Sergio Sabbatani

Unusual malignant tumours in 49 patients with HIV infection

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposis sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found. Testis carcinoma occurred mainly in patients in an early phase of HIV infection, without adversely affecting full-dose chemotherapy or radiotherapy. In situ cervical carcinoma treated with conization would suggest papanicolaou shear test screening in young IVDA. Lung carcinoma occurred in a young age group with rapid progression and resulted in death within 2 months. Intensive chemotherapy for ALL was not adversely affected by HIV infection and two complete remissions were achieved (11 and 15 months duration). This retrospective study shows that while oral and anorectal tumours were very rarely observed, a wide spectrum of other HIV-related solid tumours and leukaemias were found in this IVDA-based series. The incidence of such tumours is probably underestimated because they are not diagnostic of AIDS. The required therapeutic approaches may not necessarily be influenced by HIV infection, in contrast with the observed pattern for treatment of KS and ML in HIV-infected subjects.

The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern?

After examining the most recent scientific evidences, which assessed the role of some malaria plasmodia that have monkeys as natural reservoirs, the authors focus their attention on Plasmodium knowlesi. The infective foci attributable to this last Plasmodium species have been identified during the last decade in Malaysia, in particular in the states of Sarawak and Sabah (Malaysian Borneo), and in the Pahang region (peninsular Malaysia). The significant relevance of molecular biology assays (polymerase chain reaction, or PCR, performed with specific primers for P. knowlesi), is underlined, since the traditional microscopic examination does not offer distinguishing features, especially when the differential diagnosis with Plasmodium malariae is of concern. Furthermore, Plasmodium knowlesi disease may be responsible of fatal cases, since its clinical presentation and course is more severe compared with those caused by P. malariae, paralleling a more elevated parasitemia. The most effective mosquito vector is represented by Anopheles latens; this mosquito is a parasite of both humans and monkeys. Among primates, the natural hosts are Macaca fascicularis, M. nemestina, M. inus, and Saimiri scirea. When remarking the possible severe evolution of P. knowlesi malaria, we underline the importance of an early recognition and a timely management, especially in patients who have their first onset in Western Hospitals, after journeys in Southeast Asian countries, and eventually participated in trekking excursions in the tropical forest. When malaria-like signs and symptoms are present, a timely diagnosis and treatment become crucial. In the light of its emerging epidemiological features, P. knowlesi may be added to the reknown human malaria parasites, whith includes P. vivax, P. ovale, P. malariae, and P. falciparum, as the fifth potential ethiologic agent of human malaria. Over the next few years, it will be mandatory to support an adequate surveillance and epidemiological network. In parallel with epidemiological and health care policy studies, also an accurate appraisal of the clinical features of P. knowlesi-affected patients will be strongly needed, since some preliminary experiences seem to show an increased disease severity, associated with increased parasitemia, in parallel with the progressive increase of inter-human infectious passages of this emerging Plasmodium.

Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma in a chronic nephropathic HIV-negative patient, after fluconazole failure

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary—secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.

Reactivation of severe, acute pulmonary tuberculosis during treatment with pegylated interferon-alpha and ribavirin for chronic HCV hepatitis

The unexpected observation of severe pulmonary tuberculosis after a 7-month combined pegylated interferon-ribavirin for chronic hepatitis C, prompted us to search an eventual immunodeficiency (lymphopenia and/or depletion of CD4+ T-lymphocytes. The retrieval of a chest radiograph incidentally performed 11 y before and showing a probable primary tuberculosis, paralleled a negligible clinical history. The enlargement of interferon indications needs careful evaluation for prior (usually missed) tuberculosis, to prevent or avoid its possible reactivation. Latent tuberculosis is increasingly reported because of extended life expectancy, immigration, and recent availability of cure for multiple chronic disorders, which are often borne by primary-secondary immunodeficiency.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review

AIM To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Combined Pegylated Interferon and Ribavirin for the Management of Chronic Hepatitis C in a Prison Setting

The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31% in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67%) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patients willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

Tuberculosis in a metropolitan area of northern Italy: Epidemiological trends and public health concerns

