Basic Vaccination Research Articles

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions.

Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.

Virus Irradiation and COVID-19 Disease

Virus irradiation has been performed for many decades for basic research studies, sterilization, and vaccine development. The COVID-19 outbreak is currently causing an enormous effort worldwide for finding a vaccine against coronavirus. High doses of -rays can be used for the development of vaccines that exploit inactivated virus. This technique has been gradually replaced by more practical methods, in particular the use of chemicals, but irradiation remains a simple and effective method used in some cases. The technique employed for inactivating a virus has an impact on its ability to induce an adaptive immune response able to confer effective protection. We propose here that accelerated heavy ions can be used to inactivate SARS-CoV-2 viruses with small damage to the spike proteins of the envelope, and can then provide an intact virion for vaccine development.

The Epidemiological Framework for Biological Invasions (EFBI): an interdisciplinary foundation for the assessment of biosecurity threats

Emerging microparasite (e.g. viruses, bacteria, protozoa and fungi) epidemics and the introduction of non-native pests and weeds are major biosecurity threats worldwide. The likelihood of these threats is often estimated from probabilities of their entry, establishment, spread and ease of prevention. If ecosystems are considered equivalent to hosts, then compartment disease models should provide a useful framework for understanding the processes that underpin non-native species invasions. To enable greater cross-fertilisation between these two disciplines, the Epidemiological Framework for Biological Invasions (EFBI) is developed that classifies ecosystems in relation to their invasion status: Susceptible, Exposed, Infectious and Resistant. These states are linked by transitions relating to transmission, latency and recovery. This viewpoint differs markedly from the species-centric approaches often applied to non-native species. It allows generalisations from epidemiology, such as the force of infection, the basic reproductive ratio R0, super-spreaders, herd immunity, cordon sanitaire and ring vaccination, to be discussed in the novel context of non-native species and helps identify important gaps in the study of biological invasions. The EFBI approach highlights several limitations inherent in current approaches to the study of biological invasions including: (i) the variance in non-native abundance across ecosystems is rarely reported; (ii) field data rarely (if ever) distinguish source from sink ecosystems; (iii) estimates of the susceptibility of ecosystems to invasion seldom account for differences in exposure to non-native species; and (iv) assessments of ecosystem susceptibility often confuse the processes that underpin patterns of spread within -and between- ecosystems. Using the invasion of lakes as a model, the EFBI approach is shown to present a new biosecurity perspective that takes account of ecosystem status and complements demographic models to deliver clearer insights into the dynamics of biological invasions at the landscape scale. It will help to identify whether management of the susceptibility of ecosystems, of the number of vectors, or of the diversity of pathways (for movement between ecosystems) is the best way of limiting or reversing the population growth of a non-native species. The framework can be adapted to incorporate increasing levels of complexity and realism and to provide insights into how to monitor, map and manage biological invasions more effectively.

Do the dynamics of vaccine programs improve the full immunization of children under the age of five in Cameroon?

BackgroundAmong the eight Millennium Development Goals (MDGs), three were devoted to health. Two amongst which MDG4 in relation to the reduction of infant mortality has not been achieved in Least Developed Countries (LDC). In Africa, a significant part of infant mortality is due to vaccine-preventable diseases administered free of charge by the Extended Program on Immunization (EPI). As such, in the “social equity” pillar of Sustainable Development Goals (SDG), the MDGs related to health have yet been taken into account. The achievement of these objectives requires an understanding of the immunization behavior of children under 5 years of age through an analysis of immunization dynamics between 1991 and 2011.MethodsWe use data from Demographic and Health Surveys (DHS) of 1991, 1998, 2004 and 2011 carried out by the National Institute of Statistics (NIS). The module concerning EPI vaccines was administered to 3350, 2317, 8125 and 25,524 under 5 in 1991, 1998, 2004 and 2011 respectively. The Immunization analysis was made from the logistic model for complete immunization and the Oaxaca’s decomposition to assess the contribution of the unexplained part, which is that of the strategies/programs implemented between 1991 and 2011 by the EPI to improve immunization.ResultsIn general, children with vaccination card are more than 7 times likely to be fully immunized than their counterparts who do not have any. This result was higher in 1991 (approximately 57) and lowest in 2011 (5). In addition, the child’s birth order reduces his/her probability of being fully immunized and the impact increases with the latter’s birth order. On the other hand, the mother’s age as well as her level of education increase the child’s likelihood of receiving all basic vaccines. Moreover, the contributions of EPI partners in terms of immunization support as well as strategies to promote immunization through communication for development are of a particular importance in increasing immunization coverage. They significantly explain 67.62% of the 0.105 gain recorded within the 2011–2004 period and 72.46% of the 0.069 gain recorded within the 2004–1998 period.ConclusionThe contribution of EPI partner organizations is fundamental for the achievement of EPI objectives. Since they contribute to increase the likelihood of fully immunized children. The link with child immunization is done through the specific characteristics to the mother.

