Reactive arthritis incidence in a community cohort following a large waterborne campylobacteriosis outbreak in Havelock North, New Zealand.

OBJECTIVES: In August 2016, Campylobacter spp contaminated an untreated reticulated water supply resulting in a large-scale gastroenteritis outbreak affecting an estimated 8320 people. We aimed to determine the incidence of probable reactive arthritis (ReA) cases in individuals with culture-confirmed campylobacteriosis (CC), self-reported probable campylobacteriosis (PC) and those reporting no diarrhoea (ND). DESIGN: We conducted a retrospective cohort study to identify incidence of probable ReA cases. We identified cases with new ReA symptoms using an adapted acute ReA (AReA) telephone questionnaire. Those reporting ≥1 symptom underwent a telephone interview with the study rheumatologist. Probable ReA was defined as spontaneous onset of pain suggestive of inflammatory arthritis in ≥1 previously asymptomatic joint for ≥3 days occurring ≤12 weeks after outbreak onset. SETTING: Population-based epidemiological study in Havelock North, New Zealand. PARTICIPANTS: We enrolled notified CC cases with gastroenteritis symptom onsets 5 August 2016-6 September 2016 and conducted a telephone survey of households supplied by the contaminated water source to enrol PC and ND cases. RESULTS: One hundred and six (47.3%) CC, 47 (32.6%) PC and 113 (34.3%) ND cases completed the AReA telephone questionnaire. Of those reporting ≥1 new ReA symptom, 45 (75.0%) CC, 13 (68.4%) PC and 14 (82.4%) ND cases completed the rheumatologist telephone interview. Nineteen CC, 4 PC and 2 ND cases developed probable ReA, resulting in minimum incidences of 8.5%, 2.8% and 0.6% and maximum incidences of 23.9%, 12.4% and 2.15%. DISCUSSION: We describe high probable ReA incidences among gastroenteritis case types during a very large Campylobacter gastroenteritis outbreak using a resource-efficient method that is feasible to employ in future outbreaks.

High Incidence of Congenital Syphilis in New Zealand: A New Zealand Pediatric Surveillance Unit Study.

BACKGROUND: Syphilis, a disease once in decline, has made a resurgence worldwide. New Zealand has had increasing syphilis rates since enhanced syphilis surveillance was initiated in 2013. This study reports epidemiologic, descriptive and treatment data on management of infants prenatally exposed or vertically infected with syphilis across New Zealand as reported by pediatricians. METHODS: Over a 26-month period from April 2018 to May 2020 (inclusive), pediatricians throughout New Zealand notified potential, probable and confirmed cases of congenital syphilis to the New Zealand Pediatric Surveillance Unit. National reporting numbers were concurrently ascertained to demonstrate reporting accuracy. RESULTS: Thirty-two cases were notified, comprised of 25 infants born to women with positive antenatal syphilis serology (5 whom developed congenital syphilis), and 7 infants diagnosed with congenital syphilis after birth where syphilis was not diagnosed in pregnancy. There were 12 cases of congenital syphilis; an incidence rate of 9.4 cases per 100,000 live births. Nine of the 12 infants had clinical features of congenital syphilis. One-third of maternal infections were early syphilis, and the women who gave birth to infected infants were less likely to have received antenatal care, adequate treatment and follow-up monitoring of treatment for syphilis during pregnancy. CONCLUSIONS: This study quantifies an important burden of disease from congenital syphilis in our population. Case finding and treatment of syphilis in pregnancy are critical to prevent this. Our findings support the urgent need for measures such as repeat maternal syphilis screening in early third trimester; whether by affected region or instituted for all, in the context of rising cases.

Genomic Surveillance of a Globally Circulating Distinct Group W Clonal Complex 11 Meningococcal Variant, New Zealand, 2013-2018.

Genomic surveillance is an essential part of effective disease control, enabling identification of emerging and expanding strains and monitoring of subsequent interventions. Whole-genome sequencing was used to analyze the genomic diversity of all Neisseria meningitidis isolates submitted to the New Zealand Meningococcal Reference Laboratory during 2013-2018. Of the 347 isolates submitted for whole-genome sequencing, we identified 68 sequence types belonging to 18 clonal complexes (CC). The predominant CC was CC41/44; next in predominance was CC11. Comparison of the 45 New Zealand group W CC11 isolates with worldwide representatives of group W CC11 isolates revealed that the original UK strain, the 2013 UK strain, and a distinctive variant (the 2015 strain) were causing invasive group W meningococcal disease in New Zealand. The 2015 strain also demonstrated increased resistance to penicillin and has been circulating in Canada and several countries in Europe, highlighting that close monitoring is needed to prevent future outbreaks around the world.

Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand.

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nationwide 'lockdown' of all non-essential services to curb the spread of COVID-19. Here, we generate 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected during the 'first wave', representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. These data helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, Re of New Zealand's largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in ongoing transmission of more than one additional case. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.

Potential Early Identification of a Large Campylobacter Outbreak Using Alternative Surveillance Data Sources: Autoregressive Modelling and Spatiotemporal Clustering.

BACKGROUND: Over one-third of the population of Havelock North, New Zealand, approximately 5500 people, were estimated to have been affected by campylobacteriosis in a large waterborne outbreak. Cases reported through the notifiable disease surveillance system (notified case reports) are inevitably delayed by several days, resulting in slowed outbreak recognition and delayed control measures. Early outbreak detection and magnitude prediction are critical to outbreak control. It is therefore important to consider alternative surveillance data sources and evaluate their potential for recognizing outbreaks at the earliest possible time. OBJECTIVE: The first objective of this study is to compare and validate the selection of alternative data sources (general practice consultations, consumer helpline, Google Trends, Twitter microblogs, and school absenteeism) for their temporal predictive strength for Campylobacter cases during the Havelock North outbreak. The second objective is to examine spatiotemporal clustering of data from alternative sources to assess the size and geographic extent of the outbreak and to support efforts to attribute its source. METHODS: We combined measures derived from alternative data sources during the 2016 Havelock North campylobacteriosis outbreak with notified case report counts to predict suspected daily Campylobacter case counts up to 5 days before cases reported in the disease surveillance system. Spatiotemporal clustering of the data was analyzed using Local Moran's I statistics to investigate the extent of the outbreak in both space and time within the affected area. RESULTS: Models that combined consumer helpline data with autoregressive notified case counts had the best out-of-sample predictive accuracy for 1 and 2 days ahead of notified case reports. Models using Google Trends and Twitter typically performed the best 3 and 4 days before case notifications. Spatiotemporal clusters showed spikes in school absenteeism and consumer helpline inquiries that preceded the notified cases in the city primarily affected by the outbreak. CONCLUSIONS: Alternative data sources can provide earlier indications of a large gastroenteritis outbreak compared with conventional case notifications. Spatiotemporal analysis can assist in refining the geographical focus of an outbreak and can potentially support public health source attribution efforts. Further work is required to assess the location of such surveillance data sources and methods in routine public health practice.

A large scale waterborne Campylobacteriosis outbreak, Havelock North, New Zealand.

BACKGROUND: We describe the investigation of a Campylobacter outbreak linked to contamination of an untreated, groundwater derived drinking water supply. METHODS: We analysed epidemiological data collected from clinician-confirmed diarrheal cases and estimated the total burden of Havelock North cases using an age-adjusted cross-sectional telephone survey. Campylobacter isolates from case fecal specimens, groundwater samples, and sheep fecal specimens from paddocks adjacent to the drinking water source were whole genome sequenced. FINDINGS: We estimate between 6260 and 8320 cases of illness including up to 2230 who lived outside the reticulation area, were linked to the contaminated water supply. Of these, 953 cases were physician reported, 42 were hospitalized, three developed Guillain-Barré syndrome, and Campylobacter infection contributed to at least four deaths. Of the 12 genotypes observed in cases, four were also observed in water, three were also observed in sheep and one was also observed in both water and sheep. INTERPRETATION: The contamination of the untreated reticulated water supply occurred following a very heavy rainfall event which caused drainage of sheep feces into a shallow aquifer. The existence of a routine clinical surveillance system for campylobacteriosis facilitated identification of the outbreak, recovery of clinical isolates, and early testing of the water for pathogens. Genotyping of the Campylobacter jejuni helped define the source of the outbreak and confirm outbreak periods and cases. Expected increases in heavy rainfall events and intensification of agriculture mean that additional safeguards are needed to protect populations from such drinking water outbreaks. FUNDING: NZ Ministry of Health, Health Research Council, ESR SSIF, Royal Society.

Genomic Insights into a Sustained National Outbreak of Yersinia pseudotuberculosis.

In 2014, a sustained outbreak of yersiniosis due to Yersinia pseudotuberculosis occurred across all major cities in New Zealand (NZ), with a total of 220 laboratory-confirmed cases, representing one of the largest ever reported outbreaks of Y. pseudotuberculosis. Here, we performed whole genome sequencing of outbreak-associated isolates to produce the largest population analysis to date of Y. pseudotuberculosis, giving us unprecedented capacity to understand the emergence and evolution of the outbreak clone. Multivariate analysis incorporating our genomic and clinical epidemiological data strongly suggested a single point-source contamination of the food chain, with subsequent nationwide distribution of contaminated produce. We additionally uncovered significant diversity in key determinants of virulence, which we speculate may help explain the high morbidity linked to this outbreak.

