An overview of the lesson learned in almost 20 years of fight against the "tiger" mosquito.

Since its introduction in Italy in 1990, Aedes albopictus has spread quickly across the country, being at present reported in scattered foci in all regions below 600 m of altitude. The most important items of the lesson learned in almost 20 years of fight against the "Tiger" in Italy are here reported and discussed.

Infection with chikungunya virus in Italy: an outbreak in a temperate region.

BACKGROUND: Chikungunya virus (CHIKV), which is transmitted by Aedes spp mosquitoes, has recently caused several outbreaks on islands in the Indian Ocean and on the Indian subcontinent. We report on an outbreak in Italy. METHODS: After reports of a large number of cases of febrile illness of unknown origin in two contiguous villages in northeastern Italy, an outbreak investigation was done to identify the primary source of infection and modes of transmission. An active surveillance system was also implemented. The clinical case definition was presentation with fever and joint pain. Blood samples were gathered and analysed by PCR and serological assays to identify the causal agent. Locally captured mosquitoes were also tested by PCR. Phylogenetic analysis of the CHIKV E1 region was done. FINDINGS: Analysis of samples from human beings and from mosquitoes showed that the outbreak was caused by CHIKV. We identified 205 cases of infection with CHIKV between July 4 and Sept 27, 2007. The presumed index case was a man from India who developed symptoms while visiting relatives in one of the villages. Phylogenetic analysis showed a high similarity between the strains found in Italy and those identified during an earlier outbreak on islands in the Indian Ocean. The disease was fairly mild in nearly all cases, with only one reported death. INTERPRETATION: This outbreak of CHIKV disease in a non-tropical area was to some extent unexpected and emphasises the need for preparedness and response to emerging infectious threats in the era of globalisation.

[Combined antimalarial therapy using artemisinin]. / Terapia antimalarica combinata con derivati dell'artemisinina.

The existing armamentarium of drugs for the treatment and prevention of malaria is limited primarily by resistance (and cross-resistance between closely related drugs). However, most of these drugs still have a place and their life-span could be prolonged if better deployed and used, and also by rationally combining them based on pharmacodynamic and pharmacokinetic properties. Newer compounds are also being developed. The nature of malaria disease and its prevalence in the developing world call for innovative approaches to develop new affordable drugs and to safeguard the available ones. According to WHO, the concept of combination therapy is based on the synergistic or additive potential of two or more drugs, to improve therapeutic efficacy and also delay the development of resistance to the individual components of the combination. Combination therapy (CT) with antimalarial drugs is the simultaneous use of two or more blood schizontocidal drugs with independent modes of action and different biochemical targets in the parasite. In the context of this definition, multiple-drug therapies that include a nonantimalarial drug to enhance the antimalarial effect of a blood schizontocidal drug are not considered combination therapy. Similarly, certain antimalarial drugs that fit the criteria of synergistic fixed-dose combinations are operationally considered as single products in that neither of the individual components would be given alone for anti-malarial therapy. An example is sulfadoxine-pyrimethamine. Artemisinin-based combination therapies have been shown to improve treatment efficacy and also contain drug resistance in South-East Asia. However, major challenges exist in the deployment and use of antimalarial drug combination therapies, particularly in Africa. These include: 1) the choice of drug combinations best suited for the different epidemiological situations; 2) the cost of combination therapy; 3) the timing of the introduction of combination therapy; 4) the operational obstacles to implementation, especially compliance. As a response to increasing levels of antimalarial resistance, the World Health Organization (WHO) recommends that all countries experiencing resistance to conventional monotherapies, such as chloroquine, amodiaquine or sulfadoxine/pyrimethamine, should use combination therapies, preferably those containing artemisinin derivatives (ACTs--artemisinin-based combination therapies) for malaria caused by Plasmodium falciparum. There is a promising role of such compounds in replacing or complementing current options. Since 1979, several different formulations of artemisinin and its derivatives have been produced and studied in China in several thousand patients for either P. falciparum or P. vivax malaria. To date, there is no evidence of drug resistance to these compounds. The use of artemisinin, artemether, arteether and artesunate for either uncomplicated or severe malaria is now spreading through almost all malarious areas of the world, although some of they have no patent protection, their development (with few exceptions) has not followed yet full international standards. Both artesunate, artemether and arteether are rapidly and extensively converted to their common bioactive metabolite, dihydroarte-misinin. WHO currently recommends the following therapeutic options: 1) artemether/lumefantrine; 2) artesunate plus amodiaquine; 3) artesunate plus sulfadoxine/pyrimethamine (in areas where SP efficacy remains high); 4) artesunate plus mefloquine (in areas with low to moderate transmission); and 5) amodiaquine plus sulfadoxine/pyrimethamine, in areas where efficacy of both amodiaquine and sulfadoxine/pyrimethamine remains high (mainly limited to countries in West Africa). This non artemisinin-based combination therapy is reserved as an interim option for countries, which, for whatever reason, are unable immediately to move to ACTs.

