Giuseppe Ippolito

Tuberculosis and AIDS: a retrospective, longitudinal, multicentre study of Italian AIDS patients

We report the results of a retrospective, longitudinal, multicentre study which estimated the cumulative incidence of tuberculosis in patients who eventually develop AIDS, investigated the characteristics of AIDS patients in relation to the development of tuberculosis, and endeavoured to determine the degree of HIV-induced immunosuppression at which tuberculosis occurs. The Infectious Disease Units of 23 hospitals located in 11 of the 20 regions of Italy participated in this study. We investigated 1691 patients with AIDS diagnosed in 1988 and 1989 and reported to the National AIDS Registry by participating units before the end of December 1990. By that time M. tuberculosis had been cultured from 193 patients (11.4%). Compared with intravenous drug users (the largest HIV transmission category), only homosexual men had a statistically significant lower risk of tuberculosis (relative risk = 0.65; 95% confidence interval 0.43-0.99). The median count of CD4+ lymphocytes at the time tuberculosis was diagnosed was 82/mm3 (range 1-752); only four patients (2.1%) had CD4+ lymphocyte counts of more than 500/mm3, and 36 (18.7%) of over 200/mm3. We conclude that in Italy the proportion of AIDS patients who develop tuberculosis is higher than in other industrialised countries and differences in the incidence of tuberculosis among various HIV-transmission categories are less marked than in other western countries. Tuberculosis associated with HIV infection may occur in those with widely differing CD4+ counts, although the risk increases consistently in proportion to the degree of immunosuppression.

Evaluation of a rapid and sensitive RT-qPCR assay for the detection of Ebola Virus

BACKGROUNDnThe 2013-2016 Ebola virus disease (EVD) outbreak showed a lack of diagnostic point-of-care methods. Currently, EBOV diagnosis relies on quantitative reverse-transcription-PCR (RT- qPCR), highly specific and sensitive, but requiring skilled personnel and well-equipped laboratories. In field settings, these factors and others, such as samples time of collection and transportation, determine a prolonged turnaround-time to final results. In outbreak scenarios, a rapid and transportable method could eliminate issues of cohorting suspected and actual EVD patients for lack of diagnostic certainty. The aim of this study was the field evaluation of the new fast, easy-to-use and reliable RT-qPCR assay and platform for EBOV detection, developed in the framework of the EbolaMoDRAD project by CLONIT S.r.l. and STMicroelectronics S.r.l.nnnSTUDY DESIGNnWe evaluated its performance during the outbreak and in further studies in the EVD laboratory at the Princess Christian Maternity Hospital (PCMH) in Freetown (Sierra Leone) run by Emergency NGO and the Italian National Institute for Infectious Diseases (INMI). The assay was tested on residual aliquots of clinical specimens from EBOV-positive or -negative patients (n=116, EVD prevalence 37%).nnnRESULTS AND CONCLUSIONnOverall, the test was very easy-to-use and the instrument was robust and reliable in field-settings. The sensitivity of the assay was 100% and the specificity was 98.63% (95%CI: 96.34-100.92%). The positive and negative predictive values were 97.73 (95%CI:94.77-100.68%) and 100%, respectively. The high sensitivity and specificity of this new assay indicate that it is promising for laboratory diagnosis, especially in resource-limited settings.

Occupational transmission of an Orthopoxvirus infection during an outbreak in a colony of Macaca tonkeana in Lazio Region, Italy, 2015

Orthopoxviruses spill over from animal reservoirs to accidental hosts, sometimes causing human infections. We describe the surveillance and infection control measures undertaken during an outbreak due to an Orthopoxvirus occurred in January 2015 in a colony of Macaca tonkeana in the province of Rieti, Latio, Italy, which caused a human asymptomatic infection. According to the epidemiological investigation, the human transmission occurred after an unprotected exposure. The contacts among wild, captive and domestic animals and humans, together with decreased immunity against Orthopoxviruses in the community, may put animal handlers at risk of infection, especially after the cessation of smallpox vaccination. To reduce these threats, standard precautions including respiratory hygiene and transmission‐based precautions should be carefully applied also in veterinary medicine.

Emerging and Re-emerging Viral Infections

Natural focal diseases are caused by biological agents associated with specific landscapes. The natural focus of such diseases is defined as any natural ecosystem containing the pathogen’s population as an essential component. In such context, the agent circulates independently on human presence, and humans may become accidentally infected through contact with vectors or reservoirs. Some viruses (i.e., tick-borne encephalitis and Congo-Crimean hemorrhagic fever virus) are paradigmatic examples of natural focal diseases. When environmental changes, increase of reservoir/vector populations, demographic pressure, and/or changes in human behavior occur, increased risk of exposure to the pathogen may lead to clusters of cases or even to larger outbreaks. Intervention is often not highly cost-effective, thus only a few examples of large-scale or even targeted vaccination campaigns are reported in the international literature. To develop intervention models, risk assessment through disease mapping is an essential component of the response against these neglected threats and key to the design of prevention strategies, especially when effective vaccines against the disease are available.

