Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Concurrent Trypanosoma cruzi and Cytomegalovirus Reactivation in an Immunosuppressed Patient With Limited Cutaneous Systemic Sclerosis.

Chagas disease, a multisystem infection caused by the protozoan Trypanosoma cruzi, is primarily found in Latin America. In recent years, prevalence has increased in the United States, where reactivation is the most common clinical scenario. Here, we describe cutaneous reactivation of T. cruzi in a patient with limited cutaneous systemic sclerosis on immunosuppression therapy who simultaneously presented with cytomegalovirus reactivation. Histopathology showed parasitized histiocytes in the superficial and deep dermis. Occasional epidermal keratinocytes were also parasitized, and rare organisms were also seen in the walls of blood vessels. Also noted were viral cytopathic changes within the vascular endothelium, and immunostaining confirmed cytomegalovirus. In this report, we describe the difference in cutaneous findings between reactivated and acute Chagas disease, and we also review the histopathologic features that help distinguish T.cruzi from other intracellular organisms.

Diagnosis of Chagasic Encephalitis by Sequencing of 28S rRNA Gene.

We report a case of chagasic encephalitis diagnosed by 28S rRNA sequencing. The diagnosis of chagasic encephalitis is challenging, given the broad differential diagnosis for central nervous system lesions in immunocompromised patients and low sensitivity of traditional diagnostics. Sequencing should be part of the diagnostic armamentarium for potential chagasic encephalitis.

Role of Toxoplasma IgA as Part of a Reference Panel for the Diagnosis of Acute Toxoplasmosis during Pregnancy.

This study evaluated the usefulness of adding the Toxoplasma gondii IgA antibody enzyme-linked immunosorbent assay (ELISA) to the serologic panel of tests done for the diagnosis of acute toxoplasmosis in pregnant women in a reference laboratory in the United States. We conducted a retrospective study of 690 consecutive pregnant women with positive T. gondii IgG antibody test results who also had T. gondii IgA and IgM antibody tests performed. Patients were defined as acutely or chronically infected with T. gondii based on a panel of serologic tests performed at the Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL). Among the 81 women who were positive by T. gondii IgA antibody ELISA testing, 61 (75.3%) were acutely infected with T. gondii, while of the 547 who were negative by IgA testing, only 24 (4.4%) were acutely infected (P < 0.001). Among the 71 women who were positive by both IgA and IgM antibody tests, 61 (85.9%) were acutely infected, whereas 24 (19.2%) of the 125 women who were positive by only the IgM ELISA were acutely infected (P < 0.001). These results demonstrate that pregnant women with T. gondii IgA antibodies are more likely than pregnant women without T. gondii IgA antibodies to have had a recent infection with T. gondiiToxoplasma IgA antibody testing can therefore improve the accuracy of a serologic panel for the diagnosis of acute toxoplasmosis during pregnancy. Physicians who ordered testing only for T. gondii IgG and IgM should also request additional testing for IgA and IgG avidity, if both IgG and IgM are positive. This further testing should, ideally, be performed in a reference laboratory.

Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease - United States.

The term "chronic Lyme disease" is used by some health care providers as a diagnosis for various constitutional, musculoskeletal, and neuropsychiatric symptoms (1,2). Patients with a diagnosis of chronic Lyme disease have been provided a wide range of medications as treatment, including long courses of intravenous (IV) antibiotics (3,4). Studies have not shown that such treatments lead to substantial long-term improvement for patients, and they can be harmful (1,5). This report describes cases of septic shock, osteomyelitis, Clostridium difficile colitis, and paraspinal abscess resulting from treatments for chronic Lyme disease. Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks.

First case of infectious endocarditis caused by Parvimonas micra.

P. micra is an anaerobic Gram-positive cocci, and a known commensal organism of the human oral cavity and gastrointestinal tract. Although it has been classically described in association with endodontic disease and peritonsillar infection, recent reports have highlighted the role of P. micra as the primary pathogen in the setting of invasive infections. In its most recent taxonomic classification, P. micra has never been reported causing infectious endocarditis in humans. Here, we describe a 71 year-old man who developed severe native valve endocarditis complicated by aortic valvular destruction and perivalvular abscess, requiring emergent surgical intervention. Molecular sequencing enabled identification of P. micra.

