TY - JOUR
AU - Shogbamimu,, Yeside
AB - Abstract Background Multimorbidity is increasingly being recognized as a serious public health concern in the control of both drug-susceptible and drug-resistant tuberculosis (DR-TB). This study assessed the pattern of comorbidities and their prevalence in DR-TB patients at treatment initiation in Lagos, Nigeria. Methods A cross-sectional study was conducted. The baseline laboratory records (human immunodeficiency virus [HIV] status, fasting blood sugar, audiometry, thyroid function tests, serum electrolyte, haemoglobin level and pregnancy test) of DR-TB patients initiated on treatment in Lagos, Nigeria between 1 August 2014 and 31 March 2017 were reviewed. Results A total of 565 DR-TB patients’ laboratory records were reviewed, of which 397 (70.3%) had comorbidities. The proportion with one, two, three and four comorbidities was 60.2%, 29.7%, 8.1% and 2.0%, respectively. Anaemia was the most common (48.1%) comorbid condition, while anaemia and hypokalaemia (7.3%), anaemia and hypothyroidism (6.5%) and anaemia and HIV (5%) were most common among patients with more than one comorbid condition. DR-TB patients with comorbidity were significantly older (34.8±12.3 y) than those without comorbidity (32.0±12.8 y) (p=0.038). Of the 176 females in the reproductive age group, 8 (4.5%) were pregnant at baseline. Conclusions The prevalence of comorbidity among DR-TB patients was high. There is a need for the national TB program to expand its DR-TB council of experts and also integrate reproductive health services into DR-TB management in Nigeria. comorbidity, drug-resistant tuberculosis, Nigeria, prevalence, treatment initiation Introduction Multidrug-resistance tuberculosis (MDR-TB) is the emergence of resistance to at least isoniazid and rifampicin.1 In 2016, about 490 000 and 110 000 MDR-TB and rifampicin-resistant TB (RR-TB) cases, respectively, were notified globally and 47% of these cases were from China, India and the Russian Federation.2 Nigeria is one of the 14 countries globally with a high burden of TB, TB/human immunodeficiency virus (HIV) and MDR-TB.2 The incidence of MDR-TB/RR-TB in the country was 11/100 000 population; 4.3% of new and 25% of previously treated TB patients were drug-resistant TB (DR-TB) in 2016. In Nigeria, about 74% of the 1686 laboratory-confirmed MDR-TB/RR-TB cases were commenced on treatment in 2016 and the treatment success for MDR-TB/RR-TB was put at 74% by the World Health Organization (WHO).2 Multimorbidity is increasingly being recognized as a serious public health concern and an obstacle to the control of both drug-sensitive TB (DS-TB) and DR-TB globally.3 There is sufficient evidence to suggest that comorbidities such as HIV infection, diabetes mellitus (DM), chronic kidney disease, cigarette smoking and alcohol abuse are associated with the risk of developing DS-TB and DR-TB and treatment outcomes.3–7 Previous systematic reviews and meta-analyses have demonstrated a higher proportion of comorbidities among MDR-TB patients because of longer treatment duration and adverse drug reactions.3,8 Since comorbidities play an important role in the risk of developing DR-TB and treatment outcomes, early identification and prompt treatment will impact the patients’ well-being, and the National TB control program, especially in a high-burden DR-TB country like Nigeria. Presently, no study from Nigeria has addressed this concern. This study assessed the pattern of comorbidities and their prevalence among DR-TB patients at treatment initiation in Lagos, Nigeria. Methods A cross-sectional study was conducted. Laboratory records of DR-TB patients (diagnosed using Xpert (Mycobacterium tuberculosis/rifampin [MTB/RIF] assay) initiated on treatment between 1 August 2014 and 31 July 2017 under the Lagos State TB and Leprosy Control Program (LSTBLCP) were reviewed. Study setting Lagos State is one of the smallest states in Nigeria in terms of landmass. It is a megacity occupying about 3577.28 km2 with a projected population of 24 821 418 in 2017.9 Lagos State is the commercial nerve centre of Nigeria and is divided into 20 local government areas (LGAs) and 37 local development council areas (LCDAs) for administrative purposes. The LSTBLCP is responsible for the coordination of TB programs in the state with support from the WHO, US Agency for International Development (USAID) and the Dutch Tuberculosis Foundation (KNCV). The Lagos TB program is coordinated by a TB control officer and assisted at the local government level by LGA TB supervisors. The LGA TB supervisors send a quarterly report to the state of TB activities from all TB treatment centres in their LGA. The state data are sent quarterly to the national TB program (NTP). However, for DR-TB, the state is notified of each case electronically once a diagnosis is made by the Xpert MTB/RIF assay and patients are contacted directly by the state TB program. Lagos State contributed approximately 17% of all DR-TB cases diagnosed in 2016 in the country. There were 314 public and private health facilities providing TB services as of December 2016. Management approaches to DR-TB Management of DR-TB starts with an accurate diagnosis. To enhance this, all presumptive TB patients were required by the NTP to have an Xpert MTB/RIF assay to determine their bacteriological status and resistance to rifampicin. However, in centres where the Xpert MTB/RIF assay was not available, the use of sputum acid-fast bacillus for diagnosis was allowed. Priority was given to symptomatic contacts of confirmed DR-TB patients, TB patients who failed the first-line treatment, previously treated DS-TB patients, HIV patients with symptoms of TB and patients with symptoms suggestive of extrapulmonary TB. This category of patients is required to do have an Xpert MTB/RIF assay.10 Treatment initiation of DR-TB patients commenced with baseline laboratory tests that were performed on all newly diagnosed DR-TB patients at a designated hospital in the state. During baseline laboratory tests, patients were educated on the mode transmission of TB infection, development of resistant TB, differences between DS-TB and DR-TB, treatment duration of