Retrospective Study of the Pattern of Pulmonary and Extrapulmonary Tuberculosis Cases in Ain Shams University Hospitals during the Period of 2016– 2022

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INTRODUCTION
Tuberculosis (TB) is an infectious bacterial disease.It can present with pulmonary or extrapulmonary TB [1].It represents a global health concern.Millions of people are diagnosed with TB every year worldwide, mostly in developing countries [2].According to the reports of the World Health Organization (WHO), the estimated count of new cases was 8.6 million in 2012.It rose to 10 million in 2019 [3,4].It follows human immunedeficiency virus (HIV) as a leading infectious cause of death, accounting for 1.2 million deaths in 2019 [1].Although vaccines and antimicrobial treatment are widely used, the infection rates have been rising after an initial fall.This problem is compounded by the spread of multidrug resistance among Mycobacterium tuberculosis (MTB) strains [5].
In Egypt, the estimated incidence is approximately 11-14 new cases/100,000 population, with a death rate of 0.43/100,000 population [6].Therefore, the TB burden in Egypt is considered low to moderate [7].Despite efforts to control the spread of TB in the Egyptian community, it is still a public health issue [6].Centers everywhere in Egypt have participated in the screening, diagnosing, notifying, and registering of TB cases under the umbrella of the National Tuberculosis Control Program (NTP) [2].This is essential for early detection, adequate treatment, and control of spread to new cases [1].
The aim of the current work is to assess the TB pattern at Ain Shams University Hospitals (ASUH) and correlate it with the characteristics of TB patients or suspects presenting to the hospital during the period from January 2016 through July 2022.

Study design:
This retrospective study was conducted at the Central Microbiology Laboratory, Clinical Pathology Department, ASUH.This study included the records of all TB patients or suspects presenting to the hospital who underwent diagnostic tests for tuberculosis, either smear analysis, Polymerase chain reaction (PCR), GeneXpert or culture, during the period from January 2016 through July 2022.The inpatients were admitted to the different departments of surgery, medicine, pediatrics, gynaecology and obstetrics hospitals, and the various intensive care units.The records were collected using the data gathered from the laboratory information system, excluding duplicate samples.

Study procedures:
Information regarding the following was collected and recorded using the records of all patients who underwent diagnostic testing for tuberculosis:  Demographic data: age and sex. Forms of tuberculosis; either pulmonary or extrapulmonary (and its site as LN, intestine, meninges, tissue, renal).
 Complete blood count (CBC) of the tuberculosis-positive patients.

Statistical Analysis:
The data were tabulated and analyzed using Microsoft Excel.Qualitative data were described as frequency and percentage and compared using the chi-square test (χ2)testing, while the quantitative one was presented as mean ± SD and was compared using Student's t-test.Statistical significance was set at P ≤ 0.05.

