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Background: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old.Methods: ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to <12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28-56 days after the additional dose of Rotarix or placebo.Results: Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events.Conclusions: An additional dose of Rotarix administered to Australian Aboriginal infants 6 to <12 months old increased the proportion with a vaccine seroresponse.Clinical Trials Registration: NCT02941107. [ABSTRACT FROM AUTHOR]

Background: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016.Methods: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing.Results: A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens.Conclusions: G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era. [ABSTRACT FROM AUTHOR]

Secretor status controls mucosal histo-blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings. Clinical Trials Registration. NCT01375647. [ABSTRACT FROM AUTHOR]

Background: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction.Methods: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018.Results: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction.Conclusions: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks. [ABSTRACT FROM AUTHOR]

Background: Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old.Methods: Articles published from January 1, 2006 to December 31, 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQRs).Results: We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR, 46-74) in rotavirus hospitalizations, 36% (IQR, 23-47) in AGE hospitalizations, and 36% (IQR, 28-46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR, 28-45) before rotavirus vaccine introduction and 20% (IQR, 20-20) 4 years after introduction.Conclusions: Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation. [ABSTRACT FROM AUTHOR]

Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Furthermore, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear. [ABSTRACT FROM AUTHOR]

In Tunisia, we observed that rotavirus P[8]-3 and P[4] strains in young children with gastroenteritis associate with secretor histo-blood group phenotype. In contrast, the emerging P[8]-4 strain, representing 10% of cases, was exclusively found in nonsecretor patients. Unlike VP8* from P[8]-3 and P[4] strains, the P[8]-4 VP8* protein attached to glycans from saliva samples regardless of the donor's secretor status. Interestingly, a high frequency of FUT2 enzyme deficiency (nonsecretor phenotype) was observed in the population. This may allow cocirculation of P[8]-3 and P[8]-4 strains in secretor and nonsecretor children, respectively. [ABSTRACT FROM AUTHOR]

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens. [ABSTRACT FROM AUTHOR]

Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8-10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi. [ABSTRACT FROM AUTHOR]

Background: Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low-resource countries.Methods: We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 infants aged 9-11 months to receive measles vaccine (MV), yellow fever vaccine (YFV), and meningococcal A conjugate vaccine (MenAV) with or without pentavalent rotavirus vaccine (PRV). We assessed the noninferiority (defined as a difference of ≤10%) of seroconversion and seroresponse rates to MV, YFV, and MenAV. We compared the seroresponse to PRV.Results: Seroconversion to MV occurred in 255 of 261 PRV recipients (97.7%) and 246 of 252 control infants (97.6%; difference, 0.1% [95% confidence interval {CI}, -4.0%-4.2%]). Seroresponse to YFV occurred in 48.1% of PRV recipients (141 of 293), compared with 52.2% of controls (153 of 293; difference, -4.1% [95% CI, -12.2%-4.0%]). A 4-fold rise in meningococcus A bactericidal titer was observed in 273 of 292 PRV recipients (93.5%) and 276 of 293 controls (94.2%; difference, -0.7% [95% CI, -5.2%-3.8%]). Rises in geometric mean concentrations of immunoglobulin A and immunoglobulin G antibodies to rotavirus were higher among PRV recipients (118 [95% CI, 91-154] and 364 [95% CI, 294-450], respectively), compared with controls (68 [95% CI, 50-92] and 153 [95% CI, 114-207], respectively).Conclusions: PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels.Clinical Trials Registration: NCT02286895. [ABSTRACT FROM AUTHOR]

Background: A spillover of simian foamy virus (SFV) to humans, following bites from infected nonhuman primates (NHPs), is ongoing in exposed populations. These retroviruses establish persistent infections of unknown physiological consequences to the human host.Methods: We performed a case-control study to compare 24 Cameroonian hunters infected with gorilla SFV and 24 controls matched for age and ethnicity. A complete physical examination and blood test were performed for all participants. Logistic regression and Wilcoxon signed rank tests were used to compare cases and controls.Results: The cases had significantly lower levels of hemoglobin than the controls (median, 12.7 vs 14.4 g/dL; P = .01). Basophil levels were also significantly lower in cases than controls, with no differences for other leukocyte subsets. Cases had significantly higher urea, creatinine, protein, creatinine phosphokinase, and lactate dehydrogenase levels and lower bilirubin levels than controls. Cases and controls had similar frequencies of general, cutaneous, gastrointestinal, neurological, and cardiorespiratory signs.Conclusions: The first case-control study of apparently healthy SFV-infected Cameroonian hunters showed the presence of hematological abnormalities. A thorough clinical and laboratory workup is now needed to establish the medical relevance of these observations because more than half of cases had mild or moderate anemia.Clinical Trials Registration: NCT03225794. [ABSTRACT FROM AUTHOR]

Background: Rotavirus is a common cause of acute gastroenteritis and has also been associated with generalized tonic-clonic afebrile seizures. Since rotavirus vaccine introduction, hospitalizations for treatment of acute gastroenteritis have decreased. We assess whether there has been an associated decrease in seizure-associated hospitalizations.Methods: We used discharge codes to abstract data on seizure hospitalizations among children <5 years old from the State Inpatient Databases of the Healthcare Cost and Utilization Project. We compared seizure hospitalization rates before and after vaccine introduction, using Poisson regression, stratifying by age and by month and year of admission. We performed a time-series analysis with negative binomial models, constructed using prevaccine data from 2000 to 2006 and controlling for admission month and year.Results: We examined 962899 seizure hospitalizations among children <5 years old during 2000-2013. Seizure rates after vaccine introduction were lower than those before vaccine introduction by 1%-8%, and rate ratios decreased over time. Time-series analyses demonstrated a decrease in the number of seizure-coded hospitalizations in 2012 and 2013, with notable decreases in children 12-17 months and 18-23 months.Conclusions: Our analysis provides evidence for a decrease in seizure hospitalizations following rotavirus vaccine introduction in the United States, with the greatest impact in age groups with a high rotavirus-associated disease burden and during rotavirus infection season. [ABSTRACT FROM AUTHOR]

Background: Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE.Methods: We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models.Results: Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels.Conclusions: Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE. [ABSTRACT FROM AUTHOR]

Background: In a multicountry birth cohort study, we describe rotavirus infection in the first 2 years of life in sites with and without rotavirus vaccination programs.Methods: Children were recruited by 17 days of age and followed to 24 months with collection of monthly surveillance and diarrheal stools. Data on sociodemographics, feeding, and illness were collected at defined intervals. Stools were tested for rotavirus and sera for antirotavirus immunoglobulins by enzyme immunoassays.Results: A total of 1737 children contributed 22646 surveillance and 7440 diarrheal specimens. Overall, rotavirus was detected in 5.5% (408/7440) of diarrheal stools, and 344 (19.8%) children ever had rotavirus gastroenteritis. Household overcrowding and a high pathogen load were consistent risk factors for infection and disease. Three prior infections conferred 74% (P < .001) protection against subsequent infection in sites not using vaccine. In Peru, incidence of rotavirus disease was relatively higher during the second year of life despite high vaccination coverage.Conclusions: Rotavirus infection and disease were common, but with significant heterogeneity by site. Protection by vaccination may not be sustained in the second year of life in settings with high burdens of transmission and poor response to oral vaccines. [ABSTRACT FROM AUTHOR]

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs).Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children.Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea. [ABSTRACT FROM AUTHOR]

Biomarkers of inflammation and immune activation were correlated with rotavirus vaccine responses in 68 human immunodeficiency virus type 1 (HIV-1)–infected (and 116 HIV-exposed but uninfected (HEU) African infants receiving pentavalent rotavirus vaccine (RV5) in a clinical trial. Prevaccination, HIV-1+ infants had significantly higher concentrations of interferon γ (IFNγ), interleukin1β, interleukin 2, interleukin 6, interleukin 10 (IL-10), and soluble CD14 compared with HEU infants. Postvaccination concentrations of neutralizing antibodies to RV5 were negatively correlated with prevaccination concentrations of IL-10 (RV5 surface proteins G1 and P1) and IFNγ (G1) in the HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not. Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA responses associated with protection from rotavirus disease. [ABSTRACT FROM AUTHOR]

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings. [ABSTRACT FROM AUTHOR]

Background:  Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings.Methods:  We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip.Results:  We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009).Conclusions:  The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. [ABSTRACT FROM AUTHOR]

Background: Rotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children.Methods: The present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (≤42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV.Results: A postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients.Conclusions: Unvaccinated neonates and infants ≤42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed. [ABSTRACT FROM AUTHOR]

The article offers information about studies on rotavirus vaccine and rotavirus strains, which are often classified according to the two surface capsid proteins, such as G (VP7) and P (VP4), that induce neutralizing antibodies. Other information related to surveillance systems in medicine and the development of a vaccine is presented.

