2017 Article - "Goal directed therapy for suspected acute bacterial meningitis in adults and adolescents in sub-Saharan Africa" (pdf, 2MB)

Summary: Mortality from acute bacterial meningitis (ABM) in sub-Saharan African adults and adolescents exceeds 50%. This group tested if Goal Directed Therapy (GDT) was feasible for adults and adolescents with clinically suspected ABM in Malawi.

Sequential patient cohorts of adults and adolescents with clinically suspected ABM were recruited in the emergency department of a teaching hospital in Malawi using a before/after design. Routine care was monitored in year one (P1). In year two (P2), nurses delivered protocolised GDT (rapid antibiotics, airway support, oxygenation, seizure control and fluid resuscitation) to a second cohort. The primary endpoint was composite mean number of clinical goals attained. Secondary endpoints were individual goals attained and death or disability from proven or probable ABM at day 40.

563 patients with suspected ABM were enrolled in the study; 273 were monitored in P1; 290 patients with suspected ABM received GDT in P2. 61% were male, median age 33 years and 90% were HIV co-infected. ABM was proven or probable in 132 (23%) patients. GDT attained more clinical goals compared to routine care: composite mean number of goals in P1 was 0·55 vs. 1·57 in P2 GDT (p<0·001); Death or disability by day 40 from proven or probable ABM occurred in 29/57 (51%) in P1 and 38/60 (63%) in P2 (p = 0·19).

Kit used: FTD Bacterial meningitis

2017 Article - "Diagnostic Approach to Viral Acute Encephalitis Syndrome (AES) in Paedriatric Age Group: a study from New Delhi" (pdf, 110KB)

Summary: Acute Encephalitis Syndrome has heralded the emergence of multiple virulent pathogens, which may result in severe morbidity and mortality. In India, encephalitis is not notified and there has been a dearth of analysis for trends in encephalitis death rates and causation. A downward trend has been observed in encephalitis deaths, due to ‘known’ causes, which can be largely explained by improvement in diagnostic, treatment, and prevention methods. There is still a very high proportion of encephalitis deaths in developing countries, where the aetiological diagnosis of the pathogen is not established and thus, lies the importance of monitoring encephalitis morbidity and mortality with a view to improve pathogen diagnosis and identify emerging infectious diseases.

The aim of the study was to formulate a diagnostic approach to viral acute encephalitis syndrome in paediatric age group. A cross-sectional study including 50 paediatric patients, clinically diagnosed with acute encephalitis syndrome using WHO criteria was conducted. The CSF of all the patients was evaluated to diagnose the aetiology for viral pathogens. ELISA was used for diagnosing Japanese encephalitis and dengue encephalitis; and multiplex real time PCR was used for detecting HSV-1, HSV-2, Varicella zoster virus, Mumps virus, Enterovirus and Parechovirus (FTD Viral meningitis).

Confirmed diagnosis was established in 11 (22%) of 50 cases. A confirmed or probable viral agent of encephalitis was found in 7 (14%), bacterial agent was found in 2 (4%), non-infectious aetiology was found in 2 (4%). Fatal outcome was independently associated with patient age.

Despite extensive testing, the aetiologies of more than three fourth of the cases remains elusive. Nevertheless the result from the present study may be useful for future design of early diagnosis and treatment of the disease. New strategies for pathogen identification and continued analysis of clinical features and case histories should help us improve our ability to diagnose, treat and prevent encephalitis.

Overall, the multiplex assay accommodates lower costs and faster turn-around times for the detection of common pathogens found in CSF. The sensitivity and specificity of FTD Viral meningitis surpasses that of culturing techniques. It has shown comparable sensitivity to the singleplex Light cycler assays and improved ability to distinguish HSV-1 and HSV-2.

Kit used: FTD Viral meningitis

2017 Article - "Real-time PCR Detection of the Most Common Bacteria and Viruses Causing Meningitis"

Summary: Central nervous system (CNS) infections require prompt diagnosis, as the clinical condition progresses rapidly and may lead to severe permanent sequelae or death. The causative agents include viruses, bacteria, fungi, and parasites. This study retrospectively evaluated the results of 470 CSF specimens that had been sent to the Molecular Unit of our hospital with a pre-diagnosis of CNS infection and had been tested with the PCR method between January 2014 and December 2015. Specimens were tested using multiplex real-time PCR assay for Adenovirus (AdV), Cytomegalovirus (CMV), Enteroviruses (EV) (Polioviruses, Coxackieviruses, Echoviruses, and other enteroviruses), Epstein- Barr virus (EBV), Herpes simplex virus 1 and 2, Human Herpes virus 6 and 7, Varicella-zoster virus (VZV), Human Parecho viruses and Parvovirus B19, Hemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis. (FTD NEURO9 and FTD Bacterial meningitis, multiplex real-time PCR Kit). A bacterial or viral agent was identified in 98 (21%) of the 470 CSF samples. Of the patients, 85% were children and 15% were adults. While Enterovirus (25%) was the most frequently identified agent, Adenovirus ranked second (22%) and Streptococcus pneumoniae ranked third (15%) in total. Positivity was highest in the 0 - 5-year age range. Bacteria were detected with the PCR method in 22 patients: S. pneumonia in 14, and N. meningitidis in 8. Early diagnosis and treatment of meningitis are very important for reducing its mortality and morbidity. In patients with suspected meningitis, early detection of the responsible agents may be possible with molecular methods, such as PCR. Significant economic benefits may be obtained by preventing unnecessary antibiotic use and hospitalizations through the early detection of the microbial agents.