Tubercúlide papulonecrótica

As tubercúlides são reações de hipersensibilidade cutânea aos antígenos do Mycobacterium tuberculosis. Este é o caso de uma mulher de 45 anos que procurou a Unidade Básica de Saúde (UBS) com um quadro de eritema nodoso com mais de 10 anos de evolução, de etiologia desconhecida, e que evoluía como nódulos em pescoço e membros, que se tornavam úlceras necróticas, cicatrizavam e recidivavam periodicamente. Biópsias das lesões evidenciavam um processo inflamatório granulomatoso com extensa necrose, sugestivo de tuberculose, mas sem a presença do bacilo. Após anos sem tratamento adequado, finalmente levantou-se a hipótese de tubercúlide papulonecrótica. A paciente iniciou tratamento com o esquema básico (2RHZE/4RH) e dessensibilização vacinal, recebendo alta por cura.

Decomposition of socioeconomic inequalities in child vaccination in Ethiopia: results from the 2011 and 2016 demographic and health surveys

ObjectivesMonitoring and addressing unnecessary and avoidable differences in child vaccination is a critical global concern. This study aimed to assess socioeconomic inequalities in basic vaccination coverage among children aged 12–23...

Urban-rural differences in factors associated with incomplete basic immunization among children in Indonesia: A nationwide multilevel study

Identifying risk factors of incomplete immunization among children is crucial to developing relevant policies to improve immunization coverage. In this study, we investigated factors associated with incomplete immunization among children in Indonesia and elucidated differences in risk factors between urban and rural areas. The data came from a national-wide survey, the 2017 Indonesia Demographic Health Surveys. In total, 3264 children aged 12-23 months were included in the study. An incomplete immunization status was defined as a child who did not complete the ten doses of basic vaccinations, consisting of one dose of bacille Calmette-Guérin, one dose of hepatitis B, three doses of pentavalent vaccine (diphtheria, pertussis, tetanus, hemophilus influenza type B, and hepatitis B vaccine), four doses of polio vaccine, and one dose of measles vaccine. Generalized linear mixed models were constructed to examine the effects of different levels of risk factors on the incomplete immunization status. We further conducted stratified analyses by urban and rural areas. About 40% of the 3264 children were incompletely immunized, among whom 45.3% were in urban areas and 54.7% were in rural areas. Eight of the 34 provinces had incomplete immunization rates exceeding 50%, and the Papua and Maluku regions had the highest rates of incomplete child immunization. The multivariate analyses showed that when women attended fewer than four antenatal care sessions and resided outside the Nusa Tenggara region, their children were more likely to have incomplete immunization in both urban and rural areas. On the other hand, having no health insurance was positively associated with incomplete immunization in urban areas, whereas having received a tetanus vaccination during pregnancy was negatively associated with incomplete immunization in rural areas. Results of this study suggest that tailored interventions should be developed to address significant risk factors in rural and urban areas.

