Imported Malaria in Adults and Children: Epidemiological and Clinical Characteristics of 380 Consecutive Cases Observed in Verona, Italy

Marta Mascarello MD, Benedetta Allegranzi MD, DTM&H, Andrea Angheben MD, Mariella Anselmi MD, Ercole Concia MD, PhD, Stefano Laganà, Lamberto Manzoli MD, MPH, Stefania Marocco MD, Geraldo Monteiro MD, Zeno Bisoffi MD, DTM&H
DOI: 229-236 First published online: 1 July 2008


Background Since the year 2000, in Italy, there has been a constant decrease in the number of cases of imported malaria in immigrants. Nevertheless, immigrants still account for about 70% of reported cases. To our knowledge, no data are yet available on imported malaria in children. This paper describes the main characteristics of malaria cases observed in recent years in the three main hospitals in Verona (roughly representing 10% of all cases reported in Italy in the period), with a special focus on the poorly known problem of imported malaria in children.

Method All malaria cases occurring from 2000 to 2004 were retrospectively examined. Semi‐immune and nonimmune patients were analyzed for clinical, laboratory, and parasitological findings. A separate analysis was carried out for children who traveled to endemic areas to visit relatives and friends (VRF) and children born in endemic countries who came to Italy for immigration purposes.

Results A total of 380 cases of imported malaria occurred in Verona in the 5‐year period, 43 being children. Semi‐immune patients had a significantly lower parasitemia (p = 0.0032) and parasite clearance time and significantly shorter fever duration than nonimmune (p = 0.025 and p = 0.0026). VRF children presented significantly higher parasitemia and significantly lower platelet count (p = 0.016 and p = 0.042) than recent immigrants. Parasitemia clearance time and fever duration were longer in VRF children than in recent immigrants (p = 0.014 and p = 0.0085). We observed 23 cases of severe malaria, including 4 cases in immigrants.

Conclusions Our data confirm a significant difference both in clinical and in parasitological findings between semi‐immune and nonimmune patients. We identified two populations of immigrant children: semi‐immune (recent immigrants) and nonimmune (VRF). The latter is a high‐risk group for severe malaria. Educational actions should be specially designed for immigrants traveling to VRF, focusing on the risk of severe malaria for both adults and children.

In industrial countries, malaria remains the most important cause of fever in travelers arriving from endemic areas. Every year, many international travelers are affected by malaria while visiting endemic countries and well over 10,000 are reported to fall ill after their return.1

From 1990 to 1998, the yearly number of cases of imported malaria in Italy increased by 100% due to the rising rate of both immigration and international travel. Until 1990, most cases were Italian travelers. After that year, a constant increase in the number of cases in immigrants from endemic areas was observed, and since 1995, they have outnumbered the cases reported for Italian travelers.2 In 1999, the number of reported malaria cases reached a peak of 1,100 cases. Since the year 2000, a constant decrease in the number of cases in immigrants was observed, while the number of cases in Italian travelers has remained almost constant. Nevertheless, from 2000 to 2004, immigrants still accounted for about 70% of total reported cases3 (Figure 1). To our knowledge, data on imported malaria in children have not been reported yet in systematic case series. The aim of this study was to describe the pattern of imported malaria in the three main hospitals in Verona (Ospedale Sacro Cuore di Negrar, Ospedale Civile Maggiore, and Policlinico G.B. Rossi) from 2000 to 2004, with a special focus on imported malaria in children, a poorly investigated group.

Figure 1

Cases of imported malaria in Italian travelers and in immigrants notified to the Italian Ministry of Health and recorded by Istituto Superiore di Sanità from 1990 to 2004 (Source: Romi).3


We retrospectively examined all malaria cases in patients hospitalized from January 1, 2000, to December 31, 2004, in the three hospitals in Verona (Ospedale Sacro Cuore di Negrar, Ospedale Civile Maggiore, and Policlinico G.B. Rossi). The diagnosis was based on microscopic examination of Giemsa‐stained thick and thin blood smears. Only inpatients’ records were analyzed. Data were entered in a computerized database (Microsoft Access, 2002, Microsoft Italia, Segrate, Italy) and were analyzed with Stata statistical package.

Patient characteristics were classified according to the TROPNETEUROP categories4 as follows: (1) patient classification (immigrants, refugees, expatriates, foreign visitors to Italy, business travelers, military, missionary, students, and tourists) and (2) reason for travel [visiting relatives and friends (VRF), immigration, missionary/volunteers/humanitarian aid, tourism, business, and research/education].

