Stressed snails release Angiostrongylus cantonensis (rat lungworm) larvae in their slime.

This study investigated the influence of stress on release of Angiostrongylus cantonensis larvae from a snail host, Parmarion martensi. We subjected 140 infected, wild-caught P. martensi to three stress-inducing treatments (heat, molluscicide, physical disturbance) and an unstressed control treatment for 24 h, after which larval presence and abundance in the slime were quantified by qPCR targeting the ITS1 region of the parasite's DNA, and compared among treatments. The significance of stress and host infection load on larval release was determined by generalized linear mixed models and permutation tests. The results indicated that stress significantly increased the probability of larval presence in slime and the number of larvae released, and highly infected snails were also more likely to release larvae. Among stressed snails, 13.3% released larvae into slime, the number of larvae present in the slime ranging from 45.5 to 4216. Unstressed controls released no larvae. This study offers a partial explanation for conflicting results from prior studies regarding A. cantonensis presence in snail slime and sheds light on the broader One Health implications. Stress-induced larval release highlights the potential role of slime as a medium for pathogen transmission to accidental, paratenic, definitive and other intermediate hosts. These findings emphasize the importance of considering stress-mediated interactions in host-parasite systems and their implications for zoonotic disease emergence. As stressors continue to escalate because of anthropogenic activities and climate change, understanding the role of stress in pathogen shedding and transmission becomes increasingly important for safeguarding human and wildlife health within the One Health framework.

Comparative biology of parasitic nematodes in the genus Angiostrongylus and related genera.

The rise to prominence of some Angiostrongylus species through associated emerging disease in humans and dogs has stimulated calls for a renewed focus on the biology of this genus and three related genera. Although significant research efforts have been made in recent years these have tended to focus on individual species and specific aspects such as diagnosis and treatment of disease or new records of occurrence and hosts. This comprehensive review takes a comparative approach, seeking commonalities and differences among species and asking such questions as: Which species belong to this and to closely related genera and how are they related? Why do only some species appear to be spreading geographically and what factors might underlie range expansion? Which animal species are involved in the life cycles as definitive, intermediate, paratenic and accidental hosts? How do parasite larvae find, infect and develop within these hosts? What are the consequences of infection for host health? How will climate change affect future spread and global health? Appreciating how species resemble and differ from each other shines a spotlight on knowledge gaps and provides provisional guidance on key species characteristics warranting detailed study. Similarities exist among species, including the basic life cycle and transmission processes, but important details such as host range, climatic requirements, migration patterns within hosts and disease mechanisms differ, with much more information available for A. cantonensis and A. vasorum than for other species. Nonetheless, comparison across Angiostrongylus reveals some common patterns. Historically narrow definitive host ranges are expanding with new knowledge, combining with very broad ranges of intermediate gastropod hosts and vertebrate and invertebrate paratenic and accidental hosts to provide the backdrop to complex interactions among climate, ecology and transmission that remain only partly understood, even for the species of dominant concern. Key outstanding questions concern larval dynamics and the potential for transmission outside trophic relations, relations between infection and disease severity in different hosts, and how global change is altering transmission beyond immediate impacts on development rate in gastropods. The concept of encounter and compatibility filters could help to explain differences in the relative importance of different gastropod species as intermediate hosts and determine the importance of host community composition and related environmental factors to transmission and range. Across the group, it remains unclear what, physiologically, immunologically or taxonomically, delimits definitive, accidental and paratenic hosts. Impacts of infection on definitive host fitness and consequences for population dynamics and transmission remain mostly unexplored across the genus. Continual updating and cross-referencing across species of Angiostrongylus and related genera is important to synthesise rapid advances in understanding of key traits and behaviours, especially in important Angiostrongylus species that are emerging causative agents of disease in humans and other animals.

Neuroangiostrongyliasis: Global Spread of an Emerging Tropical Disease.

