Pulmonary Tuberculosis Disease Among Immigrant Detainees: Rapid Disease Detection, High Prevalence of Asymptomatic Disease, and Implications for Tuberculosis Prevention.

BACKGROUND: Rapid screening for tuberculosis (TB) disease at intake into immigrant detention facilities allows for early detection and treatment. Detention facilities with United States Immigration and Customs Enforcement (ICE) Health Service Corps (IHSC) medical staffing utilize chest radiography and symptom screening as the primary screening for pulmonary TB (PTB) disease. This analysis describes the demographic, clinical, and microbiological characteristics of individuals identified with TB disease at these facilities. METHODS: We conducted a retrospective analysis to describe the population of immigrant detainees identified via chest radiography with PTB disease between 1 January 2014 and 31 December 2016 at facilities with IHSC medical staffing. We collected demographic variables, clinical presentation, diagnostic testing results, and microbiological findings. We generated descriptive statistics and examined univariate and multivariate associations between the variables collected and symptomatic status. RESULTS: We identified 327 patients with confirmed PTB disease (incidence rate, 92.8 per 100 000); the majority of patients were asymptomatic (79.2%) at diagnosis. Adjusting for all other variables in the model, the presence of cavitary lesions, acid-fast bacillus smear positivity, and multilobar presentation were significantly associated with symptomatic status. Among all patients identified with TB disease who had a tuberculin skin test (TST) result recorded, 27.2% were both asymptomatic and TST negative, including those with smear-positive disease. CONCLUSIONS: Asymptomatic PTB disease is a significant clinical entity among immigrant detainees and placement in a congregate setting calls for aggressive screening to prevent transmission. Early identification, isolation, and treatment of TB disease benefit not only the health of the patient, but also the surrounding community.

Predictive factors of facilitating linkage to care for HIV-positive detainees in ICE Health Service Corps-staffed facilities.

BACKGROUND: Persons in ICE detention represent a population about whom limited health-related data is available in the literature. Since ICE detention is generally brief, facilitating linkage to care (FLC) for detainees with chronic diseases, including HIV-positive detainees, is challenging, yet critical to encourage continued treatment beyond custody. Between 2015 and 2017, IHSC-staffed facilities implemented intensive training related to HIV care and FLC and increased clinical oversight and consultations. This study examined the impact of these changes in relation to FLC. METHODS: Demographic and clinical data for detainees with known HIV-positive diagnoses at IHSC-staffed facilities entering custody in 2015 and 2017 were obtained via electronic health record. Univariate analysis and multiple logistic regressions were performed to identify factors that may increase FLC. RESULTS: After adjusting for year of entry into custody, detainees who received an infectious disease (ID) consultation had significantly higher odds (2.4, P < 0.001) of receiving FLC resources compared to those who did not receive an ID consultation. Between 2015 and 2017, the proportion of HIV-positive detainees receiving FLC resources increased from 29 to 62%. CONCLUSIONS: ID consultations significantly improved FLC for HIV-positive detainees. Continued provider training and education is essential to continue improving the rate of FLC for HIV-positive ICE detainees.

Rabies death attributed to exposure in Central America with symptom onset in a U.S. detention facility - Texas, 2013.

On June 7, 2013, a man was diagnosed in a Texas hospital with rabies. He had been detained in a U.S. detention facility during his infectious period. To identify persons exposed to rabies who might require rabies postexposure prophylaxis (PEP), CDC and the Texas Department of State Health Services (DSHS) conducted investigations at four detention facilities, one medical clinic, and two hospitals. In all, 25 of 742 persons assessed for rabies exposure were advised to receive PEP. Early diagnosis of rabies is essential for implementation of appropriate hospital infection control measures and for rapid assessment of potential contacts for PEP recommendations.

Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001.

Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV.

