Enteropathogen antibody dynamics and force of infection among children in low-resource settings.

Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles demonstrated significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest antibody response can be used to measure population-level transmission of diverse enteropathogens in serologic surveillance

Lip rounding in Amoy and Mandarin high vowels: maximum dispersion, or adequate separation

There are two hypotheses about the relationship between phonological contrasts and phonetic feature scales. Some phoneticians propose that values are chosen so that contrasting phonemes are maximally separated, e.g., Lilijencrants and Lindblom, 1972, while others claim that they need only to be adequately separated, e.g., Maddieson, 1977. This paper tests the competing hypotheses by comparing lip position in Mandarin [i], [y], [u] with that of Amoy [i] and [u]. According to adequate separation, the lip spreadness/roundness of Mandarin will be more extreme than that of Amoy, since there are three high vowels in Mandarin but only two in Amoy. According to the maximum dispersion hypothesis, the degree of roundness should be the same in both languages. Amoy and Mandarin data were collected from three bilingual speakers. The results support the Adequate Separation Theory. This paper also tests Wood's (1986) claim that in a language with two high rounded vowels, /u/ and /y/, /u/ is more rounded than /y/. The result shows that this claim is not necessarily true

The vehicle emissions and performance monitoring system: analysis of tailpipe emissions and vehicle performance

This paper describes tailpipe emission results generated by the Vehicle Performance and Emissions Monitoring system (VPEMS). VPEMS integrates on-board emissions and vehicle/driver performance measurements with positioning and communications technologies, to transmit a coherent spatio-temporally referenced dataset to a central base station in near real time. These results focus on relationships between tailpipe emissions of CO, CO2, NOx and speed and acceleration. Emissions produced by different driving modes are also presented. Results are generally as one would expect, showing variation between vehicle speed, vehicle acceleration and emissions. Data is based upon a test run in central London on urban streets with speeds not exceeding about 65 km/h. The results presented demonstrate the capabilities of the system. Various issues remain with regard to validation of the data and expansion of the system capability to obtain additional vehicle performance data

Investigation on Prevalence of Canine Trypanosomiasis in the Conservation Areas of Bwindi-Mgahinga and Queen Elizabeth in Western Uganda

Nowadays, despite the instauration of several control strategies, animal trypanosomiasis continues to be reported all over Uganda. Few canine African trypanosomiasis (CAT) studies have been carried out, yet dogs are known Trypanosoma reservoirs that share identical home ranges with livestock and serve as parasite link between livestock and humans. This study evaluates the prevalence of CAT in dogs in the Bwindi-Mgahinga and Queen Elizabeth conservation areas. This information will be useful to evaluate the possible role of dogs in the transmission cycle of Trypanosoma species in livestock and wild animals. Trypanosome tests using microhematocrit centrifugation/dark ground microscopy technique (MHCT) followed by conventional polymerase chain reaction (cPCR) were performed in blood samples collected from identified indigenous dogs (n = 124). Four (3.23%) out of 124 dogs were positive for CAT. One dog was positive with Trypanosoma congolense and three with T. vivax. There was no significant statistical difference in CAT prevalence rate in relation to dog's age, sex, and site (P > 0.05). This study reports what we believe is the first time detection of T. congolense and T. vivax in the indigenous dogs found in the Bwindi-Mgahinga and Queen Elizabeth conservation areas in western Uganda. The noticed T. congolense and T. vivax could be responsible for both canine and animal trypanosomiasis and represent a serious threat to the livestock industry. Therefore, there is a need for continuous trypanosomiasis surveillance and integrated management in contiguity to wildlife reserves

Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition

Acknowledgments This work was funded in part by the William and Melinda Gates Foundation, award 42917 to JPN and OCS; US National Institutes of Health grants 5R01HG005220 to HCB, 5R01HG004885 to MP; US National Science Foundation Graduate Research Fellowship award DGE0750616 to JNP; AWW and JP are funded by The Wellcome Trust (Grant No. WT098051).Peer reviewedPublisher PD

Prevalence of classic, MLB-clade and VA-clade Astroviruses in Kenya and The Gambia.

BACKGROUND: Infectious diarrhea leads to significant mortality in children, with 40 % of these deaths occurring in Africa. Classic human astroviruses are a well-established etiology of diarrhea. In recent years, seven novel astroviruses have been discovered (MLB1, MLB2, MLB3, VA1/HMO-C, VA2/HMO-B, VA3/HMO-A, VA4); however, there have been few studies on their prevalence or potential association with diarrhea. METHODS: To investigate the prevalence and diversity of these classic and recently described astroviruses in a pediatric population, a case-control study was performed. Nine hundred and forty nine stools were previously collected from cases of moderate-to-severe diarrhea and matched controls of patients less than 5 years of age in Kenya and The Gambia. RT-PCR screening was performed using pan-astrovirus primers. RESULTS: Astroviruses were present in 9.9 % of all stool samples. MLB3 was the most common astrovirus with a prevalence of 2.6 %. Two subtypes of MLB3 were detected that varied based on location in Africa. In this case-control study, Astrovirus MLB1 was associated with diarrhea in Kenya, whereas Astrovirus MLB3 was associated with the control state in The Gambia. Classic human astrovirus was not associated with diarrhea in this study. Unexpectedly, astroviruses with high similarity to Canine Astrovirus and Avian Nephritis Virus 1 and 2 were also found in one case of diarrhea and two control stools respectively. CONCLUSIONS: Astroviruses including novel MLB- and VA-clade members are commonly found in pediatric stools in Kenya and The Gambia. The most recently discovered astrovirus, MLB3, was the most prevalent and was found more commonly in control stools in The Gambia, while astrovirus MLB1 was associated with diarrhea in Kenya. Furthermore, a distinct subtype of MLB3 was noted, as well as 3 unanticipated avian or canine astroviruses in the human stool samples. As a result of a broadly reactive PCR screen for astroviruses, new insight was gained regarding the epidemiology of astroviruses in Africa, where a large proportion of diarrheal morbidity and mortality occur

Effectiveness of monovalent rotavirus vaccine against hospitalization with acute rotavirus gastroenteritis in Kenyan children

Rotavirus remains a leading cause of diarrheal illness and death among children worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children. Between July-2014 and December-2017, we conducted surveillance for acute gastroenteritis (AGE) in three hospitals across Kenya. We analysed data from children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history. We compared RV1 coverage among those who tested rotavirus-positive (cases) versus rotavirus-negative (controls) using multivariable logistic regression; effectiveness was 1-adjusted odds ratio for vaccination x100%. Among 677 eligible children, 110 (16%) were rotavirus-positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had received 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI]: 35-80%); for children aged <12 months 67% (95%CI: 30-84%) and children aged ≥12 months 72% (95%CI: 10-91%). Significant effectiveness was seen in children with normal weight-for-age (84% [95%CI: 62-93%]), length/height-for-age (75% [95%CI: 48-88%]) and weight-for-length/height (84% [95%CI: 64-93%]); however, no protection was found among underweight, stunted nor wasted children. RV1 in the routine Kenyan immunization program provides significant protection against rotavirus AGE hospitalization. Protection was sustained beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus vaccine uptake and nutritional status are important to maximize vaccine benefit. [Abstract copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Rotavirus group : a genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018

Background Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010–June 2014) and post- (July 2014–December 2018) RVA vaccine introduction. Methods Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. Results We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. Conclusion Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity

Galectin-3C Inhibits Tumor Growth and Increases the Anticancer Activity of Bortezomib in a Murine Model of Human Multiple Myeloma

Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology