Epidemiology and serotype distribution of Streptococcus pneumoniae carriage among influenza-like illness cases in metropolitan Vientiane, Lao PDR: a community-based cohort study.

Background: Data on the epidemiology of Streptococcus pneumoniae among influenza-like illness (ILI) cases, particularly in low- and middle-income countries are scarce. This study assessed the prevalence, risk factors and serotype distribution of S. pneumoniae carriage among ILI cases in metropolitan Vientiane, Lao People's Democratic Republic. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced among infants in October 2013. Methods: Active ILI surveillance was conducted through weekly phone calls in an open community-based cohort study (April 2015-February 2019), involving 5,690 participants from 1,142 randomly selected households. Participants reporting ILI symptoms provided a nasopharyngeal swab and answered a questionnaire. S. pneumoniae and serotype pneumococcal-positive samples were screened by Multiplex PCR assays. Chi-squared tests and generalized linear mixed models were used to test for variables associated with pneumococcal positivity. Results: Among 1,621 ILI episodes, 269 (16.6%) tested positive for nasopharyngeal pneumococcal carriage, with the highest prevalence (55.4%) in children under 5 years. Pneumococcal carriage was significantly associated with concurrent detection of Hemophilus influenzae (adjusted odds ratio [aOR]: 6.93; 95% CI: 2.10-22.9) and exposure to household cigarette smoke (aOR: 1.65; 95% CI: 1.07-2.54). PCV13 serotypes accounted for 37.8% of all pneumococcal isolates. Detection of PCV13 serotypes among ILI cases aged under 5 years declined significantly between 2015/16 and 2018/19. Conclusions: Community-based surveillance of S. pneumoniae among ILI cases complement surveillance at healthcare facilities to provide a more complete picture of pneumococcal carriage. Our findings contribute also to the growing body of evidence on the effects of PCV13 introduction on circulating serotypes and their potential replacement.

Bacterial and viral etiology of acute respiratory infection among the Forcibly Displaced Myanmar Nationals (FDMNs) in fragile settings in Cox's Bazar- a prospective case-control study.

The leading infectious cause of death in children worldwide is lower acute respiratory infection (LARI), particularly pneumonia. We enrolled a total of 538 acute respiratory infection (ARI) cases according to WHO criteria and age-sex matched 514 controls in the Forcibly Displaced Myanmar National (FDMN) refugee camps in Cox's Bazar, Bangladesh, between June 2018 and March 2020 to investigate the role of bacteria, viruses, and their co-infection patterns and observe Streptococcus pneumoniae (S. pneumoniae) serotype distribution. According to the etiological findings, children ≤5 years of age have a higher bacterial positivity (90%) and viral positivity (34%) in nasopharyngeal samples (NPS) compared to those >5 years of age, in both ARI cases as well as for the control group. Among the bacteria, S. pneumoniae was predominant in both cases and controls (85% and 88%). Adenovirus (ADV)(34), influenza virus A and B (IFV-A, B)(32,23), and respiratory syncytial virus (RSV)(26) were detected as the highest number among the viruses tested for the ARI cases. The total number of viruses was also found higher in ≤5 years of age group. Within this group, positive correlation was observed between bacteria and viruses but negative correlation was observed between bacteria. Both single and co-infection for viruses were found higher in the case group than the control group. However, co-infection was significantly high for Streptococcus aureus (S. aureus) and Haemophilus influenzae b (H. influenza b) (p<0.05). Additionally, semi-quantitative bacterial and viral load was found higher for the ARI cases over control considering Cycle threshold (Ct)≤30. Pathogen identification from blood specimens was higher by qRT-PCR than blood culture (16% vs 5%, p<0.05). In the S. pneumoniae serotype distribution, the predominant serotypes in ARI cases were 23F, 19A, 16F, 35B, 15A, 20 and 10F, while 11A, 10A, 34, 35A and 13 serotypes were predominant in the control group. Pathogen correlation analysis showed RSV positively correlated with human metapneumovirus (HMPV), S. aureus and H. influenza b while S. pneumoniae was negatively correlated with other pathogens in ≤5 years age group of ARI cases. However, in >5 years age group, S. aureus and H. influenza b were positively correlated with IFVs, and S. pneumoniae was positively correlated with HMPV and ADV. Logistic regression data for viruses suggested among the respondents in cases were about 4 times more likely to be RSV positive than the control. Serotype distribution showed 30% for PCV10 serotypes, 41% for PCV13 and 59% for other serotypes. Also, among the 40 serotypes of S. pneumoniae tested, the serotypes 22F, Sg24, 9V, 38, 8, and 1 showed strong positive correlation with viruses in the case group whereas in the control group, it was predominant for serotypes 14, 38, 17F and 39 ARI cases were prevalent mostly in monsoon, post-monsoon, and winter periods, and peaked in September and October. Overall these region-specific etiological data and findings, particularly for crisis settings representing the FDMNs in Cox's Bazar, Bangladesh, is crucial for disease management and disease prevention control as well as immunization strategies more generally in humanitarian crisis settings.

Efficacy of careHPV™ human papillomavirus screening versus conventional cytology tests for the detection of precancerous and cancerous cervical lesions among women living with HIV-1 in Lao People's Democratic Republic.

