Direct Killing of Patients in Humanitarian Situations and Armed Conflicts: The Profession of Medicine Is Losing Its Meaning

Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment.     

Azithromycin vs. benzathine penicillin G for early syphilis: a meta-analysis of randomized clinical trials

The World Health Organization estimates that at least 12 million people are infected with syphilis in the world. Southeast Asia accounts for 5.8 million; Africa accounts for 3.5 million. There has been controversy in using the two kinds of antibiotics for early syphilis. A systematic review comparing these antibiotics could affect treatment guidelines. The aim of this study was to evaluate the efficacy and safety of azithromycin vs. penicillin G benzathine for early syphilis and a meta-analysis to compare these two kinds of antibiotics for early syphilis. Four randomized controlled trials met the inclusion criteria; 476 patients were evaluated for their cure rate. Cure rates were 95.0% (227/239) for azithromycin and 84.0% (199/237) for penicillin G benzathine. After pooling the data, the difference in efficacy was computed. Cure rate (OR=1.37), 95% CI (1.05, 1.77) and the risk difference for cure rate between the two drugs were statistically significant. Although the gastrointestinal adverse effect of azithromycin is five times more than the adverse effect of penicillin G benzathine, the differences are not significant. Azithromycin achieved a higher cure rate than penicillin G benzathine in a long follow-up.     

Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment

STUDY OBJECTIVES: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.     

新生儿先天性梅毒30例临床分析

目的：探讨新生儿先天性梅毒的早期诊治与预后的关系。方法对该院2005～2012年收治的30例新生儿先天性梅毒的临床资料进行回顾性分析。结果新生儿梅毒的临床表现以皮疹、黄疸为主。梅毒血清学检查快速血浆反应素环状卡片试验和梅毒螺旋体血球凝集试验均阳性。选用青霉素静滴2～3周治疗,全部治愈。结论新生儿先天性梅毒早期使用青霉素静滴,疗效满意。常规开展孕期梅毒检测,早发现、早治疗,可明显降低先天性梅毒的发病率和病死率。     

梅毒螺旋体阿奇霉素耐药的分子生物学检测方法的建立

目的建立梅毒螺旋体阿奇霉素耐药的分子生物学检测方法。方法为了提高检测的敏感性和特异性,应用套式聚合酶链反应（Nested-PCR）扩增样本DNA;限制性酶切反应检测阿奇霉素耐药突变;并对PCR产物和酶切产物进行测序以验证实验结果。结果套式PCR能很好地扩增样本DNA,耐阿奇霉素的菌株经酶切后形成188bp和440bp两个片段,而不耐药者不发生酶切反应。测序结果显示,耐药者的2058位DNA从A突变为G,而野生型者无此突变。结论利用套式PCR和限制性酶切分析法,成功建立了梅毒螺旋体阿奇霉素耐药的分子生物学检测方法 ,为梅毒螺旋体的耐药监测以及进一步的分子流行病学研究,提供了实验室基础。     

Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis.

BACKGROUND: Preventive therapy is an important element of syphilis control efforts. No currently recommended, single-dose alternatives to penicillin G benzathine are available for treatment of incubating syphilis. OBJECTIVE: To evaluate the use of a single 1.0-g dose of azithromycin for treatment of persons recently exposed to sexual partners with infectious syphilis. DESIGN: Single-center, open-label, randomized pilot study to compare azithromycin with penicillin G benzathine therapy. Participants were evaluated serologically for 3 months. SETTING: Sexually transmitted disease clinic in Birmingham, Alabama. PARTICIPANTS: 96 participants who in the preceding 30 days had been exposed to partners with infectious syphilis through sexual intercourse. MEASUREMENTS: Syphilis prevention, as indicated by nonreactive serologic tests (rapid plasma reagin and fluorescent treponemal antibody-absorbed), throughout the 3-month follow-up. RESULTS: Among 96 participants enrolled, none of 40 evaluable persons in the azithromycin group and none of 23 evaluable persons in the penicillin group developed evidence of syphilis. Significantly more penicillin-treated participants (21 of 44 [48%]) than azithromycin-treated participants (12 of 52 [23%]) became nonevaluable during follow-up (P = 0.01). CONCLUSION: A single 1.0-g dose of azithromycin seems to be efficacious for prevention of syphilis in persons exposed to infected sexual partners.     

Antimicrobial resistance in Streptococcus pneumoniae: an overview.

