ABSTRACT
Spotted fever rickettsiosis is rarely observed in solid organ transplant recipients, and all previously reported cases have been associated with tick bite months to years after transplantation. We describe a kidney transplant recipient in North Carolina, USA, who had a moderately severe Rickettsia parkeri infection develop during the immediate posttransplant period.
Subject(s)
Kidney Transplantation , Rickettsia Infections , Rickettsia , Humans , Kidney Transplantation/adverse effects , Rickettsia/genetics , Rickettsia/isolation & purification , North Carolina , Rickettsia Infections/diagnosis , Rickettsia Infections/microbiology , Male , Transplant Recipients , Middle Aged , Anti-Bacterial Agents/therapeutic use , FemaleABSTRACT
BACKGROUND: Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management. METHODS: This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results. RESULTS: Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. CLINICAL TRIALS REGISTRATION: NCT02912117. CONCLUSION: KT shows promise in the diagnosis and treatment optimization of FN.
Subject(s)
Cell-Free Nucleic Acids , Febrile Neutropenia , Anti-Bacterial Agents/therapeutic use , Febrile Neutropenia/diagnosis , Febrile Neutropenia/drug therapy , Febrile Neutropenia/etiology , Fever/etiology , High-Throughput Nucleotide Sequencing , Humans , Prospective StudiesABSTRACT
Cutaneous cryptococcosis is uncommon. It is usually a result of disseminated infection and can present with a wide variety of skin lesions. We report a case of disseminated cryptococcosis in a kidney transplant recipient who presented with nodular lesions in the forehead following a bout of acute cellular rejection.
Subject(s)
Cryptococcosis , Dermatomycoses , HumansABSTRACT
Donor-derived (DD) herpes simplex virus (HSV) hepatitis in solid organ transplant (SOT) recipients is extremely uncommon but carries a high mortality rate. The diagnosis is challenging due to the non-specific presentation and lack of clinical suspicion. We report a case of DDHSV hepatitis in a HSV2 pre-transplant seronegative kidney recipient who received the organ from a HSV2 seropositive donor. The case is highlighted by a few unusual features, namely severe thrombocytopenia and the development of cutaneous, oral and esophageal HSV lesions several weeks after symptom onset while recovering on appropriate treatment. A review of nine proven and probable DDHSV hepatitis cases (including eight previously published ones) showed that fever is a common presenting feature while gastrointestinal symptoms and cutaneous manifestations are uncommon. The symptoms almost always occurred within 2 weeks of transplant. Six out of the nine DDHSV hepatitis patients, including five patients who were on appropriate treatment, died within a month after transplant.
Subject(s)
Hepatitis, Viral, Human , Herpes Simplex , Kidney Transplantation , Humans , Simplexvirus , Tissue DonorsABSTRACT
Cytomegalovirus (CMV) is a common opportunistic infection in solid organ transplant (SOT) recipients in the first 6 months after transplant. Late onset CMV infection or disease outside the classical risk period is uncommon and can present with atypical signs and symptoms. Here, we report a case of late onset CMV presenting as a colonic stricture more than 10 years after liver transplantation in the absence of traditional CMV risk factors. We also briefly review CMV colitis presenting as a mass or stricture in SOT recipients.
Subject(s)
Colitis/virology , Colon/pathology , Cytomegalovirus Infections/diagnosis , Liver Transplantation/adverse effects , Aged , Antiviral Agents/therapeutic use , Colitis/diagnosis , Constriction, Pathologic , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Female , Humans , Male , Risk Factors , SigmoidoscopyABSTRACT
Primary Toxoplasma gondii infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for Toxoplasma infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.
Subject(s)
Antiprotozoal Agents/therapeutic use , Toxoplasmosis/drug therapy , Animals , Drug Discovery/trends , Humans , Models, AnimalABSTRACT
Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).
Subject(s)
Benzimidazoles/pharmacokinetics , Administration, Oral , Adolescent , Adult , Biological Availability , Dose-Response Relationship, Drug , Double-Blind Method , Female , Half-Life , Healthy Volunteers , Humans , Male , Middle Aged , Young AdultABSTRACT
Q fever is uncommon in solid organ transplant (SOT) recipients. We describe a case of granulomatous lung disease as an unusual presentation of chronic Q fever in a kidney-pancreas transplant recipient.
