Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola.

Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders.

A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons.

OBJECTIVES: Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. METHODS: We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. RESULTS: Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. CONCLUSIONS: Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.

Typhoid conjugate vaccine perceptions and coverage among children and adults: Findings from a post-campaign coverage survey - Harare, Zimbabwe, 2019.

BACKGROUND: In 2019, following a large outbreak of typhoid fever, the Zimbabwe Ministry of Health and Child Care conducted a typhoid conjugate vaccine (TCV) vaccination campaign in nine high-risk suburbs of Harare. We aimed to evaluate TCV vaccination coverage, vaccine perceptions, and adverse events reported after vaccination. METHODS: We conducted a two-stage cluster survey to estimate vaccination coverage in the campaign target areas among children aged 6 months-15 years and to classify coverage as either adequate (≥75 % coverage) or inadequate (<75 % coverage) among adults aged 16-45 years in one suburb. Questionnaires assessed socio-demographic factors, TCV vaccination history, reasons for receiving or not receiving TCV, adverse events following immunization, and knowledge and attitudes regarding typhoid and TCV. RESULTS: A total of 1,917 children from 951 households and 298 adults from 135 households enrolled in the survey. Weighted TCV coverage among all children aged 6 months-15 years was 85.3 % (95 % CI: 82.1 %-88.0 %); coverage was 74.8 % (95 % CI: 69.4 %-79.5 %) among children aged 6 months-4 years and 89.3 % (95 % CI: 86.2 %-91.7 %) among children aged 5-15 years. Among adults, TCV coverage was classified as inadequate with a 95 % confidence interval of 55.0 %-73.1 %. Among vaccinated persons, the most reported reason for receiving TCV (96 % across all age groups) was protection from typhoid fever; the most common reasons for non-vaccination were not being in Harare during the vaccination campaign and not being aware of the campaign. Adverse events were infrequently reported in all age groups (10 %) and no serious events were reported. CONCLUSIONS: The 2019 TCV campaign achieved high coverage among school-aged children (5-15 years). Strategies to increase vaccination coverage should be explored for younger children as part of Zimbabwe's integration of TCV into the routine immunization program, and for adults during future post-outbreak campaigns.

Evaluation of clinical characteristics of Kawasaki syndrome and risk factors for coronary artery abnormalities among children in Denmark.

AIM: To examine clinical characteristics, treatment and outcome of Kawasaki syndrome patients in Denmark. METHODS: A retrospective chart review of hospitalization records for children <15 years of age with a Kawasaki syndrome discharge diagnosis identified through the Danish National Patient Registry during 1994 through June 2008 was conducted. RESULTS: A total of 284 cases <15 years of age were identified as Kawasaki syndrome (n = 279) and atypical Kawasaki syndrome (n = 5); 70.4% were <5 years of age and 64.4% were male. Most patients (91.5%; 258/282) were treated with intravenous immunoglobulin and 74.6% of these patients (191/256) received intravenous immunoglobulin before the 10th day of illness. A total of 37 (13.3%) Kawasaki syndrome patients were diagnosed with coronary artery abnormalities. Not receiving intravenous immunoglobulin treatment before the 10th day of illness, young age and male sex were significantly associated with the development of coronary artery abnormalities. CONCLUSIONS: In Denmark, more than one in 10 children with Kawasaki syndrome develop coronary artery abnormalities. Physicians should increase their index of suspicion for early diagnosis and treatment of Kawasaki syndrome among patients susceptible to increased risk of coronary artery abnormalities, particularly in infants who may have a more atypical presentation of the illness.

Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Enhanced surveillance for adverse events following immunization during the 2019 typhoid conjugate vaccine campaign in Harare, Zimbabwe.

BACKGROUND: During February 25-March 4, 2019, Zimbabwe's Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months-15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials. METHODS: Three methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey. RESULTS: Thirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care. CONCLUSIONS: In line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.

Community-based household assessment of human papillomavirus (HPV) vaccination coverage and acceptability - HPV vaccine demonstration program, Cambodia - 2017.

