PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1061507)

Clipboard (0)
None

Related Articles

1.  Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial 
Lancet  2008;371(9630):2109-2119.
Summary
Background
Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.
Methods
We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12–18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00076232.
Findings
3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83–1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46–0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31–0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug.
Interpretation
Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.
Funding
US National Institute of Allergy and Infectious Diseases, US National Institute of Child Health and Human Development, US National Institute of Drug Abuse, US National Institute of Mental Health, US Office of AIDS Research, and GlaxoSmithKline.
doi:10.1016/S0140-6736(08)60920-4
PMCID: PMC2650104  PMID: 18572080
2.  Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years 
Background
Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management.
Methodology/Principal Findings
Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses.
Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%).
Conclusions/Significance
Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the majority of morbidity/mortality amongst patients with a confirmed/probable diagnosis is preventable by adequate vaccination/treatment, and are therefore of public health significance.
Author Summary
Central nervous system (CNS) infections are important diseases worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the causes of the diseases is of public health importance, in order to better inform immunization policy, and influence clinical management. We describe the clinical features and infectious causes of 291 adults with clinically suspected CNS infections of presumed viral origin. We show that CNS viral infections in Vietnam are associated with high morbidity and mortality. Mortality was especially high (47%) amongst those with herpes simplex encephalitis which is attributed to the limited availability specific antiviral drugs in our setting. Japanese encephalitis virus, dengue viruses, herpes simplex virus and enteroviruses were the most common viruses detected, followed by rubella virus, varicella zoster virus, mumps virus, cytomegalovirus, and rabies virus. Our study represents the broadest yet investigation of the possible viral causes of the CNS infections in adults in Vietnam, with a diagnostic yield of 32%. The results show that the majority of morbidity/mortality amongst patients with a confirmed/probable diagnosis could be prevented by adequate vaccination or treatment, and are therefore of public health significance.
doi:10.1371/journal.pntd.0003127
PMCID: PMC4148224  PMID: 25165820
3.  Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. 
BMJ : British Medical Journal  1997;314(7097):1800-1803.
OBJECTIVES: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children. DESIGN: Randomised double blind placebo controlled study. SETTING: Day care unit of a tertiary paediatric hospital. SUBJECTS: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study. MAIN OUTCOME MEASURES: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding. INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo. RESULTS: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)). CONCLUSIONS: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment.
PMCID: PMC2126953  PMID: 9224082
4.  Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group. 
Genitourinary Medicine  1997;73(2):110-116.
OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection in immunocompetent individuals. METHODS: 739 patients with a history of recurrent genital HSV infection received either oral valaciclovir (500 mg twice daily) or aciclovir (200 mg five times daily) for 5-days for treatment of their next recurrent episode in a controlled, randomised, double blind trial. Patients self initiated therapy at the first signs and/or symptoms of the HSV recurrence, then were assessed in clinic on five occasions over 7 days, and twice weekly thereafter until lesions had healed. Safety was evaluated through adverse experience reports and haematology and biochemistry monitoring. RESULTS: No significant differences were detected between valaciclovir and aciclovir for the primary endpoint, the duration of all signs and symptoms which included lesion healing and pain/discomfort. The hazard ratio [95% confidence interval] for valaciclovir v aciclovir was 0.93 [0.79, 1.08]. Lesion healing time was similar in each treatment group (hazard ratio valaciclovir v aciclovir 0.96 [0.80, 1.14]). The odds ratio of valaciclovir v aciclovir in preventing the development of vesicular/ulcerative lesions was 1.08 [0.82, 1.42]. Percentages of patients in whom all HSV cultures were negative were similar in the valaciclovir and aciclovir groups at 59% and 54% respectively; for patients having equal to or more than one positive culture result after treatment initiation, cessation of virus shedding was similarly rapid for the two treatments (hazard ratio 0.98 [0.75, 1.27]). The safety profiles of valaciclovir and aciclovir were comparable with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that valaciclovir 500 mg twice daily is equivalent in efficacy to aciclovir 200 mg five times daily as episodic treatment of recurrent genital HSV infection. Valaciclovir maintains the established efficacy and safety of aciclovir but offers a much more convenient twice daily dosing regimen.
PMCID: PMC1195783  PMID: 9215092
5.  Therapy for genital herpes in immunocompromised patients: a national survey. The Herpes Simplex Advisory Panel. 
Genitourinary Medicine  1997;73(5):391-393.