DR-TB, adherence issues to the second-line drugs and how monitoring of treatment was performed. Care and support for DR-TB patients, common side effects and adverse drug reactions of the second-line drugs and what to do in the event of any adverse drug reaction were also highlighted during baseline investigations for DR-TB patients. Laboratory tests such as electrolytes and urea, creatinine, urinalysis, full blood count, liver function test, hepatitis B surface antigen, chest X-ray, thyroid function test, fasting blood sugar, HIV test (and if positive, CD4 count and viral load) and pregnancy test were conducted at baseline as the standard testing programme to detect comorbidities. Also, anthropometric measurements (weight and height) were taken and pure tone audiometry was performed to assess the presence of hearing deficit. Sputum samples were taken for line probe assay (LPA) (to detect resistance to fluoroquinolones and second-line injectable drugs), sputum culture and drug sensitivity and testing (DST). All laboratory tests were conducted in a reference hospital using standard methods. Appropriate measures were instituted to correct any observed derangement or deficit in the laboratory or clinical parameters as much as possible before the commencement of DR-TB treatment by a consortium of experts team (CET). The CET consisted of a thoracic physician or a DR-TB-trained medical officer, a DR-TB-trained nurse, a pharmacist, a social worker or trained counsellor and an administrative assistant. They have the oversight function of all aspects of DR-TB management and collectively decide on any other form of treatment for DR-TB patients.10 Outcome measures Comorbidity In this study, comorbidity is defined as the presence of one or more of the following conditions: anaemia, hypothyroidism, hypokalaemia, hearing loss, DM and HIV co-occurring with DR-TB. Figure 1 Open in new tabDownload slide Patients’ flow chart. Figure 1 Open in new tabDownload slide Patients’ flow chart. Definitions of comorbid conditions Anaemia at baseline was defined according to WHO guidelines as haemoglobin 13 g/dl (males) or 12 g/dl (female).11 Hypothyroidism was classified into subclinical (defined as an elevated serum thyroid-stimulating hormone (TSH) above the upper limit in combination with normal free thyroxine [T4]) vs overt hypothyroidism (elevated TSH, usually >10 mIU/L, in combination with low T4). The reference ranges for TSH, T4 and T3 were 0.4–4.0 IU/ml, 59–153 nmol/L and 0.56–1.88 ng/ml, respectively.12 Hypokalaemia was defined as a serum potassium level <3.0 mmol/l.10 A calibrated diagnostic audiometer (Amplivox 240, Amplivox, Eynsham, UK), a headband and a bone stimulator were used to assess hearing loss. Pure-tone sounds were produced, which ranged from 0.25 to 8.00 kHz and 0.25 to 4.0 kHz. Audiogram outcomes were classified as normal, conductive hearing loss, sensorineural hearing loss or mixed hearing loss.13 DM was defined using the WHO definition of a fasting blood sugar of 126 mg/dl or a history of DM or a history of the use of hypoglycaemic agents.14 HIV infection was diagnosed using Determine (Alere Determine HIV-1/2 test, Matsuhidai Matsudo-shi, Chiba-ken, Japan) and Uni-Gold (Trinity Biotech, Bray, Ireland) in a parallel algorithm. In discordant cases, STAT-PAK (Chembio diagnostic systems Inc., Medford, New York, USA) was used as a tiebreaker. All DR-TB patients (n=565) who had baseline laboratory tests were included in this study. Participants flow, losses and exclusions Between August 2014 and July 2017, 694 DR-TB patients were diagnosed in Lagos State using the Xpert MTB/RIF assay. Of those diagnosed, 129 (18.5%) were excluded from the analysis; 53 declined the invitation for baseline laboratory tests, 37 gave wrong contact details and could not be reached, 21 died before baseline laboratory tests were performed, 12 were very ill and were referred to another hospital in another state for treatment and 6 travelled outside the state. A total of 565 patients (81.4%) who had baseline laboratory tests were included in the analysis, as shown in Figure 1. Ethical considerations Permission to use data was obtained from the Lagos State Ministry of Health. The data were de-identified before data capture. Data analysis The Statistical Package for Social Sciences version 22 (IBM, Armonk, NY, USA) was used to enter and analyse data. Percentages, means and standard deviations were used to represent numerical variables. The gender difference of comorbidities was determined using the odds ratio (OR). Results The age and gender distributions of the study population are shown in Table 1. A total of 565 DR-TB patients were initiated during the study period. The majority of DR-TB patients (33.8%) were between 25 and 34 y of age, while children (<15 y) constituted 2.5% of the patients initiated on treatment. The mean age of DR-TB patients was 32.4±12.5 y. More males (61.7%) were initiated on DR-TB treatment than females (38.2%). Of the total patients enrolled within the study period, a majority (41.6%) were enrolled in 2016, as shown in Table 1. Table 2 shows the gender distribution of comorbidities among DR-TB patients. The majority (70.2%) had anaemia, while the prevalence of hearing loss, hypokalaemia, HIV and DM was 13.8%, 14.7%, 10.4% and 9.0%, respectively. There was no gender difference in the prevalence of anaemia, hypokalaemia, hypothyroidism, DM and hearing loss (OR 0.6–1.3). However, the females had a 2-fold greater chance of having HIV infection than the males (OR 2.0 [95% confidence interval {CI} 1.2 to 3.6]). Of the 176 women in the reproductive age group (15–45 y), 8 (4.5%) were pregnant before initiation of DR-TB treatment. Of the 78 DR-TB patients with hearing impairment, 5.1% had a severe hearing impairment, 84.6% were sensorineural and 70.5% were affected in both ears (Table 3). Table 1 Age and gender distribution of DR-TB patients (N=565) Variable . n . % . Age group (years) <15 14 2.5 15–24 112 19.8 25–34 191 33.8 35–44 137 24.2 45–54 69 12.2 ≥55 42 7.4 Mean±SD 34.2±12.5 Gender Male 349 61.8 Female 216 38.2 Year enrolled in MDR treatment 2014 67 11.9 2015 111 19.6 2016 235 41.6 2017 152 26.9 Variable . n . % . Age