Implementation of a customised antimicrobial resistance laboratory scorecard in Cameroon, Ethiopia and Kenya.

Background: In low-resource settings, antimicrobial resistance (AMR) is detected by traditional culture-based methods and ensuring the quality of such services is a challenge. The AMR Scorecard provides laboratories with a technical assessment tool for strengthening the quality of bacterial culture, identification, and antimicrobial testing procedures. Objective: To evaluate the performance of the AMR Scorecard in 11 pilot laboratory evaluations in three countries also assessed with the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. Methods: Pilot laboratory evaluations were conducted in Cameroon, Ethiopia and Kenya between February 2019 and March 2019. Assessors with previous SLIPTA and microbiology experience were trained. Assessors performed the laboratory assessments using the SLIPTA and AMR Scorecard tools. Results: Weaknesses in technical procedures and the quality management systems were identified in all areas and all laboratories. Safety had the highest mean performance score (SLIPTA: 68%; AMR Scorecard: 73%) while management review had the lowest (SLIPTA: 32%; AMR Scorecard: 8%) across all laboratories. The AMR Scorecard scores were generally consistent with SLIPTA scores. The AMR Scorecard identified technical weaknesses in AMR testing, and SLIPTA identified weaknesses in the quality management systems in the laboratories. Conclusion: Since the AMR Scorecard identified important gaps in AMR testing not detected by SLIPTA, it is recommended that microbiology laboratories use SLIPTA and the AMR Scorecard in parallel when preparing for accreditation. Expanding the use of the AMR Scorecard is a priority to address the need for quality clinical microbiology laboratory services in support of optimal patient care and AMR surveillance.

Review of the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) version 2:2015.

BACKGROUND: In 2011 the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) was launched, aimed at strengthening the quality and competence of African clinical, public health and reference laboratories. We reviewed the first version of the SLIPTA checklist in 2011. The continued development and publication of a new version of the International Organization for Standardization (ISO) 15189 standard demands a renewed review. OBJECTIVE: This study aimed to determine the suitability of SLIPTA in guiding laboratories towards ISO 15189:2012 compliance and accreditation and provide recommendations for further SLIPTA improvement. METHODS: The study was conducted between September 2018 and April 2019. Coverage of ISO 15189:2012 by SLIPTA checklist version 2:2015 was determined and the point distribution of the scoring system over the different sections of the SLIPTA checklist was re-investigated. These findings were compared with the review of the first version of the SLIPTA checklist (based on ISO 15189:2007) and with findings published on SLIPTA implementation and roll-out. RESULTS: The coverage of ISO 15189 by the SLIPTA checklist has increased, even though ISO 15189:012 is more extensive than ISO 15189:2007. The point distribution is still skewed towards sections related to quality planning rather than quality control and improvement. Although to date 314 laboratories have been assessed, barriers for laboratories to participate in SLIPTA are high. Sustainability of SLIPTA results is insufficiently studied. CONCLUSION: SLIPTA checklist version 2:2015 has improved compared to earlier versions. We recommend increasing accessibility for laboratories to participate and increasing guidance for ISO-based quality management system implementation.

Longitudinal assessment of anti-PGL-I serology in contacts of leprosy patients in Bangladesh.