Clinical resistance to penicillin in Streptococcus pneumoniae was first reported by researchers in Boston in 1965; subsequently, this phenomenon was reported from Australia (1967) and South Africa (1977). Since these early reports, penicillin resistance has been encountered with increasing frequency in strains of S. pneumoniae from around the world. In South Africa strains resistant to penicillin and chloramphenicol as well as multiresistant strains have been isolated. Similar patterns of resistance have been reported from Spain. Preliminary evidence points to a high prevalence of resistant pneumococci in Hungary, other countries of Eastern Europe, and some countries in other areas of Europe, notably France. In the United States most reports of resistant pneumococci come from Alaska and the South, but resistance is increasing in other states and in Canada. Pneumococcal resistance has also been described in Zambia, Japan, Malaysia, Pakistan, Bangladesh, Chile, and Brazil; information from other African, Asian, and South American countries is not available. The rising prevalence of penicillin-resistant pneumococci worldwide mandates selective susceptibility testing and epidemiological investigations during outbreaks.     

Destructive osteomyelitis associated with early secondary syphilis in an HIV-positive patient diagnosed by Treponema pallidum DNA polymerase chain reaction

A 20-year old man who had sex with men (MSM) presented with destructive osteomyelitis of the sternal bone and diffuse maculopapular rash. During laboratory evaluation he was found to have secondary syphilis and HIV with viral load of 28,000 copies per milliliter and CD4 count of 251 cells per microliter. Surgical debridement and biopsy of the sternal bone was performed. The biopsy examination demonstrated bone necrosis with perivascular infiltration of plasma cells and lymphocytes and rare hystiocytes. No granulomatous lesions were identified and acid-fast, fungal, silver, and Gram's stains did not show any organism. All cultures were negative. Real-time polymerase chain reaction (PCR) using probes targeting a pathogen-specific and highly conserved TpN47 gene of Treponema pallidum was performed on the DNA, extracted from the biopsy specimen and T. pallidum amplicons were detected. Patient was initially treated empirically with vancomycin, piperacillin/tazobactam and intravenous aqueous penicillin G. After confirming the diagnosis he completed 2 weeks of intravenous aqueous penicillin G treatment with resolution of osteomyelitis confirmed at follow-up visit after 6 weeks. Osteomyelitis is a rarely described manifestation of secondary syphilis. To the best of our knowledge, this is the first case of using T. pallidum DNA PCR to confirm the diagnosis of syphilitic osteitis. We suggest that osteomyelitis may be an underrecognized problem in patients with secondary syphilis, especially in HIV-coinfected individuals and PCR seems to be a valuable method in confirming the diagnosis.     

Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States

We report on the first Neisseria gonorrhoeae isolate in the United States identified with high-level resistance to azithromycin. This report discusses the epidemiologic case investigation, the molecular studies of resistance-associated mutations and N. gonorrhoeae multiantigen sequence typing, and challenges posed by emerging gonococcal antimicrobial resistance.     

Drug-resistant <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> in community-acquired pneumonia

The emergence of Streptococcus pneumoniae isolates resistant to not only penicillin, but to other antipneumococcal agents as well, has major public health implications. Drug-resistant S. pneumoniae are distributed worldwide, and resistance has become increasingly prevalent in the United States within the past decade. The relevance of resistance, particularly to the β-lactams, to treatment outcome has been subject to debate. Pneumonia due to intermediate-level-resistant penicillinresistant isolates of S. pneumoniae appears to be adequately treated by β-lactam agents. Interpretation of resistance reports, which may be based on achievable cerebrospinal fluid levels of drug, may depend on the clinical setting, and efforts are underway to adjust breakpoints so that reports are more easily applicable to clinical practice. Infectious Diseases Society of America and American Thoracic Society guidelines, as well as others, for community-acquired pneumonia have addressed the impact of drug-resistant S. pneumoniae on antimicrobial selection.     

Azithromycin versus penicillin V for the treatment of early lyme borreliosis

Summary In a randomized multicenter therapeutic trial, 32 patients with erythema migrans received oral azithromycin 500 mg once daily and 33 patients received phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days. Follow-up was for a median of 17 (range 3–32) months. Four weeks after initiation of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given penicillin V were completely free of all signs and symptoms and did not develop new ones subsequently (no significant difference). Three months after initiation of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%) penicillin V recipients (no significant difference). There were only minor sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia. Azithromycin led to a significantly faster resolution of the erythema migrans than penicillin V (p<0.001). Significantly more patients with more severe compared with mild initial disease had an elevated IgM antibody titer prior to therapy (p<0.001). Usually mild to moderate side effects occurred in 12 patients given azithromycin and five patients given penicillin V (p<0.05). Azithromycin appears to be as effective as penicillin V for the treatment of early Lyme borreliosis and it seems to clear the erythema migrans more promptly.

