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Tuberculous meningitis (TBM) has considerable mortality and morbidity, and it often presents therapeutic challenges when complicated by paradoxical reactions (PRs). Here, the clinical course of four cases of TBM patients complicated by PRs in a longitudinal TB cohort is described while also providing insights from the larger clinical cohort. Research flow cytometry, biomarker analysis, and drug concentrations were performed on available samples. All participants were initiated on standard antituberculosis therapy (ATT) and enrolled at the onset of PRs (PR group) or 2-4 months after the start of ATT (controls). The four TBM participants highlighted here presented with fevers, headaches, neurological deficits, and fatigue at the initial presentation. Upon diagnosis, all were initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE) at standard doses and on corticosteroids. The median time to first PR was 37 days with recrudescence of initial TBM signs and symptoms at the time of PR. At the time of referral, all participants had low drug concentrations requiring dose optimization and regimen intensification as well as recrudescent flares upon corticosteroid taper, with one individual developing enlargement of tuberculoma 1 year following completion of ATT. Based on biomarkers and flow cytometry, PRs are characterized by elevated interferon-gamma and ferritin levels in the plasma compared to controls. In the TBM participants, T-cell activation with elevated levels of inflammatory biomarkers in the cerebrospinal fluid (CSF) was seen at the time of PR. These unique and highly detailed TBM cases provide insights into the pathogenesis of PRs, which may assist with future diagnostics and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gooding, Hammoud, Epling, Rocco, Laidlaw, Kuriakose, Chaturvedi, Galindo, Ma, Mystakelis, Poole, Russo, Shah, Malone, Rupert, Sereti and Manion.)

Objective: Academic plastic surgery positions have become highly competitive secondary to delayed retirement, stagnant hospital funding, and an increasing number of plastic surgery graduates. Little information is available to help residents navigate this challenging landscape. Our objectives were to evaluate the training backgrounds of all Canadian academic plastic surgeons and to develop recommendations for residents interested in an academic career. Methods: All Canadian academic plastic surgeons were included. Training histories were obtained from institutions' websites. Surgeons were subsequently emailed to confirm this information and complete missing details. Multivariate regressions were designed to analyze the effect of gender and FRCSC year on graduate and fellowship training and time to first academic position. Results: Training information was available for 196 surgeons (22% female), with a 56% email response rate; 91% of surgeons completed residency in Canada; 94% completed fellowship training, while 43% held graduate degrees; 74% were employed where they previously trained. Female gender significantly lengthened the time from graduation to first academic job, despite equal qualification. Younger surgeons were more likely to hold graduate degrees ( P < .01). Conclusions: We identified objective data that correlate with being hired at an academic centre, including training at the same institution, obtaining a graduate degree during residency, and pursuing fellowship training. In addition, we demonstrated that women take significantly longer to acquire academic positions ( P < .01), despite equal qualification. Trainees should consider these patterns when planning their careers. Future research should explore gender-based discrepancies in hiring practices., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Author(s).)

[This corrects the article DOI: 10.1371/journal.pmed.1002299.].

Background: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia., Methods and Findings: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia., Conclusions: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y., Trial Registration: ClinicalTrials.gov NCT01680406.

Background: Rapid diagnostic tests (RDTs) are now widely used for laboratory confirmation of suspected malaria cases to comply with the World Health Organization recommendation for universal testing before treatment. However, many malaria programmes lack quality control (QC) processes to assess RDT use under field conditions. Prior research showed the feasibility of using the dried tube specimen (DTS) method for preserving Plasmodium falciparum parasites for use as QC samples for RDTs. This study focused on the use of DTS for RDT QC and proficiency testing under field conditions., Methods: DTS were prepared using cultured P. falciparum at densities of 500 and 1,000 parasites/μL; 50 μL aliquots of these along with parasite negative human blood controls (0 parasites/μL) were air-dried in specimen tubes and reactivity verified after rehydration. The DTS were used in a field study in the Oromia Region of Ethiopia. Replicate DTS samples containing 0, 500 and 1,000 parasites/μL were stored at 4°C at a reference laboratory and at ambient temperatures at two nearby health facilities. At weeks 0, 4, 8, 12, 16, 20, and 24, the DTS were rehydrated and tested on RDTs stored under manufacturer-recommended temperatures at the RL and on RDTs stored under site-specific conditions at the two health facilities. Reactivity of DTS stored at 4°C at the reference laboratory on RDTs stored at the reference laboratory was considered the gold standard for assessing DTS stability. A proficiency-testing panel consisting of one negative and three positive samples, monitored with a checklist was administered at weeks 12 and 24., Results: At all the seven time points, DTS stored at both the reference laboratory and health facility were reactive on RDTs stored under the recommended temperature and under field conditions, and the DTS without malaria parasites were negative. At the reference laboratory and one health facility, a 500 parasites/μL DTS from the proficiency panel was falsely reported as negative at week 24 due to errors in interpreting faint test lines., Conclusions: The DTS method can be used under field conditions to supplement other RDT QC methods and health worker proficiency in Ethiopia and possibly other malaria-endemic countries.

Background: In the context of the massive scale up of malaria interventions, there is increasing recognition that the current capacity of routine malaria surveillance conducted in most African countries through integrated health management information systems is inadequate. The timeliness of reporting to higher levels of the health system through health management information systems is often too slow for rapid action on focal infectious diseases such as malaria. The purpose of this paper is to: 1) describe the implementation of a malaria sentinel surveillance system in Ethiopia to help fill this gap; 2) describe data use for epidemic detection and response as well as programmatic decision making; and 3) discuss lessons learned in the context of creating and running this system., Case Description: As part of a comprehensive strategy to monitor malaria trends in Oromia Regional State, Ethiopia, a system of ten malaria sentinel sites was established to collect data on key malaria morbidity and mortality indicators. To ensure the sentinel surveillance system provides timely, actionable data, the sentinel facilities send aggregate data weekly through short message service (SMS) to a central database server. Bland-Altman plots and Poisson regression models were used to investigate concordance of malaria indicator reports and malaria trends over time, respectively., Discussion: This paper describes three implementation challenges that impacted system performance in terms of: 1) ensuring a timely and accurate data reporting process; 2) capturing complete and accurate patient-level data; and 3) expanding the usefulness and generalizability of the system's data to monitor progress towards the national malaria control goals of reducing malaria deaths and eventual elimination of transmission., Conclusions: The use of SMS for reporting surveillance data was identified as a promising practice for accurately tracking malaria trends in Oromia. The rapid spread of this technology across Africa offers promising opportunities to collect and disseminate surveillance data in a timely way. High quality malaria surveillance in Ethiopia remains a resource intensive activity and extending the generalizability of sentinel surveillance findings to other contexts remains a major limitation of these strategies.

Assuming that budgetary constraints continue over the next several years, the U.S. military's overseas medical activities including medical civic action projects (MEDCAPs) and humanitarian assistance projects could comprise an increasing proportion of the contributions of U.S. government (USG) to improving global health. We have identified several issues with MEDCAPs in Ethiopia since 2009 that resulted in delays or project cancellations. These were mostly related to lack of a plan to develop sustainable capacities. Although there are many obvious medical needs for civilian populations in Ethiopia, the provision of sustainable development assistance involving these Ethiopian populations on behalf of the USG is a complex undertaking involving coordination with many partners and coordination with several other USG agencies. Military medical professionals planning MEDCAPs and other cooperative global health projects would benefit from consultation and close coordination with U.S. Centers for Disease Control and Prevention (CDC) and U.S. Agency of International Development (USAID) experts who are involved in supporting medium- and long-term health projects in Ethiopia. The establishment of durable military medical academic relationships and involvement of overseas military medical research units could also help promote sustainable projects and build robust professional relationships in global health., (Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.)

