Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort

Rajasingham, Radha; Rhein, Joshua; Klammer, Kate; Musubire, Abdu K; Nabeta, Henry W.; Akampurira, Andrew; Mossel, Eric C.; Williams, Darlisha A; Boxrud, Dave; Crabtree, Mary B.; Miller, Barry R.; Rolfes, Melissa A.; Tengsupakul, Supatida; Andama, Alfred; Meya, David B.; Boulware, David R.

doi:10.4269/ajtmh.14-0452

Cited by 67 publications

(81 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, the assay detected several additional pathogens in CSF, in particular EBV at high rates. Similar to a prior investigation in Uganda, herpes simplex virus (HSV) was not detected as a cause of viral meningitis (19). …”

Section: Discussionsupporting

confidence: 59%

“…The detection of EBV and other herpesviruses in this highly immunocompromised population is of unclear significance (19). Of note, EBV was left out of the recently FDA-approved panel which is now commercially available, and the high prevalence of EBV noted in this study should be interpreted with caution, since confirmatory PCR testing was not performed.…”

Section: Discussionmentioning

confidence: 99%

“…Confirmatory PCR testing was carried out using Argene ® (Biomerieux, Marcy l'Etoile, France) for viral pathogens and genesig ® Streptococcus pneumoniae PCR (Primerdesign, Southamptom, United Kingdom). Epstein-Barr virus (EBV) was not validated by additional confirmatory testing due to its ubiquitous nature and unclear significance in this immunocompromised population, as described previously (19). …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda

Rhein

Bahr

Hemmert

et al. 2016

Diagnostic Microbiology and Infectious Disease

Self Cite

View full text Add to dashboard Cite

Meningitis remains a worldwide problem, and rapid diagnosis is essential to optimize survival. We evaluated the utility of a multiplex PCR test in differentiating possible etiologies of meningitis. Cerebrospinal fluid (CSF) from 69 HIV-infected Ugandan adults with meningitis was collected at diagnosis (n=51) and among persons with cryptococcal meningitis during therapeutic lumbar punctures (n=68). Cryopreserved CSF specimens were analyzed with BioFire FilmArray® Meningitis/Encephalitis panel, which targets 17 pathogens. The panel detected Cryptococcus in the CSF of patients diagnosed with a first-episode of cryptococcal meningitis by fungal culture with 100% sensitivity and specificity, and differentiated between fungal relapse and paradoxical immune reconstitution inflammatory syndrome in recurrent episodes. A negative FilmArray result was predictive of CSF sterility on follow-up lumbar punctures for cryptococcal meningitis. EBV was frequently detected in this immunosuppressed population (n=45). Other pathogens detected included: CMV (n=2), VZV (n=2), HHV-6 (n=1), and Streptococcus pneumoniae (n=1). The FilmArray Meningitis/Encephalitis panel offers a promising platform for rapid meningitis diagnosis.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda

Rhein

Bahr

Hemmert

et al. 2016

Diagnostic Microbiology and Infectious Disease

Self Cite

View full text Add to dashboard Cite

show abstract

“…Africa has the highest burden, where Cryptococcus is the most common cause of adult meningitis (JARVIS et al, 2010;RAJASINGHAM et al, 2015), but Latin America is the third global region with most cases with 54,400 estimated cryptococcal meningitis cases annually in 2008 (PARK et al, 2009). More recent 2015 estimates of cryptococcal meningitis incidence in Latin America are approximately 10,000 cases annually (RAJASINGHAM, unpublished data).…”

Section: Aids-related Cryptococcal Meningitis Causes Approximately 15mentioning

confidence: 99%

Lateral Flow Assay for Cryptococcal Antigen: An Important Advance to Improve the Continuum of Hiv Care and Reduce Cryptococcal Meningitis-Related Mortality

Vidal

Boulware

2015

Rev. Inst. Med. trop. S. Paulo

Self Cite

View full text Add to dashboard Cite

SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipmentfree, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcus species. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/µL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

show abstract

“…The pathologic significance of EBV in the CSF of HIV-infected patients remains an open question. 10,[13][14][15] Cryptococcal meningitis (17%) was the most frequently detected CNS OI. The mechanism whereby cryptococcal meningitis may cause seizures is not fully understood.…”

mentioning

confidence: 99%

New-onset seizure in HIV-infected adult Zambians

et al. 2017

View full text Add to dashboard Cite

Objective: To identify the etiology of new-onset seizure in HIV-infected Zambian adults and identify risk factors for seizure recurrence.Methods: A prospective cohort study enrolling HIV-infected adults with new-onset seizure within 2 weeks of index seizure obtained clinical, laboratory, and neuroimaging data to determine seizure etiology. Participants were followed to identify risk factors for seizure recurrence. Risk factors for mortality were examined as mortality rates were unexpectedly high.Results: Eighty-one patients with CSF for analysis were enrolled and followed for a median of 306 days (interquartile range 61-636). Most (91%) were at WHO stage III/IV and 66 (81%) had a preseizure Karnofsky score $50. Prolonged or multiple seizures occurred in 46 (57%), including 12 (15%) with status epilepticus. Seizure etiologies included CNS opportunistic infections (OI) in 21 (26%), hyponatremia in 23 (28%), and other infections in 8 (10%). OIs included Cryptococcus (17%), JC virus (7%) and 5% each for tuberculosis, cytomegalovirus, and varicella-zoster virus. No etiology could be identified in 16 (20%). Thirty (37%) patients died during follow-up and 20 (25%) had recurrent seizures with survival being the only identifiable risk factor. Seizures are common in the HIV-infected population, often occurring in the setting of advanced stages of immunosuppression.1 New-onset seizure has been reported in up to 11% of HIVinfected individuals, 2,3 but seizure recurrence risk and risks factors for epilepsy development in HIV-infected individuals with new-onset seizure have not been delineated. Most African regions with high HIV prevalence continue to rely largely on older, enzyme-inducing antiepileptic drugs (AEDs) for epilepsy management. Given the potential for drug interactions between enzymeinducing AEDs and combined antiretroviral therapy (cART), their co-usage is not recommended, 4,5 but other seizure treatment options are often limited or nonexistent. 6 Data on the risk of seizure recurrence in HIV-infected people with new-onset seizure are needed to help guide the decision whether or not to initiate AEDs, particularly given the risk of increased drug toxicity

show abstract

Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort

Cited by 67 publications

References 37 publications

Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda

Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda

Lateral Flow Assay for Cryptococcal Antigen: An Important Advance to Improve the Continuum of Hiv Care and Reduce Cryptococcal Meningitis-Related Mortality

New-onset seizure in HIV-infected adult Zambians

Contact Info

Product

Resources

About