Legionella has been confirmed as the cause of a cluster of pneumonia cases associated with a health clinic in the province of Tucuman, Argentina.
As of today, a total of 11 cases of pneumonia linked to this cluster have been reported, including 4 deaths in patients with comorbidities, with onset of symptoms between 18 and 25 August 2022.
Early Alarm Bells from Unknown Pneumonia
The detection of an initial cluster of bilateral pneumonia in six patients without etiological identification was reported by far Argentina health authorities to the Pan American Health Organization/World Health Organization (PAHO/WHO) on 30 August 2022. Three additional patients presenting similar symptoms were reported on 1 September. Two additional cases have since been reported.
This small cluster of unexplained acute severe respiratory illness set off early alarm bells in the wake of the COVID-19 pandemic experience. The samples were tested by the local public health laboratory for respiratory viruses, and other viral, bacterial and fungal agents, all tested negative.
Reference Laboratory Testing Results
Further testing was undertaken at the National Administration of Laboratories and Health Institutes (Administración Nacional de Laboratorios e Institutos de Salud – ANLIS per its acronym in Spanish), including toxicological analyses. As of 3 September 2022, negative results have been obtained for COVID-19 (RT-PCR), Influenza, detection of antibodies for Coxiella, urinary antigen for Legionella spp., panel of 12 respiratory viruses, hantavirus (Elisa IgM), histoplasma (RT-PCR), Yersinia pestis (PCR) and micro agglutination for leptospirosis.
Further analyses of two bronchoalveolar lavage samples by highly sensitive total DNA sequencing (metagenomics) found readings compatible with Legionella spp. On 3 September 2022, ANLIS reported that amplification products of the 16S ribosomal gene for Legionella spp. from the two samples of bronchoalveolar lavage sequenced by metagenomics and analyzed by four different bioinformatic methods, produced results compatible with Legionella pneumophila. Confirmation of these results is expected upon completion of the sequencing processes. This laboratory result supports evidence compatible with Legionnaires’ disease. Blood culture and seroconversion tests continue to be conducted to complement the diagnosis of Legionella infection.
Epidemiology of Legionellosis
Legionellosis is a generic term describing the pneumonic and non-pneumonic forms of infection with the Legionella species of bacteria. Legionellosis varies in severity from mild to serious and can sometimes be fatal, according to the W.H.O.
Legionnaires’ disease, the pneumonic form, has an incubation period of 2 to 10 days (but up to 16 days have been recorded in some outbreaks). It is an important cause of community- and hospital-acquired pneumonia; and although uncommon, Legionnaires may cause outbreaks of public health significance. Initially, symptoms are fever, mild cough, loss of appetite, headache, malaise and lethargy, with some patients also experiencing muscle pain, diarrhoea and confusion. The severity of Legionnaires’ disease ranges from a mild cough to rapidly fatal pneumonia. Untreated Legionnaires’ disease usually worsens during the first week.
Mortality from Legionnaires’ disease depends on the severity of the disease, the use of antibiotic treatment, the setting where Legionella was acquired, and whether the patient has underlying conditions, including immunosuppression. The death rate may be as high as 40–80% in untreated immunosuppressed patients and can be reduced to 5–30% through appropriate case management, depending on the severity of the clinical signs and symptoms. Overall, the death rate is usually between 5–10%.
Applying Appropriate Response Measures
Dr. Jake Dunning, Senior Research Fellow in Emerging and High Consequence Infections, Pandemic Sciences Institute, University of Oxford (commenting on the outbreak prior to laboratory results identifying the cause of the pneumonia cases) rightly noted that in spite of our collective reactionary impulse after the past few years of the pandemic, alarmism is not productive while awaiting standard epidemiological investigation results:
“The reported, currently small cluster of cases of unexplained acute severe respiratory illness in Tucuman, Argentina is a live event and investigations are ongoing; understandably there will be interest and speculation as to the cause, especially after everyone is twitchy after the pandemic events of the last two years, but we really need to await the outcome of the public health and clinical investigations, which are ongoing. It is possible that further cases may be identified and reported going forward, as that often occurs with these sorts of events, but that does not mean this event is the start of a new pandemic.”
“Some disconcerting features have been reported, however, which will cause concern to public health agencies in Argentina and to agencies in other countries, as well as the World Health Organization. These include the reported severity of illness in many of the known cases, sadly including some fatalities, the common epidemiological link of a single health centre, and the fact that healthcare workers make up a large proportion of the recently reported cases. This suggests, but in no way proves a common exposure source, and possibilities include exposure to a patient with an infection of unknown cause that was being cared for at a health facility, either with common exposure of multiple individuals to the same source, or initial exposure of one or two individuals and then secondary transmission between individuals. Of course, this is purely speculative on many levels and also assumes the severe lung disease described is actually caused by an infection and, if it is an infection, seemingly it is one that may be easily transmitted to several people within the same location. Other potential explanations include exposure to environmental agents and toxins, and the reports state this possibility is also being investigated, as one would expect.
“Although lists of all the pathogens tested for have not been made public (which is not unusual, as it’s a complicated, specialist process), available reports suggest that the clinicians have looked for and excluded many common respiratory pathogens that occur globally and are capable of causing severe acute respiratory infections, as well as some more unusual infections that occur in some parts of Argentina, including hantavirus infections and leptospirosis. It is reassuring to hear that rapid actions are being taken by the Argentinian Ministry of Health and provincial health authorities; I expect this includes using a range of diagnostic technologies to look for alternative, specific pathogens or families of pathogens when the ‘usual suspects’ are excluded through appropriate sampling and testing. This is in addition to detailed outbreak investigations and contact tracing by public health teams. Reports state that control measures are also being applied, despite the cause of the outbreak being unclear; this is sensible and typical for such an event, assuming it may be a transmissible infection and applying precautionary control measures on that basis.
“Argentina has lots of experience in investigating and managing outbreaks of severe acute respiratory illness, particularly those caused by infections (e.g. pandemic H1N1 influenza, COVID-19, Andes hantavirus infection), so hopefully this cluster will remain relatively small and the underlying cause will be identified quickly. Sharing information with WHO and with other countries, as Argentina is doing, shows commitment to Global Health Security and should be commended and supported. In England, the experts working in UKHSA’s Epidemic Intelligence team will be monitoring this event closely, as it does for multiple events occurring globally year-round, informing and updating relevant stakeholders and performing formal risk assessments if and when they are needed.”