Case Report: Relapsing Leptospirosis in an Immunocompromised Host.

Leptospirosis is typically a self-limited febrile illness; when it occurs, meningitis usually develops early in the course. Here, we describe a patient who had engaged in freshwater activities in Kauai that was immunocompromised due to a history of mantle cell lymphoma, autologous hematopoietic cell transplant, and hypogammaglobulinemia. He developed leptospiral meningoencephalitis 11 weeks after illness onset and persistently detectable Leptospira DNA in blood and cerebrospinal fluid along with ongoing clinical illness, despite appropriate treatment.

Virtual Recruitment Is Here to Stay: A Survey of ID Fellowship Program Directors and Matched Applicants Regarding Their 2020 Virtual Recruitment Experiences.

BACKGROUND: Graduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Limited data have been published regarding the consequences of this transition. We aimed to understand (1) infectious diseases (ID) fellowship programs' recruitment efforts and the effect of virtual recruitment on application and interview numbers and (2) the number of programs to which matched applicants applied and interviewed and applicants' perspectives on virtual recruitment. METHODS: In 2020-2021, we surveyed all US ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach. RESULTS: The PD response rate was 68/158 (43%); the applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed compared with the previous year. Applicants especially valued the online program structure information, PD program overview videos, didactic and curriculum content, and fellow testimonials and profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want an option for virtual recruitment. CONCLUSIONS: Virtual recruitment enabled programs to accommodate more applicants and highlighted applicants' preferences for programs' augmented online presences and time-limited interview days. Most programs and applicants want an option for virtual interviews.

Reactivation of Chagas Disease in a Patient With an Autoimmune Rheumatic Disease: Case Report and Review of the Literature.

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.

The Struggling Infectious Diseases Fellow: Remediation Challenges and Opportunities.

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges.

Severe encephalomyelitis in an immunocompetent adult with chromosomally integrated human herpesvirus 6 and clinical response to treatment with foscarnet plus ganciclovir.

Human herpesvirus 6 has rarely been identified as a cause of encephalitis in immunocompetent adults. We describe a patient who had severe encephalomyelitis, hypoglycorrhachia, and human herpesvirus 6 identified in his cerebrospinal fluid and serum and who recovered after treatment with foscarnet and ganciclovir. Human herpesvirus 6 should be considered in immunocompetent patients with encephalitis.

High prevalence and presumptive treatment of schistosomiasis and strongyloidiasis among African refugees.

BACKGROUND: Schistosomiasis and strongyloidiasis cause substantial morbidity and mortality among hundreds of millions of infected persons worldwide. In the United States, these infections are most commonly found among international travelers, immigrants, and refugees from areas of endemicity. Refugees resettled to the United States since 2000 include >3800 "Lost Boys and Girls" of Sudan and 8000 Somali Bantu. Many Lost Boys and Girls of Sudan reported chronic abdominal pain only since arrival, and some received diagnoses of schistosomiasis or strongyloidiasis. We assessed seroprevalence of these infections among these refugees and hypothesized an association between infection and abdominal pain. METHODS: We offered a survey assessing chronic abdominal pain and serologic testing for schistosomiasis and strongyloidiasis to all 800 attendees of a Lost Boys and Girls of Sudan reunion in the United States. Serologic testing was performed on preimmigration specimens obtained from 100 United States-bound Somali Bantu refugees. RESULTS: Of the 462 Sudanese refugees (58%) tested, 44% and 46% were seropositive for schistosomiasis (primarily due to Schistosoma mansoni) and strongyloidiasis, respectively; 24% of those who tested positive for schistosomiasis had S. mansoni antigenemia. Forty-six percent reported chronic abdominal pain, which was not associated with either infection. Among 100 Somali Bantu, 73% and 23% tested seropositive for schistosomiasis (primarily due to Schistosoma haematobium) and strongyloidiasis, respectively. CONCLUSIONS: The high seroprevalence of schistosomiasis and strongyloidiasis among Sudanese Lost Boys and Girls and Somali Bantu refugees supports presumptive treatment for these refugees. Current refugee resettlement policies inadequately address these diseases; our data support consideration of predeparture presumptive therapy for all refugees from areas of endemicity.

