MATERIALS AND METHODS
This was an analytical cross-sectional study with reported cases of TB coinfected with HIV in Minas Gerais State, Brazil, in 2016, registered in the Brazilian Information System for Notifiable Diseases (SINAN), provided by the State Office of Health of Minas Gerais (SES/MG – Secretaria do Estado da Saúde de Minas Gerais). Minas Gerais State has 853 cities with 21,119,536 inhabitants (in 2017), and is considered the second most populated state in Brazil.
Due to the period of implantation and adaptation to the new TB notification in the state, 2016 was the year chosen because it contains cases after this phase and the cases had a concluded closure status with respect to treatment, considering that TB is treated for at least 6 months.
Variables selected for this study were: cases of TB/HIV, closure status (cure, abandonment, death from TB, death from other causes), age group, sex, ethnicity, education, district, pregnant woman, type of entrance, special populations (prisoners, healthcare practitioners, immigrants, homeless people), type of disease (pulmonary, extra-pulmonary or pulmonary and extra-pulmonary), associated diseases and disorders (AIDS, alcoholism, diabetes, smoking, mental illness, illicit drug abuse), sputum smear microscopy, chest X-ray, ART use and HIV test, as well as the rapid molecular test. Blank data or data specified as a not specified category was considered unknown10.
The inclusion criteria were new cases notified in 2016 with closure status defined as cured, abandoned, death from TB and death from other causes. Blank outcomes (without a defined closure status) were excluded.
Data were analyzed with the Statistica software version 10 (StatSoft, USA), through descriptive statistics, and the differences between proportions of the variables and the closure status of the case were verified through the Chi-square test. The variables with significant difference (p≤0.05) were included in the Multiple Correspondence Analysis (MCA), enabling to verify the association between the “additional” variable closure status of the case with the other “active” variables in a factorial plan11–13.
The project was approved by the Human Research Ethics Committee of the Federal University of Triangulo Mineiro (UFTM – Universidade Federal do Triângulo Mineiro), opinion N° 2.099.176. The Free and Informed Consent was not used as we dealt with secondary data from a database and had no variables identifying the participants.
Many factors increase the susceptibility to infection by Mycobacterium tuberculosis, such as impairment of the immune system by several diseases and medicines, like HIV and AIDS, type II diabetes, terminal kidney disease, alcoholism, intravenous drug abuse, certain types of cancer, chemotherapy to treat cancer, malnutrition and very young or advanced age. Some other factors include the use of tobacco, which increases the risk of contracting and dying due to TB14,15.
The insertion of the variable “diseases and disorders associated” to TB, included in the notification, was correlated with the treatment outcomes, being a favorable indication of its importance to assess and supervise the cases of TB/HIV. The insertion of the variable “special populations” showed low number of cases in which information was provided and they were not associated with the outcome in the MCA12,13.
An association between treatment abandonment and diseases associated with smoking, illicit drug use and mental illness was observed. The ratio of people abandoning the treatment was 18.9%, higher than the ratio verified in Alagoas State (10.42%) and Piaui State (4.8%)2.
Tobacco smoking interferes by suppressing the activation of the immune response inherent to bacterial infections. Nicotine may inhibit the signaling of T cells and production of antibodies, in addition to a potential inhibition of apoptosis, a defense mechanism against TB infection15,16. Studies indicate that alcohol and drug consumption favor abandonment of treatment, as well as poverty and low education7. The improper alcohol consumption also impairs the immune system, inhibiting cellular functioning and hindering the destruction of invasive microorganisms. It also interferes with the production of signaling molecules that directly help the immune response, such as cytokines, increasing the susceptibility to TB15. In a literature review study, Cruz et al.17 reported that the illicit drug abuse favors the dissemination of TB. Crack (cocaine) induces cough, favors intimate contact in closed environments and intermittent people flow. In addition, there was spread of HIV infection among malnourished drug users as malnutrition makes the users even more vulnerable. Another literature review study indicates that the illicit drug abuse favors the low adherence to and the abandonment of treatment. The stereotypes associated with drug abuse poses an obstacle in the appropriate approach to users, and the healthcare practitioners do not have a specific ability to make this approach18.