Using mobile immunization vans to cover under-served populations in hard-to-reach areas

Abstract Background In Pakistan, only 66% of children receive their basic vaccinations. However, the figure masks significant inequalities in vaccine coverage between urban and rural residences, slums and areas distantly located from EPI centers. Frequent outbreaks of vaccine-preventable diseases such as polio and measles, in urban cities like Karachi, signal the need for expanding vaccine services to underserved areas. In Apr'19, we introduced the Mobile Immunization Van initiative in Karachi in collaboration with EPI Sindh. Currently, two vans are deployed in hard-to-reach areas and slums to immunize under-2 children for routine vaccines. Methods Before the van visit, mobilization efforts are conducted in targeted areas to encourage caretakers to bring their child for vaccination. On the day of visit, the van is parked at a central location, and announcements are played on a loudspeaker to attract caregivers. All vaccinations are administered in the van, and entries are recorded in Government's Digital Immunization Registry along with GIS coordinates of immunized children. The data is then automatically transferred on to a web-dashboard for analysis and tracking. Results From Apr'19 to Jan'20, the vans have vaccinated 2,867 children, out of which 50% had never been immunized prior to the van visit. Of those who received their follow-up vaccines from the van, 80% were at least 4 weeks beyond from their vaccine due date. GIS analysis of van data confirmed that immunizations were conducted in slums, and areas distantly located from EPI centers. Moreover, compared to government outreach activity, proportion of BCG, Penta3 and Measles1 administrations in slums was higher through the vans by 5%, 6%, and 4% respectively. Conclusions The vans provide an opportunity for immunizing never-vaccinated children and children defaulting on their vaccine schedule, from the most vulnerable geographies, while simultaneously enrolling them in the Government's EPI Program for effective tracking. Key messages The mobile vans help achieve universal immunization coverage through provision of vaccine services in slum and rural hard-to-reach areas with limited access to government-provided services. The mobile vans help vaccinate and capture never-immunized children into the Government’s EPI records, reducing the number of children missed through routine services.

Geospatial Analysis of Vaccination Coverage and Predictors of Non- and Under-Vaccination of Children Aged 12–23 Months in Nigeria

This study (1) examines the spatial variation of uptake for each dose of basic vaccine and (2) identifies the predictors of non- and incomplete vaccine uptake among children aged 12–23 months in 2018 using data from NDHS. Spatial statistical techniques and multinomial logistic regression analyses were employed. Findings indicate wide variation of coverage at regional, urban/rural, and district levels. Coverage for all the vaccines exhibited statistically significant spatial dependence nationally. Locally, vaccination coverage hotspot for all the vaccines clustered among 16 states in the south while cold spots were in seven northern states. Of the 6059 children, 25, 56, and 9 percent were fully vaccinated, under-vaccinated, and non-vaccinated, respectively. Children who did not receive postnatal care, had no health card, resided in poorer households, and whose mothers did not receive tetanus injection had higher odd of being non-vaccinated. Children, who were delivered at home, did not receive postnatal care, whose mothers could not read and lived in poorest, poorer, and middle households had increased risk of being under-vaccinated. Findings suggest that increased access to immunization, community-level health education and communication are required particularly in rural and northern districts.

Audit of Post-Splenectomy Prophylaxis in a Single Tertiary Center in Slovenia: Where Are We and What Should Be Done?

Background: Patients who have had splenectomies are at increased risk for severe infections and overwhelming sepsis caused by pneumococci, meningococci, Haemophilus influenzae, and other encapsulated pathogens. Prophylactic measures are important to reduce mortality in this group; among them are vaccinations, antibiotic prophylaxis, and education. We performed a retrospective audit of post-splenectomy prophylactic measures, focusing on vaccinations and antibiotic prophylaxis coverage. Patients and Methods: We included 156 adult patients who had splenectomies between January 2010 and December 2018 in a study conducted at a single tertiary medical center. Data regarding vaccinations, antibiotic prophylaxis, and severe infections in the post-splenectomy period were obtained from medical records and supplemented by a patient-devised questionnaire. Results: Overall 121 of 156 (77.5%) of patients received a basic pneumococcal vaccination, although only 27 of 70 (38.6%) received re-vaccination after five years. Lower vaccination coverage was observed for meningococcal diseases and Haemophilus influenzae type b (Hib) disease with 57.0% (89/156) and 55.7% (87/156) vaccination coverage, respectively. A difference in pneumococcal vaccination coverage between patients after elective splenectomy (81/91; 89.0%) and non-elective splenectomy (40/65; 61.5%) was observed. However, no difference was observed among meningococcal and Hib vaccination coverage. Antibiotic prophylaxis was recommended to patients more frequently after elective splenectomy (41/82; 50.0%) than non-elective (16/56; 28.6%) yet after an elective splenectomy, patients discontinued the prophylaxis more often than those after a non-elective surgery. Overall, only 30 of 146 (20.5%) of patients received antibiotic prophylaxis over two years. In the observed period, 12.3% of patients suffered a severe infection. Conclusion: Our study shows that there is adequate basic pneumococcal vaccination coverage among patients after a splenectomy particularly after an elective splenectomy, but there is a lack of and an inadequate implementation of other prophylactic measures. There is an urgent need for an organized approach involving better education of healthcare practitioners as well as patients concerning the risk of asplenia. In addition, an improved long-term follow-up is needed including establishing a central registry for the asplenic patients in Slovenia.

