Pathogens In HIV-infected Patients Research Articles

CLINICAL AND TYPICAL IMAGING CHARACTERISTICS OF CRYPTOCOCCAL MENINGITIS IN HIV INFECTED PATIENT: A CASE REPORT

Although Cryptococcal infection is worldwide distribution, it is more seen in the immunocompromised patients. Cryptococcus neoformans is the most common central neurvous system fungal pathogen in HIV infected patients. Besides clinical features and laboratory tests, imaging findings play an important role in the evaluation of cryptococcal infection. In this paper we present an immunocompromised HIV infected case of C. neoformans meningitis with clinical features and imaging characteristics by MR image.

Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients.

Although considerable interest in metagenomic next-generation sequencing (mNGS) has been attracted in recent years, limited data are available regarding the performance of mNGS in HIV-associated central nervous system (CNS) infection. Here, we conducted a retrospectively analyzing of the cerebrospinal fluid (CSF) mNGS reports and other clinical data from 80 HIV-infected patients admitted to the Second Hospital of Nanjing, China from March, 2018 to March, 2022. In our study, CSF mNGS reported negative result, mono-infection, and mixed infection in 8.8, 36.2, and 55% of the patients, respectively. Epstein-Barr virus (EBV), positive in 52.5% of samples, was the most commonly reported pathogen, followed by cytomegalovirus (CMV), John Cunningham virus (JCV), torque teno virus (TTV), cryptococcus neoformans (CN), toxoplasma Gondii (TE), and mycobacterium tuberculosis (MTB). 76.2% of the EBV identification and 54.2% of the CMV identification were not considered clinically important, and relative less sequence reads were reported in the clinical unimportant identifications. The clinical importance of the presence of TTV in CSF was not clear. Detection of JCV, CN, or TE was 100% suggestive of specific CNS infection, however, 60% of the MTB reports were considered contamination. Moreover, of the 44 (55%) mixed infections reported by mNGS, only 4 (5%) were considered clinical important, and mNGS failed to identify one mixed infection. Additionally, except for MTB, CSF mNGS tended to have high sensitivity to identify the above-mentioned pathogens (almost with 100% sensitivity). Even all the diagnostic strategies were evaluated, the cause of neurological symptoms remained undetermined in 6 (7.5%) patients. Overall, our results suggest that mNGS is a very sensitive tool for detecting common opportunistic CNS pathogen in HIV-infected patients, although its performance in CNS tuberculosis is unsatisfactory. EBV and CMV are commonly detected by CSF mNGS, however, the threshold of a clinical important detection remains to be defined.

Diagnostic determination of Norovirus infection as one of the major causes of infectious diarrhea in HIV patients using a multiplex polymerase chain reaction assay.

Although infectious diarrhea is one of the most common complications in human immunodeficiency virus (HIV)-infected patients, robust diagnostic methods for determining potential pathogens are still limited in the clinic. Norovirus, a type of calicivirus, has been shown to be the most common cause of gastroenteritis. Here, we used multiplex polymerase chain reaction as a diagnostic tool to verify Norovirus as the diarrhea-related pathogen in HIV-infected patients with unknown etiological information. Stool specimens obtained from 81 HIV-infected patients with diarrhea were analyzed by BioFire FilmArray Gastrointestinal (GI) panel. Among 26 HIV-infected patients with unknown etiological information, we detected Norovirus in 14 stool specimens of these patients with 100% sensitivity and specificity as confirmed by reverse transcription polymerase chain reaction (RT-PCR), and one specimen showed both Norovirus and enterotoxigenic Escherichia coli infection. Among the remaining 55 patients with verified Clostridium difficile infection, nine patients also detected positive for Norovirus infection. In conclusion, using FilmArray GI panel and RT-PCR, we determined that Norovirus infection as one of the main pathogens responsible for diarrhea in HIV patients.

Treating HIV-Positive/Non-AIDS Patients for Community-Acquired Pneumonia with ART.

