White blood cells and acute phase reactants in neonatal sepsis

No single diagnostic test for neonatal sepsis is both rapid and reliable. Combining leukocyte (wbc) counts with acute phase reactants (APR) enhances diagnostic accuracy. The most helpful wbc counts are leukopenia (less than 5.0 x 10(9)/l), increased immature/total neutrophils (greater than or equal to 0.2) and profound neutropenia (less than 1.0 x 10(9)). Of the APR, C-reactive protein responds most rapidly, but alpha 1-acid glycoprotein (orosomucoid), haptoglobin and mini-ESR (greater than or equal to 15 mm/h) are also useful. Rapid, quantitative determinations of APR are now available with nephelometric techniques. Abnormal wbc counts frequently appear before APR changes in group B streptococcal infection. Sequential determinations of wbc counts and APR may provide valuable diagnostic and prognostic information.     

Diagnostic value of plasma levels of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in newborns with sepsis

The aim of this study was to examine if TNFα and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and 11), a positive test result for plasma concentration of TNFα (> 70 pg/ml) had a sensitivity of 73 % and a specificity of 94%. A positive test result for IL-6 (>500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNFα and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio =α. The combination of TNFα and IL-6 determinations appears to be a good predictor of neonatal sepsis.     

Neutropenia in an extremely premature infant treated with recombinant human granulocyte colony-stimulating factor.

Neutropenia in the newborn is often associated with sepsis, maternal hypertension, or prematurity. We describe a 654-g infant born at 30 weeks' gestation by cesarean section due to severe maternal hypertension. His course was complicated by five episodes of sepsis, including three with group B streptococcus. The results of hematologic and immunologic studies were normal except that absolute neutrophil counts were low (less than 1 x 10(9)/L) with intermittent increases during sepsis. Human recombinant granulocyte colony-stimulating factor administered subcutaneously (10 micrograms/kg per day initially) resulted in an absolute neutrophil count of greater than 30 x 10(9)/L within 2 weeks. The dosage was lowered and the absolute neutrophil counts were maintained at 8 to 12 x 10(9)/L with no further septic episodes. The human recombinant granulocyte colony-stimulating factor therapy was discontinued after 7 months, and the patient remained healthy with an absolute neutrophil count of greater than 2 x 10(9)/L. Thus, treatment with human recombinant granulocyte colony-stimulating factor may be useful as a temporary measure for neonatal neutropenia associated with sepsis. A controlled, clinical trial is warranted.     

Early diagnosis of neonatal sepsis using a hematologic scoring system

Hematologic findings and published complete blood cell count criteria were evaluated as screening tests for neonatal sepsis. From the data obtained, a hematologic scoring system was formulated that assigns a score of 1 for each of seven findings: abnormal total leukocyte count, abnormal total neutrophil (PMN) count, elevated immature PMN count, elevated immature to total PMN ratio, immature to mature PMN ratio greater than or equal to 0.3, platelet count less than or equal to 150,000/mm3, and pronounced degenerative changes in PMNs. There were 298 evaluations for sepsis (243 in the first 24 hours of life and 55 between days 2 and 30). Twenty-six of 27 (96%) infants with sepsis and all 23 infants with probable infection had scores greater than or equal to 3, compared with 35 of 248 (14%) noninfected infants. The likelihood of sepsis with score greater than or equal to 3 was 31%, and this value differed with both gestational and postnatal ages (34% vs 8% in preterm and term infants less than 24 hours of age, and 65% thereafter). The higher the score the greater was the likelihood of sepsis. With score less than or equal to 2 the likelihood that sepsis was absent was 99%. The hematologic scoring system should improve the diagnostic accuracy of the complete blood cell count as a screening test for sepsis and could simplify and standardize the interpretation of this global test.     

