Sputum culture reversion in longer treatments with bedaquiline, delamanid, and repurposed drugs for drug-resistant tuberculosis.

Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs.

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study.

Scale-Up of Rifapentine and Isoniazid for Tuberculosis Prevention Among Household Contacts in 2 Urban Centers: An Effectiveness Assessment.

Background: Scaling up a shorter preventive regimen such as weekly isoniazid and rifapentine (3HP) for 3 months is a priority for tuberculosis (TB) preventive treatment (TPT). However, there are limited data on 3HP acceptability and completion from high-burden-TB countries.

Methods: We scaled up 3HP from 2018 to 2021 in 2 cities in Pakistan.

Drug-Resistant Tuberculosis Treatment Outcomes among Children and Adolescents in Karachi, Pakistan.

Background: Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan.

Methods: We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services.

WHO Point Prevalence Survey to Describe the Use of Antimicrobials at a Tertiary Care Center in Pakistan: A Situation Analysis for Establishing an Antimicrobial Stewardship Program.

Antimicrobial stewardship is a systematic approach for promoting and monitoring responsible antimicrobial use globally. We conducted a prospective point prevalence survey of antimicrobial utilization among hospitalized adult patients during September 2021. The survey instrument was adapted from the WHO methodology for point prevalence surveys, and it was conducted at The Indus Hospital and Health Network, Karachi.

Re-evaluating the merits of decentralization as a core strategy for effective delivery of drug-resistant tuberculosis care in Pakistan.

Decentralized, person-centred models of care delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high-burden TB countries. The implementation of such models-made increasingly urgent by the COVID-19 pandemic-are key to addressing gaps in DR-TB care. We abstracted data of rifampicin-resistant (RR)/multidrug-resistant tuberculosis (MDR-TB) patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan.

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs.

Background: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.

A shorter post-exposure prophylaxis regimen for rabies, Pakistan.

Objective: To assess the cost and effectiveness of the two-site, 1-week, intradermal rabies post-exposure prophylaxis regimen recommended by the World Health Organization (WHO) in 2018.

Methods: We compared the number of rabies vaccine and rabies immunoglobulin ampoules consumed at The Indus Hospital in Karachi, Pakistan and their cost before and after implementing WHO's 2018 recommendations. In 2017, patients with suspected rabies-infected bites were treated using the two-site, 4-week, Thai Red Cross regimen, which involved administering four rabies vaccine doses intradermally over 4 weeks and infiltrating immunoglobulin into serious wounds, with the remainder injected into a distant muscle.

One Health for neglected tropical diseases.

The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021-2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context.

Risk Factors for Adverse Events in Household Contacts Prescribed Preventive Treatment for Drug-resistant Tuberculosis Exposure.

Background: Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan.

Methods: The primary outcome was development of any clinical AE during preventive treatment.

Frequency, clinical characteristics, risks, and outcomes of Paradoxical upgrading reactions during anti-tuberculosis treatment in tuberculous lymphadenitis.

Objectives: To investigate the clinical characteristics, risks and outcomes of Paradoxical upgrading reactions (PUR) during anti-tuberculosis treatment (ATT) in superficial tuberculous lymphadenitis (TBLA).

Methods: In this nested case-control study, all patients diagnosed with TBLA based on combinations of histopathology, acid-fast bacilli (AFB) microscopy, AFB culture, and GeneXpert, between February 2013 and April 2016, were enrolled. Standard ATT was given.

An Unusual Case of Extensively Drug Resistant Typhoid Fever.

Enteric fever is a potentially fatal multisystemic illness caused primarily by and, to a lesser extent, by Paratyphi A, B, and C. Emergence of resistance has depleted the antimicrobial arsenal overtime, making treatment challenging and costly. In 2016, a new extensively drug resistant (XDR) strain of emerged in Sindh, which only responds to two antibiotics--carbapenems and azithromycin.

Tuberculosis Preventive Therapy for Individuals Exposed to Drug-resistant Tuberculosis: Feasibility and Safety of a Community-based Delivery of Fluoroquinolone-containing Preventive Regimen.

Background: Observational studies have demonstrated the effectiveness of a fluoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia.

Methods: From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home.

Current status of human rabies prevention: remaining barriers to global biologics accessibility and disease elimination.

: Rabies is a serious, neglected tropical disease. Zoonotic agents are RNA viruses (Genus Lyssavirus, Family Rhabdoviridae), global in distribution. As an acute, progressive, incurable encephalitis, rabies has the highest case fatality of any infectious disease.

Raised levels of IFN-gamma and IL-13 are associated with pre-diabetes amongst newly diagnosed patients with Tuberculosis.

Objective: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status.

Methods: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital (AKUH), Karachi.

Rabies post-exposure prophylaxis: A systematic review on abridged vaccination schedules and the effect of changing administration routes during a single course.

Rabies is a fatal zoonotic disease preventable through timely and adequate post-exposure prophylaxis (PEP) to potentially exposed persons i.e. wound washing and antisepsis, a series of intradermal (ID) or intramuscular (IM) rabies vaccinations, and rabies immunoglobulin in WHO category III exposures.

Five-year Audit of Infectious Diseases at a Tertiary Care Hospital in Karachi, Pakistan.

Purpose To estimate the burden of infectious diseases and the seasonality of mosquito-borne diseases seen at The Indus Hospital, Karachi (TIH). Methodology We performed a retrospective data analysis of all infectious diseases (ID) cases, retrieved from medical records over a five-year period starting from 1 January 2012 till 31 December 2016 at The Indus Hospital (TIH), which is a 150-bed, charity-based, tertiary-care health facility. The collected data has been categorized into three groups: (A) public health-related diseases, including community and environmental IDs, i.

Histopathological and microbiological findings and diagnostic performance of GeneXpert in clinically suspected tuberculous lymphadenitis.

Objectives: The primary objective was to determine the association between histopathological and microbiological findings in patients clinically suspected to have tuberculous lymphadenitis. A secondary objective was to assess the diagnostic utility of GeneXpert in lymph node specimens.

Method: This was a single-centre prospective cohort study, performed in the Infectious Disease Clinic at The Indus Hospital.

Leprosy manifesting with type 2 leprae reaction in a patient presenting with chronic fever: A case report.

Leprosy is a chronic granulomatous disease involving the skin and nerves, leading to a debilitating condition. Leprosy has been controlled in most parts of the world; therefore physicians are not very well versed in the recognition, management and assessment of this disease. The protean manifestations of leprosy often lead to delays in diagnosis and increase the morbidity.

Assessment of diabetes among tuberculosis patients presenting at a tertiary care facility in Pakistan.

Objective/background: Pakistan ranks sixth among high-tuberculosis (TB)-burden countries worldwide and fifth worldwide for diabetes incidence. Although both these factors are independently known, the rate of diabetes among TB patients is not well known. We aimed to determine the prevalence of diabetes among patients with TB presenting at tertiary care health centers in Karachi, Pakistan.

Unusual case of non-resolving necrotizing pneumonia: A last resort measure for cure.

To our knowledge, this is an unusual case of a community-acquired pneumonia (CAP) with sepsis secondary to Streptococcus pneumoniae that required lung resection for a non-resolving consolidation. A 74 year old previously healthy woman, presented with acute fever, chills and pleuritic chest pain in Emergency Department (ED). A diagnosis of CAP was established with a Pneumonia Severity Index CURB-65 score of 5/5.

Reducing Cost of Rabies Post Exposure Prophylaxis: Experience of a Tertiary Care Hospital in Pakistan.

Background: Rabies is a uniformly fatal disease, but preventable by timely and correct use of post exposure prophylaxis (PEP). Unfortunately, many health care facilities in Pakistan do not carry modern life-saving vaccines and rabies immunoglobulin (RIG), assuming them to be prohibitively expensive and unsafe. Consequently, Emergency Department (ED) health care professionals remain untrained in its application and refer patients out to other hospitals.