This article reviews the most recent publications on community-acquired pneumonia (CAP) in the HIV-infected population on antiretroviral therapy (ART), focusing on epidemiology, prognostic factors, etiology, and antimicrobial therapy. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles. CAP remains a major cause of morbidity and mortality among HIV-infected patients and incurs high health costs despite the introduction of ART. HIV-infected patients are generally known to be more susceptible to bacterial pneumonia. Streptococcus pneumoniae is the most frequently reported pathogen in HIV-infected patients on ART, who present a higher rate of bacteremia than non-HIV-infected patients. Several studies have also examined microbial etiology and prognostic factors of CAP in HIV-infected patients on ART. Despite the high rate of bacterial pneumonia in these patients, mortality rates are not higher than in patients without HIV infection.

Influence of highly-active antiretroviral therapy on the subgingival biofilm in HIV-infected patients.

Highly-active antiretroviral therapy (HAART) has been associated with alterations in subgingival biofilm and periodontal disease. The purpose of the present study was to investigate the association between different HAART regimens and the prevalence of periodontal pathogens in HIV-infected patients with chronic periodontitis. Subgingival periodontal pathogens were determined by a DNA chip microarray in a case series in 14 HIV-infected patients receiving HAART with different drug combinations: protease inhibitor (PI)-based HAART versus non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. A statistical analysis was conducted to determine whether specific HAART regimens were associated with 10 periodontal pathogens using odds ratios (OR). At baseline and after treatment, the patients did not show significant clinical and immunological differences. In general, the highest OR for the prevalence of periodontal pathogens were found in the PI HAART group for Actinomyces viscosus (A.viscosus) (OR: 303), Campylobacter rectus (OR: 90), and Treponema denticola (OR: 25). In the NNRTI HAART group, higher OR were documented for Fusobacterium nucleatum (OR: 56) and Eikenella corrodens (OR: 25). The association between A.viscosus and PI HAART was statistically significant (P=0.03). The results demonstrated statistical associations between subgingival bacteria and antiretroviral drug therapies. Further investigation on the clinical significance and underlying mechanisms are needed to support these findings.

Sero–Prevalence, and Associated Risk Factors of Toxoplasma gondii Infection in Pregnant Women and HIV/AIDS Patients in Selected Cities of Ethiopia

Toxoplasma gondii infection is main cause of abortion, congenital defects and fatality in pregnant women and HIV/AIDS infected individuals respectively. The seroprevalence and risk factor assessment of toxoplasmosis in pregnant women and HIV/AIDS infected individuals in Addis Ababa, Jinka, Mojo and Awash towns of Ethiopia was conducted in this study. The study also assessed knowledge and perception of health professionals including physician, nurses and gynecologist, working in antenatal care in selected health institution of different parts of Ethiopia. A cross–sectional study was conducted from October 2011 to March 2012. Sera of 293 pregnant women and 190 in HIV/AIDS infected individuals were analyzed by serological method called Indirect Enzyme Linked ImmunoSorbent Assay [ELISA]. The total seropostivity of IgG and IgM T. gondii were 89.9% and 28.3% respectively. From 293 pregnant women of study 9.5% were IgG negative and IgM positive and 25.5% were both IgG and IgM positive, which means 28.6% of pregnant women had detectable IgM antibodies during pregnancy. Univariate logistic regression analysis showed that study areas, age, residential places, educational status, HIV/AIDS status, ART utilization, pregnancy status, number of pregnancy, stage of pregnancy, history of abortion and number of abortion, cat at home, contact with cat, separate cat house, raw milk and vegetables consumption were significantly associated with seropositivity of T. gondii. From health professionals, 63% know health risk of domestic animals like cat with regards to toxoplasmosis. Consumption of raw or undercooked meat and vegetables (71.2%) were recognized as common source of T. gondii infection by health professionals consumption of raw milk (18.4%), contact with cat faces (14.3%), and drinking unboiled water (6.1%) were also mentioned as important modes of transmission. In this study, 52.7% of health professionals thought toxoplasmosis as important pathogen in HIV infected patients and pregnant women. Seropositivity of T. gondii infection in HIV/AIDS infected individuals and pregnant women in Addis Ababa, Jinka, Mojo and Awash towns of Ethiopia is high. Abortion, exposure to cat faces and HIV/AIDS status are main determining risk factors to acquire T. gondii infection in study population. There is also urgent need of incorporating zoonotic diseases concept in medical education and training. These findings are helpful for optimal design of strategies in contribution of health professionals in relation to toxoplasmosis, pregnant women and immunocompromised individuals. Furthermore, health Education, screening pregnant women during their antenatal care and in depth epidemiological studies are recommended.