Our analysis focused on two main groups: nonimmune and semi‐immune patients. The nonimmune group included short‐term travelers (including African children born in Italy), regardless of the reason for travel. The semi‐immune group included patients born in malaria areas as well as long‐term Italian residents in endemic countries, mostly missionary people with a history of repeated malaria episodes. We are aware of the limitations of this classification, especially for foreign immigrants, as it is well known that immunity is lost in part after a variable period of residence in a nonendemic area. However, it has recently been made clear in France that a partial immunity tends to persist for a long period5 and even after many years, these subjects are clearly different on this respect from nonimmune patients. Pediatric patients (aged less than 15 y) were divided into two groups: (1) children born and grown in endemic areas who had come to Italy for the first time for immigration purposes and (2) children born of immigrant parents in Italy, occasionally traveling to endemic areas to VRF. In this case, we considered the reason for travel (immigration or VRF) as a proxy of immunity status (semi‐immune or nonimmune). Interestingly, no pediatric malaria cases were observed in Italian travelers .

The two main groups (nonimmune and semi‐immune patients of all ages) were separately analyzed for parasitological (parasitemia and parasite clearance time), laboratory (hemoglobin and platelets), and clinical (fever clearance time) findings. A separate analysis was carried out for pediatric cases.

Univariate analyses were used to describe the study sample. Laboratory examination results, which are continuous variables, were also categorized, and results presented as percentages in addition to means and standard deviation (SD). Differences in laboratory examination results according to patient classification and reason for traveling were examined using one‐tailed t ‐test.



From 2000 to 2004, 380 patients (337 adults and 43 children) were admitted for malaria. The main characteristics of the patient population are summarized in Table 1. Thirty‐four percent (129) were females. The mean age was 37.4 years (range 1–80 y).

View this table:
Table 1

Main characteristics of imported malaria cases admitted in the three Verona hospitals from 2000 to 2004, all patients, adult patients, and pediatric patients

CharacteristicAll patients, n = 380Adult patients, n = 337Pediatric patients, n = 43
Sex, n (%)
 Male251 (66)231 (68.5)20 (46.5)
 Female129 (34)106 (31.5)23 (53.5)
Age (mean)37.441.36.5
Patient classification, n (%)
 Immigrants181 (48)161 (47.8)20 (46.5)
 Italian citizens living in endemic countries64 (17)64 (19)0
 Short‐term travelers80 (21)57 (17)23 (53.5)
 Workers in endemic areas36 (9)36 (10.7)0
 Students or visitors born in endemic areas16 (4)16 (4.7)0
 Unknown3 (1)3 (0.8)0
Travel destination, n (%)
 Africa359 (94.5)318 (94.3)41 (95.3)
 Asia17 (4.5)15 (4.5)2 (4.6)
 Central and South America, Oceania4 (1)4 (1.2)0
Reason for travel, n (%)
 VRF154 (40.5)131 (38.9)23 (53.5)
 Immigration50 (13.2)30 (9)20 (46.5)
 Missionary or volunteer89 (23.4)89 (26.4)0
 Work38 (10)38 (11.2)0
 Tourism39 (10.3)39 (11.5)0
 Research and study5 (1.3)5 (1.5)0
 Unknown5 (1.3)5 (1.5)0
Reason for travel in immigrants, n (%)
 VRF128 (70.7)128 (79.5)0
 Immigration47 (26)27 (16.8)20
 Other reasons6 (3.3)6 (3.7)0
Chemoprophylaxis, n (%)
 Yes80 (21)73 (21.7)7 (16.3)
  Adequate21 (26.2)210
  Not adequate59 (73.7)527
 No269 (70.8)233 (69.1)36 (83.7)
 Unknown31 (8.2)31 (9.2)0
Plasmodium species, n (%)
Plasmodium falciparum292 (76.8)251 (74.5)41 (95.3)
Plasmodium ovale36 (9.5)36 (10.7)0
Plasmodium vivax20 (5.3)18 (5.3)2 (4.7)
Plasmodium malariae9 (2.4)9 (2.7)0
Mixed infections, n (%)23 (6)23 (6.8)0
P falciparum and P malariae11 (47.8)11 (47.8)0
P falciparum and P ovale5 (21.7)5 (21.7)0
P falciparum and P vivax2 (8.7)2 (8.7)0
P ovale and P vivax4 (17.4)4 (17.4)0
P ovale and P malariae1 (4.4)1 (4.4)0
Severe malaria23 (6)15 (4.5)8 (18.6)
  • VRF = visiting relatives and friends.

