Factors associated with hepatitis B vaccination in Laos: findings from the multiple indicator cluster surveys in 2011/12 and 2017.

Background: Within Laos, the vaccination coverage rates with the monovalent hepatitis B birth dose vaccine and hepatitis B antigen-containing combination vaccines remain stagnant with 75% and 64%, respectively, in 2021. In this study, we used data from the Multiple Indicator Cluster Surveys to identify possible factors that represent barriers for receiving these childhood vaccinations. Methods: Data from the Multiple Indicator Cluster Surveys in 2011/12 and 2017 were analysed to examine factors associated with receiving the hepatitis B-containing vaccines using regression modelling. Data analyses were conducted in R. Findings: In 2011/12, the weight-adjusted coverage rate for receiving the hepatitis B birth dose was 48%, while the coverage with the hepatitis B antigen-containing combination vaccine was 55.1% based on both vaccination documents and recall; compared to 69.3% and 59.4% respectively in 2017. Ethno-linguistic group, maternal education, healthcare utilization and wealth were associated with receiving the vaccinations against hepatitis B. Interpretation: National estimates of vaccination coverage rates can conceal country-specific regional or socio-economic variations. Children from Hmong-Mien households, from less wealthier households and whose mothers were less educated and were not able to or did not utilize healthcare were identified as being less likely to receive the vaccinations. These findings indicate the need for improving access to healthcare, in particular for minority groups. Funding: This work was supported by the Ministry of Foreign and European Affairs, Luxembourg and the Luxembourg Institute of Health (project "Luxembourg-Laos Partnership for Research and Capacity Building in Infectious Disease Surveillance").

Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern.

SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman's r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the "Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit" and the "Genscript cPass, kit" revealed an overall good correlation ranging from 0.8673 to -0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs.

Molecular characterization of measles viruses in Central African Republic, 2012-2016.

Despite being preventable through vaccination, measles is still one of the most important causes of morbidity and mortality in young children in Africa. In 2015, several African countries, including the Central African Republic (CAR), began implementing national measles elimination programs. However, measles remains a public health problem in Africa, particularly in the CAR. A retrospective study was conducted at the Institut Pasteur de Bangui, using blood samples (n = 255) and oral swabs (n = 7) collected between January 2012 and December 2016 from measles IgM-positive cases, to attempt genotyping of circulating measles virus strains. Overall, 50 samples were positive by real-time polymerase chain reaction, and 40 sequences of acceptable quality were obtained. The phylogenetic analysis showed that 38 strains belonged to genotype B3 suggesting that this genotype was endemic in the CAR during the study period. No genotype B2 sequences were detected, suggesting that this genotype is no longer present in the CAR.

Human Seasonal Influenza Viruses in Swine Workers in Lagos, Nigeria: Consequences for Animal and Public Health.

The influenza A virus has been scarcely investigated in pigs in Africa, with rare detection prior to 2009. The spread of A(H1N1)pdm09 changed the epidemiology due to frequent human-to-swine transmission and the emergence of various new reassortants. This study therefore aimed at estimating the level of circulation and characterizing influenza A viruses at the interface between swine workers, who are crucial players in the inter-species transmission of influenza A viruses, and their animals in several farms in Nigeria, a hub for pig production in Africa. This cross-sectional study showed that 24.6% (58/236) of the pig serum samples collected in 2013-2014 had anti-influenza A antibodies in the absence of vaccination programs, but none of the pig swabs (n = 1193) were positive according to RT-qPCR. Viral RNA was detected in 0.9% (2/229) of swine workers sampled at their place of work, and the strains were characterized as A(H1N1)pdm09 and seasonal A(H3N2). Our results highlight that more awareness of swine workers regarding the consequences of reverse zoonosis for animal and public health is warranted. Annual vaccination and the wearing of masks when experiencing influenza-like symptoms would help decrease influenza inter-species transmission, while surveillance should be adequately supported for early detection.

Low seroprotection against diphtheria and tetanus in Lao adolescents.

OBJECTIVES: There is currently no booster diphtheria or tetanus vaccine for Lao children before adolescence, despite international recommendations. We investigated seroprotection against diphtheria and tetanus among Lao adolescents. METHODS: Seven hundred seventy-nine serum samples were tested for anti-diphtheria and anti-tetanus antibodies. RESULTS: Overall, 25.8% of the adolescents had antibody titers corresponding to protection against diphtheria and 30.9% to sufficient immunity against tetanus. Female participants >16 years were more likely to be protected against diphtheria (p < 0.001) and tetanus (p < 0.029). CONCLUSION: Low protection against diphtheria and tetanus, possibly due to low vaccination coverage or antibody waning, suggests booster doses are warranted before adolescence.

