The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (<1000 copies/ mL) rates during the COVID-19 pandemic in 12 United States President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries. Data for children (0-9 years) and adolescents (10-19 years) on VLC and VLS were analyzed for 12 sub-Saharan African (SSA) countries between 2019 (pre-COVID-19) and 2020 (during COVID-19). We report the number of viral load (VL) tests, and percent change in VLC and VLS for patients on ART. For 12 countries, 181,192 children had a VL test during the pre-COVID-19 period compared with 177,683 December 2020 during COVID-19. VLC decreased from 68.8% to 68.3% overall. However, 9 countries experienced an increase ranging from a 0.7%-point increase for Tanzania and Zimbabwe to a 15.3%-point increase for Nigeria. VLS increased for all countries from 71.2% to 77.7%. For adolescents the number with a VL test increased from 377,342 to 402,792. VLC decreased from 77.4% to 77.1%. However, 7 countries experienced an increase ranging from 1.8% for Mozambique to 13.8% for Cameroon. VLS increased for all countries from 76.8% to 83.8%. This analysis shows variation in HIV VLC across 12 SSA countries. VLS consistently improved across all countries demonstrating resilience of countries during 2020. Countries should continue to improve clinical outcomes from C/ALHIV despite service disruptions that may occur during pandemic response.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2(nd) most accurate model measured by WIS in 2021-22 and the 5(th) most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication.

OBJECTIVES: Innovations to improve public sanitation facilities, especially in healthcare facilities (HCFs) in low-income countries, are limited. SaTo pans represent novel, largely untested, modifications to reduce odour and flies and improve acceptability of HCF sanitation facilities. We conducted a pilot project to evaluate acceptability, cleanliness, flies and odour within latrines in 37 HCFs in Kisumu, Kenya, randomised into intervention (SaTo pan modifications) and control arms by sub-county and HCF level. METHODS: At baseline (pre-intervention) and endline (>3 months after completion of SaTo pan installations in latrines in intervention HCFs), we surveyed users, cleaners and in-charges, observed odour and cleanliness, and assessed flies using fly tape. Unadjusted difference-in-difference analysis compared changes from baseline to endline in patient-reported acceptability and observed latrine conditions between intervention and control HCFs. A secondary assessment compared patient-reported acceptability following use of SaTo pan versus non-SaTo pan latrines within intervention HCFs. RESULTS: Patient-reported acceptability of latrines was higher following the intervention (baseline: 87%, endline: 96%, p = 0.05). However, patient-reported acceptability was also high in the control arm (79%, 86%, p = 0.34), and the between-arm difference-in-difference was not significant. Enumerator-observed odour declined in intervention latrines (32%-14%) compared with controls (36%-51%, difference-in-difference ratio: 0.32, 95% confidence interval: 0.12-0.84), but changes in flies, puddling of urine and visible faeces did not differ between arms. In the secondary assessment, fewer intervention than control latrines had patient-reported flies (0% vs. 26%) and odour (18% vs. 50%), and reported satisfaction was greater. Most cleaners reported dropholes and floors were easier to clean in intervention versus controls; limited challenges with water for flushing were reported. CONCLUSIONS: Our results suggest SaTo pans may be acceptable by cleaners and users and reduce odour in HCF sanitation facilities, though challenges exist and further evaluation with larger sample sizes is needed.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause.

