Multistate Outbreak of Melioidosis Associated with Imported Aromatherapy Spray.

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.

Subclinical Burkholderia pseudomallei Infection Associated with Travel to the British Virgin Islands.

Phylogenetic analysis of a clinical isolate associated with subclinical Burkholderia pseudomallei infection revealed probable exposure in the British Virgin Islands, where reported infections are limited. Clinicians should consider this geographic distribution when evaluating possible infection among persons with compatible travel history.

Human Melioidosis Caused by Novel Transmission of Burkholderia pseudomallei from Freshwater Home Aquarium, United States1.

Nearly all cases of melioidosis in the continental United States are related to international travel to areas to which Burkholderia pseudomallei, the bacterium that causes melioidosis, is endemic. We report the diagnosis and clinical course of melioidosis in a patient from the United States who had no international travel history and the public health investigation to determine the source of exposure. We tested environmental samples collected from the patient's home for B. pseudomallei by PCR and culture. Whole-genome sequencing was conducted on PCR-positive environmental samples, and results were compared with sequences from the patient's clinical specimen. Three PCR-positive environmental samples, all collected from a freshwater home aquarium that had contained imported tropical fish, were a genetic match to the clinical isolate from the patient. This finding suggests a novel route of exposure and a potential for importation of B. pseudomallei, a select agent, into the United States from disease-endemic areas.

Melioidosis in a Resident of Texas with No Recent Travel History, United States.

To our knowledge, environmental isolation of Burkholderia pseudomallei, the causative agent of melioidosis, from the continental United States has not been reported. We report a case of melioidosis in a Texas resident. Genomic analysis indicated that the isolate groups with B. pseudomallei isolates from patients in the same region, suggesting possible endemicity to this region.

Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019.

This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of anthrax vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No. RR-6]). The report 1) summarizes data on estimated efficacy in humans using a correlates of protection model and safety data published since the last ACIP review, 2) provides updated guidance for use of anthrax vaccine adsorbed (AVA) for preexposure prophylaxis (PrEP) and in conjunction with antimicrobials for postexposure prophylaxis (PEP), 3) provides updated guidance regarding PrEP vaccination of emergency and other responders, 4) summarizes the available data on an investigational anthrax vaccine (AV7909), and 5) discusses the use of anthrax antitoxins for PEP. Changes from previous guidance in this report include the following: 1) a booster dose of AVA for PrEP can be given every 3 years instead of annually to persons not at high risk for exposure to Bacillus anthracis who have previously received the initial AVA 3-dose priming and 2-dose booster series and want to maintain protection; 2) during a large-scale emergency response, AVA for PEP can be administered using an intramuscular route if the subcutaneous route of administration poses significant materiel, personnel, or clinical challenges that might delay or preclude vaccination; 3) recommendations on dose-sparing AVA PEP regimens if the anthrax vaccine supply is insufficient to vaccinate all potentially exposed persons; and 4) clarification on the duration of antimicrobial therapy when used in conjunction with vaccine for PEP.These updated recommendations can be used by health care providers and guide emergency preparedness officials and planners who are developing plans to provide anthrax vaccine, including preparations for a wide-area aerosol release of B. anthracis spores. The recommendations also provide guidance on dose-sparing options, if needed, to extend the supply of vaccine to increase the number of persons receiving PEP in a mass casualty event.

Melioidosis after Hurricanes Irma and Maria, St. Thomas/St. John District, US Virgin Islands, October 2017.

We report 2 cases of melioidosis in women with diabetes admitted to an emergency department in the US Virgin Islands during October 2017. These cases emerged after Hurricanes Irma and Maria and did not have a definitively identified source. Poor outcomes were observed when septicemia and pulmonary involvement were present.

Estimation of Undiagnosed Naegleria fowleri Primary Amebic Meningoencephalitis, United States1.

Primary amebic meningoencephalitis is an acute, rare, typically fatal disease. We used epidemiologic risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for primary amebic meningoencephalitis; we estimated an annual average of 16 deaths (8 male, 8 female) in the United States.

