Bidirectional relationship between acute pancreatitis and pancreatic cancer.

PURPOSE OF REVIEW: The burdens of pancreatic ductal adenocarcinoma (PDAC) and acute pancreatitis are increasing globally. We reviewed current literature on whether acute pancreatitis is a causal factor for PDAC and examined clinical manifestations of PDAC-associated acute pancreatitis. RECENT FINDINGS: Recent findings detail the timing of acute pancreatitis before and after PDAC occurrence, further solidifying the evidence for PDAC-associated acute pancreatitis and for acute pancreatitis as a causal risk factor for PDAC. The risk of PDAC remains elevated above the general population in patients with distant history of acute pancreatitis. PDAC risk also increases with recurrent acute pancreatitis episodes, independent of smoking and alcohol. Mechanisms linking acute pancreatitis to PDAC include inflammation and neutrophil infiltration, which can be attenuated by suppressing inflammation and/or epigenetic modulation, thus slowing the progression of acinar-to-ductal metaplasia. Clinical presentation and management of acute pancreatitis in the context of PDAC are discussed, including challenges acute pancreatitis poses in the diagnosis and treatment of PDAC, and novel interventions for PDAC-associated acute pancreatitis. SUMMARY: PDAC risk may be reduced with improved acute pancreatitis prevention and treatment, such as antiinflammatories or epigenetic modulators. Increased acute pancreatitis and PDAC burden warrant more research on better diagnosis and management of PDAC-associated acute pancreatitis.

Overlap and cumulative effects of pancreatic duct obstruction, abnormal pain processing and psychological distress on patient-reported outcomes in chronic pancreatitis.

OBJECTIVE: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs). DESIGN: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses. RESULTS: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress. CONCLUSION: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management. TRIAL REGISTRATION NUMBER: The study was registered with ClinicalTrials.gov (NCT03434392).

Pancreatic QST Differentiates Chronic Pancreatitis Patients into Distinct Pain Phenotypes Independent of Psychiatric Comorbidities.

BACKGROUND & AIMS: Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities. METHODS: A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups. RESULTS: A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P = .03) and rates of constant pain (P = .002) as well as decreased QoL (P < .001) and physical functioning (P =.03) in comparison with the other two pain phenotypes. In contrast, psychiatric comorbidities were similar across all groups. CONCLUSIONS: P-QST may serve as a novel unbiased pain assessment tool in CP as it categorizes patients into distinct pain phenotypes independent of their psychiatric comorbidities.

Prevalence of primary painless chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP. METHODS: MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI). RESULTS: Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10-15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73-100%), 51% (95% CI 32-70%), and 47% (95% CI 15-81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively. CONCLUSION: Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients.

Psychosocial outcomes 1-year post total pancreatectomy and autologous islet cell transplant.

BACKGROUND: A paucity of research regarding the psychosocial outcomes after TPIAT exists. METHODS: Adults (>18 years), adolescents (13-18 years), and children (5-12 years) with their parents were administered questionnaires at the time of evaluation for TPIAT and 1-year postsurgery to assess psychosocial outcomes. RESULTS: A total of 13 adults (6 male, 46%; mean age 35.2 years) and 9 children/adolescents (4 female, 44.4%; mean age 11.78 years) with CP were included in the study. A total of 69.2% of the adults and 66.7% of the children and adolescents were insulin dependent at 1-year postsurgery. In adults, improvements on the SF-36 pain (p = .001) and general health (p = .045) subscales were generally observed 1-year postsurgery. Adult patients who underwent robotic-assisted surgery compared to open surgery specifically reported better general health on the SF-36 (p < .05) at 1 year. For children and adolescents, reductions in average pain in the last week (p < .05), pain interference (p < .001), and fatigue were observed (p < .05) at 1-year postsurgery. For the entire sample, using repeated measures ANOVA and covarying for age, significant differences were found 1-year postsurgery in average pain in the last week (p = .034) and pain interference with the following categories: general activity (p < .001), walking (p = .04), normal work (p = .003), sleep (p = .002), and enjoyment in life (p = .007). CONCLUSIONS: While few transplant centers offer this treatment, the improvement in quality of life suggests this may be a viable treatment option for those with CP complicated by intractable pain. (IRB Approval PRO 19080302).