The yearly number of cases observed decreased over the study period (Figure 2) in line with the national tendency. Cases in Verona represented almost 10% of all imported malaria cases reported in Italy (Table 2).

Figure 2

Yearly number of malaria cases occurred in adults and in pediatric patients in Verona from 2000 to 2004.

View this table:
Table 2

Number of malaria cases and deaths notified to the Italian Ministry of Health and recorded by Istituto Superiore di Sanità, and number observed in the three Verona hospitals from 2000 to 2004

ItalyVeronaVerona cases (% of national data)ItalyVerona

Patient classification

As shown in Table 1 and Figure 3, of 377 patients, 181 (48%) were immigrants (both adults and children), 64 (17 %) were Italian citizens living in endemic countries, 80 (21%) were short‐term travelers (both adults and children), 36 (9%) were workers in endemic areas, and 16 (4%) were students or visitors born in endemic areas. The classification was unknown for three (1%) patients. The details for adults and children are reported in Table 1.

Figure 3

Patient classification of 380 cases of imported malaria observed in Verona from 2000 to 2004 in all patients, adult patients, and pediatric patients.

Travel destination

A total of 359 patients (94.5%) had been infected in Africa, 17 (4.5%) in Asia, and 4 (1%) in other continents (Oceania or Central and South America).

Reason for traveling

The reasons for traveling were as follows: VRF: 154 cases (40.5%), immigration: 50 cases (13.2%), missionary or volunteer: 89 cases (23.4%), tourism: 39 cases (10.3%), research and study: 5 cases (1.3%), and work: 38 cases (10%). For five cases (1.3%), the reason was unknown. Among immigrants, 128 (70.7%) traveled to VRF after an average length of stay in Italy of 8.3 years (SD 4.6 y), 47 (26%) for immigration purpose, and 6 (3.3%) for other reasons.


Details on chemoprophylaxis were available in 349 cases. Eighty patients (21%) followed a chemoprophylactic regimen, adequate for 21 (26.2%), most of whom had relapses of Plasmodium vivax or Plasmodium ovale malaria.

Plasmodium species

Plasmodium falciparum was found in 292 patients (76.8%), P ovale in 36 (9.5%), P vivax in 20 (5.3%), and Plasmodium malariae in 9 (2.4%) cases (Figure 4). Twenty‐three cases (6%) were caused by mixed infections: 11 by P falciparum and P malariae , 5 by P falciparum and P ovale , 2 by P falciparum and P vivax , 4 by P ovale and P vivax , and 1 by P ovale and P malariae . Parasitemia and parasite clearance time were calculated for P falciparum only and were missing in some cases.

Figure 4

Plasmodium species and mixed infections in 380 patients diagnosed with malaria in three Verona hospitals from 2000 to 2004.

Main laboratory findings

Findings are summarized in Table 3. Children had a higher mean parasitemia and a lower hemoglobin level on admission, while adults had a lower platelet count.

View this table:
Table 3

Main laboratory findings on admission in adult patients and in pediatric patients

Main laboratory findings on admissionAdult patients, mean (SD)Number of casesPediatric patients, mean (SD)Number of cases
Hemoglobin (g/dL)12.6 (1.9)32610.6 (1.8)43
Platelets (×109/L)122.6 (65.8)326200.3 (117.6)35
Parasitemia, trophozoites (/μL)31,057.4 (67363.6)21073,476.1 (113,603.8)35
Bilirubin (mmol/L)23.1 (19.8)31919.8 (30.5)41
Glucose (mmol/L)5.6 (1.4)2955,8 (5,6)37

Pediatric cases

Forty‐three patients (11.3%) were children (less than 15 y of age). The yearly number of pediatric cases tended to increase over the study period (Figure 2) with a peak in 2004 (7 cases in 2000, 10 in 2001, 8 in 2002, 6 in 2003, and 12 in 2004).

All cases occurred in children born to immigrant parents. Twenty‐three (53.5%) had traveled with the family to VRF, while 20 (46.5%) were children born in endemic areas who had recently come to Italy for immigration. The mean age of recent immigrants was 9 years, and the median age was also 9 years. Only three children were less than 5 years old. No single case was observed in Italian children.