The value of C-reactive protein measurement in the diagnosis of neonatal infection

We examined whether serum C-reactive protein (CRP) measurements used in conjunction with leucocyte counts help in the diagnosis of perinatally acquired and nosocomial infections in very preterm newborn infants. One hundred and twenty-five infants born at a gestational age between 23 and 31 weeks with respiratory distress were studied at birth. A similar group of 85 infants beyond 3 days of age were also studied on 100 occasions for suspected infection. The diagnosis of proven or probable infection was correlated with abnormal haematology (leucopenia less than 5000/mm3, leucocytosis greater than 20,000/mm3 or ratio of immature forms to total neutrophils of greater than 0.2) and an elevated CRP (greater than 10 mg/L) singly or in combination. The sensitivity of an elevated CRP was relatively higher than abnormal haematology in both early and late infections and the sensitivity was highest when either test was abnormal. Similarly, the specificity, positive and negative predictive values and efficiency of an elevated CRP was relatively higher than abnormal haematology. The performance of the tests in 45 infants born at 23-28 weeks gestation was similar to that in 80 infants born at 29-31 weeks gestation. It was concluded that both CRP and leucocyte counts should be determined as they provide valuable information in the diagnosis of neonatal bacterial infection.     

Clinical significance of quantitative blood cultures in newborn infants

AIM: To evaluate quantitative blood culture as a secondary test on a positive blood culture for the diagnosis of sepsis in newborn infants. METHOD: A 15-month prospective study of colony forming units (CFU) on positive blood cultures from newborn infants clinically suspected of having bacterial sepsis. Growth of bacteria in peripheral blood cultures was quantified using the isolater 1.5 microbial tube lysis direct plating culture system. Colony forming units were evaluated against a clinical assessment of infection. RESULTS: Of 137 positive blood cultures, 71 (51.8%) were taken from neonates with clinically defined infection and 66 (48.2%) were from non-infected infants. The clinical and biographical data in these two groups were similar. Coagulase negative staphylococci were the most commonly isolated organisms in each group (60.6% vs 93.9%). Eight deaths from sepsis occurred in the clinically infected group. Eighty-five per cent of sepsis was late onset. Although a CFU count > or = 30/mL predicted sepsis (sensitivity 83%, specificity 60%, positive predictive value 69%, negative predictive value 76%), a CFU count < 30/mL did not rule out serious sepsis. The higher the CFU count the greater the likelihood of sepsis. CONCLUSION: Quantitative blood culture was not shown to be a sensitive secondary test on a positive blood culture to distinguish clinical sepsis from culture contamination. Although a positive threshold of > or = 30 CFU/mL proved to be optimal, improvement in test performance would be expected with a lower incidence of culture contamination.     

Non‐specific host response markers in the differentiation between pneumococcal and viral pneumonia: What is the most accurate combination?

BACKGROUND: Serum C-reactive protein (CRP), blood white cell count (WBC), serum procalcitonin (PCT) and erythrocyte sedimentation rate (ESR) were measured in 132 children hospitalized for community-acquired pneumonia. Serological evidence for viral infection was found in 38 cases and for pneumococcal infection in 41 cases, and the infiltrate was alveolar in 46 cases and interstitial in 86 cases. The aim of the present paper was to determine if there is a combination of these four host response markers and chest radiograph findings suitable for differentiating pneumococcal from viral etiology of pneumonia. METHODS: The 50th, 75th and 90th percentiles of CRP, WBC, ESR and PCT in the total group of 132 patients were calculated. By using these cut-off limits, the likelihood ratios of a positive test result were calculated for the possible combinations of CRP, WBC, ESR and PCT, and the likelihood ratio was 1.50 or more for six combinations. RESULTS: The highest likelihood ratio (1.74) was achieved with the combination CRP > 90th (80 mg/L) or WBC > 75th (17.0 x 10(9)/L) or PCT > 75th (0.84 microg/L) or ESR > 90th (63 mm/h) percentile. For this combination, the sensitivity was 61% and the specificity 65%. When the 90th percentile cut-off limit was applied also for WBC (>22 x 10(9)/L) and PCT (>1.8 microg/L), the specificity increased to 76%, but the sensitivity decreased to 37%. When the presence of an alveolar infiltration was included in the combination, the likelihood ratio was 1.89; the specificity was as high as 82% and the sensitivity as low as 34%. CONCLUSIONS: CRP, PCT, WBC and ESR have only limited value in differentiating pneumococcal or other bacterial pneumonia from viral pneumonia. If there was a high value in at least one of the markers (CRP > 80 mg/L, PCT > 1.8 microg/L, WBC > 22 x 10(9)/L or ESR > 60 mm/h), viral infections were rare. There was no combination of these markers which was sufficiently sensitive and specific to be used in clinical pediatric practice.     

