Since 1976, each February has been host to a series of events recognizing the achievements and contributions of African Americans throughout U.S. history. It is as much a celebration as it is a time of education and reflection. Accordingly, UNMC has planned multiple events to share and commemorate African American culture. Check out the UNMC Newsroom’s post for full details and see below for an abbreviated summary of next week’s events.
Speakers and Panels
February 20th, 3pm Panel discussion about Black and Black diaspora culture and how it is represented in Omaha. Panelists include Eric Ewing, executive director of the Great Plains Black History Museum; Jade Rodgers, historian and adjunct professor at Metropolitan Community College; and Charles Ahovissi, founder of African Culture Connection. Available via YouTube.
February 21st, 10am Justin Payne, award-winning composer, playwright, international vocalist and professor of Black studies at the University of Nebraska at Omaha, speaks on the relationship between African Americans and their influence on all musical genres. Presentation via Zoom.
February 22nd, 3pm Brave Space conversation focusing on the social and ethical impacts that social determinants of health have on the community. Attendees will engage on topics such as defining health equity, health disparities and health inequities; understanding impact of social determinants of health; exploring health status, behaviors and needs of residents of Omaha through a systemic and data-drive approach; and reflect on how health care providers can promote health equity in their practices. Presentation via Zoom.
Other Events
February 6th-24th Donate to a campuswide diaper and supply drive. Donations will go to A Mother’s Love and the Nebraska Diaper Bank. A list of donations and drop-off locations can be found here.
Heads up for later next week
February 25th A two-hour guided tour of North Omaha. On this tour, attendees will learn about the rich legacy of the area, the African American community and why North Omaha is a beacon of the past and important for the future. Pre-registration is required.
Microbe Monday is a monthly installment featuring a microbe of clinical or scientific importance. This month, we discuss Halteria sp. which, while not pathogenic to humans, sheds new light on the competition dynamics between microbes. See here for our previous Microbe Monday posts.
Dr. John DeLong of UNL, who recently discovered a new trick from an old microbe. Credit
In infectious diseases, we tend to focus on the one-directional interaction from microbe to host. This is certainly an important point of view and frames how clinicians treat infections. But it is just a chapter in the lifecycle of most microbes. Many pathogens normally exist outside of humans, whether that be in soil, lakes/rivers, other animal hosts, or elsewhere in the environment. It turns out that, in this environment, microbes can compete fiercely with each other for food and resources. Certain larger microbes even have the ability to eat bacteria. Viruses, on the other hand, have been thought to be too small and contain too little nutrients to fit into the microbe food-chain. Or so we thought…
A micrograph of Halteria, the first identified virus-eating microbe.
A new paper authored by Dr. John DeLong and colleagues at the University of Nebraska-Lincoln has identified the first microbe which acts as a ‘virivore’ or virus-eating organism. Meet Halteria sp. (pictured right), a ciliate which lives in freshwater aquatic environments. This is by no means a new microbe to science; it may have been first identified as far back as 1675 and certain species are found around the world. It is not a picky eater, having been known to consume algae and bacteria for nutrients for some time. But evidence of Halteria consuming viruses is brand new, and was recently published in PNAS earlier this year.
Halteria after consuming fluorescently labeled virus (white/light areas).
In his paper, Dr. DeLong showed that when you put chloroviruses and Halteria in the same flask with no other food sources, viral titers are decreased ~10x while Halteria begin to divide. Furthermore, viral particles were detected inside the ciliate cell. Together, this indicates that the ciliate was consuming virus and using that energy to grow and reproduce. While this is the first evidence of an organism consuming virus, it is not likely the only example in nature. As more scientists start looking for this behavior, we will probably start to see many other microbes exhibiting this trick.
Halteria is not known to cause disease in humans, and it is not a pathogen we encounter in clinical infectious disease. However, this discovery does begin to rewrite the dogma surrounding how we view the microscopic world, and begs the question: what other tricks may microbes be hiding?
Since 1976, each February has been host to a series of events recognizing the achievements and contributions of African Americans throughout U.S. history. It is as much a celebration as it is a time of education and reflection. Accordingly, UNMC has planned multiple events to share and commemorate African American culture. Check out the UNMC Newsroom’s post for full details and see below for an abbreviated summary of next week’s events.
