ARTÍCULOS ORIGINALES

Multidrug-resistant pulmonary tuberculosis in Esmeraldas, Ecuador (2018–2022): prevalence and clinical–epidemiological profile from a retrospective observational study

Samuel Ibarra-Segura¹,², Jaime Angamarca-Iguago³, Kristell Coello-Zambrano2, Jaen Cagua-Ordoñez³, Raúl Pérez-Tasigchana³

¹ Master’s Program in Epidemiology with a Specialization in Clinical Research, Faculty of Health Sciences Eugenio Espejo, Universidad UTE, Quito, Ecuador. ² Delfina Torres de Concha Southern General Hospital, Esmeraldas, Ecuador. ³ Center for Public Health and Clinical Epidemiology Research, Faculty of Health Sciences Eugenio Espejo, Universidad UTE, Quito, Ecuador.

DOI: https://doi.org/10.16921/pfr.v10i2.364

PRÁCTICA FAMILIAR RURAL│Vol.10│No.2│Julio 2025│Recibido: 27/06/2025│Aprobado: 25/07/2025

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Abstract

Background: Multidrug-resistant tuberculosis (MDR-TB) remains a growing public health concern globally, particularly in settings with limited diagnostic capacity and high disease burden. In Ecuador, Esmeraldas province has reported a disproportionately high number of TB cases. However, local evidence on resistance patterns and patient characteristics is scarce.
Objective: To estimate the prevalence of MDR-TB and describe its epidemiological and clinical characteristics in the province of Esmeraldas, Ecuador, from 2018 to 2022.
Methods: A descriptive, cross-sectional study was conducted using secondary data from Ecuador's Ministry of Public Health. Confirmed pulmonary TB cases with positive culture or GeneXpert results were analyzed. MDR-TB prevalence rates were calculated, and patient characteristics were stratified by sex, age, district of residence, TB contact history, and drug resistance profile. Statistical analysis included univariate and bivariate procedures, with prevalence odds ratios (OR) and chi-square tests.
Results: Among 1,461 confirmed TB cases reported in Zone 1, 902 (61.7%) were from Esmeraldas. Of these, 49 (5.4%) were identified as MDR-TB. The mean annual MDR-TB prevalence in Esmeraldas was 1.7 cases per 100,000 population. The majority of MDR-TB patients were male (59.2%), aged 20–49 years (82%), and urban residents (79.6%). Rifampicin resistance was found in 91.8% of cases. Relapse cases showed a significantly higher odds of resistance (OR = 3.48). One case met the criteria for extensively drug-resistant TB (XDR-TB). Treatment outcomes were incomplete in 41% of cases; among reported outcomes, cure rate was 22.4%, and the case fatality rate was 10.2%.
Conclusions: MDR-TB remains a persistent threat in Esmeraldas, with relapse and urban residence as prominent risk markers. The detection of XDR-TB and treatment discontinuation rates highlight critical weaknesses in the TB control program. Targeted strategies to improve rapid diagnostics, follow-up, and data quality are urgently needed to contain the spread of resistance and achieve TB elimination goals in Ecuador.

Keywords: multidrug-resistant tuberculosis, drug resistance, pulmonary TB, epidemiology, Esmeraldas, Ecuador, XDR-TB, public health

Tuberculosis multirresistente, farmacorresistencia, TB pulmonar, epidemiología, Esmeraldas, Ecuador, TB-XDR, salud pública