BACKGROUND: In 2017, the Cambodia Ministry of Health introduced human papillomavirus (HPV) vaccine through primarily school-based vaccination targeting 9-year-old girls. Vaccination with a two-dose series of HPV vaccine took place in six districts in two provinces as a demonstration program, to better understand HPV vaccine delivery in Cambodia. METHODS: We conducted a community-based coverage survey using a one-stage sampling design to evaluate dose-specific vaccination coverage among eligible girls (those born in 2007 and residents in the areas targeted by the campaign). The household-level survey also assessed factors associated with vaccine acceptability and communication strategies. Trained data collectors interviewed caregivers and girls using a standard questionnaire; vaccination cards and health facility records were reviewed. RESULTS: Of the 7594 households visited in the two provinces, 315 girls were enrolled in the survey (188 in Siem Reap; 127 in Svay Rieng). Documented two-dose HPV vaccination coverage was 84% (95% confidence interval [CI]: 78-88%) overall [85% (95% CI: 78-90%) in Siem Reap; 82% (95% CI: 73-88%) in Svay Rieng.] Almost all girls (>99%) were reported to be enrolled in school and over 90% of respondents reported receipt of vaccine in school. Knowledge of HPV infection and associated diseases was poor among caregivers and girls; however, 58% of caregivers reported "protection from cervical cancer" as the primary reason for the girl receiving vaccine. No serious adverse events after immunization were reported. CONCLUSIONS: The HPV vaccine demonstration program in Cambodia achieved high two-dose coverage among eligible girls in both provinces targeted for vaccination in 2017, through primarily school-based vaccination. High school enrollment and strong microplanning and coordination were seen throughout the campaign. Cambodia will use lessons learned from this demonstration program to prepare for national introduction of HPV vaccine.

Oral cholera vaccination coverage after the first global stockpile deployment in Haiti, 2014.

INTRODUCTION: In 2014, an oral cholera vaccine (OCV) campaign targeting 185,314 persons aged ≥1 years was conducted in 3 departments via fixed post and door-to-door strategies. This was the first use of the global OCV stockpile in Haiti. METHODS: We conducted a multi-stage cluster survey to assess departmental OCV coverage. Target population estimates were projected from the 2003 Haiti population census with adjustments for population growth and estimated proportion of pregnant women. In the three departments, we sampled 30/106 enumeration areas (EAs) in Artibonite, 30/244 EAs in Centre, and 20/29 EAs in Ouest; 20 households were systematically sampled in each EA. Household and individual interviews using a standard questionnaire were conducted in each selected household; data on OCV receipt were obtained from vaccination card or verbal report. We calculated OCV campaign coverage estimates and 95% confidence intervals (CIs) accounting for survey design. RESULTS: Overall two-dose OCV coverage was 70% (95% CI: 60, 79), 63% (95% CI: 55, 71), and 44% (95% CI: 35, 53) in Artibonite, Centre, and Ouest, respectively. Two-dose coverage was higher in the 1-4 years age group than among those ≥ 15 years in Artibonite (difference: 11%; 95% CI: 5%, 17%) and Ouest (difference: 12%; 95% CI: 3, 20). A higher percentage of children aged 5-14 years received both recommended doses than did those ≥ 15 years (Artibonite: 14% (95% CI: 8%, 19%) difference; Centre: 11% difference (95% CI: 5%, 17%); Ouest: 10% difference (95% CI: 2%, 17%). The most common reason for not receiving any OCV dose was being absent during the campaign or not having heard about vaccination activities. CONCLUSIONS: While coverage estimates in Artibonite and Centre were comparable with other OCV campaigns in Haiti and elsewhere, inadequate social mobilization and outdated population estimates might have contributed to lower coverage in Ouest.

Descriptive assessment of rabies post-exposure prophylaxis procurement, distribution, monitoring, and reporting in four Asian countries: Bangladesh, Bhutan, Cambodia, and Sri Lanka, 2017-2018.

BACKGROUND: There are approximately 35,000 human deaths from rabies in Asia annually. Rabies can be prevented through timely post-exposure prophylaxis (PEP) consisting of wound washing, rabies vaccine, and in some cases, rabies immunoglobulin (RIG). However, access to rabies PEP often remains limited to urban areas and is cost-prohibitive. There is little information on procurement, distribution, monitoring, and reporting of rabies PEP. METHODS: We interviewed key informants in the public sector from various levels in Bangladesh, Bhutan, Cambodia, and Sri Lanka between March 2017 and May 2018 using a descriptive assessment tool to obtain information on procurement, distribution, monitoring, and reporting of rabies PEP. These four countries in Asia were chosen to showcase a range of rabies PEP systems. National rabies focal points were interviewed in each country and focal points helped identify additional key informants at lower levels. RESULTS: A total of 22 key informants were interviewed at various levels (central level to health facility level) including national rabies focal points in each country. Each country has a unique system for managing rabies PEP procurement, distribution, monitoring, and reporting. There are varying levels of PEP access for those with potential rabies exposures. Rabies PEP is available in select health facilities throughout the country in Bangladesh, Bhutan, and Sri Lanka. In Cambodia, rabies PEP is limited to two urban centers. The availability of RIG in all four countries is limited. In these four countries, most aspects of the rabies PEP distribution system operate independently of systems for other vaccines. However, in Bhutan, rabies PEP and Expanded Programme on Immunization (EPI) vaccines share cold chain space in some locations at the lowest level. All countries have a monitoring system in place, but there is limited reporting of data, particularly to the central level. CONCLUSION: Systems to procure, deliver, monitor, and report on rabies PEP are variable across countries. Sharing information on practices more widely among countries can help programs to increase access to this life-saving treatment.

