Editorial @ Clostridium difficile Infection- Is it Coming at us? Rajeev Soman’, Ayesha Sunavala” «ificile infection (CDI) has become a global health challenge due to the recent increase in incidence and severity. Populations initially thought to be at low risk are now being identified as having severe CDI. C. dificile has a very fluid ‘genome and has the potential toadaptto various circumstances, become more virulent and develop antibiotic resistance, Studies on C. difficile associated diarthoea (CDAD) in India reveal a prevalence rate ranging from 7.1-26.6% with fewer cases cf fulminant infections as compared to western literature.!? A study as the one reported by Kaneria M et al in this issue of the journal, to evaluate the changing trends in incidence and predisposing factors of C. difficile in our country is definitely a step in the right direction. Several studies have thrown light on the changing spectrum of thedisease. Additional risk actors suchas gastricacid suppression ‘with proton pump inhibitors enteral feeding. gastrointestinal surgery, cancer chemotherapy, immunosuppressants and hematopoietic stem cell transplantation among others have been shown to be strongly associated with CDAD. recent study by Ingle etal from Mumbai infact revealed that C.dificle positivity ‘was not significantly influenced by prior antibiotic use, They found that underlying malignancy, ICU stay, chemotherapeutic agents and most importantly immnosuppressive therapy with corticosteroids were strongly associated with toxin positivity. In a retrospective case review by Morrison et al, age > 150 yrs and prior use of acid suppressors were identified as associated with increased mortality in patients with CDI. Hence, discontinuation of acid suppressant medication should be ‘considered after a diagnosis of C. dificile is made.’ However, in further studies to determine novel risk factors Table 1: Diagnosis of C. difficile Diagnostic Test Sensitivity Specificity Tum Cost ° around time Toxin detection 1. Cytotoxin 99%) Bhs High, assay o4100r6) 2 Enyme — + (60-95%) ++ (75-10%) <26hvs Low Immunoassay (ela) 3. PCRofstool ++(93%) +44(97%) © Thr High 1B. Organism detection 1. Common ws Low 1545 Low antigen (96-100%) mins testing (GDH. antigen) 2. Stool culture Low 72s Labour (asymptomatic intensive ‘carriage “Consultant Physician, “Infectious Diseases Fellow, P-D. Hinduja Hospital and Medical Research Centse, Veer Savarkar Marg, Mahi Mumbai 400016. or protective factors it is essential to establish the diagnosis in the disease group and rule it out in the control group by using strict diagnostic criteria. The diagnosis of C. dificile involves two modalities of testing; toxin assays (which evaluate for evidence of toxin) and ‘organism detection assays (which evaluate for the presence of the organism) (Table 1). Since no single test fulfils all the above clinical requirements, the accepted case definition of CDI as per the IDSA/SHEA 2010 clinical practice guidelines includes the following: + The presence of diarthoea, defined as passage of 3 or more unformed stools in 4 or fewer consecutive hours + A stool test result positive for the presence of toxigenic C. dificile or its toxins or colonoscopic or histopathologic findings demonstrating pseudomembranous colitis. ‘Most laboratories in India currently use the EIA testing for C. ificile toxin A and B, despite it being a suboptimal altemative, -ause it is rapid, affordable and easy to carry out. The low sensitivity of EIA cannot be overcome by repeated testing, as the repeat test may be false positive because the test also has @ low specificity. potential strategy recommended to overcome the poor EIA sensitivity is to perform a 2-step method that "uses EIA detection of GDH as inital screening followed by cell, cytotoxicity assay or toxigenic culture asa confirmatory test for GDH-positive stool specimens only.” However, certain caveats need to be recognised. Testing of C «ificiletoxin should be performed on only unformed, diarrhoeal stools, unless ileusis suspected. Testing of asymptomatic patients isnot routinely recommended due to high colonisation rates in the community, unless for epidemiological studies. Repeated testing during the same episode of diarrhoea is of limited value because of low increasing yield and the possibility of false positive results. If clinical suspicion is strong, infection control measures must be implemented and treatment should be initiated empirically and continued despite negative laboratory results It is pertinent to briefly review the pathogenesis of this, disease." Majority of humans deyelop antibodies to C. dificile toxin when colonized asymptomatically during the frst year of life. Infants do not develop symptomatic disease as they lack ‘mucosal toxin receptors which develop later an life. Exposure to antimicrobial agents later in lifes the first event that establishes ‘susceptibility to C. difficile infection. The second event in pathogenesis is the exposure to a toxigenic and virulent strain ‘of C.dificile. The third event and one that eventually determines which patients do or do not develop symptoms is the host anamnestic serum IgG antibody response to C. difficile toxin ‘A. Those individuals with high serum IgG antibody levels are ‘more likely to remain asymptomatic carriers and not develop the disease. Itis tempting to speculate as to why this disease may be less ‘common and severe in India. Possible contributory factors are a predominantly vegetarian diet among Indians, over the countersupply and frequent use of metronidazole, non adherence to complete course of antibiotics, a robust anamnestic antibody response due to repeated infections and perhaps the virulent, ‘more toxigenic strains may not be common in our country. The above factors might offer some insight into the remarkable differences in prevalence and severity ofthe disease in India as compared to other countries. There is however hardly a place for complacency. CDIs. hhave always been found when looked for. It is much more likely that more cases will come to light as the toxin assays and more sophisticated methods of diagnosis are used on a larger scale, CDLis an important nosocomial infection with attending morbidity, mortality and costs. Therefore infection control ‘measures need tobe emphasized. The C. dificle infection control ‘bundle should include contact precautions, daily bleach wipes for frequently touched surfaces, terminal cleaning with bleach and hand hygiene with soap and water rather than alcohol hhand rubs. ‘Special illumination must be provided to reveal areas that have not been cleaned. The restriction of antibiotics, especially clindamycin and 2 and 3* generation cephalosporins will benefit in controlling outbreaks. India has the dubious distinction of having many emerging infectious diseases. We only hope that CDI does not join that list. References 1. Ingle M, Deshukh A, Desai D etal Prevalence and clinical course ‘of Clostridium difficile infection in a tertiary-care hospital: 3 retrospective analysis. Indian J Gastroenterol 2011;3089-93,