As the most widespread infectious disease all over the world, tuberculosis is borne by increasing morbidity and mortality rates, both in industrialized and in developing countries. Changes in epidemiology patterns, atypical clinical-radiological manifestations, and the spread of chemotherapy-resistant strains, are prominent problems in the management of tuberculosis [1, 2]. The recent variation of a number of predisposing factors are altering both epidemiology and presentation of tuberculosis: the HIV pandemic, advancing age and concomitant illnesses (diabetes mellitus, lung and collagen vascular diseases), increasing immunodeficiency states (including iatrogenic ones), alcoholism and drug abuse, and especially immigration from regions where tuberculosis is endemic, or predisposition to acquire tuberculosis after arrival in Western countries, due to overwhelming social and economic problems [1, 3]. The recent immigration waves occurred in Italy (regarding hundred thousands people searching for work or escaping from war), are dramatically acting on the epidemiology of infectious diseases at both inpatient and outpatient settings. Should surveillance and public health preventive measures are insufficient, a spread of this contagious disease into the general population cannot be excluded, due to the recent, explosive increase of notifications [1, 3-5]. These changing features may be anticipated by some clearly recognizable trends in epidemiological, pathogenetic, and clinical features of tuberculosis in Italy. A retrospective analysis of clinical charts of patients hospitalized from 1996 to 2001 at our inpatient

Severe staphylococcal knee arthritis responding favourably to linezolid, after glycopeptide-rifampicin failure: A case report and literature review

A puzzling case report of a septicaemic post-surgical staphylococcal knee arthritis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin, despite apparently favourable in vitro susceptibility assays, but which rapidly resolved after i.v. followed by oral administration of linezolid is presented, and discussed in the context of the most recent literature evidence. The lack of response to a 14-d-long course of glycopeptides does not find explanation from the in vitro minimum inhibitory concentrations (MIC90) of involved organisms, which showed full susceptibility of Staphylococcus aureus to vancomycin and teicoplanin, and sensitivity of an accompanying Staphylococcus epidermidis isolated from blood cultures to vancomycin and rifampicin, with borderline ‘intermediate’ values found for teicoplanin. Since neither bone involvement nor abscess formation was of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been assured. From a clinical viewpoint, the introduction of a 2-week i.v. linezolid followed by 1 further week of oral linezolid led to complete clinical and microbiological cure, and an unexpected functional success.

Capnocytophaga spp. brain abscess in an immunocompetent host: problems in antimicrobial chemotherapy and literature review.

Abstract The fourth case report of a brain abscess due to the fastidious Gram-negative organism Capnocytophaga spp. is described and discussed on the grounds of clinical, microbiological, and therapeutic evidence. A probable origin from a cat bite and/or an underlying severe mandibulary granuloma is suspected. Due to lack of clinical and neuroradiological response to neurosurgery and a combination of imipenem-amikacin-clindamycin-fluconazole, second-line empiric linezolid treatment proved rapidly successful, in the absence of further microbial isolations. In vitro antimicrobial susceptibility testing is often unpredictable for Capnocytophaga spp., and agents usually active on Gram-positive organisms may also be effective, both in vitro and in vivo. Due to its favorable brain penetration and its dual mode of administration, linezolid may be an alternative option for patients with multiple risk factors, brain abscess of suspected polymicrobial origin, and lack of response to empiric or culture-driven therapeutic attempts.

Listeria monocytogenes Meningitis and Multiple Brain Abscesses in an Immunocompetent Host. Favorable Response to Combination Linezolid-Meropenem Treatment

Central nervous system (CNS) listeriosis outside of pregnancy, the neonatal period, and immunodeficiency, is uncommon in the general population. Although Listeria sepsis-bacteremia, endocarditis, gastroenterit is, and focal infection has been described, meningitis and especially CNS abscess lead to major diagnostic and therapeutic concerns 1,2. CNS involvement should follow bacteremia, and meningitis represents the most common CNS manifestation, with brain abscesses being <1% of episodes of Listeria CNS involvement 3. Multiple predisposing factors have been described in anecdotal reports and small adult and pediatric series of patients suffering from hematologic or solid organ malignancies 1,2,4, collagen vascular disease and chronic intestinal disorders, while HIV disease is not considered a supporting factor. Isolated episodes of L. monocytogenes CNS infection were also reported in immunocompetent patients 5,6, where differential diagnosis and treatment are hampered by a low clinical suspicion. A literature review from 1945 to 1984 retrieved 45 cases of listeriosis, 54% of them occurring in apparently immunocompetent hosts, Journal of Chemotherapy Vol. 18 n. 3 (331-333) 2006