Tuberculosis (TB) is one of deadliest infectious diseases in history. The World Health Organization reports that it not only devastates patients and their families but also negatively impacts a country’s economy and social life [1] [2] . In 2021, approximately 10.6 million new TB cases were diagnosed, and 1.6 million people died from the disease [3] .

TB mortality and incidence remain high due to increasing drug resistance. Antimicrobial resistance has made TB one of the leading causes of death [4] . Tuberculosis drug resistance includes resistance to effective first-line drugs (Rifampicin and Isoniazid), as well as fluoroquinolone resistance. Treating drug-resistant TB (DRTB) is more challenging because effective first-line drugs cannot be used [2] . Globally, DRTB has worsened treatment outcomes and accounted for 47% of national TB programs’ budgets, significantly straining national health systems [5] .

Mozambique is among the 30 high-burden countries that account for 90 percent of all tuberculosis (TB) cases worldwide. The World Health Organization (WHO) reports that Mozambique has a TB incidence rate of 361 per 100,000 people. In 2021, there were approximately 450,000 cases of drug-resistant TB (DRTB) globally, marking a 3.1% increase from the 437,000 cases reported in 2020. Mozambique’s TB, TB/HIV, and DRTB burdens are among the highest globally, with 98,000 TB cases reported in 2021, including 3.7% DRTB cases [3] . The treatment success rate improved from 40% in 2017 to 72% in 2021, yet it still falls short of the WHO’s 90% target [3] [6] [7] .

New diagnostic platforms and treatment regimens have significantly advanced the detection and treatment of drug-resistant tuberculosis (DRTB) worldwide. Since 2013, Mozambique has employed molecular tests (Xpert^® MTB/RIF) as the initial tests in its tuberculosis program. By 2018, there were 109 machines across the country. This expansion increased announcements of drug-resistant cases [8] . As of 2019, Mozambique implemented oral regimens for DRTB treatment to reduce adverse effects on patients and improve adherence to treatment [9] .

Based on current guidelines, Mozambique recommends a 20-month oral regimen for drug-resistant tuberculosis (DR TB), consisting of a 6-month intensive phase and a 14-month maintenance phase. Patients are primarily treated in outpatient clinics. During the intensive phase, the regimen includes five oral medications: Linezolid (Lzd) for one month, and Bedaquiline (Bdq), Levofloxacin (Lfx), Clofazimine (Cfz), and Cicloserine (Cs) for six months. For the maintenance phase, patients continue with Levofloxacin (Lfx), Clofazimine (Cfz), and Cicloserine (Cs). Delamanid (DLM) may be added for patients meeting specific criteria, such as resistance to fluoroquinolones. To prevent neuropathy side effects from DR TB treatment, vitamin B6 (pyridoxine) is administered concurrently. Primary health care centers in Mozambique manage and report TB cases [10] .

The WHO notes that these new TB treatment regimens are more expensive than previous injectable ones [1] . To combat TB globally, an annual $13 billion is needed, yet only $5.4 billion was secured in 2021, a decrease from $6.0 billion in 2019 [3] . In 2020, Mozambique’s national TB program received $26,225,047 in funding, with 12% from domestic sources and 88% from external sources such as the Global Fund and USAID. Over half of these funds were allocated to treatment [1] [9] .

An analysis of the direct costs associated with drug-resistant tuberculosis (DRTB) treatment in low and middle-income countries (LMICs) for regimens lasting 18 - 24 months was conducted. Direct costs included drugs, hospital stays, outpatient clinic visits, laboratory tests, program supervision, and side effect management. The study found that DRTB treatment costs ranged from $2423 to $14,657 per patient, with an average cost of $13,259 per patient under the outpatient model [11] . A randomized controlled trial in Ethiopia and South Africa compared the costs of long-term (20 to 22 months) and short-term (9 to 11 months) DRTB treatment regimens. Using both bottom-up and top-down approaches to calculate health system costs, it was determined that the long regimen was significantly more expensive than the short regimen: $6096.6 versus $4552.3 in Ethiopia and $8340.7 versus $6618.0 in South Africa [12] .

