Seroprevalence of ToRCH Pathogens in Southeast Asia

ToRCH is the acronym for several pathogens associated with pregnancy complications and sequelae in the unborn or newborn child. Particularly primary infections during pregnancy are associated with increased risk. Seroprevalence data of ToRCH infections are important, especially in countries with weak disease surveillance systems, to estimate immunity and vaccination levels, as well as exposure rates and thus the risk of infection during pregnancy. A systematic literature search spanning a 30-year time period was conducted to identify serosurveys on ToRCH pathogens in Southeast Asia. The 96 identified studies showed that some pathogens were well studied, while only limited data were available for others. Studies from the better-developed countries of the region were more abundant. Moreover, seroprevalence data were often limited to a certain geographical region within the country or to certain cohorts, there was an evident lack of recent serosurveys, and the study quality was often not adequate. Well-designed and area-wide serosurveys of ToRCH pathogens are clearly warranted. If combined with risk factor analysis, these studies may guide the development and implementation of effective measures for infection prevention, especially during pregnancy. In addition, educational programs for health care workers and for pregnant women during antenatal care are urgently needed

Viral load, clinical disease severity and cellular immune responses in primary varicella zoster virus infection in Sri Lanka

Background In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied. Methodology We used IFNγ ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection. Principal Findings Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p<0.001) and were significantly higher in those over 25 years of age (P<0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNγ ELISpot responses of patients (P<0.001, r = −0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. Conclusions Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses

Lasting benefit of infant hepatitis B vaccination in adolescents in the Lao People’s Democratic Republic

Objectives Hepatitis B is endemic in Lao PDR with 8–10% of the adult population being chronically infected. We investigated the impact of hepatitis B vaccination on infection in adolescents born shortly before and after the introduction of the vaccine in 2001. Methods 779 students from Vientiane Capital and Bolikhamxay province were tested for HBV markers by ELISA. Socio-demographic information was collected with a standardized questionnaire. Predictors/risk factors for seroprotection or exposure to hepatitis B infection were assessed by bivariate and multivariable analyses. Results The prevalence of a serological vaccination profile increased significantly after the introduction of the vaccine (13.2%–21.9%, p < 0.05, in Vientiane; 3.0%–19.7%, p < 0.001, in Bolikhamxay), which translated into at least a 2-times lower prevalence of past infection. In logistic regression, older students in Bolikhamxay were less likely to be vaccinated and more likely to have been infected by HBV in the past. Conclusion Even though this study documented a sizable and lasting reduction in past hepatitis B infections in adolescents born after the introduction of infant hepatitis B vaccination, the overall levels of protective anti-HBs were low and warrant at least the introduction of a booster for adolescents. Furthermore, we suggest improving the coverage of the hepatitis B birth dose

Diphtheria in Lao PDR: insufficient coverage or ineffective vaccine?

Background During late 2012 and early 2013 several outbreaks of diphthe-ria were notified in the North of the Lao People’s Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. Methods A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12–59 months. Serum samples, socio-demographic data, nutri-tional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Results Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4–28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74–85, 4], p = 0.01) and the lack of advice on vac-cination given at birth (OR: 9.8 [95% CI: 1.5–63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008–0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Conclusions Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical defi-ciencies in the methods of storage and distribution of vaccines as well as unreliability of vac-cination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against diphtheria and recommendations are provided to prevent future outbreaks

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

Seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated infants in the Lao People’s Democratic Republic

Background Even though measles vaccination was introduced in the Lao PDR in 1984, coverage rates remain consistently low and outbreaks continue to occur frequently. This study was performed to investigate the seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated children from Central Lao PDR. Methods Antibody titres of 1090 children aged 8–29 months who were vaccinated at different levels of the health care system were assessed by ELISA. Bivariate and multivariable analyses were performed to identify factors affecting seropositivity against measles and rubella. Results Among the vaccinated children, 67.5% in Vientiane Province and 76.4% in Bolikhamxay Province were double positive/borderline for measles and rubella IgG. A high proportion of unvaccinated children at both study sites (24.4% and 38.4%) were positive/borderline for measles and/or rubella. Time since vaccination <180 days, more than two siblings, and a mother who is a farmer/labourer were negatively associated with seropositivity. Conclusions A high prevalence of measles and rubella antibodies was found in unvaccinated children, indicating widespread circulation of both viruses and underreporting of cases. The high proportion of vaccinated children still susceptible to measles suggests problems with vaccine immunogenicity, emphasizing the need for regular evaluations of vaccine efficacy and management

