History Of Herpes Simplex Virus Research Articles

Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome

Abstract Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures. Methods Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for Pneumocystis jirovecii pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis. Results Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67–533.70]) or NTM (HR, 29.09 [95% CI, 9.51–88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29–114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30–2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, P < .01) and VZV (IR, 0.006 vs 0 per person-day, P = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively. Conclusions Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.

Acyclovir extravasation in a newborn: a case report

ObjectiveExtravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation.Case reportA female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women’s Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase.ConclusionEarly diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.

The associations of herpes simplex virus and varicella zoster virus infection with dementia: a nationwide retrospective cohort study

BackgroundIn this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated.MethodsThis nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia.ResultsIn multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33–1.43) and (HR = 1.41, 95% CI:1.37–1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50–1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer’s disease (AD) and vascular dementia (VD).ConclusionsIndividual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.

A Rare Cause of Fever in a Term Neonate.

A Rare Cause of Fever in a Term Neonate.

Lumbar Skin Lesion in a Term Infant.

Lumbar Skin Lesion in a Term Infant.

Evaluation of suspected neonatal herpes simplex virus infection in preterm versus term newborns in the neonatal intensive care unit.

While national guidelines are available for the evaluation and management of term infants at risk for herpes simplex virus (HSV) infection, such guidelines are lacking for preterm infants. We sought to determine the risk factors and clinical characteristics of preterm vs. term infants who were evaluated and treated empirically for HSV infection in the neonatal intensive care unit (NICU). In a retrospective cohort study, medical records of all infants who were admitted to our NICU (2009-2016) and who were evaluated and empirically treated for HSV were reviewed for mothers' and infants' demographics, clinical characteristics, and laboratory findings. During the study period 4.2% (103/2,471) of all preterm infants, and 6.0% (112/1,865) of all term infants were evaluated and treated empirically for neonatal HSV. Among all infants who were evaluated and treated for HSV, 5.5% (12/215) had neonatal HSV disease, of whom 83.3% (10/12) were preterm infants. In comparison to term, preterm infants were more likely to be evaluated and treated, if they had a maternal history of HSV [OR 2.51 (95% CI: 1.41-4.48)], prolonged rupture of membranes [2.64 (1.221-5.73)], leukopenia [3.65 (1.94-6.87)] and thrombocytopenia [2.25 (0.85-5.89)]. HSV disease was associated with a higher mortality compared to those without disease [25% (3/12) vs. 4.4% (9/203) respectively; p = <0.05]. Preterm infants evaluated and empirically treated for HSV have a higher burden of HSV infection than term infants. HSV should be considered in the management of preterm infant with a maternal history of HSV, prolonged rupture of membranes, and thrombocytopenia.

Physician survey on pre-/postprocedure measures for injectable treatments.

Every year in the United States, over 1 billion dollars are spent on aesthetic injectables, such as soft tissue fillers and neurotoxins. In 2018, the total amount of injectable treatments performed surpassed 2671130 procedures. While often mild and transient, adverse events (AEs) can occur following these procedures. AEs may include common side effects such as bruising, or rare, but serious AEs such as infections. While previous investigators have evaluated methods of reducing risks of AEs due to the treatment procedure itself, few investigations have evaluated measures employed before and/or after treatment (ie, peri-procedure). An electronic survey was sent to aesthetic clinicians with experience performing injectable treatments. The survey collected information regarding general information (eg, demographics and specialty), type of injectable devices used, current peri-procedures, and an exploration of future options for peri-procedural measures. Most aesthetic clinicians did not use prophylactic topical or systemic antimicrobials, nor prophylactic topical antiviral therapy. However, approximately 65% of clinicians reported using prophylactic systemic antivirals for patients with a history of herpes simplex virus. A variety of products were used to prepare the skin prior to injectable procedures. Postprocedure, multiple over-the-counter wound repair products were recommended by >70% of injectors. However, there was a large variety of products recommended with no majority consensus. Currently, there are no peri-procedural standards of practice when performing aesthetic injectable treatments. Efforts are underway for the development of best-practice algorithms.

