Mycobacterial Lung Infection Research Articles

Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. A favourable response to treatment was seen in 74% of patients with a high relapse rate.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting

Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Automated Machine Learning with Radiomics for Predicting Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Automated Machine Learning with Radiomics for Predicting Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Lung infection with nontuberculous mycobacteria

ObjectiveTo describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methodsWe retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. ResultsWe included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). ConclusionThe diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

Un cas rare de mycobactériose non tuberculeuse pulmonaire à Mycobacterium thermoresistibile

Non-tuberculous mycobacterial lung infections are infrequent and occur mostly in patients having important and multiple comorbidities. Mycobacterium thermoresistibile is an environmental mycobacterium that has been rarely described as a human pathogen. We report here a rare case of an 85-year-old man with M. thermoresistibile lung infection.

Isolated Elevation in Lung Residual Volume Is Associated With Airway Diseases.

Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DLCO). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and DLCO (normal-RV group). We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non-tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.

Nontuberculous mycobacterial skin and soft tissue infection in Hawai\u02bbi

BackgroundHawaiʻi has the highest nontuberculous mycobacterial (NTM) lung infection prevalence in the United States. Limited data regarding skin and soft tissue infections (SSTI) due to NTM in Hawaiʻi exists. This study describes patient demographics, clinical courses of infection, treatment patterns, and clinical outcomes of NTM SSTIs in Hawaiʻi.MethodsA retrospective chart review (n = 50) of patients diagnosed and treated at Hawaiʻi Pacific Health facilities for NTM SSTIs between January 2010 and July 2021 was conducted. Patient demographics, clinical course, and treatment data were collected from electronic medical records.ResultsHalf of the patient population consisted of females, and the average age of patients during infection was 49 years (SD = 25.6). The majority of cases (80%) were caused by rapidly growing mycobacteria (RGM), most commonly Mycobacterium abscessus. NTM SSTI by race were Asian (48%), White (28%), and Native Hawaiian and Other Pacific Islanders (16%). Almost all Asian patients with NTM SSTI were Filipino or Japanese. Diagnosis was frequently delayed. The average time to diagnosis was 116 days. Most patients achieved complete resolution (72%) following a prolonged course of antimicrobial treatment (mean = 196 days) with surgical debridement.ConclusionIncreased awareness among physicians and the community of non-mycobacterial skin infections is essential in Hawaiʻi due to the high prevalence of NTM and the high percentage of predisposed populations. Increased awareness of NTM could reduce delayed diagnosis and improve patient care. Further studies are required to inform optimal treatment and diagnostic strategies, improve patient outcomes, and aid public health surveillance efforts.

Infección pulmonar por micobacterias no tuberculosas

ObjectiveTo describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methodsWe retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analyzed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. ResultsWe included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1%), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). ConclusionThe diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

Outcomes of Resectional Thoracic Surgery for the Treatment of Pulmonary Nontuberculous Mycobacterial Disease in 105 Patients in the United States

Outcomes of Resectional Thoracic Surgery for the Treatment of Pulmonary Nontuberculous Mycobacterial Disease in 105 Patients in the United States

A "double fistula" with Mycobacterium avium complex lung disease.

Key messageWe present a patient with a history of cavitary mycobacterial lung infection and chronic obstructive pulmonary disease (COPD) who developed two connected fistulas post thoracentesis, an alveolo‐pleural and a pleuro‐cutaneous fistula, leading to continuous air leak from a stoma on his back.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

Macrophage activating lipopeptide 2 is effective in mycobacterial lung infection

MALP-2, a synthetic lipopeptide is a Toll-like receptor 2 and -6 ligand and agonist. MALP-2 stimulates immune cells at different sites. Local stimulation in the lungs has beneficial effects in experimental pneumococci infection. The presented study investigated local effects of MALP-2 in the mycobacterial infection of lungs. MALP-2 was applied prior, simultaneously or after the pulmonary infection with Mycobacterium bovis BCG. Colony forming units were determined in the bronchoalveolar lavage fluid and lung homogenate. Numbers of Mycobacterium bovis BCG colony forming units were found to be reduced in two compartments, bronchoalveolar lavage fluid and lung homogenate after treatment with MALP-2 simultaneously to the infection for up to eight weeks. Reduction of the bacterial load in both compartments was also found up to two weeks after local treatment before and after the infection. Thus, macrophage activating lipopeptide-2 enhances the host defence in the lung in acute and long term bacterial infections.

