Evaluation of GeneXpert® in Brazil Through a Historical and Epidemiological Approach

doi:10.21203/rs.3.rs-1758482/v1

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Evaluation of GeneXpert® in Brazil Through a Historical and Epidemiological Approach

https://doi.org/10.21203/rs.3.rs-1758482/v1

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Background: The Rapid Molecular Test (RMT) Gene Xpert is widely used as a control strategies and surveillance for tuberculosis (TB). In the region of the Americas TB incidence is slowly increasing, owing to an upward trend in Brazil, which is among the high TB burden countries (HBCs) ranking the 19th position. In this context, we aimed to: (i) describe the implementation and history of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) in Brazil; (ii) to evaluate the national RMT-laboratory distribution and TB and RIF detection by RMT-TB equipment (by year, by federal units and by region); and (iii) to correlate these data the Brazilian TB incidence.

Methods: For this, we collected the quantitative data of Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assays, performed in the pulmonary TB investigation from 2014 to 2020, provided by the Brazilian Ministry of Health. A spatial visualization using ArcGIS software was performed.

Results: The Southeast region allocated about double RMT-laboratories from 39.4% - 45.9% of the total value over five which is the number of regions. Regarding the federal units, the São Paulo state allocated alone from 20.2% to 34.1% (5.0 to 8.5 times the value) of RMT-laboratories depending on the year observed. There were significant differences (p < 0.0001) in the frequency of RMT-laboratory in all years of the historical series. There was an unequal distribution of RMT-laboratory between Brazilian regions and federal units.

Conclusions: This alerts for the surveillance of rapid molecular detection of TB in different parts of the country, with the possibility of improving the distribution of tests in areas of higher incidence to achieve the disease control recommended by national and worldwide authorities.

Tuberculosis

Rapid Molecular Test

Xpert MTB/RIF

Xpert MTB/RIF Ultra

Brazil

To control Tuberculosis (TB) epidemic, the World Health Organization (WHO) has implemented the End TB Strategy with aims to reduce TB deaths by 95% and to control new cases by 90% untill 2035. To properly address this aim, an early and accurate diagnosis of all forms of TB and rapid detection of drug resistance (DR) is essential (1–3).

Regarding the health system requirements, it is necessary to improve access to rapid TB diagnosis and drug susceptibility testing (DST), by expanding and strengthening the network of diagnostic services using WHO-recommended Rapid Molecular Test (RMT) for initial diagnostic tests with drug-resistance detection, such as the Xpert® MTB/RIF Ultra (Cepheid, Sunnyvale, USA) or Truenat® MTB-RIF Dx system (Molbio Diagnostics, Goa, India) within the peripheral health-care services which allows early and accurate diagnosis of TB and rifampicin (RIF) DR, which should be prioritized for high-risk groups(1–3).

Currently, Xpert® MTB/RIF Ultra (Cepheid, Sunnyvale, USA) is the main resources in TB control strategies for rapid molecular diagnosis and surveillance test (4), that can detect within 77 minutes when positive or 66 minutes when negative (average time: 69 minutes) the presence of the Mycobacterium tuberculosis complex (MTBC) in patient specimens and the presence of the main mutations responsible for resistance to RIF (rpoB gene mutation) and it is considered a low complexity automates nucleic acid amplification test(4).

In the region of the Americas TB incidence is slowly increasing, owing to an upward trend in Brazil, which is among the high TB burden countries (HBCs) ranking the 19th position(5). In Brazil, is observed the regional variations in the TB burden among the states, that is explained by the transmission of the disease concentrated in peripheral urban areas, in clusters of patients living in precarious conditions and densely populated areas in some cities, added to the social determinants associated with the vulnerability of people affected by TB(6).

Design and study aim

This is a epidemiological study, cross-sectional, which evaluated secondary data obtained from the Brazilian Health Ministry.

We aimed to: (i) describe the implementation and history of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) in Brazil; (ii) to evaluate the national RMT-laboratory distribution and TB and RIF detection by RMT-TB equipment (by year, by federal units and by region); and (iii) to correlate these data the Brazilian TB incidence.

