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Published Date: 2011-10-22 12:47:00
Subject: PRO/EDR> Malaria, P. vivax - Greece (06): autochthonous
Archive Number: 20111022.3145

MALARIA, P. VIVAX - GREECE (06): AUTOCHTHONOUS
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Date: Thu 20 Oct 2011
Source: Eurosurveillance edition 2011; 16(42) [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19993

Autochthonous _Plasmodium vivax_ malaria in Greece, 2011
--------------------------------------------------------
[Authors: Danis K, Baka A, Lenglet A, et al.]

Between May and September 2011, 20 cases of _Plasmodium vivax_
infection were reported in Greek citizens without reported travel
history. The vast majority of those cases were confined to a delimited
agricultural area of Evrotas, Lakonia. Conditions favouring locally
acquired transmission of malaria, including the presence of competent
vectors and migrants from endemic countries exist in Greece,
underscoring the need for the development of an integrated
preparedness and response plan for malaria prevention.

In 2011, 20 malaria cases without reported travel history to endemic
countries have been notified as of 27 Sep 2011 from Evrotas, Lakonia
and other geographical areas in Greece. We conducted an investigation
to describe the geographical and temporal distribution of those cases,
determine the affected area(s) and identify the potential source of
infection, in order to better understand the transmission dynamics and
implement targeted control measures.

Malaria was officially eliminated from Greece in 1974, following an
intense national malaria eradication programme that was implemented
between 1946 and 1960 [1]. Between 1975 and 2005 approximately 50
cases of malaria were reported annually, the vast majority of whom
were imported cases from countries endemic for malaria. However,
sporadic cases of mosquito-transmitted malaria that could have been
acquired locally were reported in 1991, 1999, and 2000 [2].

Between 2005 and 2009, 171 cases of malaria were reported in Greece
with a mean number of 34 cases per year [3]. Of those, 98 per cent
were in people that likely acquired the infection in endemic countries
and 78 per cent of all cases were in migrants from those countries.

Between early August and October 2009, a cluster of 8 malaria cases
was notified to the Hellenic Centre for Disease Control and Prevention
(HCDCP) from the Evrotas area of Lakonia district, which is located in
the Peloponnese in southern Greece.

The 1st 2 cases were in migrant workers from Pakistan and Afghanistan
who reportedly arrived in Greece during the summer of 2009 and who
were working in the agricultural holdings in this particular area. 4
of the remaining 6 cases belonged to the local Roma community and the
other 2 were Greek citizens residing in the area. None of those 6
cases reported travel history to a malaria endemic country.

In 2010, another malaria case was notified from the same area in
Evrotas, who also belonged to the local Roma community. Additionally,
2 Roma children with malaria were notified in Viotia with disease
onset on 25 and 30 Aug 2010 and an unclear travel history.

Surveillance of malaria in Greece
---------------------------------
As part of the mandatory notification system, physicians in Greece are
asked to notify HCDCP of all cases of laboratory-confirmed malaria
infection.

Enhanced surveillance is implemented in areas where domestic
transmission is suspected (that is, where no clear recent travel
history to a malaria-endemic country can be established), by tracing
the reported cases, visiting their homes, and if possible conducting
face-to-face interviews. When this is not possible, telephone
interviews are conducted. Translators are used where appropriate. The
case investigation form for enhanced surveillance gathers information
on: detailed travel history, potential modes of transmission, clinical
manifestations and treatment, previous malaria clinical episodes,
possible onward transmission, and household characteristics.

In addition, active surveillance is implemented by maintaining weekly
communication with local laboratories to enquire about recent
diagnosed cases of malaria. Residents in the neighbourhoods
surrounding the homes of suspected locally-acquired cases are asked to
report febrile illnesses to the local public health office and to seek
health care promptly.

Laboratory investigation
------------------------
Light microscopic examination of Giemsa stained thick and thin blood
smears is used to identify malaria parasites in local laboratories.
Blood smears are routinely analysed when general blood count tests
identify anaemia, thrombocytopenia, or other abnormal findings.

