We have tested the T helper cell (TH ) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV-control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above.The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.

Immunodeficiency with thymoma (Good syndrome, GS) is a rare, adult-onset condition that is characterized by thymoma, hypogammaglobulinemia, and low numbers of peripheral B cells. CD4+ T lymphopenia and an inverted CD4:CD8+ T-cell ratio may be present. Here we report 5 patients with GS and infectious complications who were seen at 3 institutions between 1983 and 1999. Three patients had recurrent sinopulmonary infections, 3 had severe cytomegalovirus (CMV) disease, and 1 had Pneumocystis carinii pneumonia. Review of the literature identified 46 other reports of infections in GS patients. The infections reported in all 51 patients included recurrent sinopulmonary infection (19 cases with documented respiratory pathogens), generally with encapsulated bacteria, most often Haemophilus influenzae (11 cases); CMV disease (5 cases); bacteremia (7 cases); oral or esophageal candidiasis (6 cases); persistent mucocutaneous candidiasis (5 cases); chronic diarrhea (5 cases with documented stool pathogens); urinary tract infections (4 cases); P. carinii pneumonia (3 cases); tuberculosis (2 cases); Kaposi sarcoma (1 case); disseminated varicella (1 case); candidemia (1 case); wound infection with Clostridium perfringens (1 case); Mycoplasma arthritis (1 case); and other infections. Patients with GS present with a spectrum of sinopulmonary infections and pathogens similar to common variable immunodeficiency (CVID). Compared with patients with CVID, opportunistic infections, including severe CMV disease, P. carinii pneumonia, and mucocutaneous candidiasis, appear to be more common in patients with GS, and patients with GS may have a worse prognosis. GS should be ruled out in patients with thymoma or CVID who develop severe, especially opportunistic, infections. Treatment with intravenous immune globulin is recommended for all patients with GS.

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.

Highlights Health-care workers (HCW) are part of the frontline in the struggle against the pandemic. Many HCWs have been infected with the SARS-CoV-2 and have lost their lives worldwide during the pandemic. We performed a survey among members of the ID-IRI and requested the number of HCW deaths and total HCWs infections. Data came from 37 countries and the median of the HCW deaths per 100,000 population of the country was 0.05. Thus, the health infrastructures of many countries are apparently struck by the pandemic. We call on the WHO Director-General to highlight this tragedy and the need to stop it by posting nation-by-nation data on the WHO COVID-19 website beginning in November 2020.

Two previously healthy, immunocompetent men had persistent Rochalimaea henselae bacteremia with clinical relapses after courses of antibiotics to which the isolates were ultimately demonstrated susceptible in vitro. Both had sustained tick bites prior to their illnesses, thus demonstrating an association not previously identified, although suspected. The first patient had relapsing fever, constitutional symptoms, and an episode of aseptic meningitis despite therapy with amoxicillin, then with doxycycline, and then with ceftriaxone. Thereafter, he spontaneously became asymptomatic during a span of 2 months of persistent bacteremia. Finally, after 2 weeks of therapy with ceftriaxone plus gentamicin, followed by 4 weeks of therapy with oral ciprofloxacin, his bacteremia was cured. The second man had relapsing fever and constitutional symptoms after courses of tetracycline, then of chloramphenicol, and then of doxycycline. He became permanently asymptomatic after serial 2-week courses of chloramphenicol and erythromycin. The greater efficacy of lysis-centrifugation blood cultures in the recovery of R. henselae was noted.

A rapid (time to completion, <4 h, including DNA extraction) and quantitative touch-down (QTD) real-time diagnostic Pneumocystis carinii PCR assay with an associated internal control was developed, using fluorescence resonance energy transfer (FRET) probes for detection. The touch-down procedure significantly increased the sensitivity of the assay compared to a non-touch-down procedure. Tenfold serial dilutions of a cloned target were used as standards for quantification. P. carinii DNA has been detected in respiratory specimens from patients with P. carinii pneumonia (PCP) and from patients without clinical evidence of PCP. The latter probably represents colonization or subclinical infection. It is logical to hypothesize that quantification might prove helpful in distinguishing between infected and colonized patients: the latter group would have lower copy numbers than PCP patients. A blinded retrospective study of 98 respiratory samples (49 lower respiratory tract specimens and 49 oral washes), from 51 patients with 24 episodes of PCP and 34 episodes of other respiratory disease, was conducted. PCR-positive samples from colonized patients contained a lower concentration of P. carinii DNA than samples from PCP patients: lower respiratory tract samples from PCP and non-PCP patients contained a median of 938 (range, 2.4 to 1,040,000) and 2.6 (range, 0.3 to 248) (P < 0.0004) copies per tube, respectively. Oral washes from PCP and non-PCP patients contained a median of 49 (range, 2.1 to 2,595) and 6.5 (range, 2.2 to 10) (P < 0.03) copies per tube, respectively. These data suggest that this QTD PCR assay can be used to determine if P. carinii is present in respiratory samples and to distinguish between colonization and infection.The opportunistic fungus Pneumocystis carinii f. sp. hominis is an important cause of morbidity and mortality, causing P. carinii pneumonia (PCP) in AIDS and other immunocompromised patients. The standard method for diagnosis of PCP is microscopic examination of stained (immunofluorescent or conventional tinctorial) invasive lower respiratory tract specimens: bronchoalveolar lavage (BAL), lung biopsy, or induced sputum specimens, the latter being the least sensitive, with reports of sensitivity varying from Ͻ50% to Ͼ90% (4-6, 9, 17, 18, 21, 23). Molecular detection systems have the potential to provide a higher degree of sensitivity than microscopic examination. PCR methods have been applied to lower respiratory tract specimens, and recently to non-invasive oral washes as well (1-5, 10, 12-14, 19-36, 38-42). However, some of these techniques are cumbersome, often requiring several steps in order to increase sensitivity and leaving them open to possible contamination.A single-round, nonnested, PCR assay, with no manipulations of amplicons required, would significantly reduce risks of contamination problems and be ideal for use in clinical diagnostic laboratories. A rapid PCR assay for detection of PCP, with a turnaround time comparable to smears, would enhance the clinical utility of molecula...

Human gnathostomiasis is most frequently caused by the nematode Gnathostoma spinigerum. This disease is endemic to Southeast Asia, particularly Thailand and Japan. The clinical presentation is most commonly characterized by localized, intermittent, migratory swellings of the skin and subcutaneous tissues, often in association with localized pain, pruritus, and erythema. Since this worm can migrate to deeper tissues, any organ system may become involved. Characteristically, patients with gnathostomiasis have a moderate to severe elevation of the peripheral eosinophil count, with values not uncommonly exceeding 50% of the total white blood cell count. With modern-day travel and immigration, cases of gnathostomiasis are being diagnosed with increased frequency in the United States. Because of its rarity in this country, however, gnathostomiasis often is not included in an initial differential diagnosis despite the characteristic triad of intermittent migratory swelling, a history of travel to Southeast Asia, and eosinophilia. We report a case of cutaneous gnathostomiasis diagnosed in the United States, and we present a clinical review of the English-language literature on human gnathostomiasis.