BACKGROUND: In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. AIMS: The objective of this cross-sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid-based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV-1). MATERIALS & METHODS: Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid-based cytology, careHPV™ test, and HPV-16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. RESULTS: Of the 631 women with follow-up, 331 were human papillomavirus (HPV) negative. High-grade squamous intraepithelial lesions were found in 37 women, biopsy-proven high-grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high-grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4-8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2-6.5). careHPV™ and HPV-16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4-89.5) and specificity (92.2%; 95% CI: 89.8-94.2). HPV-16 was the most frequently detected genotype. CONCLUSIONS: careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV-1 because of higher prevalence of chronic HPV in this population.

Serotypes of Streptococcus pneumoniae in Children Aged <5 Years Hospitalized With or Without Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study.

BACKGROUND: Improving knowledge regarding Streptococcus pneumoniae distribution in pneumonia cases is important to better target preventive and curative measures. The objective was to describe S. pneumoniae serotypes in children with or without pneumonia. METHODS: It was a case-control study carried out in 8 developing and emerging countries between 2010 and 2014. Cases were children aged <5 years admitted to the hospital for pneumonia. Controls were children admitted for surgery or routine outpatient care. RESULTS: In nasopharyngeal samples, S. pneumoniae were detected in 68.2% of the cases and 47.5% of the controls (P < .001). Nasopharyngeal carriage was associated with a higher risk of being a case in 6/8 study sites (adjusted odds ratio ranged from 0.71 [95% confidence interval [CI], .39-1.29; P = .26] in India [Pune/Vadu] to 11.86 [95% CI, 5.77-24.41; P < .001] in Mongolia). The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were more frequently detected in cases with nasopharyngeal carriage (67.1%) than in controls with nasopharyngeal carriage (54.6%), P < .001. Streptococcus pneumoniae was detected in blood by polymerase chain reaction in 8.3% of the cases. Of 34 cases with an S. pneumoniae serotype detected in blood, 27 (79%) had the same serotype in the nasopharyngeal sample. CONCLUSIONS: The results confirm the assumption that the isolate carrying or causing disease in an individual is of the same serotype. Most serotypes independently associated with nasopharyngeal carriage or pneumonia are covered by PCV13, suggesting that increased PCV coverage would reduce the burden of S. pneumoniae-related pneumonia.

Mechanisms behind TB, HBV, and HIV chronic infections.

Immune evasion is critical for pathogens to maintain their presence within hosts, giving rise to chronic infections. Here, we examine the immune evasion strategies employed by three pathogens with high medical burden, namely, tuberculosis, HIV and HBV. Establishment of chronic infection by these pathogens is a multi-step process that involves an interplay between restriction factor, innate immunity and adaptive immunity. Engagement of these host defences is intimately linked with specific steps within the pathogen replication cycles. Critical host factors are increasingly recognized to regulate immune evasion and susceptibility to disease. Fuelled by innovative technology development, the understanding of these mechanisms provides critical knowledge for rational design of vaccines and therapeutic immune strategies.

Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study.

Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.

Report of the 2014 Cent Gardes HIV Vaccine Conference-Part 2: Cell-mediated immunity, mucosal protection, and clinical trials: Fondation Mérieux Conference Center, Veyrier du Lac, France, 5-7 October, 2014.

The 2014 Cent Gardes Conference took place on October 5-7, 2014, at the Fondation Mérieux Conference Center, on the shores of the Annecy Lake and aimed to review the progress and promise of HIV vaccines. The elicitation of broadly neutralizing antibodies (bNAbs), their use in passive immunization, as well as their genetic delivery (vector immunoprophylaxis) by a recombinant Adenovirus-associated virus (AAV) vector were reviewed in a preceding article [1]. Approaches to the elicitation of long-lasting T cell or mucosal immunity were also discussed and are now reviewed here. The possibility of eliciting mucosal IgAs was discussed, since it was demonstrated that transcytosis-blocking IgAs can protect monkeys against repeated vaginal challenge with a pathogenic chimeric simian and human immunodeficiency virus (SHIV). The possibility of purging the HIV reservoirs from HIV-infected persons and developing a cure of the disease was also discussed.

Report of the 2014 Cent Gardes HIV Vaccine Conference - Part 1: Neutralizing Antibodies; Fondation Mérieux Conference Center, Veyrier du Lac, France, 5-7 October 2014.

The 2014 Cent Gardes Conference took place on October 5-7 at the Fondation Mérieux Conference Center, on the shores of the Annecy Lake. The aim of the meeting was to review progress in the field of HIV vaccines during the last two years and to explore the promising avenues of future research. The identification of broadly neutralizing antibodies (bNAbs) able to neutralize a majority of circulating HIV strains has encouraged hopes for a highly effective "universal" HIV vaccine. Analysis of B-cell maturation that leads to the production of bNAbs, however, appears extremely complex, and not easily reproduced by classical active immunization. The use of bNAbs for passive immunization is thus being explored as an alternative, either for immunotherapy or prophylaxis. Their delivery by a recombinant adenovirus-associated virus (AAV), also known as vector immunoprophylaxis, has demonstrated proof-of-concept in animal models and is now in early stage clinical trials. Other approaches were discussed at the meeting, such as eliciting long-lasting T cell or mucosal immunity. In spite of remarkable progress, the quest for an efficacious HIV vaccine remains a daunting challenge.