group (years) <15 14 2.5 15–24 112 19.8 25–34 191 33.8 35–44 137 24.2 45–54 69 12.2 ≥55 42 7.4 Mean±SD 34.2±12.5 Gender Male 349 61.8 Female 216 38.2 Year enrolled in MDR treatment 2014 67 11.9 2015 111 19.6 2016 235 41.6 2017 152 26.9 Open in new tab Table 1 Age and gender distribution of DR-TB patients (N=565) Variable . n . % . Age group (years) <15 14 2.5 15–24 112 19.8 25–34 191 33.8 35–44 137 24.2 45–54 69 12.2 ≥55 42 7.4 Mean±SD 34.2±12.5 Gender Male 349 61.8 Female 216 38.2 Year enrolled in MDR treatment 2014 67 11.9 2015 111 19.6 2016 235 41.6 2017 152 26.9 Variable . n . % . Age group (years) <15 14 2.5 15–24 112 19.8 25–34 191 33.8 35–44 137 24.2 45–54 69 12.2 ≥55 42 7.4 Mean±SD 34.2±12.5 Gender Male 349 61.8 Female 216 38.2 Year enrolled in MDR treatment 2014 67 11.9 2015 111 19.6 2016 235 41.6 2017 152 26.9 Open in new tab Table 2 Gender distribution of comorbidities detected among DR-TB patients Comorbidity . Total, n (%) . Male, n (%) . Female, n (%) . OR (95% CI), p-value . HIV status Positive 55 (10.4) 25 (7.7) 30 (14.8) 2.1 (1.2 to 3.6), 0.010 Negative 472 (89.6) 299 (92.3) 173 (85.2) Reference Total 527 324 203 Potassium level Low (14.7) 39 (15.1) 21 (14.1) 0.9 (0.5 to 1.6), 0.779 Normal 347 (85.3) 219 (84.9) 128 (85.9) Reference Total 407 258 149 Thyroid function test Euthyroid 362 (86.2) 218 (84.2) 144 (89.4) Reference Subclinical hypothyroidism 20 (4.8) 14 (5.4) 6 (3.7) 0.6 (0.2 to 1.7), 0.383 Hypothyroidism 38 (9.0) 27 (10.4) 11(6.9) 0.6 (0.3 to 1.3), 0.192 Total 420 259 161 Diabetes mellitus Yes 64 (17.0) 37 (16.3) 27 (18.1) 1.1 (0.7 to 2.0), 0.646 No 312 (83.0) 190 (83.7) 122 (81.9) Reference Total 376 227 149 Hearing loss Yes 56 (13.8) 32(12.6) 24 (15.8) 1.3 (0.7–2.3), 0.367 No 350 (86.2) 222 (87.4) 128 (84.2) Reference Total 406 254 152 Anaemia Yes 337 (70.2) 207 (69.0) 130 (72.2) 1.1 (0.8 to 1.8), 0.455 No 143(29.8) 93 (31.0) 50 (27.8) Reference Total 480 300 180 Comorbidity . Total, n (%) . Male, n (%) . Female, n (%) . OR (95% CI), p-value . HIV status Positive 55 (10.4) 25 (7.7) 30 (14.8) 2.1 (1.2 to 3.6), 0.010 Negative 472 (89.6) 299 (92.3) 173 (85.2) Reference Total 527 324 203 Potassium level Low (14.7) 39 (15.1) 21 (14.1) 0.9 (0.5 to 1.6), 0.779 Normal 347 (85.3) 219 (84.9) 128 (85.9) Reference Total 407 258 149 Thyroid function test Euthyroid 362 (86.2) 218 (84.2) 144 (89.4) Reference Subclinical hypothyroidism 20 (4.8) 14 (5.4) 6 (3.7) 0.6 (0.2 to 1.7), 0.383 Hypothyroidism 38 (9.0) 27 (10.4) 11(6.9) 0.6 (0.3 to 1.3), 0.192 Total 420 259 161 Diabetes mellitus Yes 64 (17.0) 37 (16.3) 27 (18.1) 1.1 (0.7 to 2.0), 0.646 No 312 (83.0) 190 (83.7) 122 (81.9) Reference Total 376 227 149 Hearing loss Yes 56 (13.8) 32(12.6) 24 (15.8) 1.3 (0.7–2.3), 0.367 No 350 (86.2) 222 (87.4) 128 (84.2) Reference Total 406 254 152 Anaemia Yes 337 (70.2) 207 (69.0) 130 (72.2) 1.1 (0.8 to 1.8), 0.455 No 143(29.8) 93 (31.0) 50 (27.8) Reference Total 480 300 180 Of the 176 women in the reproductive age group (between 15 and 45 y), 8 (4.5%) were pregnant. Open in new tab Table 2 Gender distribution of comorbidities detected among DR-TB patients Comorbidity . Total, n (%) . Male, n (%) . Female, n (%) . OR (95% CI), p-value . HIV status Positive 55 (10.4) 25 (7.7) 30 (14.8) 2.1 (1.2 to 3.6), 0.010 Negative 472 (89.6) 299 (92.3) 173 (85.2) Reference Total 527 324 203 Potassium level Low (14.7) 39 (15.1) 21 (14.1) 0.9 (0.5 to 1.6), 0.779 Normal 347 (85.3) 219 (84.9) 128 (85.9) Reference Total 407 258 149 Thyroid function test Euthyroid 362 (86.2) 218 (84.2) 144 (89.4) Reference Subclinical hypothyroidism 20 (4.8) 14 (5.4) 6 (3.7) 0.6 (0.2 to 1.7), 0.383 Hypothyroidism 38 (9.0) 27 (10.4) 11(6.9) 0.6 (0.3 to 1.3), 0.192 Total 420 259 161 Diabetes mellitus Yes 64 (17.0) 37 (16.3) 27 (18.1) 1.1 (0.7 to 2.0), 0.646 No 312 (83.0) 190 (83.7) 122 (81.9) Reference Total 376 227 149 Hearing loss Yes 56 (13.8) 32(12.6) 24 (15.8) 1.3 (0.7–2.3), 0.367 No 350 (86.2) 222 (87.4) 128 (84.2) Reference Total 406 254 152 Anaemia Yes 337 (70.2) 207 (69.0) 130 (72.2) 1.1 (0.8 to 1.8), 0.455 No 143(29.8) 93 (31.0) 50 (27.8) Reference Total 480 300 180 Comorbidity . Total, n (%) . Male, n (%) . Female, n (%) . OR (95% CI), p-value . HIV status Positive 55 (10.4) 25 (7.7) 30 (14.8) 2.1 (1.2 to 3.6), 0.010 Negative 472 (89.6) 299 (92.3) 173 (85.2) Reference Total 527 324 203 Potassium level Low (14.7) 39 (15.1) 21 (14.1) 0.9 (0.5 to 1.6), 0.779 Normal 347 (85.3) 219 (84.9) 128 (85.9) Reference Total 407 258 149 Thyroid function test Euthyroid 362 (86.2) 218 (84.2) 144 (89.4) Reference Subclinical hypothyroidism 20 (4.8) 14 (5.4) 6 (3.7) 0.6 (0.2 to 1.7), 0.383 Hypothyroidism 38 (9.0) 27 (10.4) 11(6.9) 0.6 (0.3 to 1.3), 0.192 Total 420 259 161 Diabetes mellitus Yes 64 (17.0) 37 (16.3) 27 (18.1) 1.1 (0.7 to 2.0), 0.646 No 312 (83.0) 190 (83.7) 122 (81.9) Reference Total 376 227 149 Hearing loss Yes 56 (13.8) 32(12.6) 24 (15.8) 1.3 (0.7–2.3), 0.367 No 350 (86.2) 222 (87.4) 128 (84.2) Reference Total 406 254 152 Anaemia Yes 337 (70.2) 207 (69.0) 130 (72.2) 1.1 (0.8 to 1.8), 0.455 No 143(29.8) 93 (31.0) 50 (27.8) Reference Total 480 300 180 Of the 176 women in the reproductive age group (between 15 and 45 y), 8 (4.5%) were pregnant. Open in new tab Table 3 Types and severity of hearing impairment among DR-TB patients (N=78) Variable . n . % . Severity of hearing impairment Mild 63 80.8 Moderate 11 14.1 Severe 4 5.1 Type of hearing impairment Conductive 8 10.3 Sensorineural 66 84.6 Mixed 4 5.1 Side affected Right 7 9.0 Left 16 20.5 Both 55 70.5 Variable . n . % . Severity of hearing impairment Mild 63 80.8 Moderate 11 14.1 Severe 4 5.1 Type of hearing impairment Conductive 8 10.3 Sensorineural 66 84.6 Mixed 4 5.1 Side affected Right 7 9.0 Left 16 20.5 Both 55 70.5 Open in new tab Table 3 Types and severity of hearing impairment among DR-TB patients (N=78) Variable . n . % . Severity of hearing impairment Mild 63 80.8 Moderate 11 14.1 Severe 4 5.1 Type of hearing impairment Conductive 8 10.3 Sensorineural 66 84.6 Mixed 4 5.1 Side affected Right 7 9.0 Left 16 20.5 Both 55 70.5 Variable . n . % . Severity of hearing impairment Mild 63 80.8 Moderate 11 14.1 Severe 4 5.1 Type of hearing impairment Conductive 8 10.3 Sensorineural 66 84.6 