Risk factors associated with complications and mortality in patients with Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) has increased in frequency and severity over the past decade. An understanding of the modifiable risk factors for disease severity has considerable clinical applicability. METHODS: We performed a retrospective case review of 485 cases in patients aged 1-99 years at the Naval Medical Center San Diego from November 2004 through December 2008. We compared potential risk factors for association with complications (megacolon, surgery, intensive care unit stay, and death) or mortality alone with use of univariable and multivariable logistic regression modeling. RESULTS: Forty-seven patients (9.8%) developed ≥1 complication, and 23 (4.7%) died. We found independent associations between complications and acid suppression (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.2-4.79), admission for CDI (OR, 4.14; 95% CI, 2.17-7.92), older age (≥80 years; OR, 3.14; 95% CI, 1.46-6.73), and corticosteroid use (OR, 2.09; 95% CI, 1.01-4.35). Age ≥80 years (OR, 5.51; 95% CI, 2.25-13.49) and acid suppression (OR, 4.74; 95% CI, 1.57-14.37) were associated with increased odds of death. CONCLUSIONS: Data published elsewhere have suggested that acid suppression therapy is a risk factor for CDI acquisition and relapse. These findings suggest an additional role in increased severity of disease, including mortality, and merit further study.

Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu.

BACKGROUND: Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. METHODS: In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. RESULTS: The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. CONCLUSION: Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study observation period. The only in vivo malaria drug efficacy trial thus far published from the Republic of Vanuatu showed chloroquine/sulphadoxine-pyrimethamine combination therapy for P. falciparum and chloroquine alone for P. vivax to be highly efficacious. Although the chloroquine-resistant pfcrt allele was present in all P. falciparum isolates, mutant alleles in the dhfr and dhps genes do not yet occur to the extent required to confer sulphadoxine-pyrimethamine resistance in this population.

Opt-out Testing Pilot for Sexually Transmitted Infections Among Immigrant Detainees at 2 Immigration and Customs Enforcement Health Service Corps-Staffed Detention Facilities, 2018.

OBJECTIVES: Correctional settings (prisons, jails, detention facilities) provide a unique opportunity to screen for sexually transmitted infections (STIs) among correctional populations with a high prevalence of infection. Immigrant detainees are a distinct and poorly described correctional population. The main objective of this study was to determine the feasibility of a national STI screening program for immigrant detainees. METHODS AND MATERIALS: We developed an opt-out STI testing program that included electronic health record integration, patient education, and staff member training. We piloted this program from June 22 through August 19, 2018, at 2 detention facilities with different operational requirements and detainee demographic characteristics. We assessed STI test positivity rates, treatment outcomes, estimated cost to conduct testing and counseling, and staff member perceptions of program value and challenges to implementation. RESULTS: Of 1041 immigrant detainees approached for testing, 526 (50.5%) declined. Of 494 detainees who were tested, 42 (8.5%) tested positive for at least 1 STI; the percentage positivity rates were 6.7% (n = 33) for chlamydia, 0.8% (n = 4) for syphilis, 0.8% (n = 4) for gonorrhea, 0.6% (n = 3) for hepatitis B, and 0.2% (n = 1) for HIV. The estimated cost to detect any STI ranged from $500 to $961; the estimated cost to identify 1 person infected with HIV ranged from $22 497 to $43 244. Forty of 42 persons who tested positive began treatment before release from custody. Medical staff members had positive views of the program but had concerns about workload. PRACTICE IMPLICATIONS: STIs are prevalent among immigrant detainees. A routine screening program is feasible if operational aspects are carefully considered and would provide counseling, education, and treatment for this vulnerable population.

Severe eczema vaccinatum in a household contact of a smallpox vaccinee.

BACKGROUND: We report the first confirmed case of eczema vaccinatum in the United States related to smallpox vaccination since routine vaccination was discontinued in 1972. A 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the US military who had recently received smallpox vaccine. The father had a history of inactive eczema but reportedly reacted normally to the vaccine. The child's mother also developed contact vaccinia infection. METHODS: Treatment of the child included vaccinia immune globulin administered intravenously, used for the first time in a pediatric patient; cidofovir, never previously used for human vaccinia infection; and ST-246, an investigational agent being studied for the treatment of orthopoxvirus infection. Serological response to vaccinia virus and viral DNA levels, correlated with clinical events, were utilized to monitor the course of disease and to guide therapy. Burn patient-type management was required, including skin grafts. RESULTS: The child was discharged from the hospital after 48 days and has recovered with no apparent systemic sequelae or significant scarring. CONCLUSION: This case illustrates the need for careful screening prior to administration of smallpox vaccine and awareness by clinicians of the ongoing vaccination program and the potential risk for severe adverse events related to vaccinia virus.

