Search Results (28)

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study group. However, the documented genetic diversity of HCoSV in Nigeria is limited. Here we describe the genetic diversity of HCoSV in Nigeria using a metagenomics approach. Archived and anonymized fecal specimens from children (under 15 years old) diagnosed with non-polio AFP from five states in Nigeria were analyzed. Virus-like particles were purified from 55 pools (made from 254 samples) using the NetoVIR protocol. Pools were subjected to nucleic acid extraction and metagenomic sequencing. Reads were trimmed and assembled, and contigs classified as HCoSV were subjected to phylogenetic, pairwise identity, recombination analysis, and, when necessary, immuno-informatics and capsid structure prediction. Fifteen pools yielded 23 genomes of HCoSV. Phylogenetic and pairwise identity analysis showed that all belonged to four species (eleven, three, three, and six members of Cosavirus asiani, Cosavirus bepakis, Cosavirus depakis, and Cosavirus eaustrali, respectively) and seventeen genotypes. Ten genomes belong to seven (HCoSV-A3/A10, A15, A17, A19, A24, D3, and E1) previously assigned genotypes, while the remaining thirteen genomes belonged to ten newly proposed genotypes across the four HCoSV species, based on the near-complete VP1 region (VP1*) of the cosavirus genome. Our analysis suggests the existence of at least seven and eight Cosavirus bepakis and Cosavirus eaustrali genotypes, respectively (including those described here). We report the first near-complete genomes of Cosavirus bepakis and Cosavirus depakis from Nigeria, which contributes to the increasing knowledge of the diversity of HCoSV, raising the number of tentative genotypes from 34 to over 40. Our findings suggest that the genetic diversity of HCoSV might be broader than is currently documented, highlighting the need for enhanced surveillance. Full article

In the context of the near-global eradication of wild poliovirus, the significance of non-polio enteroviruses (NPEVs) in causing acute flaccid paralysis (AFP) and their impact on public health has gained increased attention. This research, conducted from 2001 to 2021, examined stool samples from 1597 children under 15 years in São Paulo, Brazil, through the AFP/Poliomyelitis Surveillance Program, detecting NPEVs in 6.9% of cases. Among the 100 NPEV-positive strains analyzed, 90 were genotyped through genomic sequencing of the partial VP1 region, revealing a predominance of EV-B species (58.9%), followed by EV-A (27.8%) and EV-C (13.3%). This study identified 31 unique NPEV types, including EV-A71, CVB2, and E11, as the most prevalent, along with the first documented occurrence of CVA19 in Brazil. These findings emphasize the importance of NPEV genotyping in distinguishing AFP from poliomyelitis, enhancing understanding of these viruses’ epidemiology. Moreover, it ensures that AFP cases are correctly classified, contributing to the effective surveillance and eradication efforts for poliomyelitis. Full article

The Global Polio Eradication Initiative was adopted by Ghana in 1996, and through robust AFP surveillance was able to interrupt the circulation of wild poliovirus in 2008. However, the country suffered vaccine-derived poliovirus type 2 outbreaks in 2019 and 2022. We conducted a retrospective analysis of all AFP surveillance data received by the polio program in Ghana from 2018 to 2022. An analysis of the WHO performance indicators for evaluating a surveillance system was conducted using Epi Info 3.5.4 and Microsoft Excel. Of the 4832 cases investigated, 56.3% were males, 71.1% comprised children aged 5 years and below, and more than half (65.2%) had received a maximum of three doses of OPV. Over 77% (3028) had a fever at the onset of paralysis, and 67.8% had paralysis progression within 3 days. The non-polio AFP rate of ≥2 and the stool adequacy rate exceeded the target of ≥80% in nearly every study year. The proportion of non-polio enteroviruses isolated surpassed the target of ≥10% in all years except 2018. The AFP surveillance system in Ghana is sensitive and representative. Though the surveillance became more intensive and proactive during the outbreak, the system needs to focus on improving the completeness of the data as well as the timeliness of the arrival of stool specimens within 3 days of collection. Full article

Enterovirus A71 (EV-A71) is a major cause of hand-foot-and-mouth disease (HFMD), particularly in cases that involve complications affecting the nervous system or cardiopulmonary function. In South America, EV-A71 has primarily been identified through studies of acute flaccid paralysis (AFP) and other neurological disorders. In September 2022, two children from a small city in Uruguay were hospitalized with presumptive rhombencephalitis, exhibiting symptoms of HFMD. EV-A71 was identified through RT-PCR and next-generation sequencing of stool and skin lesion samples. A maximum-likelihood phylogenetic analysis of the P1 coding region classified the Uruguayan strains as part of an emerging lineage, primarily reported in Europe over the past decade, known as the C1-like lineage. The findings presented here represent the first detection of the EV-A71 C1-like lineage in cases of HFMD and encephalitis reported from South America, underscoring the urgent need to enhance surveillance for HFMD, aseptic meningitis, encephalitis, and AFP, in countries facing challenges in establishing effective surveillance programs related to enteroviruses and associated diseases. Full article

