Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study

Mhimbira, Francis; Hiza, Hellen; Mbuba, Emmanuel; Hella, Jerry; Kamwela, Lujeko; Sasamalo, Mohamed; Ticlla, Monica R.; Said, Khadija; Mhalu, Grace; Chiryamkubi, Magreth; Schindler, Christian; Reither, Klaus; Gagneux, Sébastien; Fenner, Lukas

doi:10.1016/j.cmi.2018.03.019

Cited by 13 publications

(18 citation statements)

References 22 publications

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“…An excess mortality associated with influenza has been described among TB patients in South Africa [107]. TB patients have a similar prevalence of viral and bacterial co-infection as their household contacts but TB patients often have more severe disease if they are co-infected [108].…”

Section: Tb and Influenzamentioning

confidence: 99%

Epidemic and pandemic viral infections: impact on tuberculosis and the lung

et al. 2020

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Major epidemics including some that qualify as pandemics, such as Severe Acute Respiratory Syndrome (SARS), Middle-Eastern Respiratory Syndrome (MERS), Human Immunodeficiency Virus, pandemic H1N1/09 and most recently COVID-19 affect the lung. Tuberculosis (TB) remains the top infectious disease killer but apart from the TB-HIV syndemic, little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of the viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN) and members of ESCMID Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors, excluding the ECDC PHE team identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology, immunology of these viral infections and their interactions with TB are discussed with implications on diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

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Section: Tb and Influenzamentioning

confidence: 99%

Epidemic and pandemic viral infections: impact on tuberculosis and the lung

et al. 2020

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“…The literature on non-influenza respiratory viral co-infection and TB is very limited. An Tanzanian study reported no difference in the frequency of observed influenza and non-influenza respiratory viral infections in adults with and without pulmonary TB (138). A South African study comparing children with “definite,” “unconfirmed,” and “unlikely TB” found no clear association between TB categorization and detection of specific respiratory pathogens (139).…”

Section: Respiratory Virusesmentioning

confidence: 99%

“…On the other hand, a Tanzanian study which compared smear positive adult TB patients and household contact uninfected controls, found that respiratory bacteria were less frequently detected in the nasopharyngeal swabs of TB patients compared to controls. TB disease severity was higher only in those in whom both viruses and bacteria were detected (138). Evidence from vaccination studies is also mixed as described below.…”

Section: Respiratory Bacteriamentioning

confidence: 99%

Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children

et al. 2019

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Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis . Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis . We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.

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“…Before initiation of TB treatment, biological specimens (sputum, naso-pharyngeal swabs, blood, urine, and stool) were collected for further investigation of anemia and co-infections, as previously described (Mhimbira et al, 2017 , 2019 ; Hella et al, 2018 ). Investigated co-infections included HIV (Mhimbira et al, 2017 ; Hella et al, 2018 ), helminths (Mhimbira et al, 2017 ), and respiratory pathogens (Mhimbira et al, 2019 ). For HIV-positive patients, CD4+ T cell counts were also obtained (Mhimbira et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

“…Following the World Health Organization/International Union Against Tuberculosis and Lung Disease (WHO/IUATLD) guidelines, sputum AFB smear results were expressed as quantitative categories (“Scanty,” “1+,” “2+,” and “3+”) that grade the number of AFB per number of microscopic fields (Mhimbira et al, 2017 ). As previously described (Mhimbira et al, 2019 ), we defined sputum mycobacterial burden as high if AFB smear results were “2+” (1–10 AFB per field, 50 fields) or “3+” (> 10 AFB per field, 20 fields); and as low if AFB smear results were “Scanty” (1–9 AFB in 100 fields) or “1+” (10–99 AFB in 100 fields).…”

Section: Methodsmentioning

confidence: 99%

The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study

et al. 2021

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Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity. Microbial communities residing in the host's airways have immunomodulatory effects, but it is unclear if the inter-individual variability of these microbial communities is associated with the heterogeneity of pulmonary TB. Here, we investigated this possibility by characterizing the microbial composition in the sputum of 334 TB patients from Tanzania, and by assessing its association with three aspects of disease manifestations: sputum mycobacterial load, severe clinical findings, and chest x-ray (CXR) findings. Compositional data analysis of taxonomic profiles based on 16S-rRNA gene amplicon sequencing and on whole metagenome shotgun sequencing, and graph-based inference of microbial associations revealed that the airway microbiome of TB patients was shaped by inverse relationships between Streptococcus and two anaerobes: Selenomonas and Fusobacterium. Specifically, the strength of these microbial associations was negatively correlated with Faith's phylogenetic diversity (PD) and with the accumulation of transient genera. Furthermore, low body mass index (BMI) determined the association between abnormal CXRs and community diversity and composition. These associations were mediated by increased abundance of Selenomonas and Fusobacterium, relative to the abundance of Streptococcus, in underweight patients with lung parenchymal infiltrates and in comparison to those with normal chest x-rays. And last, the detection of herpesviruses and anelloviruses in sputum microbial assemblage was linked to co-infection with HIV. Given the anaerobic metabolism of Selenomonas and Fusobacterium, and the hypoxic environment of lung infiltrates, our results suggest that in underweight TB patients, lung tissue remodeling toward anaerobic conditions favors the growth of Selenomonas and Fusobacterium at the expense of Streptococcus. These new insights into the interplay among particular members of the airway microbiome, BMI, and lung parenchymal lesions in TB patients, add a new dimension to the long-known association between low BMI and pulmonary TB. Our results also drive attention to the airways virome in the context of HIV-TB coinfection.

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Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study

Abstract: Respiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co-infected with both bacteria and viruses.

Cited by 13 publications

References 22 publications

Epidemic and pandemic viral infections: impact on tuberculosis and the lung

Epidemic and pandemic viral infections: impact on tuberculosis and the lung

Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children

The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study

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