OBJECTIVES: To estimate the extent of aciclovir refractory herpes simplex virus (HSV) infection in HIV coinfected patients in the United Kingdom and survey clinicians on their approaches to its management. DESIGN: Questionnaire survey of representative sample of one third of United Kingdom HIV physicians. MAIN OUTCOME MEASURES: Use of antiviral therapies for genital HSV infections in HIV positive patients, reported frequency of aciclovir refractory HSV infection, its therapy, and access to antiviral susceptibility testing facilities. RESULTS: 53 responses were obtained (response rate 61%), representing a sample size of 23% of United Kingdom HIV physicians. Use of non-standard antiviral regimens for HSV infections in HIV coinfected patients was widely practised, irrespective of the clinical characteristics of the HSV infection. Aciclovir refractory HSV infection has been observed by 37 (70%) respondents. Although foscarnet was the most frequently used therapy, used by 27/37 (73%) respondents, in only seven of these 27 (19%) was it a first line treatment for aciclovir refractory cases, frequently being used at a late stage in the clinical course. Antiviral susceptibility testing facilities were available to 46 (87%) clinicians. No respondents reported any evidence of transmission of aciclovir resistant strains. CONCLUSIONS: HIV coinfection has a stronger influence on therapeutic choice than clinical immunosuppression or severity of herpetic infection. Aciclovir treatment failure is commoner than hitherto recognised. There is a need for wider awareness of use of foscarnet at an earlier stage in management of refractory HSV infection.
Images
PMCID: PMC1195900  PMID: 9534751
6.  Diagnostic delay in a case of herpes simplex encephalitis 
BMJ Case Reports  2009;2009:bcr12.2008.1350.
Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic fatal encephalitis in the Western world. Definitive diagnosis by viral PCR of cerebrospinal fluid (CSF) and treatment with aciclovir have improved the prognosis significantly. Nevertheless, the condition is rare and presents with non-specific symptoms that can easily be mistaken for systemic infection or non-infective encephalopathy. We report a case of HSE which was not recognised by four separate doctors, leading to substantial delay in diagnosis and treatment. Our patient presented with fever, headaches, altered behaviour and generalised bradykinesia. This was initially diagnosed as otitis interna (labyrinthitis) and, subsequently, an ischaemic stroke. There was a delay of 10 days in the initiation of aciclovir from symptom onset. MRI and CSF PCR confirmed herpes simplex virus type-1 (HSV-1) infection. The patient improved on aciclovir, but is disabled with word-finding difficulties and cognitive slowing.
doi:10.1136/bcr.12.2008.1350
PMCID: PMC3028237  PMID: 21686359
7.  Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection 
Critical Care  2009;13(3):R101.
Introduction
Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in septic shock, but its role in central nervous system infection (CNS) remains to be defined.
Methods
We investigated cerebrospinal fluid (CSF) levels of MIF in 171 patients who were clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis of known aetiology, 20 purulent meningitis of unknown aetiology, 59 lymphocytic meningitis and 11 encephalitis, whereas 50 were suspected of having but had no evidence of CNS infection.
Results
CSF MIF levels were significantly higher in patients with purulent meningitis of known aetiology (median [interquartile range]: 8,639 [3,344 to 20,600] ng/l) than in patients with purulent meningitis of unknown aetiology (2,209 [1,516 to 6,550] ng/l; Mann-Whitney test, P = 0.003), patients with lymphocytic meningitis (1,912 [1,302 to 4,105] ng/l; P < 0.001) and patients suspected of having but without evidence of CNS infection (1,472 [672 to 3,447] ng/l; P < 0.001). Also, patients with encephalitis (6,937 [3,961 to 8,353] ng/l) had higher CSF MIF than did patients without CNS infection (P < 0.01). Among patients with purulent meningitis, CSF MIF levels were significantly higher in patients infected with pneumococci than in those with meningococcal infection (11,569 [8,615 to 21,935] ng/l versus 5,006 [1,717 to 10,905] ng/l; P = 0.02), in patients who required versus those not requiring assisted ventilation (10,493 [5,961 to 22,725] ng/l versus 3,240 [1,563 to 9,302] ng/l; P = 0.003), and in patients with versus those without impaired consciousness (8,614 [3,344 to 20,935] ng/l versus 2,625 [1,561 to 7,530] ng/l; P = 0.02). CSF MIF levels correlated significantly with meningeal inflammation (P < 0.05) but not with systemic inflammatory response (P > 0.05) in patients with purulent meningitis of known aetiology, those with lymphocytic meningitis and those with encephalitis.
