Olanrewaju Oladimeji

Intensive-phase treatment outcomes among hospitalized multidrug-resistant tuberculosis patients: results from a nationwide cohort in Nigeria.

Background Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6–8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them. Methods In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012. Results Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01). Conclusions End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for selected high-risk groups.

Doing no harm? Adverse events in a nation-wide cohort of patients with multidrug-resistant tuberculosis in Nigeria

Background Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria. Method This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed. Results Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28–42] and median weight was 51 kg (IQR: 45–59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1–2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs. Conclusion Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated.

Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy

Background Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation. Methods We assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed. Results Changes in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients. Conclusions Monitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation.

The hidden costs of installing Xpert machines in a tuberculosis high-burden country: experiences from Nigeria.

Introduction Since the endorsement of GeneXpert MTB/RIF by the WHO, many countries have embarked on implementing this technology. Objective: We outline the cost of installing GeneXpert in district hospitals in Abuja, Nigeria. Methods We prospectively documented costs related to the installation of GeneXpert at five sites. Costs were collected from receipts received from suppliers and normalized to USD 2012 values. Results Costs were often identified after initiating installation for many reasons. Installation varied widely between sites with sufficient space and power supply; sites with insufficient space or power supply and costs not directly associated with site installation. The basic cost for installation was USD 2,621.98 per machine. Sites that required additional space cost close to USD 7,000.00. Conclusion Space and power requirements have a significant effect on installation costs. Countries need to carefully consider the placement of Xpert machines based on the quality and size of the available infrastructure.

Testing Pooled Sputum with Xpert MTB/RIF for Diagnosis of Pulmonary Tuberculosis To Increase Affordability in Low-Income Countries

ABSTRACT Tuberculosis (TB) is a global public health problem, with the highest burden occurring in low-income countries. In these countries, the use of more sensitive diagnostics, such as Xpert MTB/RIF (Xpert), is still limited by costs. A cost-saving strategy to diagnose other diseases is to pool samples from various individuals and test them with single tests. The samples in positive pool samples are then retested individually to identify the patients with the disease. We assessed a pooled testing strategy to optimize the affordability of Xpert for the diagnosis of TB. Adults with presumptive TB attending hospitals or identified by canvassing of households in Abuja, Nigeria, were asked to provide sputum for individual and pooled (4 per pool) testing. The agreement of the results of testing of individual and pooled samples and costs were assessed. A total of 738 individuals submitted samples, with 115 (16%) being Mycobacterium tuberculosis positive. Valid Xpert results for individual and pooled samples were available for 718 specimens. Of these, testing of pooled samples detected 109 (96%) of 114 individual M. tuberculosis-positive samples, with the overall agreement being 99%. Xpert semiquantitative M. tuberculosis levels had a positive correlation with the smear grades, and the individual sample-positive/pooled sample-negative results were likely due to the M. tuberculosis concentration being below the detection limit. The strategy reduced cartridge costs by 31%. Savings were higher with samples from individuals recruited in the community, where the proportion of positive specimens was low. The results of testing of pooled samples had a high level of agreement with the results of testing of individual samples, and use of the pooled testing strategy reduced costs and has the potential to increase the affordability of Xpert in countries with limited resources.

Knowledge of tuberculosis management using directly observed treatment short course therapy among final year medical students in South Western Nigeria

Introduction Equipping medical graduates with the competence to manage tuberculosis is not just imperative but also urgent as the diseases have been consistently listed as one of the major causes of morbidity and mortality in Nigeria. However, there were no baseline studies done on knowledge of final year medical students on various aspects of TB diagnosis and management under directly observed treatment short course therapy (DOTS) which forms the basis of this study. Methods A total of 241 final year medical students from three medical colleges in Nigeria were interviewed. The questions assessed their knowledge about various modes of transmission, symptoms and management of tuberculosis under DOTS. Results More than half of the respondents (i.e. 69%) had poor knowledge on TB disease. Only 33.6% mentioned sputum smear as the best tool of diagnosing TB according to guideline. Poor knowledge was also exhibited when asked of various categories under DOTS treatment regimen, as 46.1% correctly mentioned cat 1 and 2. Minority 18.7% and 6.7% had complete knowledge of 6 months duration for new TB cases and 8 months for re-treatment cases respectively. Less than one tenth, i.e. 4.6% and 2.9% could correctly defined what is called a new TB case and re-treatment cases according to standard guideline. Conclusion The study reveals gross inadequacies in TB knowledge and management practices among Nigerian final year medical students. There is urgent need for incorporation of National TB guideline into existing undergraduate medical education curriculum as well as students rotation through activities in DOTS clinic.

Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons.

Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to people with latent tuberculosis (TB) infection (LTBI) to prevent progression to active TB disease. Despite being life-saving for human immunodeficiency virus (HIV)-infected persons who do not have active TB, IPT is poorly implemented globally due to misconceptions shared by healthcare providers and policy makers. However, amongst HIV-infected patients especially those living in resource-limited settings with a high burden of TB, available evidence speaks for IPT: Among HIV-infected persons, active TB- the major contraindication to IPT, can be excluded with symptom screening; chest X-ray and tuberculin skin testing are unreliable and often lead to logistic delays resulting in increased numbers of people with LTBI progressing to active TB; the use of IPT has not been found to increase the risk of the development of INH mono-resistance; IPT is cost-effective and cheaper than the cost of treating cases of active TB that would develop without IPT; ART and IPT have an additive effect on the prevention of TB, and both are safe and beneficial even in children. In order to sustain the recorded gains from ART scale-up and to further reduce TB-related morbidity and mortality, more efforts are needed to scale-up IPT implementation globally.

Tuberculosis case detection in Nigeria, the unfinished agenda

Underdetection of TB is a major problem in sub‐Saharan Africa. WHO recommends countries should have at least 1 laboratory per 100 000 population. However, this recommendation is not evidence based.

Resistance of Mycobacterium Tuberculosis to First and Second Line AntiTuberculosis Drugs in South West, Nigeria

Setting: Tuberculosis treatment centers in Oyo and Osun States, Nigeria nObjective: This study was aimed to determine the proportion and resistance pattern of Mycobacterium tuberculosis isolates among category 2 failures in Nigeria. nDesign: This is a retrospective study of TB Category 2 failures from Oyo and Osun states (Nigeria), from July 2007 to December 2010. Sputum and culture growth of Pulmonary Tuberculosis (PTB) patients were tested for Drug Susceptibility Testing (DST) to first and second line anti-TB drugs in the supra national laboratory at Antwerp, Belgium. nResults: Of the 82 patients, acquired resistance to all first line drugs (RHE and S), were 31(37.8%), while MDR was observed in 46 (56.1%) of the patients under the study. nConclusion: MDR TB was high (56.1%) among patients previously treated with anti-TB drugs, however XDR TB was not observed in the study population. DST services should be made available and accessible to all MDR-TB suspects in the country.

Are patients with pulmonary tuberculosis who are identified through active case finding in the community different than those identified in healthcare facilities

The lack of healthcare access contributes to large numbers of tuberculosis (TB) cases being missed and has led to renewed interest in outreach approaches to increase detection. It is however unclear whether outreach activities increase case detection or merely identify patients before they attend health facilities. We compared adults with cough of >2 weeks duration recruited in health facilities (1202 participants) or in urban slums (2828 participants) in Nigeria. Participants provided demographic and clinical information and were screened using smear microscopy. The characteristics of smear-positive and smear-negative individuals were compared stratified by place of enrolment. Two hundred nine health facility participants (17.4%) and 485 community-based participants (16.9%) were smear positive for pulmonary TB. Community-based smear-positive cases were older (mean age, 36.3 vs. 31.8 years), had longer cough duration (10.3 vs. 6.8 weeks) and longer duration of weight loss (4.6 vs. 3.6 weeks) than facility-based cases; and they complained more of fever (87.4% vs. 74.6%), chest pain (89.0% vs. 67.0%) and anorexia (79.5% vs. 55.5%). Community smear-negative participants were older (mean, 39.4 vs. 34.0 years), were more likely to have symptoms and were more likely to have symptoms of longer duration than smear-negative facility-based participants. Patients with pulmonary TB identified in the community had more symptoms and longer duration of illness than facility-based patients, which appeared to be due to factors differentially affecting access to healthcare. Community-based activities targeted at urban slum populations may identify a different TB case population than that accessing stationary services.