All Publications


  • Post-vaccination SARS-CoV-2 infections and incidence of presumptive B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jacobson, K. B., Pinsky, B. A., Montez Rath, M. E., Wang, H., Miller, J. A., Skhiri, M., Shepard, J., Mathew, R., Lee, G., Bohman, B., Parsonnet, J., Holubar, M. 2021

    Abstract

    BACKGROUND: Although mRNA-based SARS-CoV-2 vaccines report ≥90% efficacy, breakthrough infections occur. Little is known about the effectiveness of these vaccines against SARS-CoV-2 variants, including the highly-prevalent B.1.427/B.1.429 variant in California..METHODS: In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as health care personnel (HCP) with positive SARS-CoV-2 NAAT after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y and E484K mutations by RT-PCR. Mutation prevalence was compared among unvaccinated, early post-vaccinated (<=14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and ≤14 days after dose 2) and fully vaccinated (>14 days after dose 2) PVSCs.RESULTS: From December 2020-April 2021, >=23,090 HCPS received at least1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%) and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had L452R mutation presumed to be B.1.427/B.1.429,. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk for infection with B.1.427/B.1.429 compared with unvaccinated HCP.CONCLUSIONS: Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly ≤14 days post-vaccination, and continued variant surveillance in PVSCs is imperative to control future SARS-CoV-2 surges.

    View details for DOI 10.1093/cid/ciab554

    View details for PubMedID 34137815

  • Patients with uncomplicated COVID-19 have long-term persistent symptoms and functional impairment similar to patients with severe COVID-19: a cautionary tale during a global pandemic. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jacobson, K. B., Rao, M., Bonilla, H., Subramanian, A., Hack, I., Madrigal, M., Singh, U., Jagannathan, P., Grant, P. 2021

    Abstract

    To assess the prevalence of persistent functional impairment after COVID-19, we assessed 118 individuals 3-4 months after their initial COVID-19 diagnosis with a symptom survey, work productivity and activity index questionnaire, and 6-minute walk test. We found significant persistent symptoms and functional impairment, even in non-hospitalized patients with COVID-19.

    View details for DOI 10.1093/cid/ciab103

    View details for PubMedID 33624010

  • Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nature communications Jagannathan, P. n., Andrews, J. R., Bonilla, H. n., Hedlin, H. n., Jacobson, K. B., Balasubramanian, V. n., Purington, N. n., Kamble, S. n., de Vries, C. R., Quintero, O. n., Feng, K. n., Ley, C. n., Winslow, D. n., Newberry, J. n., Edwards, K. n., Hislop, C. n., Choong, I. n., Maldonado, Y. n., Glenn, J. n., Bhatt, A. n., Blish, C. n., Wang, T. n., Khosla, C. n., Pinsky, B. A., Desai, M. n., Parsonnet, J. n., Singh, U. n. 2021; 12 (1): 1967

    Abstract

    Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

    View details for DOI 10.1038/s41467-021-22177-1

    View details for PubMedID 33785743

  • Reactivation of Chagas Disease in a Patient With an Autoimmune Rheumatic Disease: Case Report and Review of the Literature. Open forum infectious diseases Czech, M. M., Nayak, A. K., Subramanian, K. n., Suarez, J. F., Ferguson, J. n., Jacobson, K. B., Montgomery, S. P., Chang, M. n., Bae, G. H., Raghavan, S. S., Wang, H. n., Miranti, E. n., Budvytiene, I. n., Shoor, S. M., Banaei, N. n., Rieger, K. n., Deresinski, S. n., Holubar, M. n., Blackburn, B. G. 2021; 8 (2): ofaa642

    Abstract

    Reactivation of Chagas disease has been described in immunosuppressed patients, but there is a paucity of literature describing reactivation in patients on immunosuppressive therapies for the treatment of autoimmune rheumatic diseases. We describe a case of Chagas disease reactivation in a woman taking azathioprine and prednisone for limited cutaneous systemic sclerosis (lcSSc). Reactivation manifested as indurated and erythematous cutaneous nodules. Sequencing of a skin biopsy specimen confirmed the diagnosis of Chagas disease. She was treated with benznidazole with clinical improvement in the cutaneous lesions. However, her clinical course was complicated and included disseminated CMV disease and subsequent septic shock due to bacteremia. Our case and review of the literature highlight that screening for Chagas disease should be strongly considered for patients who will undergo immunosuppression for treatment of autoimmune disease if epidemiologically indicated.