RESULTS
This retrospective study included the records of 7704 patients admitted to ASUH and suspected to have tuberculosis during the period from the first of January 2016 to the 31 st of July 2022.We found that 124 out of 7704 patients (1.61%) were positive for TB by either of the diagnostic tests.
The majority of the collected samples were lower respiratory samples (92.16%); 2.91% were blood, and 2.17% were pleural fluid.The least common sample type was urine (0.09%).Most of the positive samples were lower respiratory samples (92.74%), followed by pleural fluid (2.42%).All ascitic fluid, synovial fluid, tissue, and urine samples were negative for TB.
The age of the total positive TB cases was 41.84±16.06years, with 58.87% in the productive age group (31-60 years) and 65.52% in males.The comparison between the positive and negative cases revealed that there was a statistically significant difference between the two groups regarding age, age group, and sex (Table 1).
A higher percentage of cases were below 50 years old (60.48%).Of them, 56% were males and 42.1% were females; however, for the elderly group (> 50 years), 77.55% were men and 22.45% were women.There were significant differences between young and elderly patients according to sex (P value=0.0142)(Tables 2, 3).
As per the distribution of hemoglobin (HB) (gm/dl) and total white blood cells (WBC) (x10 9 /L) levels among positive TB cases, table (4) shows that the mean HB was 10.66 gm/dl, with 96 patients with HB level less than 12 gm/dl.For WBCs, the mean was 9.4 x10 9 /L, and 35 cases exhibited leucocytosis.Table (5) demonstrates that there were significant differences between the age of patients and HB level (p=0.0273).However, there were insignificant differences in WBC levels (P = 0.7766).Table (7) shows that during the 7 years of study, most of the positive TB cases were among the productive age group (31-60 years), except for 2017, where a higher rate was found among the 16-30 years group.For the sex distribution, the number of cases was higher among males except for 2020, when higher numbers were observed among females.It is worth noting that starting in 2018, high positivity rates were observed among females.Regarding the sample type, pulmonary TB cases outnumbered the extrapulmonary cases (EPTB).No cases of EPTB were detected in 2016 and 2018, and the highest numbers were found in 2022 (Figure 2).In In May 2020, the WHO stated that TB and COVID-19 cases disseminate through close contact.Thus, similar measures can control both.However, it was concerned about the medical status of TB patients.The WHO stressed ensuring the availability of diagnostic techniques and therapeutics for TB patients when all efforts were directed at containing the COVID-19 pandemic.The WHO warned against the potential deterioration in progress achieved in lowering the death rate of TB patients in the last five years [29].
Alene and coworkers (2022) alerted that reallocating the available sources to control COVID-19 will threaten the lives of TB patients and might result in disastrous health problems.Hence, a balanced direction of expenses and services in case of an epidemic is mandatory to maintain supplying the requirements to TB patients [30].
On the other hand, Wu and colleagues (2022) from China offered an interestingly different opinion assuming that the decline in TB cases was true owing to the effect of the strict measures posed by the Chinese authorities for containing the COVID-19 crisis, such as social distancing, wearing masks, and frequently washing hands.Therefore, they studied the impact of these measures by introducing three models for the prediction of variation in the incidence of PTB cases in China after January 2020.One of them was noninterventional, and the other two were interventional with regular and strict interventions.They observed a marked overall reduction in PTB occurrence during 2020, which probably was the outcome of the intervening actions against COVID-19.They concluded that by applying the aforementioned strategy for the following two years, the incidence of PTB would decrease by approximately 1.03 per 100,000 people each month compared with the incidence predicted by the noninterventional model.They estimated that the annual incidence would be reduced from 59.15 to 50.65 per 100,000 in 2021 by performing strict instead of regular interventions.Based on their results, they suggested that the continuous application of regular interventions would play an important role in the future prevention and control of PTB [31].
They explained the difference between their study and the other studies in that they quantified the potential effect of preventive measures based on limiting close contact between infected people and uninfected people, which may exert positive effects in preventing PTB if continued to be implemented post-COVID-19 [31].However, other studies stressed the compromising impact of these measures on TB diagnosis, thus resulting in an artificial decline in the number of TB cases [32,33].
In summary, our findings have important implications for clinical and public health policies for tuberculosis prevention via the disruption of the chain of tuberculosis transmission.We recommend several strategies for the regular prevention of TB, including wearing masks in endemic regions, providing government-subsidized masks for crowded public places, maintaining good hand hygiene, avoiding large crowded indoor gatherings, and controlling the number of people in gatherings.
The limitations of the present work were the unavailability of data regarding clinical conditions, radiologic findings, smoking, residence rural/urban, socioeconomic status, history of previous treatment, and whether the infection was new or old.Additionally, different methods of diagnosis were used, and not all the samples were tested by Gene Xpert.Sputum analysis for acid fast bacilli was used as it is an affordable and quick test for diagnosis, but it might yield negative results with poor sample quality.

CONCLUSION
TB is more prevalent among the productive age group, especially PTB.Although TB is more common among men, we noted an increasing trend among females.Thus, it is suggested that the TB control approach should provide more care for those patients and propagate awareness to avoid unhealthy practices that participate in the dissemination of positive cases, such as tobacco smoking.The frequency of TB-positive cases was the highest (2.26%) in 2018.It reached its lowest level (0.84%) in 2021, in concurrence with COVID-19.We recommend encouraging hygienic practices similar to those used to control COVID-19, such as washing hands and wearing masks in crowded places.In our opinion, this would help us achieve our dream and minimize the number of TB patients, thus decreasing the financial burden.Additionally, we recommend conducting large-scale studies to propagate awareness and study the effect of implementing health practices on the number of TB cases.

Figure ( 1 )
Figure (1): The TB-positive cases in relation to the total number of cases from 2016 to 2022.

Table ( 1
): Comparison between the positive and negative cases regarding age, sex and sample type.

Table ( 2
): Correlation of the studied patients according to age/distribution of cases in relation to age.

Table ( 3
): Correlation between age and sex among studied patients.

2 Chi-squared test Table (4):
Distribution of HB and WBC levels among positive TB cases.
(5)le(5): Correlation between young and elderly individuals according to HB and WBC levels.Table (6):The frequency of TB-positive cases and their relation to the total patient number from 2016 to 2022.

Table ( 7
): Distribution of cases according to age group, sex and sample type during the study period.
70.87%) than males (29.13%) admitted to the Assiut Chest Hospital from 2005 to 2009.That variance can be attributed to the fact that in Upper Egypt, the female shares the male the responsibility of work both outside and inside the home, with a greater chance of exposure to infection.
These findings were in agreement with several Egyptian studies.They found that there was a male predominance among the TB patients, with much higher cases among reproductive age.They stated that pulmonary TB cases surpassed extrapulmonary cases [2, 7, 9-12].Shafiek and colleagues (2022) stated that the majority of EPTB patients in their study had tuberculous pleural effusion (32%) [6].Another cause is the prevalence of the attitude of cigarette and shisha smoking among men [1].On the other hand, Mohamed and his team (2010) [13] found that TB was more prevalent among female patients (