The Government of India, in collaboration with the World Health Organization (WHO), established the National Polio Surveillance Project (NPSP) in 1997 and initiated acute flaccid paralysis (AFP) surveillance to achieve the goal of polio eradication. The WHO South-East Asia Region, comprising of 11 countries, including India, was certified as polio-free in March 2014. India was also validated to have eliminated maternal and neonatal tetanus in May 2015. Over the years, the surveillance of other vaccine-preventable diseases (VPDs) was integrated with AFP surveillance in the country. Outbreak-based measles–rubella (MR) surveillance was initiated in 2005 using AFP surveillance as a platform, case-based fever–rash (FR) surveillance started in 2021 as one of the strategies to achieve measles and rubella elimination in the country. The surveillance of diphtheria, pertussis, and neonatal tetanus was integrated with AFP surveillance in a phased manner during 2015–2022. The surveillance system for VPDs in India, supported by a laboratory network of 10 polio laboratories, 28 measles–rubella laboratories, and 20 diphtheria–pertussis laboratories, has enhanced the national health capacity and security. The setting up and expansion of the surveillance system in the country involved the important component of capacity building of personnel on various components of surveillance, including case identification, case investigation, sample collection and shipment, data analysis and public health response. These capacities have been used effectively during other emergencies, such as the recent COVID-19 pandemic, as well as during outbreaks of other diseases and natural calamities. Full article

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting. Full article

Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended. Full article

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. Full article

More than 100 types of non-polio enteroviruses (NPEVs) are ubiquitous in the human population and cause a variety of symptoms ranging from very mild to meningitis and acute flaccid paralysis (AFP). Much of the information regarding diverse pathogenic properties of NPEVs comes from the surveillance of poliovirus, which also yields NPEV. The analysis of 265 NPEV isolations from 10,433 AFP cases over 24 years of surveillance and more than 2500 NPEV findings in patients without severe neurological lesions suggests that types EV-A71, E13, and E25 were significantly associated with AFP. EV-A71 was also significantly more common among AFP patients who had fever at the onset and residual paralysis compared to all AFP cases. In addition, a significant disparity was noticed between types that were common in humans (CV-A2, CVA9, EV-A71, E9, and E30) or in sewage (CVA7, E3, E7, E11, E12, and E19). Therefore, there is significant evidence of non-polio viruses being implicated in severe neurological lesions, but further multicenter studies using uniform methodology are needed for a definitive conclusion. Full article

West Nile virus (WNV), a mosquito-borne flavivirus, is endemic to South Africa. However, its contribution to acute febrile and neurological disease in hospitalized patients in South Africa is unknown. This study examined two patient cohorts for WNV using molecular testing and IgM serology with confirmation of serological results by viral neutralization tests (VNT) to address this knowledge gap. Univariate analysis was performed using collected demographic and clinical information to identify risk factors. In the first cohort, 219 cerebrospinal fluid (CSF) specimens from patients with acute neurological disease in Gauteng hospitals collected in January to June 2017 were tested for WNV. The study identified WNV in 8/219 (3.65%, 95.00% CI (1.59–7.07)) patients with unsolved neurological infections. The second cohort, from 2019 to 2021, included 441 patients enrolled between January and June with acute febrile or neurological disease from urban and rural sites in Gauteng and Mpumalanga provinces. West Nile virus was diagnosed in 40/441 (9.07%, 95.00% CI (6.73–12.12)) of patients, of which 29/40 (72.50%, 95.00% CI (56.11–85.40)) had neurological signs, including headaches, encephalitis, meningitis, and acute flaccid paralysis (AFP). Notably, most of the cases were identified in children although adolescents and senior adults had a significantly higher risk of testing WNV positive. This suggests a previously underestimated disease burden and that WNV might be underrecognized as a cause of febrile and neurological diseases in hospitalized patients in South Africa, especially in children. This emphasizes the importance of further research and awareness regarding arboviruses of public health concern. Full article

Polio surveillance in the Global Polio Eradication Initiative has been conducted with virus isolation from stool samples of acute flaccid paralysis (AFP) cases. Under the current biorisk management/regulations, challenges arise in the timelines of the report, sensitivity of the test and containment of poliovirus (PV) isolates. In the present study, we evaluated protocols of previously reported direct detection (DD) methods targeting the VP1 or VP4–VP2 regions of the PV genome in terms of sensitivity and sequencability. An optimized protocol targeting the entire-capsid region for the VP1 sequencing showed a high sensitivity (limit of detection = 82 copies of PV genome) with a simpler and faster reaction than reported ones (i.e., with the addition of all the primers at the start of the reaction, the RT-PCR reaction finishes within 2.5 h). The DD methods targeting the VP1 region detected PV in 60 to 80% of PV-positive stool samples from AFP cases; however, minor populations of PV strains in the samples with virus mixtures were missed by the methods. Sequencability of the DD methods was primarily determined by the efficiency of the PCRs for both Sanger and nanopore sequencing. The DD method targeting the VP4–VP2 region showed higher sensitivity than that targeting the VP1 region (limit of detection = 25 copies of PV genome) and successfully detected PV from all the stool samples examined. These results suggest that DD methods are effective for the detection of PV and that further improvement of the sensitivity is essential to serve as an alternative to the current polio surveillance algorithm. Full article

