Risk Factors for Sporadic Cryptosporidiosis in the Netherlands: Analysis of a 3-Year Population Based Case-Control Study Coupled With Genotyping, 2013-2016.

BACKGROUND: In 2012, cryptosporidiosis cases increased in the Netherlands, but no single source was identified. In April 2013, we began a 3-year population-based case-control study coupled with genotyping to identify risk factors for sporadic cryptosporidiosis. METHODS: Cryptosporidium cases were laboratory confirmed (by microscopy or polymerase chain reaction), and the species (ie, C. hominis or C. parvum) was determined. We analyzed data by study year, combined and by species. We performed single-variable analysis, and variables with a P value of ≤ .10 were included in a multivariable logistic regression model adjusting for age, sex, and season. RESULTS: The study included 609 cases and 1548 frequency-matched controls. C. parvum was the predominant species in the first 2 study years, shifting to C. hominis in the third year. Household person-to-person transmission and eating barbequed food were strongly associated with being a case. Eating tomatoes was negatively associated. When the analysis was stratified by study year, person-to-person transmission was an independent risk factor. Analysis by species identified different risk factors for cases infected with C. parvum and C. hominis. CONCLUSION: This was the first case-control study examining risk factors for sporadic cryptosporidiosis in the Netherlands. Providing information about Cryptosporidium exposure during outdoor activities and improvements in hygiene within households could prevent future sporadic infections.

Using data from a behavioural survey of men who have sex with men (MSM) to estimate the number likely to present for HIV pre-exposure prophylaxis (PrEP) in Ireland, 2017.

In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition. We estimated MSM numbers likely to present for PrEP by applying French PrEP criteria to Irish MSM behavioural survey data. We adjusted for survey bias, calculated proportions accessing testing services and those likely to take PrEP. We estimated 1-3% of MSM in Ireland were likely to present for PrEP.

Measles Outbreak Among Previously Immunized Healthcare Workers, the Netherlands, 2014.

BACKGROUND: We investigated a measles outbreak among healthcare workers (HCWs) by assessing laboratory characteristics, measles vaccine effectiveness, and serological correlates for protection. METHODS: Cases were laboratory-confirmed measles in HCWs from hospital X during weeks 12-20 of 2014. We assessed cases' severity and infectiousness by using a questionnaire. We tested cases' sera for measles immunoglobulin M, immunoglobulin G, avidity, and plaque reduction neutralization (PRN). Throat swabs and oral fluid samples were tested by quantitative polymerase chain reaction. We calculated attack rates (ARs) by vaccination status and estimated measles vaccine effectiveness as 1 - [ARvaccinated/ARunvaccinated]. RESULTS: Eight HCWs were notified as measles cases; 6 were vaccinated with measles vaccine twice, 1 was vaccinated once, and 1 was unvaccinated. All 6 twice-vaccinated cases had high avidity and PRN titers. None reported severe measles or onward transmission. Two of 4 investigated twice-vaccinated cases had pre-illness PRN titers of >120 mIU/mL. Among 106 potentially exposed HCWs, the estimated effectiveness of 2 doses of measles vaccine was 52% (95% confidence interval [CI], -207%-93%). CONCLUSIONS: Measles occurred in 6 twice-vaccinated HCWs, despite 2 having adequate pre-exposure neutralizing antibodies. None of the twice-vaccinated cases had severe measles, and none had onward transmission, consistent with laboratory findings suggesting a secondary immune response. Improving 2-dose MMR coverage among HCWs would have likely reduced the size of this outbreak.

Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission.

Efficient transmission of Plasmodium species between humans and Anopheles mosquitoes is a major contributor to the global burden of malaria. Gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and Plasmodium genetic diversity. Nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication are also capable of inhibiting gametocyte development and blocking malaria transmission. Here we provide genetic and pharmacological evidence indicating that the pathway for synthesis of phosphatidylcholine in Plasmodium falciparum membranes from host serine is essential for parasite gametocytogenesis and malaria transmission. Parasites lacking the phosphoethanolamine N-methyltransferase enzyme, which catalyzes the limiting step in this pathway, are severely altered in gametocyte development, are incapable of producing mature-stage gametocytes, and are not transmitted to mosquitoes. Chemical screening identified 11 inhibitors of phosphoethanolamine N-methyltransferase that block parasite intraerythrocytic asexual replication and gametocyte differentiation in the low micromolar range. Kinetic studies in vitro as well as functional complementation assays and lipid metabolic analyses in vivo on the most promising inhibitor NSC-158011 further demonstrated the specificity of inhibition. These studies set the stage for further optimization of NSC-158011 for development of a class of dual activity antimalarials to block both intraerythrocytic asexual replication and gametocytogenesis.