Resumen

Antecedentes: La tuberculosis multirresistente (TB-MDR) sigue siendo un problema de salud pública creciente a nivel mundial, especialmente en entornos con capacidad diagnóstica limitada y una alta carga de enfermedad. En Ecuador, la provincia de Esmeraldas ha reportado un número desproporcionadamente alto de casos de TB. Sin embargo, la evidencia local sobre los patrones de resistencia y las características de los pacientes es escasa.
Objetivo: Estimar la prevalencia de TB-MDR y describir sus características epidemiológicas y clínicas en la provincia de Esmeraldas, Ecuador, de 2018 a 2022.
Métodos: Se realizó un estudio descriptivo transversal utilizando datos secundarios del Ministerio de Salud Pública del Ecuador. Se analizaron los casos confirmados de TB pulmonar con cultivo positivo o resultados de GeneXpert. Se calcularon las tasas de prevalencia de TB-MDR y se estratificaron las características de los pacientes por sexo, edad, distrito de residencia, antecedentes de contacto con TB y perfil de farmacorresistencia. El análisis estadístico incluyó procedimientos univariados y bivariados, con razones de probabilidades (OR) de prevalencia y pruebas de chi-cuadrado. Resultados: De los 1461 casos confirmados de TB reportados en la Zona 1, 902 (61,7%) provinieron de Esmeraldas. De estos, 49 (5,4%) fueron identificados como TB-MDR. La prevalencia anual media de TB-MDR en Esmeraldas fue de 1,7 casos por 100 000 habitantes. La mayoría de los pacientes con TB-MDR fueron hombres (59,2%), con edades comprendidas entre 20 y 49 años (82%) y residentes urbanos (79,6%). Se encontró resistencia a la rifampicina en el 91,8% de los casos. Los casos de recaída mostraron una probabilidad significativamente mayor de resistencia (OR = 3,48). Un caso cumplió los criterios de TB extremadamente resistente a fármacos (TB-XDR). Los resultados del tratamiento fueron incompletos en el 41% de los casos; entre los resultados reportados, la tasa de curación fue del 22,4% y la tasa de letalidad del 10,2%.
Conclusiones: La TB-MDR continúa siendo una amenaza persistente en Esmeraldas, siendo la recaída y la residencia urbana marcadores de riesgo prominentes. La detección de TB-XDR y las tasas de interrupción del tratamiento ponen de relieve deficiencias críticas en el programa de control de la tuberculosis. Se necesitan urgentemente estrategias específicas para mejorar el diagnóstico rápido, el seguimiento y la calidad de los datos a fin de contener la propagación de la resistencia y alcanzar los objetivos de eliminación de la tuberculosis en Ecuador.

Keywords: tuberculosis multirresistente, farmacorresistencia, TB pulmonar, epidemiología, Esmeraldas, Ecuador, TB-XDR, salud pública

 

Introducción

Pulmonary tuberculosis (TB) remains a major public health concern worldwide despite advancements in early diagnosis and effective treatment. Misuse of antibiotics and poor adherence to treatment regimens have contributed significantly to the emergence of drug-resistant tuberculosis (DR-TB)(1,2). It is estimated that only 58% of previously treated patients and 12% of treatment-naïve individuals have access to drug susceptibility testing (DST). In 2020, TB affected an estimated 9.9 million people globally, impacting all countries and age groups. Although TB is both preventable and curable(3), its burden remains disproportionate in high-risk populations.

In Ecuador, TB prevalence among individuals deprived of liberty is reported at 1.9%(4), and studies in prison settings have identified a drug resistance prevalence of 6.1%(5,6). Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampicin, affects approximately 3.5% of new TB cases, 27% of previously treated patients, and 18.8% of those co-infected with HIV(7). Notably, the loss to follow-up rate for MDR-TB cases in Ecuador exceeds the regional average in the Americas(6).

The World Health Organization (WHO) recommends the use of rapid molecular diagnostics as the initial diagnostic tool in all individuals with suspected TB. These include Xpert MTB/RIF, Xpert Ultra, and Truenat, which provide high diagnostic accuracy(8). Risk factors for drug-resistant TB include age over 40, unemployment, lack of health insurance, pulmonary cavitation, history of TB, and non-adherence to anti-TB therapy(9,10). Additional determinants such as male sex, marital status, urban residence, inadequate housing, and prior incarceration have also been associated with drug resistance(4). Moreover, primary resistance to anti-TB drugs among HIV/TB co-infected patients remains elevated in Latin America(11).

