Active Tuberculosis Case Finding and Detection of Drug Resistance - Essay Example

Critical Analysis al affiliation Introduction People living with human immunodeficiency virus HIV are more susceptibleto opportunistic infections compared to those that are HIV negative. This is because HIV weakens their immune system. HIV increases the risk of reactivating latent Mycobacterium tuberculosis and increase the risk of rapid TB progression after infection and reinfection. Tuberculosis (TB) is one of the leading opportunistic infections that lead to significant morbidity and mortality. Diagnosis of TB is usually difficult because of non-specific symptoms, negative results of sputum smear microscopy, atypical or normal chest findings of the radiograph and lack of culture facilities in settings that have limited resources. This delays diagnosis and may lead to transmission within the community. World Health Organisation (WHO) recommends routine screening for active TB disease among patients living with HIV, with treatment for active TB or isoniazid preventive therapy for latent TB. However, due to resource limited settings, only a few individuals have been screened for TB. Moreover, the emergence of Multidrug resistance (MDR) is also a limiting factor in combating TB. Drug resistant TB exists in areas with high risk of infection with HIV. MDR-TB has progressed to extensively-drug resistant status (XDR-TB) and totally drug resistant (TDR-TB) infections in some areas. Other factors that contribute to development of active TB in HIV-positive patients include the degree of immunosuppression, lifestyle, high risk behaviour, and TB contact history. This paper is a critical analysis of a study done at Gondar, Northwest Ethiopia by Alemayehu, et al., (2014). The main hypothesis of the study was to establish the prevalence of undiagnosed pulmonary tuberculosis cases through active case finding and including multi-drug resistant TB (MDR-TB) among HIV-infected patients. The other hypothesis was to determine the causative agent for tuberculosis in the study population. The study area was appropriate because Ethiopia is ranked among top among countries with high burden of TB incidence. It has also a high prevalence rate of newly diagnosis and retreatment cases. Two XDR-TB cases were reported from a total of 45 MDR-TB cases in a study done at St. Peter’s TB Specialised Hospital and Nutrition Research Institute. In HIV positive patients, diagnosis is difficult because of lack of cavitary lesions in the advanced stages which cause a paucibacillary state in sputum. Current studies show that people living with HIV are at a higher risk of developing active TB, which may be the main cause of death in the population. A cross-sectional survey done on male prisoners through tuberculosis screening using symptoms, chest radiograph, culture and microscopy. It was established that 3.5 % were culture positive for Mycobacterium tuberculosis among those not taking tuberculosis treatment. The prevalence for HIV was 25.3%. The positive HIV status was associated with undiagnosed tuberculosis (Telisinghe, et al., 2014). According to Tabarsi, et al., (2015), HIV patients are prone to tuberculosis disease and screening of the patients was important. In the study there was a high rate of active TB about 38%. It is therefore recommended that careful and frequent screening of patients with signs and symptoms, X-ray and sputum examination must be performed. Intensive training of physicians should be dne to increase the awareness of TB and that TB can occur in any stage of HIV infection in addition to atypical presentation in mmunosuppressed individuals. Methods The study design was a cross-sectional study conducted among HIV patients attending the ARV clinic at a tertiary level teaching and referral hospital in Northwest Ethiopia called Gondar University Hospital between February 2012 and November 2012. This type of study is an observational study that involves analysis of data collected from a population at a specific point in time. This study is descriptive because it is used to assess the prevalence of undiagnosed pulmonary tuberculosis cases among HIV patients. Cross-sectional studies are often used for prevalence studies (Bonita, et al., 2006). The participants were 250 consecutive HIV patients, aged over 18 years and had at least one of the TB symptoms, that is cough, night sweats, fever or weight loss but undiagnosed during their visit at the clinic and the patients that had a history of previous TB and those on antiretroviral treatment (ART) or pre-ART were enrolled. This sample size is large enough to estimate the prevalence of undiagnosed TB cases. Patients who had severe illness and were unable to provide sputum and had started anti-TB treatment or IPT were excluded. The participants gave a written informed consent. The study also received an ethical approval from the ethics board of the University of Gondar and the AHRI/ALERT Ethics Review Committee. This is in accordance with the World Medical Association Declaration has enacted principles for medical principles for medical research involving human subjects. Using structured questionnaires, the socio-demographic features, clinical data and x-ray findings were collected. From the characteristics the Tuberculosis negative and positives were indicated, and the p value evaluated. The clinical presentation of HIV positive cases were non-specific such as an acute mononucleosis like illness accompanied by fevers. The potential bias in this study could be non-response in the questionnaires which could affect the outcome. The advantages of a questionnaire is that they are cheap, easy to get information within a short period, and it does not face interviewer bias. However this method may not be useful in case of illiterate respondents, clarification may be difficult when there are misunderstandings (Gillham, 2007). According to Hennekens & Buring (1987), cross-sectional studies are important in assessing the burden of disease in the specified population in prevalence of disease. They are helpful in assessing health care needs in populations. This type of study is also useful for descriptive analyses and generating hypothesis. The prelance for all factors can also be measured in addition to being quick easy to conduct with no long periods of follow up. However, the disadvantages include difficult to measure incidence, susceptible to bias and is not suitable for studying rare diseases for a short duration. The method is also prone to bias caused by low response. To test the hypothesis, three sputum samples were collected from all the eligible participants, pooled and using the conventional Ziehl-Neelsen staining technique, a direct acid fast bacilli smear microscopy was performed. The remaining aliquots of sputa were transported in a cold chain from the Gondar Microbiology Laboratory to the P3 TB laboratory facility for Mycobacterium culture, RD typing and drug susceptibility testing at Armauer Hansen Research Institute. Mycobacterium culture was done by decontaminating and homogenising the sputum sputum samples by the modified Petroff’s method. About 1ml of the sediment was inoculated into the conventional Lowenstein-Jensen (LJ) egg slant medium containing 0.6% sodium pyruvate and glycerol for primary isolation. The slants were held for 8 weeks at 37°C after inoculation and visually inspected for growth every day for the first and twice a week for 8 more weeks for the presence of mycobacterial colonies. In order to select AFB positive isolates, microscopic examinations of the colonies were performed using Ziehl-Nielsen staining method. Bacrteriology confirmed tuberculosis s defined as positive microscopy or M. tuberculosis culture. In molecular typing, heat killed cells were prepared from AFB positive isolates by mixing two loops full of colonies in 200µl of distilled water and by heating at 80 °C for an hour. To check for the presence or absence of regions of difference-9 for the identification of Mycobacterium tuberculosis from other species of bacteria, Polymerase Chain Reaction (PCR)-based deletion typing was performed. This method was applied to heat-killed mycobacterial suspensions. A multiplex PCR was designed to amplify the non-deleted RD9 region. Two external primers and one reverse primer were used per locus. RD9 is identified as the genomic segment that is present in Mycobacterium tuberculosis. Based on proportion method on 24 well tissue culture plates, indirect testing was done for the first line anti-TB drugs using Middlebrook 7H10 medium supplememented with glycerol and 10% oleic acid albumin dextrose catalase. Primary isolates grown within 2 to 3 weeks used for preparing the suspension. The DST plates were inoculated by adding 10 µl of the suspension which was adjusted with McFarland standard. The plates were securely sealed with Parafilm and incubated at 35 ˚C in a 5% CO2 incubator with a water reservoir. Drug susceptibility was determined by visually comparing the drug containing media with a drug free control on which 1:100 bacterial suspensions was inoculated. The drug sensitivity of the bacterial isolate and was later determined using the critical concentration level. Data