Speakers and Panels
February 13th, 7pm Local media panelists including Terri D. Sanders, publisher of the Omaha Star Newspaper; William King, owner of Media King Communications; Monique Farmer, CEO and founder of Anvil Ready; Serese Cole, KMTV news anchor; and KETV reporters Waverle Monroe and Jonah Gilmore. Available via YouTube.
Other Events
February 6th-24th Donate to a campuswide diaper and supply drive. Donations will go to A Mother’s Love and the Nebraska Diaper Bank. A list of donations and drop-off locations can be found here.
Heads up for later this month
February 25th A two-hour guided tour of North Omaha. On this tour, attendees will learn about the rich legacy of the area, the African American community and why North Omaha is a beacon of the past and important for the future. Pre-registration is required.
192 years ago today, Dr. Lee Crumpler, the first Black woman to receive an M.D. in the United States, was born. We now recognize her birthday as National Black Women Physicians Day to celebrate the contributions of African American woman physicians to medicine.
It is fitting to celebrate Dr. Lee Crumpler’s life and this day of recognition in the broader context of Black History Month and along with the events planned as part of UNMC’s celebration of black history.
Throughout her life, she made essential contributions to medicine, including providing care for newly emancipated slaves under the Freedman’s Bureau, later serving the larger African-American community in Boston, and writing a medical text composed of her notes throughout her career particularly pertaining to the care and prevention of disease in children and mothers. All of these achievements were realized in the face of blatant racism and sexism from colleagues, pharmacists, and the public. Though no known verified image exists of Dr. Lee Crumpler, her triumphs in the face of adversity are inspiring and illustrate the first in a long history of contributions to medicine by African-American woman physicians.
Join us today as we celebrate all African-American woman physicians and their profound contribution to their patients and the medical field.
For more information about Dr. Lee Crumpler, see this article written by Dr. Howard Markel for PBS.
Since 1976, each February has been host to a series of events recognizing the achievements and contributions of African Americans throughout U.S. history. It is as much a celebration as it is a time of education and reflection. Accordingly, UNMC has planned multiple events to share and commemorate African American culture. Check out the UNMC Newsroom’s post for full details and see below for an abbreviated summary of this week’s events.
Speakers and Panels
February 6th, 7pm Tiffany Gamble, executive director of Emerging Ladies Academy and CEO of Gamble Tech Firm, along with David Pollock, founder of Code Black, will discuss the need for more African Americans in IT. Presentation via YouTube.
February 7th, 12pm Presentation by Kia Noelle Johnson, PhD, associate director of the Arthur M. Blank Center for Stuttering Education and Research Satellite in Atlanta and chair of the board of directors for the National Black Association for Speech-Language and Hearing. Zoom link here.
February 8th, 1pm Preston Love Jr., former University of Nebraska Cornhusker football player, Nebraska Black Sports Hall of Fame inductee and founder of 4Urban, will present “Recent Attempts to Turn Wine into Water.” Love will discuss the fullness and richness of Black history and the deep waters of racism and politics. RSVP here for RSVP here for Zoom link.
Other Events
February 6th-24th Donate to a campuswide diaper and supply drive. Donations will go to A Mother’s Love and the Nebraska Diaper Bank. A list of donations and drop-off locations can be found here.
Heads up for later this month
February 25th A two-hour guided tour of North Omaha. On this tour, attendees will learn about the rich legacy of the area, the African American community and why North Omaha is a beacon of the past and important for the future. Pre-registration is required.
It is with profound sadness that the university of Nebraska medical center division of infectious diseases announces the passing of Dr. Diana Florescu. She was a mentor to countless trainees and faculty in Transplant ID, and an inspiration to many more. She was recently honored with the UNMC Scientist Laureate Award, the highest recognition given to UNMC faculty researchers for their contributions to advancing the science of healthcare.
Dr. Florescu will be remembered for her tenacity, grit, kindness, determination, and a positive energy that lit up every room, especially the ballroom when she danced.
We were blessed to have her as an esteemed faculty member in our division and are so grateful that she got her flowers while she was still with us. Our division of ID, and department of internal medicine are devastated, heartbroken as we surround her family with the love and support they need during this time.
More details can be found in this remembrance posting from UNMC, and information about her memorial service can be found in her obituary. Please keep her home and work families in your prayers.
The following post exploring a switch from IV to oral antibiotics for treatment of bacteremia was written by Molly Miller, PharmD, ID Pharmacist at Nebraska Medicine.
How do we usually treat bloodstream infections?