Setting of the study

We stratified the Brazilian map into the five Major Regions (North-N, Northeast-NE, Southeast-SE, Central West-CW, and South-S), and into the 27 federal units (states) to perform the epidemiological historical series approach of the GeneXpert equipments in Brazil (Fig. 1).

GeneXpert MTB/RIF equipment data (RMT-TB equipment)

The GeneXpert includes the equipment system and the individual cartridges of assays Xpert MTB/RIF (Cepheid, Sunnyvale, USA), or Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, USA). The technology was implemented in Brazilian Unified Health System (Sistema Único de Saúde – SUS) in 2014 with the Xpert MTB/RIF cartridge and was updated in 2020 to Xpert MTB/RIF Ultra version(7, 8).

Data Collection of the Historical Context

To discuss the history of the GeneXpert technology in Brazil, we carried out a research from August to September 2021 from official Brazilian documents that guided the implementation of this diagnostic tool in the SUS by the Brazilian Ministry of Health (9), in three websites: (1) Biblioteca Virtual em Saúde do Ministério da Saúde (https://bvsms.saude.gov.br/); (2) Diário Oficial da União (https://www.gov.br/imprensanacional/pt-br) and (3) Ministry of Health (https://www.gov.br/saude/pt-br).

For analysis, we addressed the following subjects: (i) the GeneXpert equipment regulation in Brazil; (ii) the interest of the Brazilian Ministry of Health for the implementation of GeneXpert equipment in SUS; (iii) process for GeneXpert implementation; (iv) authorization to use GeneXpert; and (v) beginning of the operation of RMT-TB equipment in SUS.

GeneXpert Quantitative Data Collection

We obtained the quantitative data of Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assays results of pulmonary TB (diagnosed from 2014 to 2020) in collaboration with the General Coordination for the Monitoring of Chronic Conditions Respiratory Transmission Diseases (Coordenação-Geral de Vigilância das Doenças de Transmissão Respiratória de Condições Crônicas – CGDR) from the Brazilian Ministry of Health on the Electronic Citizen Information System (Sistema Eletônico de Informações ao Cidadão - e-SIC).

Health Care Indicators

We choose the health care indicators based on the Pan American Health Organization: (i) absolute and relative frequency per region and federal units of RMT-laboratory and the cases of TB and TB RIF resistance detected by GeneXpert in the human population; (ii) ratio of RMT-laboratory per 10⁶ inhabitants of regions and federal units; (iii) absolute and relative frequency of positive Mycobacerium tuberculosis (MTB) detected by GeneXpert in new cases of TB and; (iv) Incidence of TB per region and federal units .

Absolute and relative frequency of RMT-laboratory and the cases of MTB positive and RIF resistance detected by GeneXpert were calculated as of data given by CGDR. The Ratio of RMT-laboratory per 10⁶ inhabitants was calculated as of data given by CGDR and Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística - IBGE) population data. While the absolute and relative frequency of positive MTB detected by GeneXpert in new TB cases were calculated from the data provided by CGDR and the data collected from the National System of Information on Noticeable Disease (Sistema de Informação de Agravos de Notificação - SINAN) available on the website of the Department of Informatics of the Unified Health System (Departamento de Informática do Sistema Único de Saúde - DATASUS) (https://datasus.saude.gov.br/) on 07/27/2021.

The TB incidence coefficient was calculated using reports from the TB database (http://tabnet.datasus.gov.br/). Therefore, to calculate the TB incidence coefficient of the regions and federal units, we used the Tab for Windows-TabWin program to apply the formula used by(10, 11), a number of new cases of TB per place of residence/ estimated population x 100,000 inhabitants. New TB cases are considered the sum of the entry types "new case", "unknown" and " post-death" as recommended by the brazilian data system. New TB cases for the period 2014 to 2020 were collected from the SINAN available on the website of the DATASUS (https://datasus.saude.gov.br/) on 07/27/2021. The estimated population from 2014 to 2020 was also collected on 07/27/2021 from the website of IBGE (https://www.ibge.gov.br/).

