Tuberculosis in Upper and Lower Egypt before and after directly observed treatment short-course strategy: a multi-governorate study

Background Tuberculosis (TB) is a major problem in developing countries. TB in Egypt is considered an important public health problem. Egypt is ranked among the mid-level incidence countries. Objective To evaluate TB status in 19 governorates and to compare the TB situation in Upper and Lower Egypt over 20 years from 1992 to 2012 before and after the application of directly observed treatment short-course strategy (DOTS). Patients and methods This is a retrospective study involving record review. The registered data were collected from TB registration units in the 19 governorates. Results The highest percentage of TB cases was in the age group 15–30 years. Infection was higher in males than females and in rural areas more than urban areas. Pulmonary TB and smear positivity at diagnosis, second, third, and fifth month were higher in Lower Egypt. Treatment after failure or relapse was significantly higher in Upper Egypt, whereas default rate, failure rate, and death rate were significantly higher in Lower Egypt. Regarding treatment outcome, cure, complete treatment, and transfer out were significantly increased after DOTS than before. Failure, default, and death were significantly reduced after DOTS than before DOTS. Upper Egypt included higher incidence rates of TB, new adult smear-positive cases, new extrapulmonary TB cases, and sputum conversion rate at the end of the initial phase of treatment. Cure rate and treatment success rate were significantly higher among patients of Upper Egypt, whereas transfer out rate and retreatment failure rate were significantly higher among Lower Egypt patients. Conclusion TB is still a health problem in Egypt, with pulmonary TB more in Lower Egypt, whereas extrapulmonary more in Upper Egypt, but after the introduction of DOTS, there is a significant increase in cure and success rate, with markers of success being more in Upper Egypt.


Introduction
Tuberculosis (TB) is one of the major public health threats, competing with the HIV as the cause of death owing to infectious diseases worldwide [1]. According to the WHO, nearly 8.6 million cases were estimated to have occurred in 2012. Most cases are estimated to be in Asia and Africa (58 and 27%, respectively) [2].
Near the end of the 20th century, TB prevention and care in Egypt faced numerous issues. The most significant of these issues were the rejection of the patients with TB to be hospitalized for their management, high lost follow-up rate, rising levels of resistance against anti-TB drugs, and inadequate health education to both general population and healthcare workers [3].
Major progress in TB prevention and care followed the widespread implementation of directly observed treatment short-course (DOTS) strategy. Efforts must continue to pursue high-quality DOTS expansion and enhancement [4]. DOTS implies that a trained healthcare worker or other assigned individual provides prescribed anti-TB medications and watches the patient while taking each dose [5].

Aim
The aim was to evaluate TB status in 19 governorates and to compare the TB situation in Upper and Lower Egypt over 20 years from 1992 to 2012 before and after the application of DOTS.

Patients and methods
This is a retrospective study involving record review (from June 2017 to January 2018), which was carried out at 19 governorates. The registered data about all TB cases covering a period of 20 years (1992-2012) were collected from the TB registration units in the 19 governorates. Governorates included in the study were based on accessibility of records. This period included two stages: before the application of DOTS and after it. This research was accepted by research ethics committee of our institution. All the methodology performed was in agreement with the ethical standards of the institutional and/or national research council and with 1964 Helsinki assertion and its later amendments.
The gathered data entailed the following: TB registration code and the year; sociodemographic data, which included name, age, sex, and residence; forms of TB, either pulmonary (either smear positive or smear negative) or extrapulmonary (sites other than lungs, such as lymph node, intestine, meninges, breast, and renal); history of previous treatment if present (category of patients or type of the patient); new or relapse; treatment after failure; treatment after lost to follow-up; transfer in or others; and schedule of treatment (recommended standardized treatment regimen) according to NTP (2008) [6].
The recorded follow-up for smear-positive pulmonary TB included sputum smear microscopic examination for acid-fast bacilli, at the end of second month, fifth month, and at the end of treatment [7]. Outcomes included cure, treatment completed, treatment failure, died, lost to follow-up, and transfer out.