BACKGROUND: Despite elimination efforts, the number of Mycobacterium leprae (M. leprae) infected individuals who develop leprosy, is still substantial. Solid evidence exists that individuals living in close proximity to patients are at increased risk to develop leprosy. Early diagnosis of leprosy in endemic areas requires field-friendly tests that identify individuals at risk of developing the disease before clinical manifestation. Such assays will simultaneously contribute to reduction of current diagnostic delay as well as transmission. Antibody (Ab) levels directed against the M.leprae-specific phenolic glycolipid I (PGL-I) represents a surrogate marker for bacterial load. However, it is insufficiently defined whether anti-PGL-I antibodies can be utilized as prognostic biomarkers for disease in contacts. Particularly, in Bangladesh, where paucibacillary (PB) patients form the majority of leprosy cases, anti-PGL-I serology is an inadequate method for leprosy screening in contacts as a directive for prophylactic treatment. METHODS: Between 2002 and 2009, fingerstick blood from leprosy patients' contacts without clinical signs of disease from a field-trial in Bangladesh was collected on filter paper at three time points covering six years of follow-up per person. Analysis of anti-PGL-I Ab levels for 25 contacts who developed leprosy during follow-up and 199 contacts who were not diagnosed with leprosy, was performed by ELISA after elution of bloodspots from filter paper. RESULTS: Anti-PGL-I Ab levels at intake did not significantly differ between contacts who developed leprosy during the study and those who remained free of disease. Moreover, anti-PGL-I serology was not prognostic in this population as no significant correlation was identified between anti-PGL-I Ab levels at intake and the onset of leprosy. CONCLUSION: In this highly endemic population in Bangladesh, no association was observed between anti-PGL-I Ab levels and onset of disease, urging the need for an extended, more specific biomarker signature for early detection of leprosy in this area. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN61223447.

A new matrix for scoring the functionality of national laboratory networks in Africa: introducing the LABNET scorecard.

BACKGROUND: Functional national laboratory networks and systems are indispensable to the achievement of global health security targets according to the International Health Regulations. The lack of indicators to measure the functionality of national laboratory network has limited the efficiency of past and current interventions to enhance laboratory capacity in resource-limited-settings. SCORECARD FOR LABORATORY NETWORKS: We have developed a matrix for the assessment of national laboratory network functionality and progress thereof, with support from the African Society of Laboratory Medicine and the Association of Public Health Laboratories. The laboratory network (LABNET) scorecard was designed to: (1) Measure the status of nine overarching core capabilities of laboratory network required to achieve global health security targets, as recommended by the main normative standards; (2) Complement the World Health Organization joint external evaluation tool for the assessment of health system preparedness to International Health Regulations (2005) by providing detailed information on laboratory systems; and (3) Serve as a clear roadmap to guide the stepwise implementation of laboratory capability to prevent, detect and act upon infectious threats. CONCLUSIONS: The application of the LABNET scorecard under the coordination of the African Society of Laboratory Medicine and the Association of Public Health Laboratories could contribute to the design, monitoring and evaluation of upcoming Global Health Security Agenda-supported laboratory capacity building programmes in sub Saharan-Africa and other resource-limited settings, and inform the development of national laboratory policies and strategic plans. Endorsement by the World Health Organization Regional Office for Africa is foreseen.

Longitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal.

BACKGROUND: Acute inflammatory reactions are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. In leprosy, an infectious disease initiated by Mycobacterium leprae (M. leprae), these reactions represent the major cause of permanent neuropathy. However, laboratory tests for early diagnosis of reactional episodes which would significantly contribute to prevention of tissue damage are not yet available. Although classical diagnostics involve a variety of tests, current research utilizes limited approaches for biomarker identification. In this study, we therefore studied leprosy as a model to identify biomarkers specific for inflammatory reactional episodes. METHODS: To identify host biomarker profiles associated with early onset of type 1 leprosy reactions, prospective cohorts including leprosy patients with and without reactions were recruited in Bangladesh, Brazil, Ethiopia and Nepal. The presence of multiple cyto-/chemokines induced by M. leprae antigen stimulation of peripheral blood mononuclear cells as well as the levels of antibodies directed against M. leprae-specific antigens in sera, were measured longitudinally in patients. RESULTS: At all sites, longitudinal analyses showed that IFN-γ-, IP-10-, IL-17- and VEGF-production by M. leprae (antigen)-stimulated PBMC peaked at diagnosis of type 1 reactions, compared to when reactions were absent. In contrast, IL-10 production decreased during type 1 reaction while increasing after treatment. Thus, ratios of these pro-inflammatory cytokines versus IL-10 provide useful tools for early diagnosing type 1 reactions and evaluating treatment. Of further importance for rapid diagnosis, circulating IP-10 in sera were significantly increased during type 1 reactions. On the other hand, humoral immunity, characterized by M. leprae-specific antibody detection, did not identify onset of type 1 reactions, but allowed treatment monitoring instead. CONCLUSIONS: This study identifies immune-profiles as promising host biomarkers for detecting intra-individual changes during acute inflammation in leprosy, also providing an approach for other chronic (infectious) diseases to help early diagnose these episodes and contribute to timely treatment and prevention of tissue damage.