Geoprocessing

The boundaries of the regional divisions of Brazil (States and Major Regions) applied presently were obtained on the website of the IBGE (https://www.ibge.gov.br/). The coordinates were obtained from the centroids of the states using the tool "Polygon To Point" from ET GeoWizards (https://www.ian-ko.com/ETGeoWizards.html) in ArcGIS software (https://www.arcgis.com/). Data processing, interpretation, visualization, and spatial analysis were performed via ArcGIS software (http://www.arcgis.com/). TB incidence was classified into four levels according to the WHO: low cases (0-9.9 - green color), medium (10-24.9 - yellow), high (25-49.9 cases - orange) and very high (> 50 - red) cases/100,000 inhabitants. RMT-TB detected MTB cases and rifampicin resistance cases, thus as RMT-laboratory were distributed by the incidence map by quartile (MTB cases detected by RMT-TB and RIF resistance cases were distributed by the incidence map by quartile). The maps were divided into seven years (2014–2020) for better visualization, being the limits by federal units and major regions (N, NE, CW, SE and S).

Statistics Analysis

Chi-square test of adherence was used to examine the differences between RMT-laboratory’s region frequencies in each year and Chi-square test for trend was used to assess the trend in MTB frequency or RIF resistance throughout the historical series. Furthermore, Spearman's rank correlation test was applied to estimate the correlation between the number of RMT-laboratory equipment, TB incidence in the region and federal units and MTB frequency by region and federal units and between RMT-laboratory ratio in each region and federal units and TB incidence, per year. The Friedman test was applied to compare RMT-laboratory quantitative between 2014 versus 2015; 2014 versus 2016; 2014 versus 2017; 2014 versus 2018; 2014 versus 2019; 2014 versus 2020.

Historical Background of GeneXpert in Brazil

The historical background of GeneXpert in Brazil was built based on three official documents(12–14); two published studies(15, 16); and an official document from the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária –ANVISA). The GeneXpert equipment was registered by ANVISA in 2009 to be used by the private sector(17).

The interest of the Brazilian Ministry of Health for the implantation of GeneXpert equipment in SUS

The Brazilian Health Ministry showed interest in the performance of the equipment between the years 2012 and 2013. To this end, it signed a partnership with the Bill and Melinda Gates Foundation (BMGF) and the Ataulpho de Paiva Foundation, as it would promote innovation in the diagnosis and treatment of TB in Brazil, in addition to the allocation of resources for the progress of the demands of the National Tuberculosis Control Program (Programa Nacional de Controle da Tuberculose-PNCT) in improving the detection and treatment of TB in Brazil (12).

Process for deployment of the GeneXpert equipment in SUS

The partnership gave rise to the pilot project to deploy the assay Xpert MTB/RIF realized by GeneXpert equipment to pulmonary TB diagnosis in two Brazilian cities as a substitute for direct sputum smear microscopy under routine conditions to assess whether it would increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and reduce the time to initiation of TB treatment, as well as to estimate the impact that the adoption of this equipment would provide in the detection of cases of RIF resistant TB (RR-TB) used in treatment (18). In parallel to the pilot study, a cost analysis of the assay Xpert MTB/RIF and of the GeneXpert equipment to pulmonary TB diagnosis by SUS was performed(16).

During the pilot study, the implementation of a national network of GeneXpert equipment was addressed by the PNCT. To this end, it had some priorities: (i) Municipalities that notified more than 200 TB cases in 2011 and that had a laboratory with physical and biosafety structure equivalent to the performance of the microscopy; (ii) The cutoff point of 200 new cases, because it is the operational capacity of an GeneXpert equipment with two modules, being able to perform eight to 16 tests per day. In addition, they included: (i) State capitals that did not notify more than 200 new cases in 2011; (ii) Municipalities that are the seat of prisons or with indigenous population that notified at least 50 cases in 2011; (iii) Central Public Health Laboratories (Laboratório Central de Saúde Pública-LACEN) for being the coordinators of the state network of laboratories and responsible for training and quality control of the tests performed (12).