analysis was done using SPSS software package Version 20.0. in this test a p value of less than 0.05 were considered statistically significant. The degree of association between different variables were measured using the logistic regression and odds ratio. Results The results were presented in tables. The socio-demographic variables included sex, residence area, marital status, educational background, and occupational status were presented appropriately on Table 1 in terms of frequency and percentage. The mean and the standard deviation of age was indicated to describe the study population. The clinical data of the 250 study participants were presented on Table 2. Table 3 showed immunological status of the study participants as depicted by CD4, T-cell count while Table 4 showed analyses of the risk factors for pulmonary TB among the study participants. Risk factors may be effect modifiers that is they have an influence on TB infection among HIV patients. The numerical data were discrete variables and they were presented in a table. The frequency distribution for the categorical variables are presented effectively in the table. The absolute frequencies were obtained by counting the number of observations in each category. The relative frequencies that is the percentage values were also presented. Moreover, appropriate legends were included and they allowed proper identification of each of the categories of the variable and the type of information provided (Duquia, et al., 2014). It was found out that 6% of the 250 participants were identified as having TB, 9 were newly detected cases and positive by both smear microscopy and culture and the others were previously treated TB cases and were only detected using culture. RD9 typing also showed that ten of the isolates were M. tuberculosis species, one belonged to Mycobacterium genus which could not be specified due to inaccessibility of the test kits and the remaining four isolates were non-tuberculosis therefore indicating the prevalence of undiagnosed pulmonary TB disease as 4.4%. As shown in Table 3, the overall CD4 T-cell count was relatively higher among non-TB cases compared with TB cases. In Table 4, logistic regression analysis indicated no significant associations between different variables and risk factors for pulmonary TB but for the presence of pneumonia. Regression models aid in investigation of common influence on several potential influence factors on the target parameter. Moreover, the analysis of drug susceptibility testing showed that all the Mycobacterium isolates became sensitive to all first line anti-TB drugs except for one isolate which was obtained from a newly diagnosed TB case that was resistant to streptomycin. In the study cohort, no MDR-TB was detected in both the newly diagnosed cases and previously treated TB cases. Discussion It was concluded from the overall findings that through active case finding, it was possible to identify more undiagnosed cases based on the 4.4% of undiagnosed pulmonary TB among cohort of HIV infected individuals visiting ART clinics in the Gondar area. The majority of the individuals were either smear positive or culture positive. It could also be established that there was a risk for transmission of the disease especially among family members. This is consistent with previous studies done that showed that the prevalence of undiagnosed TB among HIV patients. Corbett, et al., (2004), found a prevalence of undiagnosed TB to be 3.8% among 1773 systematically rectruited miners. The rate of smear positive was 0.4%. Wood, et al., (2007) identified a 9% prevalence of pulmonary tuberculosis in the HIV individuals with 5% being previuosly undiagnosed. This significantly higher than the current study. From the RD9 typing, it was found out that M. tuberculosis is the dominant causative agent for TB in the study population, since more than 60% of the isolates were M. tuberculosis. No association was found between the occurrence of TB and risk factors such as age, sex, residence, occupation, education, marital status, alcohol intake, shisha or tobacco use, previous TB contact history, stages of HIV or ART or CD4 count. This is inconsistent with findings by (Hinta , et al., 2015) who found out that there was a high burden of tuberculosis among drug users. They also found out that poor compliance to treatment, lower utilisation of health services, and low completion rates among drug users may lead to prolonged or severe tuberculosis. Low CD4 count is a major hindrance in excluding active TB in HIV infected individuals (Balabanova, et al., 2011). Moreover, all the drugs