B. A., Banaei, N. 2023: e0038523

  View details for DOI 10.1128/jcm.00385-23

  View details for PubMedID 37466426

• Trimmed central venous catheters do not increase endothelial injury in an ovine model. The journal of vascular access Wang, H., Williams, K. M., Elde, S., Bulterys, P. L., Thakore, A. D., Lucian, H. J., Farry, J. M., Mullis, D. M., Zhu, Y., Paulsen, M. J., Woo, Y. J. 2023: 11297298231153716

  Abstract

  Central venous catheters (CVCs) are often trimmed during heart transplantation and pediatric cardiac surgery. However, the risk of endothelial injury caused by the cut tip of the CVC has not been evaluated. We hypothesized that there is no difference in the degree of endothelial injury associated with trimmed CVCs versus standard untrimmed CVCs.In four adult male sheep, the left external jugular vein was exposed in three segments, one designated for an untouched control group, one for the trimmed CVC group, and one for the untrimmed CVC group. Trimmed and untrimmed CVC tips were rotated circumferentially within their respective segments to abrade the lumen of the vein. The vein samples were explanted, and two representative sections from each sample were analyzed using hematoxylin and eosin (H&E) staining, as well as with immunohistochemistry against CD31, von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and caveolin. Higher immunohistochemical stain distributions and intensities are associated with normal health and function of the venous endothelium. Data are presented as counts with percentages or as means with standard error.H&E staining revealed no evidence of endothelial injury in 6/8 (75%) samples from the untouched control group, and no injury in 4/8 (50%) samples from both the trimmed and untrimmed CVC groups (p = 0.504). In all remaining samples from each group, only mild endothelial injury was observed. Immunohistochemical analysis comparing trimmed CVCs versus untrimmed CVCs revealed no difference in the percentage of endothelial cells staining positive for CD31 (57.5% ± 7.2% vs 55.0% ± 9.2%, p = 0.982), vWF (73.8% ± 8.0% vs 62.5% ± 9.6%, p = 0.579), eNOS (66.3% ± 4.2% vs 63.8% ± 7.5%, p = 0.962), and caveolin (53.8% ± 5.0% vs 51.3% ± 4.4%, p = 0.922). There were no significant differences between the groups in the distributions of stain intensity for CD31, vWF, eNOS, and caveolin.Trimmed CVCs do not increase endothelial injury compared to standard untrimmed CVCs.

  View details for DOI 10.1177/11297298231153716

  View details for PubMedID 36765464

• Validated transport conditions maintain the quality of washed red blood cells. Transfusion Baker, S. A., Wong, L. K., Wieland, R., Bulterys, P., Allard, L., Nguyen, L., Quach, T., Nguyen, A., Chaesuh, E., Cheng, P., Bowen, R., Virk, M. 2022; 62 (9): 1860-1870

  Abstract

  BACKGROUND: Washing red blood cell (RBC) units prior to transfusion is indicated for certain patients. In the United States, units stored at 1°C-6°C or transported at 1°C-10°C are available for issue up to 24h, if not used immediately. The washing procedure commonly utilizes room temperature saline resulting in units starting out above the allowed temperature range. This leads to wastage if units are issued and returned too quickly before having a chance to equilibrate in a transport cooler.STUDY DESIGN AND METHODS: Here we performed an experimental study of washed RBC quality comparing "ideal" storage conditions in a blood bank refrigerator to a "real-world" simulation of unit transport, including holding in a transport cooler. Twelve RBC units were washed and allocated evenly into either condition.RESULTS: Measurements at 0, 1, 3, 6, 12, and 24h post-washing revealed that placement in a transport cooler was associated with higher unit temperature prior to 12h (p=.013) with a maximum difference of 9.3°C. Despite this difference, several measures of unit quality including extracellular potassium, pH, lactate, and free hemoglobin were indistinguishable between conditions (p=.382, .224, .286, .691, respectively). We selected half of the tested units from our irradiated inventory and confirmed increased potassium leak (p<.001) and accumulation of free hemoglobin (p=.012) in irradiated units.DISCUSSION: Washed units stored under approved transport conditions are acceptable to return to inventory up to 24h after washing and we provide a prediction interval-based temperature threshold for rejecting these units, permitting reduced waste.

  View details for DOI 10.1111/trf.17062

  View details for PubMedID 36084205

• Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Yang, L. M., Costales, C., Ramanathan, M., Bulterys, P. L., Murugesan, K., Schroers-Martin, J., Alizadeh, A. A., Boyd, S. D., Brown, J. M., Nadeau, K. C., Nadimpalli, S. S., Wang, A. X., Busque, S., Pinsky, B. A., Banaei, N. 2022; 153: 105217

  Abstract

  BACKGROUND: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.METHODS: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naive individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.RESULTS: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P<0.001), sphingosine 1-phsophate (S1P) receptor modulators (P<0.001), mycophenolate (P=0.002), and B cell lymphoma (P=0.004); those associated with low cellular response rates included S1P receptor modulators (P<0.001) and mycophenolate (P<0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.CONCLUSIONS: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

  View details for DOI 10.1016/j.jcv.2022.105217

  View details for PubMedID 35714462

• Expression of CD47 Protein in Hematolymphoid Neoplasms: Implications for CD47-Mediated Cancer Immunotherapy Zhang, J., Bulterys, P., Fernandez-Pol, S., Younes, S., Zhao, S., Mansoor, A., Natkunam, Y. SPRINGERNATURE. 2022: 1052-1053

  View details for Web of Science ID 000770361802312

• Expression of CD47 Protein in Hematolymphoid Neoplasms: Implications for CD47-Mediated Cancer Immunotherapy Zhang, J., Bulterys, P., Fernandez-Pol, S., Younes, S., Zhao, S., Mansoor, A., Natkunam, Y. SPRINGERNATURE. 2022: 1052-1053

  View details for Web of Science ID 000770360202312

• Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen: a case report and approach to differential diagnosis. Radiology case reports Nguyen, A., Negrete, L. M., Bulterys, P. L., Shen, L. 2021; 16 (11): 3213-3216

  Abstract

  We present a case of an inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen. The patient is a 44-year-old woman, without significant underlying history, who presented with nonspecific abdominal pain for a few months. Both a contrast enhanced computed tomography and magnetic resonance imaging revealed a new 2.5 cm enhancing splenic lesion, which demonstrated hypermetabolic activity on subsequent positron emission tomography and computed tomography scan. Since the lesion was new compared to more remote imaging and hypermetabolic, a splenectomy was performed. Pathology confirmed the diagnosis and demonstrated positivity for Epstein-Barr Virus .

  View details for DOI 10.1016/j.radcr.2021.07.078

  View details for PubMedID 34484521

• Diagnosis of Dengue in a returning traveler from Pakistan suspected of COVID-19, California, USA. Diagnostic microbiology and infectious disease Bulterys, P. L., Solis, D., Verghese, M., Huang, C., Sibai, M., Costales, C., Sahoo, M. K., Pinsky, B. A. 2021; 101 (4): 115517

  Abstract

  Dengue and COVID-19 cocirculation presents a diagnostic conundrum for physicians evaluating patients with acute febrile illnesses, both in endemic regions and among returning travelers. We present a case of a returning traveler from Pakistan who, following repeated negative SARS-CoV-2 tests, was found to have a Dengue virus serotype 2 infection.

  View details for DOI 10.1016/j.diagmicrobio.2021.115517

  View details for PubMedID 34537475

• A spatio-temporal analysis of scrub typhus and murine typhus in Laos; implications from changing landscapes and climate. PLoS neglected tropical diseases Roberts, T., Parker, D. M., Bulterys, P. L., Rattanavong, S., Elliott, I., Phommasone, K., Mayxay, M., Chansamouth, V., Robinson, M. T., Blacksell, S. D., Newton, P. N. 2021; 15 (8): e0009685