Recurrence of Guinea Worm Disease in Chad after a 10-Year Absence: Risk Factors for Human Cases Identified in 2010-2011.

A decade after reporting its last case of Guinea worm disease (GWD), a waterborne parasitic disease targeted for eradication, Chad reported 20 confirmed human cases from 17 villages-10 cases in 2010 and 10 cases in 2011. In 2012, the first GWD dog infections were diagnosed. We conducted a case-control study during April-May 2012 to identify human transmission risk factors and epidemiologic links. We recruited 19 cases and 45 controls matched by age, sex, time, and location of exposure based on the case patients' periods of infection 10-14 months earlier. Data were analyzed with simple conditional logistic regression models using Firth penalized likelihood methods. Unusually, GWD did not appear to be associated with household primary water sources. Instead, secondary water sources, used outside the village or other nonprimary sources used at home, were risk factors (matched odds ratio = 38.1, 95% confidence interval = 1.6-728.2). This study highlights the changing epidemiology of GWD in Chad-household primary water sources were not identified as risk factors and few epidemiologic links were identified between the handfuls of sporadic cases per year, a trend that continues. Since this investigation, annual dog infections have increased, far surpassing human cases. An aquatic paratenic host is a postulated mode of transmission for both dogs and humans, although fish could not be assessed in this case-control study due to their near-universal consumption. GWD's evolving nature in Chad underscores the continued need for interventions to prevent both waterborne and potential foodborne transmission until the true mechanism is established.

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Cholera epidemic associated with consumption of unsafe drinking water and street-vended water--Eastern Freetown, Sierra Leone, 2012.

During 2012, Sierra Leone experienced a cholera epidemic with 22,815 reported cases and 296 deaths. We conducted a matched case-control study to assess risk factors, enrolling 49 cases and 98 controls. Stool specimens were analyzed by culture, polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE). Conditional logistic regression found that consuming unsafe water (matched odds ratio [mOR]: 3.4; 95% confidence interval [CI]: 1.1, 11.0), street-vended water (mOR: 9.4; 95% CI: 2.0, 43.7), and crab (mOR: 3.3; 95% CI: 1.03, 10.6) were significant risk factors for cholera infection. Of 30 stool specimens, 13 (43%) showed PCR evidence of toxigenic Vibrio cholerae O1. Six specimens yielded isolates of V. cholerae O1, El Tor; PFGE identified a pattern previously observed in seven countries. We recommended ensuring the quality of improved water sources, promoting household chlorination, and educating street vendors on water handling practices.

The short- and long-term risk of stroke after herpes zoster - a nationwide population-based cohort study.

BACKGROUND AND OBJECTIVE: Varicella zoster virus (VZV) is known to cause VZV vasculopathy, which may be associated with stroke. A recent study found an increased risk of stroke within one year of herpes zoster. We aimed to investigate the short and long-term effects of herpes zoster on the risk of stroke. METHODS: Using Danish national registers, we constructed a cohort consisting of all Danish adults ≥18 years old between 1995 and 2008 (n = 4.6 million; person-years of follow-up = 52.9 million). Individual-level information on prescriptions for herpes zoster antiviral treatment and diagnoses of stroke was obtained from national registers. We compared the risk of stroke in persons who had received the specific dosage of acyclovir for herpes zoster with persons who had never received antiviral treatment by Poisson regression. RESULTS: During follow-up, 2.5% received treatment for herpes zoster and 5.0% were diagnosed with stroke. Individuals who had received medication had a 127% (95% CI 83-182%) increased risk the first two weeks, 17% (CI 9-24%) between two weeks and one year, and 5% (2-9%) after the first year. The increased risk was greatest in the youngest age group (<40). To control for healthcare-seeking behaviour, we conducted parallel analyses investigating the risk of selected fractures after herpes zoster and found no similar increased risks. CONCLUSIONS: This large nationwide cohort study found an increased risk of stroke after treatment for herpes zoster. Although the short-term risk was particularly high, we cannot rule out the possibility of a small but important long-term risk.