Kurien Thomas

Spread of Drug-Resistant Streptococcus pneumoniae in Asian Countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.

Prospective multicentre hospital surveillance of Streptococcus pneumoniae disease in India

BACKGROUND Although Streptococcus pneumoniae is recognised as an important cause of morbidity and mortality worldwide, in India few data are available on the pattern of invasive disease, serogroup/type prevalence, and antimicrobial susceptibility pattern of the organism. METHODS We studied the characteristics of invasive pneumococcal infections in six hospitals in India over 4 years, in patients with suspected pneumonia (3686), pyogenic meningitis (1107), septicaemia (257), or localised pus-forming lesions (688). Blood, cerebrospinal fluid (CSF), or other normally sterile body fluids were cultured, and CSF was tested for pneumococcal antigens. All pneumococcal isolates were serotyped and their antimicrobial susceptibility tested by standard methods. FINDINGS S. pneumoniae was isolated from blood, other normally sterile body fluids, or deep-seated pus in 307 patients, and antigen was detected in CSF in a further seven. 71 patients were younger than 2.0 years, 32 were 2.0-4.9 years, and 211 were older than 5.0 years. The clinical syndromes associated with pneumococcal infection were meningitis (117; case-fatality rate 34%), pneumonia (93; 19%), septicaemia (24; 21%), peritonitis (23; 4%), and others (empyema thoracis, pericarditis, or arthritis 57; 6%). Overall, 215 (70%) of the isolates were of serotypes 1, 6, 19, 7, 5, 15, 14, 4, 16, and 18 (in order of frequency). The most common serotypes in children under 5 years were 6, 1, 19, 14, 4, 5, 45, 12, and 7. Serotypes 1 and 5 accounted for 29% (92 of 314) of disease. Intermediate resistance to penicillin was noted in only four (1.3%) isolates; however, resistance to co-trimoxazole (trimethoprim-sulphamethoxazole) and chloramphenicol was seen in 173 (56%) and 51 (17%) isolates, respectively. INTERPRETATION Hospital-based surveillance of community-acquired infections can provide data useful for planning. Two pneumococcol serotypes accounted for a significant proportion of the disease. Although penicillin resistance was infrequently present, continued surveillance will be prudent.

Carriage of Antibiotic-Resistant Pneumococci among Asian Children: A Multinational Surveillance by the Asian Network for Surveillance of Resistant Pathogens (ANSORP)

To investigate the nasal carriage of antibiotic-resistant pneumococci by children, anterior nasal swabs were done for 4963 children <5 years old in 11 countries in Asia and the Middle East. In total, 1105 pneumococci isolates (carriage rate, 22.3%) were collected, 35.8% of which were found to be nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and Vietnam (70.4%). Penicillin resistance was related to residence in urban areas, enrollment in day care, and a history of otitis media. The most common serogroups were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to strains of invasive isolates from adult patients. Data in this study documented the high rate of penicillin or multidrug resistance among isolates of pneumococci carried nasally in children in Asia and the Middle East and showed that this is due to the spread of a few predominant clones in the region.

Predictors of multi-organ dysfunction in heatstroke

Background: Heatstroke is a medical emergency that results from failure of thermoregulatory mechanism coupled with an exaggerated acute phase response, causing an elevation in core body temperature that rises above 40°C, producing multi-organ dysfunction. It carries a high mortality rate, and in survivors, a risk of permanent neurological damage. Objective: To investigate predictors of multiple organ dysfunction syndrome in patients presenting with heatstroke. Methods: We investigated 28 patients admitted to a hospital in southern India during the period January 1998 to December 2001. Using a standard form, we collected data on the patients’ characteristics, laboratory data, and outcome, and compared those with multiple organ dysfunction with those without such dysfunction. Results: We found that more than three quarters of the studied patients developed multiple organ dysfunction, with the most common dysfunction being respiratory failure. Among the selected predictors, metabolic acidosis 14 of 16 patients, 87.5%; p = 0.011, elevated CPK 17 of 19 patients, 89.5%; p = 0.005, and liver enzymes elevated more than twice the normal (11 of 18 patients, 61%; p = 0.02) had the highest correlation with dysfunction of two or more organs. Conclusions: The high mortality observed in heatstroke is secondary to multi-organ dysfunction, and among the various parameters assessed, high levels of CPK (>1000 IU/l), metabolic acidosis, and elevated liver enzymes are predictive. Aggressive measures to lower the body temperature with other supportive therapy could substantially reduce the mortality.