Subject(s)
Kidney Transplantation/adverse effects , Lung/microbiology , Pancreas Transplantation/adverse effects , Q Fever/diagnosis , Antibodies, Bacterial/blood , Child, Preschool , Coxiella burnetii/isolation & purification , Female , Granuloma/microbiology , Humans , Lung/diagnostic imaging , Male , Middle Aged , Q Fever/blood , Tomography, X-Ray ComputedABSTRACT
We report a case of disseminated histoplasmosis in a renal transplant recipient who presented with a nodular pulmonary lesion and elevated serum and bronchoalveolar lavage (BAL) Aspergillus galatomannan. This almost led to an erroneous diagnosis of invasive aspergillosis since the donor respiratory tract was known to be colonized with Aspergillus terreus. However, distinctive intracelluar Histoplasma yeasts on peripheral blood smear led to early diagnosis and appropriate treatment. The cross-reactivity between Aspergillus galactomannan and Histoplasma antigen is discussed further.
Subject(s)
Histoplasmosis/blood , Histoplasmosis/diagnosis , Kidney Transplantation/adverse effects , Mannans/blood , Transplant Recipients , Antifungal Agents/therapeutic use , Aspergillosis/blood , Aspergillus/immunology , Azure Stains , Blood/microbiology , Bronchoalveolar Lavage Fluid/microbiology , Female , Galactose/analogs & derivatives , Histoplasma/immunology , Histoplasma/isolation & purification , Histoplasmosis/drug therapy , Humans , Middle AgedABSTRACT
PURPOSE OF REVIEW: Unlike immunocompetent hosts, solid organ transplant (SOT) recipients with posttransplant histoplasmosis (PTH) often present with disseminated disease and have an attributable mortality of approximately 10%. In this review, we discuss currently available diagnostic tests and treatment strategies in PTH. RECENT FINDINGS: None of the available tests have a 100% diagnostic accuracy. Histoplasma antigen assays are the most sensitive commercially available tests. However, crossreactivity of histoplasma antigen with aspergillus galactomannan and false positive histoplasma antigen tests because of rabbit antithymocyte globulin may cause difficulty in interpreting positive test results in transplant recipients. Molecular assays such as amplification and sequencing of 'panfungal' portions of the 28S ribosomal RNA from clinical specimens appear to be promising.Lipid formulations of amphotericin B and itraconazole are the drugs of choice in the treatment of PTH. Other extended spectrum azoles also appear to be effective, but, like itraconazole, problems with drug interactions and prolongation of the QTc interval (except for isavuconazole, which shortens the QTc interval) remain. Mycophenolate therapy is associated with severe disease and should be stopped during active disease and, if feasible, calcineurin inhibitors and steroids should be reduced. SUMMARY: A combination of various tests (culture, antigen tests, nucleic amplification tests, etc.) should be used to optimize diagnostic yield. The role of unbiased next generation sequencing for early diagnosis and newer azoles in the treatment needs to be further explored.
Subject(s)
Histoplasmosis/diagnosis , Histoplasmosis/etiology , Organ Transplantation/adverse effects , Antifungal Agents/therapeutic use , Antigens, Fungal/immunology , Biomarkers , Disease Management , Histoplasmosis/drug therapy , Histoplasmosis/microbiology , Humans , Immunoassay , Immunocompromised Host , Molecular Diagnostic Techniques , Serologic Tests , Transplant RecipientsABSTRACT
PURPOSE OF REVIEW: Unlike in orthotopic heart transplant (OHT) setting where toxoplasma prophylaxis is a standard practice in pretransplant toxoplasma seronegative recipients who have received donor hearts from seropositive donors (D+/R-), there is no consensus regarding prophylaxis in non-OHT recipients. RECENT FINDINGS: The incidence of toxoplasma disease in non-OHT recipients is less than 1% but its true burden is underestimated. Among 31 cases of toxoplasma disease reported from 2004 through 2017, renal and liver transplant recipients comprised of 90% of cases. A total of 94% of 18 recipients with known pretransplant serology were seronegative recipients (mostly D+/R-). Out of 16 recipients with adequate information, 10 (63%) and five (31%) were deemed to be donor derived and nondonor-derived primary toxoplasmosis respectively. Tissue invasive reactivation was uncommon. Almost all cases were described in patients not on prophylaxis at the time of presentation. Universal screening of donor/recipient toxoplasma serology for risk stratification is beneficial as illustrated by reports of fatal cases of toxoplasmosis due to unavailability of positive donor serology results. SUMMARY: Toxoplasma disease in non-OHT predominantly occurs in pretransplant seronegative recipients- mostly in D+/R- group and is rare in seropositive recipients. Posttransplant prophylaxis should be targeted against the high-risk D+/R- group and should be considered in seropositive recipients in whom unusually high immunosuppression is implemented. Toxoplasma serologies and PCR should be used in combination for the diagnosis of toxoplasmosis in non-OHT patients.
