Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India.

BACKGROUND: The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level. METHODS: We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. RESULTS: Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities. CONCLUSIONS: Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.

The lasting influence of Ebola: a qualitative study of community-level behaviors, trust, and perceptions three years after the 2014-16 Ebola epidemic in Liberia.

The majority of disease transmission during the 2014-16 West Africa Ebola epidemic was driven by community-based behaviors that proved difficult to change in a social paradigm of misinformation, denial, and deep-seated distrust of government representatives and institutions. In Liberia, perceptions and beliefs about Ebola during and since the epidemic can provide insights useful to public health strategies aimed at improving community preparedness. In this 2018 study, we conducted nine focus groups with Liberians from three communities who experienced Ebola differently, to evaluate behaviors, attitudes, and trust during and after the epidemic. Focus group participants reported that some behaviors adopted during Ebola have persisted (e.g. handwashing and caretaking practices), while others have reverted (e.g. physical proximity and funeral customs); and reported ongoing distrust of the government and denial of the Ebola epidemic. These findings suggest that a lack of trust in the biomedical paradigm and government health institutions persists in Liberia. Future public health information campaigns may benefit from community engagement addressed at understanding beliefs and sources of trust and mistrust in the community to effect behavior change and improve community-level epidemic preparedness.

Evaluation of Vaccine Safety After the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

BACKGROUND: In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV; Typbar-TCV). While no safety concerns were identified in pre- and postlicensure studies, WHO's Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July-August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world's first public sector TCV introduction. Per administrative reports, 113 420 children 9 months-14 years old received TCV. METHODS: We evaluated adverse events following immunization (AEFIs) using passive and active surveillance via (1) reports from the passive NMMC AEFI surveillance system, (2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days postvaccination, and (3) chart abstraction for adverse events of special interest (AESIs) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. RESULTS: We identified 222/113 420 (0.2%) vaccine recipients with AEFIs through the NMMC AEFI surveillance system: 211 (0.19%) experienced minor AEFIs, 2 (0.002%) severe, and 9 serious (0.008%). At 48 hours postvaccination, 1852/5605 (33%) caregivers reported ≥1 AEFI, including injection site pain (n = 1452, 26%), swelling (n = 419, 7.5%), and fever (n = 416, 7.4%). Of the 4728 interviews completed at 7 days postvaccination, the most reported AEFIs included fever (n = 200, 4%), pain (n = 52, 1%), and headache (n = 42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESIs were causally associated with TCV. CONCLUSIONS: No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months-14 years old.

The Effects of Methamphetamine Use on the Sexual Lives of Gender and Sexually Diverse People in Dhaka, Bangladesh: A Qualitative Study.

Methamphetamine use has increased among gender and sexually diverse people in several countries, including Bangladesh. This study aimed to explore the effects of methamphetamine on the sexual lives of these people in Dhaka, Bangladesh. An exploratory qualitative study was conducted, comprising 30 in-depth interviews with gender and sexually diverse people including males having sex with males, male sex workers, and transgender women (hijra) under HIV intervention coverage. Ten key informant interviews were also conducted with individuals who have expertise in relevant disciplines such as drug use, harm reduction, and HIV and AIDS. Digitally recorded data were manually analyzed under the thematic analysis framework. Findings indicated that many participants reported that methamphetamine brought changes in their sexual lives such as increased sexual drive, engagement in group sex, the increased ability to perform serial sex, transactional sex, impulsive and coercive sex, initiation and switching of male-to-male sexual practices, and limited condom use. Key informants noted that there is a dearth of methamphetamine-related services in Bangladesh. Methamphetamine use was found to lead to diverse effects on the sexual lives of gender and sexually diverse people, thus making it a driving force for shaping sexual practices and, hence, sexual risks. Therefore, it is essential for policy-level stakeholders and program managers to consider the risks of methamphetamine use due to their negative ramifications on sexual health, including HIV risks.

Environmental Surveillance as a Tool for Identifying High-risk Settings for Typhoid Transmission.

Enteric fever remains a major cause of morbidity in developing countries with poor sanitation conditions that enable fecal contamination of water distribution systems. Historical evidence has shown that contamination of water systems used for household consumption or agriculture are key transmission routes for Salmonella Typhi and Salmonella Paratyphi A. The World Health Organization now recommends that typhoid conjugate vaccines (TCV) be used in settings with high typhoid incidence; consequently, governments face a challenge regarding how to prioritize typhoid against other emerging diseases. A key issue is the lack of typhoid burden data in many low- and middle-income countries where TCV could be deployed. Here we present an argument for utilizing environmental sampling for the surveillance of enteric fever organisms to provide data on community-level typhoid risk. Such an approach could complement traditional blood culture-based surveillance or even replace it in settings where population-based clinical surveillance is not feasible. We review historical studies characterizing the transmission of enteric fever organisms through sewage and water, discuss recent advances in the molecular detection of typhoidal Salmonella in the environment, and outline challenges and knowledge gaps that need to be addressed to establish environmental sampling as a tool for generating actionable data that can inform public health responses to enteric fever.

Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

BACKGROUND: Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. METHODS: We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel-based tool to estimate the financial and economic vaccination campaign costs. RESULTS: The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July-August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. CONCLUSION: The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.

Community trust of government and non-governmental organizations during the 2014-16 Ebola epidemic in Liberia.

The West African Ebola Virus Disease epidemic of 2014-16 cost more than 11,000 lives. Interventions targeting key behaviors to curb transmission, such as safe funeral practices and reporting and isolating the ill, were initially unsuccessful in a climate of fear, mistrust, and denial. Building trust was eventually recognized as essential to epidemic response and prioritized, and trust was seen to improve toward the end of the epidemic as incidence fell. However, little is understood about how and why trust changed during Ebola, what factors were most influential to community trust, and how different institutions might have been perceived under different levels of exposure to the outbreak. In this large-N household survey conducted in Liberia in 2018, we measured self-reported trust over time retrospectively in three different communities with different exposures to Ebola. We found trust was consistently higher for non-governmental organizations than for the government of Liberia across all time periods. Trust reportedly decreased significantly from the start to the peak of the epidemic in the study site of highest Ebola incidence. This finding, in combination with a negative association found between knowing someone infected and trust of both iNGOs and the government, indicates the experience of Ebola may have itself caused a decline of trust in the community. These results suggest that national governments should aim to establish trust when engaging communities to change behavior during epidemics. Further research on the relationship between trust and epidemics may serve to improve epidemic response efficacy and behavior uptake.

Barriers and Opportunities for Sustainable Hand Hygiene Interventions in Rural Liberian Hospitals.

Hand hygiene is central to hospital infection control. During the 2014-2016 West Africa Ebola virus disease epidemic in Liberia, gaps in hand hygiene infrastructure and health worker training contributed to hospital-based Ebola transmission. Hand hygiene interventions were undertaken post-Ebola, but many improvements were not sustainable. This study characterizes barriers to, and facilitators of, hand hygiene in rural Liberian hospitals and evaluates readiness for sustainable, locally derived interventions to improve hand hygiene. Research enumerators collected data at all hospitals in Bong and Lofa counties, Liberia, in the period March-May 2020. Enumerators performed standardized spot checks of hand hygiene infrastructure and supplies, structured observations of hand hygiene behavior, and semi-structured key informant interviews for thematic analysis. During spot checks, hospital staff reported that handwashing container water was always available in 89% (n = 42) of hospital wards, piped running water in 23% (n = 11), and soap in 62% (n = 29). Enumerators observed 5% of wall-mounted hand sanitizer dispensers (n = 8) and 95% of pocket-size dispensers (n = 53) to be working. In interviews, hospital staff described willingness to purchase personal hand sanitizer dispensers when hospital-provided supplies were unavailable. Low-cost, sustainable interventions should address supply and infrastructure-related obstacles to hospital hand hygiene improvement.

Receptor tyrosine phosphatase-dependent cytoskeletal remodeling by the hedgehog-responsive gene MIM/BEG4.

During development, dynamic remodeling of the actin cytoskeleton allows the precise placement and morphology of tissues. Morphogens such as Sonic hedgehog (Shh) and local cues such as receptor protein tyrosine phosphatases (RPTPs) mediate this process, but how they regulate the cytoskeleton is poorly understood. We previously identified Basal cell carcinoma-enriched gene 4 (BEG4)/Missing in Metastasis (MIM), a Shh-inducible, Wiskott-Aldrich homology 2 domain-containing protein that potentiates Gli transcription (Callahan, C.A., T. Ofstad, L. Horng, J.K. Wang, H.H. Zhen, P.A. Coulombe, and A.E. Oro. 2004. Genes Dev. 18:2724-2729). Here, we show that endogenous MIM is induced in a patched1-dependent manner and regulates the actin cytoskeleton. MIM functions by bundling F-actin, a process that requires self-association but is independent of G-actin binding. Cytoskeletal remodeling requires an activation domain distinct from sequences required for bundling in vitro. This domain associates with RPTPdelta and, in turn, enhances RPTPdelta membrane localization. MIM-dependent cytoskeletal changes can be inhibited using a soluble RPTPdelta-D2 domain. Our data suggest that the hedgehog-responsive gene MIM cooperates with RPTP to induce cytoskeletal changes.

Effect of household relocation on child vaccination and health service utilisation in Dhaka, Bangladesh: a cross-sectional community survey.

OBJECTIVE: To explore the relationship between household relocation and use of vaccination and health services for severe acute respiratory illness (ARI) among children in Dhaka, Bangladesh. DESIGN: Analysis of cross-sectional community survey data from a prior study examining the impact of Haemophilus influenzae type b vaccine introduction in 2009 on meningitis incidence in Bangladesh. SETTING: Communities surrounding two large paediatric hospitals in Dhaka, Bangladesh. PARTICIPANTS: Households with children under 5 years old who either recently relocated <12 months or who were residentially stable living >24 months in their current residence (total n=10 020) were selected for this study. PRIMARY OUTCOME MEASURES: Full vaccination coverage among children aged 9-59 months and visits to a qualified medical provider for severe ARI among children under 5 years old. RESULTS: Using vaccination cards with maternal recall, full vaccination was 80% among recently relocated children (n=3795) and 85% among residentially stable children (n=4713; χ2=37.2, p<0.001). Among children with ARI in the prior year, 69% of recently relocated children (n=695) had visited a qualified medical provider compared with 82% of residentially stable children (n=763; χ2=31.9, p<0.001). After adjusting for demographic and socioeconomic characteristics, recently relocated children were less likely to be fully vaccinated (prevalence ratio [PR] 0.97; 95% CI 0.95 to 0.99; p=0.016) and to have visited a qualified medical provider for ARI (PR 0.88; 95% CI 0.84 to 0.93; p<0.001). CONCLUSIONS: Children in recently relocated households in Dhaka, Bangladesh, have decreased use of vaccination and qualified health services for severe ARI.

Understanding the reasons for using methamphetamine by sexual minority people in Dhaka, Bangladesh.

BACKGROUND: Internationally, methamphetamine use is prevalent among males who have sex with males (MSM) and transgender women (hijra), with studies showing its association with risky sexual behaviours leading to HIV transmission. This study aimed to explore the underlying reasons for methamphetamine use among MSM and hijra in Bangladesh. METHODS: We conducted 30 in-depth interviews with MSM and hijra and six focus groups with MSM, hijra and service providers. Data were thematically analysed using manual data analysis procedures. FINDING: Reasons cited for using methamphetamine varied across feminized MSM (i.e. kothis), masculine MSM (i.e. panthis), male sex workers and hijra. For sex workers, increased sexual pleasure and consequent ability to take more clients increased their income. For panthis, methamphetamine enhanced feelings of masculinity and sexual prowess. Kothis were able to feel more feminine due to their ability to receive multiple partners each night. For all participants, methamphetamine restored self-esteem and relieved the stress resulting from stigma. CONCLUSIONS: Findings indicate that reasons for using methamphetamine are not only rooted in the individual's psyche but also grounded in the socio-cultural expectations about masculinities and femininities in Bangladeshi society. Limited knowledge about the complexities concerning methamphetamine use mean that appropriate counselling and treatment services are non-existent in Bangladesh. The study findings can be used to refine national and international harm reduction policies so as to incorporate and address methamphetamine use.

Health-Care Facility Water, Sanitation, and Health-Care Waste Management Basic Service Levels in Bangladesh: Results from a Nation-Wide Survey.

We conducted a nationally representative cross-sectional study of 875 health-care facilities (HCFs) to determine water, sanitation, and health-care waste disposal service levels in Bangladesh for doctors, staff, and patients/caregivers in 2013. We calculated proportions and prevalence ratios to compare urban versus rural and government versus other HCFs. We report World Health Organization (WHO)-defined basic HCF service levels. The most common HCF was nongovernmental private (80%, 698/875), with an average of 25 beds and 12 admissions per day. There was an improved water source inside the HCF for doctors (79%, 95% confidence intervals [CI]: 75, 82), staff (59%, 95% CI: 55, 64), and patients/caregivers (59%, 95% CI: 55, 63). Improved toilets for doctors (81%, 95% CI: 78, 85) and other staff (73%, 95% CI: 70, 77) were more common than for patients/caregivers (54%, 95% CI: 50, 58). Forty-three percentage (434/875) of HCFs had no disposal method for health-care waste. More urban than rural and more government than other HCFs had an improved water source on the premises and improved toilets for staff. WHO-defined basic service levels were detected in > 90% of HCFs for drinking water, among 46-77% for sanitation, and 68% for handwashing at point of care but 26% near toilets. Forty-seven percentage of HCFs attained basic health-care waste management service levels. Patient/caregiver access to water, sanitation, and hygiene facilities is inadequate in many HCFs across Bangladesh. Improving facilities for this group should be an integral part of accreditation.

Use of mobile phones for improving vaccination coverage among children living in rural hard-to-reach areas and urban streets of Bangladesh.

In Bangladesh, full vaccination rates among children living in rural hard-to-reach areas and urban streets are low. We conducted a quasi-experimental pre-post study of a 12-month mobile phone intervention to improve vaccination among 0-11 months old children in rural hard-to-reach and urban street dweller areas. Software named "mTika" was employed within the existing public health system to electronically register each child's birth and remind mothers about upcoming vaccination dates with text messages. Android smart phones with mTika were provided to all health assistants/vaccinators and supervisors in intervention areas, while mothers used plain cell phones already owned by themselves or their families. Pre and post-intervention vaccination coverage was surveyed in intervention and control areas. Among children over 298 days old, full vaccination coverage actually decreased in control areas--rural baseline 65.9% to endline 55.2% and urban baseline 44.5% to endline 33.9%--while increasing in intervention areas from rural baseline 58.9% to endline 76*8%, difference +18.8% (95% CI 5.7-31.9) and urban baseline 40.7% to endline 57.1%, difference +16.5% (95% CI 3.9-29.0). Difference-in-difference (DID) estimates were +29.5% for rural intervention versus control areas and +27.1% for urban areas for full vaccination in children over 298 days old, and logistic regression adjusting for maternal education, mobile phone ownership, and sex of child showed intervention effect odds ratio (OR) of 3.8 (95% CI 1.5-9.2) in rural areas and 3.0 (95% CI 1.4-6.4) in urban areas. Among all age groups, intervention effects on age-appropriate vaccination coverage were positive: DIDs +13.1-30.5% and ORs 2.5-4.6 (p<0.001 in all comparisons). Qualitative data showed the intervention was well-accepted. Our study demonstrated that a mobile phone intervention can improve vaccination coverage in rural hard-to-reach and urban street dweller communities in Bangladesh. This small-scale successful demonstration should serve as an example to other low-income countries with high mobile phone usage.

Endocarditis due to Coccidioides spp: The Seventh Case.

Coccidioides, a dimorphic fungus endemic within the Americas, primarily causes pulmonary disease but may disseminate. We describe a case of confirmed Coccidioides endocarditis, the seventh reported in literature. Coccidioides endocarditis often requires tissue diagnosis and combined surgical and medical treatment.

MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription.

Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a new Shh-responsive gene. Together, Gli1 and MIM recapitulate Shh-mediated epidermal proliferation and invasion in regenerated human skin. MIM is part of a Gli/Suppressor of Fused complex and potentiates Gli-dependent transcription using domains distinct from those used for monomeric actin binding. These data define MIM as both a Shh-responsive gene and a new member of the pathway that modulates Gli responses during growth and tumorigenesis.