A diffusion model of Zika virus with human-vector transmission dynamics and control strategy including social distancing study

Zika virus infection is caused by the Zika Virus belonging to the Flaviviridae family. The virus is transmitted to people through the bite of an infected Aedes mosquito. However, although rare, sexual and mother-to-child are also other modes of transmission. The incubation time in infected humans is a few days to a week. The spread of the disease still presents in some developing countries and remote areas that cannot afford basic public health intervention and vaccine, hence, investigating other options are necessary. In this study, we formulate a diffusion mathematical model of the Zika virus with controls (personal protection, medical treatment, and insecticide). In this model, we will be able to observe the spatial movement of individuals and investigate if the disease can be controlled by performing social distancing combined with other control strategies. Further, we investigate the essential dynamics of the model through equilibrium analyses. The basic reproduction number with the spatial movement of the model is derived. Meanwhile, a time-dependent optimal control study is applied to the model to seek a cost-effective strategy to eradicate Zika virus outbreaks. Numerical results show that strategically deployed personal protection, treatment, and insecticide can significantly reduce the number of infectious individuals and mosquitoes. Also, applying a social connection program can additionally reduce the spread from one place to another, and thus the number of infections in total is reduced.

Duration of immunity against heterologous porcine parvovirus 1 challenge in gilts immunized with a novel subunit vaccine based on the viral protein 2

BackgroundPorcine parvovirus 1 (PPV1) is widespread in commercial pig farms worldwide and has a significant impact to the swine industry. Long-lasting immunity achieved by means of vaccination is the main tool to prevent PPV1 infection and its associated clinical signs. Here we evaluated the duration of immunity (DOI) conferred by a novel subunit vaccine based on the viral protein (VP) 2 of PPV1, named ReproCyc® ParvoFLEX. The DOI was assessed at 6 months post-vaccination following the standard vaccination scheme (phase I) or after re-vaccination (phase II) with a single injection administered 24 weeks after the basic vaccination scheme. A total of 46, five to six-month-old gilts, free of PPV1 and porcine reproductive and respiratory syndrome virus (PRRSV), were randomly assigned to 6 groups (three in each phase): the negative control groups were inoculated with sodium chloride (NaCl), the vaccinated groups were immunized with the PPV1 subunit vaccine and the strict controls were neither treated nor challenged. Subsequently, the negative control and vaccinated groups from each phase were challenged with a heterologous PPV1 strain. Infection of fetuses was the primary outcome parameter for efficacy, though other supportive parameters were PPV1 viremia and serological status of the gilts and the condition of their fetuses (i.e. normal, autolytic, or mummified).ResultsAll gilts vaccinated against PPV1 tested seropositive at challenge and viremia after challenge was detectable only in the non-vaccinated animals. In this regard, fetuses positive to PPV1 by PCR were only found in litters from non-vaccinated sows.ConclusionsThese results point out that the immunity developed by the PPV1 subunit vaccine is effective in terms of preventing viremia, transplacental infection of fetuses and fetal death caused by PPV1 infection. ReproCyc® ParvoFLEX was demonstrated to protect fetuses against heterologous PPV1 challenge with a DOI of 6 months after vaccination.

Immunization coverage and its determinant factors among children aged 12\u201323\u2009months in Ethiopia: a systematic review, and Meta- analysis of cross-sectional studies

BackgroundImmunization is the process by which a person is made immune or resistant to an infectious disease, typically by the administration of vaccine. Vaccination coverage for other single vaccines ranged from 49.1% for PCV to 69.2% for BCG vaccine. The vaccination coverage for basic vaccinations was 39.7% in Ethiopia. There have been epidemiological studies available on immunization in Ethiopia. Yet, these studies revealed a wide variation over time and across geographical areas. This systematic review and Meta-analysis aim to estimate the overall immunization coverage among 12–23 months children in Ethiopia.MethodsCross-sectional studies that reported on immunization coverage from 2003 to August 2019 were systematically searched. Searches were conducted using PubMed, Google Scholar, Cochrane library, and gray literature. Information was extracted using a standardized form of Joanna Briggs Institute. The search was updated 20 Jan 2020 to decrease time-lag bias. The quality of studies assessed using Joanna Briggs Institute cross-sectional study quality assessment criteria. I-squared statistics applied to check the heterogeneity of studies. A funnel plot, Begg’s test, and Egger’s regression test was used to check for publication bias.ResultsOut of 206 studies, 30 studies with 21,672 children with mothers were included in the Meta-analysis. The pooled full immunization coverage using the random-effect model in Ethiopia was 58.92% (95% CI: 51.26–66.58%). The trend of immunization coverage was improved from time to time, but there were great disparities among different regions. Amhara region had the highest pooled fully immunized coverage, 72.48 (95%CI: 62.81–82.16). The I2 statistics was I2 = 99.4% (p = 0.0001). A subgroup meta-analysis showed that region and study years were not the sources of heterogeneity.ConclusionThis review showed that full immunization coverage in Ethiopia was 58.92% (95% CI: 51.26–66.58%). The study suggests that the child routine immunization program needs to discuss this low immunization coverage and the current practice needs revision.

Improvement in the Growth and α-toxin Production of Clostridium septicum by Magnesium Sulfate.

Clostridium septicum, the anaerobic toxigenic bacterium is the agent that causes dangerous disease in man and animals. There is a lethal toxin of the bacterium namely alpha toxin. The ɑ-toxin has hemolytic, necrotic and lethal activities. Today, Razi Vaccine and Serum Research Institute of Iran produced the C. septicum vaccine in the form of bacterin/toxoid. Because of some problems, the vaccine needs to improve on an industrial scale. The study is going to find an appropriate supplement to improve growth and ɑ-toxin production. Three strains of C. septicum (vaccine, NH1 and NH8 strains) were cultured in the basic vaccine media. Magnesium sulfate, Copper, Ferrous, yeast extract, and trace elements plus vitamins' solution were added to the basic vaccine media in different cultures. The effect of the ingredients on the growth was measured by a spectrophotometer and the α-toxin secretion was assayed by hemolysin test. Growth of the bacterium and α-toxin secretion were increased by Magnesium (80 mg/l) in NH8 and vaccine strains significantly. The black precipitate was difficult to dissolve in magnesium media that must be solved. Trace elements plus vitamins solution mildly influence on NH1strain growth and toxin secretion. Other supplements (Cu, Fe, yeast extract) were not showen any significant changes in the growth and α-toxin production of C. septicum. Overflowing peptone (4%) in the vaccine media, fixes essentials of proteolysis activity, allows the sufficient growth and toxin production without Cu, Fe, and yeast extract. Due to essentially of Mg for growth, extra magnesium was added for improvement of media culture. The study suggests for Magnesium addition in the C. septicum vaccine media during production procedure after precipitation solving problem.