Invasive Pneumococcal Disease in Kanti Children's Hospital, Nepal, as Observed by the South Asian Pneumococcal Alliance Network

BACKGROUND Pneumonia accounts for approximately 2 million deaths annually among children aged <5 years, with most of these deaths occurring in Africa and southern Asia. The South Asian Pneumococcal Alliance (SAPNA) network in Nepal is generating local epidemiological data to assist in the development of national and regional policies for prevention of pneumococcal and Haemophilus influenzae (Hib) disease. METHODS Children aged 2 months to 5 years with suspected invasive bacterial disease were recruited from Kanti Children Hospital, Kathmandu, Nepal. Specimens of blood, CSF, and normally sterile body fluids were cultured, and analysis of antimicrobial susceptibility patterns and serotyping of Streptococcus pneumoniae isolates were performed. CSF specimens were also tested for S. pneumoniae and Hib antigens by a latex agglutination test and an immunochromatographic test of pneumococcal antigen (NOW S. pneumoniae Antigen Test; Binax). RESULTS A total of 2528 children with suspected invasive bacterial disease were recruited, of whom 82% had pneumonia, 9.6% had meningitis, 2% had very severe disease, and 0.4% had bacteremia; the remainder received another diagnosis. Before hospitalization, 26.7% had received antibiotic treatment. Fifty children had S. pneumoniae identified as the etiological agent of invasive disease. Of 2461 blood cultures performed, 22 were positive for S. pneumoniae. Of 33 cases of S. pneumoniae meningitis, 11 were detected by CSF culture, and 21 were detected by latex agglutination and pneumococcal antigen tests. The rate of detection of S. pneumoniae in CSF was 3.6% by culture, compared with 7.8% by latex agglutination and 10% by pneumococcal antigen testing. The rate of detection of H. influenzae in CSF was 1.7% by culture and 6.5% by latex agglutination. The most common serotypes found were 1, 5, 2, and 7F, followed by 12A, 19B, and 23F. Of all the invasive isolates, 3.8% were resistant to penicillin, and 68% were resistant to trimethoprim-sulfamethoxazole. CONCLUSIONS The SAPNA network has identified Hib and pneumococci as causes of significant disease in Nepal.

Scrub typhus: an unrecognized threat in South India - clinical profile and predictors of mortality.

Summary Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus.

Acute undifferentiated febrile illness in adult hospitalized patients: the disease spectrum and diagnostic predictors – an experience from a tertiary care hospital in South India

Local prevalences of individual diseases influence the prioritization of the differential diagnoses of a clinical syndrome of acute undifferentiated febrile illness (AFI). This study was conducted in order to delineate the aetiology of AFI that present to a tertiary hospital in southern India and to describe disease-specific clinical profiles. An 1-year prospective, observational study was conducted in adults (age >16 years) who presented with an undifferentiated febrile illness of duration 5–21 days, requiring hospitalization. Blood cultures, malarial parasites and febrile serology (acute and convalescent), in addition to clinical evaluations and basic investigations were performed. Comparisons were made between each disease and the other AFIs. A total of 398 AFI patients were diagnosed with: scrub typhus (47.5%); malaria (17.1%); enteric fever (8.0%); dengue (7.0%); leptospirosis (3.0%); spotted fever rickettsiosis (1.8%); Hantavirus (0.3%); alternate diagnosis (7.3%); and unclear diagnoses (8.0%). Leucocytosis, acute respiratory distress syndrome, aseptic meningitis, mild serum transaminase elevation and hypoalbuminaemia were independently associated with scrub typhus. Normal leukocyte counts, moderate to severe thrombocytopenia, renal failure, splenomegaly and hyperbilirubinaemia with mildly elevated serum transaminases were associated with malaria. Rash, overt bleeding manifestations, normal to low leukocyte counts, moderate to severe thrombocytopenia and significantly elevated hepatic transaminases were associated with dengue. Enteric fever was associated with loose stools, normal to low leukocyte counts and normal platelet counts. It is imperative to maintain a sound epidemiological database of AFIs so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Acute kidney injury in tropical acute febrile illness in a tertiary care centre—RIFLE criteria validation