Recent advances in nontuberculous mycobacterial lung infections.

Nontuberculous mycobacteria (NTM) are members of the Mycobacterium genus other than Mycobacterium tuberculosis complex and Mycobacterium leprae. NTM are widely distributed in the environment and are increasingly recognized as causes of chronic lung disease that can be challenging to treat. In this brief review, we consider recent developments in the ecology, epidemiology, natural history, and treatment of NTM lung disease with a focus on Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex .

Gr1int/high Cells Dominate the Early Phagocyte Response to Mycobacterial Lung Infection in Mice.

Lung infection by Mycobacterium tuberculosis is characterized by chronic infection of lung-resident macrophages, long considered to be the primary hosts and determinants of the outcome of the early immune response. Although alveolar macrophages are well-known to host intracellular mycobacteria at later stages of disease, little is known about the earliest events of the innate immune response. The phagocytes that take up mycobacteria immediately following infection, and how the early lung phagocyte response is altered by vaccination with M. bovis bacille Calmette-Guérin (BCG) were unknown. Using BCG expressing the bright red fluorescent protein tdTomato and flow cytometry, we modeled early infection in C57BL/6 mice and tracked phagocyte population kinetics and uptake of mycobacteria, to better understand the involvement of specific phagocyte subsets. By 1 day post-infection, dose-dependent accumulation of neutrophils was observed and surprisingly, granulocytes comprised a greater proportion of infected phagocytes than alveolar macrophages. By 7 days post-infection alveolar macrophages had become the dominant BCG-associated phagocytes. Prior mucosal BCG exposure provided immunized mice with greater frequencies and numbers of lung macrophage subsets, and a significantly greater proportion of alveolar macrophages expressed CD11b prior to and following challenge infection. These data provide the first evidence of granulocytes as the dominant infected phagocyte subset early after mycobacterial infection, and highlight enhanced recruitment of lung macrophages as a factor associated with protection in BCG-immunized mice.

Ecological Analyses of Mycobacteria in Showerhead Biofilms and Their Relevance to Human Health.

Bacteria within the genus Mycobacterium can be abundant in showerheads, and the inhalation of aerosolized mycobacteria while showering has been implicated as a mode of transmission in nontuberculous mycobacterial (NTM) lung infections. Despite their importance, the diversity, distributions, and environmental predictors of showerhead-associated mycobacteria remain largely unresolved. To address these knowledge gaps, we worked with citizen scientists to collect showerhead biofilm samples and associated water chemistry data from 656 households located across the United States and Europe. Our cultivation-independent analyses revealed that the genus Mycobacterium was consistently the most abundant genus of bacteria detected in residential showerheads, and yet mycobacterial diversity and abundances were highly variable. Mycobacteria were far more abundant, on average, in showerheads receiving municipal water than in those receiving well water and in U.S. households than in European households, patterns that are likely driven by differences in the use of chlorine disinfectants. Moreover, we found that water source, water chemistry, and household location also influenced the prevalence of specific mycobacterial lineages detected in showerheads. We identified geographic regions within the United States where showerheads have particularly high abundances of potentially pathogenic lineages of mycobacteria, and these "hot spots" generally overlapped those regions where NTM lung disease is most prevalent. Together, these results emphasize the public health relevance of mycobacteria in showerhead biofilms. They further demonstrate that mycobacterial distributions in showerhead biofilms are often predictable from household location and water chemistry, knowledge that advances our understanding of NTM transmission dynamics and the development of strategies to reduce exposures to these emerging pathogens.IMPORTANCE Bacteria thrive in showerheads and throughout household water distribution systems. While most of these bacteria are innocuous, some are potential pathogens, including members of the genus Mycobacterium that can cause nontuberculous mycobacterial (NTM) lung infection, an increasing threat to public health. We found that showerheads in households across the United States and Europe often harbor abundant mycobacterial communities that vary in composition depending on geographic location, water chemistry, and water source, with households receiving water treated with chlorine disinfectants having particularly high abundances of certain mycobacteria. The regions in the United States where NTM lung infections are most common were the same regions where pathogenic mycobacteria were most prevalent in showerheads, highlighting the important role of showerheads in the transmission of NTM infections.