Rubella virus infection in endothelial cells reduces angiogenesis via interferon beta-induced CXCL10.

Rubella virus (RuV) infection during pregnancy can lead to abortion, stillbirth, and embryonic defects, resulting in congenital rubella syndrome (CRS). It is estimated that there are still 100,000 cases of CRS per year in developing regions with a mortality rate of over 30%. The molecular pathomechanisms remain largely unexplored. Placental endothelial cells (EC) are frequently infected with RuV. RuV reduced the angiogenic and migratory capacity of primary human EC, as confirmed by treatment of EC with serum from RuV IgM-positive patients. Next generation sequencing analysis revealed the induction of antiviral interferon (IFN) type I and III and CXCL10. The RuV-induced transcriptional profile resembled the effects of IFN-ß treatment. The RuV-mediated inhibition of angiogenesis was reversed by treatment with blocking and neutralizing antibodies targeting CXCL10 and the IFN-ß receptor. The data identify an important role for antiviral IFN-mediated induction of CXCL10 in the control of EC function during RuV infection.

Hepatitis B virus and other transfusion-transmissible infections in child blood recipients in Lao People's Democratic Republic: a hospital-based study.

INTRODUCTION: Children requiring multiple blood transfusions are at high risk of transfusion-transmissible infections (TTIs). Lao People's Democratic Republic is a low-resource setting where donor blood screening faces challenges. This study aimed to determine the burden of TTIs in children in Vientiane Capital. METHODS: 300 children with transfusion history and 300 controls were recruited. In addition, 49 newly diagnosed transfusion recipients were followed for up to 12 months. Serum was tested for hepatitis B surface antigen and IgG antibodies against parvovirus B19, hepatitis B, C and E viruses. RESULTS: The patients had a similar prevalence of anti-hepatitis B core antibodies (56; 18.7%) and hepatitis B surface antigen (8; 2.7%) as the controls (58; 19.3% and 9; 3.0%, respectively). However, there was a higher prevalence of an antibody profile suggestive of hepatitis B vaccination (anti-hepatitis B surface antibody positive/anti-hepatitis B core antibody negative) in the transfused group (140/299; 46.8%) than in controls (77/300; 25.7%, p<0.01). All other markers were similar in the patients and controls or higher in the controls: anti-hepatitis C virus (2.7% and 3.3%, p=0.6), anti-hepatitis E virus (7.5% and 12.7%, p=0.006) and anti-parvovirus B19 (2.4% and 8.5%, p=0.001). The longitudinal cohort did not show an increase in any marker over time. CONCLUSION: Our results suggest no significant role of TTIs in Lao children. The higher prevalence of the hepatitis B vaccination profile in transfusion recipients showed that recommendations to vaccinate before commencing transfusions is at least partially implemented, although there is room for improvement.

Hepatitis E virus in Cuba: A cross-sectional serological and virological study in pigs and people occupationally exposed to pigs.

Surveillance of hepatitis E virus (HEV) in risk groups is an important strategy to monitor its circulation pattern and to timely detect changes thereof. The aims of this cross-sectional study were to estimate the prevalence of HEV infections in pigs and humans from different regions of the country, to identify risk factors for increasing anti-HEV IgG prevalence and to characterize HEV strains. The presence of anti-HEV antibodies was assessed by commercial ELISA in serum samples from the general population, farm and slaughterhouse employees, as well as pigs sampled in the three regions of Cuba from February to September 2016. Overall, individuals with occupational exposure to swine or swine products (70/248, 28.2%) were 4 times more likely to be seropositive compared to the general population (25/285, 8.7%; OR: 4.18; p < .001). Within the risk group, risk factors included age, number of years working in a professional activity with direct exposure to swine, geographic region and distance between residence and closest professional swine setting, while wearing gloves had a protective effect. Prevalence of total anti-HEV antibodies in swine was 88.2% (165/187) and HEV RNA was detected by real-time RT-PCR in 9.2% (16/173) swine stools. All HEV strains sequenced clustered within genotype 3. Some strains clearly belonged to subtype 3a, while another group of strains was related with subtypes 3b and 3 k but partial HEV sequences did not allow unequivocal subtype assignment. These findings suggest that the high HEV exposure in Cuban individuals with swine-related occupations could be due to enzootic HEV in certain regions, direct contact with infectious animals or their products as well as environmental contamination.

Evolutionary and temporal dynamics of emerging influenza D virus in Europe (2009-22).