Standard management of bloodstream infections (BSIs) due to Gram-negative rods (GNRs) is empiric IV therapy with an active antimicrobial agent (typically a third or fourth generation cephalosporin, piperacillin-tazobactam, a fluoroquinolone, or a carbapenem) followed by eventual narrowing to definitive therapy based on culture results and susceptibilities. In addition to antibiotic therapy, perhaps the most important aspect of management is source control, which is accomplished by eliminating any nidus of infection (i.e., removing infected catheters/devices, draining abscesses or fluid collections). Treatment of GNR bacteremia is generally recommended for a duration of 7-14 days, but this can be extended for longer durations if the infection is complicated and source control is not achieved.
There has been recent interest in using oral therapy for many serious infections which were traditionally treated exclusively with IV therapy. Recent studies include the POET and OVIVA trials for endocarditis and bone and joint infections, respectively.1,2 Current evidence shows that there are several potential benefits to using oral therapy over extended courses of IV therapy, including reduction in catheter-related complications such as infection and thrombosis, reduction in length of stay (LOS), improvement in patient satisfaction and comfort, and reduction in healthcare costs.1-5
What specifically is the evidence for the use of oral antibiotics in this infection?
Though there have been no prospective, randomized, controlled trials published thus far regarding the use of oral therapy for GNR bacteremia (the SOAB trial is in progress), there is a growing body of observational data supporting this approach. In 2019, Tamma and colleagues published a multicenter, propensity-matched, retrospective cohort study comparing outcomes between adults with monomicrobial bacteremia due to Enterobacterales species who received oral step-down therapy versus continued IV therapy.3 Eligible patients had source control, clinical improvement on initial therapy, an active oral agent available to treat the causative organism, and the ability to take and absorb oral medication. Of the patients transitioned to oral therapy, most (84%) received a “highly bioavailable” antibiotic (fluoroquinolone or trimethoprim-sulfamethoxazole). The median time to oral switch was 3 days of IV therapy. There was no difference in all-cause mortality or recurrent bacteremia at 30 days between the oral and IV therapy groups; however, there was a shorter median time to discharge (5 days vs 7 days) in the oral step-down group.3 A number of smaller retrospective studies have shown similar results, with transition to oral therapy resulting in similar clinical outcomes with reductions in hospital LOS and IV line-associated complications.4,5
In 2016, a retrospective study was published by Kutob and colleagues, which included patients with GNR BSI and compared outcomes between patients receiving high, moderate, and low bioavailability agents.6 This study found that high bioavailability oral agents were effective definitive therapy; however, a higher failure rate was observed in patients receiving a moderate to low bioavailability agent compared to a high bioavailability agent (12-14% vs 2%). This poses the question: which oral antibiotics are suitable for use as step-down therapy in GNR BSI? A recent meta-analysis compared outcomes of oral step down to fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) versus oral beta-lactams (OBLs) for Enterobacterales BSI.7 This meta-analysis pooled a population of 2,289 patients, of whom 65% received FQs, 7.7% received TMP-SMX, and 27.2% received OBL therapy. Across the studies, patients were transitioned to oral therapy after a median of 3-5 days of IV therapy. There was no difference in mortality noted between groups receiving FQ or TMP-SMX compared to OBL (5.1% vs 3.5%, p = 0.63); however, patients receiving OBLs had a 2x higher odds of recurrent infection versus FQs. An important thing to note, however, is that bioavailability is only part of the equation, and other pharmacokinetic and pharmacodynamic (PK/PD) principles are important to consider when dosing oral antibiotics to treat serious infections. One specific concern the authors of this meta-analysis had was that 30-50% of patients in the included studies received suboptimal doses of OBLs. Another concern is that OBLs require every 6-8 hour dosing to attain target levels compared to every 12-24 hour dosing for TMP-SMX or FQs, which may introduce adherence issues and therefore increase the risk of treatment failure as well.
Though FQs and TMP-SMX have benefits compared to OBLs for the reasons discussed above, note that these therapies have significant toxicities, and it is important to consider drug- and patient-specific factors when choosing an oral antibiotic. FQs have many boxed warnings for serious adverse events, including tendon rupture, aortic aneurysm rupture, central nervous system effects, QT prolongation, dysglycemias, and increased risk of C. difficileinfection. TMP-SMX may cause blood dyscrasias, severe dermatologic reactions, hyperkalemia, and increased serum creatinine, and it also carries some drug-drug interactions, particularly with warfarin and other agents causing increased serum potassium. In comparison, OBLs are fairly well-tolerated, with rash and gastrointestinal side effects being most common. As always, patient co-morbidities, allergies/intolerances, and drug-drug interactions should be taken into account when choosing appropriate therapy.
In summary…
Patients who have achieved effective source control and are clinically stable (including hemodynamically stable and afebrile) who are able to tolerate and absorb oral antibiotics with no contraindications can be considered for transition to oral therapy if there is assurance of good adherence and close monitoring and follow-up. Oral antibiotics with high bioavailability have the most supportive evidence for use in these circumstances. While most often this is a FQ or potentially TMP-SMX, there is emerging evidence that some OBLs may be acceptable if dosed appropriately. Other considerations include patient-specific factors (allergies, co-morbidities, and drug-drug interactions), antibiotic penetration to the site of infection, and antimicrobial susceptibility. By transitioning patients to oral therapy when possible, we can reduce the risk of IV line-related complications, reduce length of stay, and improve patient satisfaction and comfort.
References:
Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New Engl J Med. 2019;380(5):415-24.
Li H-K, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. New Engl J Med. 2019;380(5):425-36.
Tamma PD, Conley AT, Cosgrove SE, Harris AD, Lautenbach E, Amoah J, Avdic E, Tolomeo P, Wise J, Subudhi S, Han JH; Antibacterial Resistance Leadership Group. Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia. JAMA Intern Med. 2019 Mar 1;179(3):316-323. doi: 10.1001/jamainternmed.2018.6226. Erratum in: JAMA Intern Med. 2019 Nov 1;179(11):1607. PMID: 30667477; PMCID: PMC6439703.
Rieger KL, Bosso JA, MacVane SH, Temple Z, Wahlquist A, Bohm N. Intravenous-only or intravenous transitioned to oral antimicrobials for Enterobacteriaceae-associated bacteremic urinary tract infection. Pharmacotherapy. 2017;37(11): 1479-1483. doi:10.1002/phar.2024
Thurber KM, Arnold JR, Narayanan PP, Dierkhising RA, Sampathkumar P. Comparison of intravenous and oral definitive antibiotic regimens in hospitalised patients with Gram-negative bacteraemia from a urinary tract infection. J Glob Antimicrob Resist. 2019 Sep;18:243-248. doi: 10.1016/j.jgar.2019.03.013. Epub 2019 Mar 26. PMID: 30926468.
Kutob LF, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. Int J Antimicrob Agents. 2016;48(5):498-503.
Punjabi C, Tien V, Meng L, et al. Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs beta-lactams as step-down therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis. Open Forum Infect Dis. 2019; 6(10): ofz364.
Last week Dr. Diana F. Florescu was honored at a celebration recognizing her recent achievement of being named the UNMC Scientist Laureate, the highest award UNMC bestows upon its researchers.
Dr. Florescu is a Professor in the Division of Infectious Diseases here at UNMC. She came to UNMC first in 2009 as a phenomenal clinician with a focus in treating infections in immunocompromised hosts (solid organ transplant recipients and individuals with malignancy), and over the next 14 years would develop a distinguished research career focused on viral infections in solid organ transplant recipients, including treatment and vaccines. This work has been nationally and internationally recognized with nearly 100 peer-reviewed articles, and in 2020, she was a recipient of the UNMC Distinguished Scientist award, recognizing the most productive researchers at UNMC in the previous 5 years. She did not slow this work during the COVID-19 pandemic, in fact, she escalated her clinical research, leading investigation as a top enrolling site for the Novovax (NVX-CoV2373) COVID-19 vaccine clinical trial, as well as other COVID-19 treatment trials and other non-COVID-19 studies in immunocompromised patients.
In addition to her extraordinary contributions to research and clinical care, Dr. Florescu has served as an invaluable mentor to the UNMC ID Faculty, residents, and APPs in the transplant ID service line. Outside of the hospital, she has been an advocate for her immunocompromised patients and patients experiencing homelessness in Omaha, and combines her love (and talent!) for ballroom dancing with this service, competing in and winning many dance competition fundraisers. UNMC ID is immensely proud of Dr. Florescu and excited to celebrate this recognition with her.
Here are some highlights of her outstanding accomplishments and comments made by a few of her mentors, colleagues, mentees, and friends celebrating her recognition. Congratulations, Dr. Florescu!
A #PharmToExamTable question about the evidence for using voriconazole in disseminated Histoplasmosis infection, answered by Molly Kernan, PharmD, a graduate of the UNMC College of Pharmacy and current pharmacy resident at Nebraska Medicine.
(Reviewed by Andrew Watkins, PharmD)
What is Histoplasma?
Histoplasma capsulatum is a dimorphic fungus that is endemic in the Ohio and Mississippi River valleys in the United States. It is primarily found in soil contaminated with bat and bird droppings.1 In immunocompetent patients, infection with H. capsulatum typically produces mild to no symptoms; however, in immunocompromised patients, the infection can spread systemically leading to pneumonia, pericarditis, or meningitis. Most immunocompetent patients will clear the infection without treatment, but more severe manifestations require systemic antifungal treatment.2
How do we treat it?
Current IDSA treatment guidelines stratify treatment by both site and severity of infection. In general, the preferred treatment for moderate to severe histoplasmosis of any body site is one to two weeks of intravenous (IV) amphotericin B followed by maintenance oral itraconazole for at least 12 weeks with the potential for life-long suppression in some patients. The guidelines also recommend voriconazole, among all three other available triazoles, as a second-line agent if itraconazole is not tolerated, failed, or contraindicated.3 There are many reasons itraconazole could be inappropriate for a specific patient. Itraconazole is not appropriate for patients with a history of cardiac or liver disease, chronic obstructive pulmonary disease (COPD), or preexisting hearing loss. There is rather intensive monitoring that is required with itraconazole therapy due to its unpredictable absorption and intrapatient variability. For these reasons, many patients and clinicians have chosen to use voriconazole as a second-line option for oral antifungal therapy, but there is limited evidence regarding its efficacy in treating histoplasmosis.
What evidence does exist?
Freifeld et al. followed nine patients with disseminated histoplasmosis who had failed amphotericin B or itraconazole and were placed on voriconazole as second-line therapy. All nine patients clinically improved during their voriconazole course. Random drug levels obtained ranged from undetectable (<0.125 μg/mL) to 8 μg/mL. While it is impossible to determine if the patients with undetectable blood levels had adequate blood levels of the drug, the fact that all nine patients clinically improved led to the conclusion that voriconazole is a potential treatment for histoplasmosis in some patients, but monitoring of blood levels is essential.5 Accordingly, IDSA guidelines suggest routine monitoring of blood levels if voriconazole is chosen for histoplasmosis treatment.3
In addition to the above PK study, there have been several case reports of patients with histoplasmosis who recovered after treatment with voriconazole. Dhawan et al. followed a three-year-old child diagnosed with disseminated cutaneous histoplasmosis who cleared the infection after treatment with voriconazole was started at a dose of 70 mg by mouth daily following treatment failure with the first-line agents.8 Another case study by Nakamura et al. followed a patient with AIDS who presented with disseminated histoplasmosis and was initially treated with 18 days of amphotericin B; he was then switched to oral itraconazole and started antiretroviral therapy. After two weeks, C-reactive protein and (1,3)-β-D glucan were still elevated, so he was switched to oral voriconazole. He clinically improved and was discharged from the hospital two weeks later. After two and a half years of voriconazole therapy, his (1,3)-β-D glucan was still positive, but he showed no residual symptoms of infection.9
Are there any large studies investigating these different treatment options?
Although there are no prospective studies available comparing itraconazole and voriconazole, the largest available data set comes from a retrospective cohort study performed by Hendrix et al. The study included 194 patients with confirmed histoplasmosis infection, with 40.7% classified as immunocompetent and 59.3% considered immunosuppressed in some manner (including malignancy, transplant recipient, HIV, or receiving chemotherapy, prednisone, a biologic agent or a nonsteroidal immunosuppressive agent). Amphotericin B induction was used in 45.9% of patients before switching to oral azole therapy, 90.2% of whom were placed on itraconazole and 9.8% of whom were placed on voriconazole. The results of this study indicate that voriconazole should not be chosen as a first line option if amphotericin B induction is not used, but that similar outcomes might be expected with maintenance therapy of itraconazole and voriconazole.7
Conclusion
In summary, there is limited data available to justify using voriconazole for the treatment of histoplasmosis infection. While there have been several case reports of patients successfully treated with voriconazole, PK data indicates there may be resistance emerging. In the only retrospective study available, there was a significant increase in mortality with voriconazole vs itraconazole when used as monotherapy with no amphotericin B induction. There was, however, no difference in mortality between voriconazole and itraconazole when amphotericin B induction was used. These data suggest that itraconazole should be used as a first-line option, but voriconazole may be an appropriate alternative option for patients who cannot take or tolerate itraconazole, especially if amphotericin B induction was used.