Seroprevalence of chronic hepatitis B virus infection and immunity to measles, rubella, tetanus and diphtheria among schoolchildren aged 6–7 years old in the Solomon Islands, 2016

The Western Pacific Region (WPR) established a goal to decrease chronic hepatitis B virus (HBV) infection among children to <1% and to achieve ≥95% hepatitis B vaccine birth dose (HepB-BD) and ≥95% three-dose (HepB3) coverage by 2017. In 2016, we conducted a national serosurvey in the Solomon Islands among 6–7-year-old school children to assess progress towards the control goal and immunity to measles, rubella, tetanus and diphtheria. Eighty schools were selected systematically proportional to their 6–7-year-old population; all 6–7-year-olds were enrolled. We collected basic demographic information and vaccination history. Children were tested for HBV surface antigen (HBsAg) using a rapid test, and for immunity to measles, rubella, tetanus, and diphtheria using a multiplex bead assay. In total, 1,249 out of 1,492 children (84%) were enrolled, among whom 1,169 (94%) underwent HBsAg testing and 1,156 (93%) provided dried blood spots. Almost 80% (n = 982) of enrolled children had vaccination cards, among whom 59% (n = 584) received a timely HepB-BD (within 24 hours of birth), 95% (n = 932) received HepB3, and >90% received vaccines for diphtheria, tetanus, and measles (rubella vaccine was not available at the time). HBsAg prevalence was 3.1% (95% confidence interval (CI): 2.0%–4.9%), with 55% of identified cases from one province. Among 982 children with vaccination cards, HBsAg prevalence was higher among children who had not received a timely HepB-BD and at least two HepB doses compared to those who had (4% vs. 2%). Of 1,156 tested children, immunoprotection estimates were 99% (95% CI: 98%–99%) for measles, 99% (95% CI: 97%–100%) for rubella, 85% (95% CI: 83%–87%) for tetanus, and 51% (95% CI: 47%–55%) for diphtheria. Improving timely HepB-BD coverage and maintaining high HepB3 coverage could help Solomon Islands reach the regional HBV control goal. Low immunity to tetanus and diphtheria suggests the need to introduce booster doses to ensure long-term protection.

Opinions and Knowledge of Parents Regarding Preventive Vaccinations of Children and Causes of Reluctance toward Preventive Vaccinations.

Background: Despite the stability of global vaccination coverage, over 19 million children worldwide do not currently receive basic vaccines. Over the past several years, there has been a dramatic drop in the number of vaccinated children worldwide. The implementation of the vaccination program and the scope of protection depend on the parents or legal guardians, who decide whether to vaccinate their child or not. Studies were conducted to assess parents’ knowledge, attitudes, and beliefs about vaccines, as well as the role of healthcare providers in parents’ decisions. Methods: A population survey was conducted in 2018–2019. Parents or legal guardians of the children were invited to participate in the study during their visits to the clinic for healthy or sick children. The method used in the research was a diagnostic survey. Results: According to the conducted research, men and women constituted 45% and 55% of participants, respectively. The average age of men was 44, while, for women, it was 41. Internal research showed that as much as 71% of parents declared the need for vaccination, although 41% of parents vaccinated their children according to the vaccination calendar. The most frequently mentioned concerns included the possibility of adverse vaccination reactions (22%), the occurrence of autism (7%), and child death (6%). General practitioners had, by far, the greatest impact on the use of protective vaccination in children (73% women and 80% men), although there were cases of discouraging the performance of compulsory vaccinations (41%), and mentioning a doctor (38%) or nurse (3%). Conclusions: Modifiable determinants of the negative attitude toward vaccinations are caused mainly by the lack of knowledge. These obstacles in vaccinations can be overcome by improving health education in terms of the vaccination program.

Studies on the Mechanism of Electrochemical Detection of Haemophilus Influenzae at Diamond-Based Electrodes

