Incidence of adverse drug events among patients on second line anti-tuberculosis regimen in the littoral region of cameroon.

Background: An adverse drug event (ADE) is an injury resulting from medical intervention associated with a drug. This study assesses the incidence of ADEs among participants on second-line drugs for tuberculosis (TB) in Cameroon. Methods: This was a longitudinal observational study including 65 participants and carried out from January 2017 to December 2017. Markers of ADEs were obtained from creatinine, transaminase audiogram, and clinical data. Multivariate analysis was used to determine the association between predictors and ADEs. Results: Forty-eight (73.8%) of the 65 participants developed 72 ADEs. Fifty-four (75%), 11 (15.3%), and 7 (9.7%) of the 72 ADEs were classified as Grades 1, 2, and 3, respectively. Gastrointestinal disorders were most common (35 [46.6%]) followed by auditory injuries (16 [22.2%]), hepatotoxicity (11 [15.3%]), neurological disorders (6 [8.3%]), and kidney disorders (4 [5.6%]). The follow-up duration of this study was 11,250-person day (PDY). The incidence rate for ADEs was 4.3/1000 PDY and that for gastrointestinal disorders, auditory injuries, hepatotoxicity, neurological disorders, and kidney disorders was 3.1, 1.4, 1.0, 0.5, and 0.2 (/1000PDY), respectively. Kanamycin (65 [90.3%]), isoniazid (4 [5.6%]), and ethambutol (3 [4.2%]) were incriminated with ADEs. Most (29 [60.4%]) of the ADEs occurred during the first 2 months of drug initiation. There was an association between poor treatment outcome and ADEs (P = 0.04, odds ratio = 1.20, 95% confidence of interval = 0.21-6.80]. Conclusions: The incidence of ADEs is associated with several factors and most of them occurred during the intensive phase of treatment. Kanamycin was the most associated drug linked to ADEs requiring its replacement with a less toxic one.

Predictors of Drug-Resistant Tuberculosis among High-Risk Population Diagnosed under National Program Conditions in the Littoral Region, Cameroon.

Multiple drug resistance TB (MDR-TB) has greatly jeopardized the effective control of tuberculosis in Africa. This study is aimed at determining the incidence and predictors of drug resistant-TB amongst bacteriologically diagnosed cases in the Littoral region of Cameroon. This was a descriptive cross-sectional survey conducted from January 2016 to December 2017. A total of 1665 participants were enrolled from 32 diagnostic and treatment centers (DTCs) in the Littoral region. Demographic, clinical, socioeconomic, and behavioral data were obtained using a pretested structured questionnaire. Drug susceptibility testing was performed using Gene Xpert MTB/RIF assay and line probe assay (LPA). Consent was obtained from participant/guidance. Data analysis was carried with SPSS version 21. Univariate and multiple logistic regression was performed at 5% significance level. The incidence of rifampicin and MDR-TB was 86 (5.2%) and 75 (4.5%), respectively. More (11.3%) cases of drug resistance were diagnosed in 2016 compared to 2017 (3.7%). Eleven (0.7%) were resistant to rifampicin only. A total of 19 (4.4%) cases of rifampicin resistance were detected from newly diagnosed cases and 67 (5.4%) from previously retreated cases. Pre-XDR-TB was detected in 2 (2.7%) of the MDR-TB cases amongst whom 1 (1.3%) was extensive drug resistance TB (XDR-TB). Age greater than 60 years old (OR = 4.98, p = 0.047), being married (OR = 1.91, p = 0.006), being currently incarcerated (OR = 1.74, p = 0.027), and having contact with known TB cases (OR = 1.88, p = 0.007) were associated to MDR-TB in a univariate analysis. This study highlights the declining rates of TB drug resistance in the region over the years probably due to the introduction of Gene Xpert that results in early detection of RR-TB. It also shows that age greater than 60 years, being married, and incarcerated are predictors of drug resistant-TB, while the year of patient enrolment and previous exposure to TB treatment were independent predictors of drug resistance in the Littoral region of Cameroon.

Evaluation of the performance of an in-house duplex PCR assay targeting the IS6110 and rpoB genes for tuberculosis diagnosis in Cameroon.