In Ecuador, the number of confirmed cases of drug-resistant TB increased from 95 in 2013 to 252 in 2018, with rifampicin resistance present in approximately 89% of cases(1,12). This growing burden highlights the need for localized evidence, particularly in the province of Esmeraldas, where no prior studies have addressed the prevalence or characteristics of drug-resistant TB.

This study aims to estimate the prevalence of multidrug-resistant pulmonary tuberculosis (MDR-TB) in Esmeraldas, Ecuador, and to describe its epidemiological and clinical profile by age, sex, residence, and prior contact with TB infection between 2018 and 2022.

Methods

Study Design and Population

A cross-sectional, observational, and descriptive study was conducted using secondary data reported by the Ecuadorian Ministry of Public Health (MSP). The study included all bacteriologically confirmed cases of pulmonary tuberculosis (TB) — through either culture or GeneXpert MTB/RIF — diagnosed between January 1, 2018, and December 31, 2022. The dataset was obtained from the registry maintained by the National Strategy for Tuberculosis Control and Prevention for Health Zone 1, which includes the provinces of Carchi, Sucumbíos, Imbabura, and Esmeraldas.

Data Analysis

To estimate TB prevalence in the province of Esmeraldas, all cases diagnosed as drug-susceptible TB were analysed by year and by health district: 08D01 (Esmeraldas-Rioverde), 08D02 (Eloy Alfaro), 08D03 (Muisne-Atacames), 08D04 (Quinindé), and 08D05 (San Lorenzo). This disaggregation enabled the identification of the geographic origin (urban or rural) of each case.

For the analysis of multidrug-resistant TB (MDR-TB), only confirmed cases from the province of Esmeraldas were included. Cases from other provinces in Zone 1 were excluded. The MDR-TB proportion was calculated, and patients were characterized using the following variables: age, sex, prior TB contact, presence of comorbidities, prior use of anti-TB drugs, type of drug resistance, urban or rural residence, and treatment outcome.

Statistical Methods

Data were entered and cleaned in Microsoft Excel 365, and statistical analyses were performed using RStudio version 2025.05.0. Descriptive analyses included frequency distributions, proportions, and measures of central tendency. Prevalence rates per 100,000 population were calculated. To explore potential associations, prevalence ratios and odds ratios (OR) were estimated for key variables. All statistical analyses were univariate.

Ethical Considerations

The study protocol was reviewed and approved by the Human Research Ethics Committee of Universidad UTE (Quito, Ecuador). Permission to access the anonymized database was granted by the Zonal Health Coordination of Zone 1. All data were fully anonymized before analysis, and no identifiable information was accessible to the research team. The database was used exclusively by authorized investigators in accordance with national and institutional research ethics guidelines.

Results

Tuberculosis Burden in Zone 1: The Disproportionate Impact in Esmeraldas

Over the five-year study period (2018–2022), a total of 1,461 bacteriologically confirmed cases of pulmonary tuberculosis (PTB) were recorded across Ecuador’s Health Zone 1, which comprises the provinces of Carchi, Imbabura, Sucumbíos, and Esmeraldas. Of these, 1,371 (93.84%) were drug-susceptible TB (DS-TB), while 90 (6.16%) were classified as drug-resistant TB (DR-TB), including multidrug-resistant TB (MDR-TB). Remarkably, the province of Esmeraldas accounted for 902 of all cases in the zone, representing 62% of the regional TB burden. This disproportionate clustering of cases within Esmeraldas highlights the province as a priority area for intensified TB control measures.

Within Esmeraldas, 853 cases (94.56%) were drug-susceptible and 49 (5.44%) were drug-resistant. The latter included cases with resistance to rifampicin alone, isoniazid alone, or both. The magnitude of resistance observed in Esmeraldas aligns with national trends reported by the Ministry of Health but also raises concern about the possible silent expansion of MDR-TB in vulnerable coastal populations. A detailed case classification flow is illustrated in Figure 1, where TB cases are stratified by zone, resistance status, district of residence, and TB contact history. This visual framework aids in understanding the hierarchical flow of clinical and epidemiological profiles.

Figure 1. Flowchart of laboratory-confirmed pulmonary tuberculosis cases in Zone 1, Ecuador (2018–2022), highlighting drug resistance profiles and case distribution in Esmeraldas Province. This flowchart summarizes 1,461 patients with laboratory-confirmed pulmonary tuberculosis reported in Zone 1 between 2018 and 2022. Cases were stratified by drug-susceptibility profile (drug-sensitive vs. drug-resistant TB) and geographic location (Esmeraldas vs. other provinces). Among the 49 drug-resistant cases from Esmeraldas, 85.7% were new and 14.3% were relapses. Previous contact with TB was documented in 46.9% of new cases and 54.1% of relapses. All data were obtained from the National Tuberculosis Program of Ecuador.

Temporal Trends in Prevalence and Mortality

Annual prevalence rates for drug-susceptible and drug-resistant TB were calculated using projected population denominators for Esmeraldas. The mean prevalence rate of DS-TB over the five-year period was 29 cases per 100,000 population. The lowest value was registered in 2020, coinciding with the first year of the COVID-19 pandemic, and a marked resurgence was observed in 2021 and 2022. This rebound may be attributed to both improved post-pandemic reporting and the resumption of TB screening services. In contrast, the mean prevalence of DR-TB was 1.7 per 100,000 population. The year 2022 saw the highest prevalence for DR-TB at 2.4 per 100,000. These trends are graphically represented in Figure 2, which contrasts DS-TB and DR-TB prevalence by year.

Figure 2. Prevalence rate of drug-sensitive and drug-resistant pulmonary tuberculosis in Esmeraldas Province, Ecuador, from 2018 to 2022. Prevalence rates are expressed per 100,000 population. Drug-sensitive tuberculosis cases showed a marked increase in 2021 and 2022, whereas drug-resistant tuberculosis rates remained low and stable throughout the study period. Rates were calculated based on notified cases reported by the Ministry of Public Health of Ecuador and population estimates from the National Institute of Statistics and Censuses

Mortality analysis revealed that the TB-specific mortality rate remained zero for the initial three years (2018–2020) but increased to 0.5 per 100,000 population in 2021 and declined slightly to 0.3 in 2022. These modest but significant increases may reflect delayed diagnoses, treatment interruptions, or weaknesses in pharmacovigilance and case management amid pandemic-related health service disruptions. The trend is illustrated in Figure 3.

Figure 3. Mortality rate of multidrug-resistant tuberculosis (MDR-TB) in Esmeraldas Province, Ecuador, from 2018 to 2022. The mortality rate is expressed per 100,000 population. No MDR-TB-related deaths were reported from 2018 to 2020. A peak was observed in 2021 (0.5 per 100,000), followed by a slight decline in 2022 (0.3 per 100,000). Data were derived from national surveillance reports of the Ministry of Public Health of Ecuador and population estimates from the National Institute of Statistics and Censuses.

Demographic and Clinical Profile of Drug-Resistant TB Cases

A total of 49 patients were diagnosed with DR-TB in Esmeraldas during the study period. The demographic distribution revealed that 59.2% (n = 29) were male, and the mean age was 33.6 years (SD: 12.6; range: 18–72), with a median of 30. The age group most affected was between 20 and 49 years, representing 82% of all DR-TB cases. This reflects the well-documented tendency of TB to affect individuals in their productive years, with broad implications for economic stability and household vulnerability.

In terms of geographical distribution, most DR-TB cases (64.4%) were reported in the 08D01 health district (Esmeraldas-Rioverde), while 79.6% resided in urban areas. These findings support the hypothesis that population density, mobility, and socioeconomic disparities play significant roles in TB transmission dynamics.

Regarding microbiological characteristics, rifampicin resistance was observed in 91.8% (n = 45) of DR-TB cases, and 6.1% (n = 3) had resistance to isoniazid. Notably, one case (2%) met the criteria for extensively drug-resistant TB (XDR-TB), defined as resistance to at least rifampicin and isoniazid plus resistance to a fluoroquinolone and a second-line injectable drug. The presence of XDR-TB in a decentralized province like Esmeraldas raises serious concerns regarding referral systems, access to second-line treatment, and diagnostic delays.

Comorbidity analysis revealed that 6.1% (n = 3) of patients were co-infected with HIV and 10.2% (n = 5) had a diagnosis of diabetes mellitus. History of previous TB contact was reported in 51% (n = 25) of cases, while 14.3% (n = 7) were documented as relapse cases, and 85.7% were incident (new) cases. These characteristics are summarized in Table 1, which provides a comprehensive overview of sociodemographic, clinical, and treatment-related variables.

Table 1. Clinical and epidemiological characteristics of patients with multidrug-resistant tuberculosis (MDR-TB) in Esmeraldas Province, Ecuador (2018–2022).   

Note: Data are presented as absolute frequencies and percentages (n, %). All patients included had confirmed MDR-TB, defined as resistance to at least isoniazid and rifampicin. Variables include demographic characteristics, diagnostic method, type of drug resistance, and treatment outcomes. Percentages may not total 100% due to rounding.

Outcomes were available for 59% of patients. Among them, 22.4% were cured, 18.4% remained on treatment at the time of data collection, and 10.2% died. Alarmingly, 8.2% abandoned treatment, and 40.8% of cases had no recorded outcome. This significant data gap reveals critical issues in case monitoring, database updating, and continuity of care within the regional TB program.

Association Between MDR-TB and Prior TB History

Among the drug-resistant cases, 7 were classified as relapses. A bivariate analysis revealed that patients with a history of TB relapse had significantly higher odds of being MDR-TB cases. The prevalence odds ratio (OR) was 3.48, indicating that relapse cases were more than three times as likely to present with multidrug resistance compared to new cases. This association reinforces evidence that incomplete or poorly supervised treatments facilitate the selection of resistant mycobacterial strains, with profound clinical and public health implications.

No statistically significant associations were observed between MDR-TB status and other variables such as sex, age group, comorbidity, urban vs. rural residence, or HIV status (p > 0.05 in all comparisons using Pearson’s chi-square test). While these null findings may suggest no strong bivariate relationships, the limited statistical power of small subgroup sizes must be acknowledged.

Discussion

This study provides a detailed epidemiological characterization of pulmonary multidrug-resistant tuberculosis (MDR-TB) in Esmeraldas province, Ecuador, between 2018 and 2022. The findings reveal a persistent, albeit low, prevalence of MDR-TB (5.4%), concentrated disproportionately in urban areas and among working-age adults. These results underscore the growing threat of drug resistance within localized high-burden pockets and the need for strengthened public health responses tailored to regional contexts.

The overall proportion of MDR-TB observed aligns with national estimates from the Ecuadorian Ministry of Health and WHO’s Global Tuberculosis Reports, which cite MDR-TB rates of approximately 3.5% among new cases and up to 27% among previously treated cases(13,14). The detection of a single XDR-TB case in this study, while isolated, is an alarming sentinel event(15). It reflects the complex interplay of programmatic gaps, delayed diagnosis, and treatment nonadherence, especially in settings with limited access to second-line drugs and laboratory capacity(16).

One of the key findings was the strong association between TB relapse and MDR-TB, with a prevalence odds ratio of 3.48. This result is consistent with prior studies in Latin America and globally, which have consistently shown that previous treatment is one of the most significant predictors of drug resistance(17,18). Factors contributing to this include incomplete or interrupted therapy, suboptimal regimens, and inadequate follow-up—particularly relevant in regions where social vulnerability and health system fragmentation converge(9).

The urban predominance of MDR-TB cases (nearly 80%) in Esmeraldas supports the hypothesis that densely populated environments with poor ventilation, overcrowding, and irregular health-seeking behaviors facilitate transmission and complicate case detection. Similar patterns have been documented in other coastal cities in Latin America and sub-Saharan Africa, where urbanization has outpaced health infrastructure expansion(19,20).

The low mortality observed during the early years of the study period (2018–2020) shifted sharply in 2021, coinciding with post-pandemic surveillance recovery. This aligns with WHO alerts regarding underreporting and delayed TB diagnoses during the COVID-19 pandemic. The rebound in TB prevalence and mortality seen in this study confirms the collateral impact of health emergencies on TB programs and underscores the need for resilient surveillance systems(21).

Our results also raise important concerns regarding data completeness. Approximately 41% of DR-TB cases lacked treatment outcome data. This compromises program evaluation, hinders cohort monitoring, and may obscure the real burden of mortality and treatment abandonment. Previous analyses in Ecuador and Peru have highlighted similar weaknesses in TB information systems and called for improved integration of electronic medical records and real-time laboratory reporting(14,22,23).

While the bivariate analyses did not reveal statistically significant associations with variables such as sex, age, or comorbidity, this may reflect limited statistical power rather than true absence of effect. The high prevalence of resistance to rifampicin (91.8%) suggests an opportunity to optimize molecular diagnostic algorithms. The use of Xpert MTB/RIF and, more recently, Xpert Ultra, is critical not only for early detection of resistance but also for stratification of patients into appropriate therapeutic pathways(24,25).

From a public health perspective, the findings call for urgent actions to strengthen TB control in Esmeraldas. These should include: (1) expanded access to rapid molecular diagnostics in all health districts; (2) intensified contact tracing and preventive therapy in urban hotspots; (3) targeted adherence support for high-risk patients, especially those with a history of treatment; and (4) reinforcement of pharmacovigilance for second-line drug regimens.

Finally, this study contributes to the limited body of evidence on MDR-TB in coastal Ecuadorian provinces, where publication gaps have historically hindered the design of evidence-informed policies. By documenting the local epidemiology of resistance, this work provides a foundation for operational research, health system strengthening, and alignment with global TB elimination goals by 2035.

Strengths and Limitations

This study has several strengths. First, it represents the most recent and comprehensive epidemiological description of MDR-TB in the province of Esmeraldas, a high-burden coastal region historically underrepresented in national TB research. Second, the study was based on laboratory-confirmed cases and integrated multiple variables (demographic, clinical, geographic, and programmatic) to describe resistance patterns. Additionally, the use of robust analytical methods and adherence to STROBE recommendations strengthens the internal validity of the findings.

However, some limitations must be acknowledged. The retrospective design relies on secondary data sources, which were subject to missing or incomplete variables, particularly regarding treatment outcomes (41% missing). This compromises the ability to accurately assess program performance and may underestimate rates of mortality or treatment abandonment. Furthermore, the sample size of MDR-TB cases was limited, restricting the power to detect associations with sociodemographic variables or comorbidities. Lastly, genotypic resistance profiles were unavailable beyond rifampicin and isoniazid, limiting the capacity to assess the burden of pre-XDR or XDR-TB with molecular precision.

Conclusion

Multidrug-resistant tuberculosis remains a significant public health challenge in Esmeraldas, disproportionately affecting young, urban, and economically active populations. Although the overall prevalence is relatively low, the detection of relapse-associated resistance and the identification of XDR-TB highlight the need for urgent interventions. Strengthening access to molecular diagnostics, improving data quality, and expanding treatment monitoring are key priorities. This study contributes critical local evidence to inform Ecuador's National TB Program and aligns with global goals to reduce drug-resistant TB incidence by 90% by 2035. Continued operational research and investment in surveillance systems will be essential to interrupt transmission chains and improve patient outcomes in this vulnerable region.

Acknowledgments

The authors express their sincere gratitude to the Ecuadorian Ministry of Public Health, particularly the Zonal Coordination 1 – National Tuberculosis Control Program, for providing access to the anonymized database used in this study. We extend our appreciation to the health personnel and epidemiology teams of the Esmeraldas provincial districts for their continued efforts in tuberculosis surveillance, reporting, and case management.

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