The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene. We examined the impact of the APOBEC3B gene deletion in 14000 individuals from 5 human immunodeficiency virus type 1 (HIV-1) natural history cohorts. The hemizygous genotype had no effect on either acquisition of HIV-1 infection or progression to AIDS. However, the homozygous deletion was significantly associated with unfavorable outcomes for HIV-1 acquisition (odds ratio, 7.37; P = .024), progres- sion to AIDS (relative hazard, 4.01; P = .03), and viral set point (P = .04). These findings suggest that the loss of APO- BEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study. [ABSTRACT FROM AUTHOR]

Background. In China, 30 human cases of avian influenza A (H5N1) virus infection were identified through July 2008. We conducted a retrospective case-control study to identify risk factors for influenza H5N1 disease in China. Methods. A questionnaire about potential influenza H5N1 exposures was administered to 28 patients with influenza H5N1 and to 134 randomly selected control subjects matched by age, sex, and location or to proxies. Conditional logistic regression analyses were performed. Results. Before their illness, patients living in urban areas had visited wet poultry markets, and patients living in rural areas had exposure to sick or dead backyard poultry. In multivariable analyses, independent risk factors for influenza H5N1 were direct contact with sick or dead poultry (odds ratio [OR], 506.6 [95% confidence interval {CI}, 15.7-16319.6]; P < .001), indirect exposure to sick or dead poultry (OR, 56.9 [95% CI, 4.3-745.6]; P = .002), and visiting a wet poultry market (OR, 15.4 [95% CI, 3.0-80.2]; P = .001). Conclusions. To prevent human influenza H5N1 in China, the level of education about avoiding direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of influenza H5N1 at live poultry markets should be implemented. [ABSTRACT FROM AUTHOR]

Background. We conducted investigations in 2 villages in Cambodia where outbreaks of influenza H5N1 occurred among humans and poultry to determine the frequency of and risk factors for H5N1 virus transmission. Methods. During May 2006, ∼7 weeks after outbreaks of influenza H5N1 among poultry occurred, villagers living near households of 2 patients with influenza H5N1 were interviewed about potential H5N1 exposures and had blood samples obtained for H5N1 serological testing by microneutralization assay. A seropositive result was defined as an influenza H5N1 neutralizing antibody titer of ⩾1:80, with confirmation by Western blot assay. A case-control study was conducted to identify risk factors for influenza H5N1 virus infection. Control subjects, who had seronegative results of tests, were matched with H5N1-seropositive persons by village residence, households with an influenza H5N1-infected poultry flock, sex, and age. Results. Seven (1.0%) of 674 villagers tested seropositive for influenza H5N1 antibodies and did not report severe illness; 6 (85.7%) were male. The 7 H5N1-seropositive persons, all of whom were aged ⩽18 years, were younger than participants who tested seronegative for H5N1 antibodies (median age, 12.0 years vs. 27.4 years; P = .03) and were more likely than were the 24 control subjects to report bathing or swimming in household ponds (71.4% vs. 20.8%; matched odds ratio, 11.3; P = .03). Conclusions. Avian-to-human transmission of influenza H5N1 virus remains low, despite extensive poultry contact. Exposure to a potentially contaminated environment was a risk factor for human infection. [ABSTRACT FROM AUTHOR]

Background. Human leukocyte antigen (HLA) class I variation influences the progression of untreated human immunodeficiency virus (HIV) disease; however, it is not known whether HLA class I variation may influence clinical outcomes after initiation of highly active antiretroviral therapy (HAART). Methods. Associations between HLA class I genotypes and pretherapy clinical parameters were investigated in a cohort of 765 antiretroviral-naive adults initiating HAART. Cox proportional hazards regression was used to investigate the effects of HLA class I genotypes on time to suppression of the viral load to <500 HIV RNA copies/ mL, time to an increase in the CD4 cell count to >100 cells/mm³ above the baseline count, and time to nonaccidental death over a >5-year period after initiation of HAART. Results. Homozygosity at any HLA class I locus and possession of common HLA alleles were associated with a higher pretherapy viral load (P < .05). In multivariate analyses controlling for sociodemographic and clinical parameters at baseline, HLA class I homozygosity was significantly associated with a poorer CD4 cell response (P = .008), whereas possession of uncommon HLA alleles was associated with slower virologic suppression after initiation of HAART (P = .02). We observed no significant association between HLA parameters and time to nonaccidental death after initiation of HAART (P> .05, univariate analysis). Conclusion. HLA class I zygosity-dependent and frequency-dependent effects may influence short-term HAART outcomes, and, thus, they deserve further investigation. No effects of these HLA parameters on survival after initiation of HAART were observed. [ABSTRACT FROM AUTHOR]