We agree with Tamohiko Sato and colleagues that a paucity of ferritin measurements to detect iron deficiency in high-income, middle-income, and low-income countries restricts how well research can quantify the magnitude of the disease burden and prevent and treat the disease. Following Sato and colleagues’ suggestions, we reanalysed ferritin concentration data from the US National Health and Nutrition Examination Survey (NHANES) by age, body-mass index, and income and found no meaningful correlations. In our Article,1 we proposed a method to derive physiologically based ferritin thresholds for iron deficiency among apparently healthy young children and non-pregnant women. We concluded that this approach needs validation in non-US populations before specific threshold values are adopted. Although Sato and colleagues highlight the scarcity of ferritin data for Japan, there is also a paucity of data in the USA for populations at high risk of iron deficiency, hindering surveillance and clinical practice. NHANES measures ferritin but does not collect blood among infants younger than 12 months. Ferritin is an acute phase protein and should be adjusted for inflammation, but NHANES does not measure inflammation in all age groups consistently. Sample sizes for pregnant women are small, requiring the combining of data from approximately 10 years for dependable estimates; after 2013, NHANES stopped recording the trimester of pregnancy. The US Public Health Task Force has also emphasised the paucity of prevalence data for iron deficiency anaemia among pregnant women.2 Analysis of electronic health records for first-trimester pregnancies found that anaemia screening is virtually universal, but ferritin screening for iron deficiency is not,3 despite recommendations by the American College of Obstetrics and Gynecologists.4 We continue to search for suitable anonymised databases to examine the proposed method for deriving physiologically based thresholds for serum ferritin concentration for iron deficiency among apparently healthy individuals. Having found that some national datasets from other countries have prohibitive restrictions on their use, we welcome any suggestions of publicly available and representative ferritin data.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms.

INTRODUCTION: In 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), with CDC as a major U.S. government implementing agency, began providing HIV antiretroviral therapy (ART) worldwide. Through suppression of HIV viral load, effective ART reduces morbidity and mortality among persons with HIV infection and prevents vertical and sexual transmission. METHODS: To describe program impact, data were analyzed from all PEPFAR programs and from six countries that have conducted nationally representative Population-based HIV Impact Assessment (PHIA) surveys, including PEPFAR programmatic data on the number of persons with HIV infection receiving PEPFAR-supported ART (2004-2022), rates of viral load coverage (the proportion of eligible persons with HIV infection who received a viral load test) and viral load suppression (proportion of persons who received a viral load test with <1,000 HIV copies per mL of blood) (2015-2022), and population viral load suppression rates in six countries that had two PHIA surveys conducted during 2015-2021. To assess health system strengthening, data on workforce and laboratory systems were analyzed. RESULTS: By September 2022, approximately 20 million persons with HIV infection in 54 countries were receiving PEPFAR-supported ART (62% CDC-supported); this number increased 300-fold from the 66,550 reported in September 2004. During 2015-2022, viral load coverage more than tripled, from 24% to 80%, and viral load suppression increased from 80% to 95%. Despite increases in viral load suppression rates and health system strengthening investments, variability exists in viral load coverage among some subpopulations (children aged <10 years, males, pregnant women, men who have sex with men [MSM], persons in prisons and other closed settings [persons in prisons], and transgender persons) and in viral load suppression among other subpopulations (pregnant and breastfeeding women, persons in prisons, and persons aged <20 years). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Since 2004, PEPFAR has scaled up effective ART to approximately 20 million persons with HIV infection in 54 countries. To eliminate HIV as a global public health threat, achievements must be sustained and expanded to reach all subpopulations. CDC and PEPFAR remain committed to tackling HIV while strengthening public health systems and global health security.

INTRODUCTION: External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasibility study for conducting an EQA scheme for influenza serology methods. METHODS: We invited participant laboratories from industry, contract research organizations (CROs), academia and public health institutions who regularly conduct hemagglutination inhibition (HAI) and microneutralization (MN) assays and have an interest in serology standardization. In total 16 laboratories returned data including 19 data sets for HAI assays and 9 data sets for MN assays. RESULTS: Within run analysis demonstrated good laboratory performance for HAI, with intrinsically higher levels of intra-assay variation for MN assays. Between run analysis showed laboratory and strain specific issues, particularly with B strains for HAI, whilst MN testing was consistently good across labs and strains. Inter-laboratory variability was higher for MN assays than HAI, however both assays showed a significant reduction in inter-laboratory variation when a human sera pool is used as a standard for normalization. DISCUSSION: This study has received positive feedback from participants, highlighting the benefit such an EQA scheme would have on improving laboratory performance, reducing inter laboratory variation and raising awareness of both harmonized protocol use and the benefit of biological standards for seasonal influenza serology testing.