Bloodstream infections in patients given treatment with intravenous prostanoids.

OBJECTIVE: In September 2006, the Centers for Disease Control and Prevention was notified of cases of gram-negative bloodstream infection (BSI) occurring among outpatients who received an intravenous formulation of the prostanoid treprostinil. An investigation was conducted to determine rates of prostanoid-associated BSI in this patient population and possible risk factors for infection. METHODS: We performed a retrospective cohort study of patients who had received intravenous formulations of at least 1 of the 2 approved prostanoids (epoprostenol and treprostinil) from January 1, 2004, through late 2006. Chart reviews were conducted at 2 large centers for pulmonary arterial hypertension, and a survey of infection control practices was conducted at 1 center. RESULTS: A total of 224 patients were given intravenous prostanoid treatment, corresponding to 146,093 treatment-days during the study period. Overall, there were 0.55 cases of BSI and 0.18 cases of BSI due to gram-negative organisms per 1,000 treatment-days. BSI rates were higher for patients who received intravenous treprostinil than for patients who received intravenous epoprostenol (1.13 vs. 0.42 BSIs per 1,000 treatment-days; P < .001), as were rates of BSI due to gram-negative organisms (0.81 vs. 0.04 BSIs per 1,000 treatment-days; P < .001). Adjusted hazard ratios for all BSIs and for BSIs due to gram-negative organisms were higher among patients given treatment with intravenous treprostinil. The survey identified no significant differences in medication-related infection control practices. CONCLUSION: At 2 centers, BSI due to gram-negative pathogens was more common than previously reported and was more frequent among patients given treatment with intravenous treprostinil than among patients given treatment with intravenous epoprostenol. Whether similar results would be found at other centers for pulmonary arterial hypertension warrants further investigation. This investigation underscores the importance of surveillance and evaluation of healthcare-related adverse events in patients given treatment primarily as outpatients.

Serological Susceptibility to Varicella Among U.S. Immigration and Customs Enforcement Detainees.

U.S. Immigration and Customs Enforcement (ICE) is responsible for detaining unauthorized aliens during immigration proceedings. During 2014 to 2015, adult ICE detainees at a California facility were invited to complete a survey concerning self-reported varicella history and risk factors. Participants underwent serological testing for varicella-zoster virus (VZV) IgG; susceptible individuals were offered varicella vaccination. Among 400 detainees with available serology results, 48 (12%) were susceptible to varicella. Self-reported varicella history was negatively associated with susceptibility (adjusted odds ratio = 0.16; 95% confidence interval [0.07, 0.35]). Among 196 detainees reporting a positive history, 95% had VZV IgG levels suggestive of varicella immunity. Among 44 susceptible detainees offered vaccination, 86% accepted. Given relatively high varicella susceptibility, targeted screening and vaccination among ICE detainees lacking a positive history might reduce varicella transmission risks.

Progressive ORF virus infection in a patient with lymphoma: successful treatment using imiquimod.

Orf virus is a parapoxvirus that infects small ruminants worldwide. We present the case report of a 73-year-old woman with non-Hodgkins lymphoma who developed progressive orf virus lesions that were unresponsive to surgical debridement and to cidofovir therapy. The patient's orf virus infection was successfully treated with topical imiquimod despite progression of her malignancy.

ORF virus infection in children: clinical characteristics, transmission, diagnostic methods, and future therapeutics.

Orf virus leads to self-limited, subacute cutaneous infections in children who have occupational or recreational contact with infected small ruminants. Breaches in the integument and contact with animals recently vaccinated for orf may be important risk factors in transmission. Common childhood behaviors are likely important factors in the provocation of significant contact (ie, bites) or in unusual lesion location (eg, facial lesions). Clinician recognition is important in distinguishing orf infection from life-threatening cutaneous zoonoses. Recently developed molecular techniques provide diagnostic precision and newer topical therapeutics may hasten healing.