Severe malaria

According to World Health Organization criteria, 23 cases were classified as severe malaria.6 Detailed epidemiological data were available for 13 adults and eight children. Of the adults, four were born in endemic areas (three VRF and one immigrant), three were long‐term Italian residents in endemic countries, and six were Italian short‐term travelers. The mean age in adults with severe malaria was 52.4 years of age versus 40.8 for uncomplicated malaria. Thirty‐nine percent of adults with severe malaria were aged 60 or older. As shown in Figure 5, the percentage of complicated malaria in adults increased with age: 10.3% (7) of patients older than 55 years (68) had a severe disease versus only 2.2% (6) of patients aged 15 to 54 years (269) (odds ratio 5.03, 1.45–17.63; p = 0.007, Fisher exact test).

Figure 5

Distribution of severe and uncomplicated malaria cases according to age groups.

Among children, seven had traveled to VRF, while one had come to Italy for immigration purposes. The mean age was 3.1 years.

Immunity status

Patients were grouped according to their presumable immunity status (nonimmune or semi‐immune) as described in the Methods section and separately analyzed for the main variables (Table 4).

View this table:
Table 4

Main findings in nonimmune and in semi‐immune patients

Main findingsNonimmune, mean (SD)Number of casesSemi‐immune, mean (SD)Number of casesp (t ‐Test)
Parasitemia, trophozoites (/μL)106,436 (156,933)5141,885 (82,083)1740.0032
Parasite clearance time (d)3.2 (1.6)512.7 (1.3)1740.025
Fever duration (d)3.4 (1.7)752.4 (4.4)2050.0026
Hemoglobin (g/dL)12.3 (2.4)7412.4 (1.8)2510.445
Platelets (×109/L)133.4 (74.2)74129.5 (76.8)2510.28

Semi‐immune patients (data available for 174 cases) were found to have a parasitemic level on admission significantly lower than those recorded in nonimmune patients (data available for 51 cases) (mean 41,885 vs 106,436 trophozoites/μL, p = 0.0032).

The parasite clearance time after treatment was significantly shorter in semi‐immune than in nonimmune patients (2.7 vs 3.2 d, p = 0.025).

Similarly, fever duration was significantly shorter in semi‐immune (data available for 205 patients) than in nonimmune patients (data available for 75 patients) (2.4 vs 3.4 d, p = 0.0026).

No significant difference in the mean values of hemoglobin and platelet count was detected.

Pediatric malaria

A separate analysis was carried out for pediatric patients. We compared parasitological (parasitemia and parasite clearance time), laboratory (platelets), and clinical (fever duration) outcomes in two pediatric groups: children born and grown in endemic areas who had recently come to Italy for immigration purpose (recent immigrants, 20 cases) and children who were living in Italy and occasionally made short visits to their parents’ native country (VRF, 23 cases).

Parasitemia was available for 17 VRF children and for 18 recent immigrants.

As shown in Table 5, recent immigrant children had a significantly lower parasitemic level and higher average platelet count on admission and showed a significantly shorter parasitemia clearance time after treatment and fever duration.

View this table:
Table 5

Main findings in pediatric patients who traveled to VRF and in pediatric patients who traveled for immigration

Main findingsNonimmune VRF, mean (SD)Number of casesSemi‐immune immigration, mean (SD)Number of casesp (t ‐Test)
Parasitemia, trophozoites (/μL)126,897 (123,236)1742,414 (99,350.9)180.016
Parasite clearance time (d)3.9 (1.3)172.7 (1.3)180.014
Fever duration (d)2.7 (1.4)201.7 (0.9)120.0085
Platelet count (×109/L)177.7 (97.9)17244.5 (123.2)180.042
  • VRF = visit relatives and friends.


The number of cases of imported malaria observed in the three Verona hospitals from 2000 to 2004 (380 cases) accounts for 9.4% of total cases reported in Italy (Table 2) in the same period (4,036 cases). In line with national figures reported for the same time frame, the most frequently diagnosed Plasmodium species in Verona was falciparum .

Plasmodium ovale was found comparatively more frequently in Verona (9.5% of total cases) than in Italy as a whole (6.7% of total cases), the opposite being true for P vivax (5.3% of total cases in Verona vs 9.1% in Italy as a whole).

Very surprisingly, 58% (23) of the total cases of mixed infections reported in Italy during the study period were diagnosed in Verona, presumably reflecting a high accuracy of malaria microscopy. Early diagnosis of mixed infection is crucial to avoid later relapses when P vivax or P ovale is the second species involved.

