A hidden dilemma; post COVID-19 first detection of Varicella zoster M4 genotype from Pakistan.

OBJECTIVES: During the COVID-19 pandemic, the risk of childhood infectious diseases was increased. Post-COVID-19 escalation of chickenpox cases, becoming an emerging public health concern. Thus, the study was designed to compare chickenpox prevalence and Varicella zoster virus (VZV) genotypes circulating before, during, and post-COVID-19 in Pakistan. METHODS: A total of 267 lesion specimens collected from tertiary care hospitals, and chickenpox outbreaks from Pakistan were analysed by a two-amplicon approach with phylogenetic analysis. RESULTS: Among suspected cases, overall 178/267 were VZV positive. Majority (84.2 %; 150/178) cases were of post-COVID-19 pandemic time. Small outbreaks occurred soon after COVID-19 in Rawalpindi and Islamabad (Pakistan), 40 positive cases out of 178 cases were outbreak cases. There was first time detection of the M4 genotype, which was significantly associated with disease severity (p = 0.0006) and post-COVID-19 chickenpox outbreaks in 2021 (77.9 %; 46/59; p < 0.00001). However, in pre-COVID-19 only M2 genotype was detected. The M2 prevalence varied from 2019 (100 %; 19/19) to 2022 (3.2 %; 3/91). However, the most prevalent strain of 2022 belonged to the M1 genotype (64.8 %; 59/91). CONCLUSION: A significant rise in chickenpox cases detected soon after COVID-19 in Pakistan, and oscillation of different VZV genotypes with first time detection of M4 genotype is an alarming situation. This demands further detailed genotypic studies on transmission dynamics of a rare M4 with other genotypes to protect the local population and restrict spread in other regions.

Position statement on infection screening, prophylaxis, and vaccination of pediatric patients with rheumatic diseases and immunosuppressive therapies, part 3: precautions in situations of surgery, fever, and opportunistic infections.

The objective of this study is to provide practical recommendations on the management of pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The recommendations specifically address the cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, invasive fungal disease). A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify publications on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the Infection Prevention and Treatment Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process; this was extended to members of the Spanish Society of Pediatric Rheumatology and Spanish Society of Pediatric Infectious Disease of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (totally disagree) to 10 (totally agree). Agreement was defined as a vote ≥ 7 by at least 70% of participants. The literature review included more than 400 articles. Overall, 63 recommendations (19 on surgery, fever, and opportunistic infections) were generated and voted by 59 pediatric rheumatologists and other pediatric specialists. Agreement was reached for all 63 recommendations. The recommendations on special situations cover management in cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, and invasive fungal disease).  Conclusions: Hereby, we provided consensus and updated of recommendations about the management of special situations such as surgery, fever, and opportunistic in children with immune-mediated rheumatic diseases receiving immunosuppressive therapies. Several of the recommendations depend largely on clinical judgement and specific balance between risk and benefit for each individual and situation. To assess this risk, the clinician should have knowledge of the drugs, the patient's previous situation as well as the current infectious disease, in addition to experience. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • Information on how to manage the treatment in situations of fever, opportunistic infections, and surgery in children is limited, and guidelines for action are often extrapolated from adults. What is New: • In the absence of strong evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could support the clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.

Genomic characterization of the first mpox and varicella-zoster co-infection in Pakistan (2023) through next-generation sequencing.

The global mpox outbreak spanning 2022-2023 has affected numerous countries worldwide. In this study, we present the first report on the detection, whole-genome sequence, and coinfection of the mpox virus and varicella zoster virus (VZV) from Pakistan. During April-May 2023, samples from 20 suspected cases of mpox were tested at the National Institutes of Health, Islamabad among which 4 tested positive. All four cases had a travel history of Saudi Arabia. All the suspected samples were processed by using a Zymo research kit for DNA extraction, followed by qRT-PCR amplification by using a DaAn Gene detection kit for the mpox virus. Further, two of the positive samples with a low Ct value (<20) were subjected to whole-genome sequencing using a metagenomic approach on the iSeq (Illumina) platform. The sequencing results revealed Clade IIb and genotype A.2.1 of MPXV, which clustered with viruses from Slovenia and the UK in July and June 2022, respectively. Our analysis identified two novel nonsynonymous substitutions in mpox virus, namely V98I in OPG046 and P600S in OPG109. Furthermore, we successfully retrieved the complete genome of VZV from the same sample, belonging to Clade 5. This study represents the first positive case of MPXV in Pakistan and the coinfection of mpox and VZV by using a metagenome approach providing insights into their complete genomes. Our results highlight the importance of surveillance at the point of entries, strengthening lab capacities including next-generation sequencing, and using differential diagnosis for timely and accurate detection of mpox cases.

Varicella vaccine meningoencephalitis in a child receiving autologous bone marrow transplantation.

BACKGROUND: Varicella vaccine, a live-attenuated Oka-strain of varicella zoster virus (VZV), is a recommended childhood vaccine by many countries. As with wild varicella strain, after primary infection, the live-attenuated virus can establish latency in sensory ganglia and reactivate causing vaccine-strain illnesses: herpes zoster (HZ), visceral or peripheral and central nervous system dissemination. We report a case of early reactivation of live-attenuated virus-HZ and meningoencephalitis-in an immunocompromised child. METHODS: This is a retrospective descriptive report of a case, in a tertiary pediatric hospital, CHU Sainte-Justine (Montréal, Canada). RESULTS: An 18 month-year old girl diagnosed with a primitive neuro-ectodermal tumor (PNET) received the day prior to diagnosis, a first varicella vaccine (MMRV). She received chemotherapy 20 days post MMRV vaccine and autologous bone marrow transplantation 3 months post vaccination. She was considered not eligible, to acyclovir prophylaxis prior transplantation (positive for VZV IgG and negative for herpes simplex virus IgG by ELISA). At day 1 post transplantation, she developed dermatomal HZ and meningoencephalitis. Oka-strain varicella was isolated, she was treated with acyclovir and foscarnet. Neurologic status improved in 5 days. Control of VZV viral load in cerebrospinal fluid showed a slow decrease to from 5.24 log 10 copies/mL to 2.14 log 10 copies/mL in 6 weeks. No relapse was observed. She recovered without neurological sequelae. CONCLUSIONS: Our experience highlights the importance of conducting a thorough medical history regarding vaccination and serological status of newly immunocompromised patients. Intensive chemotherapy succeeding live vaccine administration <4 weeks could have influenced early and severe viral reactivation. Early initiation of prophylactic antiviral treatment is questioned in such circumstances.

Rapid detection of varicella-zoster virus based on an immunochromatographic strip.

Varicella-zoster virus (VZV) is a highly infectious DNA virus that can cause varicella (chickenpox) and herpes zoster (HZ). A simple, sensitive and specific detection method is desirable for the VZV infection. In this study, VZV gE protein, expressed in CHO cells, was used to immunize BALB/c mice for the generation of monoclonal antibodies (mAbs). For the first time, we developed a colloidal gold-based immunochromatographic strip for rapid detection of VZV using a pair of mAbs against gE protein. The limit of detection (LOD) of the strip was 30 ng mL-1 of purified VZV gE antigen, and it could specifically test VZV without cross-reactivity with Enterovirus 71 (EV-71), Herpes simplex virus 1 (HSV-1) and Herpes simplex virus 2 (HSV-2). The coincidence rate between the strip and commercial real-time PCR diagnostic kit was 100% using vesicle as the clinical sample. Our strip provided a technical support for rapid and specific detection of VZV.

The clinical course of herpes zoster is similar in immunocompetent and immunocompromised paediatric patients.