Authorization of the use of GeneXpert equipment by SUS

The members of the National Commission for Technology Incorporation at SUS (Comissão Nacional de Incorporação de Tecnologias no SUS - CONITEC) present at the 11th ordinary meeting in plenary on 12/07/2012, unanimously recommended the assay Xpert MTB/RIF realized by GeneXpert equipment as a test for diagnosing TB and for detecting resistance to RIF(12).

However, the following year, they conducted a public consultation between January 15 and February 04, 2013, characterized as suggestion and questioning, respectively. Finally, on March 7, 2013, the final decision of CONITEC members was to recommend the incorporation of the GeneXpert MTB/RIF Xpert assay for TB diagnosis and detection of resistance to RIF within the scope of the PNCT and according to the criteria established for its implementation (12).

Ordinance No. 48, of September 10, 2013, made public CONITEC's decision to incorporate the assay Xpert MTB/RIF into SUS for TB diagnosis and detection of RIF resistance(14).

Start of operation of GeneXpert equipment in SUS

The GeneXpert equipment was distributed to SUS in May 2014, starting to use assay Xpert MTB/RIF in the same month and monitored by the national Rapid Test Network-TB (RTN-TB) created for this purpose in the following month(7).

Quantitative analysis of GeneXpert in Brazil

In the first year (2014) of introduction of RMT-TB in SUS there were (n = 88 laboratories) with 149 RMT-TB equipment, in 2020, this number increased to (n = 203 laboratories) with 257 RMT-TB equipment, the identified increase was 130. 68% in the number of RMT-laboratory and 72.48% in the amount of RMT-TB equipment in the evaluated period. Furthermore, by Friedman's test, it only had a significant difference (p < 0.0001) in the number of RMT-laboratories between the years 2014 versus 2018; 2014 versus 2019 and 2014 versus 2020.

To evaluate the distribution of RMT-laboratories among the regions, we considered that there would be proportionally, 20% RMT-laboratories per region, however we observed that in the Southeast Region it was about twice as much 39.41–45.93% (Fig. 2A). Regarding the federal units, the equal distribution would be about 4% RMT-laboratory for each, but the state of São Paulo alone had 20.20% − 34.09% (5.0 to 8.5 times the value) of RMT-laboratory in the evaluated period (Fig. 2B). There were significant differences (p < 0.0001) in the frequency of RMT-laboratory in all years of the historical series.

The RMT-laboratory ratio/population in the Brazilian regions over the evaluated period demonstrates that in the last three years the highest ratio was obtained in the North region, which varied approximately from 60–80% more than in the Central West region, the second region with the highest ratio, and about 80% more compared to Brazil as a whole (Fig. 2C). Calculating for the federal units individually, Rondônia was the one with the highest ratio in the last three years, surpassing Acre and Roraima (Fig. 2D).

In addition, we can observe the number of RMT-laboratory in some states in which the TB incidence coefficient ranged from high to very high as in Acre (0–3 laboratories); Roraima (1–2 laboratories); Pernambuco (5–11 laboratories) and Pará (3–6 laboratories) (Fig. 3).

In seven years, (n = 508,381 new cases of MTB) were registered in Brazil, RMT-TB was responsible for detecting 205,585 (40.44%) of these new cases. The Southeast region had the highest number of new cases of MTB (n = 232,242 cases), 106,631 (45.91%) cases were detected by RMT-TB. The state of São Paulo, among the federal units, had the largest number of new cases (n = 121,748 cases), 59,150 (48.58%) cases were identified by the equipment.

There was a higher number of tests for MTB (n = 1,117,645) by RMT-TB in the SUS in the Southeast Region, where 106,631(9.54%) were positive. Regarding the federal units, the state of São Paulo, was the one that tested the most for MTB (n = 842,557 tests), obtaining 59,150 (7.02%) positives using only RMT-TB.

