Research digest: Diagnosing and managing tuberculosis in immunocompromised children

11th September 2024

A new study has shown children and adolescents with immunocompromise who contract tuberculosis (TB) experience increased rates of non-respiratory TB and more severe forms of the disease, leading to a higher incidence of associated long-term health complications.

The study also revealed that standard immune-based TB detection tests are not accurate in immunocompromised children and therefore the researchers highlight a need to design prevention and management plans for these children who contract TB to minimise later health issues.

The researchers conducted a retrospective, multicentre, case-control study within the Pediatric Tuberculosis Network (pTBnet) European Trials Group. All participants were aged under 18 and had been treated for or diagnosed with TB at a European centre between 2000 and 2020.

Of the 417 TB cases included, 139 were immunocompromised, including those with human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions. A control group of 278 non-immunocompromised patients with TB was also included. All data was sourced from the pTBnet database.

Increased rates of non-respiratory TB were found in immunocompromised children compared to controls (32.4% vs 21.2%), and these patients had an increased likelihood of presenting with severe disease (57.6% vs 38.5%).

These children also had significantly higher rates of false-negative tuberculin skin test (31.9% vs 6.0%) and QuantiFERON-TB Gold assay (30.0% vs 7.3%) results at diagnosis. However, the microbiological confirmation rate was similar in immunocompromised and control cases (58.3% vs 49.3%).

Overall, the mortality rate of immunocompromised children was low (<1%), but the rate of long-term health complications resulting from the TB infection was significantly higher in immunocompromised children versus children in the control group (14.8% vs 6.1%).

To improve the long-term health outcomes and decrease the severity of the infection for immunocompromised children, the researchers suggest that future studies focus on better immune-based tests to diagnose TB in these children effectively.

In addition, the researchers emphasise the need for a better understanding of why immunocompromised children have an increased rate of associated long-term health so these children can be better managed at diagnosis and prevention strategies can be put in place to improve outcomes.

Reference
Rodríguez-Molino, P et al. Tuberculosis Disease in Immunocompromised Children and Adolescents: A Pediatric Tuberculosis Network European Trials Group Multicenter Case-control Study. Clinical Infectious Diseases 2024; Jul 15: doi.org/10.1093/cid/ciae158.

Seroconversion rates low after COVID-19 vaccination among immunocompromised

18th March 2022

Seroconversion rates among immunocompromised patients are low after the first COVID-19 vaccine dose but increase upon receipt of the second

Seroconversion rates after a single COVID-19 vaccination among immunocompromised patients is low but improves after a second dose according to the findings of a systematic review and meta-analysis by researchers from the Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Immunocompromised patients are at an increased risk severe COVID-19 illness and death. Moreover, it is recognised that among immunocompromised, solid organ transplant patients, a wide range of respiratory viruses cause significant morbidity and mortality among transplant recipients.

In a 2020 review of COVID-19 in cancer patients, it was noted how those with cancer are susceptible to severe clinically adverse events and a higher mortality from COVID-19 infection as well as morbidity and mortality from their underlying malignancy.

Although one 2018 systematic review found that  seroconversion and sero-protection rates for influenza antigens were low in solid organ transplant recipients, no such reviews on the immunogenicity of COVID-19 vaccines and the overall seroconversion rates among cohorts of immunocompromised patients and been undertaken.

For the present study, the Singaporean team compared the seroconversion rates among groups of immunocompromised patients compared to immunocompetent controls. The team searched for studies that included patients with active cancer of solid organs, haematological cancers, organ transplant recipients, those with active immune mediated inflammatory disorders and for which a comparator group was included.

The primary outcomes of interest were seroconversion after the first and second COVID-19 vaccine doses.

Seroconversion rates after vaccination

A total of 82 studies were included in the meta-analysis.

Among those with haematological cancers, compared to immunocompetent individuals, the seroconversion rate after the first vaccination was less than half (risk ratio, RR = 0.40, 95% CI 0.32 – 0.50) and similar for those with solid cancers (RR = 0.55, 95% CI 0.46 – 0.65) and immune mediated inflammatory disorders (RR = 0.53, 95% CI 0.39 – 0.71). However, it was significantly lower for organ transplant patients (RR = 0.06, 95% CI 0.04 – 0.09).

After the second vaccination, the rates of seroconversion increased. For example, for haematological cancers (RR = 0.63) and among those with solid cancer (RR = 0.90) and whilst higher, remained very low, among organ transplant patients (RR = 0.39).

The authors did not include studies where a third COVID-19 dose had been administered in the meta-analysis because most studies did not include a comparator for control purposes. Nevertheless, based solely on a systematic review, they found that conversion rates for organ transplant patients improved by 36 and 66.7%.

The authors concluded that administration of a third vaccine dose (which has now become standard practice for everyone) is warranted for immunocompromised patients.

Citation
Lee ARYB et al. Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis BMJ 2022