Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

Understanding the factors influencing mosquitoes' fecundity and longevity is important for designing better and more sustainable vector control strategies, as these parameters can impact their vectorial capacity. Here, we address how mating affects midgut growth in Aedes aegypti, what role Juvenile Hormone (JH) plays in this process, and how it impacts the mosquito's immune response and microbiota. Our findings reveal that mating and JH induce midgut growth. Additionally, the establishment of a native bacterial population in the midgut due to JH-dependent suppression of the immune response has important reproductive outcomes. Specific downregulation of AMPs with an increase in bacteria abundance in the gut results in increased egg counts and longer lifespans. Overall, these findings provide evidence of a cross-talk between JH response, gut epithelial tissue, cell cycle regulation, and the mechanisms governing the trade-offs between nutrition, immunity, and reproduction at the cellular level in the mosquito gut.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Pyrethroid resistance in Aedes aegypti has become widespread after almost two decades of frequent applications to reduce the transmission of mosquito-borne diseases. Because few insecticide classes are available for public health use, insecticide resistance management (IRM) is proposed as a strategy to retain their use. A key hypothesis of IRM assumes that negative fitness is associated with resistance, and when insecticides are removed from use, susceptibility is restored. In Tapachula, Mexico, pyrethroids (PYRs) were used exclusively by dengue control programs for 15 years, thereby contributing to selection for high PYR resistance in mosquitoes and failure in dengue control. In 2013, PYRs were replaced by organophosphates-insecticides from a class with a different mode of action. To test the hypothesis that PYR resistance is reversed in the absence of PYRs, we monitored Ae. aegypti's PYR resistance from 2016 to 2021 in Tapachula. We observed significant declining rates in the lethal concentration 50 (LC50), for permethrin and deltamethrin. For each month following the discontinuation of PYR use by vector control programs, we observed increases in the odds of mosquitoes dying by 1.5% and 8.4% for permethrin and deltamethrin, respectively. Also, knockdown-resistance mutations (kdr) in the voltage-gated sodium channel explained the variation in the permethrin LC50s, whereas variation in the deltamethrin LC50s was only explained by time. This trend was rapidly offset by application of a mixture of neonicotinoid and PYRs by vector control programs. Our results suggest that IRM strategies can be used to reverse PYR resistance in Ae. aegypti; however, long-term commitment by operational and community programs will be required for success.

BACKGROUND: The novel oral poliovirus vaccine type 2 (nOPV2) is now authorised by a WHO emergency use listing and widely distributed to interrupt outbreaks of circulating vaccine-derived poliovirus type 2. As protection of vulnerable populations, particularly young infants, could be facilitated by shorter intervals between the two recommended doses, we aimed to assess safety and non-inferiority of immunogenicity of nOPV2 in 1-week, 2-week, and 4-week schedules. METHODS: In this phase 3, open-label, randomised trial, healthy, full-term, infants aged 6-8 weeks from a hospital or a clinic in the Dominican Republic were randomly allocated (1:1:1 ratio) using a pre-prepared, computer-generated randomisation schedule to three groups to receive two doses of nOPV2 immunisations with a 1-week interval (group A), 2-week interval (group B), or 4-week interval (group C). The nOPV2 vaccine was given at a 0·1 mL dose and contained at least 10(5) 50% cell culture infective dose. Neutralising antibodies against poliovirus types 1, 2, and 3 were measured before each immunisation and 4 weeks after the second dose. The primary outcome was the type 2 seroconversion rate 28 days after the second dose, and the non-inferiority margin was defined as a lower bound 95% CI of greater than -10%. Safety and reactogenicity were assessed through diary cards completed by the parent or guardian. The trial is registered with ClinicalTrials.gov, NCT05033561. FINDINGS: We enrolled 905 infants between Dec 16, 2021, and March 28, 2022. 872 infants were included in the per-protocol analyses: 289 in group A, 293 in group B, and 290 in group C. Type 2 seroconversion rates were 87·5% (95% CI 83·2 to 91·1) in group A (253 of 289 participants), 91·8% (88·1 to 94·7) in group B (269 of 293 participants), and 95·5% (92·5 to 97·6) in group C (277 of 290 participants). Non-inferiority was shown for group B compared with group C (difference in rates -3·7; 95% CI -7·9 to 0·3), but not for group A compared with group C (-8·0; -12·7 to -3·6). 4 weeks after the second nOPV2 dose, type 2 neutralising antibodies increased in all three groups such that over 95% of each group was seroprotected against polio type 2, although final geometric mean titres tended to be highest with longer intervals between doses. Immunisation with nOPV2 was well tolerated with no causal association to vaccination of any severe or serious adverse event; one death from septic shock during the study was unrelated to the vaccine. INTERPRETATION: Two nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2-week interval were non-inferior to those after the standard 4-week interval, but marked responses after a 1-week interval suggest that schedules with an over 1-week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine-derived poliovirus type 2 outbreaks. FUNDING: Bill & Melinda Gates Foundation.

Epigenetic mechanisms, like DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth co-infections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and BCG-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared to age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA methylated genes with 72% hyper-methylated. Gene ontology pathway analysis identified inhibition of IFN-γ signaling, cellular proliferation, and the Th1 pathway. Targeted RT-PCR after methyl-specific endonuclease digestion confirmed DNA hyper-methylation of the transcription factors BATF3, ID2, STAT5A, IRF5, PPARg, RUNX2, IRF4 and NFATC1 and cytokines or cytokine receptors IFNGR1, TNFS11, RELT (TNF receptor), IL12RB2 and IL12B (p< 0.001; Sidak-Bonferroni). Functional blockage of the IFN-γ signaling pathway was confirmed with helminth-infected individuals having decreased up-regulation of IFN-γ-inducible genes (Mann-Whitney p < 0.05). Hypo-methylation of the IL-4 pathway and DNA hyper-methylation of the Th1 pathway was confirmed by antigen-specific multidimensional flow cytometry demonstrating decreased TB-specific IFN-γ and TNF and increased IL-4 production by CD4+ T cells (Wilcoxon signed rank P <0.05). In S.haematobium infected individuals, these DNA methylation and immune phenotypic changes persisted at least six months after successful deworming. This work demonstrates that helminth infection induces DNA methylation and immune perturbations that inhibit TB-specific immune control and that the duration of these changes are helminth-specific.

We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks.

In 2023, three autochthonous DENV-3 cases were detected in Roraima and one imported case in Parana, fifteen years after the last DENV-3 outbreak in Brazil. Phylogenetic analyses confirmed all belonging to a new Asian lineage recently introduced in the Americas, raising concerns about future large dengue outbreaks in this region. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

BACKGROUND: After a pilot project in 2014-15 Zimbabwe introduced the human papillomavirus (HPV) vaccine nationally in 2018 for girls aged 10-14years through a primarily school-based vaccination campaign with two doses administered at 12-month intervals. In 2019, a first dose was delivered to a new cohort of girls in grade 5 of girls age 10years if out-of-school (OOS), along with a second dose to the 2018 multiple cohorts. Additional effort was made to identify and mobilize OOS girls by Village Health Workers (VHWs) in the community. Zimbabwe reported 1,569,905 doses of HPV vaccine administered during the 2018 and 2019 campaigns. This analysis evaluated the cost of Zimbabwe's national HPV vaccine introduction. METHODS: A retrospective, incremental, ingredients-based cost analysis from the provider perspective was conducted in 2018 and 2019. Financial and economic cost data were collected at district and health facility levels using a two-stage cluster sampling approach and four cost dimensions: program activity, resource input, payer, and administrative level. Costs are presented in 2020 US$ in total and per dose. RESULTS: The total weighted costs for combined district and health facility administrative levels were US$ 828,731 (financial) and US$ 2,060,943 (economic). For service delivery, the total weighted cost per dose was US$ 0.16 (financial) and US$ 0.59 (economic). The program activities with the largest share of total weighted financial cost were training (37% of total) and service delivery (30%), while the largest shares of total weighted economic costs were service delivery (45%) and training (19%). Efforts by VHWs to reach OOS girls resulted in an additional US$ 2.99 in financial cost per dose and US$ 7.79 in economic cost per dose. CONCLUSION: The service delivery cost per dose was lower than that documented in the pilot program cost analysis in Zimbabwe and studies elsewhere, reflecting a campaign delivery approach that spread fixed costs over a large vaccination cohort. The additional cost of reaching OOS girls with the HPV vaccine was documented for the first time in low- and middle-income countries, which may provide information on potential costs for other countries.

INTRODUCTION: In 2018, Senegal introduced human papillomavirus (HPV) vaccine into its routine immunization program for all nine-year-old girls nationwide. We evaluated the costs of Senegal's introduction of HPV vaccine via this delivery approach. METHODS: We conducted a retrospective, incremental, ingredients-based cost evaluation from the provider perspective. The study timeframe included Senegal's first planning meeting in 2018 through data collection in early 2020. We collected costs from all involved units at the national and regional levels. A multi-stage cluster sampling approach was used to obtain a nationally representative sample of districts and health facilities. Weights were applied to costs from sampled units to estimate costs across all units. The cost evaluation was based on four dimensions: program activity, resource input, payer, and administrative level. Total costs were divided by the number of HPV doses administered to determine cost per dose and per dimension. RESULTS: Excluding vaccine program activity costs, the total financial and economic delivery costs of Senegal's HPV vaccination program were US$ 1,152,351 and US$ 2,838,466, respectively (US$ 3.07 and US$ 7.56 per dose, respectively). A total of 375,608 HPV vaccine doses were administered during the cost evaluation. Training and per diem represented the largest shares of financial costs. Service delivery and personnel time accounted for the largest shares of economic costs. By administrative level, district and health facility levels had the largest shares of financial and economic costs, respectively. Senegal's Ministry of Health accounted for the largest share of financial and economic costs. Including vaccine program activity costs (US$ 4.68/per dose), the total financial cost was US$ 2,911,343 (US$ 7.75 per dose). CONCLUSION: This cost evaluation can support Senegal's future vaccine introductions and inform other countries planning to introduce HPV vaccine nationwide. These findings support previous costing studies which anticipated potential economies of scale during the transition from HPV vaccine pilot demonstration projects to national introduction.

On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras. | | Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions (e.g., hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes) and the use of certain immunosuppressive medications (1). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated medical treatments, such as systemic corticosteroids and other immunomodulatory drugs (e.g., tocilizumab), which impair the immune response against mold infections (2). In India, an apparent increase in mucormycosis cases (which was referred to by the misnomer “black fungus”) was attributed to COVID-19 (3).

OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy are not optimal, however, antigen tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis. METHODS: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 to and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and antigen test. RESULTS: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analyzed in this study, 94 (59%) were diagnosed using only an antigen assay. CD4 cell count data was available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200 and 90 (66%) had counts <50 CD4 cells per µL. Antiretroviral therapy utilization at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs. CONCLUSION: More than half of the patients in this study were diagnosed only by rapid laboratory antigen tests. A high percent of the patients had advanced HIV disease.

BACKGROUND: Enteric fever is endemic in Nepal and its economic burden is unknown. The objective of this study was to estimate the cost of illness due to enteric fever (typhoid and paratyphoid) at selected sites in Nepal. METHODS: We implemented a study at 2 hospitals in Nepal to estimate the cost per case of enteric fever from the perspectives of patients, caregivers, and healthcare providers. We collected direct medical, nonmedical, and indirect costs per blood culture-confirmed case incurred by patients and their caregivers from illness onset until after enrollment and 6 weeks later. We estimated healthcare provider direct medical economic costs based on quantities and prices of resources used to diagnose and treat enteric fever, and procedure frequencies received at these facilities by enrolled patients. We collected costs in Nepalese rupees and converted them into 2018 US dollars. RESULTS: We collected patient and caregiver cost of illness information for 395 patients, with a median cost of illness per case of $59.99 (IQR, $24.04-$151.23). Median direct medical and nonmedical costs per case represented ~3.5% of annual individual labor income. From the healthcare provider perspective, the average direct medical economic cost per case was $79.80 (range, $71.54 [hospital B], $93.43 [hospital A]). CONCLUSIONS: Enteric fever can impose a considerable economic burden on patients, caregivers, and health facilities in Nepal. These new estimates of enteric fever cost of illness can improve evaluation and modeling of the costs and benefits of enteric fever-prevention measures.

BACKGROUND: We conducted a cost of illness study to assess the economic burden of pediatric enteric fever (typhoid and paratyphoid) in Bangladesh. Results can inform public health policies to prevent enteric fever. METHODS: The study was conducted at 2 pediatric health facilities in Dhaka. For the patient and caregiver's perspective, we administered questionnaires on costs incurred from illness onset until the survey dates to caregivers of patients with blood culture positive cases at enrollment and 6 weeks later to estimate the direct medical, direct nonmedical, and indirect costs. From the perspective of the health care provider, we collected data on quantities and prices of resources used by the 2 hospitals to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Bangladeshi takas and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: Among the 1772 patients from whom we collected information, the median cost of illness per case of enteric fever from the patient and caregiver perspective was US $64.03 (IQR: US $33.90 -$173.48). Median direct medical and nonmedical costs per case were 3% of annual labor income across the sample. From the perspective of the healthcare provider, the average direct medical cost per case was US $58.64 (range: US $37.25 at Hospital B, US $73.27 at Hospital A). CONCLUSIONS: Our results show substantial economic burden of enteric fever in Bangladesh, with higher costs for patients receiving inpatient care. As antimicrobial resistance increases globally, the cost of illness could increase, due to more expensive and potent drugs required for treatment.

BACKGROUND: The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan. METHODS: We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later. From the health care provider perspective, we collected data on quantities and prices of resources used at 3 of the hospitals, to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Pakistani rupees and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: We collected patient and caregiver information for 1029 patients with blood culture-confirmed enteric fever or with a nontraumatic terminal ileal perforation, with a median cost of illness per case of US $196.37 (IQR, US $72.89-496.40). The median direct medical and nonmedical costs represented 8.2% of the annual labor income. From the health care provider perspective, the estimated average direct medical cost per case was US $50.88 at Hospital A, US $52.24 at Hospital B, and US $11.73 at Hospital C. CONCLUSIONS: Enteric fever can impose a considerable economic burden in Pakistan. These new estimates of the cost of illness of enteric fever can improve evaluation and modeling of the costs and benefits of enteric fever prevention and control measures, including typhoid conjugate vaccines.

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert(®) MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

This article presents a selection of practical issues, questions, and tradeoffs in methodological choices to consider when conducting a cost of illness (COI) study on enteric fever in low- to lower-middle-income countries. The experiences presented are based on 2 large-scale COI studies embedded within the Surveillance for Enteric Fever in Asia Project II (SEAP II), in Bangladesh, Nepal, and Pakistan; and the Severe Typhoid Fever Surveillance in Africa (SETA) Program in Burkina Faso, Ethiopia, Ghana, and Madagascar. Issues presented include study design choices such as controlling for background patient morbidity and healthcare costs, time points for follow-up, data collection methods for sensitive income and spending information, estimating enteric fever-specific health facility cost information, and analytic approaches in combining patient and health facility costs. The article highlights the potential tradeoffs in time, budget, and precision of results to assist those commissioning, conducting, and interpreting enteric fever COI studies.

BACKGROUND: Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used. METHODS AND PRINCIPAL FINDINGS: A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing. CONCLUSIONS/SIGNIFICANCE: We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs.

BACKGROUND: Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas. METHODS: Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and >/=65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates. RESULTS: Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged >/=65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000). CONCLUSIONS: Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.

BACKGROUND: On April 29, 2015, the Florida Department of Health in Miami-Dade County (DOH-Miami-Dade) was notified by a local dermatologist of three patients with suspect nontuberculous mycobacterial (NTM) infection after receiving tattoos at a local tattoo studio. METHODS: DOH-Miami-Dade conducted interviews and offered testing, described below, to tattoo studio clients reporting rashes. Culture of clinical isolates and identification were performed at the Florida Bureau of Public Health Laboratories (BPHL). Characterization of NTM was performed by the Centers for Disease Control and Prevention (CDC) and the United States Food and Drug Administration (FDA), respectively. Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analyses were used to construct a phylogeny among 21 Mycobacterium isolates at FDA. RESULTS: Thirty-eight of 226 interviewed clients were identified as outbreak-associated cases. Multivariate logistic regression revealed individuals who reported grey tattoo ink in their tattoos were 8.2 times as likely to report a rash [95% CI: 3.07-22.13]. Multiple NTM species were identified in clinical and environmental specimens. Phylogenetic results from environmental samples and skin biopsies indicated that two M. fortuitum isolates (greywash ink and a skin biopsy) and 11 M. abscessus isolates (five from the implicated bottle of greywash tattoo ink, two from tap water, and four from skin biopsies) were indistinguishable. In addition, M. chelonae was isolated from five unopened bottles of greywash ink provided by two other tattoo studios in Miami-Dade County. CONCLUSIONS: WGS and SNP analyses identified the tap water and the bottle of greywash tattoo ink as the sources of the NTM infections.

OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level. RESULTS: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively). CONCLUSIONS: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4(+) T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guerin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated. Gene ontology pathway analysis identified inhibition of IFN-gamma signaling, cellular proliferation, and the Th1 pathway. Targeted real-time quantitative PCR after methyl-specific endonuclease digestion confirmed DNA hypermethylation of the transcription factors BATF3, ID2, STAT5A, IRF5, PPARg, RUNX2, IRF4, and NFATC1 and cytokines or cytokine receptors IFNGR1, TNFS11, RELT (TNF receptor), IL12RB2, and IL12B (p < 0.001; Sidak-Bonferroni). Functional blockage of the IFN-gamma signaling pathway was confirmed, with helminth-infected individuals having decreased upregulation of IFN-gamma-inducible genes (Mann-Whitney p < 0.05). Hypomethylation of the IL-4 pathway and DNA hypermethylation of the Th1 pathway was confirmed by Ag-specific multidimensional flow cytometry demonstrating decreased TB-specific IFN-gamma and TNF and increased IL-4 production by CD4+ T cells (Wilcoxon signed-rank p < 0.05). In S. haematobium-infected individuals, these DNA methylation and immune phenotypic changes persisted at least 6 mo after successful deworming. This work demonstrates that helminth infection induces DNA methylation and immune perturbations that inhibit TB-specific immune control and that the duration of these changes are helminth specific.

Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp.) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species [1,2]. In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication and shedding via in vivo bioluminescent imaging, viral culture and real time PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million (uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2 million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1.4 million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Excessive and/or risky alcohol use resulted in $249 billion in economic costs in 2010 (1) and >88,000 deaths in the United States every year from 2006 to 2010 (2). It is associated with birth defects and disabilities (e.g., fetal alcohol spectrum disorders [FASDs]), increases in chronic diseases (e.g., heart disease and breast cancer), and injuries and violence (e.g., motor vehicle crashes, suicide, and homicide).dagger Since 2004, the U.S. Preventive Services Task Force (USPSTF) has recommended alcohol misuse screening and brief counseling (also known as alcohol screening and brief intervention or ASBI) for adults aged ≥18 years (3). section sign Among adults, ASBI reduces episodes of binge-level consumption, reduces weekly alcohol consumption, and increases compliance with recommended drinking limits in those who have an intervention in comparison to those who do not (3). A recent study suggested that health care providers rarely talk with patients about alcohol use (4). To estimate the prevalence of U.S. adults who reported receiving elements of ASBI, CDC analyzed 2014 Behavioral Risk Factor Surveillance System (BRFSS) data from 17 states paragraph sign and the District of Columbia (DC). Weighted crude and age-standardized overall and state-level prevalence estimates were calculated by selected drinking patterns and demographic characteristics. Overall, 77.7% of adults (age-standardized estimate) reported being asked about alcohol use by a health professional in person or on a form during a checkup, but only 32.9% reported being asked about binge-level alcohol consumption (3). Among binge drinkers, only 37.2% reported being asked about alcohol use and advised about the harms of drinking too much, and only 18.1% reported being asked about alcohol use and advised to reduce or quit drinking. Widespread implementation of ASBI and other evidence-based interventions could help reduce excessive alcohol use in adults and related harms.

Purpose: Using the Academy of Nutrition and Dietetics benchmarks as a framework, this study examined childcare providers' (Head Start [HS], Child and Adult Care Food Program [CACFP] funded, and non-CACFP) perspectives regarding communicating with parents about nutrition to promote children's health. Design: Qualitative. Setting: State-licensed center-based childcare programs. Participants: Full-time childcare providers (n = 18) caring for children 2 to 5 years old from varying childcare contexts (HS, CACFP funded, and non-CACFP), race, education, and years of experience. Methods: In-person interviews using semi-structured interview protocol until saturation were achieved. Thematic analysis was conducted. Results: Two overarching themes were barriers and strategies to communicate with parents about children's nutrition. Barriers to communication included - (a) parents are too busy to talk with providers, (b) parents offer unhealthy foods, (c) parents prioritize talking about child food issues over nutrition, (d) providers are unsure of how to communicate about nutrition without offending parents, and (e) providers are concerned if parents are receptive to nutrition education materials. Strategies for communication included - (a) recognize the benefits of communicating with parents about nutrition to support child health, (b) build a partnership with parents through education, (c) leverage policy (federal and state) to communicate positively and avoid conflict, (d) implement center-level practices to reinforce policy, and (e) foster a respectful relationship between providers and parents. Conclusion: Policy and environmental changes were recommended for fostering a respectful relationship and building a bridge between providers and parents to improve communication about children's nutrition and health.

BACKGROUND: Alcohol is a teratogen.* Prenatal alcohol exposure is associated with a range of adverse reproductive outcomes and can cause fetal alcohol spectrum disorders (FASDs) characterized by lifelong physical, behavioral, and intellectual disabilities. FASDs are completely preventable if a woman does not drink alcohol while pregnant. METHODS: CDC analyzed data from the 2011-2013 National Survey of Family Growth to generate U.S. prevalence estimates of risk for an alcohol-exposed pregnancy for 4,303 nonpregnant, nonsterile women aged 15-44 years, by selected demographic and behavioral factors. A woman was considered at risk for an alcohol-exposed pregnancy during the past month if she had sex with a male, drank any alcohol, and did not (and her partner did not with her) use contraception in the past month; was not sterile; and had a partner (or partners) not known to be sterile. RESULTS: The weighted prevalence of alcohol-exposed pregnancy risk among U.S. women aged 15-44 years was 7.3%. During a 1-month period, approximately 3.3 million women in the United States were at risk for an alcohol-exposed pregnancy. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Alcohol use in pregnancy is associated with low birthweight, preterm birth, birth defects, and developmental disabilities. Women of reproductive age should be informed of the risks of alcohol use during pregnancy, and contraception should be recommended, as appropriate, for women who do not want to become pregnant. Women wanting a pregnancy should be advised to stop drinking at the same time contraception is discontinued. Health care providers should advise women not to drink at all if they are pregnant or there is any chance they might be pregnant. Alcohol misuse screening and behavioral counseling (also known as alcohol screening and brief intervention) is recommended for all adults in primary care, including reproductive-aged and pregnant women, as an evidenced-based approach to reducing alcohol consumption among persons who consume alcohol in excess of the recommended guidelines.

One of the great pleasures of being the Editor in Chief of Preventing Chronic Disease: Public Health Research, Practice, and Policy (PCD) is to read the papers submitted by the next generation of public health professionals for the annual PCD Student Contest. This year was no exception. We received 59 papers on a range of critical public health topics that used novel analytic methods. In collaboration with members of the Editorial Board, it is my pleasure to announce that Nelly Mejia at the Pardee RAND Graduate School has won the 2015 PCD Student Contest. In this paper, Mejia and colleagues describe their analysis of the association between living in a food desert and eating fruits and vegetables (1). Understanding the influence of food deserts on public health is critical to designing, implementing, and evaluating the impact of policy and environmental changes to improve access to nutritious foods. | Much of the published literature has documented both the prevalence of food deserts and disparities in access to nutritious foods (2–5). In the past several years, there has been a substantial effort to place farmers markers in areas considered to be food deserts (4–6). These interventions have documented some success; however, there are a number remaining challenges. Access to healthier foods is necessary but not sufficient to improve nutrition and mitigate the short-term and long-term health effects of suboptimal nutritional intake. Interventions must also address issues of preparation of these healthier foods for consumption. Access and purchasing behavior are first steps in changing dietary intake.

BACKGROUND: Since 2004, the uptake of seasonal influenza vaccines in Latin America and the Caribbean has markedly increased. However, vaccine effectiveness (VE) is not routinely measured in the region. We assessed the feasibility of using routine surveillance data collected by sentinel hospitals to estimate influenza VE during 2012 against laboratory-confirmed influenza hospitalizations in Costa-Rica, El Salvador, Honduras and Panama. We explored the completeness of variables needed for VE estimation. METHODS: We conducted the pilot case-control study at 23 severe acute respiratory infections (SARI) surveillance hospitals. Participant inclusion criteria included children 6 months-11 years and adults ≥60 years targeted for vaccination and hospitalized for SARI during January-December 2012. We abstracted information needed to estimate target group specific VE (i.e., date of illness onset and specimen collection, preexisting medical conditions, 2012 and 2011 vaccination status and date, and pneumococcal vaccination status for children and adults) from SARI case-reports and for children ≤9 years, inquired about the number of annual vaccine doses given. A case was defined as an influenza virus positive by RT-PCR in a person with SARI, while controls were RT-PCR negative. We recruited 3 controls per case from the same age group and month of onset of symptoms. RESULTS: We identified 1,186 SARI case-patients (342 influenza cases; 849 influenza-negative controls), of which 994 (84 %) had all the information on key variables sought. In 893 (75 %) SARI case-patients, the vaccination status field was missing in the SARI case-report forms and had to be completed using national vaccination registers (36 %), vaccination cards (30 %), or other sources (34 %). After applying exclusion criteria for VE analyses, 541 (46 %) SARI case-patients with variables necessary for the group-specific VE analyses were selected (87 cases, 236 controls among children; 64 cases, 154 controls among older adults) and were insufficient to provide precise regional estimates (39 % for children and 25 % for adults of minimum sample size needed). CONCLUSIONS: Sentinel surveillance networks in middle income countries, such as some Latin American and Caribbean countries, could provide a simple and timely platform to estimate regional influenza VE annually provided SARI forms collect all necessary information.