Leprosy in New Zealand: an epidemiological update.

AIM: To examine the current epidemiological trends of leprosy in New Zealand and raise awareness of this disease in the health professional community. METHOD: Epidemiological data of leprosy, a notifiable disease in New Zealand, was accessed for the 10 year time period 2004 to 2013. Using an illustrative case as an introduction, all 38 case reports from the study period are summarised. RESULTS: Most cases of leprosy in New Zealand notified during the study period are immigrants from countries with endemic leprosy, reflecting the origin of disease. Delay to diagnosis is common. CONCLUSION: Leprosy remains a clinical problem in New Zealand. Cases are more likely to arise in geographical areas with higher numbers of immigrants from endemic countries.

Particle size coarsening induced by valve silicone in a metered dose inhaler.

The objective of this study was to evaluate the effect of valve silicone on the delivered particle size distribution of a suspension metered dose inhaler (MDI). Valves were manufactured with distinct levels of silicone, which could be differentiated with Fourier transform infrared spectroscopy (FT-IR). The amount of silicone in the valve was proportional to the amount of silicone that entered the formulation and the subsequent decrease in fine particle fraction (FPF) of the active pharmaceutical ingredient (API) measured by Andersen cascade impaction. The effect of silicone content was not linear as even small amounts of silicone made a significant contribution to particle size coarsening. This coarsening was also a function of storage time and temperature. Accelerated stability conditions greatly increased coarsening kinetics as 1 month at 40 degrees C and 75% RH induced significantly more coarsening than 12 months at room temperature. Field emission scanning electron micrograph images suggest that the primary mechanism of particle size change may be aggregation as particle clusters were seen. This study indicates that silicone can be a critical process parameter for particle size distribution of a suspension MDI product. Thus, the amount of silicone in the valves needs to be minimized and controlled.

Influence of the size of micronized active pharmaceutical ingredient on the aerodynamic particle size and stability of a metered dose inhaler.

Pharmaceutical inhalers are often used to treat pulmonary diseases. Only active pharmaceutical ingredient (API) particles from these inhalers that are less than approximately 5 microm are likely to reach the lung and be efficacious. This study was designed to investigate the impact of micronized API particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler (MDI) containing propellant HFA-227 (1,1,1,2,3,3,3 heptafluoropropane) and a corticosteroid. The median API particle size ranged from 1.1 microm to 1.8 microm (97% to 70% of particles <3 microm, respectively). This study showed that increasing the particle size of the API used to manufacture a suspension MDI product increased the aerodynamic PSD of the MDI product. Furthermore, upon storage of the MDI product under temperature cycling conditions, samples containing larger-size API particles were less stable with respect to their aerodynamic PSD than those with smaller-size API particles. It was found that size-dependent particle growth and/or aggregation of the suspended API may be occurring as a result of temperature cycling. In conclusion, this study has shown that the particle size of the raw API impacts the properties and stability of the emitted aerosol spray. Based on the findings from this study, it is recommended that the API particle size be carefully controlled in order to meet specifications set for the finished MDI product.

A three-dimensional osteochondral composite scaffold for articular cartilage repair.

There is a recognized and urgent need for improved treatment of articular cartilage defects. Tissue engineering of cartilage using a cell-scaffold approach has demonstrated potential to offer an alternative and effective method for treating articular defects. We have developed a unique, heterogeneous, osteochondral scaffold using the TheriForm three-dimensional printing process. The material composition, porosity, macroarchitecture, and mechanical properties varied throughout the scaffold structure. The upper, cartilage region was 90% porous and composed of D,L-PLGA/L-PLA, with macroscopic staggered channels to facilitate homogenous cell seeding. The lower, cloverleaf-shaped bone portion was 55% porous and consisted of a L-PLGA/TCP composite, designed to maximize bone ingrowth while maintaining critical mechanical properties. The transition region between these two sections contained a gradient of materials and porosity to prevent delamination. Chondrocytes preferentially attached to the cartilage portion of the device, and biochemical and histological analyses showed that cartilage formed during a 6-week in vitro culture period. The tensile strength of the bone region was similar in magnitude to fresh cancellous human bone, suggesting that these scaffolds have desirable mechanical properties for in vivo applications, including full joint replacement.