Haemophilus influenzae (HI) is a Gram-negative pathogenic bacterium whose infections occur worldwide and mainly affect unvaccinated children and those who have not completed the basic vaccination course. Type B of this bacterium (Hib) can cause sepsis, and other invasive diseases as dermatitis or arthritis but the most dangerous is pneumonia meningitis. The most reliable method for recognizing Hib infections is isolation in microbiological culture. Serological tests are also performed to diagnose Hib infections. They rely on the detection of the presence of bacterial antigens or antibodies which have the ability to bind to specific antigens. Detection of antibodies doesn’t mean disease but only indicate contact with a given bacterium in the past. Recognition of bacteria using presently known methods takes a long time and requires expensive equipment although fast and sensitive detection of Haemophilus influenzae is crucial l to start treatment early enough.In this work, we present electrochemical detection of HI on diamond-based pastes electrodes using binding specific antibodies (ap. D) with proteins occurring on the surface of bacteria (protein D). The measuring system consisted of a specially prepared printed circuit board (PCB) and diamond-based electrode, which was prepared by screen printing in special conditions. Places printed on it, served as a working electrode, counter electrode and reference. Ceramics was first used as a substrate, but it was quickly changed to Teflon, which showed better adhesion to diamond pastes. Better sample strength was also obtained, so it could be washed in an ultrasonic cleaner without fear of damage. Before detection, the electrode had to be modified by electrochemical reduction of the aminobenzoic acid diazonium salt, antibodies deposition via EDC / NHS and blocking the unmodified electrode sites by incubating in solution of Bovine Serum Albumin (BSA). The last step of modification prevents unspecific adsorption on electrode surface which would lead to false detection results.Electrochemical Impedance Spectroscopy Fig. 1) were used to bacteria detection. The electron transfer resistance rises with each step of electrode modification and increased bacterial concentration in solution. Then a calibration curve was constructed.Three pathogens were selected to check the biosensor selectivity: S. pyogenes, S. pneumoniae, B. parapertussis. For each pathogen responses were significantly lower than for HI at similar concentrations. For example, the response of sensor for S. pyogenes (67474,28 CFU/ml) and B. parapertussis (17819,27 CFU/ml) were less than 5%, which are much smaller in comparison to response at level of 30% for HI (47003,48 CFU/ml). Acknowledgments The authors gratefully acknowledge financial support from the National Centre for Science and Development Grant Techmatstrateg No. 347324 2015/16/T/ST7/00469. Figure 1

Vaccine Supply Chains in Resource-Limited Settings: Mitigating Rainy Season Disruptions

Immunization is widely recognized as one of the most successful and cost-effective health interventions, preventing two to three million deaths from vaccine-preventable diseases each year. Although progress has been made in recent years, substantial operational challenges persist in resource-limited settings with frequent stock-outs contributing to sub-optimal immunization coverage and inequality in vaccine access. In this paper, we investigate the role of rainy season induced supply chain disruptions on vaccination coverage and inequalities. We develop a modeling framework combining spatial modeling — to predict flood disruptions in road networks — and a discrete-event simulation of a multi-tiered vaccine supply chain (VSC). Our models are fitted and validated using data from the Malagasy VSC network. Our baseline simulation predicts the national vaccination coverage with good accuracy and suggests that 67% of regions with low reported immunization coverage are affected by rainy season disruptions or operational inefficiencies, causing significant geographical inequalities in vaccine access. We investigate various mitigation strategies to increase the resiliency of VSCs and find that by strategically placing buffer inventory at targeted facilities prior to the rainy season the proportion of children receiving all basic vaccines in these areas is increased by 7% and the geographical inequality in vaccination coverage is reduced by 11%. By also increasing the replenishment frequency from every third month to every month, the national vaccination coverage improves by 37%. Our results contribute to achieving the UN Sustainable Development Goals (SDGs) by providing actionable insights for improving vaccination coverage (SDG 3) and investigating the resiliency of the VSC to increased flooding due to climate change (SDG 13).

Human Papilloma Virus Vaccination Compliance in a Military Aviation Training Community