Prevalence of antibodies against orthopoxviruses among residents of Likouala region, Republic of Congo: evidence for monkeypox virus exposure.

Monkeypox virus is a zoonotic orthopoxvirus (OPX) of west and central sub-Saharan Africa. We conducted a cross-sectional serosurvey in Likouala region, Republic of Congo to assess exposure to OPX. Whole blood was collected using Nobuto blood filter strips (NBFS). Titers of IgM and IgG to OPX were assessed using an enzyme-linked immunosorbent assay. Demographic and clinical characteristics were compared with serostatus using the chi-square test or Fisher's exact test. Multivariate logistic regression was performed to evaluate factors for independent association with serostatus. A total of 994 specimens were analyzed; the overall seroprevalence for OPX IgM was 1.7%. Age < 25 years reduced the likelihood of OPX exposure, and persons living in Ngangania village had independently higher odds (odds ratio = 33.5, 95% confidence interval = 7.2-166). Blood collection for serosurveys using NBFS is feasible and practical. Adult activities such as hunting and carcass preparation may play an important role in exposure to Monkeypox virus.

Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia.

BACKGROUND: Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable. METHODS: This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ). RESULTS: After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006). CONCLUSION: Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study.

Production and validation of durable, high quality standardized malaria microscopy slides for teaching, testing and quality assurance during an era of declining diagnostic proficiency.

BACKGROUND: Sets of Giemsa-stained, blood smear slides with systematically verified composite diagnoses would contribute substantially to development of externally validated quality assurance systems for the microscopic diagnosis of malaria. METHODS: whole blood from Plasmodium-positive donors in Cambodia and Indonesia and individuals with no history of risk for malaria was collected. Using standard operating procedures, technicians prepared Giemsa-stained thick and thin smears from each donor. One slide from each of the first 35 donations was distributed to each of 28 individuals acknowledged by reputation as having expertise in the microscopic diagnosis of malaria. These reference readers recorded presence or absence of Plasmodium species and parasite density. A composite diagnosis for each donation was determined based on microscopic findings and species-specific small subunit ribosomal RNA (ssrRNA) DNA polymerase chain reaction (PCR) amplification. RESULTS: More than 12,000 slides were generated from 124 donations. Reference readers correctly identified presence of parasites on 85% of slides with densities <100 parasites/microl, which improved to 100% for densities >350 parasites/microl. Percentages of agreement with composite diagnoses were highest for Plasmodium falciparum (99%), followed by Plasmodium vivax (86%). CONCLUSION: Herein, a standardized method for producing large numbers of consistently high quality, durable Giemsa-stained blood smears and validating composite diagnoses for the purpose of creating a malaria slide repository in support of initiatives to improve training and competency assessment amidst a background of variability in diagnosis is described.

Imported malaria in Jakarta, Indonesia: passive surveillance of returned travelers and military members postdeployment.

BACKGROUND: Autochthonous malaria does not currently occur in Jakarta, the most populous city in Indonesia. Military, forestry, mining, and tourist activities draw Jakarta residents to distant parts of the archipelago with high rates of malaria. Although malaria is a reportable disease in Jakarta, little has been published. METHODS: We collected demographic and travel information from patients in Jakarta with microscopically confirmed malaria from January 2004 to February 2005, using a standardized data collection form. These results were compared to regional rainfall statistics and transit patterns of Jakarta residents to and from rural areas. RESULTS: Data from 240 patients were collected. Aceh Province was the travel destination most commonly recorded for military members, while Papua and Bangka Island were the most frequently cited by civilians. Plasmodium falciparum accounted for 53% of cases, of which 15% had detectable gametocytemia. The most common admission diagnoses were malaria (39%), febrile illness not otherwise specified (23%), viral hepatitis (19%), and dengue (11%). The median time from admission to microscopic diagnosis was 2 days for civilian patients and 2.5 days for military patients. The highest number of cases occurred in May, July, and December with the nadir in October. CONCLUSIONS: The diagnosis of malaria may be overlooked and therefore delayed, in nonendemic areas such as Jakarta. Travel destinations associated with contracting malaria vary significantly for civilian and military populations. The factors affecting the peak months of importation likely include rainfall, holiday transit, military flight availability, and referral center locations.