    View details for DOI 10.1093/ofid/ofaa642

    View details for PubMedID 33575423

    View details for PubMedCentralID PMC7863873

  • Post-vaccination SARS-CoV-2 infections and incidence of the B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center. medRxiv : the preprint server for health sciences Jacobson, K. B., Pinsky, B. A., Rath, M. E., Wang, H., Miller, J. A., Skhiri, M., Shepard, J., Mathew, R., Lee, G., Bohman, B., Parsonnet, J., Holubar, M. 2021

    Abstract

    Distribution of mRNA-based SARS-CoV-2 vaccines to healthcare personnel (HCP) in the United States began in December 2020, with efficacy > 90%. However, breakthrough infections in fully vaccinated individuals have been reported. Meanwhile, multiple SARS-CoV-2 variants of concern have emerged worldwide, including the B.1.427/B.1.429 variant first described in California. Little is known about the real-world effectiveness of the mRNA-based SARS-CoV-2 vaccines against novel variants including B.1.427/B.1.429.In this quality improvement project, post-vaccine SARS-CoV-2 cases (PVSCs) were defined as individuals with positive SARS-CoV-2 nucleic acid amplification test (NAAT) after receiving at least one dose of a SARS-CoV-2 vaccine. Chart extraction of demographic and clinical information was performed, and available specimens meeting cycle threshold value criteria were tested for L452R, N501Y and E484K mutations by RT-PCR.From December 2020 to March 2021, 189 PVSCs were identified out of 22,729 healthcare personnel who received at least one dose of an mRNA-based SARS-CoV-2 vaccine. Of these, 114 (60.3%) occurred within 14 days of first vaccine dose (early post-vaccination), 49 (25.9%) within 14 days of the second vaccine dose (partially vaccinated), and 26 (13.8%) > 14 days after the second dose (fully vaccinated). Of 115 samples available for mutation testing, 42 were positive for L452R alone, presumptive of B.1.427/B.1.429; three had N501Y mutation alone and none were found with E484K mutation. Though on univariate analysis partially- and fully-vaccinated PVSCs were more likely than early post-vaccination PVSCs to be infected with presumptive B.1.427/B.1.429, when adjusted for community prevalence of B.1.427/B.1.429 at the time of infection, partially- and fully-vaccinated PVSC did not have statistically significantly elevated risk ratios for infection with this variant (RR 1.40, 95% CI 0.81-2.43 and RR 1.13, 95% CI 0.59-2.16, respectively).The great majority of PVSCs occurred prior to the expected onset of full, vaccine-derived immunity. Although the B.1.427/B.1.429 variant did not represent a significantly higher proportion of PVSCs than expected, numbers were small and there was a trend towards higher representation in the partially- and fully-vaccinated subset. Continued infection control measures in the workplace and in the community including social distancing and masking, particularly in the early days post-vaccination, as well as continued variant surveillance in PVSCs, is imperative in order to anticipate and control future surges of infection.

    View details for DOI 10.1101/2021.04.14.21255431

    View details for PubMedID 33907767

    View details for PubMedCentralID PMC8077590

  • Interferon-gamma release assay for accurate detection of SARS-CoV-2 T cell response. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Murugesan, K. n., Jagannathan, P. n., Pham, T. D., Pandey, S. n., Bonilla, H. F., Jacobson, K. n., Parsonnet, J. n., Andrews, J. R., Weiskopf, D. n., Sette, A. n., Pinsky, B. A., Singh, U. n., Banaei, N. n. 2020

    Abstract

    We investigated feasibility and accuracy of an interferon-gamma release assay (IGRA) for detection of T cell responses to SARS-CoV-2. Whole blood IGRA accurately distinguished between convalescents and uninfected healthy blood donors with a predominantly CD4+ T cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the COVID-19 pandemic.

    View details for DOI 10.1093/cid/ciaa1537

    View details for PubMedID 33035306

  • Anal Dysplasia in Human Immunodeficiency Virus-Infected Men Who Have Sex With Men With Sexually Acquired Early Hepatitis C Virus Infection. Open forum infectious diseases Jacobson, K. B., Gaisa, M. M., Sigel, K. n., Foster, A. L., Fierer, D. S. 2019; 6 (11): ofz339

    Abstract

    Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of anorectal infection with high-risk human papillomavirus and subsequent high-grade squamous intraepithelial lesions (HSIL), the putative precursor to anal cancer. Recently, an epidemic of sexually transmitted hepatitis C virus (HCV) has emerged that shares this anorectal route of transmission. We hypothesized that the prevalence of anal HSIL would be high in HIV-infected MSM with sexually acquired early HCV infection.High-resolution anoscopy (HRA) findings from a cohort of HIV-infected MSM with sexually acquired early HCV infection were compared with HRA findings from a contemporary cohort of HIV-infected MSM without HCV infection who underwent HRA due to abnormal anal cytology found during routine screening.Sixty HIV-infected MSM with sexually acquired early HCV infection and the comparator group of 1150 HIV-infected MSM with abnormal anal cytology but without HCV underwent HRA. The HIV-infected MSM with sexually acquired early HCV had higher CD4 counts compared with the comparator group (656 and 541 cells/μL, respectively; P = .02). Despite this, the prevalence of anal dysplasia was as high among MSM with early HCV as in the comparator group of MSM with abnormal cytology (47 [78%] and 941 [82%], respectively; P = .50), as was the proportion with HSIL (25 [42%] and 379 [33%], respectively; P = .17).The prevalence of anal dysplasia in HIV-infected MSM with sexually acquired early HCV infection was as high as that of HIV-infected MSM with abnormal anal cytology. These findings suggest that primary screening with HRA may be warranted for HIV-infected MSM with early HCV.