The state of Amazonas presented a very high incidence (> 50 cases/100,000 inhabitants) in all years of the historical series and an increase in the detection of positive MTB by RMT-TB in the year 2016 (Fig. 4). On the other hand, in the state of Rio de Janeiro, which also showed very high incidence (> 50 cases/100,000 inhabitants) in all years of the historical series, the detection of positive MTB was higher in two years of the historical series (2017 and 2020) (Fig. 4).

In states where TB incidence ranged from high to very high during the period evaluated, Roraima in 2019 had an increase in RMT-TB positive MTB detection that coincided with highest moment of TB incidence (> 50 cases/100,000 population) in that state (Fig. 4). In Acre, MTB positive detection was highest for the first time in 2017, the same year that the state first had TB incidence at the highest level (> 50 cases/100,000 population) (Fig. 4). In Pernambuco, MTB-positive detection experienced an increase for the first time in 2020, one year after the state showed very high TB incidence (> 50 cases/100,000 population) for the second time (Fig. 4). Whereas in the state of Pará, in the year 2019, when the incidence of TB was very high (> 50 cases/100,000 population), the detection of positive MTB in those tested by RMT-TB was lower compared to the previous year (2018) when the incidence of TB was lower (25-49.9 cases/100,000 population) (Fig. 4).

RIF resistance was detected by RMT-TB in (n = 8,209 positive MTB) in all seven years. Given this scenario, we observed, that in 2020, the state of Mato Grosso do Sul, in the Central West region, the detection of RIF-resistant MTB was about (20.1–30.0%) of the MTB detected in the state by the RMT-TB, a higher percentage than those detected in the states of Amazonas, Rio de Janeiro and Acre, where the incidence of TB was very high (> 50 cases/100,000 inhabitants) in the same year, as well as, of those detected in the other federal units in the previous years in the historical series (Figura 5).

Furthermore, it was possible to infer that in Regions North; Southeast; South; Central West and Brazil, there was a significantly increasing trend in the frequency of positive MTB detected by RMT-TB in SUS laboratories, on the other hand in Region Northeast this trend was significantly decreasing (Supplementary Fig. 1A, Supplementary Table 1). This scenario also showed that the frequency of RIF-resistant MTB detected by RMT-TB in SUS in Regions North and Southeast, showed a significantly decreasing trend. However, a significant increasing trend was observed in the Central West Region (Supplementary Fig. 1B, Supplementary Table 1).

Considering the correlation between health indicators, we analyzed by Spearman's correlation, that there was a significant correlation (p = 0.0452) between the frequency of MTB and the number of RMT-laboratory in the federal units only in 2014 and, a significant correlation (p = 0.0080) between the number of RMT-laboratory and TB incidence by region in the historical series.

The SUS had (n = 88 laboratories) with 149 RMT-TB equipment in the year 2014, in 2020, this number increased to (n = 203 laboratories) with 257 RMT-TB equipment, indicating that there was expansion of the RMT-TB network. However, the counting of this RMT-TB network equipment by the CGDR, is impacted by the mishaps generated in the shipment of the equipment, which depends on the locations responsible for the distribution. In this way, the donation date differs from the equipment's installation and production date, making it difficult to accurately count the equipment and leading to constant quantity variations. To overcome these adversities, the CGDR database is being continuously updated.

During all years of the historical series, there was a notable heterogeneity regarding the distribution of RMT-laboratory in the states. The state of São Paulo presented in all years of the historical series a higher presence of RMT-laboratory and a single scenario of TB incidence (25-49.9 cases/100,000 population), differing from the states of Roraima, Acre, Pernambuco, and Pará, where the incidence of TB ranged from high (25–49. 9 cases/100,000 inhabitants) to very high (> 50 cases/100,000 inhabitants) during the evaluated period, the presence of RMT-laboratory was lower in all years of the historical series, and the detection of MTB positive by RMT-TB in those tested was higher than that detected in São Paulo in the years 2019 and 2020. Thus, we suggest an increase of the RMT-TB network in North and Northeast of Brazil, such as the structural, technical and maintenance capacity of the equipment.