Painful chronic pancreatitis - new approaches for evaluation and management.

PURPOSE OF REVIEW: Management of abdominal pain in patients with chronic pancreatitis is often suboptimal. We review recent data on the epidemiology and new approaches for managing pain in chronic pancreatitis. RECENT FINDINGS: Chronic pancreatitis duration does not appear to affect the pain experience. Pain pattern in chronic pancreatitis patients frequently changes and is not related to traditional patient and disease-related factors. Psychologic comorbidities, i.e. anxiety and depression, are frequent in patients with chronic pancreatitis, and are associated with more severe pain and pain interference. Adjunctive treatments, such as cognitive behavioral therapy, may positively influence pain management in chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) is an increasingly adopted treatment option in painful chronic pancreatitis. Ongoing multicenter studies will help define optimal candidates, predictors of successful pain remission and diabetes outcomes after TPIAT. Pancreatic quantitative sensory testing, a promising technique to interrogate nociception and sensory response, holds promise to identify patients with central sensitization. Initial studies show feasibility to stratify patients into defined pain profiles, and future studies will explore if these can help in prognostication of pain therapy. SUMMARY: Several lines of investigations currently under evaluation are likely to have a positive impact on the management of pain in chronic pancreatitis.

Natural course of pain in chronic pancreatitis is independent of disease duration.

OBJECTIVES: Pain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort. METHODS: We constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates. RESULTS: Pain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96-1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96-1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97-1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p < 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact. CONCLUSIONS: Only a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. METHODS: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. RESULTS: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. CONCLUSIONS: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. TRIAL REGISTRATION: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Re-assessment of schistosomiasis in nine endemic districts with cluster sampling in Sierra Leone.

Background: Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies. Methods: On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples. Results: In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools. Conclusion: Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.

Electrocardiography Assessment of Sympatico-Vagal Balance during Resting and Pain Using the Texas Instruments ADS1299.

Sympatico-vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico-vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico-vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico-vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

Progress from morbidity control to elimination as a public health problem of schistosomiasis and the status of soil-transmitted helminth infection in Togo: a second impact assessment after ten rounds of mass drug administration.

BACKGROUND: Due to the burden of schistosomiasis (SCH) and soil-transmitted helminths (STH), Togo Ministry of Health launched a program for Preventive Chemotherapy Neglected Tropical Diseases (PC-NTDs) in 2009, initiating integrated mass drug administration (MDA) the following year for the three PC-NTDs: SCH, STH and onchocerciasis. Significant reduction of infection across the country was noted in 2015 during the first impact assessment, following 5 years of high-coverage MDA implemented at the sub-district level for SCH and district level for STH. After another 5 years of effective MDA, a second survey was conducted in 2021 to re-evaluate the situation of SCH and STH. METHODS: A cross-section of school-aged children was taken across ten districts of Togo. A total of 302 schools in 92 sub-districts were sampled, with 24 school-aged children per school resulting in 7248 children surveyed. Urine samples were tested by haemastix® for Schistosoma haematobium, with urine filtration for the presence of eggs conducted on haematuria-positive samples. Stool samples were collected in a subset of 34 sub-districts in seven out of the ten surveyed districts, where STH and Schistosoma mansoni endemicity was high during the 2015 impact assessment. Duplicate (two) Kato-Katz analysis was performed for each stool sample. Sociodemographic and school-level water, sanitation and hygiene information was also collected. RESULTS: Overall, SCH prevalence was 5.90% (95% CI: 5.4-6.5), with 5.09% (95% CI: 4.64-5.67) for S. haematobium and 2.56% (95% CI: 1.98-3.29) for S. mansoni. STH prevalence was 19.7% (95% CI: 18.2-21.4), with 19.6% (95% CI: 18.1-21.3) hookworm, 0.08% (95% CI: 2.2-5.8) Trichuris trichiura and 0.04% (95% CI: 0.01-0.33) Ascaris lumbricoides. Compared to baseline, a significant reduction in both SCH (22.2% to 5.90%) and STH (29.2% t0 19.7%) prevalence was observed. Children aged 5-9 years were less infected than older peers aged 10-14 years: 4.76% vs. 7.53% (P < 0.01) for SCH and 17.2% vs. 23.0% (P < 0.01) for STH. CONCLUSIONS: After 10 years of high coverage integrated MDA, Togo has achieved low prevalence SCH infection through the sub-district MDA implementation with considerable infection heterogeneity within sub-districts. As STH infection has not reached a level where the infections are not a public health problem, the sub-district treatment strategy could also be adopted in addition to improvement of treatment coverage among preschool age children and hygiene and sanitation practices.