Impact of the malaria control campaign (1993-1998) in the highlands of Madagascar: parasitological and entomological data.

Malaria transmission in the central highlands of Madagascar was interrupted in the 1960s by a national control program that used DDT indoor spraying and mass treatment with chloroquine. At the end of the 1980s in this region, epidemic malaria reappeared. Italian health authorities provided technical assistance to the National Malaria Control Program since the beginning of the resurgence of malaria in the central highlands. Yearly residual house spraying performed for 5 years (1993-1998) and the availability of antimalarial drugs reduced malaria transmission to very low levels, with improvement in parasitologic and entomologic indexes. A significant reduction of malaria prevalence was observed in the villages located at altitudes of 1,000-1,500 m, corresponding to the stratum of unstable malaria that was the main target of the antivector interventions. A significant reduction of malaria prevalence was also observed in the villages located at altitudes of 900-1,000 m, where malaria transmission is stable. The main vector Anopheles funestus was dramatically reduced in abundance and distribution in the sprayed areas.

Could malaria reappear in Italy?

Because of concern about the possible reintroduction of malaria transmission in Italy, we analyzed the epidemiologic factors involved and determined the country's malariogenic potential. Some rural areas in central and southern Italy have high receptivity because of the presence of potential malaria vectors. Anopheles labranchiae is probably susceptible to infection with Plasmodium vivax strains, but less likely to be susceptible to infection with P. falciparum. Its vulnerability is low because of the low presence of gametocyte carriers (imported cases) during the season climatically favorable to transmission. The overall malariogenic potential of Italy appears to be low, and reintroduction of malaria is unlikely in most of the country. However, our investigations showed that the malaria situation merits ongoing epidemiologic surveillance.

Malaria incidence and mortality in Italy in 1999-2000.

In 1999-2000, a total of 2060 malaria cases were reported by the ISS. Most of the patients took inappropriate treatments or did not have any prophylaxis. Ninety-three per cent became infected in African malarious countries, 4% in Asian countries, and 3% in Latin America. P. falciparum accounted for 84% of the cases, followed by P. vivax (8%), P. ovale (5%), and P. malariae (2%). Deaths corresponded to an annual case fatality rate of 0.3% in 1999 and 0.5% in 2000. In general, imported malaria cases reflect the number of Italian travellers who underestimate the infection risk in Asian and Latin American malarious countries and permanent residents of African origin who visit their relatives in their native countries.

Current status of Aedes albopictus and Aedes atropalpus in Italy.

Eight years after the 1st record in Italy, scattered foci of Aedes albopictus are reported in 9 regions and 107 municipalities belonging to 22 provinces, mainly located in the northeastern part of the country (Veneto region). In almost all infested areas the species is well controlled and at low levels of density, through source reduction and antilarval treatments. Aedes atropalpus, 1st recorded in 1996, remains limited to the original focus in the province of Treviso. Surveillance and control of both species are carried out by local health agencies within a national program coordinated by Istituto Superiore di Sanità (national Institute of Public Health).

Malaria surveillance in Italy: 1997 analysis and 1998 provisional data.

Malaria is the commonest imported infectious disease in Italy. Malaria was endemic throughout much of the country until it was eradicated nearly 50 years ago. Since then, a malaria surveillance system has been set up to detect locally acquired cases that

[Control of congenital toxoplasmosis in Italy: The project of the Istituto Superiore di Sanità]. / Il controllo della toxoplasmosi congenita in Italia: il progetto dell'Istituto Superiore di Sanità.

Toxoplasma gondii infection during pregnancy is a public health concern; many resources are used in diagnostic and therapeutic activities, sometime with a low benefit/cost due to lack of standardization in practices. In the lack of suitable epidemiological knowledge at national level regarding the congenital toxoplasmosis trend in Italy, an evaluation of the public health impact of this pathology is required. The Istituto Superiore di Sanità (ISS) has worked out a project on a prevalence-incidence study at national level, performing standard reference methods for diagnosis and both case definition and case management. Furthermore, the ISS urges all the involved centers on congenital toxoplasmosis to set up a network for an active collaboration to this project.

Re-emerging malaria in the WHO European region: control priorities and constraints.