Statistical analysis
The recorded data were tabulated and analyzed using SPSS version 16 software (IBM inc, Chicago, USA). Categorical data were displayed as number and percentages, whereas continuous variables were displayed as mean and SD. χ 2 -Test, Fisher's exact test, and Student t-test were used. Microstat software was used to calculate "Z" test for two proportions of two independent groups. P value less than 0.05 was considered significant.  Table 3).
After DOTS implementation, infection between younger ages (30 and 45 years) was significantly reduced (31.4 and 30.0% before, whereas 25.9 and 20.1% after DOTS). The ratio of infected females was less after DOTS than before (32.0 and 45.4%, respectively). Infection among urban patients was also reduced after DOTS than before (43.6 and 50.9%, respectively) whereas infection increased among rural patients (56.4 and 49.1%) after and before DOTS ( Table 5).
Cases of pulmonary TB were less after the implementation of DOTS (68.6%) than before (84.8%). Concerning the smear results at diagnosis, they were 56.7% before DOTS and became 64.4% after. The percentages of smear-positive cases at second, third, and fifth month and end of treatment were lower after DOTS than before (19.2, 14.2, 4.7, and 1.7%, respectively, after DOTS and 28.7, 19.6, 13.5 and 7.2%, respectively, before DOTS) ( Table 6).
According to patient type, new cases, treatment after failure, relapse, and treatment after lost to follow-up decreased significantly after the introduction of DOTS. In terms of treatment outcome, the percentages of cure, complete treatment, and transfer out significantly increased after DOTS (51.2, 31.5 and 7.6%, respectively) than before (49.6, 28.3 and 5.7%, respectively) (P<0.001). On the contrary, failure, lost to follow-up, and death decreased after DOTS (4.7, 1.4 and 3.5%, respectively) than before DOTS (6.4, 7.2 and 2.8%, respectively) ( Table 6). Table 7 showed that cure rate and treatment success rate were significantly higher among patients of Upper Egypt (P<0.001), whereas transfer out rate and retreatment failure rate were significantly higher among Lower Egypt patients.

