Clarisse Martins Machado

Background: Antepartum stillbirth is an important public health issue. This study aimed to identify mediation pathways from the vegetation greenness surrounding the maternal residence to antepartum stillbirth, through stillbirth risk factors. Methods: This study is part of the FetRisks project–a population-based case–control study of stillbirth and live births in 14 public hospitals in the Municipality of São Paulo, Brazil (December 2019–December 2023). We estimated vegetation greenness using the median value of the normalized difference vegetation index (NDVI) obtained from satellite images from the study period, considering buffer radii around the residences between 50 and 500 m. We used penalized logistic regressions to select maternal, placental, fetal, and neighborhood characteristics. Based on these data, we built a Bayesian network and performed counterfactual mediation analyses. Results: We analyzed 248 antepartum stillbirths (cases) and 301 live births (controls). The maternal residence of 19.4% (48/248) of cases and 30.9% (93/301) of controls had a median NDVI within a buffer radius of 150 m (NDVI-150m) greater than 0.104. Women living in residences with a median NDVI-150m greater than 0.104 had a lower risk of antepartum stillbirth (odds ratio: 0.50; 95% confidence interval [CI]: 0.33, 0.76). Fetal growth restriction and placental inflammatory signs mediated 38.5% (natural indirect effect: −0.0604; 95% CI: −0.0916, −0.0292) and 14.7% (natural indirect effect: −0.0230; 95% CI: −0.0412, −0.0047) of the effect of a median NDVI-150m greater than 0.104 on antepartum stillbirth, respectively. Conclusion: Higher residential vegetation greenness showed protective indirect effects on antepartum stillbirth partially through a lower risk of fetal growth restriction and placental inflammatory signs.

This chapter outlines recommendations for the control and management of infections following hematopoietic cell transplantation. Given the complexity and scope of the subject, the authors chose a format that considers the various interventions available to prevent, minimize, or when appropriate treat infections relevant to the hematopoietic cell transplantation setting. We consider the active and collaborative involvement of the transplant infectious disease specialist in transplantation centers to be essential in ensuring the best possible care for this vulnerable population.

Introduction: In allogeneic HCT recipients, risk factors for PTLD and EBV end‐organ diseases are well established. Therefore, weekly monitoring of EBV reactivation with quantitative PCR is indicated for patients at risk. Although based on uncontrolled studies and supported by moderate strength of evidence, preemptive rituximab has been recommended in cases of EBV reactivation, without a clearly defined EBV DNAemia threshold. Rituximab is known to be associated with prolonged B‐cell depletion and secondary hypogammaglobulinemia, resulting in an increased risk of infectious complications and poor vaccine responses for an extended period. Methods: In this retrospective single‐center study, we evaluated the safety and effectiveness of immunosuppression (IS) reduction as the first approach in EBV reactivation in 328 HCT recipients, limiting the introduction of rituximab to patients who did not respond to IS reduction or who developed EBV end‐organ disease or PTLD. Results: During follow‐up, 178 patients experienced EBV reactivation, with a cumulative incidence of 54.6%. Among these, four patients developed EBV encephalitis (2.2%), and no cases of PTLD were identified. Rituximab was administered to only 12 patients (6.7%). In multivariate analysis, EBV reactivation was significantly associated with chronic GVHD, which may be related to EBV reactivation itself, rapid IS withdrawal, or both. EBV reactivation did not adversely affect non‐relapse mortality or overall survival in this cohort. Conclusion: IS reduction as the first‐line approach to EBV reactivation was safe and effective in most patients with increasing EBV DNAemia. Consequently, rituximab was required in fewer than 10% of cases.

Cytomegalovirus (CMV) poses a significant threat to post-hematopoietic cell transplantation (HCT). Control strategies include letermovir prophylaxis or ganciclovir pre-emptive therapy (PET). Without prophylaxis, 65–90% of seropositive recipients develop a clinically significant CMV infection. Due to PET drawbacks, letermovir prophylaxis is preferable, as it reduces CMV-related events and improves overall survival. However, refractory or resistant CMV-CS remains a challenge, with maribavir showing limited efficacy. This systematic review followed the Cochrane Manual and PRISMA guidelines and was registered in PROSPERO. Searches were conducted in PubMed, Scopus, Embase, and Web of Science. Out of 1895 identified records, 614 duplicates were removed, and subsequent screening excluded 1153 studies. Eleven included studies (2012–2024) involved 255 HCT recipients receiving adoptive immunotherapy (AI), primarily CMV-specific T-cell therapy. GvHD occurred in 1.82% of cases. Adverse events occurred in 4.4% of cases, while mild CRS was observed in 1.3% of patients. Efficacy, evaluated in 299 patients across eleven studies, showed an average response rate of 78.2%. CMV-CS recurrence was observed in 24.4% of 213 patients, and death due to CMV was reported in 9.7% of 307 patients across nine studies. Adoptive hCMV-specific T-cell immunotherapy appears to be a safe, effective alternative for refractory CMV-CS in HCT.

Purpose of review: Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH). Recent findings: Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections. Summary: Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.

Background: Cytomegalovirus (CMV) can cause tissue‐invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV‐specific cell immune recovery (CMV‐CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV‐CIR, using QuantiFERON‐CMV assay (Qiagen Group), in the first year after LTx. Methods: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV‐seropositive recipients (R+) and only CMV‐seropositive donor and negative recipient (D+/R−) received a 6‐month‐prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON‐CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. Results: Thirty‐eight patients were included. On days 45, 90, and 365 days post‐LTx, 60%, 72%, and 81% QuantiFERON‐CMV were reactive, respectively. Eleven patients (28.9%) presented CMV‐disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx ( p = .027) but failed on DNAemia/CMV infection ( p = .148). Daily prophylaxis, for D+/R− patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON‐CMV (adjusted OR .27, 95%CI .12–.60, p = .02). Conclusion: QuantiFERON‐CMV may be another diagnostic tool to help stratify CMV‐disease risk and individualized antiviral prophylaxis after LTx. image

Introduction: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live‐attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients.Methods: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included.Results: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft‐versus‐host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination.Conclusion: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem. image

Background: Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post‐HCT outside of Europe and North America.Methods: The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia‐Pacific, Latin America, and Middle East (search period: 1 January 2011–17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV‐related mortality, treatments, refractory, resistant CMV, and burden.Results: Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%–61.2% (23 studies) and 2.9%–15.7% (10 studies), respectively. Recurrence occurred in 19.8%–37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV‐related causes. In all countries, first‐line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%–10% of recipients (five studies). Patient‐reported outcomes and economic data were scarce.Conclusion: The incidence of CMV infection and disease post‐HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments. image