A study that involved the analysis of the budgetary impact of GeneXpert showed that the deployment of this equipment substantially increases the detection of new cases of TB(17). The state of São Paulo has the biggest Brazilian RMT-TB implanted since the beginning because it also includes equipment that was purchased by the local locations, which is a demonstration of the state's proactivity in expanding the RMT-TB network.

The pilot study for the implementation of GeneXpert in Brazil(16, 18) allowed to draw lessons for the good diagnosis of TB: (i) Municipalities should guarantee training to technicians of the laboratories of the public service network to feel safe when using the new technology presented; (ii) For the expansion of the use of GeneXpert in the country, a local provider is needed to maintain the GeneXpert system in addition to cartridges always available; (iii) Sputum smear microscopy should be maintained for follow-ups or sputum samples scarce, as well as for initial diagnosis of relapse/retreatment cases; (iv) The medical information system needs constant updates for the efficient use of the equipment.

In addition to the improvements in TB diagnosis, the initial test performed by GeneXpert was updated, the Xpert MTB/RIF test, now renamed as Xpert MTB/RIF Ultra. This led to surpassing the ratings in the Xpert MTB/RIF test in the diagnosis of TB in paucibacillary patients(19, 20).

However, during the research, we noticed an absence of results in places where there is GeneXpert equipment, caused by the non-automation of the sending of the GeneXpert System report to the Laboratory Environment Management System (Gerenciador de Ambiente Laboratorial - GAL). Therefore, we suggest that an interface between these two systems be made to solve the problem of not sending the cartridge consumption monitoring data.

Although we found significant correlation between the indicators MTB frequency and the number of RMT-laboratory in the federal units in the first year of the historical series, as well as between the number of RMT-laboratory and TB incidence by region in the historical series, we propose that future studies should seek to do a directly observed follow-up of the effect that the number of laboratories equipped with RMT-TB in operation for TB diagnosis has on the frequency of MTB detected and the incidence coefficient in states where there were very high TB incidence coefficients (> 50 cases/ 100 thousand inhabitants) in the evaluated period.

Despite the study's limitation of total agreement between database reports, which is explained by the continuously updated system, we concluded that, among the data analysis, there was an unequal distribution of RMT-laboratory among regions and federal units, with a higher proportion concentrated in the Southeast region and in the state of São Paulo, where there is a larger population contingent. This inequality affects the detection of new TB cases, since we found a correlation between the number of RMT-laboratory and the frequency of MTB detected by the RMT in our study.

In addition, the presence of RMT-laboratory majority to the capitals cities, metropolitan regions, or reference centers, with a need for greater interiorization of this equipment, especially in federal units where the incidence of TB is high or very high and the presence of RMT-laboratory insufficient to meet all the territorial demand. This fact may occur due to the capacity of physical and human resources that are informed to carry out the technique, in addition to the organization of the sample collection and transport network that requires a bipartite agreement.

The progress in TB burden and control is heterogeneous among regions and states. Reaching the agreed global targets established by WHO for End TB Strategy remain a challenge. In this sense, compliance with the goals agreed by the Brazilian Ministry of Health will be difficult to achieve without major and profound changes in the access, coverage, and quality of the health care provided. Therefore, efforts should be made in TB surveillance and control actions in Brazilian regions and states to diagnose early cases of active disease and start treatment convenient.

The study described the implementation and use of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) for TB diagnose in Brazil. The laboratory national distribution and dectetion of TB and RIF resistance was elavuated from 2014 to 2020 in all regions and federal unitis. The data showed an unequal distribution of RMT-laboratory between Brazilian regions and federal units, and Southeast region and Sao Paulo state allocated along the period about 39.4% − 45.9% and 20.2–34.1% of RMT-laboratories respectively. This data was correlated to Brazilian TB incidence and alerts for the improvement of the RMT-TB distribution and TB surveillance in areas of higher incidence in different parts of the country. The research expanded knowledge and strengthened evidence regarding spatial distribution of rapid molecular test to improve rapid diagnose and control of the disease.

ANVISA: Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency); BMGF (Bill and Melinda Gates Foundation); CGDR: Coordenação-Geral de Vigilância das Doenças de Transmissão Respiratória de Condições Crônicas (General Coordination for the Monitoring of Chronic Conditions Respiratory Transmission Diseases); CONITEC: Comissão Nacional de Incorporação de Tecnologias no SUS (National Commission for Technology Incorporation at SUS); CW: Central-West; DATASUS: Departamento de Informática do Sistema Único de Saúde (Department of Informatics of the Unified Health System); DR: drug resistance; DST: drug susceptibility testing; E-SIC: Sistema Eletônico de Informações ao Cidadão (Brazilian Ministry of Health on the Electronic Citizen Information System); GAL: Gerenciador de Ambiente Laboratorial (Laboratory Environment Management System); HBCs: high TB burden countries; IBGE: Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Geography and Statistics); LACEN: Laboratório Central de Saúde Pública (Central Public Health Laboratories); MTB: Mycobacerium tuberculosis; MTBC: Mycobacterium tuberculosis complex; N: North; NE: Northest; PNCT: Programa Nacional de Controle da Tuberculose (National Tuberculosis Control Program); RIF: rifampicin; RMT: Rapid Molecular Test; RR: RIF resistant; RTN-TB: Rapid Test Network-TB; S: South; SE: Southest; SINAN: Sistema de Informação de Agravos de Notificação (Notifiable Diseases Information System); SUS: Sistema Único de Saúde (Brazilian Unified Health System); TB: tuberculosis; WHO: World Health Organization.

Ethics approval and consent to participate

This research was exempted from the ethics committee because it evaluates only secondary use of data publically available which was provided without any identifier or group of identifiers that could allow attribution of private information to an individual. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable.

Availability of data and materials

All data are provided in supplementary files.

Competing interests

The authors declare that they have no competing interests.

Funding

This study did not receive any grant from funding of public, or commercial, or not-for-profit agencies.

Authors' contributions

ECC, MCSL, and KVBL conceived and planned the project. ECC, and KVBL supervised this work. ECC, MCSL, and ASS designed the database. ECC, MCSL, KVBL and ACB performed the data collection. TNSI and MLC performed data analysis. CRM and RJPSG performed geoprocessing. IPF performed statistics. All authors discussed the results and contributed to the final manuscript.

Acknowledgments

We are grateful to the Brazilian Ministry of Health (Coordenação Geral de Vigilância das Doenças de Transmissão Respiratória de Condições Crônicas) for collaboration. We are also grateful to Kleydson Andrade Alves for technical support.

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No competing interests reported.

SupplementaryFigure1.tif
Supplementary Figure 1. Mycobacterium tuberculosis (MTB) and rifampicin (RIF)-resistant MTB detected by Rapid Molecular Test (Gene Xpert) in Brazil and the regions from 2014 to 2020.
Supplementarytable1.docx
Supplementary Table 1. Trend analysis of the historical of Mycobacterium tuberculosis (MTB) and rifampicin (RIF)-resistant frequency series from 2014 to2020 by Brazilian region.

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Evaluation of GeneXpert® in Brazil Through a Historical and Epidemiological Approach

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Abstract

Figures

Background

Methods

Design and study aim

Setting of the study

GeneXpert MTB/RIF equipment data (RMT-TB equipment)

Data Collection of the Historical Context

GeneXpert Quantitative Data Collection

Health Care Indicators

Geoprocessing

Statistics Analysis

Results

Historical Background of GeneXpert in Brazil

Process for deployment of the GeneXpert equipment in SUS

Authorization of the use of GeneXpert equipment by SUS

Start of operation of GeneXpert equipment in SUS

Quantitative analysis of GeneXpert in Brazil

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

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