BACKGROUND Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear. METHODS Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement. RESULTS The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001). CONCLUSIONS The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.

Clinical profile and improving mortality trend of scrub typhus in South India

BACKGROUND Scrub typhus, a bacterial zoonosis caused by Orientia tsutsugamushi, may cause multiorgan dysfunction syndrome (MODS) and is associated with significant mortality. This study was undertaken to document the clinical and laboratory manifestations and complications and to study time trends and factors associated with mortality in patients with scrub typhus infection. METHODS This retrospective study, done at a university teaching hospital, included 623 patients admitted between 2005 and 2010 with scrub typhus. The diagnosis was established by a positive IgM ELISA and/or pathognomonic eschar with PCR confirmation where feasible. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with mortality were analyzed using multivariate logistic regression analysis. RESULTS The most common presenting symptoms were fever (100%), nausea/vomiting (54%), shortness of breath (49%), headache (46%), cough (38%), and altered sensorium (26%). An eschar was present in 43.5% of patients. Common laboratory findings included elevated transaminases (87%), thrombocytopenia (79%), and leukocytosis (46%). MODS was seen in 34% of patients. The overall case-fatality rate was 9.0%. Features of acute lung injury were observed in 33.7%, and 29.5% required ventilatory support. On multivariate analysis, shock requiring vasoactive agents (relative risk (RR) 10.5, 95% confidence interval (CI) 4.2-25.7, p<0.001), central nervous system (CNS) dysfunction (RR 5.1, 95% CI 2.4-10.7, p<0.001), and renal failure (RR 3.6, 95% CI 1.7-7.5, p=0.001) were independent predictors of mortality. Over 4 years, a decreasing trend was observed in the mortality rate. CONCLUSIONS Scrub typhus can manifest with potentially life-threatening complications such as lung injury, shock, and meningoencephalitis. MODS occurred in a third of our patients. The overall case-fatality rate was 9%, with shock, renal failure, and CNS associated with a higher mortality.

Nasopharyngeal colonization of infants in southern India with Streptococcus pneumoniae.

To investigate the dynamics of nasopharyngeal colonization with Streptococcus pneumoniae, and to determine the prevalent serogroups/types (SGT) and their antimicrobial susceptibility, we studied 100 infants attending our well-baby clinic. Nasopharyngeal swab specimens were obtained at 6, 10, 14, 18 and 22 weeks and at 9 and 18 months of age and submitted for culture, serotyping and antimicrobial susceptibility testing of S. pneumoniae. Colonization with pneumococcus was seen on at least one occasion in 81 infants. The median age of acquisition was 11 weeks and the median duration of carriage was 1 3 months. The common SGTs identified were 6, 19, 14 and 15. SGT 1, which was a common invasive isolate in children in our hospital during this period, was not isolated from these children. Sequential colonization by 2, 3 or 4 SGTs was observed in 18, 5 and 2 children, respectively. Resistance to penicillin, chloramphenicol, cotrimoxazole and erythromycin was observed in 0, 13 (6%) 11 (5 %) and 5 (3 %) isolates, respectively. There was a significant difference in susceptibility to cotrimoxazole between colonizing and invasive isolates (5 % vs. 40 %, P<0.0001).