Therapeutic Advances in Infectious Disease

Drysdale, Simon B.; Broadbent, Lindsay

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231159991pmid: 36968553

Raheel, Hira; Kopalakrishnan, Swana; Bhasker, Shveta; Makhani, Leila; Clarke, Shareese; Nicholas, Mathew N.; Mufti, Asfandyar; Boggild, Andrea K.

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231162719pmid: 37008791

Strongyloides colitis is a gastrointestinal manifestation of the parasitic infection, Strongyloides stercoralis, which may be misdiagnosed and treated as ulcerative colitis (UC) in patients presenting in non-endemic regions. Treatment of Strongyloides colitis as UC can lead to a lethal hyperinfection syndrome. Therefore, prior to commencing immunosuppressive treatment of UC, it is essential to use diagnostic markers to differentiate the two etiologies. In this case series, we discuss two migrant patients who were previously diagnosed with UC and treated accordingly who presented to our clinic for further investigation of suspected parasitic infection.

Rotsaert, Anke; Ogara, Collin; Mwanga-Amumpaire, Juliet; Kekitiinwa, Adeodata R.; Musiime, Victor; Najjingo, Elizabeth; Kisitu, Grace P.; Nazzinda, Rashidah; Nambi, Esther; Lee, Janice; Diallo, Mariama; Kyomuhendo, Flavia; Waweru, Moses; Andrieux-Meyer, Isabelle; Nöstlinger, Christiana

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231159993pmid: 36968554

Background:Worldwide, 1.7 million children younger than 15 years were living with HIV in 2021. Only 52% of them had access to antiretrovirals (ARVs). Lack of age-appropriate ARV formulations (i.e. easy to swallow for young infants, acceptable taste) remains the main obstacle to the access to ARVs. Therefore, a strawberry-flavoured Abacavir/Lamivudine/Lopinavir/Ritonavir (30/15/40/10 mg) fixed-dose combination of granules in a capsule (4-in-1) for children living with HIV weighing 3–25 kg was developed.Objective:We assessed caregivers’ perceived acceptability of the 4-in-1 compared with previous paediatric ARV formulations and factors influencing acceptability.Methods:This exploratory qualitative case study embedded in a phase I/II, open-label, randomized cross-over pharmacokinetic, safety and acceptability study (LOLIPOP) was conducted in three sites in Uganda (May 2019–October 2020). Thirty-six children weighing between 3 and 19.9 kg participated in the main study. We purposively sampled caregiver–child dyads according to weight bands, and conducted 20 semi-structured interviews with caregivers and 5 with healthcare providers. We triangulated these results with a quantitative acceptability questionnaire. We analysed interviews inductively using NVivo12 adopting a thematic analysis approach and acceptability questionnaires descriptively to assess concordance between them.Results:All caregivers found the 4-in-1 formulation highly acceptable and easier to use than previous formulations (i.e. pellets/tables/syrup). Appealing taste, ease of administration, easy storage and children’s acceptance contributed to acceptability despite structural challenges of food shortage and HIV stigma. Visible improvements in children’s health and comprehensive and tailored healthcare provider support to overcome initial difficulties such as vomiting increased caregivers’ acceptance. Concordant results from questionnaire- and interview-data confirmed high acceptability.Conclusion:Caregivers of children in all weight bands in this sample found the 4-in-1 granules highly acceptable compared with the pellets/tablets combination. Healthcare providers’ support to caregivers allowed for individual tailoring of drug administration despite challenges such as food shortage. This enabled short-term adherence. These findings informed further practical recommendations.Registration:Clinical trial number: NCT03836833

Adegboye, Oyelola A.; Alele, Faith O.; Pak, Anton; Castellanos, Maria E.; Abdullahi, Mohammed A.S.; Okeke, Malachy I.; Emeto, Theophilus I.; McBryde, Emma S.

