Maksuda Islam

Population-Based Incidence and Etiology of Community-Acquired Neonatal Bacteremia in Mirzapur, Bangladesh: An Observational Study

BACKGROUND To devise treatment strategies for neonatal infections, the population-level incidence and antibiotic susceptibility of pathogens must be defined. METHODS Surveillance for suspected neonatal sepsis was conducted in Mirzapur, Bangladesh, from February 2004 through November 2006. Community health workers assessed neonates on postnatal days 0, 2, 5, and 8 and referred sick neonates to a hospital, where blood was collected for culture from neonates with suspected sepsis. We estimated the incidence and pattern of community-acquired neonatal bacteremia and determined the antibiotic susceptibility profile of pathogens. RESULTS The incidence rate of community-acquired neonatal bacteremia was 3.0 per 1000 person-neonatal periods. Among the 30 pathogens identified, the most common was Staphylococcus aureus (n = 10); half of all isolates were gram positive. Nine were resistant to ampicillin and gentamicin or to ceftiaxone, and 13 were resistant to cotrimoxazole. CONCLUSION S. aureus was the most common pathogen to cause community-acquired neonatal bacteremia. Nearly 40% of infections were identified on days 0-3, emphasizing the need to address maternal and environmental sources of infection. The combination of parenteral procaine benzyl penicillin and an aminoglycoside is recommended for the first-line treatment of serious community-acquired neonatal infections in rural Bangladesh, which has a moderate level of neonatal mortality. Additional population-based data are needed to further guide national and global strategies.

Identification of Serotype in Culture Negative Pneumococcal Meningitis Using Sequential Multiplex PCR: Implication for Surveillance and Vaccine Design

Background PCR-based serotyping of Streptococcus pneumoniae has been proposed as a simpler approach than conventional methods, but has not been applied to strains in Asia where serotypes are diverse and different from other part of the world. Furthermore, PCR has not been used to determine serotype distribution in culture-negative meningitis cases. Methodology Thirty six serotype-specific primers, 7 newly designed and 29 previously published, were arranged in 7 multiplex PCR sets, each in new hierarchies designed for overall serotype distribution in Bangladesh, and specifically for meningitis and non-meningitis isolates. Culture-negative CSF specimens were then tested directly for serotype-specific sequences using the meningitis-specific set of primers. PCR-based serotyping of 367 strains of 56 known serotypes showed 100% concordance with quellung reaction test. The first 7 multiplex reactions revealed the serotype of 40% of all, and 31% and 48% non-meningitis and meningitis isolates, respectively. By redesigning the multiplex scheme specifically for non-meningitis or meningitis, the quellung reaction of 43% and 48% of respective isolates could be identified. Direct examination of 127 culture-negative CSF specimens, using the meningitis-specific set of primers, yielded serotype for 51 additional cases. Conclusions This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics.

Surveillance for Invasive Streptococcus pneumoniae Disease among Hospitalized Children in Bangladesh: Antimicrobial Susceptibility and Serotype Distribution

BACKGROUND Vaccines offer the prospect of primary disease prevention of pneumococcal disease in childhood. For introduction of such vaccines in developing countries, information about disease epidemiology is necessary. METHODS We evaluated antimicrobial susceptibility and serotype distribution of invasive Streptococcus pneumoniae disease in children aged <5 years in a network of 7 hospitals in Bangladesh from May 2004 through May 2007. RESULTS Of 17,969 blood cultures and 3765 cerebrospinal fluid cultures, 139 yielded S. pneumoniae isolates; 94 were from meningitis cases, 13 were from pneumonia cases, and 32 were from sepsis cases. Among the children with positive culture results, 73% were aged <12 months and 90% were aged <24 months. Complete resistance against penicillin, chloramphenicol, and cotrimoxazole was found in 0%, 6%, and 32% of isolates, respectively. Of the 37 serotypes observed, the predominant serotypes were 2 (17%), 1 (12%), 14 (7%), 5 (6%), 7F (6%), 45 (7%), and 12A (4%). Serotypes differed between meningitis cases and nonmeningitis cases, especially for serotype 2 (25% of meningitis cases vs. 0% of pneumonia cases; P < .001). The 7-, 10-, and 13-valent vaccines would cover 20% (95% confidence interval [CI], 13%-27%), 43% (95% CI, 35%-51%), and 50% (95% CI, 42%-58%) of these cases of invasive pneumococcal disease overall, with higher coverage of nonmeningitis cases, compared with meningitis cases (7-valent coverage, 23% vs. 18%; 10-valent coverage, 55% vs. 38%; 13-valent coverage, 66% vs. 42%). CONCLUSIONS High levels of nonsusceptibility to cotrimoxazole and susceptibility to penicillin suggest that penicillin may be a drug of choice for treatment of invasive pneumococcal disease. Although serotype distribution is diverse, with changes over time and differences between syndromes observed, implementation of use of the currently available 10- or 13-valent vaccines would have a substantial impact on pneumococcal disease in Bangladesh.

Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden.

Background: Streptococcus pneumoniae is the leading cause of childhood pneumonia and meningitis worldwide. Isolation of this organism, however, is uncommon in resource-poor countries, in part because of extensive use of prior antibiotics. A rapid, highly sensitive immunochromatographic test (ICT) for S. pneumoniae was evaluated for the diagnosis of meningitis. Methods: Cerebrospinal fluid (CSF) from 450 children with suspected meningitis was tested with ICT, and results were compared with CSF culture, latex agglutination test (LAT) and/or polymerase chain reaction (PCR). Serial CSF specimens from 11 patients were also evaluated for duration of positive results during effective antimicrobial therapy. Findings: All 122 cases of pyogenic pneumococcal meningitis positive either by culture (N = 87) or PCR (N = 35) were positive by ICT, yielding 100% (122 of 122) sensitivity. All purulent CSF specimens from patients with meningitis caused by other bacteria by culture (N = 149) or by LAT (N = 48) or those negative by culture, LAT and LytA and thus of unknown etiology (N = 20), and normal CSF specimens (N = 104) were negative by ICT. Thus the specificity of ICT also was 100% (321 of 321), although negativity of ICT was not confirmed by PCR, if it was positive for other organisms either by culture or LAT. Serotyping of S. pneumoniae strains revealed 28 different serotypes, indicating that outcome of ICT are independent of diverse capsular serotype of pneumococcus. Antigen was detected by ICT for at least 10 days after presentation, and 1 was still positive on day 20, which was longer than for either LAT or PCR. Interpretation: ICT for pneumococcal antigen in CSF is 100% sensitive and specific in diagnosing pyogenic pneumococcal meningitis and can detect ∼30% more pneumococcal meningitis cases than with culture alone. The simplicity of the test procedure and the longevity of CSF antigen detection suggest the potential utility of ICT to estimate the true burden of pneumococcal disease, as for Haemophilus influenzae type b using data from meningitis, and to guide selection of appropriate antibiotic treatment, especially in resource-poor countries with widespread prehospital antimicrobial use.

Invasive Pneumococcal Disease among Children in Rural Bangladesh : Results from a Population-Based Surveillance

BACKGROUND Streptococcus pneumoniae infection is recognized as a global priority public health problem, and conjugate vaccines have been shown to prevent vaccine-type invasive pneumococcal disease (IPD) in children. However, better estimates of the disease burden and reliable population-based data on serotype composition are needed for vaccine development and implementation in developing countries. METHODS We initiated a population-based surveillance in the rural Bangladesh community of Mirzapur, covering a population of approximately 144,000. Village health care workers made weekly visits to approximately 12,000 children 1-59 months of age in the study area. Children with reported fever, cough, or difficulty breathing were assessed by the village health care workers using a clinical algorithm and were referred to the hospital if required. Children from the study area who were seen in the hospital underwent clinical examination and laboratory testing if they met standardized case definitions. IPD was confirmed by blood and/or cerebrospinal fluid culture results. Isolates were identified, tested for susceptibility to antibiotics, and serotyped in accordance with standard laboratory methods. We present here the results from the first 3 years of the surveillance (July 2004-June 2007). RESULTS Village health care workers identified 5020 cases of possible severe pneumonia and/or very severe disease (165 cases per 1000 child-years)and 9411 cases of possible pneumonia (310 cases per 1000 child-years) as well as 2029 cases of suspected meningitis and/or very severe disease (67 cases per 1000 child-years) and 8967 cases of high fever and/or possible bacteremia (295 cases per 1000 child-years). Pneumonia was the single most common form of illness observed among 2596 hospitalizations (found in 977 [38%] of cases). We recovered 26 S. pneumoniae isolates (25 isolates from 6925 blood cultures and 1 isolate from 41 cerebrospinal fluid cultures), which gave an overall IPD incidence of 86 cases per 100,000 child-years. Invasive pneumococcal infection was common during infancy (with infants accounting for 23 of the 26 cases), and 50% of the total isolates were obtained from nonhospitalized patients who received a diagnosis of upper respiratory tract infection and fever. The most prevalent pneumococcal serotypes were serotypes 1, 5, 14, 18C, 19A, and 38. Ten of the 26 isolates were completely resistant to trimethoprim-sulfamethoxazole, and another 10 isolates had intermediate resistance. CONCLUSIONS IPD contributes substantially to childhood morbidity in rural Bangladesh. S. pneumoniae can cause invasive but nonsevere disease in children, and IPD incidence can be seriously under reported if such cases are overlooked. The emerging high resistance to trimethoprim-sulfamethoxazole should be addressed. Data on serotype distribution would help to guide appropriate pneumococcal conjugate vaccine formulation.

Interpretation of the Widal test in the diagnosis of typhoid fever in Bangladeshi children

The value of a Widal test in diagnosing typhoid fever was assessed in children aged between 1 and 10 years in Bangladesh. The test was done on sera specimens from 300 healthy school children, 100 patients with non-typhoidal febrile illness and 150 bacteriologically proven cases of typhoid fever. Salmonella typhi O and H agglutinin titres > 1:80 and > 1:160 were considered to be significant with 88% sensitivity and 98% specificity, respectively. Among the bacteriologically proven cases, 11.3% showed no response to either agglutinin, and in another 17.3% of cases there was no response for TO agglutinin. This study suggests that in children in an endemic area a positive Widal test is of considerable importance in diagnosing typhoid fever. Furthermore, negative results should be interpreted with caution and both the agglutinins must be considered equally important. Reliance on somatic (TO) antigen only will result in missed diagnosis.

Molecular Basis of Resistance Displayed by Highly Ciprofloxacin-Resistant Salmonella enterica Serovar Typhi in Bangladesh

ABSTRACT Highly ciprofloxacin-resistant (MIC, 512 μg/ml) strains of Salmonella enterica serovar Typhi were isolated from the blood of typhoid patients in Dhaka, Bangladesh. The strains were indistinguishable by their antibiograms, biotypes, and variable-number tandem repeat types and had matching point mutations at positions 83 and 87 of the gyrA gene. The isolation of these strains in an area of high endemicity indicates the need for continuous surveillance of antibiotic resistance of S. enterica serovar Typhi and for the rationalized use of ciprofloxacin.

Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial

BACKGROUND Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0-59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7-10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify effective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible. METHODS We did this randomised, open-label, equivalence trial in four urban hospitals and one rural field site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar efficacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratified randomisation by study site and age (<7 days or 7-59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov, number NCT00844337. FINDINGS Between July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfilled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk difference -1.5%, 95% CI -4.3 to 1.3) and 64 (8%) of 790 infants in group C (-1.7%, -4.5 to 1.1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 [2%] infants in group A vs 13 [2%] infants in group B and 10 [1%] infants in group C). INTERPRETATION Our results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable.

Effect of Topical Emollient Treatment of Preterm Neonates in Bangladesh on Invasion of Pathogens Into the Bloodstream

Topical emollient therapy may reduce the incidence of serious infections and mortality of preterm infants in developing countries. We tested whether emollient therapy reduced the burden of pathogens on skin and/or prevented bacterial translocation. Neonates <33 wk gestational age were randomized to treatment with sunflower seed oil (SSO) or Aquaphor or the untreated control group. Skin condition score and skin cultures were obtained at enrollment and on d 3, 7, and weekly thereafter, and blood cultures were obtained for episodes of suspected nosocomial sepsis. For analysis, blood cultures were paired with skin cultures obtained 0–3 d before the blood culture. Skin condition scores at 3 d were better in patients treated with either emollient compared with untreated controls; however, skin flora was similar across the groups. The SSO group showed a 72% elevated odds of having a false-positive (FP) skin culture associated with a negative blood culture (i.e. skin flora blocked from entry into blood) compared with the control group. Topical therapy with SSO reduced the passage of pathogens from the skin surface into the bloodstream of preterm infants.

The increasing burden of disease in Bangladeshi children due to Haemophilus influenzae type b meningitis

A laboratory-based study of diagnosed bacterial meningitis in the national paediatric hospital identified 852 cases of meningitis in the 8-year period 1987-1994. There were 587 culture-positive cases, of which Haemophilus influenzae (47%) and Streptococcus pneumoniae (32%) accounted for 80%. H. influenzae showed a remarkable increase of 700% during the study period. Most of the H. influenzae cases (90%) occurred in the 1st 2 years of life. Analysis of culture-negative specimens by antigen detection in the last 2 years also revealed the predominance of H. influenzae (71.4%) and S. pneumoniae (22.4%). Typing of H. influenzae isolates during this time showed that 98% of the strains were type b. This retrospective hospital-based study indicated a pronounced increase in the incidence of H. influenzae meningitis and strongly supports the need for large-scale Hib vaccination for young children. However, such nationwide intervention will probably need to be based on a prospective on a prospective and population-based surveillance of H. influenzae infections.