Subject(s)
Heart Transplantation/statistics & numerical data , Toxoplasmosis/epidemiology , Toxoplasmosis/prevention & control , Heart Transplantation/adverse effects , Heart Transplantation/methods , Humans , Incidence , Tissue Donors , Toxoplasma/isolation & purification , Toxoplasmosis/blood , Toxoplasmosis/etiologyABSTRACT
Leishmaniasis occurs in <1% of solid organ and hematopoietic stem cell transplant recipients in endemic countries in which transplants are performed. Visceral leishmaniasis (VL) makes up the bulk of reported cases. The onset generally occurs months after transplantation and the mode of acquisition is often impossible to determine, but de novo vector-borne infection and reactivation of inapparent infection are thought to be the principal means. The potential role of clinically inapparent donor infection is uncertain and screening is not currently recommended, nor is it recommended for recipients from endemic areas, some of whom may have detectable circulating protozoan nucleic acid. While transplant recipients with VL often present with the non-specific findings of fever and cytopenia, the additional presence of hepatosplenomegaly in patients from endemic areas should lead to a directed diagnostic evaluation with bone marrow examination and PCR testing of marrow and peripheral blood having a high yield. Management may often be complicated by the presence of concomitant infections. A lipid formulation of amphotericin B is the preferred treatment, especially for VL, but the relapse rate in transplant recipients is approximately 25%. PCR monitoring of blood for either secondary prophylaxis or preemptive therapy requires further study.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Leishmaniasis/etiology , Organ Transplantation/adverse effects , Humans , Immunocompromised HostABSTRACT
Histoplasma capsulatum is a dimorphic fungus that most often causes asymptomatic infection in the immunocompetent population. In immunocompromised patients, including solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, however, it is likely to cause severe life-threatening infection. Post-transplant histoplasmosis (PTH) in SOT is uncommon with an incidence of ≤1% and is even rarer in HCT patients. The majority of PTH in SOT is diagnosed in the first 2 years following transplantation. Histoplasmosis may result from endogenous reactivation of latent infection, de novo post-transplant acquisition, and donor-derived infection. Disseminated infection is common. Fever is the most common symptom and clinical features are often nonspecific, but patients with disseminated infection may present with a septic picture. Other features, including pancytopenia and hepatosplenomegaly, may not be prominent early in the course of illness. Contemporary histoplasma antigen assays are the most sensitive tests but cross-reactivity with antigens of other fungi, including with Aspergillus galactomannan, is not uncommon. Treatment should be continued for at least a year. Histoplasma antigen levels have prognostic value and can be used to monitor the response to therapy. The attributable mortality is approximately 10%. Routine screening of donors and recipients is not currently recommended.
Subject(s)
Histoplasmosis/etiology , Organ Transplantation/adverse effects , Humans , Transplant RecipientsABSTRACT
A positive Toxoplasma immunoglobulin M (IgM) result is often interpreted as a marker of an acute infection. However, IgM can persist for several years, and Toxoplasma commercial IgM diagnostic test kits can yield a number of false-positive results. For these reasons, a chronic Toxoplasma infection can be erroneously classified as an acute infection, resulting in serious adverse consequences, especially in pregnant women, leading to emotional distress and unnecessary interventions, including termination of pregnancy. Interpretation of Toxoplasma serology at a reference laboratory can help differentiate a recently acquired infection from a chronic infection. Serological test results for 451 patients with positive Toxoplasma IgM and IgG test results obtained at nonreference laboratories (NRLs) that were referred to Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) to determine whether the patient was acutely or chronically infected were retrospectively reviewed. PAMF-TSL results established that of the 451 patients, 335 (74%) had a chronic infection, 100 (22%) had an acute infection, and 7 (2%) were not infected, and for 9 (2%), results were indeterminate. Positive Toxoplasma IgM and IgG test results obtained at NRLs cannot accurately distinguish between acute and chronic infections. To do so, testing at reference laboratories is required, as mandated in 1997 in a letter from the Food and Drug Administration (FDA) to clinicians and laboratories in the United States.
