Multidrug Resistant Tuberculosis in Children in Port Harcourt – A Worrisome Trend

Background: Drug-resistant tuberculosis and multidrug-resistant tuberculosis (MDR-TB) in particular represent a major threat to the fight against tuberculosis globally. MDR-TB presents with similar features and is transmitted in the same way as drug sensitive TB but its progression is rapid and its treatment, associated drug toxicity and monitoring constitute a heavy burden to the patients and the health system. MDR-TB affect people of all age groups but very little is known about the magnitude of this problem in children. Aims/Objectives: To determine the prevalence of multidrug resistant tuberculosis among children in Port Harcourt. Materials and Methods: Information on Paediatric tuberculosis was retrieved from the patients’ case notes, TB registers at the directly observed treatment short course (DOTs) clinic and the Multidrug resistant tuberculosis (MDR-TB) treatment center of the University of Port Harcourt Teaching Hospital from January 2018 to June 2019. Obtained data was analysed and presented in prose and tables. Results: There was a total of 1,860 patients records of which 37 were Paediatrics cases giving a prevalence of Paediatric tuberculosis cases of 2.0% Out of these 37cases, four were multidrug resistant tuberculosis cases giving a prevalence of MDR-TB cases of 10.8%. There were three males and one female giving a male female ratio of 3: 1. and their ages ranged from 3months to 24months. All belonged to social class 5. Common presentation was chronic cough, prolonged fever, weight loss and lymph node swellings. Three (75%) had no prior treatment for tuberculosis while one (25%) completed 6months of anti TB drugs. All had BCG immunization within one week of delivery. One (25%) child had extra-pulmonary TB while 3(75%) children had pulmonary tuberculosis. Xpert MTB/RIF assay for all (100%) showed MTB detected, RIF resistant detected. Three (75%) of the mothers had MDRTB and the medications for their children was based on the drug sensitivity testing (DST) of their mothers. One (25%) of the children and his mother were HIV positive and the mother had died while still on the intensive phase of second line antiTB drugs. Three (75%) had completed the intensive phase of the conventional therapy with second line antiTB drugs and are closely followed up weekly on the continuation phase while one child is still on admission. Conclusions: The prevalence of MDR-TB in children in PH is high. All childhood TB (whether drug susceptible or drug resistant) is usually traced to an adult, thus effectively diagnosing and treating all adults as well as a high index of suspicion in presumptive cases is required to curb MDR-TB. Recommendations: We recommend strict use of the DOTs strategy in TB management to ensure drug adherence. Also, proper contact tracing, investigation and treatment of children of infected parents to reduce cases of MDR-TB is advocated.

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The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽

10.1186/s12916-021-01932-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chathika K Weerasuriya ◽

Rebecca C Harris ◽

C Finn McQuaid ◽

Fiammetta Bozzani ◽

Yunzhou Ruan ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Multidrug Resistant ◽

Second Line ◽

Second Line Therapy ◽

China And India ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Line Therapy ◽

Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

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Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

BioMed Research International ◽

10.1155/2017/4563826 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Y. Hu ◽

L. Xu ◽

Y. L. He ◽

Y. Pang ◽

N. Lu ◽

...

Keyword(s):

Gene Mutations ◽

Multidrug Resistant ◽

Rapid Screening ◽

Second Line ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Improper Use ◽

Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

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Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02410-17 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 7

Author(s):

Agibothu Kupparam Hemanth Kumar ◽

Alok Kumar ◽

Thiruvengadam Kannan ◽

Rakesh Bhatia ◽

Dipti Agarwal ◽

...

Keyword(s):

High Performance ◽

Linear Regression Analysis ◽

Multidrug Resistant ◽

Control Programme ◽

Second Line ◽

Time Curve ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

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Treatment of Drug-Resistant Tuberculosis: Current Status

Annals of the National Academy of Medical Sciences (India) ◽

10.1055/s-0040-1714201 ◽

2020 ◽

Author(s):

Rajendra Prasad ◽

Harsh Saxena ◽

Nikhil Gupta ◽

Mohammad Tanzeem ◽

Ronal Naorem

Keyword(s):

Total Duration ◽

World Health ◽

Current Status ◽

Current Evidence ◽

Drug Resistant ◽

Second Line ◽

Drug Resistant Tuberculosis ◽

Intensive Phase ◽

Resistant Tuberculosis ◽

Mdr Tb

AbstractDrug-resistant tuberculosis (DR-TB) has been an area of growing concern and posing threat to human health worldwide. The treatment has been defined for all types of DR-TB with or without newer anti-TB drugs. multi-DR-TB (MDR-TB) patients have now choice of two types of regimen, shorter and longer regimens. Shorter regimen for treatment of subset of MDR-TB patients who have not been previously treated with second line drugs and in whom resistance to fluoroquinolones and second-line injectable agents has been excluded is given for 9 to 11 months. A longer regimen of at least five effective anti-TB drugs (ATDs) during the intensive phase is recommended, including pyrazinamide and four core second-line ATDs. Intensive phase, including injectables, should be given for at least 8 months. The total duration of treatment is at least 20 months, which can be prolonged up to 24 months depending on the response of the patient. World Health Organization (WHO) has recently revised the grouping of ATD for use in DR-TB patients in 2018 into three groups based on individual patient data meta-analysis depending on their individual efficacy, risk of relapse, treatment failure, and death. Recently, an all oral longer regimen comprising bedaquiline, pretomanid, and linezolid (BPal regime) for 6 to 9 months for extensive-DR-TB (XDR-TB) patients and those MDR-TB patients who cannot tolerate or do not respond to conventional MDR-TB regimen. These new developments will be a step forward toward establishing universal regimen to treat all types of DR-TB. This article has summarized the current evidence from literature search to date, including prevalence of DR-TB, types of regimen used and the advancement in the regimens for effective treatment of DR-TB patients.

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Multidrug-Resistant Tuberculosis in Alberta and British Columbia, 1989 to 1998

Canadian Respiratory Journal ◽

10.1155/1999/456395 ◽

1999 ◽

Vol 6 (2) ◽

pp. 155-160 ◽

Cited By ~ 11

Author(s):

Ahmed Hersi ◽

Kevin Elwood ◽

Robert Cowie ◽

Dennis Kunimoto ◽

Richard Long

Keyword(s):

British Columbia ◽

Multidrug Resistant ◽

Drug Resistant ◽

Foreign Born ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Culture Positive

OBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (P<0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.

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Epidemiology of drug-resistant tuberculosis in Chongqing, China: a retrospective observational study from 2010 to 2017

10.1101/610048 ◽

2019 ◽

Author(s):

Bo Wu ◽

Ya Yu ◽

Changting Du ◽

Ying Liu ◽

Daiyu Hu

Keyword(s):

Observational Study ◽

Treatment Success ◽

Multidrug Resistant ◽

Policy Support ◽

Retrospective Observational Study ◽

Drug Resistant ◽

Notification Rate ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

AbstractChina is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.09 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases among all notified TB cases. The treatment success rate of MDR/RR-TB was 50.66% in this period. The rate of MDR/RR-TB in new TB cases was 6.23%, and this rate in previously treated TB cases was 32.7%. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

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Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

F1000Research ◽

10.12688/f1000research.17743.3 ◽

2020 ◽

Vol 8 ◽

pp. 498

Author(s):

Priya Rathi ◽

Kalpita Shringarpure ◽

Bhaskaran Unnikrishnan ◽

Abhinav Pandey ◽

Abhirami Nair

Keyword(s):

Multidrug Resistant ◽

Diagnosis And Treatment ◽

Patient Treatment ◽

Drug Resistant ◽

Treatment Pathways ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The Government

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however the diagnostic rate was high in public HCF. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

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Draft Genome Sequences of Two Drug-Resistant Mycobacterium tuberculosis Isolates from Myanmar

Genome Announcements ◽

10.1128/genomea.00850-16 ◽

2016 ◽

Vol 4 (5) ◽

Cited By ~ 1

Author(s):

Htin Lin Aung ◽

Thanda Tun ◽

Elizabeth Permina ◽

Wint Wint Nyunt ◽

Si Thu Aung ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Draft Genome ◽

Multidrug Resistant ◽

Drug Resistant ◽

Genome Sequences ◽

Health Concerns ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) and lately, extensively drug-resistant TB (XDR-TB) are increasing global health concerns. Here, we present the genome sequences of two MDR-TB isolates from Myanmar, one of 27 countries with a high MDR-TB burden, and describe a number of mutations consistent with these being XDR-TB isolates.

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Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis

BMC Infectious Diseases ◽

10.1186/s12879-019-4494-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Maria Musso ◽

Silvia Mosti ◽

Gina Gualano ◽

Paola Mencarini ◽

Rocco Urso ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Side Effects ◽

Chronic Infection ◽

Multidrug Resistant ◽

Hcv Infection ◽

Second Line ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

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Safety and Efficacy of Delamanid in the Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s11675 ◽

2013 ◽

Vol 5 ◽

pp. CMT.S11675 ◽

Cited By ~ 5

Author(s):

Stephen K. Field

Keyword(s):

Multidrug Resistant ◽

Phase Iii ◽

Drug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Improved Outcomes ◽

Resistance Patterns ◽

Mdr Tb ◽

Phase Iii Study

Globally, the incidence of tuberculosis (TB) is declining but the proportion of drug-resistant cases has increased. Strains resistant to both isoniazid and rifampin, and possibly other antibiotics, called multidrug-resistant (MDR), are particularly difficult to treat. Poorer outcomes, including increased mortality, occur in patients infected with MDR strains and the costs associated with treatment of MDR-TB are substantially greater. The recent recognition of MDR-TB and strains with more complex resistance patterns has stimulated the development of new TB medications including fluoroquinolones, oxazolidinones, diarylquinolines, nitroimidazopyrans, ethylenediamines, and benzothiazinones. Bedaquiline, a diarylquinoline, was approved for the treatment of MDR-TB in 2012. Addition of delamanid to WHO-approved treatment improved outcomes for MDR-TB and for extensively drug-resistant TB in a large randomized, controlled phase II clinical trial and is undergoing evaluation in a large international phase III study. This review will focus on MDR-TB and the role of delamanid in its treatment.

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