Non-imported malaria in Italy: paradigmatic approaches and public health implications following an unusual cluster of cases in 2017
Authors: Boccolini Daniela , Menegon Michela , Di Luca Marco , Toma Luciano , Severini Francesco , Marucci Gianluca , D’Amato Stefania , Caraglia Anna , Maraglino Francesco Paolo , Rezza Giovanni , Romi Roberto , Gradoni Luigi , Severini Carlo ,   The Italian Malaria Surveillance Group, Franchini Silva , Migazzi Marino , Ferranti Roberta , Castelli Francesco , Tomasoni Lina , Rizzoli Annapaola , Arnoldi Daniele , Capelli Gioia , Montarsi Fabrizio , Martini Simone , Bisoffi Zeno , Perandin Francesca , Piubelli Chiara , Pasquini Zeno , Canovari Benedetta , Pieretti Barbara , Agostini Massimo , Angeloni Giorgia , Antognini Elisa , Gavaudan Stefano , Conversano Michele , Desiante Francesco , Cipriani Rosita , Cambria Roberta , Franco Ettore , Pellegrino Angelo , Buccoliero Giovanni Battista , Cafiero Maria Assunta , Raele Donato Antonio , Galante Domenico , Ferrero Pier Angela , Bertorello Anna , Roberto Paolo , Mosca Andrea , Roversi Sandra , Gardenghi Laura , Cagarelli Roberto , Mattei Giovanna , Gualanduzzi Claudio 
Published: June 2020

Abstract
Background
The European region achieved interruption of malaria transmission during the 1970s. Since then, malaria control programs were replaced by surveillance systems in order to prevent possible re-emergence of this disease. Sporadic cases of non-imported malaria were recorded in several European countries in the past decade and locally transmitted outbreaks of Plasmodium vivax, most probably supported by Anopheles sacharovi, have been repeatedly reported from Greece since 2009. The possibility of locally-transmitted malaria has been extensively studied in Italy where the former malaria vector An. labranchiae survived the control campaign which led to malaria elimination. In this study, we present paradigmatic cases that occurred during a 2017 unusual cluster, which caused strong concern in public opinion and were carefully investigated after the implementation of the updated malaria surveillance system.

Methods
For suspected locally-transmitted malaria cases, alerts to Ministry of Health (MoH) and the National Institute of Health (ISS) were mandated by the Local Health Services (LHS). Epidemiological investigations on the transmission modes and the identification of possible infection’s source were carried out by LHS, MoH and ISS. Entomological investigations were implemented locally for all suspected locally-transmitted cases that occurred in periods suitable to anopheline activity. Molecular diagnosis by nested-PCR for the five human Plasmodium species was performed to support microscopic diagnosis. In addition, genotyping of P. falciparum isolate was carried out to investigate putative sources of infection and transmission modalities.

Results
In 2017, a cluster of seven non-imported cases was recorded from August through October. Among them, P. ovale curtisi was responsible of one case whereas six cases were caused by P. falciparum. Two cases were proved to be nosocomial while the other five were recorded as cryptic at the end of epidemiological investigations.

Conclusions
The epidemiological evidence shows that the locally acquired events are sporadic, often remain unresolved and classified as cryptic ones despite investigative efforts. The “cluster” of seven non-imported cases that occurred in 2017 in different regions of Italy therefore represents a conscious alert that should lead us to maintain a constant level of surveillance in a former malaria endemic country.