Conclusions
MIF was significantly increased in the CSF of patients with purulent meningitis and encephalitis, and was to some degree associated with severity of the infection. Our findings indicate that MIF may play an important role in CNS infection.
doi:10.1186/cc7933
PMCID: PMC2717473  PMID: 19558639
8.  The evaluation of a tailored intervention to improve the management of suspected viral encephalitis: protocol for a cluster randomised controlled trial 
Background
Viral encephalitis is a devastating condition for which delayed treatment is associated with increased morbidity and mortality. Clinical audits indicate substantial scope for improved detection and treatment. Improvement strategies should ideally be tailored according to identified needs and barriers to change. The aim of the study is to evaluate the effectiveness and cost-effectiveness of a tailored intervention to improve the secondary care management of suspected encephalitis.
Methods/Design
The study is a two-arm cluster randomised controlled trial with allocation by postgraduate deanery. Participants were identified from 24 hospitals nested within 12 postgraduate deaneries in the United Kingdom (UK). We developed a multifaceted intervention package including core and flexible components with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. The primary outcome will be a composite of the proportion of patients with suspected encephalitis receiving timely and appropriate diagnostic lumbar puncture within 12 h of hospital admission and aciclovir treatment within 6 h. We will gather outcome data pre-intervention and up to 12 months post-intervention from patient records. Statistical analysis at the cluster level will be blind to allocation. An economic evaluation will estimate intervention cost-effectiveness from the health service perspective.
Trial registration
Controlled Trials: ISRCTN06886935.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-014-0201-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s13012-014-0201-1
PMCID: PMC4314797  PMID: 25623603
Encephalitis; Cluster randomised controlled trial; Guideline implementation; Protocol
9.  Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia 
PLoS ONE  2014;9(11):e111393.
Objectives
There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis.
Methods
Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis.
Results
Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2.
Conclusions
Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia.
doi:10.1371/journal.pone.0111393
PMCID: PMC4219716  PMID: 25369023
10.  Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomised placebo-controlled trial in South Africa 
AIDS (London, England)  2009;23(4):461-469.
Background
Several studies suggest that herpes simplex virus type 2 (HSV-2) may enhance HIV-1 transmission and disease progression.
Methods
We conducted a randomised, double-blind, placebo-controlled trial of aciclovir 400mg BD for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on HAART. Participants were evaluated pre-randomisation and at monthly visits for 3 months. Primary outcomes were the detection and quantity of genital HIV-1 RNA at the month 3 (M3) visit. Analyses were also undertaken using data from all visits. The treatment effects on plasma HIV-1 RNA, CD4+ count and genital HSV-2 DNA were also assessed.
Results
At M3 fewer women has detectable genital HIV in the aciclovir group compared to placebo, but this was not significant (61/132 [46%] vs.71/137 [52%], risk ratio [RR] 0.89, 95%CI 0.70 to 1.14, p=0.36). There was also little difference in quantity of HIV-1 RNA among shedders (+0.13 log10 copies/mL, 95%CI −0.14 to 0.39) at M3. However, aciclovir significantly decreased the frequency of HIV-1 shedding over all visits (adjusted odds-ratio 0.57, 95%CI 0.36 to 0.89). Significant reductions in M3 plasma HIV-1 RNA (−0.34 log10 copies/mL 95%CI 0.15 to 0.54), genital HSV-2 DNA (8% vs. 20%, RR 0.37, 95%CI 0.19 to 0.73) and genital ulceration (8% vs. 18%, RR 0.43, 95%CI 0.22 to 0.84) were observed in the aciclovir group.
Conclusion
HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding, may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation.
doi:10.1097/QAD.0b013e32831db217
PMCID: PMC2948532  PMID: 19155993
herpes simplex virus type-2 (HSV-2); HIV-1; aciclovir; suppressive therapy; randomised controlled trial; South Africa
11.  Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study 
The Lancet Global Health  2013;1(3):e153-e160.
Summary
Background
Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia.
Methods
We did a prospective cohort study in Blantyre, Malawi. From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months and 15 years who were admitted to hospital with suspected non-bacterial CNS infections. Children with a cerebrospinal fluid (CSF) white cell count of less than 1000 cells per μL and negative bacterial microscopy and culture were deemed to have suspected viral CNS infection. Blood was examined for asexual forms of P falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to detect 15 viruses known to cause CNS infection.
Findings
Full outcome data were available for 513 children with suspected viral CNS infection, of whom 94 (18%) died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%) died. 12 different viruses were detected; adenovirus was the most common, affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus, herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513 children had both parasitaemia and viral infection, including 27 (35%) of 78 diagnosed clinically with cerebral malaria. Children with dual infection were more likely to have seizures than were those with parasitaemia alone, viral infection only, or neither (p<0·0001). 17 (38%) of the 45 children with dual infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%) of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0·0001). Logistic regression showed children with a viral CNS infection had a significantly higher mortality than did those who did not have a viral CNS infection (p=0·001).
Interpretation
Viral CNS infections are an important cause of hospital admission and death in children in Malawi, including in children whose coma might be attributed solely to cerebral malaria. Interaction between viral infection and parasitaemia could increase disease severity.
Funding
Wellcome Trust, US National Institutes of Health, and UK Medical Research Council.
doi:10.1016/S2214-109X(13)70060-3
PMCID: PMC3986031  PMID: 24748325
12.  The Spectrum of Central Nervous System Infections in an Adult Referral Hospital in Hanoi, Vietnam 
PLoS ONE  2012;7(8):e42099.
Objectives
To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam.
Methods
From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others.
Results
352 (male: 66%) patients were recruited: median age 34 years (range 13–85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%).
Conclusions
Most infections lacked microbiological confirmation. S. suis was the most common cause of BM in this setting. Improved diagnostics are needed for meningoencephalitic syndromes to inform treatment and prevention strategies.
doi:10.1371/journal.pone.0042099
PMCID: PMC3431395  PMID: 22952590
13.  YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Purulent Meningitis 
YKL-40, a member of the family 18 glycosyl hydrolases, is secreted by activated neutrophils and macrophages. It is a growth factor for connective tissue cells and a potent migration factor for endothelial cells and may function in inflammation and tissue remodeling. YKL-40 was determined in 134 cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median, 663 μg/liter [range, 20 to 8,960]) and encephalitis (5,430 μg/liter [620 to 11,600]) than in patients with lymphocytic meningitis (137 μg/liter [41 to 1,865]) or patients without meningitis (167 μg/liter [24 to 630]) (Kruskal-Wallis and Dunn multiple comparison tests, P < 0.001). CSF YKL-40 levels were also determined for 26 patients with purulent meningitis having a repuncture, and patients who died (n = 5) had significantly higher YKL-40 levels than patients who survived (n = 21) (2,100 μg/liter [1,160 to 7,050] versus 885 μg/liter [192 to 15,400], respectively; Mann-Whitney test, P = 0.018). YKL-40 was most likely locally produced, since patients with infections of the central nervous system had CSF YKL-40 levels that were at least 10-fold higher than the corresponding levels in serum (2,033 μg/liter [470 to 11,600] versus 80 μg/liter [19 to 195]). The CSF neopterin level was the biochemical parameter in CSF and blood that correlated best with CSF YKL-40 levels, indicating that YKL-40 may be produced by activated macrophages within the central nervous system. In conclusion, high levels of YKL-40 in CSF are found in patients with purulent meningitis.
doi:10.1128/CDLI.9.3.598-604.2002
PMCID: PMC119997  PMID: 11986266
14.  Management of women with recurrent genital herpes in pregnancy in Australia 
OBJECTIVE: To document clinical practice for the management of recurrent genital herpes in pregnant women in Australia. DESIGN AND PARTICIPANTS: A questionnaire to all doctors associated with the Royal Australian College of Obstetricians and Gynaecologists. MAIN OUTCOME MEASURES: Policies for antenatal herpes screening, circumstances in which delivery by caesarean section was considered appropriate, and the use of aciclovir during pregnancy. The results were analysed by college status, sex, and whether the doctor worked in a public or private facility. RESULTS: 2855 (67.3%) obstetricians returned questionnaires. 696 (34.3%) stated that their hospital had a policy for managing recurrent genital herpes in pregnancy: 44.5% examined the genitalia and 33.8% took cultures during pregnancy. Fellows were more likely to examine the genitalia (87% v 37%, p < 0.001), and more likely to perform antenatal viral cultures than members (75% v 30%, p < 0.001). Doctors working at private hospitals were significantly more likely to take viral cultures than doctors in public hospitals (39% v 33% p < 0.05). Doctors were asked to consider five scenarios and judge whether caesarean section would be appropriate. 96% considered that a caesarean section was appropriate in women with active herpes at the onset of labour. In the case of a recurrence of genital HSV at the time of presentation with ruptured membranes longer than 4 hours, diplomats (79%) were significantly more likely to recommend a caesarean section than fellows (64%), members (63%), or trainees (49%) (all p < or = 0.001). Where there were positive viral cultures before the onset of labour fellows (45%) were more likely than members (29%) (p = 0.005), males (62%) were more likely than females (55%) (p = 0.03), and doctors working in private hospitals (69%) were more likely than those in the public sector (54%) (p < 0.001) to recommend caesarean section. CONCLUSION: There is considerable divergence of opinion regarding the appropriate management of recurrent genital herpes in pregnancy. The implementation of management guidelines would provide consistency of care. 





PMCID: PMC1758183  PMID: 10448344
15.  Laboratory Diagnosis of Common Herpesvirus Infections of the Central Nervous System by a Multiplex PCR Assay 
Journal of Clinical Microbiology  2001;39(12):4426-4432.
A sensitive multiplex PCR assay for single-tube amplification that detects simultaneous herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (CMV), and Epstein-Barr virus (EBV) is reported with particular emphasis on how the method was optimized and carried out and its sensitivity was compared to previously described assays. The assay has been used on a limited number of clinical samples and must be thoroughly evaluated in the clinical context. A total of 86 cerebrospinal fluid (CSF) specimens from patients which had the clinical symptoms of encephalitis, meningitis or meningoencephalitis were included in this study. The sensitivity of the multiplex PCR was determined to be 0.01 and 0.03 50% tissue culture infective doses/the reciprocal of the highest dilution positive by PCR for HSV-1 and HSV-2 respectively, whereas for VZV, CMV and EBV, 14, 18, and 160 ag of genomic DNA were detected corresponding to 48, 66, and 840 genome copies respectively. Overall, 9 (10.3%) of the CSF samples tested were positive in the multiplex PCR. HSV-1 was detected in three patients (3.5%) with encephalitis, VZV was detected in four patients (4.6%) with meningitis, HSV-2 was detected in one neonate (1.16%), and CMV was also detected in one neonate (1.16%). None of the samples tested was positive for the EBV genome. None of the nine positive CSF samples presented herpesvirus coinfection in the central nervous system. Failure of DNA extraction or failure to remove any inhibitors of DNA amplification from CSF samples was avoided by the inclusion in the present multiplex PCR assay of α-tubulin primers. The present multiplex PCR assay detects simultaneously five different herpesviruses and sample suitability for PCR in a single amplification round of 40 cycles with an excellent sensitivity and can, therefore, provide an early, rapid, reliable noninvasive diagnostic tool allowing the application of antiviral therapy on the basis of a specific viral diagnosis. The results of this preliminary study should prompt a more exhaustive analysis of the clinical value of the present multiplex PCR assay.
doi:10.1128/JCM.39.12.4426-4432.2001
PMCID: PMC88560  PMID: 11724856
16.  Increased Detection Rate in Diagnosis of Herpes Simplex Virus Type 2 Meningitis by Real-Time PCR Using Cerebrospinal Fluid Samples▿  
Journal of Clinical Microbiology  2007;45(8):2516-2520.
Efficient and sensitive diagnostic methods are needed in the management of virus infections in the central nervous system. There is a demand for an evaluation of the sensitivity of PCR methods for early diagnosis of meningitis due to herpes simplex type 2 (HSV-2) and varicella-zoster virus (VZV). The objective of this study was to evaluate real-time PCR in the detection of HSV-2 and VZV DNA from cerebrospinal fluid (CSF) for etiological diagnoses in clinically well-characterized cases of primary and recurrent aseptic meningitis. Samples from 110 patients, 65 of whom were diagnosed with or were strongly suspected of having HSV-2 meningitis and 45 with acute aseptic meningitis of unknown causes, were analyzed. Results were compared with the outcome of nested PCR for HSV-2 infection. Clinical parameters were analyzed in relation to CSF viral load. With real-time PCR, HSV-2 DNA was found in CSF from 80% (52/65) of patients with clinical HSV-2 meningitis compared to 72% (47/65) found by nested PCR. The sensitivity of real-time HSV-2 PCR was found to be 87% (33/38) in primary and 70% (19/27) in recurrent meningitis. The HSV-2 viral load was significantly higher in primary than in recurrent meningitis and correlated with the degree of inflammation. VZV DNA was detected in 2 of 45 samples (4.4%). Real-time PCR for the diagnosis of HSV-2 meningitis was evaluated in a large, clinically well-characterized sample of material and found to identify more cases than nested PCR in the group of patients with recurrent meningitis. Quantification of DNA enables further research of disease prognosis and treatment.
doi:10.1128/JCM.00141-07
PMCID: PMC1951252  PMID: 17567785
17.  Diagnosis and treatment of viral encephalitis 
Postgraduate Medical Journal  2002;78(924):575-583.
Acute encephalitis constitutes a medical emergency. In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy. Acute disseminated encephalomyelitis is a non-infective inflammatory encephalitis that may require to be treated with steroids. Acute infective encephalitis is usually viral. Herpes simplex encephalitis (HSE) is the commonest sporadic acute viral encephalitis in the Western world. Magnetic resonance imaging of brain is the investigation of choice in HSE and the diagnosis may be confirmed by the polymerase chain reaction test for the virus in the cerebrospinal fluid. In this article, we review the diagnosis, investigations, and management of acute encephalitis. With few exceptions (for example, aciclovir for HSE), no specific therapy is available for most forms of viral encephalitis. Mortality and morbidity may be high and long term sequelae are known among survivors. The emergence of unusual forms of zoonotic encephalitis has posed an important public health problem. Vaccination and vector control measures are useful preventive strategies in certain arboviral and zoonotic encephalitis. However, we need better antiviral therapy to meet the challenge of acute viral encephalitis more effectively.
doi:10.1136/pmj.78.924.575
PMCID: PMC1742520  PMID: 12415078
18.  Detection of herpes viruses in the cerebrospinal fluid of adults with suspected viral meningitis in Malawi 
Infection  2012;41(1):27-31.
Purpose
We looked for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively), varicella zoster virus (VZV), Epstein–Barr virus (EBV) and cytomegalovirus (CMV) DNA in Malawian adults with clinically suspected meningitis.
Methods
We collected cerebrospinal fluid (CSF) from consecutive adults admitted with clinically suspected meningitis to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, for a period of 3 months. Those with proven bacterial or fungal meningitis were excluded. Real-time polymerase chain reaction (PCR) was performed on the CSF for HSV-1 and HSV-2, VZV, EBV and CMV DNA.
Results
A total of 183 patients presented with clinically suspected meningitis. Of these, 59 (32 %) had proven meningitis (bacterial, tuberculous or cryptococcal), 39 (21 %) had normal CSF and 14 (8 %) had aseptic meningitis. For the latter group, a herpes virus was detected in 9 (64 %): 7 (50 %) had EBV and 2 (14 %) had CMV, all were human immunodeficiency virus (HIV)-positive. HSV-2 and VZV were not detected. Amongst those with a normal CSF, 8 (21 %) had a detectable herpes virus, of which 7 (88 %) were HIV-positive.
Conclusions
The spectrum of causes of herpes viral meningitis in this African population is different to that in Western industrialised settings, with EBV being frequently detected in the CSF. The significance of this needs further investigation.
doi:10.1007/s15010-012-0292-z
PMCID: PMC3566386  PMID: 22798048
Adults; Africa; Central nervous system infections; Herpes virus; HIV; Viral meningitis
19.  Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis 
Objective: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality, even with appropriate antiviral therapy. In the present investigation, the first to assess efficacy of corticosteroid treatment with aciclovir therapy in HSVE, multiple logistic regression analysis was performed of predictors of outcome in adult patients with HSVE.
Methods: A non-randomised retrospective study of 45 patients with HSVE treated with aciclovir was conducted. The patients were divided into poor and good groups based on outcome at three months after completion of aciclovir treatment. The variables evaluated were: clinical variables (sex, age, days after onset at initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir, initial and maximum values for the cell numbers and protein concentration in the cerebrospinal fluid, and corticosteroid administration); neuroradiological variables (detection of lesions by initial cranial computed tomography and by initial magnetic resonance imaging); and one neurophysiological variable (detection of periodic lateralised epileptiform discharges on the initial electroencephalogram). Single variable logistic regression analysis was performed followed by multiple logistic regression analysis. The best set of predictors for the outcome of HSVE was estimated by stepwise logistic regression analysis.
Results: A poor outcome was evident with older age, lower GCS score at initiation of aciclovir, and no administration of corticosteroid. Patient age, GCS at initiation of aciclovir, and corticosteroid administration were found to be significant independent predictors of outcome on multiple logistic regression analysis, and these three variables also formed the best set of predictors (R2 = 0.594, p<0.0001).
Conclusion: Combination therapy using both aciclovir and corticosteroid represents one of the predictors of outcome in HSVE.
doi:10.1136/jnnp.2004.049676
PMCID: PMC1739396  PMID: 16227548
20.  High Viral Load in the Cerebrospinal Fluid and Brain Correlates with Severity of Simian Immunodeficiency Virus Encephalitis 
Journal of Virology  1999;73(12):10480-10488.
AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed. The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication.
PMCID: PMC113103  PMID: 10559366
21.  Subacute herpes simplex virus type 1 encephalitis as an initial presentation of chronic lymphocytic leukemia and multiple sclerosis: a case report 
Introduction
Herpes simplex virus type 1 encephalitis presents acutely in patients who are immunocompetent. We report what we believe to be the first published case of a subacute course of herpes simplex virus type 1 encephalitis in a patient with asymptomatic chronic lymphocytic leukemia who subsequently developed multiple sclerosis.
Case presentation
A 49-year-old Caucasian woman with a history of fever blisters presented to the emergency department with a history of left temporal headache for four weeks, and numbness of the left face and leg for two weeks. A complete blood count revealed white blood cell count of 11,820 cells/mL, with an absolute lymphocyte count of 7304 cells/mL. The cerebrospinal fluid contained 6 white blood cells/μL, 63 red blood cells/μL, 54 mg glucose/dL, and 49 mg total protein/dL. Magnetic resonance imaging of the brain revealed meningoencephalitis and bilateral ventriculitis. Cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 was positive, and the patient's symptoms resolved after ten days of treatment with parenteral aciclovir. Incidental findings on peripheral blood smear and flow cytometry testing confirmed chronic lymphocytic leukemia. One month later, she developed bilateral numbness of the hands and feet; a repeat cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 at this time was negative. A repeat magnetic resonance imaging scan showed an expansion of the peri-ventricular lesions, and the cerebrospinal fluid contained elevated oligoclonal bands and myelin basic protein. A brain biopsy revealed gliosis consistent with multiple sclerosis, and the patient responded to treatment with high-dose parenteral steroids.
Conclusion
Herpes simplex virus type 1 encephalitis is a rare presentation of chronic lymphocytic leukemia. Our patient had an atypical, subacute course, presumably due to immunosuppression from chronic lymphocytic leukemia. This unusual case of herpes simplex virus type 1 encephalitis emphasizes the importance of T cell function in diseases of immune dysregulation and autoimmunity such as chronic lymphocytic leukemia and multiple sclerosis. It raises the question of whether atypical presentations of herpes simplex virus encephalitis warrant deliberations on immunocompetence. The development of multiple sclerosis in our patient so soon after she received treatment for herpes simplex virus type 1 encephalitis raises the possibility that herpes simplex virus type 1 encephalitis in an immunosuppressed patient may trigger multiple sclerosis.
doi:10.1186/1752-1947-5-59
PMCID: PMC3062610  PMID: 21314934
22.  Role of the virology laboratory in diagnosis and management of patients with central nervous system disease. 
A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.
PMCID: PMC358097  PMID: 2644021
23.  Chickenpox 
Clinical Evidence  2011;2011:0912.
Introduction
Chickenpox is extremely contagious. Over 90% of unvaccinated people become infected, but infection occurs at different ages in different parts of the world — over 80% of people have been infected by the age of 10 years in the US, the UK, and Japan, and by the age of 20 to 30 years in India, South East Asia, and the West Indies.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent chickenpox in healthy adults and children? What are the effects of interventions to prevent chickenpox in children exposed prenatally? What are the effects of interventions to prevent chickenpox in immunocompromised adults and children? What are the effects of treatments for chickenpox in healthy adults and children? What are the effects of treatments for chickenpox in immunocompromised adults and children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 11 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aciclovir, famciclovir, live attenuated vaccine, valaciclovir, and varicella zoster immunoglobulin.
Key Points
Chickenpox is caused by primary infection with varicella zoster virus. In healthy people, it is usually a mild, self-limiting illness, characterised by low-grade fever, malaise, and a generalised, itchy, vesicular rash. Chickenpox is very contagious — in the UK, US, and Japan, >80% of people have been infected by the age of 10 years.The most common complications are bacterial skin sepsis in children aged <5 years, acute cerebellar ataxia in older children, and varicella pneumonia in adults (which causes 20–30 hospital admissions per 10,000 adults).
Live attenuated varicella vaccine is effective at preventing chickenpox in healthy children not knowingly exposed to varicella zoster virus. The vaccine may also reduce the incidence of chickenpox in healthy children exposed to varicella zoster virus, if administered within 3 days of exposure. In vaccinated children who develop varicella, disease is likely to be mild.
We found no RCT evidence examining the effect of the vaccine in healthy adults in either those not exposed or exposed to varicella zoster virus.
Newborns whose mothers' rashes appear in the last 5 days of pregnancy or within 2 days of birth have been reported, in small case series, to have a very high risk of severe chickenpox. In these cases, the general consensus is to administer varicella zoster immunoglobulin.We found no evidence assessing aciclovir, famciclovir, or valaciclovir for preventing chickenpox in prenatally exposed children.
The evidence for the use of live attenuated varicella vaccine for prevention of chickenpox in immunocompromised children is from small uncontrolled studies. Overall, its use is a trade-off between benefits and harms. We found no RCT or observational evidence examining the effect of the vaccine in immunocompromised adults. We don't know how effective famciclovir or valaciclovir are in preventing chickenpox in immunocompromised adults or children.In these cases, the general consensus is to administer varicella zoster immunoglobulin. Aciclovir (high dose) has been shown to be beneficial in reducing clinical chickenpox in people with HIV infection. We don't know how effective it is in other immunocompromised people to prevent chickenpox.
Oral aciclovir also seems to effectively treat chickenpox if administered within 24 hours of onset of rash. When given later than 24 hours after onset of rash, aciclovir does not seem so effective, although the evidence is sparse.We found no RCT evidence assessing famciclovir or valaciclovir for treating chickenpox in healthy people.
In children with malignancy, intravenous aciclovir seems to reduce clinical deterioration from chickenpox. We found no RCT evidence assessing how effective aciclovir, famciclovir, or valaciclovir are in treating immunocompromised adults with chickenpox.
PMCID: PMC3275319  PMID: 21486500
24.  Bell's palsy 
Clinical Evidence  2008;2008:1204.
Introduction
Bell's palsy is characterised by an acute, unilateral, partial or complete paralysis of the face, which may occur with mild pain, numbness, increased sensitivity to sound, and altered taste. Bell's palsy remains idiopathic, but a proportion may be caused by reactivation of herpes viruses from cranial nerve ganglia. Bell's palsy is most common in people aged 15-40 years, affecting 1 in 60 in their lifetime. Most make a spontaneous recovery within 1 month, but up to 30% have delayed or incomplete recovery.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in adults and children? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found eight systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiviral treatment, corticosteroids (alone or plus antiviral treatment), facial nerve decompression surgery, and mime therapy.
Key Points
Bell's palsy is characterised by unilateral, acute paresis or acute paralysis of the face, which may occur with mild pain, numbness, increased sensitivity to noise, and altered taste. Up to 30% of people with acute peripheral facial palsy have other identifiable causes, including stroke, tumours, middle ear disease, or Lyme disease. Severe pain is more consistent with Ramsay Hunt syndrome caused by herpes zoster infection, which has a worse prognosis than Bell's palsy.Bell's palsy is most common in people aged 15-40 years, and pregnant women may be at higher risk.Bell's palsy may be caused by reactivation of herpes viruses in the cranial nerve ganglia. Most people make a spontaneous recovery within 3 weeks, but up to 30% may have residual problems.
We don't know whether corticosteroids or antiviral treatment improve recovery of motor function or cosmetically-disabling sequelae compared with placebo or with other treatments. Combined treatment with aciclovir plus corticosteroids may be more effective than steroids alone.In pregnant women, antiviral treatments such as aciclovir should only be prescribed under guidance of an obstetrician.There is some consensus that valaciclovir may be more effective than aciclovir, as it is has improved bioavailability and compliance.
We don't know whether facial nerve decompression surgery is beneficial in Bell's palsy, as no studies of adequate quality have been found.
Mime therapy may improve facial stiffness and lip mobility in Bell's palsy, but the evidence is too weak to draw conclusions.
PMCID: PMC2907944  PMID: 19450338
25.  Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era 
Background
In the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF) of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments.
Methods
A prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not.
Results
HIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART.
Conclusion
Detection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in plasma but some patients showed higher CSF levels, and no difference between these two compartments was observed in patients with cryptococcal meningitis and HIV-associated dementia, suggesting the presence of intrathecal viral replication in these patients. HAART played a role in the control of CSF HIV levels even in patients with cryptococcal meningitis and neurotoxoplasmosis in whom viral replication is potentially higher.
doi:10.1186/1471-2334-7-147
PMCID: PMC2244630  PMID: 18096083

Results 1-25 (1061507)