Tjalling Leenstra’s research while affiliated with Research Institute for Tropical Medicine and other places

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole-proteome differential screening method, we identified Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) as a target of antibodies expressed by S. japonicum–resistant but not S. japonicum–susceptible individuals. In a longitudinal cohort study (n = 644) conducted in a S. japonicum–endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti–SjHDM-1 immunoglobulin G had higher levels of C-reactive protein than those with low anti–SjHDM-1. High anti–SjHDM-1 immunoglobulin G responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (weight-for-age and height-for-age z scores) and increased measures of hepatomegaly. Our results suggest that anti–SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity rates.

Background: We compared individuals' self-reported water contact from a questionnaire to direct observation of water contact. Questionnaires that accurately capture water contact are necessary to risk-stratify individuals and communities at high risk for schistosomiasis. Methods: Individuals (N=677) ages 7-30 y were included from three Schistosoma japonicum-endemic villages in Leyte, The Philippines. Each individual was observed for 12 d over the course of the 18-month study and the questionnaire was administered six times. A questionnaire index was derived that captured the number of self-reported contacts with water bodies for any purpose. An exposure index was created based on the sum of contacts that was weighted by the percentage of body surface area (BSA) exposed and exposure duration. Results: Of 16 water contact activities, only bathing and washing clothes exhibited a significant, positive correlation between self-reported contacts and the observed exposure index related to those contacts. Conclusions: We found that only the reported frequencies of bathing and washing clothes were significantly related to an individual's overall observed exposure index, while use of all reported contacts was not related to the observed exposure. This study further supports the need for questionnaires to be augmented by some measure of how much BSA is exposed and/or time is spent in the water on average for a specific activity.

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

Objectives To elucidate new risk factors for MRSA carriers without known risk factors (MRSA of unknown origin; MUO). These MUO carriers are neither pre-emptively screened nor isolated as normally dictated by the Dutch Search & Destroy policy, thus resulting in policy failure. Methods We performed a prospective case control study to determine risk factors for MUO acquisition/carriage (Dutch Trial Register: NTR2041). Cases were MUO carriers reported by participating medical microbiological laboratories to the RIVM from September 1st 2011 until September 1st 2013. Controls were randomly selected from the community during this period. Results Significant risk factors for MUO in logistic multivariate analysis were antibiotic use in the last twelve months, aOR 8.1 (5.6–11.7), screened as contact in a contact tracing but not detected as a MRSA carrier at that time, aOR 4.3 (2.1–8.8), having at least one foreign parent, aOR 2.4 (1.4–3.9) and receiving ambulatory care, aOR 2.3 (1.4–3.7). Our found risk factors explained 83% of the MUO carriage. Conclusions Identifying new risk factors for MRSA carriers remains crucial for countries that apply a targeted screening approach as a Search and Destroy policy or as vertical infection prevention measure.

SAS report–New risk factors MRSA. (PDF)

Case control questionnaire. (DOCX)

Underlying data–New risk factors MRSA. (XLSX)

SAS log–New risk factors MRSA. (TXT)

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data. © 2017, European Centre for Disease Prevention and Control (ECDC). All rights reserved.

- Carbapenemase producing Enterobacteriaceae (CPE), including Klebsiella pneumoniae and Escherichia coli, are only sporadically seen in the Netherlands and then mainly in patients who have been transferred from foreign hospitals.- CPE are resistant to virtually all beta-lactam antibiotics, including carbapenems, e.g., meropenem and imipenem. Several genes, e.g., OXA-48, KPC and NDM-1, code for carbapenemase enzymes that deactivate carbapenems.- Control of CPE focuses on timely identification of patients who are infected or are carriers and the application of preventive measures to prevent spread.- Genotypic analysis of CPE isolates submitted to the national CPE surveillance revealed close relationships between 8 NDM-1 positive K. pneumoniae isolates of patients from different parts of the Netherlands and isolates obtained through contact tracing during a known hospital outbreak.- Based on retrospective epidemiological investigation, no shared exposure could be found.- These findings indicate unnoticed spread of CPE in the Netherlands.