All blood specimens positive for malaria and a number of negative ones
are forwarded to the National Malaria Reference Laboratory (MRL) at
the National School of Public Health in Athens to be validated with
both microscopy and polymerase chain reaction (PCR). Rapid diagnostic
antigen tests are not routinely used. 20 per cent of positive samples
are being genotyped at present.

Entomological investigation
---------------------------
Following the 2010 large outbreak of West Nile Virus infection in
Greece [4], a study on vector distribution and mapping of risk areas
was carried out. The adult mosquito population is monitored using CO2
or CO2-light traps at permanent sampling stations that are collected
every 14 days. Several additional traps were used at locations of
suspected malaria transmission in order to detect _Anopheles_
mosquitoes. Collected specimens were counted and morphologically
identified.

Situation in 2011
-----------------
Epidemiological and clinical findings
-------------------------------------
Up to 27 Sep 2011, the HCDCP has received reports of 20 cases of _P.
vivax_ infection in Greek citizens who did not report travel to an
endemic country. The majority of those cases (n=14) reside in the
agricultural area of Evrotas, Lakonia district (Table, Figure 1 [all
tables and figures are available at the source URL above]). The
remaining 6 Greek cases were reported from 4 other prefectures, namely
Eastern Attiki (n=2), Evia (n=2), Viotia (n=1), and Larissa (n=1).

>From the area of Evrotas were further reported 16 cases of _P. vivax_
infection in migrant workers from endemic countries (mainly from
Pakistan) for whom no clear malaria importation status can be
determined. In addition, 2 Romanian workers who had been working and
living in the area of Evrotas developed symptoms in July 2011 and were
diagnosed with _P. vivax_ infection upon their return to Romania [5].

These 2 cases are not included in further analysis because not all the
epidemiological information is available. All 36 cases have been
confirmed as _P. vivax_ infections, by both microscopy and PCR at the
MRL.

None of the cases had a history of recent blood transfusion or
tissue/organ transplantation. (table 1 and figure 1: see URL above).
The 1st case from Evrotas reported disease onset on 23 May 2011
(figure 2: see URL above).

An increasing number of cases residing in Evrotas area was observed
during September (weeks 35-37). At the time of publication of this
report, the outbreak is still ongoing. (Figure 2) Reported cases of
malaria by week of symptom onset and region of residence, Greece,
May-September 2011 (n=36)

The age distribution of the 36 reported cases ranged from 1.5-79 years
(median: 36 years). The median age of migrant cases (24 years; range
15-55 years) was significantly lower (p less than 0.001) than of Greek
cases (47 years; range 1.5-79 years), possibly reflecting the
different age distributions of the 2 population groups. 7 of the Greek
cases were female. As the majority of the migrant worker community is
male, women with _P. vivax_ infection were not reported among
migrants.

Fever was reported as the main symptom by all cases, followed by
splenomegaly (n=14) and anaemia (n=14). 3 cases had central nervous
symptom manifestations. All cases were hospitalised; one was admitted
to an intensive care unit and has recovered fully.

To date, there has been one fatality in an elderly male case from
Evrotas area who had several underlying medical conditions, including
cardiac insufficiency, arrhythmias, and chronic obstructive pulmonary
disease, and developed acute respiratory distress syndrome. This is
the 1st death associated with _P. vivax_ infection in the last 3 years
in Greece. All other cases have fully recovered.

Almost all cases but 3 who were prescribed mefloquine and primaquine,
received the current treatment regimen for uncomplicated _P. vivax_
infection according to the national guidelines [6], which is 3-day
chloroquine treatment followed by 14-day primaquine treatment. Some
cases in Lakonia received the alternative weekly primaquine outpatient
regimen (higher dose than the daily regimen) for 8 weeks, to achieve a
higher compliance rate. Only one case among the reported 36 cases had
glucose-6-phosphate dehydrogenase deficiency and did not receive
primaquine.