AIM: We aimed to compare the clinical manifestation of HZ in immunocompetent and immunocompromised children. METHODS: Medical charts of all consecutive children hospitalized and/or consulted in the Regional Hospital for Infectious Diseases in Warsaw due to HZ were retrospectively analysed. Age, history of varicella, time interval between varicella and HZ, underlying diseases, immunosuppresive therapy, dermatome involvement and HZ complications were analyzed in both groups. RESULTS: In total 152 children were included in the analysis, 56 (36.84%) of them were hospitalsed, whereas 96 (63.16%) were consulted and discharged home due to good general condition. The median age was 10 years (IQR 5.75-12), there were 73 (48.03%) boys and 79 (51.97%) girls. In 16/152 (10.5%) one or more complications occurred, including: skin bacterial superinfection (16/17, 94.2%), sepsis (1/17, 5.9%), meningitis (1/17, 5.9%). Thoracic dermatomes were the most commonly affected (81/152, 53.29%). Most of the children didn't have any immunodeficiencies 118/152 (77.6%), and 34/152 (22.4%) of them were immunocompromised (and had been treated with intravenous acyclovir). The clinical picture of the disease was similar in both groups (Table 1). However, immunocompromised children more often had sacral dermatomes affected (5/35, 14.3% vs. 1/117, 0.9%, p < 0.001), and less often thoracic dermatomes were involved in this group (12/35, 34.3% vs. 69/117, 59%, p = 0.0102). CONCLUSIONS: To conclude, herpes zoster occurs in both immunocompetent and immunocompromised children. Clinical manifestations are similar. Serious complications, although uncommon, affect not only immunocompromised patients but also otherwise healthy children.

Disseminated varicella-zoster virus infection in an aplastic anemia- paroxysmal nocturnal hemoglobinuria syndrome patient: A case report.

Background: Varicella-zoster virus (VZV) is a common and widespread human-restricted pathogen. It is famous for its dermatological manifestations, such as varicella and herpes zoster. Patients with aplastic anemia-paroxysmal nocturnal hemoglobinuria (AA-PNH) syndrome complicated with fatal disseminated varicella zoster virus infection are very rare and in danger. Patient concerns: A 26-year-old man with a history of AA-PNH syndrome was receiving cyclosporine and corticosteroid treatment in the hematology department. During his hospitalization in our hospital, he developed fever, abdominal pain, and lower back pain, and his face, penis, trunk, and limbs developed itchy rash. Subsequently, the patient had to undergo cardiopulmonary resuscitation because of sudden cardiac arrest, and be transferred to ICU for treatment. It was presumed that the cause is unknown severe sepsis. The patient's condition quickly progressed to multiple organ failure, accompanied by liver, respiratory, and circulatory failure, and signs of disseminated intravascular coagulation. Unfortunately, the patient died after 8 h of active treatment. Finally, we collected all the evidence and concluded that the patient died of AA-PNH syndrome combined with poxzoster virus. Conclusion: AA-PNH syndrome patients treated with steroids and immunosuppressants are prone to various infections, considering that herpes virus infection with chickenpox and rash as the initial manifestations is characterized by rapid progress and often accompanied by serious complications. It is more difficult to distinguish it from AA-PNH syndrome with skin bleeding points. If it is not identified in time, it may delay the treatment opportunity, make the condition worse, and cause serious adverse prognosis. Therefore, clinicians need to pay attention to it.

Comparison of human monkeypox, chickenpox and smallpox: a comprehensive review of pathology and dermatological manifestations.

Variola virus, the causing agent of smallpox, was eradicated in 1980s and today no new cases are reported. The first human infectious illness to be eliminated globally is variola. On the contrary to Variola, monkeypox, which is a zoonotic and variola-like disease, has nowadays turned to be a major health problem worldwide. VZV is a neurotropic virus and the cause of varicella (chickenpox) and herpes zoster (shingles), which is also a highly infectious disease, especially prevalent in children. These three skin diseases-monkeypox, smallpox, and chickenpox-are frequently mistaken with one another due to similar manifestations including fever, rash, myalgia, chills and headache, but they can all be distinguished by their distinctive symptoms. Although these rash-causing disorders might present different skin lesions; diagnostic tests can be extremely useful in their differentiation. We searched for these concepts on a search engine like Google Scholar, scanning the results for alternative words and phrases, and examined relevant abstracts or articles for alternative words. The clinical diagnosis of monkeypox infection is commonly made based on the occurrence pattern of its skin rash. It is possible in varicella to concurrently identify lesions in their various stages including macular, papular, vesicular, pustular, and crusts; however, monkeypox lesions are all in the same stage and evolve with the same rate. In this review, we have tried to provide a holistic and comprehensive comparison between these three skin infections with a focus on the newly epidemic monkeypox, bringing about the most recent knowledge about its features and its diagnosis.

Rapid, sensitive, and specific lateral-flow immunochromatographic point-of-care device for detection of varicella-zoster virus immunoglobulin G antibodies in fingerstick blood.