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Azithromycin im Vergleich zu Penicillin V in der Therapie der frühen Lyme-Borreliose

Zusammenfassung Bei einer randomisierten Multicenter-Therapiestudie erhielten 32 Patienten mit Erythema migrans (EM) 10 Tage lang täglich 500 mg Azithromycin und 33 Patienten 3x täglich 1 Mill. IE Penicillin V. Die Nachbeobachtungszeit betrug 17 (3–32) Monate. Die klinischen Erscheinungen heilten bei 20 (62%) der mit Azithromycin und 17 (51%) der mit Penicillin V behandelten Patienten innerhalb von vier Wochen und bei 25 (78%) der mit Azithromycin beziehungsweise 28 (85%) der mit Penicillin V behandelten Patienten innerhalb von drei Monaten nach Therapiebeginn vollständig ab, ohne erneut zu einem späteren Zeitpunkt aufzutreten (kein signifikanter Unterschied). Die klinischen Folgeerscheinungen waren nur leichter Art. Es handelte sich z. B. um Arthralgien, Kopfschmerzen, Abgeschlagenheit, Nackensteife und Paraesthesien. Durch Azithromycin kam es zu einer signifikant schnelleren Abheilung des EM als durch Penicillin V (p<0.001). Signifikant mehr Patienten mit ausgeprägteren als mit milden Initialerscheinungen hatten einen erhöhten IgM-Antikörper-Titer vor Therapiebeginn (p<0.001). Meistens gering- bis mäßiggradige Nebenwirkungen fanden sich bei 12 mit Azithromycin und fünf mit Penicillin V behandelten Patienten (p<0.05). Azithromycin ist offensichtlich ähnlich wirksam wie Penicillin V bei der Behandlung der frühen Lyme-Borreliose, aber Azithromycin scheint das EM schneller abzuheilen.

     

Sífilis

Syphilis is an infectious disease caused by the spirochaete Treponema pallidum subsp. pallidum which is transmitted by sexual contact or vertical transmission during pregnancy. The incidence of syphilis has increased in the last years, mainly among men who have sex with men. Without treatment, the disease develops into different clinical stages, being able to present cardiovascular or irreversible neurological complications after a number of years. The disease is classified as early syphilis - primary, secondary and early latent syphilis (less than 12 months) - which is contagious, and as late syphilis - late latent and tertiary syphilis- which is rarely contagious. Diagnosis and management are often a challenge because of its diversity of manifestations and the difficulty of interpretation of serological tests. The treatment of syphilis is based on penicillin or doxycycline in allergic patients. Treatment failure because of resistance has been described with azithromycin. The follow up with a serological test is recommended in all patients with syphilis in order to ascertain cure after the treatment and to diagnose possible reinfections.     

梅毒流行病学和诊疗现状分析

梅毒是由梅毒螺旋体感染引起的一种慢性传染病,主要传播方式为性接触、血液传播和垂直传播,危害性极大。近年来,梅毒疫情呈上升趋势,已成为我国发病率最高的性传播疾病。梅毒的发病率存在地区差异性,发病人群有从高危人群向普通人群扩大的趋势,尤其是农民工、老年患者发病率较高。目前,梅毒的实验室诊断主要有病原学诊断、血清学诊断、组织病理诊断、基因诊断和脑脊液检查。血清学检查因其简便、可靠,目前临床上应用最为广泛。梅毒的治疗应遵循早期、规范、足量的原则。青霉素是治疗梅毒的首选药。     

The scope and impact of treatment of latent tuberculosis infection in the United States and Canada

RATIONALE: The scope of treatment of latent tuberculosis infection (LTBI) in the United States and Canada is unknown. Identifying the types of clinics that administer such treatment and patients who receive it could guide resource utilization and improve treatment initiation and completion. OBJECTIVES: Estimate the number of persons started on LTBI treatment; describe the types of clinics that treat LTBI. METHODS: The Tuberculosis Epidemiologic Studies Consortium, consisting of 19 United States and 2 Canadian sites, conducted a survey among clinics that initiated LTBI treatment for>or=10 patients in 2002. RESULTS: Study catchment areas from the 19 United States sites represented 8.6% of the United States population and 12.7% of all tuberculosis cases in 2000. An estimated 37,857 patients started LTBI treatment during 2002 at 244 clinics surveyed. Of these treatment starts, 29,970 (79%) occurred at general public health clinics; immigrant/refugee clinics (2,409; 6.4%) and correctional/detention facilities (2,325; 6.1%) were the next most common sites. Based on these data, United States tuberculosis case rates, and United States population data, the estimated total number of LTBI treatment starts in the United States was 291,000-433,000. When the 37,145 persons who initiated LTBI treatment in the United States were extrapolated to the entire United States population, with a 5% lifetime risk of tuberculosis without treatment, and 20-60% treatment effectiveness, approximately 4,000-11,000 tuberculosis cases were prevented in the United States. CONCLUSIONS: LTBI treatment is initiated among a substantial number of persons in the United States and Canada, primarily in the public sector. Treatment of LTBI can significantly decrease the tuberculosis burden.     

Managing syphilis in the HIV-infected patient

Syphilis has re-emerged in the United States and elsewhere, and clinicians caring for HIV-infected patients are challenged with syphilis diagnosis and management decisions. HIV alters the natural history of syphilis to an extent that is poorly understood, and initial presentation may be more varied in coinfected patients. Although commonly available diagnostic assays for syphilis should be interpreted as usual, such tests rely on antibody measurement and may be an imperfect indicator of active infection. Assessment of all available clinical and risk behavior data remains critically important in the diagnosis of syphilis in coinfected patients. Treatment of syphilis in such patients requires stage-appropriate therapy, with careful serologic monitoring to assess response. Clinicians must have heightened appreciation of the role of frequent risk assessment, serologic screening, symptom recognition, and follow-up of treated patients, as well as an understanding of public health functions such as sex partner treatment and communicable disease reporting.     

解脲脲原体对大环内酯类抗生素耐药机制的研究

目的探索解脲脲原体对大环内酯类抗生素的耐药机制。方法自行设计引物,对已知药敏结果的解脲脲原体进行编码核糖体蛋白L4/L22的基因以及23S rRNA的II区和V区的扩增并测序,比对分析其碱基和氨基酸的改变。结果在耐药株X01核糖体蛋白L4上,出现第67位谷氨酰胺→赖氨酸和71位甘氨酸→丝氨酸的改变;敏感株Y292经阿奇霉素诱导耐药后,L22核糖体蛋白上出现9个氨基酸的改变;耐药株Y187 23S rRNAV区出现第2566位碱基T→C、第2569位缺失碱基G和第2621位碱基A→T的变化。结论核糖体蛋白L4、L22以及23S rRNA上相应区域碱基、氨基酸的改变,可能是导致解脲脲原体对大环内酯类抗生素出现耐药的机制之一。     

神经梅毒实验室诊断研究进展

近10余年来,我国梅毒患病率呈上升趋势,导致神经梅毒患病率也有所上升,其防治成为重要的公共卫生问题之一。神经梅毒的早期诊断和规范化管理,对改善神经梅毒患者的疗效和预后有重要意义。本文从梅毒螺旋体中枢神经系统入侵、梅毒螺旋体中枢神经系统受累以及入侵与受累之间的关系三个方面,对目前神经梅毒的实验室诊断研究进展进行综述。     

Chromosomally mediated resistance in Neisseria gonorrhoeae in the United States: results of surveillance and reporting, 1983-1984

Between January 1983 and October 1984, 446 cases of infection due to chromosomally mediated resistance in Neisseria gonorrhoeae (CMRNG) were reported in 23 states. Eighty percent were detected as primary penicillin or ampicillin treatment failures. Gonococcal isolates were submitted from 175 (40%) for confirmation of resistance, susceptibility testing, gonococcal strain typing using monoclonal antibodies specific for outer membrane Protein I, and auxotyping. All were typed as Protein I serogroup IB (WII/WIII), and the majority were proline or prototrophic auxotypes. All were resistant in vitro to less than 1 microgram/ml of either penicillin or tetracycline. Comparing CMRNG with penicillinase-producing Neisseria gonorrhoeae (PPNG), we found that CMRNG were significantly more resistant to tetracycline and erythromycin, but PPNG were more resistant to penicillin (P less than .01). Because of increasing reports of gonococcal resistance in the United States, improved surveillance of clinical and laboratory resistance is needed in support of control and treatment recommendations for gonorrhea.     

Gastric Syphilis: A Disease with Multiple Manifestations

The resurgence of syphilis in the United States is effecting all areas of medical care. We describe a young female presenting with symptoms of peptic ulcer disease who failed to respond to H2-receptor antagonist therapy. After further evaluation, she was diagnosed with gastric syphilis and responded well to penicillin. Because gastric syphilis has no pathognomonic clinical findings, the clinician needs to be aware of this disease entity so as to make the correct diagnosis and institute the appropriate antibiotic therapy.     

Management of adult syphilis

There are several important unanswered key questions in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. A single dose of 2.4 million units of benzathine penicillin G remains the drug of choice for managing early syphilis. Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status. Although additional data on the efficacy of azithromycin in treating early syphilis have emerged, reported increases in the prevalence of a mutation associated with azithromycin resistance precludes a recommendation for its routine use. Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms. In those persons with early syphilis who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers 6-12 months after adequate therapy and those with late latent infection who do not achieve a similar decline within 12-24 months, CSF examination should be considered. Among HIV-infected persons, CSF examination among all those with asymptomatic late latent syphilis is not recommended owing to lack of evidence that demonstrates clinical benefit. HIV-infected persons with syphilis of any stages whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis. If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.