Low-resource countries like Mozambique struggle to access drug-resistant TB (DRTB) treatments due to high costs. Treatment for DRTB patients is significantly more expensive than for those with drug-sensitive TB [13] [14] . Mozambique’s national TB program, Programa Nacional de Controlo da Tuberculose (PNCT), provides free screening, diagnosis, and treatment for TB. However, a resource-constrained health system such as Mozambique’s could be further burdened by DRTB. To our knowledge, Mozambique does not collect data on the direct medical costs of DRTB treatment.

The Ministry of Health in Mozambique covers all direct costs (health staff salaries, medications, etc.) [15] [16] related to the treatment of DRTB (with the support of cooperation partners). The public health sector offers these services free of charge [10] . Activities related to the tuberculosis program are integrated with those of the national health system, and the direct costs for all programs are combined. Estimating non-medical costs of TB services, such as administrative expenses, physical facilities, and utilities, is often challenging. However, direct medical costs, including drugs, consultations, laboratory tests, and diagnostic devices, are easier to calculate. Thus, this study aims to estimate the average direct medical cost of TB treatment in 19 health centers in Maputo, Mozambique.

This study, focusing on an accounting cost analysis of drug-resistant tuberculosis (DRTB) treatment per patient, will help Mozambique’s national TB program optimize the use of limited resources. Establishing the essential financial requirements for DRTB treatment, including medication, consultations, and diagnostics costs, is crucial for adequate funding. Understanding these accounting costs can lead to more efficient financial planning and optimization, ensuring consistent and reliable funding for drug-resistant TB programs. Additionally, knowledge of the accounting costs of DRTB treatment enables beneficiaries and the public to understand how public funds are allocated in national TB programs.

Based on an analysis of 140 records, the intensive phase treatment cost per patient was estimated at $2276.74, totaling $318743.60 for all 140 patients undergoing DRTB treatment. This cost represents 50% of all direct medical costs associated with DRTB treatment in the study.

In the study, the total cost of medical interventions and medications for DRTB treatment was approximately $4789.43 per patient. This amount equates to 35.55 months of minimum wages, given that Mozambique’s minimum wage for public servants is $134.74 per month [18] . Approximately $670778.45 was covered by state funds, equivalent to 4978.32 months of minimum wages in Mozambique.

In Mozambique, the Global Fund is the primary financier of tuberculosis (TB) programs, disbursing $167,437,586 in 2019 to fight HIV/AIDS, TB/HIV co-infection, TB, and malaria. Of this, only 5.4% ($9,092,885) was allocated to TB, Table 7. Total direct medical costs incurred in diagnosing and treating DRTB per patient.

while 57.8% ($96,786,444) and 35.8% ($50,895,945) were dedicated to HIV and malaria, respectively [19] . In the same year, Mozambique reported 1398 cases of DRTB [9] . Considering the direct medical costs per patient, a significant portion of the TB budget, over 50%, would be required to cover basic treatment costs for DRTB, leaving minimal funds for other critical activities such as patient support, prevention, and community engagement, essential for TB control.

These findings align with Lange et al. (2014), who argue that the high cost of DRTB treatment can be prohibitive for some national TB programs. They suggest that, in theory, the costs of treating DRTB cases could surpass the total healthcare budgets of developing countries [20] . It is crucial to explore innovative financing methods for DRTB treatment, including alternative funding sources and increasing access to generic medicines. Cost reduction could be achieved through strategies such as early detection and diagnosis in the community, ensuring patient and healthcare provider adherence to treatment protocols, and advocating for lower prices for DRTB medications in resource-limited settings.