Protecting people against leprosy: chemoprophylaxis and immunoprophylaxis.

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.

Protecting people against leprosy: chemoprophylaxis and immunoprophylaxis

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.

Leprosy incidence: six years follow-up of a population cohort in Bangladesh.

BACKGROUND: With approximately 250,000 new leprosy cases detected annually, transmission of M. leprae appears to be ongoing in many areas of the world. By studying prospectively the number of leprosy patients found in a population sample at the beginning of the study (prevalence) and the number of new patients found during the 6-year observation period (incidence), we aim to understand better the transmission of M. leprae and the burden of disease. METHODOLOGY: To establish the prevalence and incidence rates of leprosy in the general population of a high endemic area in Bangladesh, we followed prospectively 20,218 individuals from a random cluster sample of the population and examined them at 2-yearly intervals for 6 years. RESULTS: At intake we found 27 new leprosy cases, indicating a prevalence of previously undiagnosed leprosy of 13.3/10,000. Follow-up at 2, 4 and 6 years revealed 17, 16, and eight new cases, respectively, representing incidence rates of 4.0, 4.5 and 2.3/10,000 PYAR, respectively. The incidence rate over 6 years was 3.7/10,000 PYAR. The observed incidence rate is three times higher than the new case detection rate in the same area. Of all 68 new leprosy cases, five (7%) had MB leprosy. The proportion of children under 15 years was 24%. The proportion of female patients was 60%, but the incidence rate of leprosy was the same for males and females. CONCLUSIONS: The decline in incidence of leprosy in a general population sample is less pronounced than routine data from a control programme led us to expect.

Understanding the interface between clinical and laboratory staff.

BACKGROUND: The interface between clinicians and laboratory staff is where the two meet and work together to provide quality care to their clients (patients). Effectiveness of the interface depends on the way the two groups of professionals relate to and communicate with each other. The number and type of tests requested and the use of the test results for clinical decision making can be influenced by the interface between clinicians and laboratory staff. A model to understand the factors and dynamics around the interface is lacking. OBJECTIVES: To propose a new conceptual model to gain insight and analyse factors that influence the laboratory-clinical staff interface. METHODS: To develop the conceptual model, a literature study was performed, regulatory guidelines and standards for laboratories were analysed and discussions were held with experts on the topic. RESULT: A conceptual model and analytical framework provided good guidance in understanding and assessing the organisational and personal factors shaping the interface. The model was based on three elements: (1) the three phases of communication (pre-analytical, analytical and post-analytical); (2) the organisational and personal factors of interaction; and (3) the socio-political, economic and cultural context in which clinicians and laboratory staff operate. CONCLUSION: Assessment of the interface between clinicians and laboratory workers can be performed in a systematic way. Applying this model will provide information to managers of health institutions and heads of laboratories and clinical departments about what happens when clinicians and laboratory staff interact, thus aiding them in designing strategies to improve this interface.

Response patterns to interactive SMS health education quizzes at two sites in Uganda: a cohort study.