Pertussis in Lao PDR: Seroprevalence and disease

Objectives Pertussis is a debilitating vaccine-preventable infection. The aim of this study was to determine susceptibility and exposure to pertussis in Lao PDR in different age groups and subpopulations. Methods A total 3072 serum samples were obtained from different cohorts: children with documented vaccination, pre-schoolers, schoolchildren, blood donors, healthcare workers (HCWs), and pregnant women and paired cord blood. Samples were tested for anti-pertussis toxin IgG antibodies. A history of Bordetella pertussis exposure was defined according to antibody titres. Four hundred and seventy-five throat swabs and nasopharyngeal aspirates were analysed by PCR for the presence of B. pertussis in symptomatic children at the Children's Hospital in Vientiane. Results Overall pertussis seroprevalence was 57.5%. The prevalence of titres indicating acute infection or recent vaccination or infection/vaccination within the last 12 months ranged from 7.4% (100/1356) in adults to 21.4% (25/117) in pre-schoolers (age 1–5 years). B. pertussis was detected in 1.05% (5/475) of children with respiratory symptoms in Vientiane Capital. Conclusions It is suggested that routine childhood vaccination, in particular outreach, as well as vaccination of HCWs should be strengthened. A childhood booster and vaccination of pregnant mothers should be considered. There is also a need to improve reporting and to introduce pertussis testing in at least one central facility

Varicella zoster and fever rash surveillance in Lao People’s Democratic Republic

Background In Lao PDR, the epidemiology of varicella infection is uncertain, since it is not a notifiable disease and VZV outbreaks are rarely reported as fever/rash (F/R) diseases. Methods We estimated the seroprevalence of VZV (IgG ELISA) in different age cohorts (9 months to 46 years; N = 3139) and investigated VZV and 6 other viruses in patients during F/R outbreaks and in an ad hoc sentinel site in the context of the national reporting system (IgM ELISA, PCR). Results At least 80% of the sampled population had evidence of VZV infection before the age of 15. The largest increase in seroprevalence occurred between the age groups 1 to 5 and 6 to 7 year-olds. A VZV outbreak (clade 2) also occurred in this age group mostly during the first year of primary school (median age 6 years, interquartile range 4.0–7.5). During a dengue outbreak, 6% had varicella. At our F/R sentinel site, 14% of children with viral etiology were laboratory diagnosed as varicella and among others, a sizeable number of measles (N = 12) and rubella cases (N = 25) was detected compared to those reported for the whole country (N = 56 and 45), highlighting nationwide a large challenge of underreporting or misdiagnosis of these notifiable diseases because of lack of diagnostic laboratory capacity. Conclusion We recommend strengthening the clinical and laboratory diagnosis of VZV, measles and rubella, the surveillance and reporting of notifiable F/R diseases by retraining of healthcare workers and by setting up sentinel sites and enhancing laboratory capacity

Hepatitis B virus in the Lao People’s Democratic Republic: a cross sectional serosurvey in different cohorts

Background Despite hepatitis B vaccination at birth and at 6, 10 and 14 weeks of age, hepatitis B virus (HBV) infection continues to be endemic in the Lao People’s Democratic Republic (PDR). We carried out a cross-sectional serological study in infants, pre-school children, school pupils and pregnant women to determine their burden of disease, risk of infection and vaccination status. Methods A total of 2471 participants between 9 months and 46 years old were recruited from urban (Vientiane Capital, Luang Prabang), semi-urban (Boulhikhamxai and Savannakhet) and remote rural areas (Huaphan). All sera were tested for anti-HBs and anti-HBc. Sera testing positive for anti-HBc alone were further tested for the presence of HBsAg. Results A low prevalence of HBsAg (0.5%) was detected among infants from Vientiane and Luang Prabang, indicating some success of the vaccination policy. However, only 65.6% had protective anti-HBs antibodies, suggesting that vaccination coverage or responses remain sub-optimal, even in these urban populations. In pre-school children from remote areas in Huaphan, 21.2% were positive for anti-HBc antibodies, and 4.6% were for HBsAg positive, showing that a significant proportion of children in these rural regions have early exposure to HBV. In pre-school children with 3 documented HBV vaccinations, only 17.0% (15/55) were serologically protected. Among school-children from semi-urban regions of Luang Prabang, Boulhikhamxai and Savannakhet provinces, those below the age of 9 who were born after HBV vaccine introduction had anti-HBc and HBsAg prevalence of 11.7% and 4.1%, respectively. The prevalence increased to 19.4% and 7.8% of 10–14 year olds and to 27% and 10.2% of 15–19 year olds. Pregnant women from Luang Prabang and Vientiane had very high anti-HBc and HBsAg prevalence (49.5% and 8.2%), indicating high exposure and risk of onward vertical transmission to the unborn infant. Conclusions Overall, the results demonstrate a dramatic deficiency in vaccination coverage and vaccine responses and/or documentation within the regions of Lao PDR studied, which included urbanized areas with better health care access. Timely and effective hepatitis B vaccination coverage is needed in Lao PDR