Since the year 2000, a decrease in imported malaria cases was observed mainly in immigrant patients, while the trend in Italian travelers remained quite stable. A similar tendency was observed nationwide.7 The reason for the decline of malaria cases in immigrants is not clear. Immigration and travel (VRF) were not shown to decrease, nor was an increasing adherence to chemoprophylaxis reported in this group. In other European countries, immigrants account for an increasing proportion of malaria cases; a recent study in the Netherlands describes a steady decrease of malaria cases in nonimmune (Dutch) patients, while the number of cases in immigrants has remained constant.8

We were particularly interested in investigating the differences between the two main groups of patients. Two previous studies conducted in Italy in the past decade analyzed the clinical and parasitological findings of falciparum malaria in semi‐immune and nonimmune patients.

In the first study (Di Perri and colleagues),9 immigrants were found to have significantly lower parasitemia on admission than short‐term travelers. However, in the second study (Castelli and colleagues),10 parasitemia on admission and parasitemia clearance time after treatment were found to be similar in both groups, while fever clearance time was significantly shorter in immigrants. Our data on a large sample confirm significant differences both in clinical (fever clearance time) and in parasitological (parasitemia and parasite clearance time) findings. The so‐called “semi‐immunity” requires frequent exposure to infecting bites and is progressively lost after a long period in a nonendemic area. The mean time required to lose semi‐immunity has not yet clearly been established.5 We found a high titer of antimalarial antibodies (immune fluorescent antibody test; Bio‐Mérieux) in African immigrants after up to 15 years of residence in Italy with no reported visit to their native countries (Bisoffi Z, unpublished data, 2002). However, antibody titer does not necessarily correlate with clinically relevant immunity. The limitations of our classification have already been discussed in the Methods section; however, it is clear from our findings as well as from French data5 that this group maintains clear differences with truly nonimmune patients, even many years after leaving the endemic area.

In the 1990s, severe malaria was a rare occurrence in Italy, essentially limited to classical “nonimmune” patients, coinciding with short‐term Italian travelers. Severe cases in immigrants were an exceedingly rare exception.11

Since the year 2000, in Verona, we have observed an increasing number of severe malaria cases. While most cases occurred in Italian patients, four were observed in Africans (three VRF and one recent immigrant), while none had been recorded in this group in the previous 15 years (when the average length of stay in Italy was much shorter). The increasing number of immigrants who have lived for a long time in Italy and occasionally made short visits to their native countries may cause a change in the clinical presentation of imported malaria in this group and a higher percentage of severe cases may be expected. Adult immigrants who travel for VRF after many years might probably be considered as an intermediate group between nonimmune and semi‐immune subjects. The risk of complicated malaria in adults in our series increased with age. These results confirm the findings of a recent TROPNETEUROP study, identifying age as a risk factor for severe P falciparum malaria in nonimmune subjects.12

While the total number of imported malaria decreased over the study period, we observed an increasing number of pediatric cases. National data about pediatric malaria are not available. In France, the country with the highest number of imported malaria cases in Europe, an increasing number of pediatric cases has been reported during the past decade. Until 1989, about two thirds of those cases occurred in African children, while from 1995 to 1997, the number of cases in French children increased to almost half the total number of cases.13

Conversely, all 43 children in our series were African, with no malaria case occurring in Italian children during the study period. It is worth pointing out that under Italian law, children born in Italy to immigrant couples keep their parents’ nationality; the latter group accounts for about half the pediatric cases in our series. These children must be considered as nonimmune (like Italian children), with a potentially high risk of acquiring severe malaria when they travel (for VRF purpose) to malaria‐endemic countries. Our data confirm the presence of two different populations of “immigrant” children: semi‐immune and nonimmune. The clinical, laboratory, and parasitological findings were significantly different in the two groups, confirming that they must be viewed as a high‐risk group of travelers.

No cases were observed in Italian children, probably reflecting adequate preventive care. But the risk of malaria is probably underestimated by immigrants traveling with their children for VRF purposes. With the tendency to stabilize in the country of immigration, we may expect an increasing number of malaria cases and of severe presentations in this group, especially in nonimmune children born in Italy.

Preventive travel advice should be more focused on risk assessment.

Travel clinics should give priority to this neglected high‐risk group, and educational actions should be specially designed for immigrants, focusing on the risk of severe malaria for both children and adults.

Declaration of interests

The authors state that they have no conflicts of interest.


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