Evaluation of interleukin-6, tumour necrosis factor-α and interleukin-1β for early diagnosis of neonatal sepsis

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.     

Immunological events in acute measles influencing outcome.

77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.     

Febrile infants less than eight weeks old. Predictors of infection

Febrile infants less than eight weeks old frequently are admitted and receive parenteral antibiotics for treatment of possible sepsis. The authors assess 52 infants less than eight weeks old with a rectal temperature of 38.1 degrees C or higher as having either a readily identifiable focus of infection by physical examination, appearing "toxic" without a focus, or appearing well. The authors screened patients by using white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and chest radiographs in addition to blood, cerebrospinal fluid and urine cultures. The authors found a 9.6% incidence of bacteria in the 52 infants evaluated, with a 4.3% incidence in those febrile infants who appeared well. Five patients had positive blood cultures with Group B B Hemolytic streptococcus (four patients), and Viridans streptococcus (one patient). A clinical assessment of toxicity and a total band count greater than or equal to 0.5 x 10(3) cells/uL together were sensitive indicators of bacteremia, as were toxicity and a positive CRP. A "toxic" appearance, a WBC count greater than or equal to 15 x 10(3) cells/uL and an ESR greater than 30 were specific indicators of bacteria. Based on these data, identification of bacteremia in febrile infants may be possible with clinical assessment and screening laboratory tests. Because of the relatively small sampling size of this study, the authors feel that evaluation of a larger number of patients is warranted to evaluate these sensitivities in a more diffuse patient population.     

Immunological events in acute measles influencing outcome

77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.     

Heart rate characteristics and clinical signs in neonatal sepsis

To test the hypothesis that heart rate characteristic (HRC) monitoring adds information to clinical signs of illness in diagnosing neonatal sepsis, we prospectively recorded clinical data and the HRC index in 76 episodes of proven sepsis and 80 episodes of clinical sepsis in 337 infants in the University of Virginia NICU more than 7 d old. We devised an illness severity score based on clinical findings and tests relevant to sepsis. Point scores were derived from coefficients of multivariable regression models, and we internally validated a total score. We determined relationships of the HRC index with individual clinical signs, laboratory tests, and the total score. We found highly significant correlations of the clinical score and individual clinical signs with the HRC index. The clinical score and HRC index added independent information in predicting sepsis, and were similar in clinical and proven sepsis. The clinical score and the HRC index rose before sepsis, and the HRC index rose first. We conclude that clinical signs of illness and HRC monitoring add independent information to one another in the diagnosis of neonatal sepsis.     

Failure of the urinary group B streptococcal antigen test as a screen for neonatal sepsis.

The accuracy of the urinary group B streptococcal antigen latex agglutination (LA) test for screening infants at risk of group B streptococcal (GBS) sepsis in the first 24 hours of life was prospectively studied in 236 infants for six months. Infection with GBS was defined by a positive blood culture while colonisation was defined by GBS cultured from any other site. The combination of infection and colonisation was used as the gold standard for the LA test. Although the LA test had a sensitivity of 90%, the specificity was only 70%, the positive predictive value 12% and the false positive rate 30%. The overall accuracy was only 71%. The LA test was unable to predict GBS sepsis in infants at risk of the disease. The false positive rate was unacceptably high and could not be potentially accounted for in 11 infants. However, a negative test was useful in excluding GBS disease.     

Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis

This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram-stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars.     

Polymerase chain reaction in rapid diagnosis of neonatal sepsis

In a prospective study a total of hundred neonates who fulfilled the American College of Obstetrics and Gynecology's (ACOG) criteria for probable sepsis admitted to NICU of tertiary care armed forces hospital were investigated for evidence of sepsis. The investigation protocol included sepsis screen, blood culture and 1 mL of venous blood for molecular analysis by polymerase chain reaction (PCR) for bacterial DNA component encoding 16 s RNA in all cases. 100 newborns with probable sepsis were studied to evaluate the molecular diagnosis of sepsis using PCR amplification of 16 S RNA in newborns with risk factors for sepsis or those who have clinical evidence of sepsis. We compared the results of PCR with blood culture and other markers of sepsis screen (total leucocyte count (TLC), absolute neutrophil count (ANC), immature/total neutrophil count ratio (I/T ratio), peripheral blood smear, micro ESR and C reactive protein (CRP). Controls consisted of 30 normal healthy newborns with no overt evidence of sepsis. Sepsis screen was positive in 24 (24%) of cases in study group with sensitivity and specificity of 100% and 83.5% respectively. Blood culture was positive in 09(9%t) with sensitivity of 69.2% and specificity of 100%. PCR was positive in 13(13%) of cases (9% are both blood culture and sepsis screen positive and 4% are positive by sepsis screen); the sensitivity of PCR was 100% and specificity was 95.6%. Blood culture is the most reliable method for diagnosis of neonatal sepsis. Polymerase chain reaction is useful and superior to blood culture for early diagnosis of sepsis in neonates.     

儿童传染性单核细胞增多症B淋巴细胞及其活化状况的研究

目的　研究EB病毒 (EBV)感染儿童传染性单核细胞增多症 (IM)急性期B淋巴细胞及其活化状况 ,以及与临床的关系。方法　用流式细胞术测定 2 2例IM急性期、恢复期外周血单个核细胞膜CD19、CD2 3 /CD19 表达 ,配对比较并与 2 1例相同年龄健康儿童组成的对照组比较。同时记录患儿的发热时间。结果　 (1)IM急性期CD19[(5 6 3± 2 91) % ,(387± 178) /mm3 ]CD19 /CD2 3 [(2 4 5± 1 87) % ,(16 0± 99) /mm3 ]恢复期CD19[(12 4 9± 5 70 ) % ,(4 2 8± 15 6 ) /mm3 ]CD19 /CD2 3 [(5 0 5± 2 79) % ,(172± 78) /mm3 ],均较对照组CD19[(16 2 0± 2 80 ) % ,(5 4 5± 15 0 ) /mm3 ]CD19 /CD2 3 [(7 0 8± 2 78) % ,(2 4 9± 136 ) /mm3 ]低 (P <0 0 1或 0 0 5 )。病程越早 ,下降越明显。 (2 )IM急性期与恢复期的CD19、CD2 3 /CD19 表达均成正相关 (P <0 0 1) ;急性期和恢复期CD19与CD2 3 /CD19 表达均成正相关 (P <0 0 1)。 (3)发热时间与CD2 3、CD2 3 /CD19 表达成负相关 (P <0 0 1)。结论　 (1)在IM急性期 ,B淋巴细胞及其活化受到明显抑制 ,随着病情恢复而减轻 ;累及越显著、恢复越慢 ,同时症状越重。 (2 )CD19、CD2 3 /CD19 表达水平对于儿童IM的诊断及严重程度的预测有一定的     

Hemostasis in Glanzmann's thrombasthenia (GT): GT platelets interfere with the aggregation of normal platelets