Microarray detection of human parainfluenzavirus 4 infection associated with respiratory failure in an immunocompetent adult.

A pan-viral DNA microarray, the Virochip (University of California, San Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in an immunocompetent adult presenting with a life-threatening acute respiratory illness. The virus was identified in an endotracheal aspirate specimen, and the microarray results were confirmed by specific polymerase chain reaction and serological analysis for HPIV-4. Conventional clinical laboratory testing using an extensive panel of microbiological tests failed to yield a diagnosis. This case suggests that the potential severity of disease caused by HPIV-4 in adults may be greater than previously appreciated and illustrates the clinical utility of a microarray for broad-based viral pathogen screening.

Successful integration of insecticide-treated bed net distribution with mass drug administration in Central Nigeria.

In Africa anopheline mosquitoes transmit malaria and lymphatic filariasis (LF); insecticide-treated bed nets significantly reduce transmission of both. Insecticide-treated bed net provision to children under 5 (U5) and pregnant women (PW) is a major goal of malaria control initiatives, but use in Africa remains low because of cost and logistics. We therefore integrated insecticide-treated bed net distribution with the 2004 LF/onchocerciasis mass drug administration (MDA) program in Central Nigeria. Community volunteers distributed 38,600 insecticide-treated bed nets, while simultaneously treating 150,800 persons with ivermectin/albendazole (compared with 135,600 in 2003). This was subsequently assessed with a 30-cluster survey. Among surveyed households containing U5/PW, 80% (95% CI, 72-87%) owned > or = 1 insecticide-treated bed net, a 9-fold increase from 2003. This first linkage of insecticide-treated bed net distribution with mass drug administration resulted in substantial improvement in insecticide-treated bed net ownership and usage, without adversely affecting mass drug administration coverage. Such integration allowed two programs to share resources while realizing mutual benefit, and is one model for rapidly improving insecticide-treated bed net coverage objectives.

Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.

BACKGROUND: More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire. METHODS: We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted. FINDINGS: Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities. INTERPRETATION: Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment. FUNDING: Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.

Antiparasitic therapy.

Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world's poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis.

High prevalence of Wuchereria bancrofti infection as detected by immunochromatographic card testing in five districts of Orissa, India, previously considered to be non-endemic.

India accounts for over one-third of the world's burden of lymphatic filariasis (LF). Although most coastal districts of Orissa state (eastern India) are LF-endemic, the western districts of Orissa are considered non-endemic. During a large-scale insecticide-treated bed net/microfinance trial, we tested one randomly selected adult (age 15-60 years) for LF from a random sample of microfinance-member households in five districts of western Orissa, using immunochromatographic card testing (ICT). Overall, 354 (adjusted prevalence 21%, 95%CI 17-25%) of 1563 persons were ICT positive, with district-wide prevalence rates ranging from 15-32%. This finding was not explained by immigration, as only 3% of subjects had ever lived in previously known LF-endemic districts. These results therefore suggest ongoing autochthonous transmission in districts where LF control programs are not operational. Our results highlight the importance of broad, systematic surveillance for LF in India and call for the implementation of LF control programs in our study districts.

Eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in Hawaii: clinical characteristics and potential exposures.

The most common infectious cause of eosinophilic meningitis is Angiostrongylus cantonensis, which is transmitted largely by consumption of snails/slugs. We previously identified cases of angiostrongyliasis that occurred in Hawaii from 2001 to 2005; the highest incidence was on the island of Hawaii. We now report symptoms, laboratory parameters, and exposures. Eighteen patients were evaluated; 94% had headache, and 65% had sensory symptoms (paresthesia, hyperesthesia, and/or numbness). These symptoms lasted a median of 17 and 55 days, respectively. Three persons recalled finding a slug in their food/drink. Case-patients on the island of Hawaii were more likely than case-patients on other islands to consume raw homegrown produce in a typical week (89% versus 0%, P < 0.001) and to see snails/slugs on produce (56% versus 0%, P = 0.03). Residents and travelers should be aware of the potential risks of eating uncooked produce in Hawaii, especially if it is from the island of Hawaii and locally grown.