Burkholderia thailandensis Isolated from Infected Wound, Arkansas, USA.

The bacterium Burkholderia thailandensis, a member of the Burkholderia pseudomallei complex, is generally considered nonpathogenic; however, on rare occasions, B. thailandensis infections have been reported. We describe a clinical isolate of B. thailandensis, BtAR2017, recovered from a patient with an infected wound in Arkansas, USA, in 2017.

Notes from the Field: Travel-Associated Melioidosis and Resulting Laboratory Exposures - United States, 2016.

In mid-July 2016, a Pennsylvania resident aged 15 years who had recently returned from Thailand was treated by a pediatrician for sore throat, fever, and bilateral thigh abscesses at the sites of mosquito bites (Figure). She had traveled to northeast Thailand with nine other teens as part of an 18-day service-oriented trip run by an Ohio-based youth tour company that arranges travel to Thailand for approximately 500 persons annually. This trip included construction and agricultural activities and recreational mud exposures. The patient subsequently developed right inguinal lymphadenopathy and worsening abscesses, which prompted specimen collection for culture on August 25. This specimen was sent to a commercial laboratory in New Jersey, which identified Burkholderia pseudomallei, the causative organism of melioidosis, on August 30. The patient did not experience pneumonia or bacteremia, and recovered fully after 2 weeks of intensive therapy with parenteral ceftazidime and a 6-month outpatient course of eradication therapy with doxycycline.

Cytokine and chemokine profiles in lung tissues from fatal cases of 2009 pandemic influenza A (H1N1): role of the host immune response in pathogenesis.

Pathological studies on fatal cases caused by 2009 pandemic influenza H1N1 virus (2009 pH1N1) reported extensive diffuse alveolar damage and virus infection predominantly in the lung parenchyma. However, the host immune response after severe 2009 pH1N1 infection is poorly understood. Herein, we investigated viral load, the immune response, and apoptosis in lung tissues from 50 fatal cases with 2009 pH1N1 virus infection. The results suggested that 7 of the 27 cytokines/chemokines showed remarkably high expression, including IL-1 receptor antagonist protein, IL-6, tumor necrosis factor-α, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-ß, and interferon-inducible protein-10 in lung tissues of 2009 pH1N1 fatal cases. Viral load, which showed the highest level on day 7 of illness onset and persisted until day 17 of illness, was positively correlated with mRNA levels of IL-1 receptor antagonist protein, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-ß, interferon-inducible protein-10, and regulated on activation normal T-cell expressed and secreted. Apoptosis was evident in lung tissues stained by the TUNEL assay. Decreased Fas and elevated FasL mRNA levels were present in lung tissues, and cleaved caspase-3 was frequently seen in pneumocytes, submucosal glands, and lymphoid tissues. The pathogenesis of the 2009 pH1N1 virus infection is associated with viral replication and production of proinflammatory mediators. FasL and caspase-3 are involved in the pathway of 2009 pH1N1 virus-induced apoptosis in lung tissues, and the disequilibrium between the Fas and FasL level in lung tissues could contribute to delayed clearance of the virus and subsequent pathological damages.

Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases.

September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.

Neutrophilic bacterial meningitis: pathology and etiologic diagnosis of fatal cases.

The frequency of fatalities due to acute bacterial meningitis has decreased significantly due to vaccinations, early diagnoses, and treatments. We studied brain tissues of patients with fatal neutrophilic meningitis referred to the Centers for Disease Control for etiologic diagnosis from 2000-2009 to highlight aspects of the disease that may be preventable or treatable. Demographic, clinical, and laboratory data were extracted from records. Of 117 cases in the database with a diagnosis of meningitis or meningoencephalitis, 39 had neutrophilic inflammation in the meninges. Inflammatory cells infiltrated the superficial cortex in 16 of 39 (41%) cases. Bacteria were found using Gram and bacterial silver stains in 72% of cases, immunohistochemistry in 69% (including two cases where the meningococcus was found outside the meninges), and PCR in 74%. Streptococcus pneumoniae was the cause of the meningitis in 14 patients and Neisseria meningitidis in 9. In addition, Streptococcus spp. were found to be the cause in six cases, while Staphylococcus aureus, Staphylococcus spp., Enterococcus spp., and Fusobacterium were the cause of one case each. There were six cases in which no specific etiological agent could be determined. The mean age of the patients with S. pneumoniae was 39 years (range 0-65), with N. meningitidis was 19 years (range 7-51), whereas that for all others was 31 years (range 0-68). In summary, our study shows that S. pneumoniae continues to be the most frequent cause of fatal neutrophilic bacterial meningitis followed by N. meningitidis, both vaccine preventable diseases.