NK Cell-Derived IFN-γ Protects against Nontuberculous Mycobacterial Lung Infection.

In developed countries, pulmonary nontuberculous mycobacteria (NTM) infections are more prevalent than Mycobacterium tuberculosis infections. Given the differences in the pathogenesis of NTM and M. tuberculosis infections, separate studies are needed to investigate the pathological effects of NTM pathogens. Our previous study showed that anti-IFN-γ autoantibodies are detected in NTM-infected patients. However, the role of NK cells and especially NK cell-derived IFN-γ in this context has not been studied in detail. In the current study, we show that NK1.1 cell depletion increases bacterial load and mortality in a mouse model of pulmonary NTM infection. NK1.1 cell depletion exacerbates NTM-induced pathogenesis by reducing macrophage phagocytosis, dendritic cell development, cytokine production, and lung granuloma formation. Similar pathological phenomena are observed in IFN-γ-deficient (IFN-γ-/-) mice following NTM infection, and adoptive transfer of wild-type NK cells into IFN-γ-/- mice considerably reduces NTM pathogenesis. Injection of rIFN-γ also prevents NTM-induced pathogenesis in IFN-γ-/- mice. We observed that NK cells represent the main producers of IFN-γ in the lungs and production starts as soon as 1 d postinfection. Accordingly, injection of rIFN-γ into IFN-γ-/- mice 1 d (but not 2 wk) postinfection significantly improves immunity against NTM infection. NK cells also stimulate mycobacterial killing and IL-12 production by macrophages. Our results therefore indicate that IFN-γ production by NK cells plays an important role in activating and enhancing innate and adaptive immune responses at early stages of pulmonary NTM infection.

Adjuvant lung resection in the management of nontuberculous mycobacterial lung infection: A retrospective matched cohort study.

Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is considered when medical therapy alone fails to provide long term control. Data regarding comparative and long-term outcomes are limited. We aimed to review indications and outcomes of adjuvant lung resection for NTM-PD compared with controls. We retrospectively studied 27 surgically treated patients, matched 1:1 for age, sex, NTM species, and radiologic pattern of disease, with control patients treated exclusively with antibiotics. In the surgical group, the median (IQR) age was 55 (49-61) years and 74.1% were female. Eighteen patients had Mycobacterium avium complex, and 9 had M. xenopi. Operations included 8 pneumonectomies, 20 lobectomies, one segmentectomy and one lobectomy plus segmentectomy. Post-surgical complications occurred in 6 patients (20%), including 2 acute respiratory distress syndrome, 1 bronchopleural fistula, 1 pericardial tamponade, and 2 empyema. Complications were more common among patients operated upon for progressive disease despite medical therapy (OR 10, p = 0.025). Of 24 matched pairs followed for ≥1 year, sustained culture conversion was observed in 21 (87.5%) patients in the surgical group and in 11 (45.8%) patients in the non-surgical group (RR 2.36, 95%CI 1.37-4.03, p = 0.002). Median (IQR) percentage of follow-up time on antibiotics was 14% (0-100%) in the surgical group and 83% (10.8%-100%) in the non-surgical group (p = 0.195) during a median (IQR) follow-up of 16 (2-36) months. NTM-PD patients who underwent adjuvant lung resection experienced significant morbidity and more frequently achieved sputum culture conversion. Long term antibiotic requirements may have been reduced.