Other factors may also contribute to the non-adherence to treatment, such as the use of other medicines, the type of medicine, history of previous treatment of TB and previous abandonment, the lack of training of healthcare practitioners, low doctor-patient interaction, need to hospitalization, operational problems to follow the treatment, fear to be stigmatized and discriminated after the disclosure of the HIV diagnosis, side effects and drugs toxicity, the patient's disbelief in the treatment efficacy, complexity of treatment, different place to treat TB and HIV/AIDS, difficulty to give the TB diagnosis to patients with AIDS, depression and no social support18.
It is known that the pulmonary TB is relevant to the public health due to its high infectivity and the easy diagnosis in comparison to other types of TB, helping to interrupt the chain of transmission2,19. Pulmonary TB was predominant (60.6%), followed by extrapulmonary TB (28.9%). A similar result of 62.7% was observed in a study carried out in the city of Contagem, Minas Gerais State20. In a national-based study, a similar result was also observed, between 37% and 40% for extrapulmonary TB, and 59% and 62% for pulmonary TB21. The results are also similar to the ones found in Ethiopia, where 51.8% of the patients had pulmonary TB and 44% had extrapulmonary TB22.
In 2014, the Rapid Molecular Test Network (RTR-TB – Rede de Teste Rápido Molecular) was implemented in the public health system in order to diagnose TB and there was progress during the first years of RTR-TB use. The test is important to reduce the spread of the disease, since it detects the presence or absence of the bacillus, quickly shows the resistance to rifampicin, facilitating the work process of healthcare teams and the epidemiological surveillance, speeding up the beginning of treatment, whether TB is resistant or not to the drugs23. In Minas Gerais State, many individuals were not submitted to the molecular test (70.45%) and to the drug-sensitivity test (57.1%), being an indication that RTR-TB has not shown epidemiological impacts in Minas Gerais State so far according to the results, probably due to the fact that Minas Gerais was the 15th state to perform the test and one of the states with higher rates of underused equipments23–25.
Most cases of TB/HIV were in male adults (75.6%), with acquired immunodeficiency syndrome (AIDS) and pulmonary TB. Belo et al.26 found a significant difference between sex and delay in the diagnosis of the disease, being higher in women than in men (p<0.05), which can be explained by the differences in behavior between genders, being reported that men had early and rapid access to quality health services. The high proportion of cases in males with working age between 30 and 49 years old (63.3%), being most of mixed ethnicity (black and white) (49.4%), was also observed in other researches using SINAN in different states of Brazil2,21. Magno et al.21 verified predominance in males (>71%), in the age group between 25 and 40 years old (>53%), in mixed ethnicity (black and white) patients (>83%). A study carried out in Piaui State between 2007 and 2016 with cases of TB/HIV coinfection has also observed predominance in males (75.4%), in the age group between 20 and 49 years old (79.5%) and in mixed ethnicity (black and white) patients (73.8%)2.
Considering that almost every patient had AIDS and that a little more than half of them used ART (57.4%), which is important for the the immune system function, the low percentage of cure (40%) and the significant number of patients abandoning treatment may be related to the low adherence to ART and to diseases and disorders associated with TB. All cases were of TB coinfected with HIV and, therefore, they should be on medication recommended to all HIV-positive patients regardless of their CD4 count and the virus count, according to a 2013 recommendation24, and that the treatment of the TB/HIV coinfection follows the same principles that the one in non-HIV infected individuals27. ART reduces the risk of TB among people living with HIV/AIDS in 67% and, if expanded, may contribute to reduce TB rates at the population level28–30.
TB/HIV coinfection may favor resistance to drugs, attributed to the immunological state and potential abandonments prior to treatment. The proportion of TB multi-resistant to other first-class drugs was 2.9%, a rate higher than the one verified in a study by Gaspar et at.31 who reported it in 0.17% in patients coinfected with TB/HIV and in a study by Silva et al.32 in 0.14%, in TB cases without HIV coinfection.
The TB cure rate of 40.0% was lower than the rate verified by Oliveira et al.2 in Piaui State (60.8%), by Silva et al.32 in Alagoas State (57.03%), and in Brazil between 2002-2012 (50.74%)31. The low cure rate must be analyzed with special attention by health authorities, as cure benefits not only the patient, but the entire social scope in which the patient is inserted, breaking the chain of transmission32, particularly in smear-positive pulmonary cases, the majority group in this study (60.6%).