Inter- and intra-observer variability of computed tomography-based parenchymal- and ductal diameters in chronic pancreatitis: a multi-observer international study.

PURPOSE: The need for incorporation of quantitative imaging biomarkers of pancreatic parenchymal and ductal structures has been highlighted in recent proposals for new scoring systems in chronic pancreatitis (CP). To quantify inter- and intra-observer variability in CT-based measurements of ductal- and gland diameters in CP patients. MATERIALS AND METHODS: Prospectively acquired pancreatic CT examinations from 50 CP patients were reviewed by 12 radiologists and four pancreatologists from 10 institutions. Assessment entailed measuring maximum diameter in the axial plane of four structures: (1) pancreatic head (PDhead), (2) pancreatic body (PDbody), (3) main pancreatic duct in the pancreatic head (MPDhead), and (4) body (MPDbody). Agreement was assessed by the 95% limits of agreement with the mean (LOAM), representing how much a single measurement for a specific subject may plausibly deviate from the mean of all measurements on the specific subject. Bland-Altman limits of agreement (LoA) were generated for intra-observer pairs. RESULTS: The 16 observers completed 6400 caliper placements comprising a first and second measurement session. The widest inter-observer LOAM was seen with PDhead (± 9.1 mm), followed by PDbody (± 5.1 mm), MPDhead (± 3.2 mm), and MPDbody (± 2.6 mm), whereas the mean intra-observer LoA width was ± 7.3, ± 5.1, ± 3.7, and ± 2.4 mm, respectively. CONCLUSION: Substantial intra- and inter-observer variability was observed in pancreatic two-point measurements. This was especially pronounced for parenchymal and duct diameters of the pancreatic head. These findings challenge the implementation of two-point measurements as the foundation for quantitative imaging scoring systems in CP.

Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.

BACKGROUND: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. METHODS: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. RESULTS: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). CONCLUSIONS: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.

Association between water, sanitation, and hygiene access and the prevalence of soil-transmitted helminth and schistosome infections in Wolayita, Ethiopia.

BACKGROUND: The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing infection with soil-transmitted helminths (STH) and schistosome parasites in combination with deworming in Wolayita zone, Ethiopia. METHODS: A population-based, cross-sectional census and parasitological mapping activity was conducted between 2018 and 2019. Individuals in the census were identified using either a registered study ID card or biometric fingerprint to enable linkage of their household WaSH data with baseline STH and schistosome prevalence for risk analysis. RESULTS: Prevalence of STH was 15.5% for any STH species, 9.47% for Ascaris lumbricoides, 1.78% for Trichuris trichiura, and 7.24% for hookworm. Intestinal schistosomiasis (Schistosoma mansoni) infection prevalence was 0.85% by Kato Katz, 21.6% by POC-CCA trace positive (Tr +), and 13.3% trace negative (Tr-). Microhaematuria was 2.77%, with 0.13% of people examined with S. haematobium eggs detected by urine filtration. At the household level, increased (> 30 min) time taken to collect drinking water, sharing a latrine, and lack of handwashing facilities were all associated with a greater risk of A. lumbricoides, hookworm, and S. mansoni infection. Not disposing of infant stool at the household and clothes washing/recreational freshwater contact were significantly associated with higher risk of schistosomiasis infection. Aggregating WaSH data at the community level showed odds of A. lumbricoides, hookworm, and T. trichiura infection were significantly lower as both community sanitation coverage and access to improved drinking water improved. CONCLUSIONS: The principal finding of this study is that lack of access to WaSH, such as improved drinking water and shared toilet and hand-washing facilities, were linked to an increased risk of infection with STH and schistosome parasites. These associations are difficult to establish at an individual household level because of wide variability in access between houses but are detectable when coverage is aggregated at the community level. Maintenance of WaSH facilities as well as increased access within the whole community is important in influencing the community-wide prevalence of infection with STH and schistosome parasites.