Influenza D virus (IDV) is an emerging influenza virus that was isolated for the first time in 2011 in the USA from swine with respiratory illness. Since then, IDV has been detected worldwide in different animal species, and it was also reported in humans. Molecular epidemiological studies revealed the circulation of two major clades, named D/OK and D/660. Additional divergent clades have been described but have been limited to specific geographic areas (i.e. Japan and California). In Europe, IDV was detected for the first time in France in 2012 and subsequently also in Italy, Luxembourg, Ireland, the UK, Switzerland, and Denmark. To understand the time of introduction and the evolutionary dynamics of IDV on the continent, molecular screening of bovine and swine clinical samples was carried out in different European countries, and phylogenetic analyses were performed on all available and newly generated sequences. Until recently, D/OK was the only clade detected in this area. Starting from 2019, an increase in D/660 clade detections was observed, accompanied by an increase in the overall viral genetic diversity and genetic reassortments. The time to the most recent common ancestor (tMRCA) of all existing IDV sequences was estimated as 1995-16 years before its discovery, indicating that the virus could have started its global spread in this time frame. Despite the D/OK and D/660 clades having a similar mean tMRCA (2007), the mean tMRCA for European D/OK sequences was estimated as January 2013 compared to July 2014 for European D/660 sequences. This indicated that the two clades were likely introduced on the European continent at different time points, as confirmed by virological screening findings. The mean nucleotide substitution rate of the hemagglutinin-esterase-fusion (HEF) glycoprotein segment was estimated as 1.403 × 10-3 substitutions/site/year, which is significantly higher than the one of the HEF of human influenza C virus (P < 0.0001). IDV genetic drift, the introduction of new clades on the continent, and multiple reassortment patterns shape the increasing viral diversity observed in the last years. Its elevated substitution rate, diffusion in various animal species, and the growing evidence pointing towards zoonotic potential justify continuous surveillance of this emerging influenza virus.

Haemophilus influenzae serotype b seroprevalence in central Lao PDR before and after vaccine introduction.

INTRODUCTION: Vaccination has dramatically reduced invasive Haemophilus influenzae type b (Hib) disease worldwide. Hib vaccination was introduced in the Lao PDR in 2009, as part of the pentavalent vaccine. To contribute to the understanding of the epidemiology of Hib in Lao PDR and the protection levels before and after the introduction of the vaccination, we tested serum samples from existing cohorts of vaccine age-eligible children and unvaccinated adolescents for antibodies against Hib. METHODS: Serum samples from 296 adolescents born before vaccine introduction and from 1017 children under 5 years (vaccinated and unvaccinated) were tested for anti-Hib antibodies by ELISA. Bivariate analyses were performed to investigate factors associated with long-term protection. RESULTS: The vast majority of all participants showed evidence of short- (42.7%) or long-term (56.1%) protection against Hib. Almost all of the unvaccinated adolescents had antibody titers indicating short-term protection and almost half (45.6%) were long-term protected. Nearly all children (>99.0%) were at least short-term protected, even those that were unvaccinated or whose vaccination status was unknown. Among vaccinated children, participants vaccinated more than 1 or 2 years ago and with a mid-upper arm circumference z-score < -2 were less likely to be long-term protected. DISCUSSION: Nearly all adolescents born before the introduction of Hib vaccination in the Lao PDR had antibody titers corresponding to at least short-term protection, indicating a high burden of Hib disease at that time. After vaccine introduction, all but four children (>99%) showed at least short-term protection. Possible explanations for the proportion of protected, yet apparently unvaccinated children, may be past infections, cross-reacting antibodies or faulty vaccination documentation. Our results highlight the need for robust surveillance and reporting of invasive Hib disease to determine the burden of disease despite vaccination.

Primate Erythroparvovirus 1 Infection in Patients with Hematological Disorders.

Primate erythroparvovirus 1, commonly referred to as Parvovirus B19 (B19V), is a DNA virus that normally results in a mild childhood infection called "erythema infectiosum". Besides respiratory spread, B19V can also be transmitted through transfusions, which may result in persistent anemia in immunodeficient hosts. Dialysis patients often face acute or chronic anemia after infection with B19V. Here, we describe the laboratory investigation of 21 patients with hematological disorders for B19V infections. B19V DNA was detected in 13 (62%) of them, with specific IgM antibodies in three of the DNA positives. All 13 patients received treatment and were laboratory-monitored over a period of one year. In only two patients (a 14-year-old child with a kidney transplantation and a 39-year-old patient with aplastic anemia), markers of recent B19V infection were still detectable in follow-up samples. For four B19V DNA positive samples, short sequences could be obtained, which clustered with genotype 1a reference strains. Our findings suggest that all cases of hematological disorders should be examined for specific B19V antibodies and DNA for accurate diagnosis and appropriate patient management.

Usutu Virus Africa 3 Lineage, Luxembourg, 2020.

We detected Usutu virus in a dead Eurasian blackbird (Turdus merula) in Luxembourg in September 2020. The strain clustered within the Africa 3.1 lineage identified in Western Europe since 2016. Our results suggest maintenance of the virus in Europe despite little reporting during 2019-2020, rather than a new introduction.