Malaria has been identified by some of the countries in the European Region of the World Health Organization as a priority, due to the re-emergence of the problem. This paper aims to present the situation of indigenous malaria in the Region and the strategy to be adopted to roll back malaria.

Malaria surveillance in Italy : 1986-1996 analysis and 1997 provisional data.

A surveillance system for malaria was established in Italy to prevent a possible return of disease transmission after the eradication. Reporting malaria and 43 other infectious diseases is mandatory. Local laboratories diagnose clinical cases of malaria m

Prevention and morbidity of malaria in non-immune subjects; a case-control study among Italian troops in Somalia and Mozambique, 1992-1994.

The impact of malaria on Italian troops taking part in 1992-1994 in the United Nations Organization humanitarian missions in Somalia and Mozambique is discussed. In Somalia, 18 cases of Plasmodium falciparum malaria occurred among 11,600 soldiers; the overall attack rate was 0.4 cases/1000/month of exposure and the risk of malaria was effectively reduced by chemoprophylaxis with chloroquine plus proguanil (C+P) (odds ratio [OR] = 0.05, 95% confidence limits [95% CL] 0.02-0.16). In Mozambique, 119 cases of P.falciparum malaria occurred among 4800 soldiers; most cases (100) occurred in the first months of deployment (late March-June 1993), with an attack rate of 17 cases/1000/month, when C+P was the recommended chemoprophylactic regimen; the remaining 19 cases occurred subsequently, with an attack rate of 1.8 cases/1000/month, after C+P was replaced by mefloquine in July 1993. Protection achieved by C+P was unsatisfactory (OR = 0.37, 95% CL 0.21-0.67), while chemoprophylaxis with mefloquine effectively reduced the risk of malaria in Mozambique (OR = 0.03; 95% CL 0.01-0.10). A significant number of malaria infections was also detected among soldiers following their return home from Somalia (147 cases) and Mozambique (40 cases); these were due mainly to P. vivax. Fifteen of 113 P. vivax primary infections imported from Somalia (13.3%) relapsed 2-13 months after the primary attack. Because of the small proportion of relapsing P. vivax tropical strains, primaquine may be limited to radical treatment of relapses or, more extensively, of all P. vivax infections, but it should not be necessarily given to all asymptomatic subjects returning from tropical endemic areas, as is generally suggested for particular groups at risk.

Age-related prevalence of Plasmodium falciparum circumsporozoite antibody in an hyperendemic area of Madagascar, and its relationship with parasite prevalence.

An epidemiologic survey on malaria endemicity levels, including entomologic, parasitologic, and immunologic indicators, was carried out in a village of the Madagascar highlands (Analaroa) at the end of the 1990-1991 rainy season. The results indicate that malaria is hyperendemic and Anopheles funestus is the main vector in the area. The prevalence of parasitemia decreased with age from a maximum level of about 60% in children less than five years of age to a minimum of about 16% among those more than 29 years of age. The prevalence of Plasmodium falciparum circumsporozoite antibodies (Ab-Cs) increased with age from a minimum level of about 10% in children less than five years of age to a maximum of 71.7% among those more than 29 years of age. An inverse correlation was observed between P. falciparum prevalence and levels of Ab-Cs and parasite prevalence. The study confirmed that prevalence and Ab-Cs levels are reliable indicators of malaria endemicity in hyperendemic areas. Schoolchildren between five and 14 years of age are considered the most practical and susceptible group for this kind of epidemiologic study.

Occurrence and spread in Italy of Aedes albopictus, with implications for its introduction into other parts of Europe.

Aedes albopictus is considered second only to Ae. aegypti in its importance to man as a disease vector of dengue and dengue hemorrhagic fever. The first sighting in 1979 of the vector species in Europe came from Albania; however, it was only when Ae. albopictus was introduced into Italy in 1990, through the importation of used tires, followed by its subsequent spread, that the species was considered as a threat to public health. At the close of 1995, Ae. albopictus infestations have been reported from 10 Italian regions and 19 provinces. The risk for greater distribution of Ae. albopictus in Europe can potentially be projected, based on well-established criteria such as: where the winter monthly mean temperature is 0 degree C, where at least 50 cm of mean annual rainfall occurs, and where the mean summer temperature is approximately 20 degrees C. Those countries where climatic conditions meet such criteria and that may be vulnerable to a potential introduction of Ae. albopictus include Spain, Portugal, Greece, Turkey, France, Albania, and the former Republic of Yugoslavia. The Italian plan of action, established for the surveillance and control of Ae. albopictus, is presented in detail.