Major Opportunistic Infection Research Articles

Prevention and Treatment of Cancer-Related Infections, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy. The NCCN Guidelines for the Prevention and Treatment of Cancer-Related Infections address infection concerns that may be observed in these immunocompromised populations and characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This paper highlights 2 recently updated sections of the guidelines, namely, infection concerns related to CAR T-cell therapy and antimicrobial prophylaxis recommendations, including vaccination, in patients at high-risk for infections.

Isoniazid prophylaxis based on tuberculosis risk factors in living kidney transplantation recipients: A retrospective cohort study

BackgroundTuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain. MethodsThis study included all living-donor kidney transplant recipients between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with INH (R-INH), the risk group without INH (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed. ResultsA total of 1348 patients were divided into R-INH (n = 108), R-NINH (n = 371), and NR (n = 869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (hazard ratios, 0.55, 95% confidence interval, 0.07–4.21, P = 0.564), whereas it was significantly higher in R-NINH (hazard ratios, 5.04, 95% confidence interval, 2.64–9.62, P < 0.001). The median time from transplantation to TB was 19 months (interquartile range: 6–39), and 18 patients (38.3%) were diagnosed within 1 year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%). ConclusionsA 6-month INH regimen based on TB risk factors is effective and well-tolerated for preventing post-transplant TB in kidney transplant recipients.

Potential Efficacy of Toxoplasma gondii Extracellular Vesicles in Protection against Acute Experimental Toxoplasmosis

Abstract Toxoplasmosis is a zoonotic disease thought to infect 1.5 billion people worldwide. It is a significant food- and water-borne illness that can lead to a major opportunistic infection in patients with impaired immune systems. As a result, there is a pressing need to provide better alternatives for effective long-term disease control, such as vaccinations, as there is no treatment that can eradicate bradyzoites within tissue cysts. Exosomes are multivesicular entities that fuses with plasma membranes to form nanograde membrane-bound vesicles that are secreted by the majority of cell types. Exosomes play important functions in intercellular communication and several of them are well described and known to have immunomodulatory capabilities. Exosomes generated from Toxoplasma gondii (T. gondii) were isolated and their protective effectiveness and immunological responses against acute T. gondii infection in mice was investigated. T. gondii exosomes were isolated and identified by transmission electron microscopy. Mice were immunized with T. gondii tachyzoites derived exosomes (100 μg, 3 doses intramuscular with 2 weeks interval) to investigate the vaccine’s efficiency by challenging the mice with T. gondii RH strain tachyzoites administered intraperitoneal. Exosomes from T. gondii were successfully isolated and characterized. T. gondii exosome-immunized mice showed a longer survival rate compared to the unimmunized group. T. gondii derived exosomes could be a promising vaccine candidate for protection against toxoplasmosis.

Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis.

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

Time to tuberculosis development and its predictors among HIV-positive patients: A retrospective cohort study.

To assess the incidence and predictors of time to Tuberculosis (TB) development among Human Immunodeficiency Virus (HIV) positive patients attending follow-up care in health facilities of Hawassa, Ethiopia. We conducted a retrospective cohort study from April 1-30, 2023. A total of 422 participants were selected using a simple random sampling method. Data was collected from the medical records of patients enrolled between January 1, 2018 -December 31, 2022, using the Kobo toolbox. We used Statistical Package for Social Studies (SPSS) version 26.0 for data analysis. To estimate the duration of TB-free survival, we applied the Kaplan-Meier survival function and fitted Cox proportional hazard models to identify the predictors of time to TB development. Adjusted hazard ratios (AHR) with 95% confidence intervals were calculated and statistical significance was declared at a P-value of 0.05. The overall incidence rate of TB among HIV-positive patients was 6.26 (95% CI: 4.79-8.17) per 100 person-years (PYs). Patients who did not complete TB Preventive Therapy (TPT) were more likely to have TB than those who did (AHR = 6.2, 95% CI: 2.34-16.34). In comparison to those who began antiretroviral therapy (ART) within a week, those who began after a week of linkage had a lower risk of TB development (AHR = 0.44, 95% CI: 0.21-0.89). Patients who received ART for six to twelve months (AHR = 0.18, 95% CI: 0.05-0.61) and for twelve months or longer (AHR = 0.004, 95% CI: 0.001-0.02) exhibited a decreased risk of TB development in comparison to those who had ART for less than six months. The incidence of TB among HIV-positive patients is still high. To alleviate this burden, special attention should be given to regimen optimization and provision of adherence support for better completion of TPT, sufficient patient preparation, thorough clinical evaluation for major (Opportunistic Infections) OIs prior to starting ART, and ensuring retention on ART.

Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients.

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.

This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.

Atypical Presentations of Progressive Disseminated Histoplasmosis in an Immunocompetent Adult: Ectopic Calcification (Aneurysm of Sinus of Valsalva) and Large Vessel (Left Subclavian Artery) Stenosis in the Background of Adrenal Insufficiency

Histoplasmosis is a systemic fungal disease caused by the dimorphic fungus Histoplasma capsulatum and is more common in immunocompromised patients. Histoplasmosis can present with a wide range of clinical manifestations from asymptomatic illness to severe organ dysfunctions and may need hospitalization. Histoplasmosis is a major opportunistic infection in North and Central America. Disseminated histoplasmosis is a progressive extrapulmonary infection, caused by hematogenous spread, mostly found in immunosuppressed patients.&#x0D; Reports of histoplasmosis in nonendemic regions are very rare. Due to the varied and nonspecific clinical manifestations of histoplasmosis, most of the infections are misdiagnosed or underreported.&#x0D; Here, we report a case of disseminated histoplasmosis in an immunocompetent individual from a non-endemic zone in eastern India, presented with long term fever along with ectopic calcification (Aneurysm of Sinus of Valsalva) and large vessel (left subclavian artery) stenosis in the background of adrenal insufficiency.

Association Between Soluble Cluster of Differentiation 14 Levels and Active Tuberculosis Infection in Human Immunodeficiency Virus Patients

BACKGROUND: Tuberculosis is the major opportunistic infection and the leading cause of death among the HIV population worldwide. Indonesia is included among the countries seriously affected by both TB and HIV. HIV increases the lifetime risk of TB infection. One of the parameters related to TB infection in HIV patients is the level of sCD14, which is part of monocytes and macrophages and can bind to lipoarabinomannan in Mycobacterium tuberculosis. METHODS: This study uses cross-sectional analysis. The research subjects were determined by the purposive consecutive method at the Sanglah Hospital, Bali, in 2021–2022. The sCD14 level was measured by the ELISA method. The diagnosis of active tuberculosis was confirmed by examining patient specimens using the molecular rapid test method RT-PCR GeneXpert MTB/RIF. RESULTS: There were 60 subjects with HIV infection, consisting of 42 (70%) men and 18 (30%) women. The mean age was 39.13 ± 11.734 years. The median body mass index was 18.8 (16.3–23.4), clinical stage 1–2 was 17 (28.3%), and stage 3–4 was 43 (71.7%). A total of 46 (76.7%) people had other opportunistic infections besides TB. The cut-off point for sCD14 levels was 2900 ng/mL. Subjects with active TB infection were 18 (30%) people and 42 (70%) people without TB. The results of bivariate analysis using the Chi-Square test found a significant relationship between sCD14 levels and active tuberculosis infection in HIV patients (p &lt; 0.001). Multivariate analysis with logistic regression showed that high sCD14 levels were independently associated with active tuberculosis infection in HIV patients (AOR 13.64; 95% CI: 2.89–64.42; p = 0.001), while other confounding factors were not significantly associated with active tuberculosis infection in HIV patients. CONCLUSION: sCD14 levels are associated with active tuberculosis infection in HIV patients.

Advanced HIV disease: A review of diagnostic and prophylactic strategies.

Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Cerebral toxoplasmosis, miliary tuberculosis and HIV co-infection with CD4 count of 446 cells/mm3: an unsual case report

Cerebral toxoplasmosis and tuberculosis miliaria are major and serious opportunistic infections, usually occurring in HIV-positive individuals with CD4 counts&lt; 200 cells/mm3. We report here a case in a 56-year-old patient with toxoplasmosistuberculosis- HIV co-infection with CD4 count of 446 cells/mm3. Under multidrug therapy (cotrimoxazole and first-line antituberculosis drugs), the favorable evolution (clinical improvement) was observed on the fourteenth day of cotrimoxazole treatment. High antiretroviral therapy (HAART) was reintroduced on the fifteenth day of anti-tuberculosis treatment, after two sessions of psychotherapy. Through this clinical case, the practitioner should be warned about the possibility of concomitant opportunistic infections in an HIV immunocompromised patient, especially without chemoprophylaxis, whatever his CD4 count.

Immunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation

Human cytomegalovirus reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we use mass cytometry to define patterns of innate and adaptive immune cell reconstitution at key phases of human cytomegalovirus reactivation in the first 100 days post haematopoietic stem cell transplantation. Human cytomegalovirus reactivation is associated with the development of activated, memory T-cell profiles, with faster effector-memory CD4+ T-cell recovery in patients with low-level versus high-level human cytomegalovirus DNAemia. Mucosal-associated invariant T cell levels at the initial detection of human cytomegalovirus DNAemia are significantly lower in patients who subsequently develop high-level versus low-level human cytomegalovirus reactivation. Our data describe distinct immune signatures that emerged with human cytomegalovirus reactivation after haematopoietic stem cell transplantation, and highlight Mucosal-associated invariant T cell levels at the first detection of reactivation as a marker that may be useful to anticipate the magnitude of human cytomegalovirus DNAemia.

A case report of a brain herniation secondary to cryptococcal meningitis with elevated intracranial pressure in a patient with Human Immunodeficiency Virus/Acquired immunodeficiency syndrome (HIV/AIDS)

BackgroundCryptococcal meningitis is a major opportunistic infection in individuals with HIV. The worldwide annual incidence is estimated to be approximately one million cases per year, with the most significant burden in sub-Saharan Africa. HIV-associated cryptococcal meningitis continues to have a high mortality rate despite widespread availability and use of HAART.Case36-year-old male with a past medical history of AIDS and a CD4 count of 35 cells/mm3 presented with altered mental status initially thought to be related to using crystalline methamphetamine as reported by EMS. However, a lumbar puncture performed in the emergency department showed elevated CSF opening pressure of 29 cmH2O and positive CSF and serum cryptococcal antigen. The patient was admitted and commenced treatment according to the current IDSA guideline but continued to have waxing and waning mental status. On the fourth day of admission, he complained of headache, had a witnessed seizure, and was taken emergently for a CT scan of the brain, which was negative for any acute intracranial process, but suffered a cardiac arrest before it could be done. He was intubated and transferred to the intensive care unit. CT brain follow-up showed anoxic encephalopathy, development of marked cerebral edema, and complete effacement of the basilar cisterns, suggestive of downward transtentorial herniation; he continued to deteriorate and expired on the seventh day of admission.Objectives1.Describe a case of brain death secondary to increased intracranial pressure due to cryptococcal meningitis in a patient with HIV/AIDS.2.Explain the mechanisms of elevation in intracranial pressure in patients with cryptococcal meningitis.3.Discuss the options for managing elevated intracranial pressure in patients with cryptococcal meningitis.4.Create awareness in the medical community about the importance of prompt and efficient management of increased intracranial pressure in patients with cryptococcal meningitis.ConclusionThis case highlights the importance of aggressive management of elevated intracranial pressure in cryptococcal meningitis. It reiterates the need for more data regarding the optimal timing and frequency of therapeutic lumbar puncture and the use of temporary lumbar drainage catheters and ventriculostomy to manage this potentially fatal complication.

A retrospective study of survival and risk factors for mortality among people living with HIV who received antiretroviral treatment in a resource-limited setting

BackgroundThe availability and accessibility of effective antiretroviral therapy (ART) for people living with HIV (PLWH) has substantially improved in the past two decades in resource-limited settings. Therefore, evaluation of survival is needed in the current setting.MethodWe retrospectively analyzed secondary data of the national AIDS program database from national health security region number 4 among PLWH who were ART-naive between January 2014 and December 2018. All PLWH were followed until December 2019 to evaluate their survival status and possible risk factors related to death.ResultsA total of 42,229 PLWH were identified, of which 14,053 were ART-naive and thus enrolled in the study. Sixty-seven percent were male, the mean ± SD age was 35 ± 12 years, and the median (IQR) baseline CD4 count was 162 (44–353) cells/mm3. Regarding medical care benefits, 46% had a universal health coverage scheme, 34% had a national social security scheme, and 2% had a civil servants medical benefit scheme. A total of 2142 (15%) mortalities occurred during the total follow-up period of 28,254 patient-years. The mortality rate was 7.5 (95% CI 7.2–7.9) per 100 person-years. Survival rates at 1, 2, 3, 4 and 5 years after HIV registration were 88.2% (95% CI 87.6–88.7%), 85.3% (95% CI 84.6–85.9%), 82.9% (95% CI 81.9–83.4%), 81.3% (95% CI 80.5–82.0%) and 75.1% (95% CI 73.5–76.8%), respectively. The Cox proportional hazards model showed that all-cause mortality was associated with a history of ART switching (HR = 7.06, 95% CI 4.53–11.00), major opportunistic infections during ART (HR = 1.93, 95% CI 1.35–2.77), baseline CD4 count ≤ 200 vs. > 500 cells/mm3 (HR = 4.00, 95% CI 1.45–11.11), age ≥ 50 vs. < 30 years (HR = 1.77, 95% CI 1.12–2.78), and receiving nevirapine-based regimens(HR = 1.43, 95% CI 1.04–1.97).ConclusionsThis study demonstrated the substantial mortality rate over the consecutive 5 years of the follow-up period among PLWH who received ART in a resource-limited setting. Early case finding and prompt initiation of ART as well as continuous HIV care are a cornerstone to improve survival.

Cryptococcal meningitis: A delineating presentation peeping toward HIV status

Cryptococcal meningitis is an ominous presentation of the most common opportunistic fungal infection in patients affected by the Human immunodeficiency virus (HIV). Cryptococcus neoformans is the commonly associated species in immunocompromised patients. It is the first AIDS-defining illness in 6–10% of patients. Cryptococcosis is reported as a major opportunistic infection in India. The case of cryptococcal meningitis presented here is of a young, chronic alcoholic 28-year-old male patient with non-specific symptoms having the only significant history that he was sexually active with a woman whose husband died of unknown cause which draws attention to look for HIV status of the patient which was found to be reactive confirming it as one of the AIDS-defining illness.

Deficiency of mannose-binding lectin is a risk of Pneumocystis jirovecii pneumonia in a natural history cohort of people living with HIV/AIDS in Northern Thailand.

Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS. We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched. Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002). Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs.

Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis.

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.

Prevention of Opportunistic Infections in Women With HIV Infection

Opportunistic infections are those that are either more frequent or more severe as a result of the patient's immunosuppressed condition. Opportunistic infections are, of course, the distinguishing feature of HIV infection, and they can be the cause of serious morbidity and even mortality. Some opportunistic infections can be prevented by vaccination, for example, pneumococcal infection, meningococcal infection, influenza, hepatitis A and B, and varicella. Other major opportunistic infections require prophylactic antibiotics or antiviral medications. In obstetric patients, pneumocystis infections and toxoplasmosis are most effectively prevented by the administration of trimethoprim-sulfamethoxazole. The most effective agents for prevention of reactivation of tuberculosis are isoniazid, rifampin, and rifapentine. Fluconazole is of value in preventing cryptococcal infection and candidiasis. Acyclovir, valacyclovir, and famiclovir are effective in preventing recurrent outbreaks of herpes simplex virus. Ultimately; however, the best way to prevent opportunistic infections is to treat the patient with highly active antiretroviral agents and restore her immune competence.

Genetic Polymorphisms of Superoxide Dismutase Locus of Pneumocystis jirovecii in Spanish Population.

Objective: Pneumocystis pneumonia remains a major opportunistic infection in immunocompromised patients worldwide. Colonization with Pneumocystis jirovecii has recently gained attention as an important issue for understanding the complete cycle of human Pneumocystis infection. P. jirovecii Superoxide Dismutase (SOD) gene could be a molecular target with high clinical relevance, but the epidemiological information about SOD genotypes distribution is scarce. The aim of this work was to provide information about the prevalence of genotypes of Pneumocystis SOD among Spanish patients and to describe possible differences between colonized and Pneumocystis pneumonia patients.Methods: we developed a cross-sectional study analyzing broncho-alveolar lavage fluid samples from 30 Pneumocystis pneumonia patients, 30 colonized patients, and 20 controls using a nested PCR protocol designed to amplify the sodA gene of P. jirovecii. The diagnostic yield of SOD Nested PCR was evaluated against the routine practice of mtLSUrRNA Nested PCR, which is considered the gold standard.Results: SOD locus was amplified in 90% of Pneumocystis pneumonia patients, 10% of colonized patients, and none of controls. Genotype SOD1 was observed in 11 cases (52.4%) and genotype SOD2 in 10 cases (47.6%). Genotype SOD2 was observed only in Pneumocystis pneumonia patients while the genotype SOD1 was observed in both colonized and Pneumocystis pneumonia patients.Conclusions: This study provides epidemiological information about SOD genotypes distribution in Spain, showing a low genetic diversity and a predominant presence of genotype SOD1 in colonized patients. SOP Nested PCR was more sensitive and accurate assay in Pneumocystis pneumonia patients than in colonized individuals.