Delay of alternative antiviral therapy and poor outcomes of acyclovir-resistant herpes simplex virus infections in recipients of allogeneic stem cell transplant - a retrospective study.

Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV) reactivation after hematopoietic cell transplant (HCT), and only few reports have been published on acyclovir-resistant HSV in HCT recipients. We reviewed the medical records of patients with a microbiologic diagnosis of acyclovir-resistant HSV by plaque reduction test who received an HCT from 2002 through 2014. A total of 4 028 HCTs were performed during the study period, and 18 of the recipients met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic corticosteroid therapy for graft-versus-host disease (GVHD). The median time between diagnosis and susceptibility testing was 15 days, and antiviral therapy was changed at a median of 27 days. Patients required prolonged therapy (~80 days), and many had serious complications including renal failure and hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely during the period of profound deficit in T-cell-mediated immunity and is associated with significant morbidities. Higher doses of acyclovir prophylaxis might be needed for patients with history of HSV during pre-engraftment or GVHD treatment. In patients who do not respond or progress after 1 week of acyclovir therapy, testing for drug-resistant HSV, and early switch to an alternative antiviral should be considered.

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

Herpesvirus: an underestimated virus.

Herpes simplex virus (HSV) infections are common and widespread; nevertheless, their outcome can be of unpredictable prognosis in neonates and in immunosuppressed patients. Anti-HSV therapy is effective, but the emergence of drug-resistant strains or the drug toxicity that hamper the treatment is of great concern. Vaccine has not yet shown relevant benefit; therefore, palliative prophylactic measures have been adopted to prevent diseases. This short review proposes to present concisely the history of HSV, its taxonomy, physical structure, and replication and to explore the pathogenesis of the infection, clinical manifestations, laboratory diagnosis, treatment, prophylaxis and epidemiology of the diseases.

Molecular diagnostics and newborns at risk for genital herpes simplex virus.

Herpes simplex virus (HSV) infection in the newborn carries a high mortality rate and can result in lifelong neurologic impairment. The severity of HSV infection in the newborn has always dictated conservative management when prodromal symptoms or active genital lesions (or those suggestive of genital herpes) are present during labor and delivery. The risk of intrapartum infection, however, is related to the presence or absence of maternal immunity (neutralizing antibody) to HSV. The most significant risk of transmission is in first-episode primary infections with active lesions at delivery. Recent recommendations from the American Academy of Pediatrics Committees on Infectious Diseases and the Fetus and Newborn use rapid serologic and virologic screening in the management of asymptomatic infants born to mothers with active genital herpes. The revised guidelines highlight infants at greatest risk for HSV disease but do not apply to asymptomatic infants born to mothers with a history of HSV but no genital lesions at delivery. The current guidelines also stipulate that maternal serologic screening and molecular assays for HSV in newborn blood and cerebrospinal fluid must be available and reported in a timely fashion.

Safe Prevention of the Primary Cesarean Delivery

Safe Prevention of the Primary Cesarean Delivery

Clinical and Laboratory Characteristics of Disseminated Herpes Simplex Virus Infection in Neonates

Disseminated herpes simplex virus (HSV) infection is the most fulminant type of neonatal HSV infection and has the highest mortality. Early diagnosis and treatment are essential for patient survival. We describe the clinical presentation, laboratory characteristics, and outcomes of neonates with disseminated HSV infection at our institution. A retrospective review of electronic medical records from 2006 to 2013 was performed. Only neonates with disseminated HSV infection, confirmed by using polymerase chain reaction or viral culture results, were included. Twenty-two cases were identified; the age range was 1 to 14 days. The majority of patients did not have a maternal history of HSV or a history of maternal fever at delivery. Eleven of the patients were delivered by cesarean delivery, and 3 of these patients did not have prolonged rupture of membranes. Neonatal fever, the most common historical characteristic, was present in only one-half of the patients. Pneumonia and respiratory distress were present in one-half of the patients. Serum aspartate aminotransferase and alanine aminotransferase levels were elevated in most, but not all, patients. The blood HSV polymerase chain reaction was positive in all patients tested. Of the 22 study patients, 16 survived and 6 died. The majority of the patients who died had respiratory disease and a delay in the initiation of acyclovir therapy. Disseminated HSV infection in neonates can be challenging to diagnose and is associated with high mortality. Clinicians must strongly consider this diagnosis, test the blood for HSV polymerase chain reaction, and initiate early treatment in the appropriate clinical scenarios.