OBJECTIVE: The use of mobile phones can improve and strengthen (preventive) health care in low- and middle-income countries. We aimed to retrospectively assess the response patterns of participants in free SMS health education quizzes in Uganda. METHODS: Study participants were employees of two companies and their community networks. We investigated how quickly individuals responded to quiz question(s) and assessed possible influencing factors. Cox regression and anova analyses were used. RESULTS: Fifty percentage of responders answered within 50 min. The response chance declined with every additional day after sending an incentive via SMS (Hazard Ratio 0.993, CI 95% 0.981-0.984). Quiz topics influenced both participation rates and response time. Response time was shortest for questions on HIV and sexual behaviour. Response rates were high for HIV (79%) and malaria (78.4%), but only 37.4% for demographic topics. Network providers had a substantial effect on response behaviour. CONCLUSION: Interactive SMS programs are a fast method to reach the target population and incentives increase response rates. The most important factor influencing response time and participation rate is the network provider. Future research should focus on developing evidence-based guidelines for the design, implementation and evaluation of SMS-based interventions.

A qualitative exploration of social contact patterns relevant to airborne infectious diseases in northwest Bangladesh.

In South Asia, the burden of infectious diseases is high. Socioeconomically and culturally-defined social interaction patterns are considered to be an important determinant in the spread of diseases that are transmitted through person-to-person contact. Understanding of the contact patterns in this region can be helpful to develop more effective control measures. Focus group discussions were used in exploring social contact patterns in northwest Bangladesh. The patterns were assessed for perceived relevance to the spread of airborne infectious diseases, with special focus on diseases, like leprosy and tuberculosis, in which the role of social determinants is well-recognized. Highly-relevant social contact patterns inside the home and the neighbourhood, across age and sex groups, were reported in all group discussions. Outside the home, women and girls reported relevant contacts limited to the close neighbourhood while men mentioned high relevant contacts beyond. This implies that, in theory, infectious diseases can easily be transmitted across age and sex groups in and around the home. Adult men might play a role in the transmission of airborne infectious diseases from outside this confined area since only this group reported highly-relevant social contacts beyond the home. This concept needs further exploration but control programmes in the South Asian region could benefit from considering differences in social contact patterns by gender for risk assessments and planning of preventive interventions.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

Survey of the diagnostic retooling process in national TB reference laboratories, with special focus on rapid speciation tests endorsed by WHO in 2007.

BACKGROUND: Successful integration of new diagnostics in national tuberculosis (TB) control programs, also called 'retooling', is highly dependent on operational aspects related to test availability, accessibility and affordability. This survey aimed to find out whether recommendations to use new diagnostics lead to successful retooling in high TB endemic countries, using immunochromatographic tests (ICTs) for TB culture speciation as a case study. ICTs are recommended to accurately confirm the presence of bacteria of the Mycobacterium tuberculosis complex in liquid culture isolates. METHODS AND FINDINGS: Questionnaires were sent to national TB reference laboratories (NRLs) in 42 high TB endemic countries to address their access to information on ICT implementation, logistics related to availability, accessibility and affordability of ICTs, and testing algorithms. Results from 16 responding countries indicated that half of the NRLs were aware of the contents of WHO guidance documents on liquid culture and ICT implementation, as well as their eligibility for a negotiated pricing agreement for ICT procurement. No major issues with availability and accessibility of ICTs were raised. When asked about testing algorithms, ICTs were not used as stand-alone or first test for TB culture identification as recommended by WHO. CONCLUSIONS: The low response rate was a limitation of this survey and together with NRLs managers' unawareness of global guidance, suggests a lack of effective communication between partners of the global laboratory network and NRLs. TB tests could become more affordable to high TB endemic countries, if the possibility to negotiate lower prices for commercial products is communicated to them more successfully. NRLs need additional guidance to identify where available technologies can be most usefully implemented and in what order, taking into account long-term laboratory strategies.

[Lucio's phenomenon in a patient with leprosy on Aruba]. / Luciofenomeen bij een patiënt met lepra op Aruba.

BACKGROUND: Lucio's phenomenon is a rare leprosy reaction characterised by bizarrely-shaped, purpuric skin lesions and ulceration. It occurs in diffuse lepromatous leprosy and it is mainly reported in patients from Mexico and the Caribbean. CASE DESCRIPTION: We describe the case of a 90-year-old Aruban man with recurrent leg ulcers and flexion contractures of the lower extremities. Occurrence of Lucio's phenomenon led to a diagnosis of diffuse lepromatous leprosy. Presence of Mycobacterium leprae was demonstrated in skin, bone marrow and lymph nodes. CONCLUSION: Lucio's phenomenon led to a diagnosis of leprosy. Leprosy is still endemic in Aruba.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal.

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh.

OBJECTIVES: The COLEP trial in Bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (SDR). We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention. DESIGN: The cohort of 1037 patients and their 28 092 contacts that participated in the randomised placebo controlled field trial with single dose rifampicin was followed for 6 years. The leprosy status of contacts was established at 2, 4 and 6 years after the intervention. We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression. RESULTS: The protective effect of SDR was seen only in the first 2 years, with no additional effect after 4 and 6 years. However, the total impact of the intervention was still statistically significant (P = 0.025) after 6 years and no excess cases were observed in the SDR arm at a later stage. The intervention prevented leprosy in contacts that actually received SDR, but did not offer protection to members of the same contact group who did not take chemoprophylaxis. The intervention was most effective in contact groups of female index patients, an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well. CONCLUSION: These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures, such as early detection or chemoprophylaxis.

Critical review of the Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA): suggestions for harmonization, implementation and improvement.

OBJECTIVE: Clinical laboratories in low- and middle-income countries (LMIC) need fundamental improvement because quality laboratory services are essential for the decision-making capacity of clinicians, health workers and public health authorities. To this end, a tiered accreditation scheme Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA) was developed by WHO-AFRO, CDC and others for clinical laboratories in LMIC. One to five stars are accredited to laboratories based on the level of compliance with a checklist. Our aim was to evaluate the quality and applicability of this accreditation scheme compared with international quality standards. METHODS: We performed a critical review of this scheme to formulate recommendations for implementation, harmonization and improvement. Two analyses were performed: one assessing its coverage of the ISO 15189:2007 standard and one to identify and evaluate priorities of the accreditation checklist. RESULTS: Although the content of the checklist covers all aspects of total quality management, it strongly prioritizes resource management activities. We recommend identifying critical requirements for each tier of accreditation to assure a certain level of quality for each tier or instead using a pass/fail approach towards accreditation. In addition, the checklist should include more questions for assessing proper management, ethics and continuous improvement to meet ISO 15189. CONCLUSION: Launching accreditation schemes for laboratories in LMIC should be encouraged. After further optimization of SLIPTA, clinical laboratories may certainly benefit, leading to more correctly diagnosed patients and less waste of resources.

Review and comparison of quality standards, guidelines and regulations for laboratories.

BACKGROUND: The variety and number of laboratory quality standards, guidelines and regulations (hereafter: quality documents) makes it difficult to choose the most suitable one for establishing and maintaining a laboratory quality management system. OBJECTIVES: There is a need to compare the characteristics, suitability and applicability of quality documents in view of the increasing efforts to introduce quality management in laboratories, especially in clinical diagnostic laboratories in low income and middle income countries. This may provide valuable insights for policy makers developing national laboratory policies, and for laboratory managers and quality officers in choosing the most appropriate quality document for upgrading their laboratories. METHOD: We reviewed the history of quality document development and then selected a subset based on their current use. We analysed these documents following a framework for comparison of quality documents that was adapted from the Clinical Laboratory Standards Institute guideline GP26 Quality management system model for clinical laboratory services. RESULTS: Differences were identified between national and international, and non-clinical and clinical quality documents. The most salient findings were the absence of provisions on occurrence management and customer service in almost all non-clinical quality documents, a low number of safety requirements aimed at protecting laboratory personnel in international quality documents and no requirements regarding ethical behaviour in almost all quality documents. CONCLUSION: Each laboratory needs to investigate whether national regulatory standards are present. These are preferred as they most closely suit the needs of laboratories in the country. A laboratory should always use both a standard and a guideline: a standard sums up the requirements to a quality management system, a guideline describes how quality management can be integrated in the laboratory processes.