Acute gastroenteritis (AGE) has a major impact on morbidity and mortality worldwide. The viral aetiology of diarrhoeal diseases may remain unknown due to limited diagnostic facilities. Non-polio enteroviruses (NPEVs) are the third most frequent pathogen detected in stool specimens from AGE cases, yet their potential role in AGE is uncertain. In Nepal, limited data are available on NPEVs, due to both the lack of an adequate surveillance program and the availability of tests. The global polio eradication initiative effort of the WHO has eradicated the incidence of poliomyelitis and acute flaccid paralysis (AFP) from many parts of the world, including Nepal. However, cases of AFP associated with NPEVs have been reported in different countries, including the neighbouring India. This study aims to investigate the diarrhoeal stool samples from a birth cohort until the age of 36 months for NPEVs and the genotype diversity of NPEV in community children with diarrhoea. A total of 280 longitudinal diarrhoeal stool samples that were negative for other enteric pathogens were tested using RT-PCRs. NPEVs was detected in 97 stool specimens (34.6%) and were significantly more frequent in infants up to one year of age. This study identified 17 various NPEV types, with the dominating species being Enterovirus B (EV-B). Ten different types of echoviruses were recorded in this study, with the two rare NPEVs B74 and A120. Based on prevalence, seasonality, and diversity, further studies are warranted to investigate the role of enterovirus in diarrhoeal disease. Full article

Hand-foot-and-mouth disease (HFMD) is the most common enteroviral infection in South-East Asia. When evaluating the role of enterovirus 71 (EVA71) as an etiological agent of infectious disease in South Vietnam, we revealed a high proportion of EVA71 among identified species A enteroviruses found in 3542 samples from HFMD cases; 125 samples from cases of enteroviral meningitis; and 130 samples from acute flaccid paralysis (AFP) cases. These represent 50%, 54.8%, and 51.5%, respectively. According to molecular analysis, 90% of EVA71 were attributed to genotype C4 and 10% were attributed to genotype B5. The predominance of EVA71 circulation among the population proves the need to strengthen surveillance (with monitoring of enterovirus circulation for facilitation of HFMD outbreak prediction) and to increase the effectiveness of preventative measures by the implementation of vaccination against EVA71-associated infections. A phase III trial of a Taiwanese vaccine (EV71vac) in Taiwan and South Vietnam showed its safety, tolerability, and efficacy in children aged 2–71 months. This B4 genotype-based vaccine, which features cross-protection against B5 and C4 genotypes, and other existing EV71 vaccines can serve as a good approach to solving the HFMD problem, which is so important for Vietnam. Full article

Background: Poliovirus post-eradication containment of wild-type 2 poliovirus (PV2) requires the destruction of all materials containing, or potentially containing, PV2. Acute flaccid paralysis (AFP) cases in Israel between 1973 and 1988 were caused by all three serotypes; thus, isolates from cases and case-contacts were either PV2 or potentially contaminated with PV2. Aims: To provide a proof-of-concept that whole genome sequences (WGS) of wild-type 3 poliovirus (PV3s) could be salvaged from the RNA extracted directly from archived poliovirus stocks avoiding re-amplification of neurovirulent viruses, we link WGSs to case histories and determine the phylogenetic relationships among the PV3s. Methods: Data retrieved from 427 poliovirus-positive cases reported between 1973 and 1988 identified 85 PV3-associated cases. A total of 71 archived PV3 isolates were available from PV3-positive cases and contacts. WGSs were obtained by NGS from cDNA libraries constructed from RNA extracted directly from archived viral stocks. Sequences were subjected to phylogenetic analysis and linked to case data. Results: WGSs were successfully constructed for 55 isolates. Phylogenetic analysis revealed the circulation of seven lineages of PV3. One lineage, with 23 isolates, presented as an outbreak of six-year duration. Isolates from six other lineages were consistent with subsequent separate introductions, sporadic cases, and limited transmission. Recombinant vaccine-like PV3 recombinants were isolated from some cases. Conclusions: Whole or near-whole genome sequence information, obtained from RNA extracted directly from the archived material, safely provided detailed genetic information linked to patient data from a time when limited sequence information was previously available and revealed the pattern of transmission of wild PV3 in Israel. Full article