Globally, tuberculosis (TB) is a major public health problem and remains one of the world’s deadliest communicable diseases. The World Health Organization (WHO) launched the “End TB Strategy” aimed at reducing TB incidence by 90% and mortality by 95% by 2030 (Uplekar et al., 2015). Each year, nearly 6 million people are diagnosed with pulmonary tuberculosis (PTB), of whom about 55% have their diagnosis confirmed with laboratory testing (World Health Organization, 2020). The recent WHO global TB report 2020 ranked Nigeria as the first in Africa and sixth globally among the 30 high TB burden countries, with a TB incidence of 219/100,000 population and 120,266 cases notified. Nigeria is on the list of 14 countries with the triple burden of TB, HIV-associated TB, and multidrug-resistant (MDR) TB with a population incidence of MDR-TB of 11/100,000 (World Health Organization, 2020).

Tuberculosis patients face various challenges such as physical restrictions, psychological and emotional issues, and economic and social problems. These known challenges impact on the quality of life of the patients (Hansel et al., 2004; Guo et al., 2009). Clinically, the therapeutic modalities, the side effects of the drugs, and the sequelae of the disease also impact on the quality of life (QoL) of the patients (Hansel et al., 2004; Muniyandi et al., 2007). PTB also results in residual anatomical and functional changes, despite microbiological cure (Pasipanodya et al., 2007). These changes are associated with post-TB lung disease (Pasipanodya et al., 2007). PTB patients often have pulmonary cavities, which can become colonized and infected by inhaled Aspergillus spores resulting in chronic pulmonary aspergillosis (CPA) (Denning et al., 2018). Other structural sequelae include fibrosis, chronic obstructive pulmonary disease (COPD) (Denning et al., 2018), and bronchiectasis, as well as sensitization to Aspergillus (IgE response), itself linked to worse lung function, independently of CPA (Dhooria et al., 2014). Worsening clinical status can be assumed to be MDR-TB.

TB services and clinical research in Nigeria have focused on the outcomes of mortality and microbiologic cure and have neglected the preferences of the patient, such as the quality of life of the patient, a crucial component of outcome. Health-related quality of life (HRQoL) involves assessing the perceptions of a person of his or her physical and mental health. Both physical and mental distress are common in TB patients leading to decreased compliance with medical care (Liefooghe et al., 1995; Rajeswari et al., 1999). The impact of PTB on HRQoL has been reported in a systematic literature review (Kastien-Hilka et al., 2016). This systematic review found that PTB had a negative impact on the HRQoL and overall wellbeing of the patients, even after PTB cure.

Quality of life assessment tools can be used in both high resource settings and in LMICs. Despite the availability of these standard instruments for assessing health-related quality of life, the feasibility, reliability, and validity of such instruments among TB patients in different populations of sub-Saharan Africa, where the burden of TB is of concern, are still limited.

This longitudinal study aimed to evaluate patient-reported HRQoL in pulmonary TB in Lagos, Nigeria, using two QoL assessment tools, namely, the generic WHOQOL-Bref (The WHOQOL Group, 1998; Skevington et al., 2004) and the specific St. George’s Respiratory Questionnaire (SGRQ) (American Thoracic Society (ATS); Welling et al., 2015). The study sought to identify persons with post-TB lung disease following “microbiological cure” 6 months post-therapy and understand the overall impact of TB on the QoL and important domains of qualities of life identified by the WHO.

The WHO ascertains that patient involvement in their healthcare is a social, economic, and technical necessity (Guo et al., 2009; Kastien-Hilka et al., 2016). Disease-specific health status questionnaires have proven their ability to discriminate between different levels of disease severity (Hays et al., 1995; Kastien-Hilka et al., 2016). However, generic measures like the WHOQOL-Bref (Skevington et al., 2004) are designed to be completed by patients with almost any disease or condition and may be designed to be completed by healthy people, too. Such generic instruments provide a systematic way to usefully compare patient and proxy assessments of QoL and health status across different organ systems and geographies. They also provide information beyond those obtained from clinical and microbiological parameters. Patient experience is assessed using a patient-reported outcome measure (PRO). PROs for CPA have included SGRQ, but this can only be compared among other lung diseases, not other conditions, and is poorly validated in countries with English as a second or third language.

In this study, we observed that most participants were ill at enrollment, with the lowest WHOQO-Bref and the highest SGRQ scores. Scores improved in relation to the length of TB therapy in the different QoL domains, with the highest at 12 months. Moreover, most respondents at 3 months had good perceptions of their overall QoL and general health. However, during this same period, a significant number of respondents were found to have positive Aspergillus IgG ( Figure 1 ). Overall QoL and general health demonstrated the highest elevation of scores from baseline to 6 months. This most likely reflects the known efficacy of anti-TB therapy and the compliance of the patients.

Research studies using the HRQoL among patients treated for TB in Africa are few (Adeyeye et al., 2014), and to our knowledge, none has been longitudinal. Furthermore, this study is the first to investigate both TB and Aspergillus IgG levels and CPA and its effect on HRQoL. Studies like these are urgently needed (Brown et al., 2015) to better manage these large populations.

The finding of progressive improvement in QoL due to anti-TB therapy accords with the findings from similar studies that used the WHOQOL-Bref, for <12 months (Dhuria et al., 2009; Balgude and Sontakke, 2012; Aggarwal et al., 2013; Aggarwal, 2019). This was also the trend in other studies that did not use the WHOQOL-Bref (Babikako et al., 2010; Kruijshaar et al., 2010; Atif et al., 2014). All these studies revealed a gradual increase in scores and improved QoL, as treatment progressed.

Some societal factors that could influence QoL were assessed in our study. Domain scores were generally better among men, urban residents, younger patients, and those with higher socioeconomic status, less severe disease, higher education, better social security, or close family support (Duyan et al., 2005; Babikako et al., 2010; Adeyeye et al., 2014). Independent predictors of low quality of life scores included depression, illiteracy, self-stigma, low monthly income, duration of illness, concomitant illnesses, unemployment, advancing age, no family support, and sociodemographic and other economic factors (Duyan et al., 2005; Adeyeye et al., 2014). Although some of our findings are comparable to other studies, the impact of gender is not clear. We recruited more men, and being male has been associated with good domain scores (Adeyeye et al., 2014; Brown et al., 2015), although not universally (Hays et al., 1995). As expected, treatment with antituberculosis drugs improves the HRQoL of patients (Deribew et al., 2009). From a programmatic perspective, it is important to ensure adherence to medications and avoid treatment default.

In our study, the 12-month means of physical and psychological QoL in this study were lower than the means at the 9-month visit. This finding was previously reported in a study by Mamani et al. in 2014 (Mamani et al., 2014) and may be attributed to a recurrence of symptoms. If so, these symptoms could be due to the re-emergence of TB or the presence of aspergillosis; this is further supported by CXR reports ( Figures 2B, C ). Alternatively, it could represent co-infection of TB and aspergillosis, bronchiectasis, or Aspergillus bronchitis complicating bronchiectasis. Further studies involving fungal culture and chest imaging would be helpful to measure the prevalence of pulmonary aspergillosis complicating tuberculosis among this cohort.

There was, however, a significant difference (p < 0.05) between respondents with positive and negative Aspergillus IgG at 6 months of assessment, in all the domains of the WHOQOL-Bref. This could result from the continuous presence of symptoms, as reported by a previous longitudinal study of CPA (Bongomin et al., 2018). A Ugandan study has reported that Aspergillus-specific IgG antibodies were elevated in 4% of HIV-infected adults at the start of TB treatment and in 9% at the end (Kwizera et al., 2017). This is likely due to colonization and either the development of CPA, a reflection of Aspergillus co-infection that needs to be resolved, or Aspergillus bronchitis complicating bronchiectasis among TB patients. Given the slow genesis of CPA, longitudinal follow-up and CT scanning are required, but our radiological data appear to supports this hypothesis ( Figure 2 ). Reduced pulmonary function persists in patients cured of TB (Pasipanodya et al., 2007).

A drop in the number of respondents with each visit was observed in this study. Reasons include transfers of patients to sites closer to home, treatment default, death, and hospitalization. Other studies have reported that the dropout at the second and third follow-up visits was mostly among younger patients with no physical impairment as well as among male patients and due to poverty, severe psychological distress, or alcohol misuse (Louw et al., 2012; Atif et al., 2014; Olufemi et al., 2018). It is important to note that the treatment of TB was completed for these patients at 6 months. Thus, the need to return to the clinic may have not been vital to them visiting the facility again, as they may have achieved a complete cure to the disease. Also with improved QoL, there is a higher likelihood that treatment default may be high due to reduced motivation to improve it.

Some limitations of the study were the continuous drop in respondent numbers at 9 and 12 months, which may have had some impact on the results. A defined cutoff for Aspergillus IgG levels has not been established for Africans, although the European-derived cutoff (Wilopo et al., 2020) performs well in Vietnam (Nguyen et al., 2021). CT scan, which is a better representative imaging tool, was not used due to cost, and its inclusion would have allowed confirmation of the diagnosis of CPA. Also, patients underwent HIV testing when diagnosed with TB before starting treatment. HIV testing was not repeated during the treatment and any change in HIV status was therefore unknown. The severity of PTB was not accessed since it was not the focus of the study.

In conclusion, different domains of HRQoL can be a helpful tool for the assessment of the patient and outcome prediction. HRQoL is hindered in patients with PTB and improves significantly with program-based treatment. HRQoL-based disease appraisals in resource-limited countries have become an important instrument to grasp health outcomes and provide focused and empirically informed ways to manage care and treatment better. Aspergillus IgG levels were significantly raised in patients being managed for PTB, probably reflecting colonization by Aspergillus or early CPA, which alters treatment outcomes among TB patients. Routine screening of Aspergillus IgG at the DOTS facility would assist with improving the QoL of patients who may have been misdiagnosed as having PTB. Further follow-up studies and additional imaging, preferably CT scan, are required to determine when these patients develop CPA and its clinical impact.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Human Research Ethics Committee (HREC), Lagos University Teaching Hospital, Lagos, Nigeria; HREC, National Institute of Medical Research, Lagos, Nigeria; and HREC, The University of Manchester. The patients/participants provided their written informed consent to participate in this study.

RO, SS, and DD conceptualized and designed the study. RO, TG, and NI collated the data. RO, SS, and DD analyzed and interpreted the data. All authors contributed to the writing and review of the manuscript.

This work was supported with funds from University Hospital South Manchester Charity Trust (Grant award number: TREG 006).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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