A unique measles B3 cluster in the United Kingdom and the Netherlands linked to air travel and transit at a large international airport, February to April 2014.

This report describes a joint measles outbreak investigation between public health officials in the United Kingdom (UK) and the Netherlands following detection of a measles cluster with a unique measles virus strain. From 1 February to 30 April 2014, 33 measles cases with a unique measles virus strain of genotype B3 were detected in the UK and the Netherlands, of which nine secondary cases were epidemiologically linked to an infectious measles case travelling from the Philippines. Through a combination of epidemiological investigation and sequence analysis, we found that measles transmission occurred in flight, airport and household settings. The secondary measles cases included airport workers, passengers in transit at the same airport or travelling on the same flight as the infectious case and also household contacts. This investigation highlighted the particular importance of measles genotyping in identifying transmission networks and the need to improve vaccination, public health follow-up and management of travellers and airport staff exposed to measles.

Economic Costs of Measles Outbreak in the Netherlands, 2013-2014.

In 2013 and 2014, the Netherlands experienced a measles outbreak in orthodox Protestant communities with low measles-mumps-rubella vaccination coverage. Assessing total outbreak costs is needed for public health outbreak preparedness and control. Total costs of this outbreak were an estimated $4.7 million.

Key Learnings from the Development and Early Use of Global Guidance on the Integration of COVID-19 Vaccination into Broader Health Systems.

More than 13.5 billion COVID-19 vaccine doses were delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the continued circulation of SARS-CoV2 and the need for periodic boosters being most likely, countries were required to plan for more sustainable approaches to provide COVID-19 vaccinations. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programs and as part of broader health systems was published jointly by the WHO and UNICEF to respond to country needs. This paper summarizes the approach to, and lessons learned during, the development of a global guidance document and describes some examples of its early use in low- and middle-income countries (LMICs). The guidance leveraged existing health system frameworks, proposed four steps for planning and implementing the COVID-19 vaccination integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support countries with the integration of COVID-19 vaccination. The rapid dissemination of the guidance document allowed countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programs (beyond immunization) remain challenges, particularly in LMICs. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders within and beyond immunization towards a common objective is powerful and can allow progress to be made in terms of integrating health services and better preparing for future pandemics.

Use of catch-up vaccinations in the second year of life (2YL) platform to close immunity gaps: A secondary DHS analysis in Pakistan, Philippines, and South Africa.

BACKGROUND: Immunity gaps caused by COVID-19-related disruptions highlight the importance of catch-up vaccination. Number of countries offering vaccines in second year of life (2YL) has increased, but use of 2YL for catch-up vaccination has been variable. We assessed pre-pandemic use of 2YL for catch-up vaccination in three countries (Pakistan, the Philippines, and South Africa), based on existence of a 2YL platform (demonstrated by offering second dose of measles-containing vaccine (MCV2) in 2YL), proportion of card availability, and geographical variety. METHODS: We conducted a secondary data analysis of immunization data from Demographic and Health Surveys (DHS) in Pakistan (2017-2018), the Philippines (2017), and South Africa (2016). We conducted time-to-event analyses for pentavalent vaccine (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenzae type b [Hib]) and MCV and calculated use of 2YL and MCV visits for catch-up vaccination. RESULTS: Among 24-35-month-olds with documented dates, coverage of third dose of pentavalent vaccine increased in 2YL by 2%, 3%, and 1% in Pakistan, Philippines, and South Africa, respectively. MCV1 coverage increased in 2YL by 5% in Pakistan, 10% in the Philippines, and 3% in South Africa. In Pakistan, among 124 children eligible for catch-up vaccination of pentavalent vaccine at time of a documented MCV visit, 45% received a catch-up dose. In the Philippines, among 381 eligible children, 38% received a pentavalent dose during an MCV visit. In South Africa, 50 children were eligible for a pentavalent vaccine dose before their MCV1 visit, but only 20% received it; none with MCV2. CONCLUSION: Small to modest vaccine coverage improvements occurred in all three countries through catch-up vaccination in 2YL but many missed opportunities for vaccination continue to occur. Using the 2YL platform can increase coverage and close immunity gaps, but immunization programmes need to change policies, practices, and monitor catch-up vaccination to maximize the potential.

Promising practices for the collaborative planning of integrated health campaigns from a synthesis of case studies.