Mixed 4 5.1 Side affected Right 7 9.0 Left 16 20.5 Both 55 70.5 Open in new tab The pattern of comorbidity among DR-TB patients is illustrated in Table 4. Of the study population, 397 (70.3%) had comorbid conditions, of which 60.2%, 29.7%, 8.1% and 2.0% had one, two, three and four comorbid conditions, respectively. Anaemia was the most common (48.1%) comorbid condition among patients with one comorbidity, while anaemia and hypokalaemia (7.3%), anaemia and hypothyroidism (6.5%) and anaemia and HIV (5%) were most commonest among patients with more than one comorbid condition. The proportion of DR-TB patients with comorbidities increased from 64.3% among patients <15 y of age to 83.3% among patients >54 y of age. The mean age of patients with a comorbidity was higher (34.8±12.3 vs 32.0±12.8 y). The odds of having a comorbidity were equal in males and females (OR 1.0 [95% CI 0.7 to 1.5]) (Table 5). Table 4 Pattern of comorbidity among DR-TB patients (N=397) Variable . n . % . Number of comorbidities 1 239 60.2 2 118 29.7 3 32 8.1 4 8 2.0 Clustering pattern of comorbidity One comorbidity HIV 8 2.0 Hypothyroidism 5 1.3 Anaemia 191 48.1 Hearing defect 16 4.0 Hypokalaemia 9 2.3 Diabetes 10 2.5 Two comorbidities Anaemia and hypokalaemia 29 7.3 Anaemia and hypothyroidism 26 6.5 Anaemia and HIV 20 5.0 Anaemia and hearing defect 19 4.8 Anaemia and diabetes 14 3.5 Other 7 combinations 10 2.5 Three comorbidities Anaemia, HIV and hypothyroidism 5 1.2 Anaemia, HIV and hearing defect 5 1.2 Anaemia, hypothyroidism and hypokalaemia 5 1.2 Anaemia, hearing defect, hypokalaemia 5 1.2 Anaemia, hypothyroidism and hearing defect 4 1.0 Other 5 combinations 8 2.0 Four comorbidities Anaemia, HIV, hypothyroidism and hypokalaemia 3 0.7 Anaemia, HIV, hypothyroidism and hypokalaemia 2 0.5 Other 3 combinations 3 0.7 Variable . n . % . Number of comorbidities 1 239 60.2 2 118 29.7 3 32 8.1 4 8 2.0 Clustering pattern of comorbidity One comorbidity HIV 8 2.0 Hypothyroidism 5 1.3 Anaemia 191 48.1 Hearing defect 16 4.0 Hypokalaemia 9 2.3 Diabetes 10 2.5 Two comorbidities Anaemia and hypokalaemia 29 7.3 Anaemia and hypothyroidism 26 6.5 Anaemia and HIV 20 5.0 Anaemia and hearing defect 19 4.8 Anaemia and diabetes 14 3.5 Other 7 combinations 10 2.5 Three comorbidities Anaemia, HIV and hypothyroidism 5 1.2 Anaemia, HIV and hearing defect 5 1.2 Anaemia, hypothyroidism and hypokalaemia 5 1.2 Anaemia, hearing defect, hypokalaemia 5 1.2 Anaemia, hypothyroidism and hearing defect 4 1.0 Other 5 combinations 8 2.0 Four comorbidities Anaemia, HIV, hypothyroidism and hypokalaemia 3 0.7 Anaemia, HIV, hypothyroidism and hypokalaemia 2 0.5 Other 3 combinations 3 0.7 Open in new tab Table 4 Pattern of comorbidity among DR-TB patients (N=397) Variable . n . % . Number of comorbidities 1 239 60.2 2 118 29.7 3 32 8.1 4 8 2.0 Clustering pattern of comorbidity One comorbidity HIV 8 2.0 Hypothyroidism 5 1.3 Anaemia 191 48.1 Hearing defect 16 4.0 Hypokalaemia 9 2.3 Diabetes 10 2.5 Two comorbidities Anaemia and hypokalaemia 29 7.3 Anaemia and hypothyroidism 26 6.5 Anaemia and HIV 20 5.0 Anaemia and hearing defect 19 4.8 Anaemia and diabetes 14 3.5 Other 7 combinations 10 2.5 Three comorbidities Anaemia, HIV and hypothyroidism 5 1.2 Anaemia, HIV and hearing defect 5 1.2 Anaemia, hypothyroidism and hypokalaemia 5 1.2 Anaemia, hearing defect, hypokalaemia 5 1.2 Anaemia, hypothyroidism and hearing defect 4 1.0 Other 5 combinations 8 2.0 Four comorbidities Anaemia, HIV, hypothyroidism and hypokalaemia 3 0.7 Anaemia, HIV, hypothyroidism and hypokalaemia 2 0.5 Other 3 combinations 3 0.7 Variable . n . % . Number of comorbidities 1 239 60.2 2 118 29.7 3 32 8.1 4 8 2.0 Clustering pattern of comorbidity One comorbidity HIV 8 2.0 Hypothyroidism 5 1.3 Anaemia 191 48.1 Hearing defect 16 4.0 Hypokalaemia 9 2.3 Diabetes 10 2.5 Two comorbidities Anaemia and hypokalaemia 29 7.3 Anaemia and hypothyroidism 26 6.5 Anaemia and HIV 20 5.0 Anaemia and hearing defect 19 4.8 Anaemia and diabetes 14 3.5 Other 7 combinations 10 2.5 Three comorbidities Anaemia, HIV and hypothyroidism 5 1.2 Anaemia, HIV and hearing defect 5 1.2 Anaemia, hypothyroidism and hypokalaemia 5 1.2 Anaemia, hearing defect, hypokalaemia 5 1.2 Anaemia, hypothyroidism and hearing defect 4 1.0 Other 5 combinations 8 2.0 Four comorbidities Anaemia, HIV, hypothyroidism and hypokalaemia 3 0.7 Anaemia, HIV, hypothyroidism and hypokalaemia 2 0.5 Other 3 combinations 3 0.7 Open in new tab Table 5 Age and sex distribution of DR-TB patients with comorbidity Variable . Presence of comorbidity, n (%) . Yes (n=397) . No (n=168) . Age group (years) <15 9 (64.3) 5 (35.7) 15–24 72 (64.3) 40 (35.7) 25–34 128 (67.0) 63 (33.0) 35–44 100 (73.0) 37 (27.0) 45–54 53 (76.8) 16 (23.2) ≥ 55 35 (83.3) 7 (16.7) Mean±SD 34.8±12.3 32.0±12.8 Gender Male 245 (70.2) 104 (29.8) Female 152 (70.4) 64 (29.6) Variable . Presence of comorbidity, n (%) . Yes (n=397) . No (n=168) . Age group (years) <15 9 (64.3) 5 (35.7) 15–24 72 (64.3) 40 (35.7) 25–34 128 (67.0) 63 (33.0) 35–44 100 (73.0) 37 (27.0) 45–54 53 (76.8) 16 (23.2) ≥ 55 35 (83.3) 7 (16.7) Mean±SD 34.8±12.3 32.0±12.8 Gender Male 245 (70.2) 104 (29.8) Female 152 (70.4) 64 (29.6) Open in new tab Table 5 Age and sex distribution of DR-TB patients with comorbidity Variable . Presence of comorbidity, n (%) . Yes (n=397) . No (n=168) . Age group (years) <15 9 (64.3) 5 (35.7) 15–24 72 (64.3) 40 (35.7) 25–34 128 (67.0) 63 (33.0) 35–44 100 (73.0) 37 (27.0) 45–54 53 (76.8) 16 (23.2) ≥ 55 35 (83.3) 7 (16.7) Mean±SD 34.8±12.3 32.0±12.8 Gender Male 245 (70.2) 104 (29.8) Female 152 (70.4) 64 (29.6) Variable . Presence of comorbidity, n (%) . Yes (n=397) . No (n=168) . Age group (years) <15 9 (64.3) 5 (35.7) 15–24 72 (64.3) 40 (35.7) 25–34 128 (67.0) 63 (33.0) 35–44 100 (73.0) 37 (27.0) 45–54 53 (76.8) 16 (23.2) ≥ 55 35 (83.3) 7 (16.7) Mean±SD 34.8±12.3 32.0±12.8 Gender Male 245 (70.2) 104 (29.8) Female 152 (70.4) 64 (29.6) Open in new tab Discussion In our study, 70.3% of the DR-TB patients initiated within the study period had at least one comorbid condition. This prevalence was high compared with 37% and 40.1% reported in studies from India.15,16 The types of comorbid conditions considered and differences in