Local,regional,and continental trends in tuberculosis mortality rates across the Americas at the beginning of the XXI century

Introduction

Tuberculosis (TB) is one of the most relevant infectious diseases worldwide. ¹ Indeed, only in 2022, roughly 10.6 million people attained TB, and 1.3 million deceased from it, with the majority of deaths occurring in resource-limited areas. ² Furthermore, TB presents a substantial economic burden. In case, some estimates suggest that its annual global economic cost, including direct and indirect expenses, exceeds US$20 billion. ²

Multidrug-resistant TB (MDR-TB) further aggravates this burden.^1,2 Its treatment costs on average 10 times more and lasts 2–4 times longer than for drug-susceptible TB, often with lower success rates. ² In 2022, there were 410,000 new cases of MDR-TB, yet only two in five patients accessed appropriate treatment. ²

In the American continent, TB mortality remains a critical and poorly explored issue.^3,4 In fact, many countries do not have up-to-date analyses of their mortality rates and trends. Moreover, regional comparisons are often scarce or even absent in the literature. ⁵ This knowledge gap hinders the design of context-specific strategies and obscures the full scope of the TB burden across diverse socio-political and health system landscapes.^3–5

In order to deal with this situation, the Pan American Health Organization (PAHO) has made strides in TB surveillance by consolidating mortality data from national sources. ⁶ However, such reports are typically presented as raw numbers without deeper temporal or comparative analyses, limiting their utility for guiding action. ⁶

Therefore, this study aims to evaluate the local, regional, and continental trends in TB mortality rates across the American continent between 2000 and 2019.

Materials and methods

Ours was a retrospective study with a population-based approach. All employed data in this study were derived from the PAHO public database, accessible at: https://www.paho.org/en.

Recognised as the oldest international public health agency, PAHO acts as the regional office for the World Health Organization (WHO) in the Americas. It plays a key role in health surveillance, disease prevention, and the evaluation of epidemiological indicators across the region, proposing actions to deal with the regional challenges.

Data were manually extracted from an archive published by PAHO on 15 January 2025. The author transferred them into Microsoft Excel^® spreadsheets, stratifying them by country, year of record, sex, and age-adjusted TB mortality rates per 100,000 population.

In order to avoid transcription errors, double data entry was performed for a random 10% sample of the dataset, and discrepancies were checked against the original source. Furthermore, data were cross-referred within national databases from the evaluated countries, as well as with the WHO and the Global Burden of Disease databases.

Only countries with complete annual data for the entire study period (2000–2019) were included in the analysis. Countries with incomplete information and/or missing data and/or even with inconsistencies observed between the evaluated databases were excluded. The descriptive analysis from the data was performed using the R software 4.4.3^®, and the temporal trends were fitted with Jointpoint software 5.4.0^®.

Temporal trends were calculated using a logarithmic regression model, using time and mortality rates as variables. This allowed obtaining annual percentage changes (APC), their 95% confidence intervals (CIs), and p-values, which, together, indicate the behavioural trend of TB mortality rates over the years. For statistically significant CIs (p < 0.05), a positive APC suggests an increasing trend, while a negative APC indicates a decreasing trend, where the absolute value of the APC indicates the magnitude of the observed trend; in parallel, a non-significant CI (p ≥ 0.05) suggests a stationary trend.

Results

Among the evaluated countries, Bolivia, Mexico, Nicaragua, Honduras, and Peru, as well as Central America, stood out for having recorded the highest TB mortality rates during the observed timeframe, as illustrated in Figures 1–3.

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Figure 1.

Heatmap showing the trends in age-adjusted mortality rates for tuberculosis across the American continent between 2000 and 2019 for both sexes.

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Figure 2.

Heatmap showing the trends in age-adjusted mortality rates for tuberculosis across the American continent between 2000 and 2019 for women.

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Figure 3.

Heatmap showing the trends in age-adjusted mortality rates for tuberculosis across the American continent between 2000 and 2019 for men.

From a regional perspective, all subregions of the Americas exhibited declining trends in TB mortality for most of the study period, albeit with varying intensities. Periods of statistical stability were observed between 2014 and 2019 in Central America and between 2007 and 2019 in North America for women; between 2013 and 2019 in South America and from 2007 to 2011 in North America, as well as from 2014 to 2019 across the continent for men; and between 2013 and 2019 in South America and 2005 to 2008 across the Americas for both sexes, as highlighted in Table 1.

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Table 1.

Temporal trends in tuberculosis age-adjusted mortality rates by 100,000 individuals across the American continent.

	Women		Men		Both sexes
	Segment	APC; 95% CI; p-value	Segment	APC; 95% CI; p-value	Segment	APC; 95% CI; p-value
South America	2000–2005	−4.18; −5.57 to −1.32; 0.02	2000–2013	−4.40; −5.67 to −4.06; <0.01	2000–2013	−4.57; −5.52 to −4.22; <0.01
	2008–2008	−8.21; −9.84 to −0.25; 0.04	2013–2019	−1.98; −3.48–2.49; 0.18	2013–2019	−1.82; −3.36–2.78; 0.20
	2008–2019	−2,81; −6.44 to −0.08; 0.02	–	–	–	–
Central America	2000–2014	−6.51; −9.24 to −5.94; <0.01	2000–2019	−6.39; −7.21 to −5.74; <0.01	2000–2019	−6.26; −6.98 to −5.69; <0.01
	2014–2019	−2.94; −5.98–5.24; 0.33	–	–	–	–
Insular America	2000–2019	−5.09; −5.65 to −4.61; <0.01	2000–2019	−5.28; −6.71 to −5.08; <0.01	2000–2019	−5.57; −6.26 to −4.98; <0.01
North America	2000–2007	−9.00; −14.74 to −7.19; <0.01	2000–2007	−8.19; −11.53 to −6.24; <0.01	2000–2006	−8.12; −12.60 to −6.67; <0.01
	2007–2019	−4.92; −6.19–1.03; 0.07	2007–2011	−1.25; −8.37–2.96; 0.54	2006–2019	−4.41; −5.25 to −2.78; 0.01
			2011–2019	−5.47; −13.00 to −3.88; <0.01
Overall	2000–2005	−4.66; −5.27 to −3.51; <0.01	2000–2014	−5.22; −7.07 to −4.85; <0.01	2000–2014	−5.25; −5.95 to −4.96; <0.01
	2005–2008	−8.23; −9.10 to −6.41; <0.01	2014–2019	−2.86; −4.77–2.57; 0.17	2014–2019	−2.71; −4.39–1.69; 0.14
	2008–2019	−3.70; −4.05 to −3.24; <0.01	––	–	–	–

For both sexes, in countries such as Bolivia, Brazil, Colombia, Costa Rica, El Salvador, Guatemala, Nicaragua, and the Dominican Republic, there have been consistently decreasing trends. Some countries, including Argentina, Belize, Canada, Chile, and the United States, displayed significant decreases initially, followed by periods of stabilisation. Honduras presented decreasing trends between 2000 and 2014, followed by an increase since then. Antigua, Barbuda, Jamaica, Saint Lucia, Guyana, Suriname, and Uruguay presented complex patterns with variable periods of increase, decline, and stability depending on the evaluated period.

For women, trends in Canada, Chile, Colombia, and Brazil maintained steady and significant decreases throughout the study's duration. In parallel, Mexico, Haiti, Ecuador, and Argentina showed early declines that gave way to stabilisation trends. Stable trends, without statistically significant changes, were observed across the full period in countries such as Barbados, Suriname, and Uruguay.

Honduras presented a concerning reversal: after a long period of decline from 2000 to 2014, it transitioned into a phase of statistically significant increase between 2014 and 2019. Antigua and Barbuda, Jamaica, Saint Lucia, and Guyana presented complex and oscillating trends.

For men, instances of stable or stationary trends were relatively less common but still noteworthy. Canada, Chile, Cuba, Ecuador, Haiti, Mexico, Peru, Suriname, Uruguay, and the United States all demonstrated at least one segment with non-significant change. In some of these cases, such as Canada and the United States, stability followed prior periods of significant decline. In parallel, across the majority of countries analysed, TB mortality rates exhibited a general tendency to decline over the study period. However, some countries, such as Barbados, St Lucia, and Jamaica, experienced either episodes of increase or periods of statistical stability, defining complex trends. Honduras presented a declining trend till 2013, followed by an increase till 2019.

Supplementary figures and supplementary tables provide the detailed trends observed for each evaluated country.

Discussion

The overall declining trends in TB mortality across the American continent reflect progress in disease control. However, the variability in the pace and the presence of some stabilisation or even increasing trends underscore persistent inequalities in health system performance and social determinants of health.

The concentration of high mortality rates in countries such as Bolivia, Mexico, Nicaragua, Honduras, and Peru suggests structural vulnerability. Conversely, the steady progress seen in countries such as Chile, Colombia, and Brazil probably reflects sustained investment in healthcare delivery, surveillance, and social protection. The erratic trends observed in several Caribbean nations may indicate fragile surveillance systems or inconsistent programme implementation. The stagnation observed in the latter part of the decade, especially among men and in Central and South America, points to a possible plateau effect: once the most accessible and treatable cases are addressed, remaining cases are often linked to harder-to-reach populations and complex barriers – including stigma, comorbidity, and health service fragmentation.