The transfusion requirements for a 6-year-old Glanzmann's thrombasthenia (GT) patient undergoing tonsillectomy and adenoidectomy were studied. Transfusion of pheresed platelets from a single normal donor increased the platelet count by 63 x 10(9)/L but did not correct the bleeding time. Since the ratio of normal:GT platelets in vivo was approximately 1:5, it was possible that GT platelets interfered with the function of normal platelets. To test this hypothesis, mixtures of platelet-rich plasma (PRP) from a normal donor and the patient were studied to determine a ratio of normal:GT platelets that would yield acceptable in vitro aggregation. Normal:GT ratios of 1:4 and 3:2 resulted in 25% and 59% aggregation, respectively. Mixtures of normal and nonfunctional ethylene glycol tetra-acetic acid-treated platelets gave similar results. Aggregates from mixtures of normal and patient platelets were also examined morphologically by light microscopy and were proportional in size to the normal:GT platelet ratio. Transfusion of platelets from the pheresis of four donors increased the patient's platelet count by greater than 300 x 10(9)/L (normal:GT ratio 1:1), produced 53% aggregation, and resulted in satisfactory postoperative hemostasis. The platelet transfusion requirement for this GT patient was much greater than would have been expected in the absence of aggregation-defective platelets.     

Pet sensitivities in asthmatic children

A history of pet contact and/or apparent clinical sensitivity was obtained in 65 (55%) of 118 unselected asthmatic children. These 65 children were skin tested and their sera examined for specific IgE using the radioallergosorbent test. Those children who had apparent clinical sensitivities had larger skin test reactions and were more likely to have positive specific IgE results than those without apparent sensitivities. Positive skin tests were very common (80%), but the larger the skin test reaction (weal diameter greater than 4 mm diameter) the more likely was there to be a positive history or a positive specific IgE result. Hence a large skin test reaction can provide a helpful pointer to animal allergy of clinical importance. Commercially available animal extracts have limitations for diagnostic tests. A questionnaire survey of 150 day schools emphasized the potential opportunities for contact with animal allergens at school.     

Is urine interleukin-8 level a reliable laboratory test for diagnosing late onset sepsis in premature infants?

The present study is aimed to determine serum and urine interleukin-8 (IL-8) levels in premature infants with late onset sepsis (LOS) and to evaluate if urine IL-8 is a useful test for LOS diagnosis. Fifty-six premature infants admitted to the NICU over 1 year had serum and urine IL-8 determined by ELISA. They were divided into three groups: I definite sepsis, II probable sepsis and III non-infected. Results were expressed as mean or median. Differences between groups were assessed by ANOVA, Kruskal-Wallis ANOVA and Dunn's Method. Sensitivity, specificity and positive and negative predictive values were calculated and a receiver operator characteristic curve was constructed to determine serum and urine IL-8 accuracy. There were no differences between groups for birth weight, and gestational and post-natal age. Median serum and urine IL-8 levels were significantly higher in GI and GII: 929 x 906 x 625 pg/ml; P = 0.024, and 249 x 189 x 42 pg/mgCr; P < 0.001. Optimal cut-off point was 625 pg/ml for serum IL-8 with 69% sensitivity and 75 pg/mgCr for urine IL-8 with 92% sensitivity. IL-8 can be determined in urine from premature infants with LOS and is an accurate and feasible diagnosis method.     

Pet sensitivities in asthmatic children.

A history of pet contact and/or apparent clinical sensitivity was obtained in 65 (55%) of 118 unselected asthmatic children. These 65 children were skin tested and their sera examined for specific IgE using the radioallergosorbent test. Those children who had apparent clinical sensitivities had larger skin test reactions and were more likely to have positive specific IgE results than those without apparent sensitivities. Positive skin tests were very common (80%), but the larger the skin test reaction (weal diameter greater than 4 mm diameter) the more likely was there to be a positive history or a positive specific IgE result. Hence a large skin test reaction can provide a helpful pointer to animal allergy of clinical importance. Commercially available animal extracts have limitations for diagnostic tests. A questionnaire survey of 150 day schools emphasized the potential opportunities for contact with animal allergens at school.