Clinical Practice in Prevention of Neonatal HSV Infection: A Survey of Obstetrical Care Providers in Alberta

ObjectiveTo identify the current practice patterns of physicians providing prenatal care in Alberta with respect to prevention of neonatal herpes simplex virus (HSV) infection. MethodA 22-item questionnaire was mailed to all obstetricians and family physicians providing obstetrical care in Alberta. The questionnaire included demographic and practice details, and details of management of patients with a history or symptoms of HSV lesions, including practice in prescribing antiviral therapy, recommending elective Caesarean section, and ordering serology. Two reminders were mailed as necessary. ResultsResponses were received from 89 obstetricians (57%) and 94 family physicians (54%). Antiviral therapy was prescribed for the prevention of neonatal HSV infection in the third trimester by 97% of obstetricians versus 84% of family physicians (P = 0.007), with acyclovir being the most commonly prescribed agent. Caesarean section was offered “most of the time” to women with primary HSV infection in the third trimester by 65% of physicians, to women with prodromal symptoms during the intrapartum period by 57% (no significant differences between groups), and to women with HSV lesions by 92% of obstetricians and 82% of family physicians (P = 0.032). Women with a negative HSV history but whose partner had known HSV were offered serological testing “most of the time” by 30% of physicians (no significant difference between groups). ConclusionDespite the encouraging survey results, obstetrical providers should be encouraged to offer Caesarean section to women with a primary HSV infection in the third trimester and to offer serological testing in discordant couples. These simple strategies can help to prevent neonatal HSV infection and its long-term consequences.

Intrauterine Herpes Simplex Virus Infection in a Monochorionic Twin Gestation.

Herpes simplex virus (HSV) of the newborn affects 1 in 3200 [1] live births in the United States, and can be acquired by the intrauterine or intrapartum route, or postnatally. Intrauterine or congenital infection represents the rarest form (5% of cases) [2] and frequently has devastating consequences such as congenital brain malformation and severe neurocognitive impairment leading to fetal or neonatal death [3]. Here we present two cases of fatal intrauterine HSV infection in monochorionic twin infants. CASE A 21-year-old secundigravida mother with twin gestation of 26-4/7 weeks presented with spontaneous rupture of membranes of clear amniotic fluid 11 hours prior to delivery. She had negative prenatal laboratory studies for hepatitis B, syphilis, human immunodeficiency virus (HIV), and an unknown group B streptococcus status. Her sexually transmitted infection history included chlamydia trachomatis infection treated during early pregnancy and no history of HSV in herself or her sexual partner. A structural survey 1 week prior to delivery revealed severe hydrops and hydranencephaly in the first twin, and moderate hydrocephalus in the second twin. The mother was afebrile, well-appearing, and reported no history of recent illness or genital lesions before or during either of her pregnancies. Both mother and father refused HSV serologic testing. The first twin boy was delivered via cesarean section with Apgar scores of 1, 2, and 3, at 1, 5, and 10 minutes, respectively. The infant was apneic, unresponsive to resuscitation efforts, and died shortly after birth. On autopsy, gestation was shown to be monochorionic–monoamniotic, and the placenta had evidence of acute chorioamnionitis; however, it was not tested for the presence of HSV. The intracranial cavity was composed of hemorrhagic fluid and fragments of parenchymal tissue with extensive necrosis and chronic inflammation, consistent with meningoencephalitis, and the liver was calcified and necrotic. Viral immunostaining revealed the presence of HSV in the adrenal gland and brain parenchyma, and no virus was detected in the liver. No viral cultures were performed on autopsy tissue due to formalin fixation, and surface cultures for HSV were not performed. The second twin boy had Apgar scores of 5, 7, and 8 at 1, 5, and 10 minutes, respectively. He was immediately intubated for respiratory distress, received inotropes and intravenous fluids for hypotension, and was given ampicillin and gentamicin for presumed sepsis. At 5 hours of life, vesicular skin lesions on the neck were noted on physical examination (PE). PE was otherwise unremarkable. HSV studies were sent from the skin lesion (neck), mucosal surfaces (eyes, mouth, rectum), and cerebrospinal fluid (CSF), and empiric acyclovir 20 mg/kg every 8 hours was started. Initial white blood cell (WBC) count, platelet count, liver function, and serum electrolytes were normal. The CSF revealed 111 WBC/mm 3 with a lymphocytic predominance, 7600 red blood cells/mm 3 , protein 1245 mg/dL, and glucose 21 mg/dL. Blood and CSF bacterial cultures were sterile. Toxoplasma immunoglobulin M antibody, cytomegalovirus (CMV), and parvovirus B-19 polymerase chain reaction (PCR) yielded negative results. PCR was positive for HSV type 2 (HSV-2) and negative for HSV type l from all five tested sites.