It was verified that the cure was associated with individuals between 40 and 49 years old, without diseases related to TB, probably because this group is composed by people who are more careful with their health since they do not use drugs, tobacco, and they do not drink alcoholic beverages in an abusive way and are possibly favored as they do not have diabetes, mental illness and other diseases concurrent to HIV/AIDS. A study carried out by Gaspar et al.31 has shown that patients with TB/HIV have 48% less chance to be cured, 50% are more likely to stop the treatment and 94% are more likely to die from TB with respect to those without coinfection.
The deaths from other causes, excepting for TB, were associated with the ages between 30 and 39 years old, having AIDS and other diseases associated with TB registered as unknown, probably because the notification was made at the time of the death, explaining why the practitioner who made the notification failed to collect the information from the patient itself or from their family members. Deaths from TB totaled 7.2% of the notifications and deaths from other causes totaled 33.9%. A study carried out in Amazonas State with cases of TB/HIV reported that deaths took place in the age group between 25 and 39 years old and were more likely to be notified, increasing the chance of TB notification by 40%21. In Piaui State, the death rate was lower than the one in this study (3.5%), and the same happened in a research carried out with national data (3.63%) for patients with TB/HIV31 coinfection, and deaths from other causes have also shown a lower rate (3.8%)2.
Prisoners totaled 3.9% of the cases. A study carried out in Alagoas State reported that people confined in overcrowded and unhealthy environments with inadequate ventilation had a higher exposure to risk factors related to the infection by Mycobacterium tuberculosis, but they found a lower proportion of cases (2.84%)32.
On the other hand, homeless people in this study were 4.4%, a fact that concerns the sanitary authorities, since they perpetuate the disease, particularly with respect to the optimization of treatment strategies in this target audience. Purely biomedical approaches have a limited effect on the cure, since they do not consider important factors predisposing to the disease33,34. Interventions should go beyond approaches to individual lifestyle factors, considering health inequalities that lead to exclusion, malnutrition, poor access to diagnostic services and health care, in addition to improper use of legal substances such as alcohol and tobacco, and illicit substances, like crack (cocaine). A study evaluated the experience of healthcare practitioners in the care of homeless people with TB, concluding that a complete human resource staff is not enough to provide health care for this population, as the adherence to treatment is complex. Factors such as intersectionality and availability of resources and government incentives are important, such as public transportation vouchers, basic food basket and the directly observed treatment35.
There was no registration of cases in healthcare practitioners. Despite being a risk group for this infection due to exposure to patients during the workday and shortage of administrative, environmental control, and individual protection measures36. Even in the absence of cases, it is necessary to be alert to the early diagnosis in this target audience, since the study carried out in the city of Vitoria, Espirito Santo State, with primary care health practitioners found a high prevalence of latent infection by Mycobacterium tuberculosis in this population, ranging from 39.4% to 54.1%, with a higher proportion among the community health workers37.
As one of the main challenges of the Brazilian National Plan for the End of Tuberculosis as a Public Health Problem, it is important to improve the diagnostic network for TB and resistant TB; expand and maintain the RTR-TB; implement surveillance of TB deaths, latent infection and resistant TB; improve information systems for monitoring and decision-making purposes; strengthen the disease control actions in the most vulnerable populations; approach the disease in the perspective of social determinants; expand the decentralization and qualification of coping actions in basic care and improve the treatment outcome indicators24.
The limitations of the study include the use of secondary data sources with predetermined variables, with possible lack of information and underreporting of cases. However, since TB is a disease whose treatment is offered only in the public health network, the underreporting of this disease is likely to be reduced. A recent study in Amazonas State has indicated an underreporting rate of HIV cases of 7.7%, while the national average was 6.9%21.
People with communicable chronic diseases such as TB and HIV/AIDS are more likely to develop chronic non-communicable diseases, and if they coexist with TB/HIV, they increase the risk or the effect of the other. Generally, resource-constrained healthcare services are unprepared to deal with the dual burden of the disease, and the care and specific approaches to the disease are not the most efficient response to treat the coinfection. Traditional approaches need to be reevaluated, with greater emphasis on the multidisciplinary approach with the assistance of integrated care management33,38–40.