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Assessment of Household Catastrophic Total Cost of Tuberculosis and Its Determinants in Cairo: Prospective Cohort Study

Background One goal of the End tuberculosis (TB) Strategy is to see no TB-affected households experiencing catastrophic costs. Therefore, it is crucial for TB-elimination programs to identify catastrophic costs and their main drivers in order to establish appropriate health and social measures. This study aimed to measure the percent of catastrophic costs experienced by Egyptian TB patients and to identify its determinants. Methods We conducted a prospective cohort study with 151 Egyptian TB patients recruited from two chest dispensaries from the Cairo governate from May 2019 to May 2020. We used a validated World Health Organization TB patient-cost tool to collect data on patients’ demographic information, household income, and direct and indirect expense of seeking TB treatment. We considered catastrophic TB costs to be total costs exceeding 20% of the household’s annual income. Results Of the patients, 33% experienced catastrophic costs. The highest proportion of the total came in the pretreatment stage. Being the main breadwinner, experiencing job loss, selling property, and the occurrence of early coronavirus disease 2019 lockdown were independent determinants of the incidence of catastrophic costs. Borrowing money and selling property were the most-often reported coping strategies adopted. Conclusion Despite the availability of free TB care under the Egyptian National TB Program, nearly a third of the TB patients incurred catastrophic costs. Job loss and being the main breadwinner were among the significant predictors of catastrophic costs. Social protection mechanisms, including cash assistance and insurance coverage, are necessary to achieve the goal of the End TB Strategy.


Introduction
Tuberculosis (TB) is an infectious disease of major importance public health, and it is among the top 10 causes of death globally, with 95% of its burden reported in low and middleincome countries 1 . In addition to health-related burden (e.g., morbidity and mortality), TB poses significant economic burden for patients, their households, and to the society. TB patients suffer from a substantial financial load in the form of direct out-of-pocket expenses for medical and nonmedical costs, incurred during seeking care 1 . In addition, each year, a TB patient loses an average of 3 to 4 months of work and up to 30% of household earnings 2, 3 . One target of the End TB Strategy is that by 2030, no TB patient or household should face catastrophic costs due to TB 3, 4 .
While there is no specific international metric to define catastrophic costs, TB-related direct and indirect income and out-of-pocket expenses exceeding 20% or more of the patient's annual household income have widely been accepted as a threshold to classify TB patients experiencing catastrophic costs 5 . In 2016, the WHO adopted a definition that demarcates the threshold for catastrophic costs as 20% or more of a household's total annual income in out-of-pocket and lost income costs due to TB 6, 7 . Globally, it is estimated that TB patients and their households may experience catastrophic costs for health that range from 27% to 71% 8, 9 . Catastrophic costs reflect the economic burden of TB and barriers that negatively influence accessing care for TB patients.
The magnitude of the costs and the coping strategies adopted by patients' families in response can be a significant burden. This creates an adherence barrier to diagnostic procedures and treatment, resulting in poor outcomes and financial suffering 4, 10 .
In Egypt, the National TB Control Program began to offer free TB-DOTS program to TB patients in the public sector from 2003 11, 12 . However, there currently are no social protection services for TB patients that help patients cope with out-of-pocket and indirect costs during their treatment 12, 13 . Currently, there is insufficient evidence available regarding catastrophic costs experienced by Egyptian TB patients. To reduce access and adherence barriers and minimize the economic burden for TB-affected patients and their households, it is crucial that TB elimination programs identify the main cost drivers, monitor financial hardship, and identify what further health and social policy measures should be taken 4, 7, 13 .
To the best of our knowledge, programmatic data on the catastrophic costs incurred by Egyptian TB patients are not routinely collected, and few published studies are available on this topic. Due to the importance of the topic and its novelty in Egypt, this study measured the incidence of catastrophic cost by TB patients in different phases of the treatment and identified its determinants among a sample of Egyptian patients.

