Ensitrelvir eradicates persistent SARS-CoV-2 infection in a follicular lymphoma patient treated with anti-CD20 antibodies.

Patients with hematological malignancies, especially B-cell malignancies, who received anti-CD20 antibodies exhibit a poor immune response to the mRNA coronavirus disease 2019 (COVID-19) vaccine within 6-12 months after the last administration. These patients occasionally present with severe COVID-19 symptoms. Additionally, patients with hematologic diseases who have persistent COVID-19 after receiving anti-CD20 antibodies, postpone chemotherapy for the primary disease. Despite the efficacy of ensitrelvir in shortening the duration of symptoms, evidence of improved prognosis is lacking. However, prognosis might be improved if ensitrelvir treatment could reduce the viral load and shorten the time to postpone chemotherapy. It is unclear whether viral reduction directly improves prognosis. However, faster viral reduction may lead to faster resumption of chemotherapy for the underlying disease, resulting in better prognosis. Here, we present a case wherein we administered ensitrelvir fumaric acid to a 75-year-old woman with persistent COVID-19 after anti-CD20 antibody treatment. Her symptoms resolved quickly, with a reduction of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, and she could continue receiving chemotherapy for lymphoma. Our findings suggest that ensitrelvir administration should be considered in patients with SARS-CoV-2 infection after anti-CD20 antibody treatment.

Posterior reversible encephalopathy syndrome (PRES) associated with SARS-CoV-2 infection in a patient under maintenance haemodialysis: a case report.

BACKGROUND: Endothelial dysfunction is common in patients undergoing chronic haemodialysis, and is a major cause of posterior reversible encephalopathy syndrome (PRES). Recently, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause endothelial dysfunction by infecting vascular endothelial cells. Several cases of neurological complications in patients without kidney dysfunction, and only a few cases in patients with chronic kidney disease, have been reported in the literature. However, no previous report has yet described PRES associated with SARS-CoV-2 infection among patients undergoing maintenance dialysis. CASE PRESENTATION: A 54-year-old woman undergoing maintenance haemodialysis was admitted to our hospital for status epilepticus. She had developed end-stage kidney disease (ESKD) secondary to diabetic nephropathy. Seven days prior to admission, she had developed fever and was diagnosed with COVID-19. Subsequently her blood pressure increased from 160/90 mmHg to 190/100 mmHg. On admission, she presented with severe hypertension (> 220/150 mmHg), unconsciousness, and epilepticus. CT tomography revealed no signs of brain haemorrhage. Cranio-spinal fluid (CSF) examination revealed no signs of encephalitis, and CSF polymerase chain reaction (PCR) for SARS-CoV-2 was negative. MRI findings revealed focal T2/FLAIR hyperintensity in the bilateral parietooccipital regions, leading to the diagnosis of PRES. Deep sedation and strict blood pressure control resulted in a rapid improvement of her symptoms, and she was discharged without sequelae. CONCLUSIONS: We report the first case of PRES associated with SARS-CoV-2 infection in a patient undergoing maintenance haemodialysis. Patients undergoing maintenance haemodialysis are at high risk of PRES because of several risk factors. SARS-CoV-2 infection causes direct invasion of endothelial cells by binding to angiotensin-converting enzyme 2 (ACE2), initiating cytokine release, and hypercoagulation, leading to vascular endothelial cell injury and increased vascular leakage. In the present case, SARS-CoV-2 infection possibly be associated with the development of PRES.

A longitudinal study of Candida bloodstream infections in a Japanese university hospital: species distribution, drug susceptibility, clinical features, and mortality predictors.

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Difference of compliance rates for the recommendations in Japanese Guideline on Febrile Neutropenia according to respondents' attributes: the second report on a questionnaire survey among hematology-oncology physicians and surgeons.

PURPOSE: The Japanese Society of Medical Oncology (JSMO) published a guideline (GL) on febrile neutropenia (FN) in 2017. This study aims to identify promoting factors and disincentives for complying with GL recommendations according to attributes of doctors providing chemotherapy. METHODS: A questionnaire survey was conducted with SurveyMonkey™ for physician members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed according to the respondents' attributes. RESULT: Seven hundred eighty-eight out of retrieved 801 responses were available for analysis. Multivariable analysis demonstrated that the percentage of GL users was higher among women and Japanese Society of Clinical Oncology members. The overall compliance rate was higher among women, JSMO members, and board-certified medical oncologists. Internists emphasized the significance of collecting blood cultures at FN onset, and surgeons stressed the importance of G-CSF prophylaxis. Hematologists were less likely to adhere to recommendations on risk assessment of FN by the Multinational Association of Supportive Care in Cancer score and administration of gammaglobulin products. However, those are acceptable due to the characteristics of their practice. Eight recommendations had no difference in compliance rates between users and non-users, some of whose statements were ambiguous and discretionary. CONCLUSION: Women were more likely to use and adhere to GL. The recommendations should be developed considering the characteristics of specialty and subspecialty and avoiding ambiguity and discretionary statements.

Evaluation of minocycline combined with favipiravir therapy in coronavirus disease 2019 patients: A case-series study.

The aim of this study was to investigate the efficacy and safety of minocycline (MIN) and favipiravir combination therapy in patients with coronavirus disease 2019 (COVID-19) admitted to our hospital in Fukui Prefecture, Japan, in March and April of 2020. In this retrospective study, a favipiravir monotherapy group (Control group, n = 9) was compared with a combined favipiravir plus MIN therapy group (MIN group, n = 12). No severe cases were present. The primary comparative endpoints evaluated were duration of fever, duration of hospitalization, duration from treatment initiation to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-negative results, and changes in cytokine and chemokine production. Median duration from start of treatment to negative PCR test was significantly shorter in the MIN group than in the Control group. Mean rates of cytokine and chemokine reduction were significantly greater for interleukin-6 and interleukin-8 in the MIN group. No difference in adverse event rates were seen between groups, and only minor adverse events were encountered. MIN has been reported to have not only broad antibacterial activity, but also antiviral and anti-inflammatory activity. The present results support the efficacy and safety of MIN plus favipiravir therapy for the treatment of COVID-19.

A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons.

PURPOSE: The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study's purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. METHODS: A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. RESULT: A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score "always" or "more than half." Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10-20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0-92.8) and 77.8% (range 35.4-98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment. CONCLUSION: GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

MALDI-TOFMS-oriented early definitive therapy improves the optimal use of antibiotics for Enterococcus spp. bloodstream infection.

Enterococci is one of a major cause of bloodstream infection (BSI). Because of its intrinsic drug-resistant nature, empiric antibiotic treatment tends to be inappropriate. We conducted a single-center retrospective cohort study to evaluate the impact of Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOFMS) on the improvement of early antibiotic treatment for enterococcal infection. We also investigated the 28-day mortality, length of hospitalization and duration of antibiotic treatment for enterococcal bacteremia. A total of 173 BSI episodes (172 patients) between June 2012 and June 2019 were enrolled. Patients were divided into 2 groups before (n = 82) and after (n = 91) the implementation of MALDI-TOFMS (Control group and MALDI-TOF group, respectively). Almost an equal number of Enterococcus faecalis and Enterococcus faecium cases were identified in each group (51.2% and 48.8%, and 47.3% and 52.7% in each group). By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly improved (median 3 vs 1 days, p < 0.001). The 28-day mortality (29.3% vs 26.4%, p = 0.63) and length of hospitalization (median 16 vs 19 days, p = 0.58) were not significantly different. The duration of antibiotic treatment did not significantly differ between the two groups (median 11 vs 11 days, p = 0.78), but the duration was often shorter in older patients (>74 years old) in MALDI-TOF group, excluding those in the terminal phase of malignancy. By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly shortened. Although associated outcomes did not significantly differ, the duration of antibiotic treatment may be shortened.

Successful Treatment of Breakthrough Trichosporon asahii Fungemia by the Combination Therapy of Fluconazole and Liposomal Amphotericin B in a Patient with Follicular Lymphoma.

Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with echinocandins since Trichosporon spp. are resistant to these antifungal agents. We report a case of breakthrough Trichosporon asahii fungemia. A 62-year-old Japanese woman with relapsed follicular lymphoma was treated empirically with broad-spectrum antibiotics and micafungin due to an intermittent fever during reinduction chemotherapy. After four cycles of anti-cancer chemotherapy, she experienced a high neutropenic fever and T. asahii was subsequently detected from a blood culture. The patient was not given voriconazole due to the contraindication for use with carbamazepine, and she was successfully treated with fluconazole plus liposomal amphotericin B without any serious complications. The combined therapy of fluconazole and liposomal amphotericin B may therefore be useful in treating T. asahii fungemia, especially in patients receiving antiepileptic agents.

Collaboration with an infection control team promoted appropriate antibiotic use for third molar extraction at a Japanese hospital.

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P < 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P < 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction.

Successful management of a Bacillus cereus catheter-related bloodstream infection outbreak in the pediatric ward of our facility.