Kit used: FTD Neuro 9
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2017 Article - "Neisseria meningitidis nasopharyngeal carriage during the Hajj: A cohort study evaluating the need for ciprofloxacin prophylaxis" (limited access)

Summary: The annual Muslim pilgrimage has the potential of increase risk for acquisition of Neisseria meningitidis. Here, the authors evaluate the Hajj impact on the prevalence of N. meningitidis carriage with the help of culture and PCR in a paired and non-paired cohort of pilgrims. Secondary objectives were to calculate the compliance with recommended vaccination. This is a prospective paired (arriving and departing), non-paired arriving and non-paired departing cohort study with the collection of nasopharyngeal samples at the start and the end of the Hajj. The study included unpaired arriving pilgrims at King Abdul Aziz International Airport (N = 1055), unpaired departing cohort (N = 373), and a paired cohort (N = 628) who were tested on arrival and departure. This the largest study of the epidemiology of N. meningitidis among pilgrims. The study showed a significant difference in the carriage between pilgrims from high endemicity and other pilgrims with a predominance of serogroup B. The continued use of ciprofloxacin as prophylactic antibiotics should be reconsidered as well as the consideration to add serogroup B as a required vaccination.

Kit used: FTD Bacterial meningitis
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2017 Article - "The aetiologies of central nervous system infections in hospitalised Cambodian children" (pdf, 590KB)

Summary: Central nervous system (CNS) infections are an important cause of childhood morbidity and mortality.
The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.
This is a one year prospective study with children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens.
CNS infection was microbiologically confirmed in 55/284 children (19.3%). Enteroviruses (21/55), Japanese encephalitis virus (17/55), and Streptococcus pneumoniae (7/55) accounted for 45 (81.8%) of all pathogens identified.
Of the pathogens detected, 74.5% (41/55) were viruses and 23.6% (13/55) were bacteria. The majority of patients were treated with ceftriaxone empirically. The case fatality rate was 2.5%. In conclusion, enteroviruses, JEV and S. pneumoniae are the most frequently detected causes of CNS infection in hospitalised Cambodian children.

Kit used: FTD Bacterial meningitis, FTD Viral meningitis

2016 Article - "Autopsy prevalence of tuberculosis and other potentially treatable infections among adults with Advanced HIV Enrolled in Out-Patient Care in South A" (pdf, 1MB)

Summary: This study aimed to determine the autopsy prevalence of TB and other infections in HIV-positive adults enrolled at South African PHCs in the context of a pragmatic trial of empiric TB treatment (“TB Fast Track”). A striking finding in this study was the high proportion of decedents with evidence of two or more infections at autopsy, sometimes at different sites, or concurrent at the same site. The FTD Neuro 9 test was used to detect viral infections in CSF samples.

Kits used: FTD Neuro 9

2016 Article - "Predominance of enterovirus B and echovirus 30 as cause of viral meningitis in a UK population" (limited access)

Summary: Enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Midlands population, a retrospective regional surveillance study was performed.

Kit used: FTD EPA
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2014 Article - "Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia" (pdf, 184KB)

Summary: This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. 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, Haemophilus influenzae type B (HiB) and Neisseria meningitidis. A multiplex PCR test from Fast-Track Diagnostics (FTD Viral Meningitis) was used to detect HSV-1, HSV-2, mumps, enterovirus, and VZV. In-house singleplex PCR was performed to detect HiB, N. meningitidis, and S. pneumoniae. Out of 140 enrolled patients, bacterial or viral etiologies were determined in 51% of patients. Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort.

Kits used: FTD Viral meningitis

2014 Poster - "Real-time PCR diagnostic of bacterial meningitis using the FTD Bacterial meningitis kit" (pdf, 1MB)

Summary: A total of 55 CSF samples collected in the meningitis belt were tested by gel-based in-house singleplex PCR developed by the MRC Unit and compared with FTD Bacterial meningitis multiplex real time PCR kit. The study concluded that Multiplex real-time PCR can save time and costs compared to singleplex in-house tests as there is less enzyme required, less hands-on time, less time for analysis and in-house validation is not required. In addition to this, viruses and bacteria can be tested using the same extract, the same technical staff and the same real-time PCR machine. Real-time PCR also allows quantification which allows judgment about bacterial loads in children e.g. in different age groups, gender and health conditions. The Fast-track diagnostics tests include an internal control to detect extraction failure, sample inhibition and technical error. Commercially available kits guarantee consistency and avoid initial and ongoing work associated with in-house tests.

Kit used: FTD Bacterial Meningitis

2013 Poster - "Clinical validation of the FTD Bacterial meningitis panel in collaboration with the Medical Research Council, the Gambia" (pdf, 193KB)

Summary: In this validation it was found that The FTD Bacterial meningitis showed in comparison to in-house tests and currently applied gold standards sensitivies and specificities of 100%. The use of Real-time multiplex PCR in the detection of bacterial meningitis saves time and costs compared to singleplex in-house tests since less enzyme, less hands-on time and time for analysis is needed.The detection limit (not shown here) of Nm, Sp and Hi with the FTD Bacterial meningitis was determined to be as low as 0.1-1 target copies/µl. Commercial assays do not require further in-house validation.

Kit used: FTD Bacterial meningitis