Evaluating progress towards triple elimination of mother-to-child transmission of HIV, syphilis and hepatitis B in the Netherlands.

BACKGROUND: In 2014 the World Health Organisation (WHO) established validation criteria for elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. Additionally, the WHO set targets to eliminate hepatitis, including hepatitis B (HBV). We evaluated to what extent the Netherlands has achieved the combined WHO criteria for EMTCT of HIV, syphilis and HBV. METHODS: Data of HIV, syphilis and HBV infections among pregnant women and children (born in the Netherlands with congenital infection) for 2009-2015, and data required to validate the WHO criteria were collected from multiple sources: the antenatal screening registry, the HIV monitoring foundation database, the Perinatal Registry of the Netherlands, the national reference laboratory for congenital syphilis, and national HBV notification data. RESULTS: Screening coverage among pregnant women was > 99% for all years, and prevalence of HIV, syphilis and HBV was very low. In 2015, prevalence of HIV, syphilis and HBV was 0.06, 0.06 and 0.29%, respectively. No infections among children born in the Netherlands were reported in 2015 for all three diseases, and in previous years only sporadic cases were observed In 2015, treatment of HIV positive pregnant women was 100% and HBV vaccination of children from HBV positive mothers was > 99%. For syphilis, comprehensive data was lacking to validate WHO criteria. CONCLUSIONS: In the Netherlands, prevalence of maternal HIV, syphilis and HBV is low and congenital infections are extremely rare. All minimum WHO criteria for validation of EMTCT are met for HIV and HBV, but for syphilis more data are needed to prove elimination.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

OBJECTIVE:  To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined. SETTING:  Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting. PARTICIPANTS:  25 789 RhD negative pregnant women. MAIN OUTCOME MEASURES:  Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. RESULTS:  A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. CONCLUSIONS:  Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.

[Foetal Rhesus-D typing added to antenatal screening for infectious diseases and erythrocyte immunisation]. / Foetale resus-D-typering toegevoegd aan prenatale screening op infectieziekten en erytrocytenimmunisatie.

OBJECTIVE: Investigation of the accuracy and national implementation of foetal Rhesus-D typing (fRhD), introduced in 2011 for RhD-negative pregnant women. DESIGN: Descriptive, national study. METHOD: Results of fRhD in pregnant women in the first year after implementation were compared to results from cord blood RhD typing of the child. RESULTS: 0.05% of the fRhD results was false negative (9/18.383; 95% CI: 0.02-0.09), and 0.85% was false positive (157/18.383; 95% CI: 0.73-1.00). fRhD was incorrectly omitted in fewer than 1% of pregnant women. In 96.1% of the pregnant women, antenatal administration of anti-D prophylaxis was recorded. Recording of postnatal anti-D administration turned out to be lower (92%), but locally recorded data showed that postnatal anti-D was omitted in fewer than 2% of cases. CONCLUSION: The percentage of false negative fRhD was statistically significantly lower (p < 0.05) than the critical limit of 0.25% determined beforehand by the Programme Committee of the Dutch Antenatal Screening Programme for Infectious Diseases and Erythrocyte Immunisation. The percentage of false positive fRhD was considered acceptable, and implementation of fRhD was more or less complete. Routine RhD-typing on cord blood was therefore omitted from January 2013. Antenatal and postnatal anti-D administration is now specifically indicated for RhD-negative pregnant women when fRhD is positive, thus saving about 10,000 unnecessary antenatal anti-D administrations per year. RhD-typing on cord blood is now performed only if the RhD blood type of the child of a RhD-negative mother is unknown at delivery, if a positive fRhD was found for multiple births, and in exceptional situations, e.g. if fRhD typing is not possible due to a rare genetic variation.

Preexisting poliovirus-specific IgA in the circulation correlates with protection against virus excretion in the elderly.

BACKGROUND: Epidemiological studies have indicated that at least 10% of the Dutch elderly do not have poliovirus serotype-specific neutralizing antibody titers and might be at risk for poliovirus infection. Previously we established that memory immunity does not protect the elderly against poliovirus replication. In this study, we investigated whether preexisting immunoglobulin (Ig) A protects against poliovirus infection. METHODS: Elderly individuals (n = 383), divided into seronegative and seropositive groups, were challenged with monovalent oral poliovirus vaccine (mOPV), either serotype 1 or serotype 3. After challenge, poliovirus serotype-specific circulating and salivary IgA responses were measured by enzyme-linked immunosorbent assays, and poliovirus excretion in stool was measured. RESULTS: The majority of elderly persons without preexisting IgA excreted poliovirus in the stool. In contrast, most elderly persons seropositive for IgA did not excrete poliovirus. Significant inverse correlations were found between preexisting titers of poliovirus serotype-specific circulating IgA and virus excretion. Challenge with mOPV (re)induced IgA responses; low salivary IgA responses correlated with that in the circulation but not with virus excretion. CONCLUSIONS: These results indicate that preexisting IgA values in the circulation correlate with protection against poliovirus infection in the elderly. This further implies that persons without preexisting IgA might contribute to the circulation of poliovirus and therefore may threaten its eradication.

Determinants of monovalent oral polio vaccine mutagenesis in vaccinated elderly people.

Live oral poliovirus vaccine (OPV) strains can mutate and recombine during replication in the host. Trivalent OPV has long been used to restrain wild-type poliovirus in developing countries. However, recently WHO advocates using monovalent OPV (mOPV) to finally eradicate poliovirus world-wide. We analysed polioviruses recovered from the faeces of 101 elderly patients (divided into three groups by immune status) challenged with mOPV-1 or mOPV-3. A high number of nucleotide mutations was found in the viral capsid-protein-encoding regions. Some of these mutations caused amino acid changes in or near regions with neutralizing epitopes, especially in mOPV-1-derived strains. The quantities of mutations in recovered poliovirus strains correlated with prevaccination immune status (seronegatives have more mutations) and excretion duration. Duration of excretion appears to be the dominant factor for the accumulation of mutations in mOPV-derived strains in vaccinated elderly people.

Poliovirus-specific memory immunity in seronegative elderly people does not protect against virus excretion.

BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and may have escaped natural infection because of reduced poliovirus circulation. We examined whether people with low or undetectable antibody levels are susceptible to infection and whether memory immunity provides protection against virus excretion. METHODS: A total of 429 elderly participants were challenged with monovalent oral poliovirus vaccine (type 1 or 3) and followed for 8 weeks. Immune responses and virus excretion were compared for 4 groups, defined on the basis of seronegativity for poliovirus type 1 or 3, natural immunity, and IPV-induced immunity. RESULTS: On the basis of the rapidity of the antibody response and the absence of immunoglobulin M, we saw clear evidence of memory immune responses in 33% of the participants without detectable antibodies against poliovirus type 1 and in 5% of the participants without detectable antibodies against poliovirus type 3. Fecal virus-excretion patterns were not significantly different for seronegative participants, regardless of whether they showed evidence of memory immunity. CONCLUSIONS: Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.