Low prevalence of hepatitis C infection among HIV-infected individuals in Slovenia: a nationwide study, 1985–2013

After introduction of highly active antiretroviral therapy and consecutive successful control of HIV infection hepatitis C virus (HCV) has become an important pathogen in HIV infected patients. HIV infection in a person who is also HCV infected results in reduced rate of spontaneous HCV RNA clearance, faster liver disease progression and more aggressive course of liver disease. A total of 639 individuals were cumulatively reported as HIV-infected in Slovenia until the end of 2013. The majority of HIV-infected were men (553/639; 86.5%) and among them 68.2% were men who have sex with men. The predominant HIV-1 subtype in Slovenia is subtype B, which is present in 85.8% of the infected individuals. We tested 575 (90.0%) of 639 Slovenian individuals who were confirmed as HIV positive by the end of 2013 for HCV infection. All individuals included in a study were tested for both anti-HCV and HCV RNA. Out of 575 HIV-infected individuals 44 (7.6%) had anti-HCV specific antibodies, and 32 of them (72.7%) were also HCV RNA positive. We didn’t detect HCV RNA alone in any of the 531 anti-HCV-negative individuals. Anti-HCV positivity was significantly more frequent in HIV-infected individuals who acquired HIV by parenteral route (73.3%) comparing with those who acquired HIV by sexual route (2.6%). The most prevalent HCV genotype among HIV-infected individuals was genotype 1 (70.8%), followed by genotype 3 (16.7%), genotype 4 (8.3%) and genotype 2 (4.2%). HCV genotypes distribution didn’t significantly differ between HIV-positive and HIV-negative, HCV-positive Slovenian patients. Our study which was performed on the highest proportion per entire population of HIV-infected individuals from a certain country identified Slovenia as the country with the lowest prevalence of HCV infection among HIV-infected individuals. The predominance of sexual transmission of HIV (79.2%) in Slovenia and the fact that HIV has not yet entered the intravenous drug users’ community in Slovenia are the two most likely reasons for low prevalence of HIV-HCV co-infection. However, the present epidemiological situation in Slovenia needs to be monitored closely since it could quickly change in a case of an increase in the incidence of acute hepatitis C among HIV-infected men who have sex with men and/or increase of HIV infection among intravenous drug users in the country, as it happened recently in some neighboring countries.

Intestinal parasitic and candida infection associated with HIV infection in Cameroon

HIV causes progressive impairment of the cellular immune system leading to increased susceptibility to infectious agents. Parasitic infestations are common in HIV-infected patients and usually lead to diarrhoea. Few studies have addressed the issue of intestinal parasites among HIV-infected persons in Cameroon. This investigation was conducted in Douala, Cameroon, to assess the prevalence of gastrointestinal parasites in HIV-infected patients, taking into account their immune status and treatment course. Stool and blood samples were collected from 201 HIV-positive patients for the investigation of intestinal pathogens and CD4+ counts. Fifty-six (27.9%) patients harbored pathogens. The most frequent pathogens were Candida spp. (14.9%), Cryptosporidium spp. (7.5%), Entamoeba histolytica, and Entamoeba dispar (3%). The presence of pathogens was significantly associated with diarrhoea, as they were found in 48.6% of diarrhoeic stools and 23.2% of non-diarrhoeic stools (OR = 3.14, p= 0.0018). Prevalence of pathogens and diarrhoea were significantly higher in patients with CD4+ counts ≤ 200 cells/µL (OR = 2.17, p = 0.0349 and OR = 8.46, p = 0.000019 respectively). This study highlights the need for investigating intestinal pathogens in HIV-infected patients presenting with diarrhoea, especially when their CD4+ counts are low.