Discussion
This study was aimed at comparing TB status in Upper Egypt versus Lower Egypt before and after the  below the average among the Egyptian population, which can be owing to the widespread application of TB stop strategies [8].
Age distribution of patients was similar between Lower and Upper Egypt as the highest percentage of cases was between 15 and less than 30 years, and the lowest  percentage was for extremes of age less than 15 years and after 60 years. These results are in agreement with many individual Egyptian governorate studies that showed same results [9][10][11][12][13][14][15][16][17][18][19][20][21]. However, in Alexandria, the highest percentage of cases was in the age range 30-45 years [22]. A study by Eldahshan et al. [23], in Suez Canal showed that the highest age group was 30-50 years followed by patients more than 50 years. The explanation of increased TB cases in this age group (15-30) may be the increased smoking in this age group. In addition; poorness, inadequate nutrition, physical, mental stress, along with more exposure to infection may also contribute.
The highest percentage was in males (66.1 and 62.7%, respectively), with statistically significant difference between males and females (Table 2), which was in concordance with most individual governorate studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. This difference may be owing to low notification rates in females as many female patients do not seek medical advice because of factors such as illiteracy and the traditions predominant in the society, which may prohibit them from going out and seeking medical advice. TB stigma is felt more strongly in females [24]. Moreover, notification rates in men are higher, indicating differences in exposure owing to more outdoor activities and contact. Progression from infection to disease owing to sex differences were related to other risk factors for TB such as cigarette and shisha smoking [13]. In this study, TB cases were more in urban (51.3 and 57.4) than rural (42.6 and 48.7%) areas in both Lower and Upper Egypt, respectively. There is a difference in distribution of TB between governorates studies where El-Behira [13], Dakahlia [20], Qalyobia [9], Minofia [10], Assiut [25], Sohag [21], and Aswan [16] showed that TB cases were more in rural areas. Those studies explained the higher TB cases in rural areas owing to poverty, drinking contaminated milk, exposure to cough spray from infected cattle, or by close physical contact with infected animals. However, in Sharkia [19] and Ismailia [17], despite the rural population is more than the urban, TB cases were higher in the urban areas, and their explanation for that was the possibility of overcrowding at the urban areas, especially slums with lack of proper aeration and increase of air pollution, whereas the awareness among the rural population about TB especially after implementation of DOTS in all primary healthcare units may be the cause for lower percentage of cases. In Port Said, which is mainly urban governorate, cases were more common among the urban areas. In addition to the reasons described by Nafae et al. [19], demographic changes with population growth in urban areas resulting from the migration of people from rural to urban areas could be a cause [15].
The study also revealed that the percentage of pulmonary TB was lower in Upper Egypt (71.1%) than Lower Egypt (75.0%). The percentages of smear-positive cases at the second, third, and fifth month and end of treatment were higher in Lower Egypt compared with Upper Egypt. This can be explained by heterogeneous population distribution, with the two largest Metropolitan cities Cairo and Alexandria lying in Lower Egypt; this leads to crowdedness, spread of slums, low socioeconomic conditions, poor housing with poor ventilation, and more exposure between people to the infectious aerosols [26][27][28].
According to the type of patient, treatment after failure and relapse were significantly higher in Upper Egypt. Moreover, the percentages of cure were significantly higher in Upper Egypt (55.8%) than Lower (45.4%) (P<0.001). Conversely, increased failure rate, death, lost to follow-up, and transfer out were higher in Lower Egypt. These differences between Upper and Lower Egypt could be owing to the increased knowledge of the disease leading to increased percentage of people seeking medical care which increased the notified cases including relapse and treatment after failure in the Upper Egypt together with improvement and availability of health services per Capita which increased the percentage of cure cases relative to Lower Egypt which has more treatment failure rate and death rate. The increased death rate in Lower Egypt especially between urban more than rural areas can be attributed to the high demand for health services available in big cities such as Cairo and Alexandria; thus, many patients travel to these metropolitan areas to seek heath treatment. When deaths occur, they are registered in these metropolitan areas, which results in higher death rate [29].
After DOTS implementation in 1996 [7], infection between younger ages (30 and 45) declined significantly (31.4 and 30.0% before DOTS and 25.9 and 20.1% after DOTS). There was significant decrease in infection among females after DOTS than before (32.0 and 45.4%, respectively). This reflects the improvement in health awareness between patients, especially among females, who could overcome the TB stigma and seek medical care. This reflects also the success of TB stop strategy to reach the productive young community and females. Infection among urban patients was also reduced after DOTS than before (43.6 and 50.9%, respectively), whereas increased among rural patients (56.4 and 49.1%, respectively) after DOTS than before. This could be a false increase owing to increased case notification as a result of increased health awareness and availability of primary health services in rural areas.
Pulmonary TB infection was lesser after the introduction of DOTS (68.6%) than before (84.8%).
The percentages of smear-positive cases at second, third, and fifth month and end of treatment were decreased after DOTS than before (19.2, 14.2, 4.7, and 1.7%, respectively, after DOTS, whereas 28.7, 19.6, 13.5 and 7.2%, respectively, before DOTS). This reflects greater treatment success, which is because of new regimens of treatment with rifampicin for 6 months, direct observation of cases on treatment, and better follow-up of patients [15]. On the contrary, there was an increase in extrapulmonary cases from 15.2% before DOTS to 31.4% after DOTS. This could be owing to more availability of diagnostic techniques like specific radiographs, ultrasound (US), computed tomography (CT) scans, or biopsy procedures, which are essential for diagnosing extrapulmonary TB [20].The smear positivity at diagnosis was 56.7% before DOTS and became 64.4% after; the rise in the smear positivity at diagnosis without increase in the overall pulmonary cases could be owing to improvement in the laboratory diagnosis, or increase in the notification rate of smearpositive cases.
Upper Egypt has higher incidence rates of new adult smear-positive cases, new extrapulmonary TB cases, and sputum conversion rate at the end of the initial phase of treatment, whereas new pulmonary TB cases, cases with no smear result, and new TB cases with no smear conversion result were significantly higher among TB residents of Lower Egypt (P<0.05). This can be explained by better case notification, laboratory diagnosis of sputum smears, and follow-up of patients with sputum smear at second, third, and fifth month in Upper Egypt. Increased life expectancy may reactivate quiescent TB lesion from extrapulmonary areas, and more physical contact with infected animals by drinking or handling contaminated milk may also contribute [20].

Conclusion
TB is still a health problem in Egypt, which affects the young active age group with pulmonary TB more in Lower Egypt, whereas extrapulmonary cases were more in Upper Egypt, especially in the rural community, but after the introduction of DOTS, there is a significant increase in cure and success rate with decrease in treatment failure and death rates, with markers of success being more in Upper Egypt.

Limitations
Owing to difficult accessibility to records, the study did not cover all the Egyptian governorates. Additionally, there was a lack of recording before DOTS in four governorates, and cultures were not done for all patients, and if done, results were inconclusive, so not added in the study. Multidrug resistant status was not studied owing to technical or recording problems.

Recommendations
Health education is a vital part in implementing DOTS strategy with focusing on removing the TB stigma and encouraging patients to seek medical advice with more efforts needed, especially in Lower Egypt. Moreover, better recording of cases is essential for follow-up DOTS and putting future plans. The use of new technologies in the diagnosis to improve culture results is needed and also for extrapulmonary disease diagnosis.

Financial support and sponsorship
Nil.

Conflicts of interest
There are no conflicts of interest.