Susceptibility to Vaccine-Preventable Diseases in Four Districts of Xaysomboun Province, Lao People's Democratic Republic.

Xaysomboun province has some of the lowest health indicators in Lao People's Democratic Republic (PDR). This cross-sectional study aimed to determine the vaccination, susceptibility and exposure status of the population to hepatitis B virus (HBV), measles, rubella, and tetanus. Participants aged 5 years and older were randomly selected from four districts. From each enrolled participant, demographic data and 5 mL of blood sample were taken. HBV surface antigen (HBsAg) and antibodies against HBV, measles, rubella, and tetanus were detected by ELISA. A total of 363 participants (age 5 to 80 years) were included. HBV exposure, as determined by anti-HBV core (anti-HBc) antibodies, was 56.2% overall, and was significantly higher among those aged ≥21 years (78.1%). HBsAg was detected in 9.4% overall and increased to 20% in ages 31-40 years. Only 13.8% of participants had serology indicative of vaccination (anti-HBs positive, anti-HBc negative). Seroprotection against measles was 74.6% overall but only 41.7% in children aged 5-10 years. Anti-rubella IgG was 94.2% overall and high in all age groups. Tetanus seroprevalence was only 47.4% overall but significantly higher in females aged 31-40 (75.6%). We suggest strengthening of routine and booster HBV, measles, and tetanus vaccine coverage in Xaysomboun province.

Prevalence of hepatitis E virus antibodies in cattle in Burkina Faso associated with swine mixed farming.

BACKGROUND: Endemic circulation of human-specific hepatitis E virus (HEV) genotypes 1 and 2 may occult the importance of sporadic zoonotic HEV transmissions in Africa. Increasing numbers of studies reporting anti-HEV antibodies in cattle and the discovery of infectious HEV in cow milk has raised public health concern, but cattle exposure has seldom been investigated in Africa. OBJECTIVES: This study aimed at investigating the role of cows in the epidemiology of HEV in Burkina Faso and farmers habits in terms of dairy product consumption as a prerequisite to estimate the risk of transmission to humans. METHODS: Sera from 475 cattle and 192 pigs were screened for the presence of anti-HEV antibodies while HEV RNA in swine stools was detected by reverse transcription polymerase chain reaction. Data on mixed farming, dairy product consumption and selling habits were gathered through questionnaires. RESULTS: The overall seroprevalence in cattle was 5.1% and herd seroprevalence reached 32.4% (11/34). Herd seropositivity was not associated with husbandry practice or presence of rabbits on the farms. However, herd seropositivity was associated with on-site presence of pigs, 80.7% of which had anti-HEV antibodies. The majority of farmers reported to preferentially consume raw milk based dairy products. CONCLUSIONS: Concomitant presence of pigs on cattle farms constitutes a risk factor for HEV exposure of cattle. However, the risk of HEV infections associated with raw cow dairy product consumption is currently considered as low.

Measles.

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

Low prevalence of hepatitis delta infection in Cuban HBsAg carriers: Prospect for elimination.

Introduction: Infection with hepatitis delta virus (HDV) is one of the most severe hepatitis B virus (HBV) complications, with a more rapid progression to cirrhosis and an increased risk of hepatic decompensation and death. Data on HDV infection in Cuba are limited. The aims of our study were to determine the HDV prevalence in HBsAg carriers and to characterize the HDV strains circulating. The data were used to assess the possibility of HDV elimination in the Cuban HBV epidemiological setting. Methods: Five hundred and two serum samples from the same number of HBsAg carriers collected in the period 2006-2019 from all over the country were tested for anti-HDV total antibodies. If positive, the samples were analyzed for HDV-RNA using Real-Time RT-PCR targeting the ribozyme and HD antigen domains followed by genotyping based on phylogenetic analysis. Results: Two samples were anti-HDV positive [0.39% (95% CI 0.11-1.44)]. One of them was also HDV-RNA positive. Clinically, the patient with active HDV infection had compensated liver cirrhosis. Phylogenetic analysis showed that the virus belonged to genotype 1 and thus clustered with contemporary strains from North America, Europe, Middle East, and Asia. Discussion: This is the first HDV study, including molecular detection and virus characterization, done after the introduction of the universal childhood anti-hepatitis B vaccination. The very low prevalence of HDV infection in HBsAg carriers combined with the high HBV vaccination coverage of all newborn children, of previously identified risk groups, and of the general population currently under 40 years of age suggests that HDV elimination is feasible in Cuba if the success in HBV control is maintained.

Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

BACKGROUND: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. OBJECTIVE: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. METHODS: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. RESULTS: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. CONCLUSIONS: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity.