Patients with syphilis investigated for neurosyphilis—Inclusion criteria, clinical and diagnostic features.

<p>Patients with syphilis investigated for neurosyphilis—Inclusion criteria, clinical and diagnostic features.</p

Neurosyphilis in Africa: A systematic review

<div><p>Introduction</p><p>Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on neurosyphilis in Africa. The aim of this study is to review data on neurosyphilis in Africa since the onset of the HIV epidemic.</p><p>Methods</p><p>We searched the literature for references on neurosyphilis in Africa for studies published between the 1^st of January 1990 and 15^th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have neurosyphilis, and the proportion of patients with neurological syndromes who had neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken.</p><p>Results</p><p>Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and neurosyphilis, in association with ocular disease.</p><p>Discussion</p><p>This is the first systematic review of the literature on neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of neurosyphilis in Africa and to better define interactions with HIV in this setting.</p></div

Sensitivity analysis by background antigen prevalence.

<p>The results of one-way sensitivity analysis varying the background cryptococcal antigen prevalence in patients entering ART programmes with CD4 cell counts <100 cells/µL. The cost of current standard of care (no prevention, or status quo) is shown by the dotted line, and the cost of the CRAG screening with targeted treatment of CRAG positive individuals with high dose fluconazole (no LPs) is shown by the solid line. The screen and treat strategy dominated the standard of care at antigen prevalences of 0.6% and higher. The shaded area represents the range of baseline CRAG prevalence figures reported in patients with CD4 counts <100 cell/µL at ART programme entry. Costs are expressed as mean cost per patient/year in the ART programme.</p

Costs.

*<p>Medication costs were from government tender prices, test costs were from the National Health Laboratory Services, and lumbar puncture costs were based on the Uniform Patient Fee Schedule. The overhead and staff cost per inpatient day at the secondary level and the overhead and staff cost per outpatient department visit was taken from Cleary et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone.0069288-Cleary1" target="_blank">[48]</a>. The overhead components of these costs were inflated using the Consumer Price Index, while clinical staff costs were recalculated using 2010 government salary scales. Costs were expressed in 2010 prices, and were converted to United States Dollars (US$) based on the average exchange rate between 1 January and 31 December 2010 (US$1 = ZAR7.34; <a href="http://www.oanda.com" target="_blank">www.oanda.com</a>).</p

Simplified markov model structure.

<p>Transition probabilities are listed as C1, C2, S1 etc. Variable names, descriptions and values are derived from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone-0069288-t001" target="_blank">table 1</a>, as follows: <b><i>S1</i></b> - Proportion with subclinical CM at baseline, CD4<50 cells/µL = 0.13, CD4 50–100 cells/µL = 0.03. <b><i>S2</i></b> - Of those with subclinical CM, Proportion with CSF infection = 0.5. <b><i>P1</i></b> - Proportion starting ART with CD4<50 cells/µl = 0.5. <b><i>C1</i></b> - Probability of developing CM, by baseline CD4 category and time on ART: <i>CD4<50 cells/µl = </i>252 per 1000 patient years (pyo) up to 3 months on ART, 72 per 1000 pyo 4–6 months on ART, 36 per 1000 pyo 7–9 months on ART, 0 per 1000 pyo 10–12 months. <i>CD4 50–100 cells/µl</i> = 56 per 1000 pyo up to 3 months on ART, 16 per 1000 pyo 4–6 months on ART, 8 per 1000 pyo 7–9 months on ART, 0 per 1000 pyo 10–12 months. <b><i>R1</i></b> - Relative risk of CM with low dose fluconazole prophylaxis = 0.21. <b><i>R2</i></b> - Relative risk of CM for CRAG positive taking high dose fluconazole prophylaxis = 0.1. <b><i>R3</i></b> - Relative risk of CM for CRAG positive with amphotericin for CSF positive patients, fluconazole for CSF negative patients = 0. <b><i>D1</i></b> - Probability of dying of acute CM = 45% dead at 1 month with CM. <b><i>D2</i></b> - Probability of dying of CM within 1 year = 55% dead at 12 months on ART.</p

Baseline input assumptions and transition probabilities.

*<p>The incidence of CM varied according to CD4 count strata, and time on ART to account for CD4 cell count increases and the acompanying reduction in risk of developing CM. The time stratification was into 3 month blocks according to time from ART initiation, and the data used to derive these probabilities was from a large South African cohort <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069288#pone.0069288-Jarvis5" target="_blank">[45]</a>.</p

Cost-effectiveness.

<p>Mean cost = Mean per-patient cost for prevention and/or treatment of CM, US$, during first year of ART.</p><p>Life years = Mean life expectancy one year after ART programme entry.</p><p>ICER = ratio of difference in cost to difference in outcome.</p>*<p>Uncertainty interval.</p>†<p>Higher cost than more effective option(s).</p

Baseline characteristics of the patients.

<p>Baseline characteristics of the patients.</p

Relationship between CSF MCP-1 concentrations and CD4 cell counts, cerebrospinal fluid lymphocyte counts, and immune reconstitution syndrome.

<p>Associations between baseline MCP-1 concentrations and baseline CD4 cell count, concentrations, cerebrospinal fluid (CSF) lymphocyte count and immune reconstitution syndrome (IRIS). The IRIS association was adjusted for treatment group. Best-fit regression lines are shown with 95% confidence intervals. Box plots show the median and extend to the inter-quartile range, with whiskers denoting minimum and maximum values. These associations all remained significant when controlling for a family wise error rate of 0.05.There was no significant difference in CSF MCP-1 concentrations between those who survived (749.1 pg/ml) and those who died (858.4 pg/ml), <i>p = 0</i>.<i>76</i>.</p

Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis - Table 4

<p>Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis</p> - Table