Wheat LJ, Frreifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-25.
Freifeld A, Arnold S, Ooi W, Chen F, Meyer T, Wheat JL, et al. Relationship of Blood Level and Susceptibility in Voriconazole Treatment of Histoplasmosis. Antimicrob Agents Chemother. 2007 Jul;51(7):2656-57.
Wheat JL, Connolly P, Smedema M, Durkin M, Brizendine E, Mann P, et al. Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who railed fluconazole. J Antimicrob Chemoth. 2006 April 20;57:1235-1239.
Hendrix MJ, Larson L, Rauseo AM, Rutjanawech S, Franklin AD, Powderly WG, et al. Voriconazole Versus Itraconazole for the Initial and Step-down Treatment of Histoplasmosis: A Retrospective Cohort. Clin Infect Dis. 2020 Oct:1-6.
Dhawan J, Verma P, Sharma A, Ramam M, Kabra SK, Gupta S. Disseminated cutaneous histoplasmosis in an immunocompetent child, relepsed with itraconazole, successfully treated with voriconazole. Pediatr Dermatol. Oct 2010;27(5):549-551.
Nakamura A, Tawara I, Ino K, Matsumoto T, Hayashi A, Imai H, et al. Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient. Medical Mycology Case Reports. 2020;27:25-28.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
In our previous post, we reviewed the merits of long-acting HIV treatments as a recent breakthrough in HIV/AIDS medical research. Briefly, these treatments may replace daily oral medication(s), instead offering injectable treatment that lasts for months between doses. This has the promise to ease the burdens of daily pills as well as help contribute to increased compliance, decreased HIV burden in the community, and potentially slow the development of antimicrobial resistance to these crucial drugs.
These same benefits touted for long-acting HIV treatment formulations theoretically can be applied to a host of other infectious diseases which require either short- or long-term antibiotic/antiviral regimens. This is a topic explored in many articles included in the Long-Acting and Extended-Release Formulations for the Treatment and Prevention of Infectious Diseases supplement in the journal Clinical Infectious Diseases. Today, we feature a few of theses articles as we explore how advances in HIV medicine may spill over and benefit all of Infectious Disease.
Tuberculosis is caused by the pathogen Mycobacterium tuberculosis and most commonly involves infection of the lung, among other tissues. Unlike most infections, tuberculosis can manifest acutely with primary tuberculosis as well as go dormant and asymptomatic for a period of years in a manifestation called latent tuberculosis. This latent type of infection can then reactivate, causing secondary tuberculosis. Despite this, it is considered a very treatable disease, but is complicated by high prevalence in developing nations where access to medical care may be suboptimal, a long course of antibiotic treatment needed (sometimes upwards of 6-9 months) for effective clearance, and a significant side effect profile of medications used. These factors make tuberculosis treatments ideal candidates for long-acting formulation. Indeed, this is the idea that is explored in this article, co-authored by Dr. Susan Swindells. Check out the full manuscript for an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies. With more research, this technology could be leveraged to generate a one-shot-cure for latent TB.
Hepatitis B and Hepatitis C are two additional infectious diseases where treatment may be substantially improved with long-acting formulation technology. The considerations of this are explored in two articles included in the supplement (Long-Acting Treatments for Hepatitis B and Prospects for Long-Acting Treatments for Hepatitis C). In the case of HBV, weekly injections of pegylated interferon alpha are already currently in use as a semi-long acting formulation. Even longer acting formulations may, with additional research, further effectively combat this virus and help prevent mother-to-infant transmission, which is the predominant route of transmission worldwide. This is crucially important as there is no current cure for hepatitis B infection, making long-term pharmaceutical treatment our only tool to prevent transmission. HCV, on the other hand, can now be cured in most people with 2-3 months of treatment. Much like in the case of tuberculosis, this requires adherence to consistent dosing of an oral medication. It follows then that the same benefits that long-acting formulations may provide to tuberculosis also extend to HCV infection, with the hope of a one-shot-cure that would benefit those living with HCV in areas without robust access to pharmacies or medical care. Read both articles (here and here) for the full details on the progress and work still needed before these treatments can be utilized to improve care for people living with hepatitis B or C.
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