Background: In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used., Methods and Findings: In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml., Conclusions: In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections., Trial Registration: ClinicalTrials.gov NCT01052584.

The complexities of professional ethics are best understood and interpreted within their sociohistorical context. This paper focuses on the experience of 20 rural psychologists from across Canada, a context rife with demographic and practice characteristics that may instigate ethical issues. Employing hermeneutic phenomenology, these qualitative research results are indicative of professional struggles that impacted the participants' experience of professional ethics and raised key questions about policy and practise. Concerns regarding competition highlight potential professional vulnerability, beget the idea of fostering general psychological practice, and question the role of professional bodies in addressing rural shortages. Dependency on government funding models and decisions highlights the benefits and medical cost-offset effect of psychological services' role in funded medical care. The controversial prescriptive authority debate for psychologists raises myriad concerns that are particularly salient to rural practitioners. These include changes to training and practice, with risks of psychopharmacology gaining prominence over behavioural health interventions. National inconsistencies in level of registration add to the growing shortage of practitioners. Finally, the results illuminate the need for advocacy to move beyond the literature and into public policy to increase public awareness, decrease the stigma of mental illness, and develop rural Canadian psychology. Although limited to this study, these results allowed for a fuller and more robust understanding of rural practice in consideration of professional ethics, which may inform policy, science, or ethical clinical practice.

Context: This article provides a first person account of the experience of professional ethics for a psychologist who has worked in several Aboriginal communities in Alberta, Canada., Issues: These small rural communities tend to have few services and health services are typically provided by multidisciplinary health teams. Team members are predominantly community members, creating an embedded service environment that highlights the need for integrity in relationships. As the psychologist travelling to these communities I require sensitivity to cultural considerations, multiple party responsibilities, and community pressure on service delivery., Lessons Learned: In these settings, in consideration of the principle of respect for the dignity of persons, there is enhanced need for non-discrimination, particularly as most community members are vulnerable persons. Also, the context of small community clinics highlights issues of privacy and confidentiality. Responsible caring in these kinds of general practice also raise ongoing questions about competence and the need for daily risk-benefit analysis. Finally, responsibility to society is also an overarching consideration given the conditions of Canadian Aboriginal communities.

Background: In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004., Methods: Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively., Results: Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events., Conclusions: AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed., Trial Registration: NCT01052584.

This study was conducted to estimate the current prevalence of multiple sclerosis (MS) in Jefferson County, Missouri, USA, and to address community concerns about a perceived excess of MS around an active lead smelter. The study population consisted of the residents of Jefferson County, Missouri between 1998 and 2002. An aggressive MS case finding with capture-recapture analysis was used. The spatial clustering was examined using a spatial scan statistic. The capture-recapture analysis showed the case ascertainment to be 95%. The crude five-year period prevalence of MS in Jefferson County was 105 per 100,000 population (95% confidence interval [CI], 91-121), and 107 per 100,000 (95% CI, 95-119) when age-standardized to the 2000 U.S. population. No significant spatial clusters of MS cases were identified in the study area. The estimates of MS prevalence in Mid-western community of USA appeared to be comparable to estimates from other areas of similar latitude in the United States and Western Europe. The MS cases did not appear to cluster around the lead smelter.

Amyotrophic lateral sclerosis (ALS) cases diagnosed between 1998 and 2002 were identified to study ALS prevalence and spatial clustering in Jefferson County, Missouri, where an active lead smelter is located. The study used the El Escorial criteria for ALS diagnosis, the capture-recapture analysis for ALS case ascertainment, and the spatial scan statistic for cluster analysis. The estimated crude prevalence of ALS in Jefferson County was 3.9 per 100,000 population (95% CI, 1.7-7.7) at the time point on December 31, 2002. After age-adjustment to the 2002 U.S. population, the prevalence was 4.2 per 100,000 (95% CI, 1.9-6.6). This prevalence estimate was comparable to recent prevalence estimates from Western Europe. A small but significant cluster (p=0.04) was detected around the smelter area. An ALS registry utilizing outpatient, inpatient, and death certificate data is needed to provide comprehensive information for ALS case ascertainment. Etiologic studies are needed to assess whether living in proximity to a lead smelter is associated with the development of ALS.