Varicella zoster virus (VZV) causes childhood chickenpox, becomes latent in sensory ganglia and reactivates years later to cause shingles (Zoster) and postherpetic neuralgia in the elderly and immunosuppressed individuals. Serologic IgG tests can be used to determine if a person has antibodies to VZV from past varicella infection or had received varicella or zoster (shingles) vaccination. Commercial enzyme-linked immunosorbent assays (ELISAs) are currently used for the detection of VZV IgG antibodies in patient serum samples. However, ELISA tests require collection and processing of blood samples in a CLIA laboratory to separate serum or plasma for further testing. In this paper, we describe the development and testing of an antibody based Lateral Flow Immunochromatographic assay (LFA) device for the detection of VZV IgG in fingerstick whole blood. Analytical and clinical analyses were performed to compare the performance characteristics of the Viro VZV IgG LFA (VZV LFA) and the Diamedix VZV IgG ELISA. Analytical studies demonstrated the higher sensitivity of the VZV LFA compared to the ELISA by testing dilutions of the WHO VZV IgG serum International Standard. Clinical performance characteristics of the VZV LFA fingerstick whole blood assay were assessed at three point of care (POC) facilities by untrained users testing samples from 300 prospectively enrolled study subjects. VZV LFA results were compared with results obtained by testing serum samples obtained from the same study participants by the Diamedix VZV IgG ELISA. Two specimens with invalid results by the LFA assay were not included in the LFA performance calculations and nine equivocal ELISA results were included as positive for IgG results. The results from all three POC clinical sites demonstrated the higher sensitivity/positive percent agreement (PPA) (99.26%, 95% CI: 97.34-99.80) of the VZV LFA compared to the Diamedix VZV IgG ELISA (94.08%, 95% CI: 90.72-96.27). The specificity/negative percent agreement (NPA) of the VZV LFA compared to the ELISA test was calculated initially to be 39.29% (95% CI: 23.57-57.59) with 19 discordant test results out of 298 test results between the two assays (17 LFA positive/ELISA negative and two LFA negative/ELISA positive). The PPA and true NPA of the VZV LFA were determined by testing all 298 samples, including the discordant (19) and all concordant negative and positive (279) study subject serum samples, before and after blocking VZV gE antibody sites in the samples by spiking with VZV LFA gE capture antigen. The NPA improved to 100% (95% CI: 74.12-100) after the procedure when compared to the ELISA test results. The comparator ELISA PPA based on the spiking/blocking study remained as 94.08%, (95% CI: 90.72-96.27), comparable to test results from untreated samples. The VZV LFA has been demonstrated to be simple and sufficiently robust for use in CLIA-waived POC facilities by untrained healthcare professionals and to detect VZV IgG in 20 min from fingerstick whole blood. The VZV LFA therefore provides a fast, reliable, and highly sensitive method of determining prior VZV viral infection or varicella and zoster vaccination status.

Cold antibody autoimmune hemolytic anemia following varicella infection.

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare complication of chicken pox. In adults, such AIHA is due to warm antibodies. We report a case of cold antibody AIHA following chicken pox in a young female. Case Report: A 24-year-old female presented with clinical and laboratory features consistent with hemolytic anemia 5 days after the onset of chicken pox. Her hemoglobin levels dropped rapidly during the course of admission from 7.9 to 3.8 g/dL with evidence of ongoing haemolysis in the form of rising total and indirect bilirubin. Peripheral smear revealed red cell agglutinates and erythrophagocytosis. Direct Coomb's test (DCT) was positive for C3d suggesting a cold antibody AIHA. Since test for Donath Landsteiner antibody was negative, and all other tests for common causes of hemolytic anemia were noncontributory, it was presumed to be due to chicken pox. The fulminant course necessitated a short course of oral steroids to which she responded with rise in hemoglobin and no further hemolysis. Two weeks later, her peripheral smear was normal and DCT negative. Conclusion: In patients presenting with acute onset anemia following chicken pox, possibility of cold antibody AIHA must be considered and appropriate testing pursued. Despite lack of empiric evidence, short course of steroids may be beneficial if drop in hemoglobin is rapid with evidence of fulminant hemolysis, showing no abatement after first week.