Bacillus cereus can spread easily in various environments and can contaminate medical environments, such as ventilator equipment, intravascular catheters, and linen. B. cereus is known to infect immunocompromised patients. Although nosocomial B. cereus outbreaks are often reported, effective preventive measures are not clarified. We report an outbreak of B. cereus catheter-related bloodstream infection (CRBSI) in the pediatric ward and aim at identifying risk factors and effective infection control measures for the outbreak. The nurse station at the pediatric ward and blood cultures were assessed. Sterilization of devices has been ensured thereafter. We identified common risk factors including catheter placement for liquid nutrition, use of high-caloric amino-acid-containing infusion fluid, immunocompromised patients, and contact of the catheter route with the floor. Intervention by the Infection Control Team and educating the medical staff regarding methods of disinfection, including scrubbing the facility, helped terminate the outbreak. We discuss a pre-emptive intervention to terminate the outbreak of CRBSI.

Sensitivity surveillance of Pseudomonas aeruginosa isolates for several antibacterial agents in Chubu area (2013-2014).

We investigated the susceptibility to antibacterial agents of 186 clinical isolates of Pseudomonas aeruginosa isolated from medical facilities in Gifu, Aichi, Toyama, and Fukui prefectures from October 2013 to February 2014. MIC50/90 of piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), aztreonam (AZT), ciprofloxacin (CPFX), levofloxacin (LVFX), amikacin (AMK) and colistin (CL) against P aeruginosa was 8/32, 4/32, 2/8, 2/16, 1/32, 0.5/8, 0.25/4, 8/32, 0.25/8, 0.5/16, 4/8 and 1/1pg/mLrespectively. Two strains of multidrug resistant P aeruginosa were isolated (1.1%). They were isolated from the respiratory tract, intra-abdominal, and urinary infection. The susceptible ratio against P aeruginosa derived from intra-abdominal infection for carbapenem was lower than those from respiratory tract and urinary infection. The susceptible ratio against P aeruginosa derived from urinary infection for penicillin, cephem, monobactam, and fluoroquinolone was lower than those from respiratory and intra-abdominal infection. It is meaningful to pay attention to the susceptibility to antibacterial agents in each clinical specimen from infected organ.

Spontaneous spinal epidural hematoma in a patient with acquired Factor X deficiency secondary to systemic amyloid light-chain amyloidosis.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is relatively rare. SSEH with anticoagulants including warfarin and rivaroxaban (Factor Xa inhibitor) have been reported; however, SSEH with Factor X deficiency has not been described yet. METHODS: Case report. FINDINGS: An 82-year-old woman with acquired Factor X deficiency complained of sudden onset of severe posterior neck pain. Magnetic resonance imaging demonstrated an epidural hematoma from C3 to T3 levels. Because she showed tetraparesis on the third hospital day, we performed surgery. Just before surgery, her prothrombin time-international normalized ratio was 2.49, which was immediately reversed by infusion of prothrombin complex concentrate. The patient safely underwent an emergency laminectomy from C3 to T2, in which the epidural hematoma was evacuated. Post-operatively, the patient recovered completely without rebleeding. Hematologists found acquired deficiency of Factor X in this patient with systemic amyloid light-chain amyloidosis. CONCLUSION: To our knowledge, this is the first report of a case of SSEH with Factor X deficiency. A blood coagulation disorder should be considered in patients with SSEH.

Significantly higher cytokine and chemokine levels in patients with Japanese spotted fever than in those with Tsutsugamushi disease.

Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1ß, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1ß) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD.

Should prophylactic thrombolysis be routine in clinical practice? Evidence from an autopsy case of septicemia.

BACKGROUND: Central venous catheters provide easy access for intravenous infusion and nutrition, but they can bring about complications such as catheter-related infections. Infected central venous catheters often cause nosocomial bloodstream infections with high morbidity and mortality. However, most of the morphological data that have been published are derived from in vitro and in vivo studies and few reports of direct evidence obtained from patient-derived samples have been described. Here we present visual evidence of catheter-related candidemia. To our knowledge, this is the first reported conventional histopathological evidence of a Candida-infected intraluminal thrombus in a patient's central venous catheter. CASE PRESENTATION: A 62-year-old Japanese female with obstructive jaundice, gastrointestinal bleeding, and liver metastasis from pancreatic head cancer was given an implantable subcutaneous central venous port for nutrition and chemotherapy administration. High fever ensued on day 16 after the central venous port insertion and blood cultures revealed Candida albicans. Although the patient was given 300 mg/day of fosfluconazole according to the suggestion of the infection control team, she died from respiratory failure. Postmortem computed tomography revealed findings consistent with acute respiratory distress syndrome, suggesting that the patient's course was complicated by catheter-related sepsis. Autopsy revealed a subcutaneous abscess around the port, from which C. albicans was cultured. However, no catheter-adherent thrombus, thrombosis of the great central veins, or endocardial vegetations were detected in the patient. Histological analysis revealed scattered abscesses in several organs including lungs and kidneys. Hyaline membrane formation and Candida colonies were found in the lungs. The central venous port tube, together with the part of the subclavian vein into which it had been inserted, was involved in an intraluminal fibrin thrombus containing neutrophils and macrophages, indicating that the thrombus existed while the patient was alive. Histopathological examination following use of the periodic acid-Schiff reagent and the Grocott stain revealed scattered Candida in the thrombus. CONCLUSIONS: Prophylactic thrombolysis should be encouraged to prevent central venous catheter-related candidiasis in clinical practice.

[Sudden blast crisis of chronic myeloid leukemia after a 13-year durable remission following allogeneic bone marrow transplantation and donor lymphocyte infusion].

We describe a rare case of sudden blast crisis of chronic myeloid leukemia that occurred after a 13-year durable remission, following allogeneic bone marrow transplantation and donor lymphocyte infusion. A 55-year-old Japanese man was diagnosed with chronic-phase chronic myeloid leukemia 24 years previously. He underwent allogeneic bone marrow transplantation 2 years after diagnosis. Although the disease recurred 6 years after transplantation, the patient achieved remission again by a donor lymphocyte infusion. Despite a 13-year durable remission, the disease later relapsed into a sudden blast crisis. Prednisolone and vincristine combined with imatinib mesylate effectively achieved a major molecular response. However, the disease relapsed repeatedly with central nervous system infiltration. Dasatinib and intrathecal methotrexate, cytarabine, and dexamethasone administration via the Ommaya reservoir controlled disease progression. Nevertheless, the disease became refractory to treatment with the emergence of a T315I Bcr-Abl gene mutation. The patient eventually died 43 months post crisis.

Tracheostomy wound myiasis in a patient with hypoxic encephalopathy.

•Tracheostomy wound myiasis is rarely observed in unconscious and immobile patients.•Maggots in the vicinity of the tracheostomy site should be closely monitored.•Controlling myiasis in hospitals requires fly control and patient fluid management.

Frequency and Risk Factors for Persistent and Concomitant Symptoms after Hospital Discharge for Coronavirus Disease 2019 in the Pre-omicron Period: An Exploratory Longitudinal Study.

Introduction: Many countries have reported persistent and concomitant symptoms of coronavirus disease 2019 (COVID-19). This study aimed to identify persistent COVID-19 and concomitant symptoms in discharged patients and identify the risk factors for such symptoms. Methods: This study enrolled patients with COVID-19 who were admitted to the University of Fukui Hospital, Japan, and discharged between April 3, 2020, and August 19, 2021. Persistent and concomitant symptoms were confirmed based on medical examinations approximately 2 weeks after discharge. Patient characteristics and symptoms were collected from the patients' medical records by a technical assistant. Results: This study included 120 patients (60 men and 60 women; mean age, 53.5 ± 17.0 years). Persistent COVID-19 symptoms were observed in 62 patients (51.7%). The most common persistent symptom was weakened physical function, manifesting as physical weakness (48.4%) and muscle weakness (29.0%). Binary logistic regression analysis revealed that cough with expectoration within the acute phase of COVID-19 was a risk factor predisposing patients to COVID-19 sequelae (odds ratio: 2.94, 95% confidence interval: 1.300 - 6.630, p = 0.009). Conclusions: The study findings suggest that productive cough in the acute phase is associated with subsequent physical and muscle weaknesses in the subacute phase.

Infection rate among close contacts of patients with coronavirus disease in Japan: a descriptive study and literature review.

Background: In Japan, on April 20, 2020, the definition of a close contact regarding coronavirus disease (COVID-19) was changed from a long-term contact time to a specified contact time of 15 min and from a contact distance of 2 m to 1 m. Objectives: We aimed to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate among close contacts of patients with COVID-19 and determine the impact of the infection on transmission among close contacts. Methods: The numbers of SARS-CoV-2 tests, SARS-CoV-2-positive cases, and close contacts of patients with COVID-19 were assessed between March 2020 and February 2021 in Fukui Prefecture, Japan. The study period was subdivided into 3 periods. The second and third period contained data with the changed definition of close contact. Results: Overall, 32,238 SARS-CoV-2 tests were performed. There were 545 patients with COVID-19 and 1487 close contacts, of whom 267 tested positive. The highest infection rate occurred in period 3. Distance, protective measures, and contact time with COVID-19 patients influenced the increased infection rate. The infection rate showed a rising trend from 11.1% in period 1 to 19.2% and 20.0% in periods 2 and 3, respectively (Cochran-Armitage test; P < 0.004). Multivariate analysis revealed that female sex was an independent risk factor for infection of close contacts (odds ratio: 2.23; 95% confidence interval: 1.700-2.930). Conclusions: Female sex is a risk factor for transmission by close contacts. The rate of infection among close contacts may be associated with contact time, contact distance, and protective measures.