Viral meningitis outbreak in Gaza

Clinical, epideologic and laboratory characterstics

 Abstract

 During April-July 2004 an outbreak of viral meningitis occurred in Gaza strip. This report aimed to study some epidemiological characters of this outbreak and to find differentiating criteria between viral and bacterial meningitis. The result showed that aseptic meningitis is present all through the year with peak occurrence between April and July. The reported cases in our hospital during the year 2004 were 1686 (compared to 300 in 2003) of them 1371 occurred in this 4 month period. Male/ Female ratio was 6/4. In general, symptoms are mild, and no deaths.

The main clinical manifestations were fever, vomiting, headache, lethargy and sore throat. Clinical manifestations of viral and bacterial were similar but toxic look was present in all cases of bacterial meningitis and in only 18% of cases in aseptic meningitis. CSF Neutrophils were high in 29% of cases in aseptic meningitis and CSF sugar was low in 21% of cases. Viral culture was done for 12 cases. Virus isolated Echo 4, Echo, Coxsackie A9 one from each and nonparalytic polio in 3 cases no viruses detected in 6 cases. Bacterial meningitis was confirmed in 36 cases, Neiseria meningitides, 24 Strept. pneumonia, 11 and H. influenza one case.

Conclusion: Viral meningitis outbreak is common during early summer. The outbreak occurs every 3-4 years

Bacterial meningitis during the viral outbreak still causes concern, clinical picture and CRP in the CSF is helpful in differentiating between viral and bacterial meningitis but molecular methods of enterovirus detection as PCR is needed for rapid viral detection
 

 Introduction

Aseptic meningitis is a central nervous system infection characterized by fever and meningeal symptoms with moderate increase in the CSF, WBCs, mainly lymphocytes in most cases and the absence of bacterial pathogens in CSF. The disease occurs both sporadically and in outbreaks, Enteroviruses are the most common cause of aseptic meningitis (12, 18). Outbreaks of viral meningitis occur worldwide including Palestine ( 1, 2, 3, 5, 6).     

Enteroviruses typically demonstrate a marked seasonality in temperate climates, with a typical enterovirus season in the temperate countries in summer and autumn (10,14,15,17,18). In Gaza we had an outbreak in 1997. The outbreaks usually occur between April and July. Virus culture is the standard technique for enterovirus detection, but it consumes time and resources and has limited clinical use. Molecular methods of enterovirus detection (e.g., PCR) are increasingly used (12,19); both tests are not yet available in our hospital. Testing ofadult patients with aseptic meningitis by means of PCR may be cost effective during an outbreak of enteroviral meningitis (8) Aseptic meningitis is a benign, self-limiting illness, and severe illness and death are uncommon (10,18). The treatment is symptomatic and the majority of patients recover in approximately 1 week. Enteroviruses typically are spread through the fecal-oral or oral-oral routes and through respiratory droplets and fomites. Contaminated water could be the origin of outbreaks of enteroviral infection outbreak (13).Adherence to good hygienic practices, such as frequent and thorough hand washing, disinfection of contaminated surfaces by household cleaners, and avoidance of shared utensils and drinking containers, and chlornation of water are the main lines of prevention (13,14).

Objectives: To determine the different types of meningitis i.e viral or bacterial. To determine the clinical presentations of meningitis To interpret the available laboratory findings of the meningitis patients. To find the differentiating criteria between viral and bacterial meningitis Evaluate the protocol of management
 

Methodology

Study population:

- All children admitted in the Nassr pediatric hospital diagnosed as having meningitis in the period between 18/5/2004 – 13/6/2004.

- Culture and or direct smear proved bacterial meningitis in the period between 01/01/2004 – 31/12/2004.

- Diagnosis of meningitis was based on clinical and laboratory investigations including lumbar puncture and CSF examination.

Protocol of management

Laboratory investigations; Cerebrospinal fluid and blood specimens were collected from all suspected children under aseptic conditions and sent immediately to the hospital laboratory, Cerebrospinal fluid specimens were tested for cell counts with differential, Gram stain, glucose determination, protein and bacterial cultures. Other important laboratory tests were carried out during the evaluation included bacterial cultures of blood, petechial rash Gram stain, blood glucose level and CBC and CSF for CRP. Some CSF specimens were saved for further diagnostic studies especially for viral isolation.

Working definitions; Bacterial meningitis: Cells >1000/mm3, Protein high, Glucose low. Gram stain positive, Culture positive.   Treatment: Ceftriaxone ‘Rocephin ‘100mg /kg /24hr or Cefotaxime (Claforan) 200mg/kg/24hrs divided every 6hrs combined with Vancomycin 60mg/kg/24hrs divided every 6 hrs. Duration depends on type of organism. Dexamethazone: 0.6mg/kg/24hr.divided every 6hr for 2 days. Suspected bacterial meningitis: CSF cells less than 1000/ml, mainly neutrophils, Proteins high, sugar low. Direct smear negative, Culture negative. Treatment given: Ampicillin 300 mg/kg/day divided 4 hourly and chloramphenicol 100 mg/kg/day divided 6 hourly. Aseptic meningitis: CSF cells less than 1000/ml mostly lymphocytes, protein normal or slightly increased, Gram stain negative . Culture negative. Treatment given iv Ampicillin 200mg/kg/24hr divided every 6hr. If CSF C&S is negative and good general condition stops treatment and discharge the patient

*clinical evaluation and judgment is important as Lab. investigation in deciding diagnosis and type of treatment.            

Results:

 Clinical Manifestation of Bacterial Meningitis vs. Viral Meningitis

 CSF virology results

Bacterial meningitis confirmed CSF Culture Lab. Results

Bacterial Meningitis Culture Results

Bacterial Meningitis Results Vs. Age groups

Note: Skin smear was positive in one patient 9 months old and negative in CSF and blood culture.

Pneumoccoal pneumonia:11 cases  

Three cases were positive in both CSF culture and blood culture.

Tow cases were positive in CSF culture Gram stain and blood culture.

 N. Meningitides: there is one case positive culture in both CSF and Gram      stain

CRP results in CSF

·     One case was viral meningitis the other partially treated pneumococcal meningitis

  Viral meningitis during last 10 year

Discussion :

 Meningitis is central nervous system infection affecting the meninges of the brain and spinal cord.  It is caused mainly by viral or bacterial infection. Viral infection is more common but generally mild disease bacterial infection is less common, but can be life threatening (11). Viral meningitis is world wide spread disease caused mainly by entero-viruses. It causes occasional out break especially in late summer in temperature countries (10, 20).

In Gaza as show in our study viral meningitis is present all through  the year with seasonal increase mainly in spring with periodic out breaks almost every (4) years. This is due to the accumulation of the susceptible hosts in children. In Cuba the first epidemic of Echovirus meningitis in occurred between April to September 2000 and in Japan between June and august (9), the same season as in Palestine (19). The mode of the transmission of the disease is through feco-oral route (20) and this may explain the high prevalence among children who is immune susceptible and their way of life, (playing together and sharing toys and utensils).

The contact history was positive only in 17%, this can be explained by the fact that entero-viral infection is mild disease and most cases are asymptomatic. The attack rate for enteroviral meningitis is less than one percent (14). Our reported case only for clinical meningitis but other symptomatic entero-viral infections as gastroenteritis and serology for asymptomatic contact, was not included or tested.

In the early period of the outbreak CSF culture for virology was done and of the (12) samples collected 6 proved to be different types of enterovirus and the other 6 were negative. This is because not all viruses can be cultured and only around 40-80% can the virus be cultured from the CSF (20). The isolation of different types of enteroviruses in outbreak is not unusual (7, 10)  Antigen defection by the PCR is increasingly used method for viral infection diagnosis as viral culture methods are not practical (7,20). Unfortunately both methods are not available in Gaza. Early and rapid diagnosis of viral infection is needed because there is clinical and laboratory overlap between viral and bacterial meningitis especially partially treated meningitis making correct diagnosis difficult.

The predominant clinical manifestations in viral meningitis were Fever (96.4%), Vomiting, (90.6%), Headache, (67.9%), 126, (56.3%). throat congestion, (54%) and few patients had diarrhea (6.5%) that is similar to other studies (19)

 Some of the clinical manifestations when present suggest bacterial infection more than viral as toxic look which was present in 77.8% of bacterial and 21.2% of viral infections. The presence of petechial skin rash is very significant as it usually indicates meningococcal bacterial infection; it was present in 27.8% of bacterial meningitis (meningococcal bacterial meningitis diagnosed in 60% of cases) and present in only 0.9% of viral meningitis. The clinical triad of meningitis neck stiffness, brudzinki and  kernig signs showed no significant difference between viral and bacterial, Convulsions,  irritability and shock are more common in bacterial meningitis than viral meningitis. Headache, sore throat and abdominal pain more common in viral meningitis. The gender distribution was Females were 59% and Males 41% that is similar to other studies (11,14) others found more males 62% (10) and male to female ratio 2.0: 1.0 (9) . All age groups of children were affected including the neonates (13%). In Kirscheke etal report 26% of cases were infants less than 4 months old (11). In another study 38% of patients were infants less than 3 months old with age range 2 weeks to 29 years old (10)   

 The laboratory tests are the key factor in the diagnosis of meningitis. The presence of more than 5, WBC in the CSF indicates meningitis. The higher the cell count and the prevalence of neutrophils are more suggestive of bacterial infection especially with elevated proteins and low glucose (less than 50% of blood glucose) (20)

  In our study the WBC in the CSF was significantly higher in bacterial meningitis than viral meningitis (75%-5% respectively), in which neutrophlia was present in 100% cases of bacterial and in 29% of viral infection. Leukocytosis in the CSF of patients with viral meningitis found to range from 10to 3,493 and neutrophilia more than 50% was found in 25% of cases (9).In the early stages of viral meningitis neutrophile leucocytosis may be found in the CSF making the diagnosis more difficult (20). In this case repeat lumber puncture 6-12 hours after the first show the lymphocytic predominance (20)

Blood leucocytosis and specially neutrophilia was high in bacterial meningitis (97.2%) but still 41.1% of viral infections has neutrophilia other studies showed that peripheral WBC count is not helpful in differentiating between viral and bacterial infection.

 CRP was tested in the CSF of (304) patients. It was positive in 6 cases and negative in 298 patients.  Confirmed bacterial meningitis by culture or gram stain  in which CSF was tested for CRP were 8 cases, 4 cases the CRP was positive and 4 cases was negative. The CRP was positive in 2 cases one with viral meningitis and the other relapse case of previously treated pneumococcal meningitis in which the new CSF culture and gram stain was negative.

This indicates that positive CRP is highly suggestive of bacterial meningitis while negative CRP can not rule bacterial meningitis and this agree with others who found CPR in the CSF lack sensitivity and specificity to distinguish bacterial from viral infection (14,20).

The differentiation between viral and partially treated meningitis even more difficult as the CSF and blood culture may be negative, but in general partially treated meningitis the CSF proteins and WBC counts are higher.

In our study there was a group we categorized it as suspected bacterial meningitis because of the high CSF, proteins and neutrophilic count and they were given Ampicillin and chloramphenicol for at least 5 days depending on the clinical response. These cases CPR and other tests for bacterial antigen detection is needed to prevent unnecessary prolonged antibiotic treatment or under treatment.

In conclusion; meningitis is common disease among children, viral meningitis  due to enteroviral out breaks occur every 3-4years, bacterial meningitis is less frequent but more serous.

Antigen detection laboratory tests are needed for rapid diagnosis to prevent unnecessary use of antibiotics and reduce the duration of hospitalizations

 References:

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9. Akasu Y. Outbreak of aseptic meningitis due to ECHO-9 in northern Kyushu island in the summer of 1997. Kurume Med J. 1999;46(2):97-104

10. Echovirus Type 13 --- United States, CDC MMWR September 14, 2001 / 50(36);777-780

11. Kirschke DL, Jones TF, Buckingham SC, Craig AS, Schaffner W Outbreak of aseptic meningitis associated with echovirus 13. Pediatr Infect Dis J. 2002 Nov;21(11):1034-8.

12. Thoelen I, Lemey P, Van Der Donck I, Beuselinck K, Lindberg AM, Van Ranst M. Molecular typing and epidemiology of enteroviruses identified from an outbreak of aseptic meningitis in Belgium during the summer of 2000 J Med Virol. 2003 Jul;70(3):420-9.

13. Amvros'eva TV, Bogush ZF, Kazinets ON, D'iakonova OV, Poklonskaia NV, Golovneva GP, Sharko RM. Outbreak of enteroviral infection in Vitebsk during pollution of water supply by enteroviruses. Vopr Virusol. 2004 Jan-Feb;49(1):30-4.

14.  Viral Meningitis Outbreak Strikes Prince William Sound.  States of Alaska Bulletin No. 14, October 4, 2001

15. Viral meningitis in Cyprus 12 August 1996 communicable disease surveillance and response

16. Viral meningitis in Romania - Update 3  24 September 1996 communicable disease surveillance and response

17. Ozkaya E, Hizel K, Uysal G, Akman S, Terzioglu S, Kuyucu N. An outbreak of Aseptic Meningitis due to echovirus type 30 in two cities of Turkey Eur J Epidemiol. 2003;18(8):823-6.

18. Sabine Diedrich¹ and Eckart Schreier Aseptic meningitis in Germany associated with echovirus type 13 BMC Infect Dis. 2001; 1: 14. Published online 2001 September 14.

19. Luis Sarmiento,* Pedro Mas,* Angel Goyenechea,* Rosa Palomera,* Luis Morier,* Virginia Capó,* Ibrahim Quintana,† and Manuel Santin First Epidemic of Echovirus 16 Meningitis in Cuba CDC Emerging infectious diseases

20. Dr Ben Tan, Division of Infectious Diseases, Royal University Hospital, University of Saskatchewan, Saskatoon, SaskatchewanViral meningitis Case scenario Paediatrics &Child Health 1998; 3(6): 433-436

By

Abdulrahman Issa, Raed Mahdi, Yousef Awad, Shaker Abushaaban, Bassam Hammad

  Alnassr apaediatric hospital

 Hanan project

Correspondence; Abdulrahman Issa FRCP Consultant Pediatrician, Alnassr pediatric hospital director, Gaza, Palestine