In resource-limited settings, challenges such as limited access to affordable diagnostics and drugs, insufficient healthcare infrastructure and expertise, and restricted resources for patient monitoring and support exacerbate the costs of treating drug-resistant tuberculosis (DRTB). These challenges hinder effective treatment and prevention, leading to increased transmission and poorer health outcomes for affected individuals and communities [21] [22] . Therefore, it is crucial to emphasize the importance of strengthening health systems and building capacity in these settings to effectively address DRTB treatment costs. Investing in training healthcare workers, improving laboratory infrastructure, and implementing robust surveillance systems can enhance the ability to diagnose, treat, and prevent DRTB more efficiently and sustainably. Applying such holistic approaches is essential to improving health outcomes for individuals and communities affected by DRTB. Future research could explore the cost-effectiveness of various financing strategies for DRTB treatment, such as social health insurance schemes or public-private partnerships.

While this study represents an important initial step in generating cost evidence for DRTB treatment in Mozambique, it has limitations. The study is constrained by the absence of comprehensive cost data for all components of DR-TB treatment, leading to potential underestimation or overestimation of direct medical costs. Moreover, it only accounts for direct healthcare expenditures, omitting indirect costs such as productivity losses and patient transportation expenses, thus rendering the economic burden assessment of DR-TB incomplete.

The severity of illness, presence of comorbidities, and response to treatment vary among patient populations. Our study did not account for this heterogeneity, limiting our understanding of cost variation. We only captured direct medical costs during a specific period, without considering long-term costs associated with relapses, treatment failures, or post-treatment monitoring. Since healthcare infrastructure, drug pricing, and patient demographics vary by region, our results cannot be generalized to other countries or regions. Additionally, our cost estimations may be affected by inflation over the year 2019, which was not considered in our analysis.

In Mozambique, the direct medical cost of a basic drug-resistant tuberculosis (DRTB) treatment package per patient is equivalent to about 36 months of minimum wages, significantly burdening the limited available tuberculosis resources. It is crucial to identify alternative and innovative funding sources for DRTB treatment and reduce costs by increasing access to generic medicines.

The authors would like to thank all staff and patients of the health facilities that participated in the study. The authors would like to thank all staff of the National TB Control Programme of Mozambique.

All datasets and materials of the study are available from corresponding author upon reasonable request.

• Conceptualization: Júlia Malache António, Pereira Zindoga, Simeão Nhabinde.

• Methodology: Júlia Malache António, Pereira Zindoga, Simeão Nhabinde.

• Investigation: Júlia Malache António, Pereira Zindoga, Isaías Benzana.

• Project administration, resources, supervision: Benedita José.

• Data curation: Júlia Malache António, Isaías Benzana.

• Formal analysis: Júlia Malache António, Pereira Zindoga, Simeão Nhabinde, Isaías Benzana.

• Validation and visualization: Júlia Malache António, Isaías Benzana.

• Writing original draft: Júlia Malache António, Isaías Benzana, Isabelle Munyangaju.

• Writing review & editing: Júlia Malache António, Isabelle Munyangaju, Dulce Osório, Edy Nacarapa, Benedita José, Simeão Nhabinde, Pereira Zindoga.

All authors read and approved the final version of the manuscript.

The authors have no conflict of interest to declare.

António, J.M., Benzana, I., Munyangaju, I., José, B., Osório, D., Nacarapa, E., Mutaquiha, C., Nhabinde, S. and Zindoga, P. (2024) An Analysis of the Accounting Costs Associated with 20- Month DR TB Regimens in Maputo City, Mozambique. Journal of Tuberculosis Research, 12, 73-90. https://doi.org/10.4236/jtr.2024.122005

Patient Clinical Record Data Collection Instrument

I) Identification

Health Facility: ___________________________________________________

Sex F ( ) M ( ) Age:_____ (in years)

Occupation: _____________________________________________________

Residential address: _______________________________________________

II) Follow-up at the Health Unit

III) Case Closure

( ) Cure ( ) Treatment completion ( ) Date: _____________________________

Researcher: ________________________