    View details for DOI 10.1093/ofid/ofz339

    View details for PubMedID 31777754

    View details for PubMedCentralID PMC6876538

  • Integrase inhibitor-based regimens result in more rapid virologic suppression rates among treatment-naïve human immunodeficiency virus-infected patients compared to non-nucleoside and protease inhibitor-based regimens in a real-world clinical setting: A retrospective cohort study. Medicine Jacobson, K. n., Ogbuagu, O. n. 2018; 97 (43): e13016

    Abstract

    The integrase strand transfer inhibitor (INSTI) class of antiretroviral therapy (ART) may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in time to achieve virologic suppression are not well-defined in routine clinical settings with contemporary antiretroviral agents.Study was a retrospective single-center study of treatment-naïve human immunodeficiency virus (HIV) patients initiating ART between 2013 and 2016. Among patients on different ART regimen types, we compared rates of and median time to virologic suppression [viral load (VL) <50 copies/mL].A total of 155 patients-45 (29%) female and 110 (71%) male-met study inclusion criteria. Median age was 42 years (interquartile range 31-52), and median baseline CD4 count was 288 cells/μL and VL was 60,000 copies/mL. Seventy-one (46%) initiated an INSTI-based regimen, 58 (37%) were on NNRTI-based regimens, and 26 (17%) on PI-based regimens. In total, 112 (72%) patients achieved virologic suppression at 12 months. Patients on INSTI-based regimens were more likely to achieve virologic suppression by 3, 6, and 12 months (P < .01), and had lower median time to suppression (60 vs 137 days on NNRTI-based regimens and 147 days on PI-based regimens, P < .01).Patients on INSTI-based ART regimens in a real-world setting experienced higher rates of virologic suppression and shorter time from ART initiation to virologic suppression. For HIV patients on INSTI-based ART regimens, virologic failure should be suspected in those with VLs >50 copies/mL before the current recommendation of 48 weeks.

    View details for DOI 10.1097/MD.0000000000013016

    View details for PubMedID 30412140

    View details for PubMedCentralID PMC6221636

  • "It's about my life": facilitators of and barriers to isoniazid preventive therapy completion among people living with HIV in rural South Africa. AIDS care Jacobson, K. B., Niccolai, L. n., Mtungwa, N. n., Moll, A. P., Shenoi, S. V. 2017; 29 (7): 936–42

    Abstract

    Despite the recent rollout of Isoniazid Preventive Therapy (IPT) to prevent TB in people living with HIV in South Africa, adherence and completion rates are low. To explore barriers to IPT completion in rural KwaZulu-Natal, South Africa, we conducted individual semi-structured interviews among 30 HIV patients who had completed or defaulted IPT. Interview transcripts were analyzed according to the framework method of qualitative analysis. Facilitators of IPT completion included knowledge of TB and IPT, accepting one's HIV diagnosis, viewing IPT as similar to antiretroviral therapy, having social support in the community and the clinic, trust in the healthcare system, and desire for health preservation. Barriers included misunderstanding of IPT's preventive role in the absence of symptoms, inefficient health service delivery, ineffective communication with healthcare workers, financial burden of transport to clinic and lost wages, and competing priorities. HIV-related stigma was not identified as a significant barrier to IPT completion, and participants felt confident in their ability to manage stigma, for example by pretending their medications were for unrelated conditions. Completers were more comfortable communicating with health care workers than were defaulters. Efforts to facilitate successful IPT completion must include appropriate counseling and education for individual patients and addressing inefficiencies within the health care system in order to minimize patients' financial and logistical burden. These patient-level and structural changes are necessary for IPT to successfully reduce TB incidence in this resource-limited setting.