socio-economic and environmental factors may account for our findings. Anaemia was the most common comorbid condition in our study. Our prevalence of 70.2% was low compared with the prevalence of 93.6% reported from a Nigerian study that profiled the haematological indices of pretreatment smear-positive DS-TB patients17 but high compared with 51.2% from another study from Ethiopia that compared blood levels before and after DS-TB treatment.18 The prevalence of anaemia in the general population in Nigeria is unknown, however, a WHO report stated the prevalence of anaemia among women in the reproductive age group to be 49.8%, lower than the prevalence (72.2%) obtained among women in this study.19 Anaemia is associated with delayed sputum conversion, severe TB and poor TB treatment outcomes.20–22 Anti-TB drugs have also been implicated in the reduction of haemoglobin levels during treatment.18 Second-line anti-TB drugs such as ethionamide, prothionamide and para-aminosalicylic acid are associated with hypothyroidism through a mechanism called iodine organification inhibition.23 In our study, 4.8% of DR-TB patients had subclinical hypothyroidism, lower than the 7.8% obtained in a study among MDR patients from Nigeria.24 Similarly, the 9% prevalence of hypothyroidism from this study is lower than the 34.4% reported from Botswana.25 Hypothyroidism represented 7–8.4% of thyroid disorders seen in tertiary health institutions in Nigeria.26,27 Hypothyroidism has been reported to be higher among females in Nigeria.26,27 However, our study showed no gender difference in the prevalence of hypothyroidism, similar to what was obtained among DR-TB patients from Botswana and India.25,28 Our findings underscore the need to monitor TSH during DR-TB treatment, especially in patients receiving protionamide, as recommended by the national TB program.7 Hypothyroidism has been associated with depression and poor adherence among DR-TB patients.29 Electrolyte imbalance is a common adverse reaction in DR-TB management. Capreomycin and aminoglycosides cause renal loss of electrolytes, including potassium, through induction of secondary hyperaldosteronism, which can aggravate electrolyte imbalance during DR-TB treatment.30,31 About 15% of the RR-TB patients in our study had hypokalaemia at baseline, lower than the 31.3% reported from Peru.32 A study from Nigeria reported serum potassium levels in DS-TB patients to be lower than in healthy controls.33 A possible explanation for the low potassium level in TB patients may be due to increased potassium excretion in sweat and urine as a result of the increased concentration of potassium in the intracellular spaces resulting from increased catabolism typical of chronic illnesses.34 Disease chronicity, poor nutritional status, low body weight, vomiting and dehydration have been shown to contribute to hypokalaemia in DR-TB patients.32 Mortality is higher among patients with hypokalaemia if left uncorrected.32 The injectable aminoglycosides (streptomycin, amikacin, kanamycin and capreomycin) used for the treatment of DR-TB patients are associated with nephrotoxicity, ototoxicity and vestibular damage. While nephrotoxicity caused by aminoglycosides is reversible, the damage to the auditory and vestibular system is usually permanent.35 The incidence of hearing loss associated with aminoglycosides is time- and dose-dependent and may be influenced by patients’ susceptibility.36 Hearing loss may reduce the ability to communicate with spoken language and participation in social and vocational activities, which may impact on the individual’s quality of life.37 This informs the need to monitor hearing loss in RR-TB patients taking aminoglycosides. Early detection and prompt intervention could prevent the progression of hearing loss and communication deficit, especially in children.38 In this study, the prevalence of hearing loss at baseline was about 14% and a majority were sensorineural. This finding is high compared with 8% obtained in South Africa among DR-TB patients at baseline39 and low compared with 22.7% and 90% reported from India and Nigeria, respectively, at baseline among DR-TB patients.40,41 The prevalence of hearing loss in Nigeria varies between 6.1 and 21.3% depending on the population group, method of assessment of hearing loss and study methodology.42–44 Several factors have been associated with the wide range of prevalences of hearing loss in DR-TB patients at baseline. Comorbid conditions such as DM, hypertension, HIV and the use of antiretroviral drugs may contribute to hearing loss.41 Second, the treatment of TB and HIV has been shown to have some effect on the auditory system.45 Previous TB treatment may be another possible explanation for the high prevalence of hearing loss among DR-TB patients at baseline. A WHO report showed that about 25% of DR-TB patients were previously treated for TB in Nigeria2 and the chances that the majority of the re-treated cases have been exposed to streptomycin (previously used for re-treatment of DS-TB in Nigeria) was high. Lastly, the method used to define hearing loss may also account for the difference in hearing loss. Some tests used an audiometer that does not test above 8000 Hz, thereby missing this hearing loss.40 Of the patients with hearing loss in this study, about 85% were sensorineural, similar to what was reported previously.39–41 HIV infection is the greatest risk factor for the development of drug-susceptible and drug-resistant TB. This may be due to faster disease progression and malabsorption of rifampicin and ethambutol, which could lead to drug resistance and treatment failure.46,47 They also act synergistically to cause higher mortality among DR-TB/HIV co-infected patients compared with HIV-negative DR-TB patients.48 In this study about 10.4% of the DR-TB patients had HIV infection. This was high compared with the prevalence of 4.4% reported from India.49 According to the National Agency for the Control of AIDS, the HIV prevalence in Nigeria was 1.4%,50 however, the TB/HIV co-infection rate for the country in 2017 was 14%.51 The prevalence of DM has increased globally and in 2015, 415 million people worldwide were estimated to have