BACKGROUND: The US President's Emergency Plan for AIDS Relief's (PEPFAR) first implemented pre-exposure prophylaxis (PrEP) for HIV prevention through the Determined, Resilient, Empowered, AIDS-Free, Mentored and Safe (DREAMS) partnership in 2016. PrEP is a critical intervention to achieve the main objective of DREAMS, reducing new HIV infections among 15-14 year old adolescent girls and young women (AGYW) in 15 high HIV burdened countries. METHODS: We describe uptake of PrEP among AGYW in PEPFAR. Most PrEP programs screened persons who tested HIV-negative for eligibility and offered PrEP as part of combination prevention with follow-up, including repeat HIV testing and counseling, at 3-month intervals. Platforms providing comprehensive services for AGYW were also leveraged. We examined two PEPFAR monitoring indicators, using the FY20Q4 Monitoring, Evaluation, Reporting (MER) indicator dataset to assess progress in PrEP uptake, and descriptive narratives to understand successes and challenges from fiscal year 2017 to 2020. To assess coverage, we calculated the PrEP to Need ratio (PnR) using a published methodology. RESULTS: From FY2017 to FY2020, 576570 total clients initiated PrEP and the number of PEPFAR countries offering PrEP doubled from 12 to 24. Of 360073 (62% of total) initiations among women, 52% were among AGYW with steady increases from year to year. Among all AGYW, 20-24-year-old women represented a significantly higher proportion of PrEP initiators than adolescents (15-19years) (64 versus 36%, P  < 0.05). Of all 186985 PrEP initiations among AGYW, 99% were in DREAMS countries. Barriers, such as low demand and adherence, were addressed through outreach efforts, including mobile sites, use of technology to educate and support AGYW, media campaigns, and engaging peers in program implementation. We saw a 2.5-fold increase in PrEP uptake among AGYW from 2018 to 2019; by 2020, all DREAMS countries were implementing PrEP. However, PrEP coverage among AGYW in DREAMS countries remains low (PnR range: 0-4.1); only two have a PnR greater than 1 where there were more PrEP users than new HIV diagnoses. CONCLUSION: PrEP uptake among AGYW has grown since 2016; however, challenges remain. Tools to improve adherence are needed to improve PrEP persistence among AGYW. National policies to facilitate greater PrEP uptake among adolescents would be beneficial. A greater need for PrEP in DREAMS countries is evident and if realized, will contribute to epidemic control.

The DREAMS (Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe) Partnership, a public-private partnership launched by the United States President's Emergency Plan for AIDS Relief (PEPFAR), represents the largest investment in comprehensive HIV prevention for adolescent girls and young women (AGYW) ever made in a single global initiative. This paper describes the evolution of programming over time using the triangulation of multiple data sources to develop and refine an impactful program, as well as to improve efficacy and resource investment. Methods of analysis used to evolve this programming include reviews of literature on behavioral, biomedical and structural interventions, and HIV vulnerability; PEPFAR program data; external implementation science and impact studies;observations from site visits; in-depth reviews of program materials; and inputs from AGYW and other stakeholders. Key program improvements made in response to this real-time data use are described, including the rationale for programmatic changes and the evidence base for continual program refinements. This review emphasizes the importance and process of implementing the most effective combination of structural and biomedical HIV prevention programming, based on the best available science, while also adapting to local context in a way that does not compromise effectiveness or violate core implementation principles. Data from research and evaluation are critical to move the HIV prevention field toward more impactful and efficient programming responsive to the lived realities of AGYW. A central tenant to using these data sources effectively is the inclusion of AGYW in decision-making throughout the planning and implementation of programming.

OBJECTIVE: Worldwide unmet need for contraception remains high at 21.6%. As access to health facilities is one of the potential barriers to contraceptive uptake, the aim of our study was to evaluate the effect of distance to a health facility, according to its service availability, on contraceptive uptake among married Turkish women. METHODS: To calculate respondents' distance to a health facility, we used data from a household survey conducted among married women, as well as data from a health facility survey conducted among the facilities that were visited for contraceptive services by the respondents. The data were collected from the Istanbul area of Turkey under the Willows Impact Evaluation project in 2018. Health facilities were categorised according to contraceptive availability and the accurate distance from respondents' homes to each type of health facility was calculated. Logistic regression was used to estimate the effect of distance to each type of health facility on uptake of each type of contraception. RESULTS: The prevalence of overall contraceptive use among urban Turkish women was 71.9%. The most common method was withdrawal (32.5%), followed by the intrauterine device (IUD) (14.9%) and male condoms (12.4%). Distance to a health facility that did not provide long-acting contraception was not associated with any type of contraceptive use. On the other hand, distance to a health facility that provided long-acting contraception was negatively associated with the use of long-acting methods such as the IUD but was positively associated with the use of short-acting contraception such as condoms. CONCLUSION: The effect of distance to a health facility on contraceptive use significantly differed according to contraceptive availability at the facility. Further distance to a health facility that provided long-acting contraception decreased the use of long-acting contraception but had a substitute effect on the use of short-acting contraception. We conclude that when women face an accessibility barrier to the provision of long-acting contraception, they modify their behaviour by shifting from long- to short-acting contraception, which is less effective.

Background: Maternal Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination provides antibody transfer to newborn infants and may affect their antibody response to the primary vaccination series. This study aimed to assess the effect of Tdap vaccination during pregnancy on infant antibody response to the whole cell pertussis (DTwP) primary series. Methods: Plasma from 318 pregnant women (243 Tdap-vaccinated and 75 unvaccinated) and their infants (cord blood) was collected at delivery; infant blood was again collected at 2 and 7 months, before and after their primary DTwP series. Anti-pertussis toxin (PT), pertactin (PRN), filamentous hemagglutinin (FHA), fimbriae 2/3 (FIM) and adenylate cyclase toxin (ACT) IgG antibodies were quantified by a microsphere-based multiplex antibody capture assay and anti-PT neutralizing antibodies by the Real Time Cell analysis system. Results: Infant geometric mean concentrations (GMCs) of IgG anti-Tdap antigens were significantly higher (p < 0.001) among the Tdap-vaccinated (PT: 57.22 IU/mL; PRN: 464.86 IU/mL; FHA: 424.0 IU/mL), versus the unvaccinated group (4 IU/mL, 15.43 IU/mL, 31.99 IU/mL, respectively) at delivery. Anti-FIM and ACT GMCs were similar between the two groups. At 2 months of age, anti-PT, PRN, and FHA GMCs remained higher (p < 0.001) in the Tdap-vaccinated group (12.64 IU/mL; 108.76 IU/mL; 87.41 IU/mL, respectively) than the unvaccinated group (1.02 IU/mL; 4.46 IU/mL; 6.89 IU/mL). However, at 7 months, after receiving the third DTwP dose, the anti-PT GMC was higher (p = 0.016) in the unvaccinated group (7.91 IU/mL) compared to the vaccinated group (2.27 IU/mL), but without differences for anti-PRN, FHA, FIM and ACT GMCs. Conclusion: Elevated antibody levels suggest that maternal Tdap vaccination might protect infants until 2 months of age. Reduced anti-PT levels at 7 months indicate potential blunting of immune response in infants. Surveillance would help determine if blunting alters vaccine immunity and impacts pertussis prevention in infants. © 2021 The Authors

BACKGROUND: Pertussis remains an important global public health concern, despite the presence of extensive immunization programs. Incidence and severity of pertussis are typically higher in neonates and young infants. As a strategy to protect these young infants, maternal vaccination with Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) has been recommended in Brazil. The objective of this study was to evaluate the effects of Tdap vaccination during pregnancy on the anti-pertussis toxin (PT) IgG response in mothers and their infants at birth. MATERIAL AND METHODS: Maternal and cord blood samples were collected from vaccinated (n=243) and unvaccinated (n=75) pregnant women, at the time of delivery, from July 2015 to August 2016 in Sao Paulo, Brazil. Anti-PT IgG antibodies were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) and geometric mean concentrations (GMC) were calculated. Relationship between timing of vaccination and antibody concentrations were evaluated. RESULTS: Maternal and cord blood GMCs among the vaccinated group were 5.4 and 5.6 fold higher [66.5 International Units (IU)/mL and 89.8IU/mL] compared to the unvaccinated group (12.4IU/mL and 16.1IU/mL), respectively (p<0.001). Higher anti-PT IgG GMCs were observed when vaccination occurred >/=60days before delivery compared to <60days, suggesting that vaccination early in the third trimester may be more effective than later in pregnancy. CONCLUSION: Tdap maternal vaccination results in significantly higher anti-PT IgG in newborn infants and supports the current recommendation of the Brazilian Immunization Program.

Background.: The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We report on a cluster of N. gonorrhoeae isolates demonstrating high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Methods.: Eight N. gonorrhoeae isolates collected from 7 patients on Oahu seen 21 April through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 mul/mL and elevated ceftriaxone MICs (≥0.125 mug/mL). Isolates were sent to University of Washington and CDC for confirmatory agar dilution testing, and sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. Results.: All isolates had azithromycin MICs >16 microg/mL and 5 had ceftriaxone MICs = 0.125 microg/mL by agar dilution. All isolates were beta-lactamase positive, and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use and no male patients reported male sex partners. All patients were successfully treated. Conclusions.: This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.

Background The US Centers for Disease Control and Prevention ensured adequate performance of the routine triglycerides methods used in Japan by a chromotropic acid reference measurement procedure used by the Centers for Disease Control and Prevention lipid standardization programme as a reference point. We examined standardized data to clarify the performance of routine triglycerides methods. Methods The two routine triglycerides methods were the fluorometric method of Kessler and Lederer and the enzymatic method. The methods were standardized using 495 Centers for Disease Control and Prevention reference pools with 98 different concentrations ranging between 0.37 and 5.15 mmol/L in 141 survey runs. The triglycerides criteria for laboratories which perform triglycerides analyses are used: accuracy, as bias ≤5% from the Centers for Disease Control and Prevention reference value and precision, as measured by CV, ≤5%. Results The correlation of the bias of both methods to the Centers for Disease Control and Prevention reference method was: y (%bias) = 0.516 x (Centers for Disease Control and Prevention reference value) -1.292 ( n = 495, R2 = 0.018). Triglycerides bias at medical decision points of 1.13, 1.69 and 2.26 mmol/L was -0.71%, -0.42% and -0.13%, respectively. For the combined precision, the equation y (CV) = -0.398 x (triglycerides value) + 1.797 ( n = 495, R2 = 0.081) was used. Precision was 1.35%, 1.12% and 0.90%, respectively. It was shown that triglycerides measurements at Osaka were stable for 36 years. Conclusions The epidemiologic laboratory in Japan met acceptable accuracy goals for 88.7% of all samples, and met acceptable precision goals for 97.8% of all samples measured through the Centers for Disease Control and Prevention lipid standardization programme and demonstrated stable results for an extended period of time.

In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in Sao Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naive children aged 12-23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratiox100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8-21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8-11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7-99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in Sao Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs.

INTRODUCTION: Following introduction of routine infant rotavirus vaccination, severe diarrhea hospitalization rates declined among children aged <5 years throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in countries that self-finance immunization programs. The objective of this study was to examine rotavirus vaccine impact on diarrhea admission rates among children aged <5 years in Brazil's public health system, according to area-based measures of human development in the state of Sao Paulo, Brazil. METHODS: Ecological analysis of public health system hospitalization rates for acute gastroenteritis among children aged <5 years in the state of Sao Paulo, Brazil, according to five categories of municipal development based on a modified Human Development Index for municipalities. Acute gastroenteritis hospitalization rates among children aged <5 years after national rotavirus vaccine introduction (2008-2011) were compared to rates in pre-vaccine years (2000-2005) to calculate percent decline in rates (1-rate ratio) and 95% confidence intervals (CI) for each municipal development category. Direct hospitalization costs during the two periods were compared. RESULTS: Annual rates declined by 40% (95% CI, 39-42%) from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus vaccination to 377 per 100,000 post-vaccination among children aged <5 years and 50% (95% CI, 48-52%) from 1009 to 505 per 100,000 among infants. Highest rates were observed in least developed municipalities. Significant declines of 26-52% among children <5 years and 41-63% among infants were observed in all categories of municipal development. Lower diarrhea hospitalization rates resulted in annual savings of approximately 2 million USD for the state of Sao Paulo. Savings in direct hospitalization costs benefitted municipalities in all five categories. CONCLUSION: The introduction of rotavirus vaccination was associated with substantial reductions of diarrhea-related admissions at all levels of municipal development in Sao Paulo State, Brazil.

We describe an outbreak of simultaneous Clostridium difficile and norovirus infections in a long-term-care facility. Thirty patients experienced acute gastroenteritis, and four had co-infection with identical C. difficile 027 and genotype II.4 New Orleans norovirus strains. Co-occurring infection requires improved understanding of risk factors, clinical impact, and testing strategies.

The prevalence of Bartonella species was investigated among wild carnivores of the suborder Caniformia, including 15 Japanese badgers (Meles anakuma), 8 Japanese martens (Martes melampus), 2 Japanese weasels (Mustela itatsi), 1 Siberian weasel (Mustela sibirica), 171 raccoon dogs (Nyctereutes procyonoides), and 977 raccoons (Procyon lotor) in Japan. Bartonella bacteria were isolated from one Japanese badger (6.7%) and from one Japanese marten (12.5%); however, no Bartonella species was found in other representatives of Caniformia. Phylogenetic analysis was based on concatenated sequences of six housekeeping genes (16S rRNA, ftsZ, gltA, groEL, ribC, and rpoB) and sequence of the 16S-23S internal transcribed spacer region. The sequence analysis indicated that the isolate derived from the Japanese badger (strain JB-15) can represent a novel Bartonella species and the isolate from the Japanese marten (strain JM-1) was closely related to Bartonella washoensis. This is the first report on isolation of Bartonella from badger and marten.

PURPOSE: Management of sepsis in critically ill patients remains difficult and requires prolonged intensive care. Genetic testing has been proposed as a strategy to identify patients at risk for adverse outcome of critical illnesses. Therefore, we wished to determine the influence of heredity on predisposition to poor outcome and on duration of ventilator support of intensive care unit (ICU) patients. METHODS: A study was conducted from July 2001 to December 2005 in heterogeneous population of patients from 12 US ICUs represented by the Genetic Predisposition to Severe Sepsis (GenPSS) archive. In 1057 Caucasian critically ill patients with SAPS II probability of survival of >0.2 in the US, six functional single nucleotide polymorphisms in relation to inflammatory cytokines and innate immunity (rs1800629, rs16944, rs1800795, rs1800871, rs2569190, and rs909253) were evaluated in terms of mortality and ventilator free days. RESULTS: The AA homozygote of TNF(-308) (rs1800629) was most over-represented in the deceased patient group (P=0.015 with recessive model). The carriage of the TNF(-308)*AA genotype showed significantly higher odds ratio of 2.67(1.29-5.55) (P=0.008) after adjustment with the covariates. However, the presence of 1, 2, or 3 acute organ dysfunctions was larger prognostic factors for the adverse outcome (OR(95%CI)=2.98(2.00-4.45), 4.01(2.07-7.77), or 19.95(4.99-79.72), P<0.001 for all). Kaplan-Mayer plot on ventilator duration of TNF(-308)*AA patient significantly diverged from that of TNF(-308)*(GG+GA) ((AA v GG+GA), Adjusted HR(95%CI)=2.53(1.11-5.79) with Cox regression, P=0.028). CONCLUSIONS: TNF(-308)*AA is significantly associated with susceptibility to adverse outcome and to longer ventilator duration. Therefore, heredity likely affects both predisposition to ICU prognosis as well as the resource utilization.

Cattle are major hosts of Cryptosporidium spp. Cryptosporidiosis in neonatal calves is associated with retarded growth, weight loss and calf mortality, and zoonotic infections in humans. In many areas, cow-calf grazing system is an important beef cattle rearing method with distinct advantages in terms of cost and the labor required. However, few epidemiologic studies of Cryptosporidium spp. have been conducted in this system, especially using molecular diagnostic tools. To understand the transmission of Cryptosporidium spp. in a grazing system, we followed cryptosporidiosis on a grazing farm in Osaki City, Miyagi Prefecture, in northwest Japan for one year. Fecal samples were collected from Japanese Black and Japanese Shorthorn cattle and examined by PCR-RFLP and sequence analyses. Of 113 fecal samples collected in October 2010, 23 (20%) were positive for Cryptosporidium, including 15 samples (13%) having C. bovis, 6 (5%) having C. ryanae, and 2 (2%) having mixed infections of both species. Additionally, C. bovis or C. ryanae was detected on all other sampling dates involving smaller numbers of animals. The infection rate of C. bovis was significantly different among age groups, and calve-to-calve infection might be the major route of cryptosporidiosis transmission in beef cattle. Interestingly, one animal had C. bovis infection or re-infection for one year. Our results suggest that C. bovis and C. ryanae are distributed in Japan, but might have low level of detection in grazing beef cattle.

The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic disease until a blood screening test for the detection of preclinical infection is validated for human use.

Seven isolates of a slowly growing, non-chromogenic Mycobacterium species were obtained from sputum and bronchial lavage fluid samples from elderly patients in different regions of Japan. These isolates were distinguished from related non-tuberculous species by colony morphology, positive results for Tween hydrolysis, catalase at 68 degrees C, nitrate reductase and pyrazinamidase and negative results for semi-quantitative catalase, urease and arylsulfatase. The mycolic acid pattern obtained by HPLC revealed a single cluster of late-eluting mycolic acids similar to but different from those of Mycobacterium malmoense ATCC 29571(T). The 16S rRNA gene, 16S-23S internal transcribed spacer (ITS), rpoB and hsp65 sequences were unique in comparison with those of other mycobacteria. Comparison of 16S rRNA gene sequences showed that the isolates were most closely related to Mycobacterium tuberculosis H37Rv(T) (21 base differences in 1508 bp; 98.6 % 16S rRNA gene sequence similarity). A representative strain, GTC 2738(T), showed 91.9 % rpoB sequence similarity with Mycobacterium marinum strain M, 95 % hsp65 sequence similarity with Mycobacterium kansasii CIP 104589(T) and 81.1 % 16S-23S ITS sequence similarity with Mycobacterium gordonae ATCC 14470(T). Phylogenetic analysis of concatenated sequences of the 16S rRNA, rpoB and hsp65 genes showed that strain GTC 2738(T) was located on a distinct clade adjacent to M. tuberculosis, M. ulcerans and M. marinum, with bootstrap values of 81 %. DNA-DNA hybridization demonstrated less than 70 % reassociation with type strains of genetically related species and supported the novel species status of the isolates. On the basis of this evidence, a novel species with the name Mycobacterium shinjukuense sp. nov. is proposed. The type strain, isolated from a sputum sample, is strain GTC 2738(T)( = JCM 14233(T) = CCUG 53584(T)).

BACKGROUND: Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil. METHODS: We used case-series and case-control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records. RESULTS: We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case-control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico--an increase by a factor of 1.9 to 2.6 - was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries. CONCLUSIONS: RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).