Maraviroc Induced CCR5 Blockage for HIV Infected Individuals is Associated with Increased Rates of Respiratory Tract Infections

Background: Maraviroc is an allosteric, non-competitive blocker of CCR5, interfering with its ability to bind to the HIV GP120 and thus preventing HIV cell entry. CCR5 is involved in recruiting immune cells to sites of viral invasion in the respiratory tract. This postulated role of CCR5 led us to perform a meta-analysis of the largest clinical drug trials that evaluated CCR5 antagonists, as part of antiretroviral regimens, with focus on the occurrence of respiratory infections in general and viral infections in particular in CCR5 antagonist recipients. Data source and eligibility criteria: Clinical trials involving administration of Maraviroc to HIV infected individuals were reviewed with emphasis on reported respiratory infections. We included in the analysis those studies enrolling more than 100 participants in the maraviroc treatment arm. Results: We compared individuals treated with optimized background regimen plus placebo to those receiving the background regimen along with the CCR5 anatagonist maraviroc. We found in the clinical data significantly more respiratory infections in the CCR5 blocker treated arm than in the control arm. Limitations: The studies had limited microbiological analysis of respiratory infections and the categorization differs between the studies included. Conclusions: This observation suggests that the CCR5 blockade may lead to more infections caused by other viruses and respiratory pathogens in HIV infected patients and the incidence of such infections needs to be carefully assessed.

HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection

To examine whether the HIV-1 Tat protein impairs the lipopolysaccharide (LPS)-induced cytokine responses. Concurrent infections with pathogens including bacteria and viruses are common in AIDS patients. However, cytokine and interferon responses during infection with or translocation from the gut of these pathogens in HIV-infected patients are not well studied. As HIV-1 Tat contributes partly to the HIV-induced immune dysregulation, we investigated whether the protein may play a role in perturbing the LPS-induced cytokine responses. Expression levels of cytokines in human primary blood monocytes/macrophages were determined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Expression level of the cell surface Toll-like receptor 4 was examined by flow cytometry. Activations of signaling molecules were assayed by western blot and immunofluorescence. We demonstrated that HIV-1 Tat downregulated the LPS-induction of IFN-beta and concomitantly upregulated IL-6 expression in primary blood monocytes/macrophages, whereas the viral protein had no significant effects on TNF-alpha expression. To delineate the underlying mechanism, we showed that Tat inhibited the LPS-activation of ERK1/2 but not the p38 mitogen-activated protein kinases. The viral protein suppressed the LPS-induced activation of NFkappaB p65 via its induction of IkappaBalpha expression, which resulted in retention of NFkappaB p65 in the cytosol. These findings suggest that Tat may play a role in modulating the immune responses triggered by other coinfecting pathogens and thus providing a permissive environment for both HIV and other opportunistic microbes.

Oral infectious diseases: a potential risk factor for HIV virus recrudescence?

As the highly active antiretroviral therapy (HAART) has transitioned human immunodeficiency virus (HIV) infection into a 'chronic disease' management strategy, there is growing evidence that infection with non-HIV pathogens in HIV+ patients may have important public health implications in undermining HAART success and acquired immunodeficiency syndrome progression. Several bacterial and host cell products during infections with non-HIV pathogens have shown the capacity to regulate HIV replication in latently infected cells. A high prevalence of oral infections caused by bacteria, viruses and fungi has been described in HIV+ patients, including periodontal disease. The oral cavity appears to be a site of HIV pathogenesis and potential reservoir for the disease as HIV RNA and DNA forms are present in saliva as well as in gingival crevicular fluid, and oral epithelial cells are susceptible to either cell free or cell-associated HIV infection. The clinical and biological bases of potential associations between chronic oral inflammatory disorders, such as periodontal disease, and exacerbation of HIV viraemia have received little attention. This review attempts to evaluate the current understanding of HIV reactivation as a result of co-infection and/or inflammation induced by non-HIV pathogens in HIV-infected patients, and presents a hypothetic model about the potential role of periodontitis as a global oral infection that potentially contributes to HIV recrudescence.

Urinary Infections due to Multi-Drug-Resistant Escherichia coli among Persons with HIV Disease at a Tertiary AIDS Care Centre in South India

Background: While the spectrum of opportunistic infections due to HIV infection has been widely discussed, there are very limited data available in south India on certain incident infections especially urinary tract infections (UTI) in HIV-infected subjects. Methods: Bacterial aetiology of 350 symptomatic UTI in HIV-infected subjects and the drug resistance pattern of the Escherichia coli isolates tested between June 2005 and July 2007 at the YRG Centre for AIDS Research and Education, a tertiary HIV Referral Centre in Chennai has been described here. Results:E. coli was the most common etiological agent of UTI in HIV patients, followed by Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus spp. and Staphylococcus epidermidis. Twenty-nine E. coli isolates were multi-drug-resistant and 83.3% of the isolates were resistant to sulfamethoxazole-trimethoprim. Conclusions: Urinary pathogens in HIV-infected patients demonstrate high antimicrobial resistance and with majority of therapy for UTIs being empiric, constant updates of the aetiological agents and their drug susceptibility pattern would largely be beneficial to clinicians in choosing the right drug.

Mycobacterium ulcerans infection as a cause of chronic diarrhea in an AIDS patient: A case report

Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS). Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients. Among the NTM, Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients. However, NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet. We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.

Novel Therapies for Cytomegalovirus Disease

Cytomegalovirus (CMV) infection is one of the most important infectious complications of solid-organ transplantation, a serious, life-threatining, opportunistic pathogen in HIV-infected patients, and may cause hearing defects and irreversible central nervous system disease in infants infected during gestation. Four drugs are currently licensed for prophylaxis, pre-emptive therapy, and treatment of CMV infection -- ganciclovir, and its oral prodrug valganciclovir, foscarnet, cidofovir, and fomivirsen. All four drugs are effective against CMV infection. Toxicities, drug-drug interactions, poor bioaailibility, and the development of drug resistance, however, are clinically relevant and common limitations of these drugs. Novel compounds are on the horizon that possibly will become useful alternatives to currently licensed drugs. Maribavir, a benzimidazol, is the most promising novel drug and closest to clinical application. Several phase II clinical trials proved its good tolerability and effectivity. Other compounds are currently evaluated in pre-clinical and phase I trials with promising preliminary data. In addition, analogs of cidofovir posess significantly improved pharmacological and virological characteristics allowing their oral administration. This review summarizes the current status in drug development and will introduce the most recent patents on this line of research.

Cell surface markers of regulatory T cells are not associated with increased forkhead box p3 expression in blood CD4+ T cells from HIV‐infected patients responding to antiretroviral therapy

Regulatory T (Treg) cells may attenuate host immune responses to pathogens, including HIV and opportunistic pathogens in HIV-infected patients. Treated and untreated progressive HIV disease represent a range of immunological scenarios with potentially different roles for Treg cells. A cell surface marker to determine Treg cell numbers would assist in identifying situations where Treg cells are important. Here we show that levels of Foxp3 mRNA are increased in CD4+ T cells from HIV-infected patients responding to antiretroviral therapy. However, the proportion of peripheral blood CD4+ and CD8+ T cells expressing CD25, neuropilin-1, glucocorticoid-induced TNF receptor and lymphocyte activation gene-3 did not differ as a result of treated or untreated HIV infection when compared with HIV-seronegative controls. Hence, none of the putative Treg cell surface markers identified T-cell populations in peripheral blood that mirrored the effects of HIV infection and antiretroviral therapy on Foxp3 expression.