Index of Suspicion in The Nursery

A 4-day-old male infant presents in late November to the pediatrics clinic with decreased activity and poor feeding. The mother reports that he had been feeding and acting well until 1 day before presentation. The mother states that he has not had any rhinorrhea, nasal congestion, cough, vomiting, diarrhea, rash, or any atypical movements that could be seizures. She had not taken his temperature, and she states that he has not felt hot. The pediatrician becomes immediately concerned as she recognizes a lethargic infant in respiratory distress. A code is called, and the resuscitation is begun. The infant was a 3,083-g product of a 38+1 week gestation to a 28-year-old G2P1 woman. The pregnancy was only complicated by a positive group B streptococcus screen at 35 weeks' gestation and a history of herpes simplex virus in the past, but no lesions were noted before or during delivery. On presentation to labor and delivery, the fetus was noted to be tachycardic and the mother had mild abdominal tenderness, leading to initiation of ampicillin and gentamicin 16 hours before delivery. The duration of rupture of membranes was 4 hours. The infant was born via spontaneous vaginal delivery and was vigorous, with Apgar scores of 9 and 9 at 1 and 5 minutes. Because the mother was neither febrile nor tachycardic, it was decided that she did not have chorioamnionitis, so the infant received no further laboratory evaluation or antibiotics. The mother and infant were discharged from the hospital after 2 uneventful days. In the clinic, the 4-day-old infant has initial vital signs that included a temperature of 98.9°F, a heart rate of 170 beats per minute, a respiratory rate of 71 breaths per minute, an oxygen saturation (SaO2) of 80% on room air, and blood pressure 84/35 mm …

Unilateral keratitis following death of a twin as the presenting sign of herpetic infection in a neonate

Neonatal herpes simplex virus (HSV) manifests as a disease limited to skin, eyes, and/or mucous membranes, central nervous system disease with/without skin involvement, or disseminated infection. Given the high morbidity and mortality of untreated neonatal HSV, early recognition and prompt treatment are important. We report two cases of unilateral HSV keratitis, after Cesarean section, in neonates whose twin had died. Both mothers denied history of HSV. Ophthalmic diagnosis led to full systemic workup and appropriate treatment.