Infections associated with tumor necrosis factor-alpha antagonists.

Tumor necrosis factor (TNF)-alpha antagonists are promising therapeutic agents for patients with severe autoimmune and rheumatologic conditions. Unfortunately, their use has been associated with an increased rate of tuberculosis, endemic mycoses, and intracellular bacterial infections. Infliximab, 1 of 3 available drugs in this novel class, appears to be associated with the greatest risk of infection, likely because of its long half-life and induction of monocyte apoptosis. Prospective trials are necessary to determine the exact risk associated with these agents, particularly the newer TNF-alpha antagonists. More specific TNF-alpha blockers, which reduce inflammation while maintaining adequate immunity, are needed. In the meantime, a thorough work-up is mandatory for all febrile illness occurring in TNF-alpha blocker recipients. We present 4 patients who developed severe infections during TNF-alpha antagonist therapy, review the literature, and discuss current guidelines for surveillance and prophylaxis.

History of U.S. military contributions to the study of parasitic diseases.

U.S. military researchers have made major contributions to the discovery, diagnosis, treatment, and prevention of a number of parasitic diseases. We review the paramount U.S. military contributions to the understanding of leishmaniasis, filariasis, schistosomiasis, trypanosomiasis, gastrointestinal parasites, intestinal capillariasis, and angiostrongyliasis.

A case series and focused review of nocardiosis: clinical and microbiologic aspects.

Nocardia species are ubiquitous soil organisms that often infect patients with underlying immune compromise, pulmonary disease, or a history of surgery or trauma. We report 5 cases of nocardiosis representing various aspects of this "great imitator": 1) pneumonia in the setting of underlying malignancy, 2) chronic pneumonia with drug-resistant organism, 3) bacteremia and empyema with chronic hematologic malignancy, 4) primary cutaneous disease, and 5) sternal wound infection. We present a summary of the English literature from 1966 to 2003 with a focus on the teaching points of each of our 5 cases as well as the background epidemiology and microbiology of the Nocardia genus. Isolation of the organism may be achieved with routine media but longer incubation times may be necessary, delaying diagnosis and appropriate therapy. Treatment with a sulfa-containing regimen is standard of care, but resistance testing is warranted given emerging drug resistance, high rates of discontinuation due to adverse reactions, and the potential for nephrotoxicity in transplant recipients on cyclosporine.

Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies.

Coccidioidomycosis is a fungal disease with protean manifestations endemic to the Lower Sonoran Life Zone, which includes the hot deserts of the southwestern United States and areas of Mexico. Two hundred and twenty-three patients were found to have coccidioidomycosis at our institution from 1994-2002, the largest reported cohort of coccidioidomycosis patients since the 1950s. Of these patients, 58% presented with isolated pulmonary disease, 14% had high (>1:16) complement fixation titers without clear evidence of dissemination, 22% had definite disseminated disease, and 5% had unclassified disease. Enzyme immunoassay was a reliable diagnostic tool in those with symptomatic disease, but had a low specificity in those who were asymptomatic. Complement fixation titers of > or =1:16 were associated with dissemination to bone or skin but were not helpful in evaluating central nervous system disease. Thirteen percent of patients with high complement fixation titers (>1:16) without clear evidence of dissemination on presentation and 7% of those with isolated pulmonary disease eventually progressed to disseminated disease; 30% of Filipino patients with pulmonary disease progressed to disseminated disease. Nonwhite race was a predictor for dissemination; African American patients more often developed disseminated bony disease while Filipinos were more likely to develop cutaneous or central nervous system disease. Relapse of disseminated coccidioidomycosis occurred in 24% of patients; the risk was highest (71%) among those with central nervous system disease. Azole therapy was generally inferior to amphotericin B in disseminated disease. Predictors of permanent disability included African American or Filipino race, central nervous system disease, and bony disease.