How to differentiate skin rash in covid, mononucleosis, chickenpox, sixth disease and measles.

PURPOSE OF REVIEW: Skin rashes seen during COVID-19 usually feature maculopapular or vesicular morphology, thus mimicking cutaneous eruptions occurring in other common infectious dermatoses, such as mononucleosis, chickenpox, sixth disease and measles, with possible diagnostic mistakes. In this review article, we sought to provide a practical overview about clinical appearance of skin rashes related to SARS-CoV-2 infection. RECENT FINDINGS: The study summarizes literature evidence on clinical patterns of COVID-19-associated maculopapular or vesicular rash, with a particular emphasis on the principal points of differentiation with possible mimickers. SUMMARY: Several differences do exist between rashes due to SARS-CoV-2 infection and other viral eruptions, mainly including lesions morphology, spreading pattern, symptoms and mucosal involvement. The increase of awareness of such features among clinicians may help promptly recognize COVID-19-related exanthemas in order to take proper action to manage the infection.

Diagnostic and Immunologic Testing for Varicella in the Era of High-Impact Varicella Vaccination: An Evolving Problem.

The clinical presentation of varicella in unvaccinated persons, with skin vesicles and scabs, has facilitated the use of rapid diagnostic methods for confirming disease. Polymerase chain reaction (PCR) assays are the diagnostic method of choice. The sharp decline in unmodified cases of varicella due to the US varicella vaccination program has led to fewer healthcare providers being familiar with varicella presentation and an increased reliance on laboratory diagnosis to confirm suspected cases. The mild, atypical presentation of the disease in vaccinated persons (fewer skin lesions, mostly maculopapular) has made it more challenging for providers to recognize and also to collect samples to detect the virus. Nonetheless, PCR is highly sensitive and specific in confirming modified disease if adequate samples are provided. While a positive PCR result is confirmatory, interpreting a negative result can prove to be more challenging in determining whether suspected varicella is falsely negative or attributable to other causes. Enhanced education of healthcare providers is critical for adequate specimen collection from modified varicella cases. In addition, more sensitive commercial serologic assays are needed in the United States for varicella immunity testing in the vaccine era.

Clinical Manifestations of Varicella: Disease Is Largely Forgotten, but It's Not Gone.

After 25 years of varicella vaccination in the United States, classic varicella and its complications have become an uncommon occurrence. The clinical manifestation of varicella among vaccinated persons is usually modified, with fewer skin lesions, mostly maculopapular, and milder presentation. However, the potential for severe manifestations from varicella still exists among both vaccinated and unvaccinated persons, and thus healthcare providers should keep varicella in the differential diagnosis of a maculopapular or vesicular rash. The prompt recognition and diagnosis of varicella is important because when confirmed, clinical and public health measures need to be taken swiftly.

Thrombotic Microangiopathy Secondary to Disseminated Varicella Zoster Virus Infection in an Adult Patient.

BACKGROUND Thrombotic microangiopathy (TMA) is a life-threatening condition caused by small-vessel platelet microthrombi. While various disease triggering factors, including infections, have been well described, there have been few reports of an association between TMA and varicella zoster virus (VZV) infection. VZV infection is rare among people age 20 and older, and infection-induced TMA is mostly reported in the pediatric age group. We report a case of TMA induced by a disseminated VZV infection in an adult. CASE REPORT A 43-year-old man presented with a 3-day duration of fever, headache, vomiting, and bloody diarrhea. He also reported body rash after a recent contact with a few roommates with chickenpox. On presentation, the patient developed convulsive seizures. His laboratory test results were significant for acute kidney injury (AKI) and thrombocytopenia. Atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP) were suspected but further diagnostic testing was negative. The treatment plan included acyclovir, therapeutic plasma exchange, and high-dose oral prednisolone (1.5 mg/kg). The clinical and biochemical profile significantly improved, and the patient was discharged home. CONCLUSIONS TMA is a life-threatening hematological emergency with a high mortality rate. Compared to the pediatric population, VZV infection tends to be more severe in the adult age group. This case demonstrates that a high index of suspicion for TMA in adult patients with VZV who present with thrombocytopenia, even when there is no definitive diagnosis, can result in early management with favorable outcome.