A combination of public health campaigns and routine primary healthcare services are used in many countries to maximise the number of people reached with interventions to prevent, control, eliminate or eradicate diseases. Health campaigns have historically been organised within vertical (disease-specific) programmes, which are often funded, planned and implemented independently from one another and from routinely offered primary healthcare services. Global health agencies have voiced support for enhancing campaign effectiveness, including campaign efficiency and equity, through collaboration among vertical programmes. However, limited guidance is available to country-level campaign planners and implementers about how to effectively integrate campaigns. Planning is critical to the implementation of effective health campaigns, including those related to neglected tropical diseases, malaria, vitamin A supplementation and vaccine-preventable diseases, including polio, measles and meningitis. However, promising approaches to planning integrated health campaigns have not been sufficiently documented. This manuscript highlights promising practices for the collaborative planning of integrated health campaigns that emerged from the experiences of eight project teams working in three WHO regions. Adoption of the promising practices described in this paper could lead to enhanced collaboration among campaign stakeholders, increased agreement about the need for and anticipated benefits of campaign integration, and enhanced understanding of effective planning of integrated health campaigns.

Zero- or missed-dose children in Nigeria: Contributing factors and interventions to overcome immunization service delivery challenges.

'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person who does not complete the schedule. These peopleremain vulnerable to vaccine-preventable diseases, and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. Globally, more 22.7 million children are estimated to be zero- or missed-dose, of which an estimated 3.1 million (∼14 %) reside in Nigeria.We conducted a scoping review tosynthesize recent literature on risk factors and interventions for zero- and missed-dosechildren in Nigeria. Our search identified 127 papers, including research into risk factors only (n = 66); interventions only (n = 34); both risk factors and interventions (n = 18); and publications that made recommendations only (n = 9). The most frequently reported factors influencing childhood vaccine uptake were maternal factors (n = 77), particularly maternal education (n = 22) and access to ante- and perinatal care (n = 19); heterogeneity between different types of communities - including location, region, wealth, religion, population composition, and other challenges (n = 50); access to vaccination, i.e., proximity of facilities with vaccines and vaccinators (n = 37); and awareness about immunization - including safety, efficacy, importance, and schedules (n = 18).Literature assessing implementation of interventions was more scattered, and heavily skewed towards vaccination campaigns and polio eradication efforts. Major evidence gaps exist in how to deliver effective and sustainable routine childhood immunization. Overall, further work is needed to operationalise the learnings from these studies, e.g. through applying findings to Nigeria's next review of vaccination plans, and using this summary as a basis for further investigation and specific recommendations on effective interventions.

PfNT2, a permease of the equilibrative nucleoside transporter family in the endoplasmic reticulum of Plasmodium falciparum.

The survival and proliferation of the obligate intracellular malaria parasite Plasmodium falciparum require salvage of essential purines from the host. Genetic studies have previously shown that the parasite plasma membrane purine permease, PfNT1, plays an essential function in the transport of all naturally occurring purine nucleosides and nucleobases across the parasite plasma membrane. Here, we describe an intracellular permease, PfNT2. PfNT2 is, like PfNT1, a member of the equilibrative nucleoside transporter family. Confocal and immunoelectron microscopic analyses of transgenic parasites harboring green fluorescent protein- or hemagglutinin-tagged PfNT2 demonstrated endoplasmic reticulum localization. This localization was confirmed by colocalization with the endoplasmic reticulum marker PfBiP. Using yeast as a surrogate system, we show that targeting PfNT2 to the plasma membrane of fui1Delta cells lacking the plasma membrane nucleoside transporter Fui1 confers sensitivity to the toxic nucleoside analog 5-fluorouridine. This study provides the first evidence of an intracellular purine permease in apicomplexan parasites and suggests a novel biological function for the parasite endoplasmic reticulum during malaria infection.

Assessment of missed opportunities for vaccination (MOV) in Burkina Faso using the World Health Organization's revised MOV strategy: Findings and strategic considerations to improve routine childhood immunization coverage.