BACKGROUND: Tuberculosis (TB) remains a major public health concern in many low-income countries accounting for approximately two-thirds of deaths in people living with human immunodeficiency virus (HIV) infection. With prompt, accurate and appropriate treatment, almost all TB disease can be cured. The present study was to evaluate the diagnostic performance of an in-house duplex PCR (D-PCR) using IS1610 and rpoB specific primers in sputum samples from TB suspected patients. METHODS: A hospital-based cross-sectional study was conducted at the Limbe and Buea Regional Hospitals of the South West Region of Cameroon from June 2016 to April 2017. Sputum samples, decontaminated with hypertonic saline/sodium hydroxide solution were centrifuged and pellets processed for smear microscopy, culture and DNA extraction. Suspected inhibition was resolved by serial dilution of genomic DNA. Results were compared to culture as gold standard as well as a Composite Reference Standard (CRS). RESULTS: A total of 129 participants aged between 5 to 82 years were enrolled in to the study. The median age of the participants was 37 years (interquartile range, IQR: 27-50 years), with 54.3% being male. Forty-seven samples (36.4%) were positive by direct sputum microscopy, 49 (38%) by microscopy after concentration, 51 (39.5%) by culture and 62 (40.1%) by D-PCR. PCR inhibition was resolved in 85.7% (18/21) of the samples that had inhibition. The overall sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and area under the curve AUC) of the D-PCR was 93.5, 94, 94, 94%, 15.6, 0.005 and 89.0% respectively using CRS as reference. The sensitivities of D-PCR observed among different sample categories were 95.7, 87.5 and 87.5% for smear-and culture-positives, smear-negative/culture-positive, and clinically diagnosed cases respectively. CONCLUSION: IS1610 and rpoB duplex PCR using relatively cheap decontamination and DNA extraction methods in addition to simple serial dilutions to resolve PCR inhibition shows high sensitivity in the diagnosis of paucibacillary tuberculosis.

Bacteriologically confirmed extra pulmonary tuberculosis and treatment outcome of patients consulted and treated under program conditions in the littoral region of Cameroon.

BACKGROUND: Extra-pulmonary tuberculosis (EPTB) is defined as any bacteriologically confirmed or clinically diagnosed case of TB involving organs other than the lungs. It is frequently a diagnostic and therapeutic challenge with paucity of data available. The aim of this study was to assess the prevalence of bacteriologically confirmed EPTB; to determine the most affected organs and to evaluate the therapeutic outcome of EPTB patients treated under program conditions in the littoral region of Cameroon. METHODS: A descriptive cross-sectional laboratory-based epidemiological survey was conducted from January 2016 to December 2017 and 109 specimens from 15 of the 39 diagnosis and treatment centers in the littoral region were obtained. Two diagnostic methods (Gene Xpert MTB and culture (LJ and MGIT) were used for EPTB diagnosis. Determine HIV1/2 and SD Biolinewere used for HIV diagnosis. Confirmed EPTB cases were treated following the national tuberculosis guide. RESULTS: The prevalence of bacteriologically confirmed EPTB was 41.3% (45). All 45 cases were sensitive to rifampicin. Males were predominately more infected [26 (57.8%)] likewise the age group 31-45 years with 15 (33.3%) cases. The overall prevalence for HIV was 33.6% (36). HIV infection was present in 28.9% (13) of patients with EPTB. The most affected sites with EPTB were: Lymph nodes (66.5%), pleural cavity (15.6%), abdominal organs (11.1%), neuromeningeal (2.2%), joints (2.2%) and heart (2.2%). Overall, 84.4% of the study participants had a therapeutic success with males responding better 57.9% (p = 0.442). Therapeutic success was better (71.7%) in HIV negative EPTB patients (p = 0.787). CONCLUSION: The prevalence of bacteriologically confirmed EPTB patients treated under program conditions in the littoral region of Cameroon is high with a therapeutic success of 84.4% and the lymph nodes is the most affected site.

Drug resistance profiles of Mycobacterium tuberculosis complex and factors associated with drug resistance in the Northwest and Southwest Regions of Cameroon.

BACKGROUND: Anti-tuberculosis drug resistance continues to be a major obstacle to tuberculosis (TB) control programmes with HIV being a major risk factor in developing TB. We investigated anti-TB drug resistance profiles and the impact of socioeconomic as well as behavioural factors on the prevalence of TB and drug resistance in two regions of Cameroon with such data paucity. METHODS: This was a hospital-based study in which 1706 participants, comprising 1133 females and 573 males consecutively enrolled from selected TB and HIV treatment centres of the Northwest and Southwest regions. Demographic, clinical and self-reported risk behaviours and socioeconomic data were obtained with the consent of participants using questionnaires. Culture and drug resistance testing were performed according to standard procedures. RESULTS: The prevalence of resistance to at least one anti-TB drug was 27.7% and multi-drug resistance was 5.9%. Smoking, concurrent alcohol consumption and smoking, being on antiretroviral therapy for ≤ 12 months and previous household contact with TB patient were independently associated with tuberculosis prevalence, while only previous tuberculosis infection was associated with drug resistance in a univariate analysis. CONCLUSION: The study showed a high prevalence of drug resistance TB in the study population with only previous TB infection associated with drug resistance in a univariate analysis. It also provides evidence in our context, of the role of alcohol and smoking in increasing the risk of developing TB, which is more likely in people living with HIV/AIDS. Therefore, it is important for public health authorities to integrate and intensify alcohol/smoking abstention interventions in TB and HIV control programs in Cameroon.

Mycobacterium tuberculosis is the causative agent of tuberculosis in the southern ecological zones of Cameroon, as shown by genetic analysis.

BACKGROUND: Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP). These were expected to shed light also on the transmission of TB in the country. The study was conducted from February to July 2009. During this period, 169 patients with symptomatic disease and with sputum cultures that were positive for MTBC were randomly selected for the study from amongst 964 suspected patients in the savannah mosaic zone (West and North West regions) and the tropical rainforest zone (Central region). After culture and diagnosis, DNA was extracted from each of the MTBC isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular analysis. METHODS: Genetic characterization was done by mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) and Spoligotyping. RESULTS: Molecular analysis showed that all TB cases reported in this study were caused by infections with Mycobacterium tuberculosis (98.8%) and Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any M. bovis. Comparative analyses using spoligotyping revealed that the majority of isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates (31.3%) where distributed among the minor clades. The predominant group of isolates (34.4%) corresponded to spoligotype 61, previously described as the "Cameroon family. Further analysis based on MIRU-VNTR profiles had greater resolving power than spoligotyping and defined additional genotypes in the same spoligotype cluster. CONCLUSION: The molecular characterization of MTBC strains from humans in two ecological regions of Cameroon has shown that M. tuberculosis sensu stricto is the predominant agent of TB cases in the zones. Three decades ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present findings are consistent with a major shift in the prevalence of M. tuberculosis in Cameroon.

Molecular genotyping of Mycobacterium bovis isolated from cattle tissues in the North West Region of Cameroon.

An epidemiological study was carried out to determine the Mycobacterium bovis strains causing bovine tuberculosis (TB) in cattle in North West Cameroon. Suspected TB lesions from slaughtered cattle were cultured on Lowenstein-Jensen and Middlebrook 7 H9 media to isolate mycobacteria agents for molecular genotyping using deletion analysis and spoligotyping. PCR-based genomic deletion typing showed that 54 of 103 tubercle bacilli isolated from cattle tissue were M. bovis strains and the African 1 clonal complex was widespread in affected cattle. Spoligotyping analysis revealed a closely related group of five M. bovis strains. SB0953, the dominant spoligotype pattern, and four new patterns identified as SB2161, SB2162, SB2663 and SB2664 according to the www.Mbovis.org international spoligotype database were identified. These spoligotypes were similar to other M. bovis strains recovered from bordering regions and other parts of Africa. The findings provided useful facts on the zoonotic risks of bovine TB and overwhelming evidence of the significance of M. bovis infection to human TB in the North West Region of Cameroon. The study revealed that bovine TB was widespread in cattle destined for human consumption and also has important implications for the control of TB in animals and humans in Cameroon.

Mycobacterium tuberculosis complex drug resistance pattern and identification of species causing tuberculosis in the West and Centre regions of Cameroon.

BACKGROUND: Data on the levels of resistance of Mycobacterium tuberculosis complex (MTBC) strains to first line anti-tuberculosis drugs in Cameroon, and on the species of MTBC circulating in the country are obsolete. The picture about 10 years after the last studies, and 6 years after the re-organisation of the National Tuberculosis (TB) Control Programme (NTBCP) is not known. METHODS: The study was conducted from February to July 2009 in the West and Centre regions of Cameroon. A total of 756 suspected patients were studied. MTBC species were detected by the standard Ziehl-Neelsen staining method. Bacterial susceptibility to the first line drugs [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM)] were performed on cultures using the indirect proportion method. MTBC species were identified by standard biochemical and culture methods. RESULTS: Of the 756 suspected patients, 154 (20.37%) were positive by smear microscopy. Of these, 20.77% were HIV patients. The growth of Mycobacterium was observed with the sputa from 149 (96.75%) subjects. All the isolates were identified as either M. tuberculosis or M. africanum. Among these, 16 (10.73%) were resistant to at least one drug (13.3% for the West region and 8.1% for the Centre). The initial resistance rates were 7.35% for the Centre region and 11.29% for the West region, while the acquired resistance rates were 16.66% (1/6) for the Centre region and 23.07% (3/13) for the West. Within the two regions, the highest total resistance to one drug was obtained with INH and SM (2.68% each). Multidrug-resistance (MDR) was observed only in the West region at a rate of 6.67%. No resistance was recorded for EMB. CONCLUSIONS: M. tuberculosis and M. africanum remain the MTBC species causing pulmonary TB in the West and Centre regions of Cameroon. Following the re-organisation of the NTBCP, resistance to all first line anti-TB drugs has declined significantly (p < 0.05 for West; and p < 0.01 for Centre) in comparison to previous studies. However, the general rates of anti-TB drug resistance remain high in the country, underscoring the need for greater enforcement of control strategies.