Myocardial injury and bacterial pneumonia contribute to the pathogenesis of fatal influenza B virus infection.

BACKGROUND: Influenza B virus infection causes rates of hospitalization and influenza-associated pneumonia similar to seasonal influenza A virus infection and accounts for a substantial percentage of all influenza-related hospitalizations and deaths among those aged <18 years; however, the pathogenesis of fatal influenza B virus infection is poorly described. METHODS: Tissue samples obtained at autopsy from 45 case patients with fatal influenza B virus infection were evaluated by light microscopy and immunohistochemical assays for influenza B virus, various bacterial pathogens, and complement components C4d and C9, to identify the cellular tropism of influenza B virus, characterize concomitant bacterial pneumonia, and describe the spectrum of cardiopulmonary injury. RESULTS: Viral antigens were localized to ciliated respiratory epithelium and cells of submucosal glands and ducts. Concomitant bacterial pneumonia, caused predominantly by Staphylococcus aureus, was identified in 38% of case patients and occurred with significantly greater frequency in those aged >18 years. Pathologic evidence of myocardial injury was identified in 69% of case patients for whom cardiac tissue samples were available for examination, predominantly in case patients aged <18 years. CONCLUSIONS: Our findings suggest that bacterial pneumonia and cardiac injury contribute to fatal outcomes after infection with influenza B virus and that the frequency of these manifestations may be age related.

Determinants for autopsy after unexplained deaths possibly resulting from infectious causes, United States.

We analyzed US multiple cause-of-death data for 2003-2006 for demographic and clinical determinants for autopsy in unexplained deaths possibly resulting from infectious causes. For 96,242 deaths, the definition for unexplained death was met and autopsy status was recorded. Most decedents were male, 40-49 years of age, and white. To identify factors associated with unexplained death, we used data from Arizona records. Multivariate analysis of Arizona records suggested that decedents of races other than white and black and decedents who had clinicopathologic syndromes in the cardiovascular, sepsis/shock, and multisyndrome categories recorded on the death certificate were least likely to have undergone autopsy; children with unexplained death were the most likely to have undergone autopsy. Improved understanding of unexplained deaths can provide opportunities for further studies, strengthen collaboration between investigators of unexplained deaths, and improve knowledge and awareness of infectious diseases of public health concern.

Melioidosis in Cynomolgus Macaques ( Macaca Fascicularis ) Imported to the United States from Cambodia.

Melioidosis, a potentially fatal infectious disease of humans and animals, including nonhuman primates (NHPs), is caused by the high-consequence pathogen Burkholderia pseudomallei. This environmental bacterium is found in the soil and water of tropical regions, such as Southeast Asia, where melioidosis is endemic. The global movement of humans and animals can introduce B. pseudomallei into nonendemic regions of the United States, where environmental conditions could allow establishment of the organism. Approximately 60% of NHPs imported into the United States originate in countries considered endemic for melioidosis. To prevent the introduction of infectious agents to the United States, the Centers for Disease Control and Prevention (CDC) requires newly imported NHPs to be quarantined for at least 31 d, during which time their health is closely monitored. Most diseases of public health concern that are transmissible from imported NHPs have relatively short incubation periods that fall within the 31-d quarantine period. However, animals infected with B. pseudomallei may appear healthy for months to years before showing signs of illness, during which time they can shed the organism into the environment. Melioidosis presents diagnostic challenges because it causes nonspecific clinical signs, serologic screening can produce unreliable results, and culture isolates are often misidentified on rapid commercial testing systems. Here, we present a case of melioidosis in a cynomolgus macaque (Macaca fascicularis) that developed a subcutaneous abscess after importation from Cambodia to the United States. The bacterial isolate from the abscess was initially misidentified on a commercial test. This case emphasizes the possibility of melioidosis in NHPs imported from endemic countries and its associated diagnostic challenges. If melioidosis is suspected, diagnostic samples and culture isolates should be submitted to a laboratory in the CDC Laboratory Response Network for conclusive identification and characterization of the pathogen.

A pilot study of host genetic variants associated with influenza-associated deaths among children and young adults.

We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza. No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample. Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6-32.1). Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection. Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.

2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States.

In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.

A Tale of Two Viruses: Coinfections of Monkeypox and Varicella Zoster Virus in the Democratic Republic of Congo.

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.

Differentiating New from Newly Detected: Melioidosis in Yap, Federated States of Micronesia.

Melioidosis is a bacterial infection caused by exposure to water or soil that contains Burkholderia pseudomallei (Bp). Burkholderia pseudomallei is endemic to many tropical and subtropical areas of the world. In 2013, the first case of melioidosis was recognized in Yap, the Federated States of Micronesia. Six additional cases were identified in the subsequent 3 years. An investigation was initiated to understand the epidemiology of melioidosis in Yap. Serum from family and community members of the identified cases were tested for antibodies to Bp. Archived serum from a 2007 Zika serosurvey were also tested for antibodies to Bp. Sequencing of bacterial isolates was performed to understand bacterial phylogeny. Soil and water were tested for the presence of Bp in the environment by culture and PCR. None of the affected patients had a history of travel to melioidosis-endemic countries. Two of the 34 (5.8%) samples from the field investigation and 67 (11.7%) of the historical samples demonstrated serologic evidence of prior Bp exposure. No Bp were detected from 30 soil or water samples. Genotype analysis showed highly related Bp isolates that were unique to Yap. Melioidosis is likely to be endemic to Yap; however, it has only recently been recognized by the clinical community in country. Further investigation is needed to understand the local sites that harbor Bp and represent the highest risk to the community.

Amoebic meningoencephalitis and disseminated infection caused by Balamuthia mandrillaris in a Western lowland gorilla (Gorilla gorilla gorilla).

CASE DESCRIPTION A 22-year-old male gorilla (Gorilla gorilla gorilla) housed in a zoo was evaluated for signs of lethargy, head-holding, and cervical stiffness followed by development of neurologic abnormalities including signs of depression, lip droop, and tremors. CLINICAL FINDINGS Physical examination under general anesthesia revealed a tooth root abscess and suboptimal body condition. A CBC and serum biochemical analysis revealed mild anemia, neutrophilia and eosinopenia consistent with a stress leukogram, and signs consistent with dehydration. Subsequent CSF analysis revealed lymphocytic pleocytosis and markedly increased total protein concentration. TREATMENT AND OUTCOME Despite treatment with antimicrobials, steroids, and additional supportive care measures, the gorilla's condition progressed to an obtunded mentation with grand mal seizures over the course of 10 days. Therefore, the animal was euthanized and necropsy was performed. Multifocal areas of malacia and hemorrhage were scattered throughout the brain; on histologic examination, these areas consisted of necrosis and hemorrhage associated with mixed inflammation, vascular necrosis, and intralesional amoebic trophozoites. Tan foci were also present in the kidneys and pancreas. Immunohistochemical testing positively labeled free-living amoebae within the brain, kidneys, eyes, pancreas, heart, and pulmonary capillaries. Subsequent PCR assay of CSF and frozen kidney samples identified the organism as Balamuthia mandrillaris, confirming a diagnosis of amoebic meningoencephalitis. CLINICAL RELEVANCE Infection with B mandrillaris has been reported to account for 2.8% of captive gorilla deaths in North America over the past 19 years. Clinicians working with gorillas should have a high index of suspicion for this diagnosis when evaluating and treating animals with signs of centrally localized neurologic disease.