Persistence of Plasmodium falciparum in the placenta after apparently effective quinidine/clindamycin therapy.

The persistence of Plasmodium falciparum in the placenta after apparently adequate therapy with quinine has been described. We describe this phenomenon in the placenta of a 19-year-old woman with falciparum malaria, who was treated with a combination of quinidine and clindamycin. Although this therapy was effective and diminished her peripheral blood parasitemia from 3% at presentation to almost undetectable at the time of delivery, vast numbers of P. falciparum-infected erythrocytes were present in the maternal sinusoids of the placenta. This sequestration of infected erythrocytes produced a local parasitemia in the placenta of 70% to 80%. Additionally, rare Plasmodium-infected erythrocytes were also seen in the fetal blood of the placenta. We review malaria in pregnancy, parasitic involvement of the placenta and emphasize that Plasmodium-infected erythrocytes may persist in the placenta even after clearance of parasites from the peripheral blood.

Methods to improve the reliability of histopathological diagnoses in the placenta.

The interobserver reliability of histopathological features in the placenta was examined. Two pathologists independently reviewed slides from 250 placentas. The pathologists were given a morphological description of the placenta, but were blinded to clinical status, gestational age and original diagnoses. A protocol for diagnosis and grading of features was first developed and pilot-tested. Definitions and criteria were refined and elaborated. A range of features was examined including inflammatory lesions, features indicative of reduced uterine blood flow and other miscellaneous histopathological changes. Weighted kappa coefficients were calculated. The effect of multiple features on reliability was examined by stratifying on the presence of a second feature and calculating stratum-specific kappa coefficients. Results indicated good to excellent agreement for diagnoses of chorioamnionitis, cord vasculitis, funisitis and villitis (kappa(w) range 0.70-0.83). Agreement between observers was more variable for the diagnosis of reduced uterine blood flow states. Excellent agreement was observed for the diagnosis of meconium staining of the placenta (kappaw = 0.79). In general, lower levels of agreement were observed for features in the presence of a second feature. Reproducible measures are a prerequisite to using placental histopathology for diagnostic and prognostic information. This study demonstrated reliable placental diagnoses can be achieved through a standardised protocol.

Gestational psittacosis: case report and literature review.

In Europe, Chlamydia psittaci is a relatively common cause of abortion in sheep and other mammals. Psittacosis in humans is typically described as a mild-to-moderate flu-like illness. If psittacosis is acquired during pregnancy, it can present as a severe, progressive, febrile illness, with headache, disseminated intravascular coagulation, abnormal liver enzyme studies, and impaired renal function. Only cases with significant fetomaternal morbidity and mortality have been reported. Recovery from this disease follows termination of pregnancy and appropriate antibiotic therapy. Direct exposure of gravid humans to infected products of conception is the most commonly reported mode of transmission. Diagnosis is suggested by the placental histopathologic findings, which consist of an intense, acute intervillositis, perivillous fibrin deposition with villous necrosis, and large irregular basophilic intracytoplasmic inclusions within the syncytiotrophoblast. Commercially available genus-specific monoclonal antichlamydial antibody is available for the rapid confirmation of the diagnosis. In the United States, only two cases of gestational psittacosis have been previously reported. In contrast to the experience in Europe, both cases were associated with psittacine birds. This is the first reported instance of ovine-related gestational psittacosis documented in the United States. Gravid patients should be warned to avoid contact with sheep and their products, particularly during the spring lambing period.

Congenital herpes infection: placental and umbilical cord findings.

BACKGROUND: Herpes simplex virus (HSV) fetal infections are rare, and the routes through which the virus reaches the fetus are insufficiently documented. CASE: We describe a case of congenital HSV ascending infection in an infant whose membranes were intact until cesarean delivery. The pathologic findings were remarkable for a mild lymphoplasmocytic funisitis and the presence of positive viral staining of cells in the subamniotic connective tissue, amniotic epithelium, and umbilical cord. Antigen-positive cells within the extraplacental membranes were mostly located in an area presumably adjacent to the cervix before birth. In the umbilical cord, positive viral staining was confined to cells in the subamniotic mesenchyma away from the perivascular mesenchyma of the central portion of the cord. CONCLUSION: Immunohistochemistry using herpes-specific antibodies, coupled with routine histologic examination, allows early diagnosis of congenital HSV infection and documentation of the ascending route of infection when the membranes are intact.

Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice.

Previous work in our laboratory demonstrated increased sensitivity of senescent (24-month-old) mice to cecal ligation and puncture (CLP) sepsis compared with that of mature (12-month-old) mice. In this study the median lethal dose of the strain of Escherichia coli most frequently isolated during CLP sepsis was determined. No significant age-associated difference in the mean lethal dose or the mean survival time was noted; however, sham surgery before injection of E. coli decreased the mean lethal dose by at least 100-fold. With surgical manipulation, the average time to death after bacterial injection simulated more closely that observed after CLP surgery. Host responses to CLP sepsis were investigated by measuring the levels of corticosterone, glucose, and tumor necrosis factor (TNF) in the sera of mature and senescent mice at 2-h intervals after surgery. Corticosterone levels increased gradually during the course of sepsis in mature mice; however, senescent mice demonstrated a pronounced elevation in hormone levels at 2 and 4 h after surgery. At subsequent sampling intervals the corticosterone levels remained elevated, although they were similar for both ages. At all sampling intervals, the glucose levels in serum were lower in senescent mice than in mature mice. Pronounced hypoglycemia (less than 80 mg/dl) was observed in senescent mice at 8 h postsurgery. TNF was detected in serum within a narrow time frame in both age groups at 6, 8, and 10 h postsurgery. Although elevated TNF levels in serum were not seen in every mouse in each group (approximately 50%), the data hinted that senescent animals produced larger quantities of TNF during CLP sepsis than did mature animals. E. coli lipopolysaccharide (1 mg/kg) was injected intraperitoneally, and the TNF levels in serum and peritoneal lavage fluid were measured at 30, 60, and 90 min. Senescent mice demonstrated a level of TNF in serum at 90 min after lipopolysaccharide treatment that was 20-fold higher than that of mature mice (299,877 pg/ml versus 15,594 pg/ml). The amount of TNF produced locally in the peritoneum was also substantially higher in senescent mice than in mature animals (1,716 pg/ml versus 776 pg/ml). The increased production of TNF in senescent animals, despite elevated circulating corticosterone levels, suggested an age-related defect in glucocorticoid-directed downregulation of TNF production. This was confirmed in lipopolysaccharide-treated animals given exogenous dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)

Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice.

Epidemiologic data suggest that elderly adults are more susceptible to invasive bacterial infection by indigenous gut flora than are younger adults. The purpose of this investigation was to characterize a murine model of clinically encountered peritonitis in the aged. We subjected three different age groups (young, 16 weeks; mature, 12 months; senescent, 24 months) of C57BL/6NNia mice to surgically induced peritonitis by the cecal ligation and puncture procedure. Senescent mice died in a significantly shorter time following surgery than mature mice (median time to death, 24.4 versus 38.5 h, respectively; P less than or equal to 0.001). Blood, liver, spleen and occasionally, ceca were obtained at 2 and 12 h after the cecal ligation and puncture procedure and immediately following death, to characterize the bacterial kinetics of the model. Qualitative and quantitative aerobic, anaerobic, and coliform cultures were performed. No age-related differences were found in the types of bacteria isolated throughout the time course of progressive sepsis. In mice in the mature and senescent age groups, at 2 and 12 h postsurgery, gram-negative anaerobes and gram-positive aerobes predominated in all tissues that were cultured. At the time of death, however, blood and tissue isolates consisted predominantly of coliform bacteria. The shift from mixed infection during sepsis to predominantly gram-negative bacterial infection reflected a similar progressive shift in bacterial types found in the cecum. At death, senescent mice had 100-fold fewer coliform bacteria in the bloodstream than those found in mature mice (2.5 x 10(9) versus 4.6 x 10(11), respectively). The increased sensitivity of aged mice to invasive bacterial infection documented in this series of experiments accords well with human epidemiologic experience and demonstrates the appropriateness of the model for continued investigations of sepsis in the aged.