tested in the study did not show any resistance to first-line anti-TB drugs except for the isolate that was resistant to streptomycin. Gandhi, et al., (2006) found out that Multi-drug resistant tuberculosis has been transmitted to HIV co-infected patients and was associated with high mortality. MDR-TB has been observed frequently and found in many inpatient TB patients. If undiagnosed it poses a risk for transmission to other people in the setting (Bantubani, et al., 2014). High mortality rates have been observed among patients with HIV and drug resistance TB co-infection. Early approach in management of drug resistant TB has shown positive outcomes. Multidrug resistance has been associated with poor infrastructure for diagnosis TB drug resistance. Selection of the study design has a decisive influence on the study analysis (Ressing , et al., 2010). The major limitation for this study is that only a few HIV positive cases that had at least one symptom of TB but were undiagnosed at the attending clinic, or those who completed TB treatment at least 3 months before the study were considered. This led to identification of few positive cases that may have caused underestimation of the overall prevalence of drug resistance among the HIV positive population. Conclusion The study ascertains that it is important that health care providers should critically evaluate HIV patients clinically regardless of their ART screening and actively screen for TB at least through microscopic examination of TB to detect cases early and initiate anti-TB treatments. Moreover, low case finding rates may be caused by lack of pulmonary TB symptoms among the patients. This will reduce the mortality rates among HIV infected persons. Further studies are needed to confirm this study. To ensure better adherence to treatment, social support and treatment of accompanying alcohol and drug abuse in HIV infected individuals to diagnostic procedures and treatment. Preventive measures should be enacted to enhance the immunity of the body since many HIV positive patients had tuberculosis infection. Moreover, since diagnosis may be more difficult in the individuals therefore methods such as radiologic studies, pathologic examination of the biopsy specimen and other methods must be employed to avoid misdiagnosis. Moreover, laboratory facilities, enforcing case finding standards and using appropriate treatment for tuberculosis to prevent the spread of tuberculosis must be used to optimise the diagnosis of tuberculosis. This study is relevant as it confirms the importance of active case finding among HIV positive patients in determining undiagnosed tuberculosis among the cohort. Further studies are recommended to compliment this research and establishing methods of determining pulmonary tuberculosis among people living with HIV. This will also increase the survival rate and quality of life by easing the burden of disease. Bibliography Alemayehu, M. Gelaw, B., Abate, E., Wassie, L., Belyhun, Y., Bekele, S.,Kempker, R. R., Blumberg, H. M. Aseffa, A., 2014. Active tuberculosis case finding and detection of drug resistance among HIV infected patients: A crss-sectional study in a TB endemic area, Gondar, NorthWest Ethiopia. International Journal of Mycobacteriology, Volume 3, pp. 132-138. Balabanova, Y., Tohermyshev, V., Tsigankov, I., Maximova, S., Mikheeva, N., Fedyukovitch, L., 2014. Analysis of undiagnosed tuberculosis related deaths identified at post morterm among HIV-infected patients in Russia: a descriptive study. BMC Infectitious Diseases, 8(2). Bantubani, N. Bantubani, N., Kabera, G., Connoly, C., Rustomjee, R., Reddy, T., Cohen, T., Pym, A. S. , 2014. High Rates of Potentially Infectious Tuberculosis and MultiDrug-Resistant Tuberculosis (MDR-TB) among Hospital Inpatients in Kwa-Zulu Natal, South Africa Indicate Risk of Nosocomial Transmission. PLoS ONE, 9(3). Bonita, R., Beaglehole, R., Kjellstrom, T. & Organisation, W. H., 2006. Basic epidemiology. 2nd ed. Geneva: World Health Oragnization. Corbett, E. L., Charalambous, S., Moloi, V. M., Feilding, K., Grant, A. D., Dye, C., De Cock, K M., Hayes, R J., Williams, B. G., Churchyard, G. J., 2004. Human immunodefefiency virus and the prevalence of undiagnosed tubercuosis in African Gold miners. American Journal of Critical Care Medicine, 170(6), pp. 673-9. Duquia, R. P., Bastos, J. L., Bonamigo, R. R., Gonzales-Chica, David A., & Martinez-Mesa, J., 2014. Presenting data in tables and charts. Anais Brasileiros de Dermatologia, 89(2), pp. 280-285. Gandhi, N. R., Moll, A. & Friedland, G., 2006. 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