Subject(s)
Antibodies, Protozoan/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Toxoplasma/immunology , Toxoplasmosis/diagnosis , Acute Disease , Adolescent , Adult , Aged , Antibodies, Protozoan/immunology , Child , Child, Preschool , Chronic Disease , False Positive Reactions , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Pregnancy , Pregnancy Complications, Parasitic/diagnosis , Retrospective Studies , Serologic Tests , Toxoplasmosis/parasitology , United States , Young AdultABSTRACT
PURPOSE OF REVIEW: Toxoplasmosis in haematopoietic cell transplant (HCT) recipients is associated with high morbidity and mortality rates. Prophylaxis following HCT is recommended for high-risk pre-HCT toxoplasma-seropositive (pre-HCTSP) recipients. However, there is no agreement or consistency among programmes on whether to adopt prophylaxis or not, or if used, on the chosen antitoxoplasma prophylactic regimen. This review discusses the role of prophylaxis, and preemptive treatment, for toxoplasmosis in the setting of HCT. RECENT FINDINGS: Approximately two-thirds of toxoplasmosis cases following HCT are reported in allogeneic pre-HCTSP (allo pre-HCTSP) patients. This finding confirms a major role of reactivation of latent infection in the pathogenesis of toxoplasmosis in this patient population. Toxoplasma disease-related mortality in allo pre-HCTSP patients was reported at 62%, but it can be significantly decreased with early detection and treatment of toxoplasma infection. There are no randomized trials comparing the efficacy of different prophylactic agents to prevent toxoplasmosis after HCT. Several observational studies have demonstrated the efficacy of trimethoprim-sulfamethoxazole (TMP/SMX) in decreasing the incidence of toxoplasmosis following HCT. There is limited information regarding efficacy of other prophylactic agents. Preemptive treatment using routine blood PCR monitoring seems to be beneficial in detecting infection early and preventing disease in several observational studies and has been adopted for allo pre-HCTSP HCT patients when universal prophylaxis is not possible. SUMMARY: Universal prophylaxis with TMP/SMX in allo pre-HCTSP patients should be implemented by all transplant programmes. Preemptive treatment with routine blood PCR monitoring is an option if prophylaxis cannot be used.
Subject(s)
Chemoprevention/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Toxoplasmosis/prevention & control , Transplant Recipients , Antiprotozoal Agents/therapeutic use , Humans , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useSubject(s)
COVID-19/virology , Glomerulosclerosis, Focal Segmental/virology , Kidney Failure, Chronic/virology , Kidney Transplantation , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Adult , COVID-19/complications , COVID-19/physiopathology , Female , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/therapy , Humans , Hydroxychloroquine/therapeutic use , Immunocompromised Host/drug effects , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Kidney Transplantation/rehabilitation , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/pathogenicity , Plasmapheresis , Polymerase Chain Reaction , Rituximab/therapeutic use , SARS-CoV-2/geneticsABSTRACT
Patients with cancer are increasingly vulnerable to infections, which may be more severe than in the general population. Improvements in rapid and timely diagnosis to optimize management are needed. We conducted a systematic literature review to determine the unmet need in diagnosing acute infections in immunocompromised patients with cancer and identified 50 eligible studies from 5188 records between 1 January 2012 and 23 June 2022. There was considerable heterogeneity in study designs and parameters, laboratory methods and definitions, and assessed outcomes, with limited evaluation of diagnostic impact on clinical outcomes. Culture remains the primary diagnostic strategy. Fewer studies employing molecular technologies exist, but emerging literature suggests that pathogen-agnostic molecular tests may add to the diagnostic armamentarium. Well-designed clinical studies using standardized methodologies are needed to better evaluate performance characteristics and clinical and economic impacts of emerging diagnostic techniques to improve patient outcomes.
ABSTRACT
Background: Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective single-center study of contemporary KT candidates was conducted to assess vaccination rates and vaccine uptake. Methods: All KT candidates ≥18 y evaluated between January 1, 2020, and December 31, 2020, were retrospectively reviewed for history of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine. Positive hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG were assessed as surrogate markers of immunity. Vaccine uptake among vaccine-eligible candidates was also assessed. Results: Among 150 KT candidates, the rate of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine (latter among patients ≥50 y) was found to be as low as 11%. Hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG seropositivity rates were 30%, 66%, 88%, 78%, 90%, and 96%, respectively. Only 7 (5%) of 150 patients had complete immunization or seropositivity. Five (3%) of 143 vaccine-eligible patients declined vaccination. Hepatitis A vaccine declination was relatively common with 15 (16%) of 94 vaccine-eligible patients declining it. Conclusions: KT candidates have low baseline rates of prior immunization/seropositivity against most recommended vaccines. Overall vaccine uptake among eligible candidates was high.