Pathogen‐Specific Induction of CD154 Is Impaired in CD4+T Cells from Human Immunodeficiency Virus–Infected Patients

The pathogenesis of immunodeficiency associated with human immunodeficiency virus (HIV) infection remains incompletely understood. CD154, a molecule that is expressed primarily on activated CD4(+) T cells, is pivotal for regulation of cell-mediated and humoral immunity and is crucial for control of many opportunistic infections. We investigated whether CD4(+) T cells from HIV-infected patients exhibit defective induction of CD154 in response to opportunistic pathogens. Incubation of purified human CD4(+) T cells with monocytes plus antigenic preparations of either Candida albicans, cytomegalovirus, or Toxoplasma gondii resulted in induction of CD154. Expression of CD154 in response to these pathogens was impaired in CD4(+) T cells from HIV-infected patients. This defect correlated with decreased production of interleukin (IL)-12 and interferon (IFN)-gamma in response to T. gondii. Recombinant CD154 partially restored secretion of IL-12 and IFN-gamma in response to T. gondii in cells from HIV-infected patients. Together, defective induction of CD154 is likely to contribute to impaired cell-mediated immunity against opportunistic pathogens in HIV-infected patients.

Bacteremic pneumococcal infections in immunocompromised patients without AIDS: the impact of β-lactam resistance on mortality

Background: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in the elderly, and in recent years it has arisen as an important pathogen in HIV-infected patients. However, there is a scarcity of information on clinical and therapeutic problems associated with pneumococcal infections in other immuno-compromised patients. The objective of this study was to assess the most relevant epidemiologic aspects, clinical features and prognostic factors of pneumococcal bacteremia in immunocompromised hosts without AIDS. Methods: This was a retrospective analysis of patients with pneumococcemia, carried out in a 600-bed, university-affiliated hospital in Madrid, Spain. Two-hundred and sixty patients were evaluated retrospectively; 69 (26.5%) immunocompromised patients based on strict case definitions were compared with a group composed of 191 non-immunocompromised hosts with a variety of chronic conditions. Conventional management of pneumococcal bacteremia according to clinical standards was assessed. The MICs of penicillin and other β-lactam antibiotics, and related mortality and hospital mortality at 30 days, were measured. Results: A comparison of clinical manifestations of pneumococcemia between immunocompromised patients and non-immunocompromised patients did not show differences in the presence of fever, obtundation, type of lung involvement, frequency of primary bacteremia, or meningitis. Hospital-acquired pneumococcemia was significantly more frequent in immunocompromised patients (34.7% versus 6.8%, P<0.0001), and resistance to penicillin was also more common in pneumococcal strains isolated from these patients (37.5% versus 20%, P=0.0009). Septic shock occurred more frequently in immunocompromised patients, although the overall and related mortality were not significantly different from those found in non-immunocompromised patients (33.3% versus 22.5%, P=0.07, and 28.9% versus 20.9%, P=0.7 respectively). In the multivariate analysis, multilobar pneumonia (odds ratio (OR) 15.7; 95% CI 6.00–41.30; P < 0.001), inadequate treatment (OR 12.20; 95% CI 4.10–37.20; P < 0.001), obtundation (OR 5.80; 95% CI 2.20–15.00; P<0.001) and hospital-acquired bacteremia (OR 4.80; 95% CI 1.00–14.60; P<0.006) were associated with an increased risk of mortality in patients with pneumococcemia. Only multilobar pneumonia (OR 7.90; 95% CI 4.10–15.35; P<0.001) was significantly associated with an increased risk of mortality in immuno-compromised patients. Patients with acute leukemia and lymphoma had a greater mortality rate than non-immunocompromised patients (53.8% related mortality, P=0.05). Analysis of these patients showed frequent inadequate empirical therapy with ceftazidime plus amikacin in the presence of β-lactam resistance. Conclusions: Much of the burden of pneumococcal bacteremia was attributable to immunosuppressive diseases. In immunocompromised patients, pneumococcemia was frequently acquired within the hospital during the treatment of the underlying condition, and resistance to penicillin was common. Patients with acute leukemia and lymphoma who develop fever and pneumonia should be treated with drugs active against β-lactam-resistant pneumococci, irrespective of the setting in which the infection develops.

Diarrheal disease in patients infected with human immunodeficiency virus in Bangkok, Thailand.

