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Pathogens (Basel, Switzerland) Feb 2024Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due...
Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due to control measures, non-polio paralysis cases are still reported and constitute a real problem, especially for etiological diagnosis, which is necessary for better management and response. From September 2022 to April 2023, we investigated acute flaccid paralysis (AFP) cases in Kinshasa following an alert from the Provincial Division of Health. All suspected cases and their close contacts were investigated and sampled. Among the 57 sampled patients, 21 (36.8%) were suspects, and 36 (63.2%) were contacts. We performed several etiological tests available in the laboratory, targeting viruses, including Poliovirus, Influenza virus, SARS-CoV-2, Enterovirus, and arboviruses. No virus material was detected, but the serological test (ELISA) detected antibodies against Chikungunya Virus, i.e., 47.4% (27/57) for IgM and 22.8% (13/57) for IgG. Among suspected cases, we detected 33.3% (7/21) with anti-Chikungunya IgM and 14.3% (3/21) of anti-Chikungunya IgG. These results highlight the importance of enhancing the epidemiological surveillance of Chikungunya.
PubMed: 38535541
DOI: 10.3390/pathogens13030198 -
Pathogens (Basel, Switzerland) Feb 2024Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a...
Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a priority, especially for conflict-affected populations. Recognizing these challenges, , an integrated model of maternal, newborn, and child health (MNCH), immunization, and nutrition services delivered through community mobilization, mobile outreach, and private-sector engagement was implemented in conflict-affected union councils (UCs) with high poliovirus transmission, including Kharotabad 1(Quetta, Balochistan) and Bakhmal Ahmedzai (Lakki Marwat, Khyber Pakhtunkhwa). A quasi-experimental pre-post-design was used to assess the impact of the interventions implemented between April 2021 and April 2022, with a baseline and an endline survey. For each of the intervention UCs, a separate, matched-control UC was identified. At endline, the proportion of fully immunized children increased significantly from 27.5% to 51.0% in intervention UCs with a difference-in-difference (DiD) estimate of 13.6%. The proportion of zero-dose children and non-recipients of routine immunization (NR-RI) children decreased from 31.6% to 0.9% and from 31.9% to 3.4%, respectively, with a significant decrease in the latter group. Scaling up and assessing the adoption and feasibility of integrated interventions to improve immunization coverage can inform policymakers of the viability of such services in such contexts.
PubMed: 38535529
DOI: 10.3390/pathogens13030185 -
Pathogens (Basel, Switzerland) Feb 2024The Global Polio Eradication Initiative made immense progress after its establishment in 1988 as a consequence of high coverage with various poliovirus vaccines in all... (Review)
Review
The Global Polio Eradication Initiative made immense progress after its establishment in 1988 as a consequence of high coverage with various poliovirus vaccines in all populations of the world. Problems have arisen in recent years, however, related to security issues in some countries, to the circulation of vaccine-derived polioviruses, and to the recognition that individuals with certain immune deficiencies can remain infected and infectious for many months or years. As natural infection and different vaccines have different effects on the immune system, the patterns of humoral and mucosal immunity to polioviruses in the world today are complex but are crucial to the ultimate success of the eradication initiative. This paper describes the background of the current situation and current immunological patterns and discusses their implications for managing population immunity to polioviruses in the years ahead.
PubMed: 38535527
DOI: 10.3390/pathogens13030183 -
Emerging Infectious Diseases Apr 2024Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization...
Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.
Topics: Poliovirus; Poliovirus Vaccine, Oral; Uganda; Vaccination; Immunization
PubMed: 38526214
DOI: 10.3201/eid3004.231361 -
Journal of Multidisciplinary Healthcare 2024Malnutrition is identified as a risk-factor for insufficient polioseroconversion in the context of a vaccine-derived polio virus (VDPV) outbreak prone region. To assess...
BACKGROUND
Malnutrition is identified as a risk-factor for insufficient polioseroconversion in the context of a vaccine-derived polio virus (VDPV) outbreak prone region. To assess the prevalence of malnutrition and its link to poliovirus insufficient immunity, a cross-sectional household survey was conducted in the regions of Haut- Lomami and Tanganyika, DRC.