Longitudinal monitoring of prevalence and intensity of soil-transmitted helminth infections as part of community-wide mass drug administration within the Geshiyaro project in the Bolosso Sore district, Wolaita, Ethiopia.

Mass drug administration (MDA), targeted at school-aged children (SAC) is recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds, and research suggests that only treating SAC will not be sufficient to interrupt transmission of STH. In countries with endemic infection, such as Ethiopia, the coverage, community-groups targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. In this paper, individually-linked longitudinal data from three epidemiological STH surveys conducted between November 2018 and November 2020 in the Wolaita region of Ethiopia are analysed to determine how STH prevalence and intensity changes according to individual level treatment data collected over two rounds of MDA. This study demonstrates that while community-wide MDA successfully reduces overall infection intensity across the villages treated, the observed levels of non-compliance to treatment by individuals acts to maintain levels of parasite abundance whereby transmission interruption is not possible at to, despite reasonable levels of MDA coverage in the communities studied (ranging from 65% to 84% of the village populations). This quantifies with substantial data the often-postulated difference between coverage (accepting treatment) and compliance (swallowing of treatment), the latter impacting the former to a previously unquantified level. The paper highlights the need to focus treatment to partially treated, or never treated groups of individuals within existing community wide MDA control activities to interrupt the transmission of STH, and to reduce the basic reproductive number, R0, of the parasites to less than unity in value.

Analogous interactions in initiating complexes of the classical and lectin pathways of complement.

The classical and lectin pathways of complement activation neutralize pathogens and stimulate key immunological processes. Both pathways are initiated by collagen-containing, soluble pattern recognition molecules associated with specific serine proteases. In the classical pathway, C1q binds to Ab-Ag complexes or bacterial surfaces to activate C1r and C1s. In the lectin pathway, mannan-binding lectin and ficolins bind to carbohydrates on pathogens to activate mannan-binding lectin-associated serine protease 2. To characterize the interactions leading to classical pathway activation, we have analyzed binding between human C1q, C1r, and C1s, which associate to form C1, using full-length and truncated protease components. We show that C1r and C1s bind to C1q independently. The CUB1-epidermal growth factor fragments contribute most toward binding, but CUB2 of C1r, but not of C1s, is also important. Each C1rs tetramer presents a total of six binding sites, one for each of the collagenous domains of C1q. We also demonstrate that subcomponents of the lectin and classical pathways cross-interact. Thus, although the stoichiometries of complexes differ, interactions are analogous, with equivalent contacts between recognition and protease subcomponents. Importantly, these new data are contrary to existing models of C1 and enable us to propose a new model using mannan-binding lectin-mannan-binding lectin-associated serine protease interactions as a template.

Coverage evaluation surveys following soil-transmitted helminthiasis and schistosomiasis mass drug administration in Wolaita Zone of Ethiopia-The Geshiyaro project.

INTRODUCTION: The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. METHODS: A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. RESULTS: The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9-82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). CONCLUSION: Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.

Pancreatic Pain-Knowledge Gaps and Research Opportunities in Children and Adults: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.