When comparing the date of onset of symptoms to the date of
hospitalisation (which is a proxy for receipt of anti-malaria
treatment in Greece), the time period for all cases ranged between 0
and 27 days (median: 4 days). The median delay between symptom onset
and treatment was shorter in the group of migrant workers (3 days;
range 0-19 days) compared to Greek patients (4 days; range 2-27 days).
However, this difference was not statistically significant (p=0.12).

Entomological findings
----------------------
Fifteen _Anopheles_ species occur in Greece, 5 of which are considered
as potential malaria vectors, namely _An. claviger_, _An. hyrcanus_,
_An. maculipennis_, _An. sacharovi_, and _An. superpictus_ [7-9]. In
the Evrotas area, _Anopheles_ larvae were found in rivers, reed beds,
the Vivari lake, and draining channels, but at very low densities.

>From 1 Jun to 15 Sep 2011, 23 adult _Anopheles_ specimens were
collected from 2 sampling stations in the area, most of them _An.
sacharovi_ (n=21). 2 specimens which were determined as _An. plumbeus_
need further confirmation as they were not intact.

In the wetland area of Schinias national park in, Eastern Attiki, 19
mosquito species were identified, with _An. claviger_ being the
dominant _Anopheles_ species in the area [9]. Other _Anopheles_
species that were collected in that area included: _An. algeriensis_,
_An. maculipennis s.s._, _An. pseudopictus_, and _An. sacharovi_.

In the remaining affected areas in Greece, _Anopheles_ species were
identified, but their reported densities were often low. The most
commonly identified species there were _An. sacharovi_ and _An.
claviger_.

Discussion
----------
As of 27 Sep 2011, 20 malaria cases were reported in Greece, affecting
Greek citizens who did not have any reported history of travel to a
country endemic for malaria.

The vast majority of those cases were confined to a delimited
geographical area in Evrotas, Lakonia, where a small number of malaria
cases had already occurred in the previous 2 years. All other areas
that reported cases were previously unaffected.

In addition, 16 cases in migrant farm workers with unclear malaria
importation status were notified in Evrotas. As none of these workers
were documented, it is difficult to ascertain when they first arrived
in Greece, where they travelled and worked and how long they had been
residing in the area.

Therefore, based on their self-reported travel, medical history, and
possibility of relapses, it cannot be determined conclusively whether
they were non-imported cases.

The affected area in Lakonia district is a plain agricultural area of
about 20 sq km [7.7 sq mi] in the delta of the Evrotas river. It was
one of the historical hot spots of malaria transmission before
elimination of the disease in Greece [10].

The area is characterised by freshwater springs, a complex network of
130 km [81 mi] of irrigation and drainage channels, the Evrotas river
delta, the brackish Vivari lake, which seasonally dries out, and
coastal wetlands.

All other affected sites are located in agricultural areas, often
closely associated with river deltas or wetland areas, providing
favourable conditions for the presence and reproduction of potential
malaria mosquito vectors. None of those areas are tourist
destinations.

The affected area of Evrotas has a population of 4485 and a large
community of migrant farm workers (estimated between 2000-4000
depending on the period of the year), most of whom are not registered
[11].

About 80 per cent of all migrant workers in the area come from
Pakistan, around 15 per cent from Romania, and the remaining from
Morocco. The other affected areas have high numbers of migrant
agricultural workers from malaria-endemic countries, predominantly
from the Indian subcontinent.

Following the reports of malaria in Greece, the following control
measures were introduced. Guidelines for the recognition, management,
and diagnosis of malaria were provided to healthcare professionals to
improve their awareness of the disease. Interviewed patients were
informed that people in their close environment presenting with fever
should get diagnosed as soon as possible.

Support was provided to strengthen the laboratory capacity of local
health centres in the affected areas to diagnose malaria. Surveillance
of mosquitoes was enhanced in the affected areas. Guidance for blood
and blood product safety according to European Union directives was
implemented, including deferral from blood donation for a period of 6
months of persons residing or working in the affected areas within a
radius of 10 km [6 mi].

Communication and health promotion activities were strengthened
encouraging personal protection against mosquito bites in the general
population. Intensified vector control activities were implemented
using larviciding in breeding sites, ultra-low volume spraying in the
affected villages, and outdoor residual spraying in a zone of 50
metres [55 yards] around the houses of the cases, including backyards,
neighbouring stockyards, and other installations favourable for the
resting of _Anopheles_ adults.

Furthermore, all households in the area have been visited fortnightly
since 30 Sep 2011 to detect people with fever and to ensure early
detection and prompt treatment of all malaria cases. During those
visits, multidisciplinary health teams screened blood smears from all
persons with fever of 37.5 deg C [99.5 deg F] or higher, current or
reported during the previous 15 days.

Since the malaria eradication in 1974 in Greece, sporadic cases of
probable local mosquitoborne transmission have occurred. Because of
its climate, proximity of human and mosquito populations, and the
increased number of migrants from malaria-endemic countries, Greece
and possibly other Mediterranean countries might be vulnerable to the
re-establishment of endemic malaria [12,13].

However, provided that current healthcare, mosquito control, and
public health infrastructures remain intact in Greece, the
re-establishment of endemic areas for malaria remains unlikely.

Nevertheless, conditions may exist for small clusters of locally
acquired mosquitoborne transmission to occur sporadically. The
development of an integrated preparedness and response plan for
malaria that covers all aspects from surveillance, clinical
management, laboratory diagnosis, entomological surveillance, vector
control, and communication is necessary to prevent transmission and
control the disease on the long term. Such a plan should not only
address the most affected area of Evrotas, Lakonia, but also other
parts of Greece where ecological parameters are favourable for malaria
transmission.

Acknowledgements
----------------
We would like to thank all hospital physicians and local public health
authorities who contributed to the surveillance of malaria infections
in Greece; the internists and microbiologists at the General Hospital
of Sparti; the personnel of the National Malaria Reference Laboratory
for technical support. We would like to thank Katrin Leitmeyer, Lara
Payne, and Herve Zeller at the European Centre for Disease Prevention
and Control for their continued support during this event.

References
----------
1. World Health Organization (WHO). Malaria elimination: a field
manual for low and moderate endemic countries. Geneva: WHO; 2007.
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2. Kampen H, Proft J, Etti S, et al. Individual cases of autochthonous
malaria in Evros Province, northern Greece: entomological aspects.
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3. Hellenic Centre for Disease Control and Prevention (HCDCP),
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4. Danis K, Papa A, Theocharopoulos G, et al. Outbreak of West Nile
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5. Florescu SA, Popescu CP, Calistru P, et al. _Plasmodium vivax_
malaria in a Romanian traveller returning from Greece, August 2011.
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7. Darsie RF Jr, Samanidou-Voyadjoglou A. Keys for the identification
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usual residence. Pireus: EL. STAT. [Accessed 26 Sep 2011]. Available
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12. Sabatinelli G, Ejov M, Joergensen P. Malaria in the WHO European
Region (1971-1999) . Euro Surveill. 2001; 6(4): pii=213. Available
from http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=213
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pii=19684. Available from
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[The paper in a thorough review of the outbreak of _P. vivax_ malaria
in Greece in 2011. 20 Greek citizens and 16 immigrants from Pakistan,
Morocco, and Romania were diagnosed with _P. vivax_ infestation.

An increasing number of cases residing in Evrotas area was observed
during September (weeks 35-37), and the report concludes that "At the
time of publication of this report, the outbreak is still ongoing."

In our earlier comment to the outbreak we speculated that the only
explanation for the cases was migrant labor from _P. vivax_ endemic
countries, and the information provided in the report that
"approximately 80 per cent of all migrant workers in the area come
from Pakistan‚" strongly supports that the vivax was indeed
introduced by carriers from the Indian subcontinent.

The Greek authorities has implemented active case detection in the
affected areas as well as mosquito control with using larviciding in
breeding sites, ultra-low volume spraying in the affected villages,
and outdoor residual spraying.

Malaria prophylaxis is in our view not needed for visitors to Greece.
- Mod.EP

A HealthMap/ProMED-mail interactive map of Greece can be seen at
http://healthmap.org/r/1mfV. - Sr.Tech.Ed.MJ]

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