This regional heterogeneity mirrors global TB mortality trends. ⁷ In fact, high-income European countries have achieved most of the targets of the WHO End TB Strategy. Some Central and Eastern European countries have seen a 35% reduction in TB mortality by 2020. ⁷

However, sub-Saharan African nations, for instance, continue to carry a high burden of TB, exacerbated by widespread HIV co-infection, under-resourced healthcare systems, and poor social determinants. ⁸ In Eswatini, young women and individuals living with HIV remain disproportionately affected, revealing the limitations of aggregate statistics in concealing high-risk subgroups. ⁸

Focusing on the Americas, persistent inequality explains part of the observed results. Countries with chronic underfunding in health (e.g., Honduras and Nicaragua), fragile political contexts (e.g., Venezuela), or fragmented systems (e.g., the Dominican Republic) often saw interruptions or reversals in progress in controlling TB mortality.^9,10 Otherwise, migration patterns may also influence these trends, since populations in transit or displacement (e.g., Venezuelan migrants) face delayed diagnosis and treatment due to legal, economic, and infrastructural barriers. ⁹ Similarly, the urbanisation process that occurred in the American continent in the twentieth century could explain TB transmission hotspots due to overcrowding, pollution, and health service saturation in low-income urban settlements. ¹⁰

Sex differences in TB mortality are observed, with men tending to exhibit higher rates.^11,12 This aligns with global data and reflects multiple interacting mechanisms. For instance, men are more likely to work in high-exposure environments (e.g., mining, construction), delay seeking care, and present with advanced disease. ¹¹ Biologically, oestrogen exerts immunoprotective effects, enhancing Th1 responses and macrophage activation, whereas testosterone may suppress these responses. ¹²

HIV remains the most critical comorbidity influencing TB outcomes. Immunosuppression due to HIV accelerates TB progression, increases mortality risk, and complicates its treatment.^13,14 While Brazil and Peru have integrated TB-HIV care protocols, other countries still lack adequate testing and combined treatment strategies, especially for marginalised groups such as sex workers, men who have sex with men, and people who inject drugs. ¹³ Consequently, underdiagnosed or untreated HIV among TB patients may partially explain high mortality in certain areas. ¹⁴

It is important to acknowledge the role of data quality in shaping the apparent trends. Countries vary significantly in their capacity to record and report TB deaths reliably. ¹⁵ Weak vital registration systems, especially in rural or conflict-affected areas, may lead to underreporting. ¹⁵ Moreover, cause-of-death misclassification remains a concern, particularly in cases where TB is a secondary or contributing cause not captured on death certificates. ¹⁶ These issues may skew national mortality statistics, underestimating the true burden of disease in low-capacity settings and overestimating progress in others. ¹⁶

Findings from this study, however, offer clear guidance for policy development.^17,18 First, addressing health inequities, particularly access gaps for men, migrants, and people living with HIV, should be central to TB control strategies. ¹⁷ Strengthening primary health care systems and decentralising TB diagnosis and treatment services can enhance case detection and management, especially in rural and underserved urban regions.^17,18 The gendered nature of TB risk demands sex-sensitive interventions, including health education tailored to men's behavioural patterns and occupational exposures. ¹⁷

At the regional level, harmonising TB surveillance systems, standardising treatment protocols, and incorporating migration-sensitive health services are critical.^18,19 Investments in real-time digital surveillance, mobile clinics, and contact tracing tools can bridge the implementation gap. ²⁰ Furthermore, regional co-operation under PAHO's coordination can foster shared learning and efficient resource allocation. ¹⁹

Our study's strength includes the use of a robust international database (PAHO) and the application of standardised age-adjusted rates and Joinpoint regression for trend detection. However, its limitations are noteworthy. Being an ecological study, it cannot establish causality. Data extraction was manual, posing potential transcription risks. Most importantly, the completeness and accuracy of mortality data vary by country, and some countries were excluded owing to missing or inconsistent data. These limitations may have influenced trend interpretations and reduced the generalisability of findings.

Conclusions

Although TB mortality has declined across the Americas, persistent inequalities, biological vulnerabilities, and systemic limitations continue to threaten sustained progress. This calls for renewed commitment to address the social and structural determinants of health, alongside biomedical innovations. Future research should explore the intersection of neuro-immune and hormonal pathways in TB pathogenesis, as well as the role of policy implementation fidelity in diverse sociopolitical contexts. Regional cooperation, interdisciplinary strategies, and equitable health investment are essential to accelerate progress toward TB elimination and to ensure that no population is left behind.

Supplemental Material

Supplemental Material