EBOLA Ag K-SeT rapid test: field evaluation in Sierra Leone

OBJECTIVESnEfficient interruption of Ebola virus disease (EVD) transmission chains critically depends on reliable and fast laboratory diagnosis. We evaluated the performance of the EBOLA Virus Antigen Detection K-SeT (EBOLA Ag K-SeT), a new rapid diagnostic antigen test in field settings.nnnMETHODSnThe study was conducted in a field laboratory located in Freetown (Sierra Leone) by the Italian National Institute for Infectious Diseases L. Spallanzani and the EMERGENCY Onlus NGO. The EBOLA Ag K-SeT was tested on 210 residual plasma samples (EVD prevalence 50%) from patients hospitalized at the EMERGENCY Ebola treatment center in Goderich (Freetown), comparing the results with quantitative real-time PCR.nnnRESULTSnOverall, the sensitivity of EBOLA Ag K-SeT was 88.6% (95% confidence interval (CI), 82.5-94.7), and the corresponding specificity was 98.1% (95% CI, 95.5-100.7). The positive and negative predictive values were 97.9% (95% CI, 95.0-100.8) and 89.6% (95% CI, 84-95.2), respectively. The sensitivity strongly increased up to 98.7% (95% CI, 96.1-101.2) for those samples with high virus load (≥6.2 log RNA copies/mL).nnnCONCLUSIONSnOur results suggest that EBOLA Ag K-SeT could represent a new effective diagnostic tool for EVD, meeting a need for resource-poor settings and rapid diagnosis for individuals with suspected EVD.

Preparação hospitalar e tratamento dos pacientes com febre hemorrágica vírica ou com variola no Instituto Lazzaro Spallanzani, Roma, Itália

Os casos americanos de anthrax em 2001 e o surto recente de sindrome respiratorio agudo severo (SRAS) aumentaram a necessidade de uma preparacao e resposta as infeccoes emergentes ou re-emergentes de forma natural e aos agentes patogenos disseminados deliberadamente. O presente relatorio descreve o modelo de resposta do Instituto nacional paras as doencas infecciosas (INMI, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Roma, Italia) para o tratamento de pacientes infectados – ou suspeitos de se-lo – pela variola ou a febre hemorragica, seja no contexto de uma emissao deliberada do virus ou de uma infeccao de origem natural. nEm Italia, o INMI e o hospital de referencia em termos de planos de preparacao e de resposta aos agentes infecciosos relacionados com ataques bioterroristas. Todos os quartos, simples ou duplos, estao equipados com pressao negativa do ar, portas reforcadas, filtros HEPA (high efficiency particulate air), assim como uma anticâmara totalmente equipada. Tambem esta disponivel uma unidade de alta seguranca, com um laboratorio annexo para os primeiros testes de diagnostico, para os casos esporadicos que necessitem isolamento. Para o transporte dos pacientes, o instituto dispoe de duas ambulancias totalmente equipadas e de duas macas isoladas com uma secao de pressao negativa. Os testes diagnosticos moleculares e tradicionais estao realizados actualmente nos laboratorios de bioseguridade de nivel 3/4. A educacao e formacao do pessoal hospitalar, a applicacao stricta das praticas de controle da infeccao e dispor de equipos de proteccao pessoal, sao recursos addicionais que permitem tratar os pacientes extremamente contagiosos, e manter uma equipe correctamente preparada para responder a surtos de grande escala.

Vigilância da exposição profissional aos agentes patogénicos transmitidos pelo sangue em profissionais de saúde: programa nacional italiano

Os profissionais de saude (PS) enfrentam um grave risco de adquirirem infeccoes transmitidas pelo sangue, em particular o virus da hepatite B (VHB), o virus da hepatite C (VHC) e o virus da imunodeficiencia humana (VIH); todos eles estao associados a uma morbilidade e mortalidade significativas. Em 1986, o centro coordenador do estudo Italiano sobre o risco profissional de infeccao pelo VIH (Studio Italiano Rischio Occupazionale da VIH, SIROH) iniciou um estudo prospectivo multicentrico destinado a calcular o risco de transmissao do VIH e outros agentes patogenicos transmitidos pelo sangue aos PS apos uma exposicao profissional ao sangue e outros materiais corporais, bem como para identificar dispositivos, procedimentos e profissoes de alto risco nos estabelecimentos de saude. Desde 1990 que o centro coordenador organiza o registo Italiano da profilaxia anti-retroviral apos a exposicao, de forma a monitorizar a utilizacao e a toxicidade a curto prazo da zidovudina (ZDV) e, desde 1995, da profilaxia de combinacao antiretroviral. Este artigo descreve o SIROH e apresenta resultados que ilustram o seu potencial.

Sorveglianza delle esposizioni professionali a patogeni a trasmissione ematica negli operatori sanitari: il programma nazionale italiano

Gli operatori sanitari (OS) sono ad alto rischio di acquisire infezioni a trasmissione ematica, in particolare quella da virus dellepatite B (HBV), da virus dellepatite C (HCV) e da virus dellimmunodeficienza umana (HIV). Nel 1986, il centro di coordinamento dello Studio Italiano sul Rischio Occupazionale da HIV (SIROH) ha iniziato uno studio prospettico multicentrico negli OS, per valutare il rischio di trasmissione dell’ HIV e di altri patogeni a trasmissione ematica, in seguito allesposizione professionale a sangue o ad altri materiali corporei, e per identificare strumenti, procedure e attivita lavorative a rischio in ambito assistenziale. Il centro di coordinamento ha gestito dal 1990 il registro italiano relativo alla profilassi antiretrovirale post-esposizione al fine di monitorare sia lutilizzo che la tossicita a breve termine della zidovudina (AZT) e, dal 1995, anche della profilassi antiretrovirale con farmaci in combinazione. Questo articolo descrive le caratteristiche del SIROH e presenta alcuni risultati che ne illustrano le potenzialita applicative.