Although the clinical diagnosis of meningitis is often supported by the presence of abnormal number of WBCs in the CSF (AKA pleocytosis), meningitis may be present despite its absence.
Among viral causes of meningitis in adults, enteroviruses are associated with lower CSF WBC count compared to herpes simplex and varicella zoster, with some patients (~10%) having 0-2 WBC’s/mm31,2. Of interest, among children, parechovirus (formerly echovirus 22 and 23) meningitis is characterized by normal CSF findings3.
Though uncommon, bacterial meningitis without CSF pleocytosis has been reported among non-neutropenic adults, including Neisseria meningitidis, Streptococcus pneumoniae, Hemophilus influenzae, Listeria monocytogenes, E. coli, and Proteus mirabilis4. A European study also reported normal CSF WBC in nearly 10% of patients with Lyme neuroborreliosis (including meningitis) caused primarily by Borrelia garinii5.
Cryptococcal meninigitis may also be associated with normal CSF profile in 25% of patients with HIV infection6.
- Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral meningitis in adult:significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis 2008;47:783-9. https://www.ncbi.nlm.nih.gov/pubmed/18680414
- Dawood N, Desjobert E, Lumley J et al. Confirmed viral meningitis with normal CSF findings. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-203733. http://casereports.bmj.com/content/2014/bcr-2014-203733.abstract
- Wolthers KC, Benschop KSM, Schinkel J, et al. Human parechovirus as an important viral cause of sepsis like illness and meningitis in young children. Clin Infect Dis 2008;47:358-63. https://www.ncbi.nlm.nih.gov/pubmed/18558876
- Hase R, Hosokawa N, Yaegashi M, et al. Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol 2014;25:249:51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211346/pdf/idmm-25-249.pdf
- Ogrinc K, Lotric-Furlan S, Maraspin V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis 2013; 57:501-9. https://www.ncbi.nlm.nih.gov/pubmed?term=23667259
- Darras-Joly C, Chevret S, Wolff M, et al. Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus. Clin Infect Dis 1996;23:369-76. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/23/2/10.1093/clinids/23.2.369/2/23-2-369.pdf?Expires=1501035620&Signature=FhHMHUHAMmT3rz4ld8QAMet-weu-BWgm5YR6nA4jjSGVGIeaVlMNPgeOkW2fniiel54HQhIs1Kkp3PpzT1glxhJeZvQiGXQCSOoF-jS1SK7S~kBb-oHs4qsIJzN0OJxNAXfoJi4bl7OeKaLTyIE3P8~slwH0BBi7RncSYVgVR4NkOnFpYgn27~wY7pDSUNWvzGFKoSeYGeM0TsAqna-QmXzodITB5bgr1mO6Q6OGUxCsqRwhr6xNb~4G93oqRcsO19gyUluCE0xYt0KbKWuQxJeh8AbtJkNrS08~XInMR50bQZOUb80j0~dtg9jRTGzXQaDllVByoX2Alr48hlhogw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
The most significant risk factor for PCP prophylaxis is defect in cell-mediated immunity including high-dose glucocorticoid (HDGC, ≥20 mg of prednisone daily) treatment1. A systematic review concluded that at a PCP rate of 6.2% in control groups, PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) is highly effective (85% risk reduction) in non-HIV patients with acute leukemia or solid organ/autologous bone marrow transplantation (number needed to treat 19)2.
Other Indications for PCP prophylaxis include1:
- HDGC treatment for ≥1month plus another cause of immunocompromise.
- Combination of immunosuppressive drugs, such as tumor-necrosing factor- α inhibitors plus HDGC or other immunosuppression.
- Polymyositis/dermatomyositis with interstitial pulmonary fibrosis on glucocorticoids.
- Certain primary immunodeficiencies (eg idiopathic CD4-lymphopenia, hyper-IgM syndrome).
- Granulomatosis with polyangiitis (Wegener’s) on methotrexate and HDGC
- Rheumatologic diseases on HDGC and a second immunosuppressive drug
- T-cell depleting agents (eg, fludarabine)
- Severe malnutrition
TMP/STX may be given either as double-strength 3x/week or single-strength daily1,2.
- Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.
- Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3.
Patients with newly-diagnosed TB are ~20 times more likely to be coinfected with HIV than those without TB. Unfortunately, the diagnosis of TB in HIV-infected patients is often delayed in part related to its atypical presentation1.
In HIV-infected patients with high CD4 counts, clinical manifestations of TB are usually similar to those without HIV infection (eg, subacute fever, weight loss, cough) with CXR often showing upper lobe infiltrates and/or cavitations typically seen in reactivation TB.
Lower CD4 counts, however, are associated with atypical CXR findings, including pleural effusions, lower or middle lobe infiltrates, mediastinal adenopathy, and lack of cavitary lesions1,2. A normal CXR has been reported in 21% of patients with CD4 <200 cells/μl (vs 5% in those with higher counts)2.
Advanced immune suppression in HIV infection is also associated with negative sputum smears for acid-fast bacilli, concurrent extra-pulmonary disease, and immune reconstitution symptoms after initiation of anti-TB therapy1.
- Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev 2011;24:351-376.
- Greenberg, SD, Frager D, Suster B, et al. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology 1994;193:115-9.
HJBs (Figure) are named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who filmed mitotic activity in cells. HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. They are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease, HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-3.
Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3. Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,4.
Photo courtesy of Michael S. Abers, MD
- Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97.
- Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176.
- Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717.
- Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94. doi: 10.1111/bjh.13660, Epub 2015 Aug 28.
Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland
This is a common scenario among our hospitalized patients with indwelling catheters, prior antibiotic therapy or diabetes mellitus who seem to have no clinical signs of infection. Fortunately, candidemia from urinary sources appears uncommon to rare, with up to nearly ½ of patients clearing their candiduria with removal of the indwelling catheter alone (1). The Infectious Diseases Society of America guidelines do not recommended treatment of asymptomatic candiduria unless the patient belongs to a group at high risk of dissemination, such as severely immunosuppressed or neutropenic patients, infants with low birth weight, and patients who will undergo urologic manipulation (2). Supporting such recommendation is a retrospective long-term follow-up of patients with candiduria demonstrating no significant improvement in rates of recurrences of candiduria or candidemia with treatment (3). Fluconazole is usually considered the first-line agent of choice when treatment is indicated.
1. Kauffman CA. Candiduria. Clin Infect Dis 2005;41:S371-6.
2. Pappas PG, Kauffman CA, Andes D, et al. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503–35.
3. Revankar SG, Hasan MS, Revankar VS, et al. Long-term follow-up of patients with candiduria. Eur J Clin Microbiol Infect Dis 2011;30:137-140.
Absolutely! Besides HIV infection which should be excluded in all patients with recurrent bouts of bacterial pneumonia irrespective of age, “selective polysaccharide antibody deficiency” which may account for 8% of adults with recurrent CAP, should also be excluded (1). These patients (median age 48 years) often present with recurrent bouts of bacterial pneumonia despite having normal serum total immunoglobulin (IgG, IgA, and IgM) levels (1,2). They have a normal response to tetanus toxoid (a protein) but cannot mount adequate antibody response against polysaccharide antigens of pathogens such as pneumococcus. IVIG may reduce the risk of future bouts of pneumonia in this condition (2).
1. Cohn JA, Skorpinski E, Cohn JR. Prevention of pneumococcal infection in a patient with normal immunoglobulin levels but impaired polysaccharide antibody production. Ann Allergy Asthma Immunol 2006;97:603-5.
2. Cheng YK, Kecker PA, O’Byrne MM, Weiler CR. Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome. Ann Alergy Asthma Immunol 2006;97:306-311.