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231161936pmid: 37008790

Laborde-Balen, Gabrièle; Diop, Maimouna; Sow, Khoudia; Ndiaye, Ndeye Bineta; Diop, Karim; Taverne, Bernard; ,

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231159295pmid: 36938146

Objectives:In Senegal, the dominant social norm upholds virginity before marriage and edifies abstinence for adolescents as a cardinal moral value. Currently, sex outside of marriage remains socially condemned. The onset of sex for adolescent girls born with HIV in Senegal brings up several challenges. In Dakar, initiatives, especially through digital applications, are being developed to support these young people. These programs are much rarer in rural settings. A study conducted in 2021 explored how adolescent girls born with HIV who live outside of Dakar experience sexuality, what socio-health constraints they face, and what support they receive from the healthcare system.Method:An anthropological study titled ‘Treatment Failure among Children and Adolescents Living with HIV in Senegal, Outside Dakar’ (ETEA-VIH, ANRS 12421) was conducted in 2021 in 14 regional hospitals and health centers. Semi-structured interviews were conducted with 87 HIV-positive children and adolescents, 95 parents/guardians, and 47 health care workers. Adolescent girls’ onset of sexuality was specifically analyzed for 40 adolescent girls age 12–19 years old.Results:Generally, parents feign oblivion about their children’s sexual lives. Mothers dread a pregnancy out of marriage because they are responsible for overseeing sex education and would be ‘blamed’ for the transgression. The occurrence of an unintended pregnancy can lead to exclusion from the family and a risk of transmitting HIV to the child due to the lack of medical and social support. HIV remains a stigmatizing disease that families keep secret. The risk of disclosure is a major concern. Despite sexual and reproductive health (SRH) programs, most healthcare workers are reluctant to discuss sexuality or to offer contraception to adolescent girls. Information spaces have been set up in some regional hospitals by associations trained in SRH. They are rarer in health centers. Accessibility to digital applications and discussion forums is limited due to the lack of smartphones and Internet access.Conclusion:In rural settings, HIV-positive adolescent girls are confronted with the silence that surrounds sexuality and HIV. An individualized approach and confidential access to contraception should be prioritized to support them with assistance from PLHIV associations.

Vargas Barahona, Lilian; Molina, Kyle C.; Pedraza-Arévalo, Laura C.; Sillau, Stefan; Tagawa, Alex; Scherger, Sias; Chastain, Daniel B.; Shapiro, Leland; Tuells, Jose; Franco-Paredes, Carlos; Hawkins, Kellie L.; Maloney, James P.; Thompson, George R.; Henao-Martínez, Andrés F.

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231159481pmid: 36938147

Background:HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality.Objective:We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality.Methods:We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis (n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis.Results:1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p < 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p < 0.001) or prednisone (49% versus 29%, p < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5–9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0–10.4, p < 0.0001) among HIV-negative patients with previous corticosteroid exposure.Conclusion:Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.

Polk, Christopher; Sampson, Mindy; Fairman, Robert T.; DeWitt, Michael E.; Leonard, Michael; Neelakanta, Anupama; Davidson, Lisa; Roshdy, Danya; Branner, Chris; McCurdy, Lewis; Ludden, Tom; Tapp, Hazel; Passaretti, Catherine

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231158463pmid: 36911268

Objective:Emerging infectious diseases challenge healthcare systems to implement new models of care. We aim to evaluate the rapid implementation of a new care model for monkeypox in our health system.Design:This is a retrospective case series evaluation under the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework of implementation of a testing and care model for monkeypox in a large, integrated health system.Methods:Atrium Health implemented education of providers, testing protocols, and management of potential monkeypox cases using electronic health record (EHR) data capabilities, telehealth, and collaboration between multiple disciplines. The first 4 weeks of care model implementation were evaluated under the RE-AIM framework.Results:One hundred fifty-three patients were tested for monkeypox by 117 unique providers at urgent care, emergency departments, and infectious disease clinics in our healthcare system between 18 July 2022 and 14 August 2022. Fifty-eight monkeypox cases were identified, compared with 198 cases in the state during the time period, a disproportionate number compared with the health system service area, and 52 patients were assessed for need for tecovirimat treatment. The number of tests performed and providers sending tests increased during the study period.Conclusion:Implementation of a dedicated care model leveraging EHR data support, telehealth, and cross-disciplinary collaboration led to more effective identification and management of emerging infectious diseases and is important for public health.Plain Language SummaryImpact of care model implementation on monkeypoxNew infectious diseases challenge health systems to implement new care practices. Our health system responded to this challenge by implementing a care model for education, testing, and clinical care of monkeypox patients. We analyzed results from implementing the model. We were able to identify a disproportionate number of monkeypox cases compared with the rest of our state by using our model to educate medical providers, encourage testing, and ensure patients had access to best disease care. Implementation of care models for testing and management of new diseases will improve patient care and public health.