To characterize a host polygenic profile associated with susceptibility to human T lymphotropic virus type I (HTLV-I) infection, we examined common variants in 11 immune-related genes among Jamaican children born to HTLV-I—seropositive mothers. Compared with HTLV-I seronegatives, haplotypes of IL6 (—660G/—635C/—236G) and IL10 (—6653C/—1116G) were significantly associated with HTLV-I infection in children independent of maternal provirus load and duration of breast-feeding (odds ratio [OR], 4.5 [95% confidence interval {CI}, 1.2–17.6], and OR, 3.5 [95% CI, 1.4–9.0], respectively). Our findings are the first, to our knowledge, to suggest that host variation in both proinflammatory and anti-inflammatory genes could influence susceptibility to HTLV-I infection. [ABSTRACT FROM AUTHOR]

Background. Considerable uncertainty remains as to whether early initiation of antiretroviral therapy (ART) in children with vertically acquired human immunodeficiency virus (HIV) infection increases the benefit in terms of immunological response. Methods. The association between immunological outcome and early initiation of and/or more-potent ART was investigated, using age-standardized z scores for CD4 cell counts (hereafter, ‘CD4 z scores’), in 131 HIV-infected children enrolled in the European Collaborative Study, a birth cohort study. Results. Median age at initiation of the most-potent ART was 4 years (range, 0.1–15.5 years). Initiation of treatment after 5 months of age resulted in nonsignificantly lower CD4 z scores 6 months after initiation. Time to a 20% increase in CD4 z score was associated with age at initiation of the most-potent ART (adjusted hazard ratios [AHRs], 0.37 [P<.01] and 0.43 [P = .05] for 5 months-5 years of age and 15 years of age, respectively, compared with <5 months of age), ethnicity (AHR, 0.48 [P = .01], for black vs. white), and highly active ART (HAART) with or without prior ART (AHRs, 3.16 [P<.01] and 3.95 [P<.001], vs. mono or dual ART, respectively). The risk of subsequent deterioration of CD4 z score was similar for children who initiated ART in different age groups (χ² = 0.824; P = .82). Conclusions. We confirm the effectiveness of HAART with respect to the recovery of CD4 cell count and suggest a benefit of initiating ART before the age of 5 months. Age at initiation of the most-potent ART was not associated with the likelihood of sustaining the recovery of CD4 cell count. [ABSTRACT FROM AUTHOR]

Metabolic and morphologic changes have been described in patients with human immunodeficiency virus (HIV) infection. In the short term, these disorders can be debilitating and may require medical intervention, including alterations in antiretroviral therapy regimens. The long-term consequences have not been fully realized, but are important, particularly in the era of durable HIV disease management with highly active antiretroviral therapy. This review focuses on 3 of the important morphologic or metabolic changes, namely alterations in body fat distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these disorders remains unknown due to varied definitions and difficulty in recognition of the conditions for both the patient and the clinician. Treatment regimens directed at these abnormalities are being developed, but clinical trials are needed to fully ascertain the efficacy and safety of such interventions. [ABSTRACT FROM AUTHOR]

Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for evidence of adipocyte apoptosis, the second after a randomized change to nevirapine (n = 8) or after remaining on a regimen of indinavir-based HAART (n = 6). Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end-labeling method. Patients who were switched to nevirapine had a significant decrease in insulinemia and a significant increase in the glucose: insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3 patients who were switched to nevirapine and in 3 who continued to receive indinavir but decreased in 2 patients switched to nevirapine and another 2 who continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to occur in lipotrophic areas of patients with HAART-associated lipodystrophy despite switching from indinavir to nevirapine, suggesting that such a strategy will be useless for reversal of lipoatrophy. [ABSTRACT FROM AUTHOR]

Evaluates the response of perinatally HIV-1-infected infants and children to highly active antiretroviral therapy (HAART), as measured by plasma HIV RNA levels, HIV-peripheral blood mononuclear cell (PBMC) cocultures and T cell differentiation markers. Effect of HAART on the coreceptor use of HIV-1 isolates recovered from PBMC and CD4 T cell reservoirs before and during therapy.

Presents a randomized, controlled phase II trial comparing escalating doses of subcutaneous interleukin-2 (IL-2) plus antiretrovirals versus antiretroviral alone in HIV-infected patients with CD4[sup +] cell counts of 350 per cubic millimeter. Effects of the T cell-derived cytokine IL-2 on the immune system; Efficacy of the treatment groups; Side effects of subcutaneous IL-2 administration.

Tests the hypothesis that chimeric toxins targeted to the HIV-1 envelope glycoprotein augment the in vivo activity of combination antiretroviral therapy in mice. Results demonstrating in vivo anti-HIV-1 efficacy for Env-targeted toxins; Findings supporting the potential therapeutic utility of chimeric toxins in combination with highly active antiretroviral therapy.

Assesses the effectiveness of highly active antiretroviral treatment (HAART) among HIV-positive persons. Survival analysis showing the proportion of patients with plasma HIV-1 RNA; Detection viral load in peripheral blood mononuclear cells.

Examines the immune response of HIV-positive persons undergoing an antiretroviral therapy. Measurement of protease inhibitor-containing triple therapy; Details of the strong suppression of RNA levels; Data indicating the long-term immunological recovery.

Investigates the immune restoration in patients at intermediate stages of HIV infection after initiation of a highly active antiretroviral therapy (HAART). Details of the progressive increase in both memory and naive T cells; Decrease in the expression of activation markers on CD8+ T cells.

Focuses on the identification of dual retroviral infection susceptibility with two distinct HIV type 2 isolates in a macaca nemestrina model. Factors that interfere with dual infection; Elements found to be uncorrelated with susceptibility to secondary challenges in the investigation.

Evaluates the use of zidovudine as additional antiretroviral therapy (ART) among HIV-seropositive pregnant women and their newborn infants. Factors that make ART beneficial in the prevention of mother-to-child transmission of HIV; Association of at least one mutation in the reverse transcriptase gene with reduced phenotypic susceptibility to zidovudine.

Determines whether coinfection of macaques with simian immunodeficiency virus (SIV) and simian T cell leukemia virus type 1 enhances virus burdens and disease progression. Frequency of virus isolation from peripheral blood mononuclear cells; Clinical course after infection; Serologic responses to retroviral infection.

Assesses the levels of several components of the tumor necrosis factor (TNF) system in plasma and in supernatants of peripheral blood mononuclear cells during highly active antiretroviral therapy (HAART) in HIV-infected patients. Association of TNF activation with virologic and immunologic treatment failure; Immunologic effects of HAART; Role of TNF-alpha activation in HIV infection.

Between 1972 and 1976, 585 persons attending methadone maintenance clinics at East Coast veterans hospitals were enrolled in a survey of hepatitis antibody prevalence. Sera were tested for human immunodeficiency virus (HIV) and human T lymphotropic virus (HTLV) using both HTLV-I and HTLV-II immunoblots. Clinical and death records were also reviewed. None of the sera had HIV antibodies (upper 95% confidence limit, 0.5%); however, 103 (18%) had reactivity to HTLV. The profile of reactivity suggested that these subjects had been exposed to HTLV-II rather than to HTLV-I. Prevalence was as high in the early 1970s as today and correlated with duration of drug use rather than age. Neither cancers, specific neurologic diseases, nor excess deaths from any cause (overall 14%) could be ascribed to seropositivity. Therefore, HTLV (probably HTLV-II) has been a common infection of drug users for many years but adverse outcomes following infection were not demonstrated. [ABSTRACT FROM AUTHOR]

The article offers information on the use of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for reduce the infectiousness of HIV-1–infected persons. As mentioned, the antiretroviral-based prevention, both ART and PrEP, are among the most promising strategies for reducing the number of new HIV-1 infections around the globe.

The article presents a report which determines HIV-1 subtype as a determinant of disease progression. It is posed that various factors, including plasma HIV-1 RNA level, degree of immune activation, age, CD4 cell count, and host genetics, add to determining the rate of progression of disease in an individual patient. Relative to this, it is also established that intrinsic viral properties may also affect progression rates. The report stated that HIV is classified into HIV-1 or HIV type 2 and groups HIV-1 M, N, and O.

The article discusses the data about three oncogenic agents, which includes an RNA retrovirus, a small DNA virus, and Helicobacter pylori; that have been thoroughly studied in previous researches identifying them as markers of human migrations. It discusses the geographic distribution and origin of the oncogenic agents by focusing on their genetic mutations, areas of endemicity, and molecular epidemiology. Moreover, it cites the study conducted by Cassar O. and colleagues that attempted to trace the ancestral roots of the HTLV-1 virus. Furthermore, it discusses the representation of Helicobacter pylori as a new and reliable determiner of ancient human migrations attributed to its high mutation and infection rate.

Background: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis.Methods: Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis.Results: Seroconversion (IgA ≥ 20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR, 0.04; 95% confidence interval [CI], .01-.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI, .25-.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings.Discussion: Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance. [ABSTRACT FROM AUTHOR]

The author explains how long-acting injectable antiretroviral (ARV) preparations have the potential to obviate the need for daily dosing, thereby improving adherence during exposure events, and, in theory, maximizing reductions in HIV infection incidence. The authors propose a base case rooted in an almost unthinkably high-incidence population, in which the cumulative lifetime probability of HIV acquisition is less than 60%.