The challenges and successes of implementing a sustainable antimicrobial resistance surveillance programme in Nepal

Nepal is a low-income country (as determined by the World bank) with a poorly organised healthcare delivery system, suffering from resource limitations. Political unrest and the Maoist insurgency from 2001 to 2008 affected many sectors of life including sustainable health care delivery. Furthermore, pharmaceutical manufacturing and importation is poorly regulated and drugs, including antimicrobials, are available without prescription, and antimicrobial consumption on sub-therapeutic dose, for sub-optimal duration is common. Additionally, pharmaceuticals are often stored in sub-standard conditions, compromising product quality. The public health care system in Nepal has a limited laboratory capacity for bacterial culture and AMR testing (available only at some regional hospitals).

In 1998, the Ministry of Health (MOH), Nepal and the United States Agency for International Development (USAID) launched an Infectious Disease (ID) control programme to strengthen national capacity for prevention and control of priority infectious diseases. The goals were to develop a sustainable national surveillance of AMR, develop awareness among physicians regarding AMR and rational drug use, to establish a microbiology quality assurance programme and to systematise record keeping system with data dissemination. The programme in Nepal was implemented by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) Dhaka, Bangladesh in collaboration with Rational Pharmaceutical Management Project (RPM) Arlington, VA, USA. The programme was approved by ICDDR, B research review committee and ethical review committee. The programme started with a participatory planning workshop to build the programme team and to establish a forum for stakeholders (MOH/ Government of Nepal and key organisations -USAID, Nepal and Washington; RPM; USCDC (United States Center for Disease Control and Prevention, Atlanta, Georgia);ICDDR, B; and WHO/Nepal). The workshop focused on development of strategies and approaches of the programme. The programme was designed for selected enteric pathogens (Vibrio cholerae and Shigella spp.), respiratory pathogens (Streptococcus pneumoniae and Haemophilus influenzae) and sexually transmitted pathogen (Neisseria gonorrhoeae). The National Public Health Laboratory (NPHL) and the Epidemiology and Disease Control Division (EDCD) were identified as the national coordinating laboratory and the national focal point for the programme, respectively.

A baseline assessment of 13 laboratories (in the central, eastern, western regions) was conducted in November 1998 using a pre-defined (location, infrastructure, human resource, instrumentation, shipping of bacterial isolates and willingness to share bacterial isolates and data) assessment tool and nine laboratories were selected to implement the programme. A national capacity building initiative through training and workshops were conducted by ICDDR, B and NPHL at NPHL, ICDDR, B and at the participating laboratories, through 1999–2012. The goal was to develop a pool of trainers to train technologists to compensate for transfer, replacement or separation and to facilitate expansion of trained staff. Training included i) the training of trainers, ii) bacterial isolation and Minimum Inhibitory Concentration (MIC) determination, iii) the isolation, identification and MIC determination of Salmonella Typhi, N. gonorrhoeae, S. pneumoniae and H. influenzae and iv) holding annual refresher training workshops. Additionally, consensus workshops and annual meetings were organised during 1999 to 2004. Laboratory testing and procedures were standardised by developing and implementing Standard Operating Procedures (SOPs) for the isolation, identification and AMR testing of the selected pathogens, reporting results, data/record keeping systems, AMR reporting formats, documentation and communication protocols. Each participating laboratory was supported with bacterial culture media, antimicrobial susceptibility discs and antisera at the outset and was encouraged to incorporate the supplies for surveillance of AMR in their annual procurement list. NPHL was also supported with autoclaves, computers and a -86°C freezer. Each laboratory was also supplied with ATCC (American type culture collection) strains for internal quality control (QC).

Each participating laboratory isolated and identified selected pathogens (all consecutive isolates) and performed AMR testing (selected antimicrobial agents for each pathogen using disk diffusion method [8]) and reported data monthly to NPHL and ICDDR, B and sent the isolates to NPHL. At NPHL, all isolates were verified for identification and susceptibility testing and stored at -86°C for future analysis. As very few patients were attending the participating laboratories for sexually transmitted disease (STD) symptoms, isolation of N. gonorrhoeae was established at specific STD clinics at Damak and Hetauda. To strengthen partnerships and networking among the laboratories, training visits between NPHL and participating laboratories were organised. Meetings were also organised among participating laboratories to discuss surveillance programme data, technical issues and sharing experiences and challenges in implementation of the programme. Additionally, ICDDR, B and NPHL team routinely visited the laboratories and provided technical assistance to improve the performance. A two-tier system of External Quality Assessment (EQA) programme and inter-laboratory comparison was implemented to ensure quality. The EQA programme included ICDDR, B (1999–2003)/NHPL (2003–2012) sending two isolates to each of the laboratories every three months, and the inter-laboratory comparison included retesting of 10% isolates at ICDDR, B/NPHL (1999–2003) and NHPL (2003–2012). The WHO scoring system was followed for the EQA and confidential evaluation reports were sent to the laboratories.