DM.52 DM is a known risk factor for and responsible for between 15 and 25% of active TB cases.53,54 In our study, the prevalence of DM among TB patients was 8.2%, which is low compared with the 17% and 21% prevalence reported in studies from Korea and Georgia, respectively, among DR-TB patients.55,56 A systemic review and meta-analysis on the prevalence of DM among TB patients in sub-Saharan Africa showed that Nigeria was highest (15%), followed by Tanzania (11%) and Ethiopia (10%).57 A systemic review of population-based studies from Nigeria reported the prevalence of DM in Nigeria to be between 0.8 and 11%.58 DM has been associated with delayed sputum conversion, increased mortality, recurrence and low treatment success rates among MDT-TB patients.7,55,56,59 Although DM is associated with increased susceptibility to infections due to altered immune function, it is not known whether the altered immune function increases the risk of primary DR-TB.60,46 In our study, about 5% of the women in the reproductive age group were pregnant during initiation. Management of RR-TB during pregnancy is controversial because of the limited knowledge of the safety of second-line drugs. While some have advocated for the termination of pregnancy,61 others have opined that treatment should be reduced or suspended during pregnancy.62 The national guidelines advise that treatment be delayed until after 20 weeks to reduce the risks of teratogenicity and toxicity. However, treatment of RR-TB can commence immediately if there are life-threatening situations such as respiratory failure, advanced disease or HIV infection, in which case the patient must be well informed of the potential risks involved. Capreomycin is the preferred injectable in this situation, and thrice-weekly injections are advised during the first trimester.10 Although a study from Peru reported that treatment success and birth outcomes among pregnant DR-TB patients were comparable to those of non-pregnant DR-TB patients and the general population, respectively, such findings should be interpreted with caution.63 However, our findings suggest the need for the national program to integrate reproductive health into the DR-TB program in Nigeria. Study limitations A comparison of comorbidities of DS-TB and DR-TB patients would have been ideal. This was not possible because the TB program in Nigeria does not recommend elaborate laboratory investigations as routine for DS-TB patients except when it is highly indicated. Although the causes of the comorbidities observed in this study were largely unknown, it was necessary to highlight them because of the effects of second-line TB drugs on these comorbidities. The kidney function of patients using creatinine clearance could not be assessed because the authors were not sure if the weights were measured using a standard procedure. Also, the prevalences obtained in this study may not reflect the true prevalences of comorbidities, because not all the DR-TB patients diagnosed within the study period were initiated on treatment. Of the 694 DR-TB patients diagnosed within the study period, 81.4% (565) did baseline laboratory tests (Figure 1). Generalizability Lagos State contributed about 17% of the DR-TB cases notified in Nigeria, therefore our finding may not be generalizable to the rest of the country. There is a need for a larger study. Conclusions The prevalence of comorbidity among DR-TB patients in Lagos State was high. There is a need for the NTP and its stakeholders to consider the inclusion of other professionals, including endocrinologists and ear, nose and throat specialists in its DR-TB CETs. There is also a need to integrate reproductive health services into DR-TB management, especially in facilities where the two services are co-located. Authors’ contributions MG and BOF conceived the study. OAA analysed the data and prepared the manuscript. OAA and BOF wrote the manuscript. VAA, MOO and OA were involved in the study design and literature search. HA, OM and YS collected data and took part in the review of the manuscript. All authors read and approved the manuscript before submission. OAA and BOF are guarantors of the paper. Acknowledgements The authors wish to acknowledge the Lagos State Ministry of Health for their support. The research was self-funded and the findings and the conclusions are those of the authors. Funding None. Competing interests None declared. Ethical approval Not required. References 1 Johnston JC , Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis . PLoS One. 2009 ; 4 ( 9 ):e6914. OpenURL Placeholder Text WorldCat 2 World Health Organization . Global tuberculosis report 2016 . Geneva : World Health Organization ; 2016 . Available from: http://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf [accessed August 2018]. Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 3 Samuels JP , Sood A, Campbell JR, Khan FA, Johnston JC. Comorbidities and treatment outcomes in multidrug resistant tuberculosis: a systematic review and meta-analysis . Sci Rep 2018 ; 8 : 4980 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Baker MA , Harries AD, Jeon CY et al. The impact of diabetes on tuberculosis treatment outcomes: a systematic review . BMC Med. 2011 ; 9 : 81 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Khan FA , Minion J, Pai M et al. Treatment of active tuberculosis in HIV-co-infected patients: a systematic review and meta-analysis . Clin Infect Dis. 2010 ; 50 ( 9 ): 1288 – 1299 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Gomez-Gomez A , Magana-Aquino M, Lopez-Meza S et al. Diabetes and other risk factors for multi-drug resistant tuberculosis in a Mexican population with pulmonary tuberculosis: case control study . Arch Med Res. 2015 ; 46 ( 2 ): 142 – 148 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Mollel EW , Chilongola JO. Predictors for mortality among multidrug-resistant tuberculosis patients in Tanzania . J Trop Med 2017 ; 2017 : 9241238 . OpenURL Placeholder Text WorldCat 8 Tegegne BS , Mengesha MM, Teferra AA, Awoke MA, Habtewold TD. Association between diabetes mellitus and multi-drug-resistant tuberculosis: evidence from a systematic review and meta-analysis . Syst Rev. 2018 ; 7 : 161 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Lagos State Bureau of Statistic . Abstract of local government statistics. http://mepb.lagosstate.gov.ng/wp-content/uploads/sites/29/2018/06/Abstract-of-LG-Statistics-2017editted.pdf [accessed June 2018] . 