BACKGROUND: Despite the remarkable achievements of the Expanded Programme on Immunization (EPI) in Burkina Faso, numerous challenges remain, including missed opportunities for vaccination (MOV) which occur when people visit a health facility with at least one vaccine due according to the national immunization schedule, are free of contraindications, and leave without receiving all due vaccine doses. In 2016, we used the revised World Health Organization's (WHO) MOV strategy to assess the extent of and reasons for MOV in Burkina Faso. METHODS: We purposively selected 27 primary health facilities (PHFs) from the eight health districts with the highest absolute numbers of children who missed the first dose of measles-rubella (MR1) in 2015. We conducted exit interviews with caregivers of children aged 0-23 months, and requested health workers to complete a self-administered knowledge, attitudes and practices (KAP) questionnaire. RESULTS: A total of 489 caregivers were interviewed, of which 411 were eligible for inclusion in our analysis. Medical consultation (35%) and vaccination (24.5%) were the most frequent reasons for visiting PHFs. Among the 73% of children eligible for vaccination, 76% of vaccination opportunities were missed. Among eligible children, the percentage with MOV was significantly higher in those aged ≥12 months and also in those attending for a reason other than vaccination. A total of 248 health workers completed the KAP questionnaire. Of these, 70% (n = 168/239) considered their knowledge on immunization to be insufficient or outdated; 83% failed to correctly identify valid contraindications to vaccination. CONCLUSION: Addressing MOV offers the potential for substantial increases in vaccine coverage and equity, and ultimately reducing the burden of vaccine-preventable diseases (VPDs). This will require the implementation of a series of interventions aimed at improving community knowledge and practices, raising health workers' awareness, and fostering the integration of immunization with other health services.

Phosphomannose isomerase and phosphomannomutase gene disruptions in Streptomyces nodosus: impact on amphotericin biosynthesis and implications for glycosylation engineering.

Streptomycetes synthesise several bioactive natural products that are modified with sugar residues derived from GDP-mannose. These include the antifungal polyenes, the antibacterial antibiotics hygromycin A and mannopeptimycins, and the anticancer agent bleomycin. Three enzymes function in biosynthesis of GDP-mannose from the glycolytic intermediate fructose 6-phosphate: phosphomannose isomerase (PMI), phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GMPP). Synthesis of GDP-mannose from exogenous mannose requires hexokinase or phosphotransferase enzymes together with PMM and GMPP. In this study, a region containing genes for PMI, PMM and GMPP was cloned from Streptomyces nodosus, producer of the polyenes amphotericins A and B. Inactivation of the manA gene for PMI resulted in production of amphotericins and their aglycones, 8-deoxyamphoteronolides. A double mutant lacking the PMI and PMM genes produced 8-deoxyamphoteronolides in good yields along with trace levels of glycosylated amphotericins. With further genetic engineering these mutants may activate alternative hexoses as GDP-sugars for transfer to aglycones in vivo.

Engineered synthesis of 7-oxo- and 15-deoxy-15-oxo-amphotericins: insights into structure-activity relationships in polyene antibiotics.

Site-directed mutagenesis and gene replacement were used to inactivate two ketoreductase (KR) domains within the amphotericin polyketide synthase in Streptomyces nodosus. The KR12 domain was inactivated in the DeltaamphNM strain, which produces 16-descarboxyl-16-methyl-amphotericins. The resulting mutant produced low levels of the expected 15-deoxy-15-oxo analogs that retained antifungal activity. These compounds can be useful for further chemical modification. Inactivation of the KR16 domain in the wild-type strain led to production of 7-oxo-amphotericin A and 7-oxo-amphotericin B in good yield. 7-oxo-amphotericin B was isolated, purified, and characterized as the N-acetyl methyl ester derivative. 7-oxo-amphotericin B had good antifungal activity and was less hemolytic than amphotericin B. These results indicate that modification at the C-7 position can improve the therapeutic index of amphotericin B.

Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis.

BACKGROUND: Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines. FINDINGS: Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I2=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I2=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I2=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I2=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low. INTERPRETATION: MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity. FUNDING: WHO.

Effect of measles vaccination in infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis.

BACKGROUND: Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses. METHODS: For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines. FINDINGS: Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I2=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I2=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low. INTERPRETATION: Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain. FUNDING: WHO.

Opportunities to improve vaccination coverage in a country with a fledgling health system: Findings from an assessment of missed opportunities for vaccination among health center attendees-Timor Leste, 2016.

INTRODUCTION: Since its independence in 2002, Timor Leste has made significant strides in improving childhood vaccination coverage. However, coverage is still below national targets, and children continue to have missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. Timor Leste implemented the updated World Health Organization methodology for assessing MOV in 2016. METHODS: The MOV data collection included quantitative (caregiver exit interviews and health worker knowledge, attitudes, practices surveys (KAP)) and qualitative arms (focus group discussions (FGDs) with caregivers and health workers and in-depth interviews (IDIs) with health administrators). During a four-day period, health workers and caregivers with children <24 months of age attending the selected eight facilities in Dili Municipality were invited to participate. The researchers calculated the proportion of MOV and timeliness of vaccine doses among children with documented vaccination histories (i.e., from a home-based record or facility register) and thematically analyzed the qualitative data. RESULTS: Researchers conducted 365 caregiver exit interviews, 169 health worker KAP surveys, 4 FGDs with caregivers, 2 FGDs with health workers, and 2 IDIs with health administrators. Among eligible children with documented vaccination histories (n = 199), 41% missed an opportunity for vaccination. One-third of health workers (33%) believed their knowledge of immunization practices to be insufficient. Qualitative results showed vaccines were not available at all selected health facilities, and some facilities reported problems with their cold chain equipment. CONCLUSION: This study demonstrates that many children in Timor Leste miss opportunities for vaccination during health service encounters. Potential interventions to reduce MOV include training of health workers, improving availability of vaccines at more health facilities, and replacing unusable cold chain equipment. Timor Leste should continue to scale up successful MOV interventions beyond Dili Municipality to improve vaccination coverage nationally and strengthen the health system overall.