Human Papilloma Virus (HPV) vaccination compliance as reported by the CDC in 2011 falls short of a national goal to have 80% of adolescents vaccine-complete by 2020. The Naval Aviation Schools Command, Pensacola, Florida offers a single point of contact for military aviation trainees offering near-complete capture of an HPV vaccine target population. The purpose of this study is to identify baseline HPV vaccination rates among military aviation trainees and whether or not the provision of educational materials at the start of aviation training would increase future HPV vaccination compliance. Approval to conduct this study was obtained from the Institutional Review Board of Naval Medical Center Portsmouth, Virginia. Our population of interest consisted of US Navy and Marine Corps student naval aviators, student naval flight officers (officers), and student enlisted air crew (enlisted) reporting for aviation related duty. A convenience sampling of officer and enlisted student classes checking in for training was performed over a period of 6months. The first 3months of students were assigned as the intervention group and the remaining 3months of students were assigned to the control group. This study was conducted in two parts: (1) an anonymous survey captured cross-sectional data of self-reported HPV vaccine use, and (2) prospective analysis of service members' HPV vaccine rates before and after educational intervention as documented within the military's electronic health record system, Armed Forces Health Longitudinal Technology Application (AHLTA). AHLTA immunization status was evaluated for 1,164 personnel; 114 (9.8%) were excluded for missing basic vaccination information. Of the remaining 1,050, another 199 (19%) members were excluded as already vaccine complete (evidenced by three shots documented) prior to entry into the study. Within the 199 service members with documented baseline HPV vaccination completion, 197/199 (99%) were officers and 2/199 (0.1%) were enlisted. A total of 851 personnel were included for prospective analysis. Person-time of 100 person years was used and the vaccination rate translates to 16.62/100 person years (95% CI 11.29, 23.59) within intervention vs. 2.96/100 person years (95% CI 0.80, 7.58) within control groups and are significantly different (P=0.0001). Comparing intervention and control groups, rate ratios=5.61 (95% CI 2.14, 18.64) and rate differences=13.66 (95% CI 7.13, 20.19). Among intervention group survey responders who previously reported nonvaccine use, 50.5% reported a change in opinion about obtaining the vaccination, with a higher proportion of enlisted members reporting a change in opinion (62.8% vs. 39.7%, P=0.0053). Electronic health records immunizations review noted a baseline vaccine completion rate of 19%. Our study showed a health inequity between enlisted and officers, with officers having 99% of the documented baseline completion rates per AHLTA data. Our prospective analysis noted statistically significant rate differences of 13.66% and rate ratios of 5.61 between intervention and control groups. This analysis of AHLTA data combined with survey response of 50.5% indicating a change in opinion about HPV vaccine use among those who had not yet started vaccine series suggests targeted education would be a low-cost intervention to improve HPV vaccine use rates.

Elucidating the sustained decline in under-three child linear growth faltering in Nepal, 1996-2016.

Childhood linear growth faltering remains a major public health concern in Nepal. Nevertheless, over the past 20 years, Nepal sustained one of the most rapid reductions in the prevalence of stunting worldwide. First, our study analysed the trends in height‐for‐age z‐score (HAZ), stunting prevalence, and available nutrition‐sensitive and nutrition‐specific determinants of linear growth faltering in under‐three children across Nepal's Family Health Survey 1996 and Nepal's Demographic and Health Surveys 2001, 2006, 2011, and 2016. Second, we constructed pooled multivariable linear regression models and decomposed the contributions of our time‐variant determinants on the predicted changes in HAZ and stunting over the past two decades. Our findings indicate substantial improvements in HAZ (38.5%) and reductions in stunting (−42.6%) and severe stunting prevalence (−63.9%) in Nepalese children aged 0–35 months. We also report that the increment in HAZ, across the 1996–2016 period, was significantly associated (confounder‐adjusted p < .05) with household asset index, maternal and paternal years of education, maternal body mass index and height, basic child vaccinations, preceding birth interval, childbirth in a medical facility, and prenatal doctor visits. Furthermore, our quantitative decomposition of HAZ identified advances in utilisation of health care and related services (31.7% of predicted change), household wealth accumulation (25%), parental education (21.7%), and maternal nutrition (8.3%) as key drivers of the long‐term and sustained progress against child linear growth deficits. Our research reiterates the multifactorial nature of chronic child undernutrition and the need for coherent multisectoral nutrition‐sensitive and nutrition‐specific strategies at national scale to further improve linear growth in Nepal. [Correction added on 6 November 2020, after first online publication: in abstract, the citation year in the fourth sentence has been changed from ‘2001’ to ‘2011’.]