    View details for DOI 10.1080/09540121.2017.1283390

    View details for PubMedID 28147705

    View details for PubMedCentralID PMC5545149

  • Shedding of Hepatitis C Virus Into the Rectum of HIV-infected Men Who Have Sex With Men. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Foster, A. L., Gaisa, M. M., Hijdra, R. M., Turner, S. S., Morey, T. J., Jacobson, K. B., Fierer, D. S. 2017; 64 (3): 284–88

    Abstract

    For over a decade we have known of an epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), but there still remains significant controversy over which bodily fluid(s) are responsible for HCV transmission in these men.We enrolled HIV-infected MSM with recent and chronic HCV infection and quantified HCV from rectal fluid obtained by blind swab. We compared the rectal HCV viral load (VL) with paired blood HCV VL.We found rectal HCV shedding in 20 (47%) of 43 men, only one (2%) of whom had visible bleeding. Detection of rectal HCV shedding was associated with blood VL > 5 log10 IU/mL (p = .01), and 85% with blood VL > 5 log10 IU/mL had rectal shedding. The HCV VL of the rectal fluid ranged from 2.6 to 5.5 log10 IU/mL. Based on the median rectal fluid VL, the surface of an average human penis would be exposed to at least 2,300 IU of HCV for the duration of anal intercourse.This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM.

    View details for DOI 10.1093/cid/ciw740

    View details for PubMedID 28013267

  • Porokeratotic Adnexal Ostial Nevus-Report of a Case With Unusual Clinical and Histologic Features. Skinmed Lanoue, J., Jacobson, K. B., Ooka, K., Singh, C., Camacho-Vanegas, O., Martignetti, J. A., Levitt, J., Phelps, R. G. 2016; 14 (3): 221-224

    Abstract

    An 11-year-old Tanzanian girl presented with diffuse verrucous lesions of varying morphology, scarring alopecia, and keloid scars over the face with a predilection for the ears. Physical examination revealed dark keratoderma and patches of hypopigmentation near the midline of the dorsal trunk (Figure 1a). Her forearms were densely covered by verrucous lesions with the exception of a clear linear patch on the dorsal aspect of the left forearm (Figure 1b). The perioral area was notable for white spires projecting from verrucous papules (Figure 1c) while the oral mucosa and teeth appeared normal on visual examination. The rest of her body, including the palms and soles, was covered by patchy, scaly lesions of varying severity.

    View details for PubMedID 27502264

  • Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa. PloS one Jacobson, K. B., Moll, A. P., Friedland, G. H., Shenoi, S. V. 2015; 10 (5): e0127024

    Abstract

    HIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa.We retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients' demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes.Of 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC.Decentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased patient education, active communication between hospitals and PHCs, and tracing of patients lost to follow up. Decentralized and integrated care is successful for carefully selected TB/HIV coinfected patients and should be expanded.

    View details for DOI 10.1371/journal.pone.0127024

    View details for PubMedID 25993636

    View details for PubMedCentralID PMC4438008

  • Care of the patient with XDR-TB who has failed treatment. The Lancet. Respiratory medicine Jacobson, K. B., Tate, M. n., Eksteen, F. n., Moll, A. n., Padayatchi, N. n., Friedland, G. n., Shenoi, S. n. 2015; 3 (4): 269–70

    View details for DOI 10.1016/S2213-2600(15)00109-5

    View details for PubMedID 25890645

    View details for PubMedCentralID PMC4498160

  • Comprehensive on-site medical and public health training for local medical practitioners in a refugee setting. Disaster medicine and public health preparedness Asgary, R. n., Jacobson, K. n. 2013; 7 (1): 82–88

    Abstract

    In refugee settings, local medical personnel manage a broad range of health problems but commonly lack proper skills and training, which contributes to inefficient use of resources. To fill that gap, we designed, implemented, and evaluated a curriculum for a comprehensive on-site training for medical providers.The comprehensive teaching curriculum provided ongoing on-site training for medical providers (4 physicians, 7 medical officers, 15 nurses and nurse aids, and 30 community health workers) in a sub-Saharan refugee camp. The curriculum included didactic sessions, inpatient and outpatient practice-based teaching, and case-based discussions, which included clinical topics, refugee public health, and organizational skills. The usefulness and efficacy of the training were evaluated through pretraining and posttraining tests, anonymous self-assessment surveys, focus group discussions, and direct clinical observation.Physicians had a 50% (95% CI 17%-82%; range, 25%-75%) improvement in knowledge and skills. They rated the quality and usefulness of lectures 4.75 and practice-based teaching 5.0 on a 5-point scale (1=poor to 5=excellent). Evaluation of medical officers' knowledge revealed improvements in (1) overall test scores (52% [SD 8%] to 80% [SD 5%]; P < .0001); (2) pediatric infectious diseases (44% [SD 9%] to 79% [SD 7%]; P < .001); and (3) noninfectious diseases (57% [SD 16%] to 81% [SD 10%] P < .01). Main barriers to effective learning were lack of training prioritization, time constraints, and limited ancillary support.A long-term, ongoing training curriculum for medical providers initiated by aid agencies but integrated into horizontal peer-to-peer education is feasible and effective in refugee settings. Such programs need prioritizing, practice and system-based personnel training, and a comprehensive curriculum to improve clinical decision making.

    View details for DOI 10.1017/dmp.2013.2

    View details for PubMedID 24618139