METHODS
In March 2018, we included 968 healthy children aged 6 to 59 months from eight out of 27 districts. Selection of study locations within these districts was done using a stratified random sampling method, where villages were chosen based on habitat characteristics identified from satellite images. Consent was obtained verbally in the preferred language of the participant (French or Swahili) by interviewers who received specific training for this task. Furthermore, participants contributed a dried blood spot sample, collected via finger prick. To assess malnutrition, we measured height and weight, applying WHO criteria to determine rates of underweight, wasting, and stunting. The assessment of immunity to poliovirus types 1, 2, and 3 through the detection of neutralizing antibodies was carried out at the CDC in Atlanta, USA.
RESULTS
Of the study population, we found 24.7% underweight, 54.8% stunted, and 15.4% wasted. With IC95%, underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.96; [1.52-2.54]) were significantly associated with seronegativity to polioserotype 1. Underweight (OR=1.64; [1.20-2.24]) and the non-administration of vitamin A (OR=1.55; [1.20-2.01]) were significantly associated with seronegativity to polioserotype 2. Underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.80. [1.38-2.35]) were significantly associated with seronegativity to polioserotype 3. Underweight (OR=1.68; IC95% [1.10-2.57]) and the non-administration of vitamin A (OR=1.82; IC95% [1.30-2.55]) were significantly associated with seronegativity to all polioserotypes.
CONCLUSION
This study reveals a significant association between underweight and polioseronegativity in children. In order to reduce vaccine failures in high-risk areas, an integrated approach by vaccination and nutrition programs should be adopted.
PubMed: 38524863
DOI: 10.2147/JMDH.S437351 -
Human Vaccines & Immunotherapeutics Dec 2024This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.
This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.
Topics: Humans; Infant; Antibodies, Neutralizing; Antibodies, Viral; China; Immunogenicity, Vaccine; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 38509699
DOI: 10.1080/21645515.2024.2324538 -
Vaccine Apr 2024Sabin Inactivated Poliovirus Vaccine (sIPV) has become one of the preferred vaccination options for the last step in the Poliovirus eradication program. Sequencing of...
Sabin Inactivated Poliovirus Vaccine (sIPV) has become one of the preferred vaccination options for the last step in the Poliovirus eradication program. Sequencing of poliovirus samples is needed during the manufacturing of poliovirus vaccines to assure the safety and immunogenicity of these vaccines. Next-generation sequencing analysis is the current costly and time-consuming gold standard for monitoring the manufacturing processes. We developed a low-cost and quick, highly sensitive, and allele-specific locked nucleic acid-probe-based reverse transcription quantitative PCR alternative that can accurately detect mutations in poliovirus vaccine samples during process development, scaling up, and release. Using the frequently in vitro occurring and viral replication-impacting VP1-EK mutation as a showcase, we show that this technology can accurately detect EK mutations in poliovirus 2 samples to similar levels as NGS. The qPCR technology was developed employing a synthetic dsDNA fragment-based standard curve containing mixes of EK-WT (wildtype) and Mut (mutant) synthetic dsDNA fragments ranging from 1 × 10 copies/µL to 1 × 10 copies/µL to achieve a linear correlation with R > 0.999, and PCR efficiencies of 95-105 %. Individual standard concentration levels achieved accuracies of ≥92 % (average 96 %) and precisions of ≤17 % (average 3.3 %) RSD. Specificity of locked nucleic acid (LNA)-probes was confirmed in the presence and absence of co-mutations in the probe-binding region. Application of the developed assay to Sabin Poliovirus type 2 production run samples, illustrated a linear relationship with an R of 0.994, and an average accuracy of 97.2 % of the variant (allele)-specific AS LNA qPCR result, compared to NGS. The assay showed good sensitivity for poliovirus samples, containing EK mutation levels between 0 % and 95 % (quantification range). In conclusion, the developed AS LNA qPCR presents a valuable low-cost, and fast tool, suitable for the process development and quality control of polio vaccines.
Topics: Humans; Poliomyelitis; Poliovirus Vaccine, Oral; Poliovirus; Poliovirus Vaccine, Inactivated; Mutation; Quality Control; Oligonucleotides
PubMed: 38503660
DOI: 10.1016/j.vaccine.2024.01.103 -
Neuro-oncology Practice Apr 2024Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes...
BACKGROUND
Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020.
METHODS
Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily.
RESULTS
The cohort age range was 21-74 years. Tumor types included astrocytoma ( = 14) and oligodendroglioma ( = 16), with most being grade 2 ( = 21). The best radiographic response in nonenhancing disease ( = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%.
CONCLUSIONS
Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.
PubMed: 38496920
DOI: 10.1093/nop/npad068 -
BMC Infectious Diseases Mar 2024The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive...
BACKGROUND
The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive outbreak of cVDPV2 was reported from August 2021 to December 2022. This study aims to compare the patterns of cVDPV2 outbreak, response measures taken by health authorities, and impacts in southern and northern governorates.
METHOD
A retrospective descriptive study of confirmed cases of VDPV2 was performed. The data related to cVDPV2 as well as stool specimens and environmental samples that were shipped to WHO-accredited labs were collected by staff of surveillance. Frequencies and percentages were used to characterize and compare the confirmed cases from the southern and northern governorates. The average delayed time as a difference in days between the date of sample collection and lab confirmation was calculated.
RESULTS
The cVDPV2 was isolated from 227 AFP cases reported from 19/23 Yemeni governorates and from 83% (39/47) of environmental samples with an average of 7 months delayed from sample collection. However, the non-polio AFP (NPAFP) and adequate stool specimen rates in the north were 6.7 and 87% compared to 6.4 and 87% in the south, 86% (195) and 14%(32) out of the total 227 confirmed cases were detected from northern and southern governorates, respectively. The first and second cases of genetically linked isolates experienced paralysis onset on 30 August and 1st September 2021. They respectively were from Taiz and Marib governorates ruled by southern authorities that started vaccination campaigns as a response in February 2022. Thus, in contrast to 2021, the detected cases in 2022 from the total cases detected in the south were lower accounting for 22% (7 of 32) of compared to 79% (155 of 195) of the total cases the north.
CONCLUSION
A new emerging cVDPV2 was confirmed in Yemen. The result of this study highlighted the impact of vaccination campaigns in containing the cVDPV2 outbreak. Maintaining a high level of immunization coverage and switching to nOPV2 instead of tOPV and mOPV2 in campaigns are recommended and environmental surveillance should be expanded in such a risky country.
Topics: Humans; Poliovirus; Yemen; Retrospective Studies; alpha-Fetoproteins; Poliomyelitis; Poliovirus Vaccine, Oral; Disease Outbreaks
PubMed: 38491425
DOI: 10.1186/s12879-024-09215-1 -
Journal of Infection in Developing... Feb 2024Poliovirus (PV) and non-polio enteroviruses (NPEV) belong to the Picornaviridae family. They are found worldwide and are responsible for a wide range of diseases such as...
INTRODUCTION
Poliovirus (PV) and non-polio enteroviruses (NPEV) belong to the Picornaviridae family. They are found worldwide and are responsible for a wide range of diseases such as acute flaccid paralysis (AFP). This study aimed to evaluate the detection rate of PV and NPEV in stool samples from children under fifteen years of age presenting with AFP in Cameroon and their distribution over time.
METHODOLOGY
Stool samples were collected as part of poliovirus surveillance throughout Cameroon from 2015 to 2020. Virus isolation was performed using RD and L20B cells maintained in culture. Molecular methods such as intratypic differentiation were used to identify PVs serotypes and analysis of the VP1 genome was performed.
RESULTS
A total of 12,354 stool samples were analyzed. The EV detection rate by virus isolation was 11.42% (1411/12354). This rate varied from year to year with a mean distribution of 11.41 with a 95% confidence interval [11.37; 11.44]. Of the viruses detected, suspected poliovirus accounted for 31.3% (442/1411) and NPEV 68.67% (969/1411). No wild poliovirus (WPV) was isolated. Sabin types 1 and 3 were continuously isolated. Surprisingly, from February 2020, vaccine-derived PV type 2 (VDPV2) was detected in 19% of cases, indicating its resurgence.
CONCLUSIONS
This study strongly supports the successful elimination of WPV in Cameroon and the resurgence of VDPV2. However, as long as VDPV outbreaks continue to be detected in Africa, it remains essential to monitor how they spread.
Topics: Child; Humans; Poliovirus; Enterovirus; Cameroon; alpha-Fetoproteins; Poliomyelitis; Enterovirus Infections; Myelitis; Neuromuscular Diseases; Central Nervous System Viral Diseases
PubMed: 38484358
DOI: 10.3855/jidc.18279