Study setting and participants:
The study was conducted at two chest dispensaries located in the Cairo governorate. These dispensaries provide TB treatment for the main bulk of TB patients in Cairo. They do not serve sharply distinct patient populations (both serve patients with similar socioeconomic statuses living in the capital). The study was conducted from May 2019 to May 2020. Inclusion criteria included all newly diagnosed TB patients attending the studied dispensaries and aged 18 years or more, with the exclusion of any TB patient who was more than 1 month into their TB treatment (for better recording of cost data in the pre-diagnostic period and more timely following the patients beginning from the start of their DOTS), non-Egyptian TB patients (as most of them are refugees who receive substantial financial support from the United Nations monthly) and multi-drug resistant TB cases (as they require a much more intensive treatment regimen that proceeds for a longer duration). All patients who met the inclusion criteria were enrolled consecutively by the researcher visited the chest dispensaries 3 days per week until the required sample size had been reached at each site.
Data collection was done by interviewing eligible TB patients four times (at the start of DOTS, after 2 months, after 4 months, and at the end of DOTS).
The sample size was calculated based on an assumed incidence of catastrophic costs of 32% 10 with an 8% precision (25% of the expected incidence) to estimate a 95% confidence interval ranging between 24-40%. A figure for catastrophic costs incidence from India was used to predict optimal sample size, as there are no available data regarding catastrophic costs in Egypt and because India's socioeconomic standard is close to that of Egypt, both being lower-middle-income countries with similar rankings by the World Bank. An interim analysis conducted 3 months after the beginning of the study showed a rate close to the expected one.
The expected number of new cases in the selected centers used for the calculation of sample size was 1875 (from the official list of the NTP year 2019). Following these assumptions, a sample size of 123 patients was sought. To account for participants becoming lost to follow-up during the study, we inflated our sample size by 20% to reach a final target sample size of 154 patients. This sample size was sufficient for studying the determinants of the incidence of catastrophic TB costs, as we assumed a 20% difference in the incidence of such costs at an α level of 0.05 and a power of 80%. The sample was calculated using open Epi program version 7.

Data collection tools:
A standard interview questionnaire was adopted from WHO 4 , with four sections, collecting the following information: socio-demographic characteristics; income-related data; time loss and total cost during the pre-diagnosis period; time loss, total cost, and coping strategies during and after TB treatment. The data were collected from the patients or their relatives. The same questionnaire was used during at each of the four interviews (at the start of treatment, after 2 months, after 4 months, and at the end of the treatment). The costs incurred for every 2 months of treatment were calculated from the equation (total cost -any donations or vouchers received)/total family income during this period. Annual income is calculated as the sum of the amount of money received by the household in the year before the TB episode began, in exchange for labor or services, from the sale of property, as a profit from financial investments, or in the form of welfare payments 15 . The total cost during the period of DOTS was calculated from the sum of total medical costs, total travel costs, total food costs, total accommodation costs, and total income lost. If the total costs exceeded 20% of the total annual household's pre-TB income, the cost was considered a catastrophic cost and was measured from the equation: total cost/annual family income × 100.

Definition of study variables:
1-Catastrophic costs due to TB: Total costs (indirect and direct combined) exceeding a given threshold of the household's annual income, here defined as exceeding the 20%, as recommended by WHO 4 .

2-Direct costs:
Out-of-pocket payment for medical TB care (diagnostic tests, treatments, and follow-up tests) and non-medical costs (transportation, accommodation, and food/nutritional supplement costs) 4, 13 .

3-Indirect costs of seeking TB treatment:
The productivity and economic costs of a patient or household incurred because of TB health care seeking and hospitalization during the TB episode. These are estimated using two methods: a) self-reported household income loss net of welfare payments and b) total period of absence (in hours) multiplied by hourly wage rate of the absent worker 4, 13 .

4-Poverty status:
Those falling into the first quintile of household income per month are considered poor (i.e., ≤950 Egyptian Pounds [EGP] per month). In this study, we used the international poverty line of $1.9 a day (57 US$ per month) to compare the results with other studies that classify patients according to poverty status 13 . At the beginning of the study, 1 US$ = 16 EGP at the starting time of conducting the study; accordingly, the 57 US$ = 946 EGP. The lowest quintile of the household monthly income of the study sample was 950 EGP, so we used 950 EGP per month as a cutoff point for the classification of the study subjects according to poverty status.

Statistical analysis:
The data were analyzed using SPSS statistical software version 24.0 for PC (IBM). The data were tested for normality using the K-S test. Quantitative data were described as means ± standard deviations for normal data and as medians and inter-quartile range (IQRs) for nonnormal data. Categorical data were presented as numbers and percentages. Costs were described as median and IQRs in per-patient costs in US$ using the mean UN Exchange rate for the US$ in 2019 (1 US$ = 16 EGP). The proportion of households that experienced catastrophic costs was calculated, and a binary response model was used to determine the factors most significantly associated with catastrophic costs, using χ 2 test with two-tailed p < 0.05 considered the threshold for statistical significance. Multivariate logistic regression using the enter method was used to identify differences in the model's fitness. The model used independent variables with p < 0.2 to enter the model i.e., gender, residency, crowding index, breadwinner, type of TB, loss of job, stop education, selling property, and COVID lockdown. Both the crude and adjusted ORs were calculated. The model predicted 82% of the responses correctly, and the value of Nagelkerke R 2 was 0.57.

Results
A total of 151 TB patients were contacted and gave consent to inclusion in the study, or 98% of the initial goal sample size of 154. Three cases were excluded due to failure to complete the interview. Table 1 presents the basic socio-demographic and economic characteristics of the patients. Their ages ranged from 18 to 76 years, with a mean age of 39 ± 15.7 years. More than half of the patients (60.3%) were males. Married patients represented 55.6% of the sample, and 42.4% of participants had completed secondary school or above. More than half of the patients had jobs (50.3%), and 56.3% were the main breadwinners of their families. The median number household size of the patients was 4 (with range of 1-11). The median number of rooms in the home rooms was three (with a range of two to five rooms). In 70% of the cases, the TB was pulmonary TB. The median (IQR) duration of for pre-treatment from initial care-seeking to being diagnosed for TB was 90 days (30-120). About two-thirds of participants (64.9%) began to receive their DOTS within 3 months of the start of symptoms. Table 2 that the median (IQR) of the total indirect cost equaled to 0.00 (0.0-281.3) US$, and represented 70.5% of the total cost, while the median (IQR) of the total direct cost was 48.06 (29.3-96.9) US$, representing 29.5% of the total cost. The highest median cost was for travel (21.25$), followed by the medical costs (17.5$), and the lowest median cost was for food (1.25$). As a percentage of total cost, medical costs had the highest share (11.6%), and food costs represented also lowest share (6.4%). In the pre-treatment phase, the median for the medical costs (15.63 US$) was higher than that of the travel cost (5.63 US$) or food cost (0.0$), and the percentages of the total cost showed the same trend. In the following three phases, both the median cost and the percentage for the travel cost were higher than those for medical and food costs. In general, the median of the total direct cost showed a decreasing trend through the following phases, ranging from 24.38 US$ in the pre-treatment phase to 2.5 US$ over the last 2 months. The table also shows that accommodation was not considered a burden among the study participants.

It is indicated in
All of the patients who answered the prompt regarding the negative impact of TB reported that their social and private life had been affected. Most participants had experienced psychological problems (92.8%). Almost half of patients had been socially excluded (51.1%).
Job loss was reported by about one-third of the patients (31.6%), while marital problems were reported by 15.1% of the patients. Four patients became divorced over the course of the study. To cope with the challenges, about two-thirds of the patients borrowed money (67.6%), and about 33% of the patients sold property (Table 3).
In all, 331% of the study participants and their households experienced catastrophic costs (50/151). The incidence of catastrophic cost among males (49.5%) was significantly higher than that among females (8.3%) (χ 2 = 27.6, p < 0.001). The incidence of those experiencing catastrophic costs in the older group was higher (34.8%) compared to only 31.8% among the younger age group but the difference was not statistically significant (χ 2 = 0.4, p = 0.527) ( Table 4). Table 4 shows also the main drivers of catastrophic cost among the patients' personal and demographic characteristics. Among them, there was a statistically significant association between gender (p < 0.001), type of breadwinner (p ≤ 0.001), crowdedness index (p = 0.031), and type of TB (p = 0.002), with the incidence of the catastrophic total cost. Loss of employment (p < 0.001) and selling property (p = 0.019) were also statistically associated with the incidence of the catastrophic total cost, as is clear from Cost subgroup analyses were also done for gender, type of tuberculosis, COVID-19 lockdown, and being the family breadwinner or other member (Supplement I).
Tables S1 and S5 show that the median total cost among females was not significantly higher than among males (mainly due to the significant difference between them in the median total direct cost), but at the same time, the median annual income was not significantly higher among females, which may compensate for the increase in total cost and explain why the percentage of the catastrophic total cost was higher among males than females, as shown in Table   4 of the study results.
The median total cost was higher among family members (182.19 US$) who were not breadwinners than among those who were (106.88 US$). This difference was nonsignificant (p = 0.054); but the median annual income, the denominator used for calculating the catastrophic total cost was higher among those who were not family members, neutralizing the effect of the higher cost which could also explain the higher percentage of the catastrophic total cost among nonbreadwinners (Tables S2 and S5).
The median total patient costs were non significantly decreased after COVID-19 lockdown (Tables S3 and S5). This decrease can be explained by the decrease in the patients' direct costs due to reduced care seeking after the lockdown period. However, the median annual income of post-COVID-19 TB patients was significantly lower as a result of the lockdown as well. This could help explain why the incidence of catastrophic cost increased in patients in the post-COVID-19 lockdown period.
Regarding the type of TB, the median of all the costs was non significantly higher among pulmonary TB patients than among extra-pulmonary patients (Tables S4 and S5).