10 Federal Ministry of Health, National Tuberculosis and Leprosy Control Programme . Guidelines for programmatic and clinical management of drug resistant tuberculosis in Nigeria , 2nd edn. Ministry of Health : Abuja , 2016 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 11 World Health Organisation . Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity . Geneva : World Health Organization ; 2011 . Available from: https://www.who.int/vmnis/indicators/haemoglobin/en/ [accessed September 2018]. Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 12 Garber JR , Cobin RH, Gharib H et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association . Thyroid 2012 ; 22 : 1200 – 1235 . Google Scholar Crossref Search ADS PubMed WorldCat 13 World Health Organization . Prevention of blindness and deafness. Grades of hearing impairment. Available from: http://www.who.int/pbd/deafness/hearing_impairment_grades/en/ [accessed August 2018]. 14 World Health Organization . Global health observatory data. (Mean fasting blood glucose) . Available from: www.who.int/gho/ncd/risk_factors/blood_glucose_mean_test/en/ [accessed August 2018]. 15 Kamendra SP , Ramakant D. Prevalence of comorbidities among patients having multi drug resistant tuberculosis: a retrospective analysis . J Med Sci Clin Res. 2018 ; 6 : 1029 – 1032 . OpenURL Placeholder Text WorldCat 16 Dhingra VK , Rajpal S, Mittal A et al. Outcome of multi-drug resistant tuberculosis cases treated by individualized regimens at a tertiary level clinic . Indian J Tuberc. 2008 ; 55 ( 1 ): 15 – 21 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 17 Olaniyi JA , Aken’Ova YA. Haematological profile of patients with pulmonary tuberculosis in Ibadan, Nigeria . Afr J Med Med Sci. 2003 ; 32 ( 3 ): 239 – 242 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 18 Kassa E , Enawgaw B, Gelaw A et al. Effect of anti-tuberculosis drugs on hematological profiles of tuberculosis patients attending at University of Gondar Hospital, northwest Ethiopia . BMC Hematol. 2016 ; 16 : 1 . Google Scholar Crossref Search ADS PubMed WorldCat 19 World Health Organization . Global Health Observatory data repository. World health statistics . Available at http://apps.who.int/gho/data/node.main.1?lang=en [accessed June 2019]. 20 Isanaka S , Mugusi FM, Urassa W et al. Iron deficiency and anemia predict mortality in patients with tuberculosis . J Nutr. 2012 ; 142 ( 2 ): 350 – 357 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Nagu TJ , Spiegelman D, Hertzmark E et al. Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-salaam, Tanzania . PLoS One. 2014 ; 9 ( 3 ):e91229. OpenURL Placeholder Text WorldCat 22 Kourbatova EV , Borodulin BE, Borodulina EA, del Rio C, Blumberg HM, Leonard MK Jr. Risk factors for mortality among adult patients with newly diagnosed tuberculosis in Samara . Russia. Int J Tuberc Lung Dis. 2006 ; 10 ( 11 ): 1224 – 1230 . OpenURL Placeholder Text WorldCat 23 Isaakidis P , Varghese B, Mansoor H et al. Adverse events among HIV/MDR-TB co-infected patients receiving antiretroviral and second line anti-TB treatment in Mumbai, India . PLoS One. 2012 ; 7 ( 7 ):e40781. OpenURL Placeholder Text WorldCat 24 Ige OM , Akinlade KS, Rahamon SK. Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen . Afr Health Sci. 2016 ; 16 ( 2 ): 596 – 602 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Modongo C , Zetola NM. Prevalence of hypothyroidism among MDR-TB patients in Botswana . Int J Tuberc Lung Dis. 2012 ; 16 ( 11 ): 1561 – 1562 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Ogbera AO , Fasanmade O, Adediran O. Pattern of thyroid disorders in the southwestern region of Nigeria . Ethn Dis. 2007 ; 17 ( 2 ): 327 – 330 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 27 Amballi AA , Adeleye AO, Oritogun KS et al. Pattern of thyroid dysfunction in a semiurban Nigerian population through thyroid function tests in a private laboratory, Sagamu, Ogun State, Nigeria . Int J Biochem Biotechnol. 2012 ; 1 ( 4 ): 146 – 149 . OpenURL Placeholder Text WorldCat 28 Andries A , Isaakidis P, Das M et al. High rate of hypothyroidism in multidrug-resistant tuberculosis patients co-infected with HIV in Mumbai, India . PLoS One. 2013 ; 8 ( 10 ):e78313. OpenURL Placeholder Text WorldCat 29 Yaqoob A . Subclinical hypothyroidism and its consequences . J Public Health Biol Sci. 2012 ; 1 : 53 – 60 . OpenURL Placeholder Text WorldCat 30 Elisaf M , Liberopoulos E, Bairaktari E et al. Hypokalaemia in alcoholic patients . Drug Alcohol Rev. 2002 ; 21 ( 1 ): 73 – 76 . Google Scholar Crossref Search ADS PubMed WorldCat 31 Darr M , Hamburger S, Ellerbeck E. Acid-base and electrolyte abnormalities due to capreomycin . South Med J. 1982 ; 75 ( 5 ): 627 – 628 . Google Scholar Crossref Search ADS PubMed WorldCat 32 Shin S , Furin J, Alcántara F et al. Hypokalemia among patients receiving treatment for multidrug-resistant tuberculosis . Chest. 2004 ; 125 ( 3 ): 974 – 980 . Google Scholar Crossref Search ADS PubMed WorldCat 33 Adebimpe WO , Faremi AO, Hassan AO et al. Evaluation of electrolyte imbalance among tuberculosis patients receiving treatments in southwestern Nigeria . Alexandria J Med. 2015 ; 51 ( 3 ): 255 – 260 . Google Scholar Crossref Search ADS WorldCat 34 Cheebrough M . District laboratory practice in tropical countries, part 2 . Cambridge : Cambridge University Press , 2000 ; p. 207 , 253 – 212 , 66 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 35 Seddon JA , Godfrey-Faussett P, Jacobs K et al. Hearing loss in patients on treatment for drug-resistant tuberculosis . Eur Respir J. 2012 ; 40 ( 5 ): 1277 – 1286 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Schact J , Talaska AE, Rybak LP. Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention . Anat Rec (Hoboken). 