Dan Danielsson

Decreasing incidences of gonorrhea- and chlamydia-associated acute pelvic inflammatory disease. A 25-year study from an urban area of central Sweden.

Background and Objectives: Acute pelvic inflammatory disease (PID) affects women in their reproductive years and is often a complication of a sexually transmitted disease (STD), particularly Neisseria gonorrhoeae and Chlamydia trachomatis. Infertility, ectopic pregnancy, and chronic lower abdominal pain are common long‐term sequelae to acute PID. Through different preventive measures, endemic N. gonorrhoeae is almost eliminated, and C. trachomatis has been reduced almost fourfold in Sweden. Goals: To investigate variations in STD‐associated acute PID and the extent to which this influenced the yearly incidences of patients hospitalized for this complication during a 25‐year‐period. Study Design: Hospital records of 2499 patients admitted and treated for acute PID from January 1, 1970 to December 31, 1994 were analyzed for infection with N. gonorrhoeae. Routine laboratory diagnosis for C. trachomatis infection started June 1, 1980. Detailed statistical analysis for chlamydial‐associated PID in this study, therefore, covers the period January 1, 1981 to December 31, 1994 and includes 1030 patients. Results: Gonorrhea occurred in 42% of patients with acute PID in 1970 and decreased continuously to zero in 1988 and beyond. Concomitant urogenital chlamydial infection reduced almost fourfold from 28.4% in 1985 to 7.7% in 1994. Yearly admissions for acute PID fluctuated slightly (≤16%) in the early 1970s and early 1980s but increased greatly (>60%) in the middle and late 1970s; the highest was 180 per year in 1976. This coincided with high incidence rates of gonorrhea in the general population, and probably of genital C. trachomatis infection as well, coupled with an increased use of intrauterine contraceptive device in nulliparous women. The largest increase in admissions for acute PID was in the 15‐ to 29‐year‐old group. A steady decrease started in 1987 and reached the low figure of 26 admissions in 1994. The greatest decrease occurred in the 15‐ to 19‐year‐old group, from the relative age distribution of 28.9% in the period 1970 to 1974 to 12.9% in 1990 to 1994. Yearly admissions for the ≥35‐year‐old group remained almost constant during the study period, but the relative age distribution shifted from second lowest (excluding those 14 years or younger, totaling 15 admissions for the entire study period), 9.1% at the beginning of the study period, to the second largest, 24.9% at the end of it. The study also showed that the total and relative rates of recurrence decreased. Conclusions: Measures aimed at reducing incidences of gonorrhea and genital chlamydial infection will reduce the incidences of one of the most serious complications of these STDs, acute PID, and, in turn, its long‐term sequelae.

Programmes to reduce pelvic inflammatory disease—the Swedish experience

Pelvic inflammatory disease (I’ID) is the acute clinical manifestation of ascending genital-tract infection involving the endometrium, fallopian tubes, and/or adjacent pelvic structures.’ I’ID is a serious condition that almost exclusively affects sexually active women in their fertile years. Several million women worldwide have symptomatic PID each year, and a similar number probably have symptomless PID,’ and thus face an increased risk of infertility, ectopic pregnancy, and chronic pelvic pain.‘Ja” The Swedish experience

The sialic acid binding SabA adhesin of Helicobacter pylori is essential for nonopsonic activation of human neutrophils.

Infiltration of neutrophils and monocytes into the gastric mucosa is a hallmark of chronic gastritis caused by Helicobacter pylori. Certain H. pylori strains nonopsonized stimulate neutrophils to production of reactive oxygen species causing oxidative damage of the gastric epithelium. Here, the contribution of some H. pylori virulence factors, the blood group antigen-binding adhesin BabA, the sialic acid-binding adhesin SabA, the neutrophil-activating protein HP-NAP, and the vacuolating cytotoxin VacA, to the activation of human neutrophils in terms of adherence, phagocytosis, and oxidative burst was investigated. Neutrophils were challenged with wild type bacteria and isogenic mutants lacking BabA, SabA, HP-NAP, or VacA. Mutant and wild type strains lacking SabA had no neutrophil-activating capacity, demonstrating that binding of H. pylori to sialylated neutrophil receptors plays a pivotal initial role in the adherence and phagocytosis of the bacteria and the induction of the oxidative burst. The link between receptor binding and oxidative burst involves a G-protein-linked signaling pathway and downstream activation of phosphatidylinositol 3-kinase as shown by experiments using signal transduction inhibitors. Collectively our data suggest that the sialic acid-binding SabA adhesin is a prerequisite for the nonopsonic activation of human neutrophils and, thus, is a virulence factor important for the pathogenesis of H. pylori infection.

The genital econiche: focus on microbiota and bacterial vaginosis

Ecological and evolutionary forces shaping the normal and abnormal microflora of the genital econiche are discussed, in particular those related to bacterial vaginosis, which worldwide is the most common vaginal infection, with numerous obstetrical and gynecological complications, including acquisition and transmission of HIV and other sexually transmitted infections (STIs). Characterized by a heavy overgrowth of Gram‐negative and Gram‐positive anaerobes with no signs of inflammation, bacterial vaginosis has been regarded a microbiological and immunological enigma. Immune tolerance to both normal and abnormal vaginal microbiota, mainly derived from gut microflora, as a result of coevolution with humans might explain the absence of inflammation, supported by short‐chain fatty acids, known to modulate immune responses, that are produced in large quantities by anaerobes. Recent studies have implicated the development of a vaginal biofilm with Gardnerella vaginalis and Atopobium vaginae as main players in the pathogenesis of bacterial vaginosis. Supporting this conclusion are data such as those demonstrating heavy growth of G. vaginalis and diversified anaerobes with numerous “clue cells” that are sloughing off from the biofilm. Gardnerella and Atopobium organisms attached to these clue cells can be demonstrated in the male genital econiche, likely reflecting a heterosexual transmission of the disorder.

Helicobacter pylori adhesion to carbohydrates.

Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori.

The Possible Role of Transplacentally-Acquired Antibodies to Infectious Agents, With Molecular Mimicry to Nervous System Sialic Acid Epitopes, as Causes of Neuromental Disorders: Prevention and Vaccine Implications

Proof of causality of most neuromental disorders (NMDs) is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infants blood–nervous system barriers to cause NMDs, clinically manifest years later. Further rationale is provided by relevant evolutionary/developmental (EVO–DEVO) considerations—applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow-up of the progeny for NMDs; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high-tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus). A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.

Helicobacter pylori Prevalence among Indigenous Peoples of South America

The seroprevalence of Helicobacter pylori among secluded Indian populations of South America was determined to gain insight into the evolutionary history and possible transmission patterns of the organism. Serum samples obtained from 1024 donors in 22 different villages were tested by enzyme-linked immunosorbent assay for immunoglobulin G antibodies, and the results were confirmed by Western blot. The overall seroprevalence was 92%: >80% of children tested positive by 3 years of age, the highest prevalence in populations studied to date. Comparison of H. pylori prevalence with that of herpes simplex virus type 1, which is known to be transmitted orally, demonstrated a linear correlation in their prevalence rates, suggesting that these pathogens share risk factors. However, H. pylori seroprevalence was consistently higher, indicating that additional routes of transmission exist and/or that the organism is more transmissible. Seroprevalence did not correlate with the length of contact with the outside world. These results suggest that H. pylori was indigenous to the South American Indians and was not introduced by contact with outsiders.

Gonorrhea, genital Chlamydial infection, and nonspecific urethritis in male partners of women hospitalized and treated for acute pelvic inflammatory disease

BACKGROUND AND OBJECTIVES Acute pelvic inflammatory disease (PID) is often a complication to a sexually transmitted disease (STD), the most important agents being Neisseria gonorrhoeae and Chlamydia trachomatis. However, very little is known of the genitourinary status of the male partners of women with acute pelvic inflammatory disease (PID). GOAL OF THIS STUDY To determine the presence of N. gonorrhoeae and/or C. trachomatis infection or nonspecific urethritis (NSU) in regular sexual male partners of women with acute PID. STUDY DESIGN Two hundred regular sexual male partners to 196 women admitted to a hospital for treatment of acute PID were referred by contact tracing to the sexually transmitted disease outpatient clinic for clinical and laboratory examination regarding N. gonorrhoeae and/or C. trachomatis infection, or NSU defined as the presence of > 5 polymorphonuclear leukocytes per high-power field (x1,000) in > 4 fields and with negative laboratory tests for N. gonorrhoeae and C. trachomatis. RESULTS The majority of the males was in the age group 20 to 29 years of age, female sexual partners in 15 to 24 years years of age. N. gonorrhoeae was demonstrated in 42.9% of the male partners to women with acute PID and concomitant gonorrhea. The corresponding figure for C. trachomatis was 43.7%. Nonspecific urethritis was diagnosed in 26 (33.8%) of the male partners to 77 women were diagnosed with N. gonorrhoeae and/or C. trachomatis infection, and in 45 (37.8%) partners of 119 women without such an infection. In all, N. gonorrhoeae, C. trachomatis or NSU were demonstrated in 117 (59.7%) of the 196 male partners, but only 32% of the males with N. gonorrhoeae or C. trachomatis and 8.5% of those with NSU presented subjective symptoms of urethritis. CONCLUSION The findings of the study stress the need for routine clinical and laboratory examination and treatment of sexual male partners to women with acute PID.

Serum Bactericidal Activity and Induction of Chemiluminescence of Polymorphonuclear Leukocytes: Complement Activation Pathway Requirements in Defense against Neisseria meningitidis

Serum bactericidal activity and chemiluminescence (CL) responses of polymorphonuclear leukocytes (PMNL) to pathogenic Neisseria meningitidis serogroups B and W-135 and to nonpathogenic serogroup 29E were examined with pooled normal human serum depleted of the complement proteins C1q, factor D, properdin and C5. Purified C1q, factor D, properdin and C5 were added alone or in combination. For investigation of serogroup W-135 meningococci, a C1q, factor D and properdin-depleted postvaccination serum with high concentrations of anticapsular antibodies was also used. Serogroup B and W-135 cultured to log phase were resistant to the bactericidal activity of pooled normal human serum but were efficiently killed through the classical pathway alone when the bacteria were cultured to stationary phase. Nonpathogenic serogroup 29E meningococci in log or stationary growth phases were efficiently killed in serum, predominantly through the classical pathway. Serogroup W-135 meningococci grown to log phase were resistant to classical pathway-mediated bactericidal activity in postvaccination serum but were killed on addition of alternative pathway proteins. Stationary phase serogroup W-135 meningococci were killed through both pathways in the postvaccination serum. In the pooled normal human serum CL responses of PMNL were consistently more pronounced with fully reconstituted C1q, factor D, properdin, C5-depleted serum than with serum reconstituted with C1q, factor D and properdin suggesting contribution of actions related to terminal components. In the absence of C1q, serogroup W-135 meningococci in postvaccination serum induced a significant but delayed alternative pathway-mediated CL response. CL responses induced by serum-opsonized meningococci, in contrast to serum bactericidal activity, were not influenced by culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Genotypic and Phenotypic Stability of Helicobacter pylori Markers in a Nine-Year Follow-up Study of Patients with Noneradicated Infection

The cagA gene, alleles of the vacA gene, random amplified polymorphic DNA (RAPD), and neutrophil activating capacity (HpNAC) were used to examine paired H. pylori isolates from 10 noneradicated individuals 9 years apart. Paired isolates from each patient were indistinguishable with regard to vacA alleles, RAPD, and HpNAC. Isolates from nine patients showed concordance for the cagA gene, which was not detected in the recent isolate of the tenth patient. Antibodies to CagA were, however, demonstrated in the serum specimens 9 years apart and were also present in two other patients whose paired isolates were cagA-, indicating the existence of both cagA+ and cagA− organisms, with the latter predominating in some patients. The present study suggests a greater stability of phenotypic and genotypic markers of H. pylori than previously regarded. This might be true for a community with low infection and transmission rates. Complementary techniques like microarrays might, however, disclose evolutionary changes not identified here.