Wiley, Zanthia; Hanna, Jasmah; Kobaidze, Ketino; Franks, Nicole

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231159501pmid: 36968552

Introduction:Innovative discovery begins with diverse perspectives; research teams should harness this model. Black, Indigenous, and other People of Color (BIPOC) and women are underrepresented as researchers. Team science leverages collaborative and cross-disciplinary approaches to diversify the research workforce, and introduces academic (and non-academic) faculty with limited research exposure/experience to clinical research.Methods:In 2020, two Black women academic physicians implemented an academic collaborative – COVID-19 Characteristics, Readmissions, Outcomes, and Social Determinants of Health (CROSS) – to investigate COVID-19 health inequities, with intentional recruitment of BIPOC and women. The 37 CROSS team members were of diverse races, ethnicities, sex, specialties, and disciplines, and represented eight hospitals. Team members were electronically surveyed to determine their interest, desired activities, and level of participation in research activities; concurrently, self-identified demographics (including race, ethnicity, sex, and language(s) spoken) were obtained.Results:All team members completed the survey: 78.4% (n = 29) were BIPOC and 78.4% (n = 29) were women. Team members spoke 18 languages (including English). Academic medical ranks included Assistant Professor (32.4%; n = 12), Associate Professor (16.2%; n = 6), and Full Professor (2.7%; n = 1). Each member identified desired activities (data collection, data analytics, manuscript development, abstract development/poster presentation, serving as a consultant) and the percentage of time they intended to allocate to each. Between June 2020 and February 2023, the team produced five original peer-reviewed manuscripts (including this article); five members served as first or senior authors. Twenty-one abstracts were presented at local conferences, and 10 at national and regional conferences. Five members achieved academic promotion, and team members were awarded three intramural grants resulting directly from team collaborations.Conclusion:Intentional recruitment and assessment of team members’ desired levels of participation in an integrated clinical research team is an effective strategy to engage BIPOC and women. The CROSS Collaborative is a model for diversity and inclusion in team science and clinical research.

Bergeron, Harrison C.; Kauvar, Lawrence M.; Tripp, Ralph A.

2023 Therapeutic Advances in Infectious Disease

doi: 10.1177/20499361231161157pmid: 36938145

Background:Respiratory syncytial virus (RSV) is a poor inducer of antiviral interferon (IFN) responses which result in incomplete immunity and RSV disease. Several RSV proteins alter antiviral responses, including the non-structural proteins (NS1, NS2) and the major viral surface proteins, that is, fusion (F) and attachment (G) proteins. The G protein modifies the host immune response to infection linked in part through a CX3 C chemokine motif. Anti-G protein monoclonal antibodies (mAbs), that is, clones 3D3 and 2D10 that target the G protein CX3C chemokine motif can neutralize RSV and inhibit G protein-CX3CR1 mediated chemotaxis.Objectives:Determine how monoclonal antibodies against the RSV F and G proteins modify the type I and III IFN responses to RSV infection.Design:As the G protein CX3 C motif is implicated in IFN antagonism, we evaluated two mAbs that block G protein CX3C-CX3CR1 interaction and compared responses to isotype mAb control using a functional cellular assay and mouse model.Methods:Mouse lung epithelial cells (MLE-15 cells) and BALB/c mice were infected with RSV Line19 F following prophylactic mAb treatment. Cell supernatant or bronchoalveolar lavage fluid (BALF) were assayed for types I and III IFNs. Cells were interrogated for changes in IFN-related gene expression.Results:Treatment with an anti-G protein mAb (3D3) resulted in improved IFN responses compared with isotype control following infection with RSV, partially independently of neutralization, and this was linked to upregulated SOCS1 expression.Conclusions:These findings show that anti-G protein antibodies improve the protective early antiviral response, which has important implications for vaccine and therapeutic design.Plain Language SummaryRSV is a leading cause of respiratory disease in infants and the elderly. The only Food and Drug Administration-approved prophylactic treatment is limited to an anti-F protein monoclonal antibody (mAb), that is, palivizumab which has modest efficacy against RSV disease. Accumulating evidence suggests that targeting the RSV attachment (G) protein may provide improved protection from RSV disease. It is known that the G protein is an IFN antagonist, and IFN has been shown to be protective against RSV disease. In this study, we compared IFN responses in mouse lung epithelial (MLE-15) cells and in mice infected with RSV Line19 F treated with anti-G protein or anti-F protein mAbs. The levels of type I and III IFNs were determined. Anti-G protein mAbs improved the levels of IFNs compared with isotype-treated controls. These findings support the concept that anti-G protein mAbs mediate improved IFN responses against RSV disease, which may enable improved treatment of RSV infections.