2012 ; 295 ( 11 ): 1837 – 1850 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Boothroyd A . Adult aural rehabilitation: what is it and does it work? Trends Amplif 2007 ; 11 ( 2 ): 63 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Livingstone N , McPhillips M. Motor skill deficits in children with partial hearing . Dev Med Child Neurol. 2011 ; 53 ( 9 ): 836 – 842 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Appana D , Joseph L, Paken J. An audiological profile of patients infected with multi-drug resistant tuberculosis at a district hospital in KwaZulu-Natal . S Afr J Commun Disord. 2016 ; 63 ( 1 ): a154 . OpenURL Placeholder Text WorldCat 40 Nizamuddin S , Khan FA, Khan AR. Assessment of hearing loss in multi-drug resistant tuberculosis (MDR-TB) patients undergoing aminoglycoside treatment . Int J Res Med Sci. 2015 ; 3 ( 7 ): 1734 – 1740 . Google Scholar Crossref Search ADS WorldCat 41 Sogebi OA , Fadeyi MO, Adefuye BO et al. Hearing thresholds in patients with drug-resistant tuberculosis: baseline audiogram configurations and associations . J Bras Pneumol. 2017 ; 43 ( 3 ): 195 – 201 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Olusanya BO , Okolo AA, Ijaduola GTA. The hearing profile of Nigerian school children . Int J Pediatr Otorhinolaryngol. 2000 ; 55 ( 3 ): 173 – 179 . Google Scholar Crossref Search ADS PubMed WorldCat 43 Adebola SO , Ayodele SO, Oyelakin OA, Babarinde JA, Adebola OE. Pre-school hearing screening: profile of children from Ogbomoso, Nigeria . Int J Pediatr Otorhinolaryngol. 2013 ; 77 ( 12 ): 1987 – 1991 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Lasisi AO , Abiona T, Gureje O. The prevalence and correlates of self-reported hearing impairment in the Ibadan study of ageing . Trans R Soc Trop Med Hyg. 2010 ; 104 ( 8 ): 518 – 523 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Harris T , Bardien S, Schaaf HS, Petersen L, de Jong G, Fagan JJ. Aminoglycoside induced hearing loss in HIV-positive and HIV-negative multi-drug resistant tuberculosis patients . S Afr Med J. 2012 ; 102 ( 6 ): 363 – 366 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Mesfin YM , Hailemariam D, Biadglign S, Kibret KT. Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis . PLoS One. 2014 ; 9 ( 1 ):e82235. OpenURL Placeholder Text WorldCat 47 Andrews JR , Shah NS, Weissman D, Moll AP, Friedland G, Gandhi NR. Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community . PLoS One. 2010 ; 5 ( 12 ):e15735. OpenURL Placeholder Text WorldCat 48 Kalsdorf B , Skolimowska KH, Scriba TJ et al. Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to mycobacterium tuberculosis . Eur J Immunol. 2013 ; 43 ( 2 ): 540 – 549 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Deivanayagam CN , Rajasekaran S, Venkatesan R et al. Prevalence of acquired MDR-TB and HIV co-infection . Indian J Chest Allied Sci. 2002 ; 44 : 237 – 242 . OpenURL Placeholder Text WorldCat 50 National Agency for Control of AIDS . The prevalence of HIV in Nigeria. Available at: http://naca.gov.ng/Nigeria-prevalence-rate [accessed June 2019] . 51 World Health Organization . Nigeria. Tuberculosis profile. Geneva : World Health Organization ; 2017 . Available at: https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=NG&LAN=EN&outtype=html 52 International Diabetes Federation . IDF diabetes atlas , 7th edn. Brussels : International Diabetes Federation , 2015 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 53 Jeon CY , Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies . PLoS Med. 2008 ; 5 ( 7 ): e152 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Lönnroth K , Roglic G, Harries AD. Improving tuberculosis prevention and care through addressing the global diabetes epidemic: from evidence to policy and practice . Lancet Diabetes Endocrinol. 2014 ; 2 ( 9 ): 730 – 739 . Google Scholar Crossref Search ADS PubMed WorldCat 55 Young AK , Song YK, Kyung-Wook J et al. Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis . Respiration. 2013 ; 86 ( 6 ): 472 – 478 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Salindri AD , Kipiani IM, Kempker RR et al. Diabetes reduces the rate of sputum culture conversion in patients with newly diagnosed multidrug-resistant tuberculosis . Open Forum Infect Dis. 2016 ; 3 ( 3 ): ofw126 . OpenURL Placeholder Text WorldCat 57 Alebel A , Wondemagegn AT, Tesema C et al. Prevalence of diabetes mellitus among tuberculosis patients in sub-Saharan Africa: a systematic review and meta-analysis of observational studies . BMC Infect Dis. 2019 ; 19 ( 1 ): 254 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Dahiru T , Aliyu AA, Shehu AU. A review of population based studies on diabetes mellitus in Nigeria . Sub-Saharan Afr J Med. 2016 ; 3 ( 2 ): 59 – 64 . Google Scholar Crossref Search ADS WorldCat 59 Mi F , Tan S, Liang L et al. Diabetes mellitus and tuberculosis: pattern of tuberculosis, two-month smear conversion and treatment outcomes in Guangzhou, China . Trop Med Int Health. 2013 ; 18 ( 11 ): 1379 – 1385 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Fisher-Hoch SP , Whitney E, McCormick JB et al. Type 2 diabetes and multi drug resistant tuberculosis . Scand J Infect Dis. 2008 ; 40 ( 11–12 ): 888 – 893 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Craig GM , Booth H, Story A et al. The impact of social factors on tuberculosis management . J Adv Nurs. 2007 ; 58 ( 5 ): 418 – 424 . Google Scholar Crossref Search ADS PubMed WorldCat 62 Nitta AT , Milligan D. Management of four pregnant women with multidrug-resistant tuberculosis . Clin Infect Dis. 1999 ; 28 ( 6 ): 1298 – 1304 . Google Scholar Crossref Search ADS PubMed WorldCat 63 Palacios E , Dallman IR, Munoz M et al. Drug-resistant tuberculosis and pregnancy: Management and treatment outcomes of 38 cases in Lima, Peru . Clin Infect Dis. 2009 ; 48 ( 10 ): 1413 – 1419 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - The pattern of comorbidity and its prevalence among drug-resistant tuberculosis patients at treatment initiation in Lagos, Nigeria
JF - Transactions of The Royal Society of Tropical Medicine and Hygiene
DO - 10.1093/trstmh/trz126
DA - 2020-06-01
UR - https://www.deepdyve.com/lp/oxford-university-press/the-pattern-of-comorbidity-and-its-prevalence-among-drug-resistant-GjBFSDMeHE
SP - 415
VL - 114
IS - 6
DP - DeepDyve
ER -