Improving mapping for Ebola response through mobilising a local community with self-owned smartphones: Tonkolili District, Sierra Leone, January 2015.

BACKGROUND: During the 2014-16 Ebola virus disease (EVD) outbreak, the Magburaka Ebola Management Centre (EMC) operated by Médecins Sans Frontières (MSF) in Tonkolili District, Sierra Leone, identified that available district maps lacked up-to-date village information to facilitate timely implementation of EVD control strategies. In January 2015, we undertook a survey in chiefdoms within the MSF EMC catchment area to collect mapping and village data. We explore the feasibility and cost to mobilise a local community for this survey, describe validation against existing mapping sources and use of the data to prioritise areas for interventions, and lessons learned. METHODS: We recruited local people with self-owned Android smartphones installed with open-source survey software (OpenDataKit (ODK)) and open-source navigation software (OpenStreetMap Automated Navigation Directions (OsmAnd)). Surveyors were paired with local motorbike drivers to travel to eligible villages. The collected mapping data were validated by checking for duplication and comparing the village names against a pre-existing village name and location list using a geographic distance and text string-matching algorithm. RESULTS: The survey teams gained sufficient familiarity with the ODK and OsmAnd software within 1-2 hours. Nine chiefdoms in Tonkolili District and three in Bombali District were surveyed within two weeks. Following de-duplication, the surveyors collected data from 891 villages with an estimated 127,021 households. The overall survey cost was €3,395; €3.80 per village surveyed. The MSF GIS team (MSF-OCG) created improved maps for the MSF Magburaka EMC team which were used to support surveillance, investigation of suspect EVD cases, hygiene-kit distribution and EVD survivor support. We shared the mapping data with OpenStreetMap, the local Ministry of Health and Sanitation and Sierra Leone District and National Ebola Response Centres. CONCLUSIONS: Involving local community and using accessible technology allowed rapid implementation, at moderate cost, of a survey to collect geographic and essential village information, and creation of updated maps. These methods could be used for future emergencies to facilitate response.

A novel measles outbreak control strategy in the Netherlands in 2013-2014 using a national electronic immunization register: A study of early MMR uptake and its determinants.

BACKGROUND: During a large measles outbreak in the Netherlands in 2013-2014, infants aged 6-14months living in municipalities with low (<90%) measles-mumps-rubella (MMR) coverage were individually invited for an early MMR using the national electronic immunization register, Præventis. We estimated uptake of early MMR prior to and during the 2013-2014 outbreak and assessed determinants for early MMR vaccination. METHODS: We obtained vaccination records from Præventis, and defined early MMR as vaccination before 415days (13months) of age. A multi-level multivariable logistic regression model, restricted to infants with three diphtheria-pertussis-tetanus-polio (DPTP) vaccinations was used to examine the association between early MMR uptake and sex, parents' country of birth, socioeconomic status (SES; at postcode level) and voting proportions for the Reformed Political Party (SGP; at municipal level), used as a proxy for religious objections towards vaccination. RESULTS: In the 29 municipalities with low MMR coverage, uptake of early MMR was 0.5-2.2% prior to the outbreak. Between July 2013 and March 2014, 5,800 (57%) invited infants received an early MMR. Among infants with three DPTP, 70% received an early MMR. Only 1% of infants without prior DPTP received an early MMR. Lower early MMR uptake was associated with a higher SGP voter-ship (OR 0.89 per 5% increase, 95%CI 0.83-0.96), parents' with unknown country of birth (OR 0.66 95%CI 0.47-0.93) and compared with very high SES, high SES had significantly lower early MMR uptake (OR 0.66 95%CI 0.50-0.87). DISCUSSION: This is the first study describing use of Præventis during an outbreak and to assess determinants of early MMR uptake. More than half of invited infants obtained an early MMR. SES, parents' with unknown country of birth and religious objections towards vaccination were found to be associated with lower early MMR uptake. In future outbreaks, these determinants could be used to tailor intervention strategies.