Discussion
This prospective cohort study assessed major health problems in Egypt (TB). To our knowledge, there have been no previous studies on catastrophic TB costs in Egypt. A strength of this study is its longitudinal nature and data collection through interviews at four discrete time intervals over a 6-month DOTS treatment, allowing better and accurate collection of cost data with lower dependence on patients' recollection. It did not prove feasible to interview patients each time they came to receive their DOTS, so we reduced the data collection to four interviews to improve compliance and increase the response rate. We assessed the profile and catastrophic impact of TB care costs on the households of TB patients enrolled at two chest dispensaries in the Cairo governorate.
In total, 33.1% of households experienced catastrophic costs due to TB care. This finding agrees with the results of a systematic review in low-and middle-income countries that reported that 39% of the patients studied faced catastrophic costs 16 . It is also near to the range of findings of Asian studies conducted in India and Indonesia that have reported 32.4% and 36% of households, respectively, as having experienced catastrophic costs due to TB care 10, 13 . Similarly, studies conducted in South Africa, Kenya, and Peru found that 28%, 26.1%, and 39% of participants faced catastrophic costs, respectively 7, 8, 17 . However, our results do not match the incidence rates reported by studies conducted in other regions. For instances, it is lower than the rates reported in studies conducted in China (52.8%) 18 , in India (68%) 19 , in Vietnam (63%) 9 , in South Africa (55%) 20 , and in Ethiopia (53.6%) 12 . This disagreement may be due to the inclusion of TB patients with HIV in those works, whereas only pulmonary TB cases were reviewed here; the use of a 10% threshold for annual income to define catastrophic cost; or the use of nationwide data, as opposed to our local study. However, our results were much higher than those reported in the Kassa study in Benin, which found that 14.8% of TB patients experienced catastrophic costs 5 .
Another study conducted in Delhi reported that only 7% of TB patients faced catastrophic costs 21 .
This may be because those studies included children, and, unlike this study, they were conducted prior to the COVID-19 pandemic, which had economic effects on most people globally and added more costs faced by TB patients.
About half of the studied TB patients were employed (76/151); however, 57.9% (44/76) lost their employment during the illness period. This result is higher than that reported in a previous Indonesian study conducted in 2018 by Faudy et al., who found that (32%) of the patients lost their jobs while undergoing treatment for TB 13 . Another study performed in the Philippines (2020) indicated that about (46%) of participants lost employment 21 . These differences in job loss may relate to differences in the socioeconomic status and type of the job of the participants, as 25% of our study participants were working as street peddlers or doing informal paid work. In addition, 56.3% of our participants were the main breadwinner for their families. These two factors reflect the indirect economic burden of TB and how it may deprive a family of income throughout the duration of an illness. This also highlights how important it is for governments to develop and implement strategies that provide a source of income for families during the illnesses, especially when the patient is the only breadwinner in the household. There was a statistically significant association between the incidence of catastrophic cost and certain personal, medical, and social characteristics, such the male gender, breadwinner, crowded household, pulmonary type of TB type, job loss, undergoing early COVID-19 lockdown, and sale of property. These factors and others were reported by other studies conducted in various countries 7,24,25 . This reflects that providing only free coverage of the anti-tuberculosis treatment to a patient is insufficient to alleviate the catastrophic costs faced by patients and that identifying the independent determinants of catastrophic cost is crucial for tailoring prevention and control policies.
All of our patients reported that their social and private lives were negatively affected, and most of them experienced psychological problems and social exclusion. This matches the results of many previous studies, which in which more than half of participants report that TB profoundly affected their social lives and well-being 8,22,25 . For the coping strategies adopted by the patients, our study revealed that about two-thirds of the patients borrowed money while one-third sold a property. This result is in keeping with a study conducted in Uganda 22 that revealed that >50% of the patients adopted one coping mechanism, such as borrowing money or selling assets. It also fits comfortably with the Laokri et al. 25 , who reported that 37% of the patients borrowed money and 53% sold household assets, and with another study done by which revealed that 38% of TB patients reported borrowing money. However, our figures are much higher than those in two South African studies; Foster et al. 23 found that only 5% of patients sold assets, and Mudzengi et al. 20 , found that taking a loan was reported by only 8% of the patients. This may be explained by the fact that in South Africa, disability grants are provided to patients who are unable to work due to illness 23 .
Catastrophic costs constitute a substantial economic burden due to tuberculosis and negatively impact patients and their households. Thus, implementing comprehensive screening programs for early detection of TB patients and adding additional strategies to the National TB Control Program to not only freely cover the treatment but also to target the problem of indirect costs and loss of income will be crucial in the prevention and control of this problem.

Study limitations
First, this study did not incorporate the costs experienced by multi-drug-resistant TB patients, as they undergo a different treatment regimen, which extends beyond 6 months. Our study followed patients throughout a course of treatment that lasted for only 6 months. We also excluded TB patients with HIV, as its prevalence is low in Egypt (<0.1%) 14 . The effect of hospitalization was also excluded as it was not possible to include hospitalized patients. The omission of hospitalized patients likely led to an underestimation of the catastrophic costs experienced by TB patients. Second, the health system imposes pre-diagnostic delays, and the determinants of these were not analyzed in this study, as many TB patients are not covered by a health insurance system in Egypt, and the public health system is currently only in the initial stages of reform to achieve universal health coverage. This limitation likely led to an underestimation of TB care costs and the level of catastrophic costs borne by TB patients in this study. Third, our study began in the pre-COVID-19 era and ended after the lockdown that began in March 2020. Because of this lockdown, most of the Egyptian population lost income, although the medical costs of some, who were afraid of getting an infection if they came to the chest dispensaries to receive their treatment, were decreased. Thus, the fact of this lockdown could have increased catastrophic costs. Although the inclusion of both pre-and post-COVID-19 TB patients in our study likely distorted the results, but it may be a strength, as subgroup analysis provided important insights for future research on how COVID-19 and lockdown policies impacted TB patient costs. Fourth, using a convenience sample from two similar dispensaries to assess patient costs did not guarantee adequate representation of the entire population of TB sufferers in the Cairo governorate, thus limiting the generalizability of the study's findings.

Conclusions
Despite the provision of free TB care under the Egyptian National TB Program, nearly onethird of study participants incurred catastrophic costs, with an indirect cost greater than the direct one throughout the entire illness. Being the family breadwinner, experiencing job loss, selling property, and undergoing early COVID-19 lockdown were the most significant predictors of the catastrophic total cost.
Recommendation: Continuous nationwide monitoring of the incidence and determinants of catastrophic cost for a better definition of the TB patients' needs is recommended. The provision of cash grants and vouchers to TB patients to obtain necessary nutritional and medical supplements at a reduced price is required if the goal of the End TB Strategy is to be achieved. Other issues such as health system delays, MDR TB, and the effects of hospitalization require further study.

Conflicts of interest:
No potential conflict of interest relevant to this article was reported.

Acknowledgments:
The authors thank the NTP team for enabling this research work and providing support. We are also grateful to all of the participating patients for their cooperation.