Legal Briefs

A 3,545-g, 35–3/7 weeks', large for gestational age (LGA) male is delivered to an insulin-dependent diabetic mother who became pregnant with the help of a fertility specialist. After conception, a general obstetrician managed her pregnancy. The antenatal course was uneventful except for a history of herpes simplex virus (HSV) infection. A cesarean section was planned at 38 weeks' gestation because of a relatively large fetus and a small pelvic outlet. The mother developed premature rupture of membranes (PROM) at 35 weeks' gestation, and 48 hours later, labor began. The obstetrician was out of town, and the mother was triaged to a midwife for the delivery. The mother's last HSV outbreak was 2 weeks before delivery, with lesions healing 4 days before delivery. The mother claimed in her deposition that she told the midwife about her history of herpes. The medical records from the fertility specialist and the obstetrician documented the history of HSV. The medical records reflecting the herpes were computerized and available to the midwife and the nurses who managed labor and delivery. The infant was delivered by a spontaneous vaginal vertex delivery. The Apgar scores were 8 at 1 minute and 9 at 5 minutes. The infant was asymptomatic and observed for 6 hours before rooming-in with his mother. Multiple bedside glucose evaluations were read as normal. A complete blood count (CBC) yielded unremarkable results. A blood culture was reported as negative on the final reading. Vital signs were stable. The infant was sleepy at the breast, but the mother fed him formula. The discharge examination was performed at 41 hours, and the only notable finding besides the LGA and late preterm gestation was that an ophthalmic examination could not be performed because the eyes were closed. The grandmother stated in her deposition that the baby's eyes were …

Genetic predisposition to HSV-1 encephalitis

In this issue of The Journal, Abel et al report clinical data from 85 sporadic cases of HSV-1 encephalitis (HSE) in children from several centers in France. Fifty-one families were interviewed to explore the history of HSV and other infections in relatives, as well as consanguinity. Samples for serologic and genetic testing also were collected from 49 patients. Although no familial cases of HSE were identified, 20% of cases had parental consanguinity or history of a relative with herpes keratitis at a young age. These findings, as well as young age of cases and identification of specific genetic mutations in two patients resulting in impaired interferon production, led investigators to propose that childhood HSE, although sporadic and seemingly random, may be the result of genetic predisposition in some cases. These investigations add to a body of evidence, which suggests that specific “glitches” in innate immune function, rather than bad luck, are responsible for some sporadic, uncommon manifestations of infectious diseases, especially in children. Article page 623 ▸ Age-Dependent Mendelian Predisposition to Herpes Simplex Virus Type 1 Encephalitis in ChildhoodThe Journal of PediatricsVol. 157Issue 4PreviewTo test the hypothesis that predisposition to childhood herpes simplex virus (HSV) type 1 encephalitis (HSE) may be determined in part by human genetic factors. Full-Text PDF

Selective Changes in Human Corneal Sensation Associated with Herpes Simplex Virus Keratitis

To determine corneal sensitivity to selective mechanical, chemical, and thermal (heat and cold) stimulation in patients with a history of herpes simplex virus (HSV) keratitis. Corneal sensitivity to different modalities of stimulus was determined in both eyes of 16 patients with unilateral HSV keratitis diagnosed 1 to 12 months before the study. On slit lamp examination, 13 HSV-affected eyes showed corneal scarring or opacities, and three had no signs of previous keratitis. Corneal sensitivity was determined with the Belmonte gas esthesiometer. Mechanical, chemical, heat, and cold stimuli were applied on the central cornea. Eyes from 10 healthy subjects served as controls. In all control and contralateral eyes, selective mechanical, chemical, heat, and cold stimulation evoked sensations of subjective intensity proportional to the magnitude of the applied stimulus. In one HSV patient, the affected cornea was unresponsive to all types of stimuli, four lost only corneal sensitivity to mechanical stimulation, and three lost only sensitivity to heat. Mechanical (P<0.005) and heat (P<0.05) thresholds were raised in HSV eyes, whereas thresholds for CO2 were not modified. Also, HSV subjects identified poorly the intensity of mechanical, chemical, and heat stimuli, whereas sensitivity to cold stimulation was unaffected. In eyes that had had HSV keratitis, corneal sensitivity to mechanical forces and heat was significantly impaired, suggesting that axonal damage and/or altered expression of membrane ion channels involved in transduction and membrane excitability affects primarily the mechano- and polymodal nociceptor terminals. Corneal cold-sensitive terminals remain largely unaffected.