  Abstract

  BACKGROUND: Scrub typhus (ST) and murine typhus (MT) are common but poorly understood causes of fever in Laos. We examined the spatial and temporal distribution of ST and MT, with the intent of informing interventions to prevent and control both diseases.METHODOLOGY AND PRINCIPLE FINDINGS: This study included samples submitted from 2003 to 2017 to Mahosot Hospital, Vientiane, for ST and MT investigation. Serum samples were tested using IgM rapid diagnostic tests. Patient demographic data along with meteorological and environmental data from Laos were analysed. Approximately 17% of patients were positive for either ST (1,337/8,150 patients tested) or MT (1,283/7,552 patients tested). While both diseases occurred in inhabitants from Vientiane Capital, from the univariable analysis MT was positively and ST negatively associated with residence in Vientiane Capital. ST was highly seasonal, with cases two times more likely to occur during the wet season months of July-September compared to the dry season whilst MT peaked in the dry season. Multivariable regression analysis linked ST incidence to fluctuations in relative humidity whereas MT was linked to variation in temperature. Patients with ST infection were more likely to come from villages with higher levels of surface flooding and vegetation in the 16 days leading up to diagnosis.CONCLUSIONS: The data suggest that as cities expand, high risk areas for MT will also expand. With global heating and risks of attendant higher precipitation, these data suggest that the incidence and spatial distribution of both MT and ST will increase.

  View details for DOI 10.1371/journal.pntd.0009685

  View details for PubMedID 34432800

• Impact of COVID-19 shelter-in-place order on transmission of gastrointestinal pathogens in Northern California. Journal of clinical microbiology Bulterys, P. L., Leung, N. Y., Saleem, A., Budvytiene, I., Banaei, N. 2021

  Abstract

  In response to the COVID-19 pandemic, California was the first state to impose a strict shelter-in-place (SIP) order in March 2020..

  View details for DOI 10.1128/JCM.00449-21

  View details for PubMedID 33846223

• Case-Control Study of Individuals with Discrepant Nucleocapsid and Spike Protein SARS-CoV-2 IgG Results. Clinical chemistry Wang, H. n., Wiredja, D. n., Yang, L. n., Bulterys, P. L., Costales, C. n., Röltgen, K. n., Manalac, J. n., Yee, J. n., Zehnder, J. n., Shi, R. Z., Boyd, S. D., Pinsky, B. A. 2021

  Abstract

  Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results.Over a two-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis.There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] versus 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] versus 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6.Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.

  View details for DOI 10.1093/clinchem/hvab045

  View details for PubMedID 33720347

• GloFlow: Whole Slide Image Stitching from Video Using Optical Flow and Global Image Alignment Krishna, V., Joshi, A., Vrabac, D., Bulterys, P., Yang, E., Fernandez-Pol, S., Ng, A. Y., Rajpurkar, P., DeBruijne, M., Cattin, P. C., Cotin, S., Padoy, N., Speidel, S., Zheng, Y., Essert, C. SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 519-528

  View details for DOI 10.1007/978-3-030-87237-3_50

  View details for Web of Science ID 000712019200050

• Chronic lymphoproliferative disorder of NK cells with TNFAIP3 and DNMT3A mutations. Blood Bulterys, P. L., Silva, O. 2021; 137 (24): 3460

  View details for DOI 10.1182/blood.2021011812

  View details for PubMedID 34137843

• Virulence from the rhizosphere: ecology and evolution of Burkholderia pseudomallei-complex species. Current opinion in microbiology French, C. T., Bulterys, P. L., Woodward, C. L., Tatters, A. O., Ng, K. R., Miller, J. F. 2020; 54: 18–32

  Abstract

  Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) cause the often-lethal infectious diseases melioidosis and glanders, respectively. Curiously, closely related species within the Bp complex share a nearly identical arsenal of virulence traits, yet are harmless to humans. Clues to the origin of virulence in this group can be found in their genetics and ecology. As a resident of the rhizosphere, Bp faces competition for nutrients and predation by other organisms. Adaptation over millennia has enabled Bp to accumulate mechanisms that overlap in their ability to promote fitness in the environment and virulence in mammals. Here, we review the ecology of Bp and its range of virulence attributes, and offer hypotheses on the evolution of virulence in the Bp complex which are relevant to other environmental pathogens.

  View details for DOI 10.1016/j.mib.2019.12.004

  View details for PubMedID 32028234

• Comparison of a laboratory-developed test targeting the envelope gene with three nucleic acid amplification tests for detection of SARS-CoV-2. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Bulterys, P. L., Garamani, N. n., Stevens, B. n., Sahoo, M. K., Huang, C. n., Hogan, C. A., Zehnder, J. n., Pinsky, B. A. 2020; 129: 104427

  Abstract

  Numerous nucleic acid amplification tests, including real-time, reverse transcription PCR (rRT-PCR) and isothermal amplification methods, have been developed to detect SARS-CoV-2 RNA, including many that have received emergency use authorization (EUA). There is a need to assess their test performance relative to one another.The aim of this study was to compare the test performance of a high complexity laboratory-developed rRT-PCR EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene with other tests: the Atila isothermal amplification assay targeting the nucleocapsid (N) gene and open reading frame 1ab (ORF1ab), the Altona E and spike (S) multiplex, real-time RT-PCR, and the US Centers for Disease Control and Prevention (CDC) N1 and N2 rRT-PCRs.A diagnostic comparison study was performed by testing nasopharyngeal samples from persons under investigation for coronavirus disease 2019 (COVID-19). Assay performance was assessed by percent agreement and Cohen's kappa coefficient.Positive percent agreement with the SHC EUA reference assay was 82.8 % (95 % confidence interval (CI) 65.0 to 92.9) for Atila, 86.7 % (95 % CI 69.7 to 95.3) for the Altona E and S targets, and 86.7 % (95 % CI 69.7 to 95.3) and 90.0 % (95 % CI 73.6 to 97.3), for the CDC N1 and N2 targets, respectively. All assays demonstrated 100 % negative percent agreement. Kappa coefficients ranged from 0.86 to 0.92, indicating excellent agreement.Performance was comparable among the SARS-CoV-2 nucleic acid amplification methods tested, with a limited number of discrepancies observed in specimens with low viral loads.

  View details for DOI 10.1016/j.jcv.2020.104427

  View details for PubMedID 32535398

  View details for PubMedCentralID PMC7207111

• An in situ high-throughput screen identifies inhibitors of intracellular Burkholderia pseudomallei with therapeutic efficacy PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Bulterys, P. L., Toesca, I. J., Norris, M. H., Maloy, J. P., Fitz-Gibbon, S. T., France, B., Toffig, B., Morselli, M., Somprasong, N., Pellegrini, M., Schweizer, H. P., Tuanyok, A., Damoiseaux, R., French, C. T., Miller, J. F. 2019; 116 (37): 18597–606

  Abstract

  Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Tier-1 Select Agents that cause melioidosis and glanders, respectively. These are highly lethal human infections with limited therapeutic options. Intercellular spread is a hallmark of Burkholderia pathogenesis, and its prominent ties to virulence make it an attractive therapeutic target. We developed a high-throughput cell-based phenotypic assay and screened ∼220,000 small molecules for their ability to disrupt intercellular spread by Burkholderia thailandensis, a closely related BSL-2 surrogate. We identified 268 hits, and cross-species validation found 32 hits that also disrupt intercellular spread by Bp and/or Bm Among these were a fluoroquinolone analog, which we named burkfloxacin (BFX), which potently inhibits growth of intracellular Burkholderia, and flucytosine (5-FC), an FDA-approved antifungal drug. We found that 5-FC blocks the intracellular life cycle at the point of type VI secretion system 5 (T6SS-5)-mediated cell-cell spread. Bacterial conversion of 5-FC to 5-fluorouracil and subsequently to fluorouridine monophosphate is required for potent and selective activity against intracellular Burkholderia In a murine model of fulminant respiratory melioidosis, treatment with BFX or 5-FC was significantly more effective than ceftazidime, the current antibiotic of choice, for improving survival and decreasing bacterial counts in major organs. Our results demonstrate the utility of cell-based phenotypic screening for Select Agent drug discovery and warrant the advancement of BFX and 5-FC as candidate therapeutics for melioidosis in humans.

  View details for DOI 10.1073/pnas.1906388116

  View details for Web of Science ID 000485145400067

  View details for PubMedID 31439817

• Climatic drivers of melioidosis in Laos and Cambodia: a 16-year case series analysis. The Lancet. Planetary health Bulterys, P. L., Bulterys, M. A., Phommasone, K., Luangraj, M., Mayxay, M., Kloprogge, S., Miliya, T., Vongsouvath, M., Newton, P. N., Phetsouvanh, R., French, C. T., Miller, J. F., Turner, P., Dance, D. A. 2018; 2 (8): e334-e343

  Abstract

  Burkholderia pseudomallei is the cause of melioidosis, a serious and difficult to treat infection that is endemic throughout the tropics. Melioidosis incidence is highly seasonal. We aimed to identify the climatic drivers of infection and to shed light on modes of transmission and potential preventive strategies.We examined the records of patients diagnosed with melioidosis at the Microbiology Laboratory of Mahosot Hospital in Vientiane, Laos, between October, 1999, and August, 2015, and all patients with culture-confirmed melioidosis presenting to the Angkor Hospital for Children in Siem Reap, Cambodia, between February, 2009, and December, 2013. We also examined local temperature, humidity, precipitation, visibility, and wind data for the corresponding time periods. We estimated the B pseudomallei incubation period by examining profile likelihoods for hypothetical exposure-to-presentation delays.870 patients were diagnosed with melioidosis in Laos and 173 patients were diagnosed with melioidosis in Cambodia during the study periods. Melioidosis cases were significantly associated with humidity (p<0·0001), low visibility (p<0·0001), and maximum wind speeds (p<0·0001) in Laos, and humidity (p=0·010), rainy days (p=0·015), and maximum wind speed (p=0·0070) in Cambodia. Compared with adults, children were at significantly higher odds of infection during highly humid months (odds ratio 2·79, 95% CI 1·83-4·26). Lung and disseminated infections were more common during windy months. The maximum likelihood estimate of the incubation period was 1 week (95% CI 0-2).The results of this study demonstrate a significant seasonal burden of melioidosis among adults and children in Laos and Cambodia. Our findings highlight the risks of infection during highly humid and windy conditions, and suggest a need for increased awareness among at-risk individuals, such as children.Wellcome Trust.

  View details for DOI 10.1016/S2542-5196(18)30172-4

  View details for PubMedID 30082048

  View details for PubMedCentralID PMC6076299

• Preventing malaria in HIV-infected pregnant women. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Bulterys, P. L., Kaplan, J. E., Gutman, J. 2014; 58 (5): 660-2

  View details for DOI 10.1093/cid/cit805

  View details for PubMedID 24336822

• Environmental predictors and incubation period of AIDS-associated penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Bulterys, P. L., Le, T., Quang, V. M., Nelson, K. E., Lloyd-Smith, J. O. 2013; 56 (9): 1273-9

  Abstract

  Penicillium marneffei is an emerging dimorphic mycosis endemic in Southeast Asia, and a leading cause of mortality among human immunodeficiency virus (HIV)-infected people in the region. Factors governing the seasonal incidence of P. marneffei infection are unknown, and may yield critical insights into possible reservoirs or modes of acquisition.This study included HIV-infected patients presenting with P. marneffei (n = 719) and Cryptococcus neoformans (n = 1598) infection to the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from 2004 to 2010, and temperature, humidity, wind, precipitation, and HIV-related admissions data for the corresponding period. We used multivariate regression modeling to identify factors associated with P. marneffei and C. neoformans admissions. We estimated the P. marneffei incubation period by considering profile likelihoods for different exposure-to-admission delays.We found that P. marneffei admissions were strongly associated with humidity (P < .001), and that precipitation, temperature, and wind did not add explanatory power. Cryptococcus neoformans admissions were not seasonal, and P. marneffei admissions were more common relative to C. neoformans admissions during months of high (≥85%) humidity (odds ratio, 1.49; 95% confidence interval [CI], 1.10-2.01). Maximum likelihood estimation suggested a P. marneffei incubation period of 1 week (95% CI, 0-3 weeks).Our findings suggest that humidity is the most important environmental predictor of P. marneffei admissions, and may drive exposure by facilitating fungal growth or spore release in the environment. In addition, it appears that a high proportion of penicilliosis patients present to the hospital with primary disseminated infection within 3 weeks of exposure.

  View details for DOI 10.1093/cid/cit058

  View details for PubMedID 23386634

  View details for PubMedCentralID PMC3888300

• Placental Malaria and Mother-to-Child Transmission of Human Immunodeficiency Virus-1 in Rural Rwanda AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Bulterys, P. L., Chao, A., Dalai, S. C., Zink, M. C., Dushimimana, A., Katzenstein, D., Saah, A. J., Bulterys, M. 2011; 85 (2): 202-206

  Abstract

  We conducted a nested case-control study of placental malaria (PM) and mother-to-child transmission (MTCT) of human immunodeficiency virus-1 (HIV-1) within a prospective cohort of 627 mother-infant pairs followed from October 1989 until April 1994 in rural Rwanda. Sixty stored placentas were examined for PM and other placental pathology, comparing 20 HIV-infected mother-infant (perinatal transmitter) pairs, 20 HIV-uninfected pairs, and 20 HIV-infected mothers who did not transmit to their infant perinatally. Of 60 placentas examined, 45% showed evidence of PM. Placental malaria was associated with increased risk of MTCT of HIV-1 (adjusted odds ratio [aOR] = 6.3; 95% confidence interval [CI] = 1.4-29.1), especially among primigravidae (aOR = 12.0; 95% CI = 1.0-150; P < 0.05). Before antiretroviral therapy or prophylaxis, PM was associated with early infant HIV infection among rural Rwandan women living in a hyper-endemic malaria region. Primigravidae, among whom malaria tends to be most severe, may be at higher risk.

  View details for DOI 10.4269/ajtmh.2011.10-0589

  View details for Web of Science ID 000293613000004

  View details for PubMedID 21813835

  View details for PubMedCentralID PMC3144813

• Viral Sequence Analysis from HIV-Infected Mothers and Infants: Molecular Evolution, Diversity, and Risk Factors for Mother-To-Child Transmission CLINICS IN PERINATOLOGY Bulterys, P. L., Dalai, S. C., Katzenstein, D. A. 2010; 37 (4): 739-?

  Abstract

  Great progress has been made in understanding the pathogenesis, treatment, and transmission of HIV and the factors influencing the risk of mother-to-child transmission (MTCT). Many questions regarding the molecular evolution and genetic diversity of HIV in the context of MTCT remain unanswered. Further research to identify the selective factors governing which variants are transmitted, how the compartmentalization of HIV in different cells and tissues contributes to transmission, and the influence of host immunity, viral diversity, and recombination on MTCT may provide insight into new prevention strategies and the development of an effective HIV vaccine.

  View details for DOI 10.1016/j.clp.2010.08.003

  View details for Web of Science ID 000285485400005

  View details for PubMedID 21078447

  View details for PubMedCentralID PMC3175486

• Cattle, other domestic animal ownership, and distance between dwelling structures are associated with reduced risk of recurrent Plasmodium falciparum infection in southern Zambia TROPICAL MEDICINE & INTERNATIONAL HEALTH Bulterys, P. L., Mharakurwa, S., Thuma, P. E. 2009; 14 (5): 522–28

  Abstract

  To examine the associations between household Plasmodium falciparum infection and a number of factors including domestic animal ownership, potential mosquito breeding sites, indoor darkness, density of people, distance between dwelling structures, and insecticide-treated bed net use.Analyses were based on data collected from a household survey conducted in Macha, Zambia. Thirty-four households with recurrent malaria infection in 2005-2008 were selected as case households and compared with 37 control households with no malaria infection randomly selected from the same geographic area. Logistic regression models were used to identify factors associated with household P. falciparum infection.In multivariate analysis, cattle ownership was associated with reduced risk of P. falciparum infection (adjusted odds ratio = 0.19; 95% CI = 0.05-0.69), as was increased distance between dwelling structures (aOR = 0.26; 95% CI = 0.07-0.98). Ownership of the highest category of cattle, goats, dogs, or cats dramatically reduced the risk of P. falciparum infection (aOR = 0.13; 95% CI = 0.03-0.56).Domestic animal, in particular cattle, ownership and greater distance between dwelling structures were associated with reduced risk of recurrent P. falciparum infection at the household level. These factors should be further investigated as supplemental measures for malaria control in rural African settings.

  View details for PubMedID 19389038