Diarrheal disease and its associated morbidities occur frequently in patients infected with human immunodeficiency virus (HIV) and may be associated with a decreased quality of life. We studied the spectrum of symptoms, measures of nutritional status, and the enteric pathogens associated with diarrheal disease in a group of 24 patients infected with HIV in Bangkok, Thailand compared with a group of 19 patients infected with HIV without diarrhea cared for at the same clinic. Patients with diarrhea appeared to have more advanced disease by CD4 cell counts and complained more frequently of symptoms such as anorexia, gas, and bloating than patients without diarrhea. Patients with diarrhea had a tendency toward a lower nutritional status, as measured by body mass index and mid arm circumference. Stool culture and examination revealed that enteric pathogens including Salmonella species and Cryptosporidium parvum sporidia were recovered at equal frequencies in patients with and without diarrhea (27% of the patients with diarrhea and 25% of the patients without diarrhea). Microsporidia was identified in one patient with diarrhea. It was not possible to identify a pathogen in 73% of the patients with diarrhea and 75% of the patients without diarrhea, suggesting that additional agents or factors may be responsible for the diarrheal symptoms in the patients with diarrhea. More extensive studies to identify potentially treatable pathogens in HIV-infected patients with diarrhea in Thailand are warranted and further attempts to better define the syndrome of pathogen-negative diarrheal disease in patients infected with HIV might result in the development of more targeted interventions in these patients.

Corynebacterium pseudodiphtheriticum: an easily missed respiratory pathogen in HIV-infected patients

Despite being a well-known respiratory pathogen for immunocompromised patients, Corynebacterium pseudodiphtheriticum has uncommonly been reported to occur in persons with infection attributable to HIV virus. We report three cases of respiratory tract infection attributable to C. pseudodiphtheriticum in HIV-infected patients and review the four previous cases from the medical literature. All of them were male with a median CD4 lymphocyte count of 110 cells/mm 3 (range, 18–198/mm 3); five of the seven cases occurred in persons for whom AIDS was diagnosed previously. The onset of symptomatology was usually acute and the most common radiographic appearance was alveolar infiltrate (six patients) with cavitation (two patients) and pleural effusion (two patients). In five of the seven cases, C. pseudodiphtheriticum was isolated from bronchoscopic samples and in the remaining two cases was recovered from lung biopsy (one patient) and sputum (one patient). In the three patients reported herein and in one previous case from the medical literature, quantitative culturing of bronchoscopic samples obtained through either bronchoalveolar lavage or protected brush catheter procedures yielded more than 10 3 CFU/mL. All the strains tested were susceptible to penicillin and vancomycin. Resistance to macrolides was common. Recovery was observed in six of the seven patients. C. pseudodiphtheriticum should be regarded as a potential respiratory pathogen in HIV-infected patients. This infection presents late in the course of HIV disease and it seems to respond well to appropriate antibiotic treatment in most of the cases. This easily overlooked pathogen should be added to the list of organisms implicated in respiratory tract infections in this population.

Mycobacterium avium-intracellulare complexActivates Nuclear Transcription Factor-κB in Different Cell Types Through Reactive Oxygen Intermediates

AbstractMycobacterium avium-intracellulare complex (MAC) is one of the most common opportunistic pathogens in HIV-infected patients. Their synergistic interaction leads to a rapid deterioration of the host defense. In vivo, MAC manifests as a disseminated granulomatous disease that produces a massive inflammatory tissue response perhaps through its activation of inflammatory cytokines. The intracellular signaling following interaction of the mycobacterium with host cells is incompletely understood. Because the response is dependent, in part, on the activation of NF-κB, we investigated the effect of MAC on this nuclear transcription factor in cells of macrophage and nonmacrophage lineage. We demonstrate that both high and low virulence strains of MAC potently and rapidly activated NF-κB. In supershift assays, using specific Abs against the NF-κB subunits, we identified a p50/p65 heterodimer that was formed within 5 min after incubation with the bacterium too rapidly for cytokines to be involved in the activation. This activation was instead mediated through the generation of reactive oxygen intermediates, inasmuch as preincubation of cells with a variety of antioxidants inhibited NF-κB activation. Likewise, the transfection of cells with Mn-superoxide dismutase blocked the NF-κB activation induced by the bacterium. These data suggest that NF-κB activation is a consequence of interaction of host cells with the bacterium and that the interaction may play a pivotal role in the pathogenesis of the disease.