Neuroangiostrongyliasis (NAS) is an emerging parasitic disease caused by the neurotropic nematode Angiostrongylus cantonensis. Since it was first discovered, in rats in southern China in the 1930s, this tropical to subtropical parasite has spread to much of Southeast Asia, the Pacific Islands (including Hawaii), Australia, Japan, South America, the southeastern United States, the Caribbean, Africa, the Canary Islands, and the Balearic Islands. The parasite completes its natural life cycle in snails and slugs (intermediate hosts), and rats (definitive hosts). Humans become accidental hosts after ingesting infective third-stage larvae contained within uncooked or undercooked intermediate or paratenic hosts, an event that sometimes results in NAS, also known as rat lungworm disease. Although A. cantonensis larvae cannot complete their life cycle in humans, their migration into the brain and spinal cord combined with a powerful inflammatory reaction often leads to eosinophilic meningitis and can, in rare instances, lead to coma, paralysis, and death or, in other cases, chronic, disabling neurologic sequelae. Symptoms of NAS are diverse, which often makes it difficult to diagnose. Treatment may include administration of analgesics, corticosteroids, anthelminthics, and repeat lumbar punctures to reduce intracranial pressure. Unfortunately, few medical providers, even in endemic areas, are familiar with A. cantonensis or its epidemiology, diagnosis, and treatment. As the parasite continues to spread and NAS affects more people, medical practitioners, as well as the general public, must become more aware of this emerging zoonosis and the potentially devastating harm it can cause.

Paratenic hosts of Angiostrongylus cantonensis and their relation to human neuroangiostrongyliasis globally.

The nematode parasite Angiostrongylus cantonensis (rat lungworm) has a complex life cycle involving rats (definitive hosts) and gastropods (intermediate hosts), as well as various paratenic hosts. Humans become infected and develop rat lungworm disease (neuroangiostrongyliasis) when they consume intermediate or paratenic hosts containing the infective parasite larvae. This study synthesizes knowledge of paratenic hosts of A. cantonensis and investigates their role in causing human neuroangiostrongyliasis worldwide. A literature review was conducted by searching PubMed, JSTOR and Scopus, pooling additional information from sources accumulated over many years by RHC, and snowball searching. The review identified 138 relevant articles published between 1962 and 2022. Freshwater prawns/shrimp, crayfish, crabs, flatworms, fish, sea snakes, frogs, toads, newts, lizards, centipedes, cattle, pigs and snails were reported to act as paratenic hosts in various regions including South and Southeast Asia, Pacific islands, the USA and the Caribbean, as well as experimentally. Human cases of neuroangiostrongyliasis have been reported from the 1960s onwards, linked, sometimes speculatively, to consumption of freshwater prawns/shrimp, crabs, flatworms, fish, frogs, toads, lizards and centipedes. The potential of paratenic hosts to cause neuroangiostrongyliasis depends on whether they are eaten, how frequently they are consumed, the preparation method, including whether eaten raw or undercooked, and whether they are consumed intentionally or accidentally. It also depends on infection prevalence in the host populations and probably on how high the parasite load is in the consumed hosts. To prevent human infections, it is crucial to interrupt the transmission of rat lungworm to humans, from both intermediate hosts and frequently consumed paratenic hosts, by adhering to safe food preparation protocols. Educating the general public and the medical community about this largely neglected tropical/subtropical disease is key.

The Sixth Mass Extinction: fact, fiction or speculation?

There have been five Mass Extinction events in the history of Earth's biodiversity, all caused by dramatic but natural phenomena. It has been claimed that the Sixth Mass Extinction may be underway, this time caused entirely by humans. Although considerable evidence indicates that there is a biodiversity crisis of increasing extinctions and plummeting abundances, some do not accept that this amounts to a Sixth Mass Extinction. Often, they use the IUCN Red List to support their stance, arguing that the rate of species loss does not differ from the background rate. However, the Red List is heavily biased: almost all birds and mammals but only a minute fraction of invertebrates have been evaluated against conservation criteria. Incorporating estimates of the true number of invertebrate extinctions leads to the conclusion that the rate vastly exceeds the background rate and that we may indeed be witnessing the start of the Sixth Mass Extinction. As an example, we focus on molluscs, the second largest phylum in numbers of known species, and, extrapolating boldly, estimate that, since around AD 1500, possibly as many as 7.5-13% (150,000-260,000) of all ~2 million known species have already gone extinct, orders of magnitude greater than the 882 (0.04%) on the Red List. We review differences in extinction rates according to realms: marine species face significant threats but, although previous mass extinctions were largely defined by marine invertebrates, there is no evidence that the marine biota has reached the same crisis as the non-marine biota. Island species have suffered far greater rates than continental ones. Plants face similar conservation biases as do invertebrates, although there are hints they may have suffered lower extinction rates. There are also those who do not deny an extinction crisis but accept it as a new trajectory of evolution, because humans are part of the natural world; some even embrace it, with a desire to manipulate it for human benefit. We take issue with these stances. Humans are the only species able to manipulate the Earth on a grand scale, and they have allowed the current crisis to happen. Despite multiple conservation initiatives at various levels, most are not species oriented (certain charismatic vertebrates excepted) and specific actions to protect every living species individually are simply unfeasible because of the tyranny of numbers. As systematic biologists, we encourage the nurturing of the innate human appreciation of biodiversity, but we reaffirm the message that the biodiversity that makes our world so fascinating, beautiful and functional is vanishing unnoticed at an unprecedented rate. In the face of a mounting crisis, scientists must adopt the practices of preventive archaeology, and collect and document as many species as possible before they disappear. All this depends on reviving the venerable study of natural history and taxonomy. Denying the crisis, simply accepting it and doing nothing, or even embracing it for the ostensible benefit of humanity, are not appropriate options and pave the way for the Earth to continue on its sad trajectory towards a Sixth Mass Extinction.

Biological Control of Pest Non-Marine Molluscs: A Pacific Perspective on Risks to Non-Target Organisms.

Classic biological control of pest non-marine molluscs has a long history of disastrous outcomes, and despite claims to the contrary, few advances have been made to ensure that contemporary biocontrol efforts targeting molluscs are safe and effective. For more than half a century, malacologists have warned of the dangers in applying practices developed in the field of insect biological control, where biocontrol agents are often highly host-specific, to the use of generalist predators and parasites against non-marine mollusc pests. Unfortunately, many of the lessons that should have been learned from these failed biocontrol programs have not been rigorously applied to contemporary efforts. Here, we briefly review the failures of past non-marine mollusc biocontrol efforts in the Pacific islands and their adverse environmental impacts that continue to reverberate across ecosystems. We highlight the fact that none of these past programs has ever been demonstrated to be effective against targeted species, and at least two (the snails Euglandina spp. and the flatworm Platydemus manokwari) are implicated in the extinction of hundreds of snail species endemic to Pacific islands. We also highlight other recent efforts, including the proposed use of sarcophagid flies and nematodes in the genus Phasmarhabditis, that clearly illustrate the false claims that past bad practices are not being repeated. We are not making the claim that biocontrol programs can never be safe and effective. Instead, we hope that in highlighting the need for robust controls, clear and measurable definitions of success, and a broader understanding of ecosystem level interactions within a rigorous scientific framework are all necessary before claims of success can be made by biocontrol advocates. Without such amendments to contemporary biocontrol programs, it will be impossible to avoid repeating the failures of non-marine mollusc biocontrol programs to date.

Host snail species exhibit differential Angiostrongylus cantonensis prevalence and infection intensity across an environmental gradient.

Diverse snail species serve as intermediate hosts of the parasitic nematode Angiostrongylus cantonensis, the etiological agent of human neuroangiostrongyliasis. However, levels of A. cantonensis infection prevalence and intensity vary dramatically among these host species. Factors contributing to this variation are largely unknown. Environmental factors, such as precipitation and temperature, have been correlated with overall A. cantonensis infection levels in a locale, but the influence of environment on infection in individual snail species has not been addressed. We identified levels of A. cantonensis prevalence and intensity in 16 species of snails collected from 29 sites along an environmental gradient on the island of Oahu, Hawaii. The relationship between infection levels of individual species and their environment was evaluated using AIC model selection of Generalized Linear Mixed Models incorporating precipitation, temperature, and vegetation cover at each collection site. Our results indicate that different mechanisms drive parasite prevalence and intensity in the intermediate hosts. Overall, snails from rainy, cool, green sites had higher infection levels than snails from dry, hot sites with less green vegetation. Intensity increased at the same rate along the environmental gradient in all species, though at different levels, while the relation between prevalence and environmental variables depended on species. These results have implications for zoonotic transmission, as human infection is a function of infection in the intermediate hosts, ingestion of which is the main pathway of transmission. The probability of human infection is greater in locations with higher rainfall, lower temperature and more vegetation cover because of higher infection prevalence in the gastropod hosts, but this depends on the host species. Moreover, severity of neuroangiostrongyliasis symptoms is likely to be greater in locations with higher rainfall, lower temperature, and more vegetation because of the higher numbers of infectious larvae (infection intensity) in all infected snail species. This study highlights the variation of infection prevalence and intensity in individual gastropod species, the individualistic nature of interactions between host species and their environment, and the implications for human neuroangiostrongyliasis in different environments.

Species Identity and Size are Associated with Rat Lungworm Infection in Gastropods.

Angiostrongylus cantonensis, the rat lungworm, is an emerging zoonotic pathogen that cycles between definitive rat and intermediate gastropod hosts. Zoonotic infection occurs when humans intentionally or accidentally consume infectious larvae in a gastropod host, and may manifest as neuroangiostrongyliasis, characterized by eosinophilic meningitis, severe neurological impairment, and even death. Thus, the risk of A. cantonensis zoonoses may be related to the distribution of A. cantonensis larvae across gastropod hosts. We screened 16 gastropod species from 14 communities on the island of O'ahu, Hawai'i, USA, to characterize the distribution of A. cantonensis among species and across host size. Prevalence (proportion of the population infected) and infection intensity (density of worms in host tissue) varied among gastropod species. Prevalence also varied with gastropod host size, but this relationship differed among host species. Most host species showed a positive increase in the probability of infection with host size, suggesting that within species relatively larger hosts had higher prevalence. The density of worms in an infected snail was unrelated to host size. These results suggest that variation in A. cantonensis infection is associated with demographic structure and composition of gastropod communities, which could underlie heterogeneity in the risk of human angiostrongyliasis across landscapes.

Freshwater snail feeding: lubrication-based particle collection on the water surface.

The means by which aquatic animals such as freshwater snails collect food particles distributed on the water surface are of great interest for understanding life at the air-water interface. The apple snail Pomacea canaliculata stabilizes itself just below the air-water interface and manipulates its foot such that it forms a cone-shaped funnel into which an inhalant current is generated, thereby drawing food particles into the funnel to be ingested. We measured the velocity of this feeding current and tracked the trajectories of food particles around and on the snail. Our experiments indicated that the particles were collected via the free surface flow generated by the snail's undulating foot. The findings were interpreted using a simple model based on lubrication theory, which considered several plausible mechanisms depending on the relative importance of hydrostatic pressure, capillary action and rhythmic surface undulation.

Annotated catalogue of species of Angiostrongylus and the related genera Gallegostrongylus, Rodentocaulus and Stefanskostrongylus (Nematoda: Metastrongyloidea, Angiostrongylidae).

This catalogue is concerned with the closely related angiostrongylid genera Angiostrongylus, Gallegostrongylus, Rodentocaulus and Stefanskostrongylus. Three species, Angiostrongylus cantonensis, A. costaricensis and A. vasorum, have attracted most attention because of their importance in human and domestic animal disease. Many of the remaining species are poorly known and the number of valid taxa is unclear. The catalogue lists all nomenclaturally available and unavailable genus-group and species-group names that have been applied to the above genera and the species included in them, indicating their current nomenclatural status and providing the rigorous nomenclatural basis for future work. The catalogue lists 14 published and nomenclaturally available genus-group names, with the above four treated as valid, the other ten being junior synonyms. There are 42 published species-group names: 36 are valid, two are junior synonyms, four are nomenclaturally unavailable. One additional species, described in Chabaudistrongylus (synonym of Angiostrongylus), is listed as incertae sedis in Angiostrongylidae. Also listed are two unpublished collection names. The catalogue provides bibliographic details for all published names, and for available names provides locations of type material, details of type localities, geographic distributions and details of type and other hosts, both definitive and intermediate, to the extent known. The catalogue is a work of nomenclature, not a revisionary taxonomic work. No new names or new combinations are proposed. The apparently new family-group synonymy of Cardionematinae with Angiostrongylidae is introduced, as are four genus-group synonymies, three with Angiostrongylus and one with Stefaskostrongylus.

Signatures of Divergence, Invasiveness, and Terrestrialization Revealed by Four Apple Snail Genomes.

The family Ampullariidae includes both aquatic and amphibious apple snails. They are an emerging model for evolutionary studies due to the high diversity, ancient history, and wide geographical distribution. Insight into drivers of ampullariid evolution is hampered, however, by the lack of genomic resources. Here, we report the genomes of four ampullariids spanning the Old World (Lanistes nyassanus) and New World (Pomacea canaliculata, P. maculata, and Marisa cornuarietis) clades. The ampullariid genomes have conserved ancient bilaterial karyotype features and a novel Hox gene cluster rearrangement, making them valuable in comparative genomic studies. They have expanded gene families related to environmental sensing and cellulose digestion, which may have facilitated some ampullarids to become notorious invasive pests. In the amphibious Pomacea, novel acquisition of an egg neurotoxin and a protein for making the calcareous eggshell may have been key adaptations enabling their transition from underwater to terrestrial egg deposition.

Modelling the distribution in Hawaii of Angiostrongylus cantonensis (rat lungworm) in its gastropod hosts.

Angiostrongylus cantonensis (rat lungworm), a parasitic nematode, is expanding its distribution. Human infection, known as angiostrongyliasis, may manifest as eosinophilic meningitis, an emerging infectious disease. The range and incidence of this disease are expanding throughout the tropics and subtropics. Recently, the Hawaiian Islands have experienced an increase in reported cases. This study addresses factors affecting the parasite's distribution and projects its potential future distribution, using Hawaii as a model for its global expansion. Specimens of 37 snail species from the Hawaiian Islands were screened for the parasite using PCR. It was present on five of the six largest islands. The data were used to generate habitat suitability models for A. cantonensis, based on temperature and precipitation, to predict its potential further spread within the archipelago. The best current climate model predicted suitable habitat on all islands, with greater suitability in regions with higher precipitation and temperatures. Projections under climate change (to 2100) indicated increased suitability in regions with estimated increased precipitation and temperatures, suitable habitat occurring increasingly at higher elevations. Analogously, climate change could facilitate the spread of A. cantonensis from its current tropical/subtropical range into more temperate regions of the world, as is beginning to be seen in the continental USA.

Invisible apple snail invasions: importance of continued vigilance and rigorous taxonomic assessments.

BACKGROUND: Due to the similarities of overall shell morphology among apple snail species and considerable variability within species, substantial taxonomic confusion has plagued the accurate identification of Pomacea species. Many invasive apple snails have been mistakenly identified as P. canaliculata since their introduction to Asia around 1980. In 2008, three other introduced species in addition to P. canaliculata were recognized. In 2013, a fifth, previously unrecognized lineage was reported from China, indicating that despite the taxonomic clarity brought by previous work, continued surveys and taxonomic research are necessary to prevent additional introductions and continued spread, as well as to develop effective management strategies. RESULTS: Phylogenetic analysis of mitochondrial COI sequences confirmed the presence of a widespread unidentified Pomacea lineage in China. All sequences from samples of this newly documented lineage were recovered in a monophyletic clade delineated from closely related species; however, different DNA barcoding methods yielded inconsistent species boundaries. Additionally, nuclear EF1α sequences indicated incomplete lineage sorting or recent hybridization of the unidentified lineage with the other two established species. CONCLUSION: Barcoding is a valuable tool for species discovery, and a powerful approach for delineating introduced species. However, determining the identity of the newly discovered invasive lineage in China will require an integrated taxonomic approach incorporating individuals from the native range, and examination of natural history collections at museums around the world. To manage and prevent additional spread of already established species, and to stop the introduction of new taxa, continued monitoring and rigorous taxonomic assessments must be undertaken. © 2018 Society of Chemical Industry.

Correction: Diverse Gastropod Hosts of Angiostrongylus cantonensis, the Rat Lungworm, Globally and with a Focus on the Hawaiian Islands.

[This corrects the article DOI: 10.1371/journal.pone.0094969.].

Angiostrongylus cantonensis: Agent of a Sometimes Fatal Globally Emerging Infectious Disease (Rat Lungworm Disease).

Angiostrongylus cantonensis, the rat lungworm, is a dangerous invasive species that is the agent of a potentially fatal globally emerging infectious disease. Humans are infected most commonly by ingestion, deliberately or inadvertently, of the parasite larvae in their intermediate snail hosts. The larvae make their way to the brain where they can cause severe neurological damage before eventually dying. Symptoms of the disease are diverse, making it difficult to diagnose. Treatment is primarily with corticosteroids to reduce inflammation, while treatment with anthelmintics to kill the worms remains controversial. There have been almost 3000 cases globally, the majority in southern China, but the parasite is spreading and now occurs much more widely. In the USA, almost all cases have been in Hawaii, but the parasite is also present in southeastern states. As the climate warms, this tropical/subtropical parasite is likely to spread further.

Findings on Thoracic Computed Tomography Scans and Respiratory Outcomes in Persons with and without Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

BACKGROUND: Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population. METHODS: We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up. RESULTS: About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0). CONCLUSIONS: Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function.

Undiagnosed Chronic Obstructive Pulmonary Disease Contributes to the Burden of Health Care Use. Data from the CanCOLD Study.

RATIONALE: Chronic obstructive pulmonary disease (COPD) remains undiagnosed in many individuals with persistent airflow limitation. These individuals may be susceptible to exacerbation-like respiratory events that consume health care resources. OBJECTIVES: To compare exacerbation-like respiratory events, event prevalence, and differences in the odds of using medication and/or health services between subjects with diagnosed and undiagnosed COPD. METHODS: Subjects sampled from the general population participating in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study, with at least 12 months of exacerbation-event follow-up who were classified as having physician-diagnosed or undiagnosed COPD were assessed. Exacerbation-like respiratory events were captured using a questionnaire administered every 3 months. MEASUREMENTS AND MAIN RESULTS: A total of 355 subjects were undiagnosed and 150 were diagnosed with COPD. Undiagnosed subjects were less symptomatic and functionally impaired, had been prescribed fewer respiratory medications, and had better health status. The incidence of reported exacerbation-like events was higher in diagnosed subjects and increased in both groups with the severity of airflow obstruction. Although subjects with diagnosed COPD were more often prescribed medication for exacerbation events, health service use for exacerbation events was similar in both groups. CONCLUSIONS: Most subjects with COPD in Canada remain undiagnosed. These subjects are less symptomatic and impaired, which may partly explain lack of diagnosis. Although patients with undiagnosed COPD experience fewer exacerbations than those with diagnosed COPD, they use a similar amount of health services for exacerbation events; thus, the overall health system burden of exacerbations in those with undiagnosed COPD is considerable.

Long-term Follow-up of Mycobacterium avium Complex Lung Disease in Patients Treated With Regimens Including Clofazimine and/or Rifampin.

BACKGROUND: Mycobacterium avium complex (MAC) lung disease requires prolonged treatment with multiple antibiotics. Drug intolerances and interactions are common with the current recommended treatment. There is limited information on outcomes with alternative medications. METHODS: Retrospective review including adult patients with MAC lung disease who were treated and monitored for at least 6 months posttreatment. The aim was to evaluate the clinical and microbiologic outcomes in patients treated with regimens including clofazimine and/or rifampin. RESULTS: One hundred and seven patients were included (79% were female; mean age, 67 years). Sputum samples were smear positive in 54% of patients. The majority (84%) were treated with clofazimine in combination with a macrolide and ethambutol. Fourteen patients (13%) were treated with rifampin, macrolide, and ethambutol. Most patients (95%) converted from positive to negative sputum culture results in an average of 4.5 ± 4.2 months (range, 0-30 months). A significantly greater proportion of patients treated with clofazimine converted to negative culture results compared with those treated with rifampin (100% vs 71%; P = .0002). Microbiologic relapse occurred in 52 of 107 patients (49%). Thirty-six percent of patients required retreatment. There was no difference in microbiologic relapse or re-treatment rates between the two treatment groups. CONCLUSIONS: The majority of patients with MAC lung disease achieve negative sputum culture results. Re-treatment is needed in approximately one-third of patients. In this cohort, both initial outcomes and re-treatment rates were at least as good in patients treated with clofazimine-containing regimens as in patients receiving rifampin-containing regimens. Clofazimine should be considered as an alternative drug for the treatment of MAC lung disease.