Abstract 632A: Microbiome diversity in sputum and circulating exosomes of women with breast cancer and nontuberculous mycobacterial lung disease

Abstract The nontuberculous Mycobacterial lung disease, primarily caused by Mycobacterium avium complex is an alarming health problem in the United States and worldwide. Being prevalent among Caucasian women with a history or current diagnosis of breast cancer, Nontuberculous Mycobacterial lung disease poses a significant challenge towards treatment. A large community of resident microbes, including bacteria, virus, Archeas and Fungi living in the human body are being increasingly recognized as the key components of controlling human health and disease. In this study, we examined microbiome diversity in sputa and circulating exosomes derived from women with both breast cancer and nontuberculous Mycobacterial lung disease, women with nontuberculous Mycobacterial lung infection only and healthy women by 16S rDNA sequencing. Our study identified a diverse microbiome community in the sputa and the exosomes dominated by Streptococcus, Haemophillus, Veillonella, Neisseria, Prevotella, Fusobacterium, Bacteroides, Allistipes, Faecalibacterium and Staphylococcus in women with both breast cancer and nontuberculous Mycobacterial lung disease and nontuberculous Mycobacterial lung disease only. Some of these genera, including Fusobacterium, Bacteroides, Allistipes have estrobolome activity and are associated with the development of breast and other neoplasm. This work confirms the presence of a distinct microbiome other than the Mycobacteriome in the sputa and the circulating exosomes of these patients. Further studies investigating the role of the sputa and exosome microbiome linking nontuberculous Mycobacterial pathogenesis and breast cancer are warranted. Citation Format: Julie V. Philley, David E. Griffith, Santanu Dasgupta. Microbiome diversity in sputum and circulating exosomes of women with breast cancer and nontuberculous mycobacterial lung disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 632A.

3rd World Bronchiectasis Conference.

The 3rd World Bronchiectasis Conference was held at Georgetown University in Washington, D.C., on July 12-14, 2018. The meeting brought together the expertise of the U.S. Bronchiectasis Research Registry and the European Bronchiectasis Registry principal investigators, as well as experts from Canada, Asia, Australia and New Zealand. This program benefited the entire health care team who care for patients with bronchiectasis and nontuberculous mycobacterial lung infections (NTM) including pulmonologists, infectious disease physicians, pharmacists, nurses and respiratory care practitioners. This gathering of the international community of participants highlighted an authentic world bronchiectasis conference as an extension of the previous 2 World Bronchiectasis Conferences in Milan, Italy in 2017 and Hannover, Germany in 2016. The burgeoning amount of research interest, much needed development of clinical trials, and support of international collaborative work attests to progress made in the past several years awakening the new age of research and clinical work involving bronchiectasis and nontuberculous mycobacterial lung disease. With nearly 300 attendees, the conference was a focused, cutting-edge gathering of the world’s experts on bronchiectasis and NTM. Original work spanning basic science to clinical investigations were featured during the conference presentations as well as abstracts included in this publication. Highlights included recent advances in research on disease mechanisms in bronchiectasis, including new understandings on the role of inflammation, infection and the microbiome. Clinical topics included sessions on the diagnosis and treatment of bronchiectasis and NTM infections, including small group, case-based presentations specifically aimed at understanding the role of airway clearance, anti-inflammatory treatments and antibiotics. On Saturday morning, July 14th, the program focused on the management of patients with NTM lung infections. This session was well attended by pulmonologists and infectious disease practitioners who treat patients with these challenging infections. Saturday afternoon offered a halfday workshop solely focused on patients, with educational presentations featuring ways to manage their condition and learn more about bronchiectasis and NTM infections. Much appreciation is given collectively to the large number of patients, staff, clinicians, researchers, and industry partners involved in making this conference possible. Without the generous time, effort, and support provided, progress towards advancing the science and actively addressing the current gap in knowledge would not be possible. As a result of the 3rd World Bronchiectasis Conference we can look forward optimistically to the opportunities at hand for continuing this international enthusiasm and scientific inquiry, and, most importantly, positively impacting the lives of patients with bronchiectasis and NTM lung disease. NOTE: The following abstracts have NOT been copyedited but are presented here in their original format, as presented by the authors at the 3rd World Bronchiectasis Conference July 12-14, 2018.

Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies

BackgroundIdiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. ObjectiveTo describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. MethodsIn a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. ResultsTwenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7–76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm3 (range 4–294/mm3) and 219 ± 258/mm3 (range 7–630/mm3), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. ConclusionThe pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics.