Antimicrobial and antibiotic drug resistance: Causes and more
Key Risk Factors Influencing Mortality Rates In Chronic Pulmonary Aspergillosis Patients
Older age, specific disease subtypes, and underlying conditions like malignancy identified as major contributors to higher mortality risks
Study: Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis. Image Credit: Kateryna Kon/Shutterstock.ComRecently, scientists have systemically reviewed the available literature and conducted a meta-analysis to explore the reasons for high mortality rates associated with CPA despite the availability of antifungal treatments. This review is available in Lancet Infectious Diseases.
What is CPA?CPA includes multiple lung diseases, such as chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA), caused by ubiquitous fungi of the genus Aspergillus. Individuals with modest immunocompromised conditions often develop subacute invasive pulmonary aspergillosis (SAIA). CPA has a slower disease course with high morbidity compared with pulmonary aspergillosis.
People with diabetes, tuberculosis, or low-dose systemic corticosteroid dependence are susceptible to CPA. A recent study revealed the possibility of an increase in CPA mortality by 20% in India. The annual incidence of CPA has been estimated to be 1.8 million cases with 3,04,000 deaths. In tuberculosis-endemic countries, CPAs are often misdiagnosed as sputum-negative pulmonary tuberculosis, which could be attributed to their increased prevalence cases and mortality rates.
Previous studies have documented significant variability in CPA mortality based on nomenclature, demographic background, region of publication, underlying pulmonary comorbidities, different management protocols, and the inequity of access to health care, among other factors. There is an urgent need to understand different aspects associated with CPA mortality to support clinical decisions for proper disease management that could effectively reduce mortality rates.
About the studyThe current study conducted a systematic review and meta-analysis to evaluate the factors that influence CPA mortality rates and other aspects of the disease. All relevant CPA-related articles, including clinical studies, controlled trials, observational studies, and abstracts, were obtained from MEDLINE (PubMed), Scopus, Embase, and Web of Science databases from inception to August 15, 2023. However, animal studies, case reports, literature reviews, letters, and news articles were excluded.
Subgroup analyses were conducted to analyze the overall heterogeneity in 1-year and 5-year CPA mortality, and random-effects meta-analyses were conducted to estimate pooled mortality rates.
Study findingsThis systematic review screened 1,452 citations, including 64 studies from 21 countries published between 1974 and 2023. The types of studies considered in this review included cross-sectional, case series, randomized controlled trials, cohort studies, and retrospective studies.
The sample size of the studies ranged between 10 and 1,705, which included a total of 8,778 CPA patients. The mean age of the patients ranged between 30 years and 79.1 years. The younger patients belonged to the WHO African region, and the older ones were from the Western Pacific region. Interestingly, the majority of CPA patients were identified as male.
In comparison to Europe, a greater prevalence of post-tuberculosis lung disease has been documented in South-East Asia. However, chronic obstructive pulmonary disease (COPD) was found to be highest in European cohorts, followed by Western Pacific cohorts. A higher number of non-tuberculous mycobacterial lung disease cases has been reported from the Western Pacific region.
Among CPA patients, the most common underlying lung disease in the Southeast Asian and Western Pacific cohorts was post-tuberculosis lung disease, while COPD prevailed in European cohorts. A small number of studies reported the incidence of CPA subtypes, including CCPA (common), aspergilloma, SAIA, and CFPA (rare).
The cohort of individual patient data (IPD) included 1859 patients from the UK, Japan, and France. This cohort had a male dominance, with the mean age being 61.4 years. This cohort comprised CPA subtypes, including CCPA and SAIA. The median duration of follow-up was 616 days, which exhibited a 30% mortality rate in the cohort.
In the IPD cohort, a total of 676 patients were diagnosed with tuberculosis, whose mean age was 35.7 years. The majority of these patients had at least one underlying comorbidity. Diabetes, chronic corticosteroid use, radiotherapy, HIV infection, and chronic alcoholism were found to be the risk factors for patients with SAIA. Pulmonary tuberculosis, followed by COPD, was found to be a predisposing condition that leads to increased mortality rates in patients with CPA.
Although the majority of the IPD cohort received only oral or oral and intravenous antifungal agents, few received surgical interventions. In terms of antifungal agents, itraconazole was the most frequently used first-line treatment, followed by voriconazole.
Random-effects meta-analysis indicated 15% and 32% for 1-year and 5-year mortality, respectively. The incidence rate of mortality, estimated from 47 studies, was 104.5 deaths per 1000 person-years. The multivariable analysis indicated low mortality rates in patients who underwent surgical resection.
ConclusionsThe current systematic review and meta-analysis revealed that CPA is associated with substantial mortality. CPA subtype, age, and underlying comorbidities were identified as the main factors that increased CPA mortality rates. Considering the study findings, novel treatment strategies tailored to different risk groups are needed, which could positively alleviate CPA mortality rates.
India TB: Can Vaccines Help India Triumph Over Tuberculosis?
Every two minutes one person dies of the disease in India, according to the WHO
In 2018, India set for itself the lofty goal of eliminating pulmonary tuberculosis (TB) by 2025 - five years ahead of the deadline set by the UN's Sustainable Development Goals.