Although current national response plans assume that most influenza-infected patients would stay home during a pandemic, surveillance systems might be overwhelmed and unable to monitor their health status. We explored the feasibility of using a nationwide telephone survey to monitor at-home patients. Of randomly selected adults surveyed during low influenza activity months (April-October 2006, surveillance weeks 17-41), 86% (7,268/8,449) agreed to answer questions about health status and influenza-like illness symptoms. Three percent (230/7,628) self-reported "flu." A subset (0.9%, 68/230) self-reported fever. In comparison, the Centers for Disease Control and Prevention's Sentinel Provider Network reported clinical influenza-like illness rates of 1.2%, 0.9%, and 1.2% for weeks 17, 20, and 41, respectively. The consistency between information obtained by telephone and surveillance data warrants further studies to determine whether telephone surveys can accurately monitor health status during seasonal influenza peaks and to augment current surveillance systems during a pandemic.

The Department of Defense (DoD) Global Emerging Infections Surveillance and Response System (DoD-GEIS) identifies and addresses DoD vulnerabilities to emerging infections through a global network of partners. Following the Indian Ocean tsunami of December 26, 2004, DoD-GEIS facilitated the DoD medical response and coordination with the Centers for Disease Control and Prevention and the World Health Organization. DoD-GEIS partners in Southeast Asia (U.S. Naval Medical Research Unit 2, Jakarta, Indonesia; and Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand) rapidly conducted health assessments and established surveillance for communicable diseases that threatened survivors. Preexisting collaboration with the Centers for Disease Control and Prevention, the World Health Organization, and host countries was critical for the DoD-GEIS tsunami response.

Since it was first reported in December 2003, the outbreak of avian influenza A/H5N1 has spread to at least nine countries in Asia, affected multiple species of animals, and caused at least 42 human deaths. The magnitude and extent of this zoonotic outbreak are unprecedented, continue to grow, and threaten the start of a global human influenza pandemic. Control of the H5N1 outbreak has required the implementation of integrated human and veterinary health surveillance and response efforts. These efforts have also necessitated an unprecedented level of bilateral and multilateral international communication and cooperation. This report describes the contribution of one public-health veterinarian to the H5N1 outbreak response effort in Laos, and emphasises the value of multidisciplinary approaches to addressing this and future emerging infectious disease outbreaks.

Background: Immunocompromised patients have an increased risk of experiencing progression of latent Mycobacterium tuberculosis infection (LTBI) to active tuberculosis (TB) disease. In January 2002, 2 patients with leukemia (Patients 1 and 2) developed pulmonary TB after recent exposure at 3 hospitals (Hospital A, Hospital B, and Hospital C) and at a residential facility for patients with cancer. Neither was known to have LTBI. Within 1 year, 3 other patients with malignancy and TB disease had been identified at these facilities, prompting an investigation of healthcare facility-associated transmission of M. tuberculosis., Methods: The authors performed genotypic analysis of the five available M. tuberculosis isolates from patients with malignancies at these facilities, reviewed medical records, interviewed individuals who had identical M. tuberculosis genotypic patterns, and performed tuberculin skin testing (TST) and case finding for possible exposed contacts., Results: Only Patients 1 and 2 had identical genotypic patterns. Neither patient had baseline TST results available. Patient 1 had clinical evidence of infectiousness 3 months before the diagnosis of TB was ascertained. Among employee contacts of Patient 1, TST conversions occurred in 1 of 59 (2%), 2 of 34 (6%), 2 of 32 (6%), and 0 of 8 who were tested at Hospitals A, B, and C and at the residential facility, respectively. Among the others who were exposed to Patient 1, 1 of 31 (3%), 1 of 30 (3%), 0 of 40 (0%), and 12 of 136 (9%) who were tested had positive TSTs at Hospitals A, B, and C and at the residential facility, respectively., Conclusions: Delayed TB diagnosis in 2 patients with leukemia resulted in the transmission of M. tuberculosis to 19 patients and staff at 3 hospitals and a residential facility. Baseline TB screening and earlier clinical recognition of active disease could reduce healthcare facility-associated transmission of M. tuberculosis among patients with malignancy.

A total of 853 isolates of Salmonella serotype Typhi recovered from patients with typhoid fever who were admitted to a major infectious disease hospital in Cairo, Egypt, from 1987 through 2000 underwent antibiotic susceptibility testing to determine multiple-drug resistance. The observed resurgence of chloramphenicol susceptibility (P=.002) may suggest reuse of this drug for the treatment of typhoid fever in Egypt.

Two dipstick assays for the detection of Brucella- and typhoid-specific immunoglobulin M, recently developed by the Royal Tropical Institute of The Netherlands, were evaluated by use of 85 plasma samples from Egyptian patients. Both dipsticks were simple and accurate rapid diagnostic assays, and they can be useful adjuncts for the diagnosis of typhoid fever and brucellosis.

Medical preparation of travelers to overseas locations is an important part of military medical care. We reviewed pre-travel records of patients attending the travel clinic at the National Naval Medical Center (NNMC) and used a post-travel questionnaire to determine the most frequent medical problems associated with international travel. Among 1,416 individuals who received pre-travel care at NNMC, there were 760 (54%) males and 656 (46%) females, the median patient age was 48 years, the most common reason for travel was pleasure, and the median duration of travel was 21 days. The most common destinations were Asia (27%), Africa (15%), Europe (13%), Central America/Caribbean (12%), and South America (11%). The median number of immunizations prescribed was three. Malaria chemoprophylaxis was prescribed to 45%. The average cost of vaccines and medications to medically prepare a traveler was $67. Among 271 (82%) who returned the post-travel questionnaire, the most common illnesses reported were diarrhea (23%) and upper respiratory infections (19%); medical treatment was sought by 9%. Properly informed, military physicians can provide a valuable service at a reasonable cost to reduce the risk of travel-acquired medical problems and illnesses.

Eighteen asymptomatic HIV-1-infected (HIV+) individuals were evaluated neuropsychologically before and during Interferon Alfa-n3 treatment. All 18 were evaluated twice, and 9 were evaluated three times. Analyses revealed few significant effects of treatment on cognitive, motor, and affective function. Improvements occurred over visits on measures of attention and appeared to reflect practice effects. Decrements occurred over visits on measures of procedural and supraspan learning. Examination of the data suggested that decrements were due to procedural artifacts and were not medication effects. In contrast to prior studies reporting significant neuropsychiatric side effects of interferon alpha treatment, few such effects occurred when HIV+ individuals were treated with Interferon Alfa-n3 and were evaluated neuropsychologically in a systematic manner.

The safety and tolerance of interferon alfa-n3 (IFN-alpha n3) was tested in 20 adults with asymptomatic human immunodeficiency virus type 1 (HIV-1) infection (> 400 CD4 lymphocytes/mm3). IFN-alpha n3 was self-injected three times per week for 3-6 months: 5 patients received 1 mega-IU (MIU)/dose, 10 received 5 MIU/dose, and 5 escalated to their maximum tolerated dose. Subjects were evaluated every 2-4 weeks through 2 months after cessation of treatment. Neuropsychological tests were given at 3-month intervals. Markers of IFN activity, anti-IFN neutralizing antibodies, and antiviral response were measured monthly. IFN-alpha n3 was safe and well tolerated: influenza-like symptoms were uncommon, laboratory toxicity was minimal, no adverse neurobehavioral side effects were evident, and no patient developed neutralizing antibodies against IFN. IFN-alpha n3 induced IFN-specific biologic responses and dose-related antiviral activity against HIV-1. Subjects showed stabilization of CD4 cells for > 20 months. IFN-alpha n3 should be studied in combination with other antiretroviral agents and in persons with more advanced HIV-1 infection.

Objective: To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV)., Patients and Methods: Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program., Results: Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis. Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy. Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses. The mean CD4+ T-lymphocyte count was not predictive of relapse. Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients [57%]) or the rash of secondary syphilis (4 of 14 patients [29%]) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years., Conclusion: Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

Between November 1991 and June 1993, approximately 11,000 Haitian migrants were screened for active tuberculosis and human immunodeficiency virus type 1 (HIV-1) infection at the U.S. Naval Base in Guantánamo Bay, Cuba. Cultures of specimens from 37 of these patients yielded Mycobacterium tuberculosis; eight (22%) of these isolates were resistant to standard medications, including isoniazid (22%), rifampin (0), ethambutol (3%), and streptomycin (3%). Two isolates (5.4%) were resistant to two drugs simultaneously. All but one of 340 patients who were treated for presumptive active tuberculosis and who were followed up for about 1 month had a favorable initial clinical response to a standard four-drug regimen. Among 259 HIV-1-infected patients who had normal findings on screening chest radiographs and who received prophylaxis with isoniazid, there were 1.8 incident cases of active tuberculosis per 100 person-years; this rate was 76% lower than that (reported by others) among HIV-1-infected Haitian patients who were not treated with isoniazid. No serious toxic effects due to standard four-drug regimens or to prophylaxis with isoniazid were observed. These data suggest that standard empirical therapeutic interventions for tuberculosis are adequate and well tolerated in Haitian migrants.

Measles in HIV-infected patients can be a severe, even fatal, illness. The prevalence of measles seropositivity in HIV-infected adults and the durability of these antibody levels are uncertain. A prospective survey of 210 HIV-infected adults found that 95% of the adults had demonstrable antibodies using a standard ELISA technique. Seropositivity was no different in patients with CD4 counts over 400, from those with more advanced disease and CD4 counts under 200 (p = 0.8). Six seronegative patients were vaccinated and had serial antibody determinations: two of six (33%) patients had a durable positive antibody response at 1 year, and none had any observed toxicity. Vaccination of the identified measles-seronegative HIV-infected adults who are at high risk for measles is recommended, but a measurable antibody response may be expected in only a minority of cases.

Destructive bone disease is a well-recognized complication of congenital and tertiary syphilis. Clinically significant osteitis and osteomyelitis are rare complications of primary or secondary syphilis in patients who are not infected with human immunodeficiency virus (HIV). We report a case of an HIV-infected man who presented with symptomatic, left ulnar osteitis as the initial manifestation of secondary syphilis. The patient's clinical course was complicated by a pathological fracture, but he responded to high-dose intravenous penicillin G therapy and surgical intervention. Results of physical examination on follow-up at 15 months were normal, and a serofast (rapid plasma reagin [RPR]) titer of 1:4 and a markedly decreased uptake on bone scintigraphy were observed. Our case report suggests that bone disease can represent an atypical manifestation of early acquired syphilis and that HIV-positive patients who present with orthopedic complaints or bone lesions should be evaluated for the presence of syphilitic bone disease.

Varicella is an infrequent but potentially severe infection in adult HIV-infected patients. We reviewed five cases of varicella in HIV-seropositive men; two were complicated by severe headache and meningismus, and one of these patients also had hepatitis and thrombocytopenia. All five patients responded well to acyclovir therapy, but one patient had dermatomal zoster 2 years later, and another failed to have detectable antibody after infection. We also performed a serosurvey on 181 consecutive HIV-infected patients presenting themselves for evaluation. A total of 95% of these patients had demonstrable antibody to varicella-zoster virus. Immune status to varicella did not correlate with the declining CD4 count, which was well preserved even in patients with fewer than 200 CD4 cells/mm3.

The prevalence of hepatitis A, B, C, and D viruses was studied in 467 military personnel with human immunodeficiency virus type 1 (HIV-1) infection. Antibody to hepatitis C virus (anti-HCV) by first-generation ELISA was found in 136 (29%). Of sera repeatedly reactive for anti-HCV by first-generation ELISA, two-antigen recombinant immunoblot assay (RIBA) was positive in 41 (32%) and four-antigen RIBA was positive in 55 (41%). Four-antigen RIBA was positive in 33 (30%) of the 109 with an OD on ELISA of < or = 2.0 compared with 22 (81%) of the 27 with an OD > 2.0 (P < .001). Anti-HCV detected by four-antigen RIBA was associated with increasing age, black or Hispanic race, and antibody to hepatitis B core antigen. When patients with hepatitis B surface antigen were excluded, elevated alanine aminotransferase was found in 5 (8%) of 63 with a negative RIBA and 13 (28%) of 47 with a positive RIBA (P = .006). While RIBA was negative in more than half of those with anti-HCV by ELISA, 55 (12%) of these HIV-1 infected personnel had anti-HCV detected by RIBA, which was associated with a strong reaction by ELISA, elevated liver enzymes, coinfection with hepatitis B, minority race, and older age.

Corticosteroids have proven effective as adjunctive therapy for the treatment of PCP in patients with AIDS, when begun within 72 h of conventional anti-Pneumocystis therapy. Their efficacy as rescue (or salvage) therapy in patients who have failed conventional therapy, however, remains unproven. Ths report presents our experience with 16 patients admitted to our MICU for acute respiratory failure (PaO2/FIO2 ratio less than or equal to 150) due to PCP. Five of six patients (83 percent) who received "primary" CS rescue (initial CS use prompted by acute respiratory failure after 72 h of conventional anti-Pneumocystis therapy) survived hospitalization. Our experience suggests that CSs may be effective even when started after 72 h of conventional therapy. Additional studies are needed to clarify the role of CS rescue therapy.

The study objective was to determine the causes and magnitude of absolute CD4 (T4) count variation in human immunodeficiency virus type 1 (HIV-1)-infected (+) adult males. We conducted a prospective, blinded, and controlled study of 22 adult military male outpatients, including 16 HIV(+) [12 in Walter Reed stage (WR-) 1 through 5, 4 in WR-6 (AIDS)], and 6 HIV seronegative (-) healthy controls. Ten CD4+ cell counts were drawn within a 3-day interval from each patient at the following times: 0800, 1200, 1600, and 2200 h on day 1; and 0800, 1200, and 1600 h on days 2 and 3. A significant CD4+ cell count diurnal increase of 59 cells/mm3 was detected between 0800 h and 2200 h from the WR-1-5 patients (p = 0.018), although this diurnal change was significantly blunted (p = 0.028) as compared with the 506 cells/mm3 CD4+ cell count diurnal increase observed from the HIV(-) healthy controls. The coefficients of variation [CV = (standard deviation/average) x 100] of the three daily 0800 h CD4 cell counts from each patient were 15 (median) and 19 (average) for the WR-1-5 patient group. Blood leukocyte counts, differential fractions of lymphocytes, and total lymphocyte counts contributed more to the observed CD4+ cell count variability than did the CD4% measurements [CV = 7.5 (median), 11 (average)] obtained from flow cytometry. We conclude that the large fluctuations that we observed in repeated CD4+ cell counts in HIV(+) patients can be explained in part by CD4+ cell count diurnal cycle and in part by high variability in total lymphocyte counts.(ABSTRACT TRUNCATED AT 250 WORDS)