In March 2023, Prime Minister Narendra Modi reiterated this commitment at the One World TB Summit, held in the northern city of Varanasi.
But the World Health Organization's (WHO's) Global Tuberculosis Report paints a different picture - every two minutes, one person dies of the disease in India.
According to the report, India accounted for the highest global TB burden, with 27% of the 10.6 million people diagnosed with the disease in 2022. The country is also home to 47% of people who developed multi-drug resistant infection which is unresponsive or resistant to at least two of the first line of anti-TB drugs the same year.
While experts say testing and treatment remain the best-known ways to tackle the disease, India has also invested in trying to find an effective TB vaccine - since 2019, scientists have been testing two vaccines in seven research centres.
But TB vaccines are not that easy to develop.
"We don't know what exactly we want the vaccine to do. Until we have a fundamental understanding of how humans do or do not resist the tubercle bacillus [TB bacteria], it is difficult to engineer a vaccine that capitalises on that knowledge," says Dr Marcel A Behr, director of infectious diseases division at Canada's McGill University Health Centre.
Which means that so far, there is no clarity on whether a TB vaccine should induce antibodies, antigen-specific T-cells (combative cells generated by specific bacteria parts) or boost innate immunity.
Dr Behr adds that the quest for a vaccine has also been hampered because the test for TB cannot distinguish between a current and past infection - the current test merely tells us that a person was infected with the bacteria and not whether the infection is ongoing or healed.
"Following people forward in time to learn who clears their infection and who does not is difficult when your test cannot distinguish between these outcomes," Dr Behr adds.
Several patients face stigma associated with tuberculosis
But scientists at the government-backed Indian Council of Medical Research (ICMR) have been doing exactly this - observing household contacts of TB patients for four years to determine whether they have developed TB - living with the infected increases the risk of getting the disease. If all goes well, the results of the trial will be out by March, ICMR researchers told the BBC.
The ICMR has been testing a recombinant BCG vaccine candidate named VPM1002 and a heat-killed suspension mycobacterium vaccine named Immuvac.
To put it simply, the first vaccine has the modified DNA of TB bacteria and the second is TB bacteria that have been killed by heat. If they prove effective, they could stimulate an immune response against TB.
The trial has three groups - two have been given one dose of each of the vaccines, while the third has received a placebo. But the participants - 12,000 people above the age of six years - don't know which treatment they have received.
"The vaccine efficacy study aims to reduce the incidence of TB among household contacts," says Dr Banu Rekha, who is leading the trial at ICMR's National Institute for Research in Tuberculosis, Chennai.
Some experts, such as Dr Behr, think the trial may have gone on too long. In a high transmission setting in which several people have active or latent TB, a successful vaccine "should demonstrate efficacy" in one to two years, he says.
There are other challenges too.
For a TB vaccine to be effective, first it should work, and secondly, shots will have to be administered to almost all of India's population.
"Millions in India live with latent TB," says Chapal Mehra, a public health specialist. Latent TB patients are infected with the disease but do not have any symptoms.
India has set a goal to eliminate TB by 2025
Experts also point out that a 17-year-long BCG vaccine trial held between 1968 and 1987 - involving more than 280,000 people in Tamil Nadu state - ended with disappointing results.
"BCG did not offer any protection against adult form of bacillary pulmonary TB," according to a 1999 report on the trial.
There cannot be a one-stop solution for TB, experts say, because it is a "complicated disease" that has social, economic and behavioural contributory factors.
"Why is TB often called a poor person's disease? A poor person who can only afford poor housing and bad nutrition is more susceptible to contracting TB. To eliminate TB, the disease and its contributory factors have to be understood holistically," Mr Mehra says.
India has a comprehensive DOTS (Directly Observed Treatment, Short-course) programme recommended by the WHO under which people detected with TB can get treated for free in government health facilities.
But public hospitals are stretched and sometimes ineffective, forcing tens of thousands of TB patients to turn to private health providers.
There are other challenges - in 2020 and 2021, the federal government gave 20bn rupees ($240m; £189m) to 7.5 million TB patients for treatment through a direct benefit transfer programme. But experts say the monthly figure per patient is too small to make a meaningful impact.
Nutrition experts also say that providing good nutrition to the contacts of those with TB significantly reduces the incidence of the disease. In a recent study published by Lancet, Madhavi Bhargava and Anurag Bhargava wrote that good nutrition reduced all forms of TB by 40% and infectious TB by 50% in contacts of patients they observed over six months.
"An effective TB vaccine is critical in decreasing the TB burden. But it would be desirable to see vaccination and nutritional improvements as complementary interventions," said Dr Madhavi Bhargava, a public health specialist,
Ideally, Dr Behr says, the world needs a three-pronged TB elimination system - which includes optimised testing and treatment, maximised nutrition and a vaccine which "not only prevents the disease but also blocks transmission".
Tuberculosis facts
BBC News India is now on YouTube. Click here to subscribe and watch our documentaries, explainers and features.
Read more India stories from the BBC:
Comments
Post a Comment