Imported Plasmodium vivax Malaria ex Pakistan

Authors

  • Silvia Odolini MD,

    Corresponding author
    1. University Division of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy
    • Corresponding Author: Silvia Odolini, MD, University Division of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, P.le Spedali Civili, 1-25123 Brescia, Italy. E-mail: silvia.odolini@gmail.com

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  • Philippe Gautret MD, PhD,

    1. Assistance Publique Hôpitaux de Marseille, CHU Nord, Pôle Infectieux, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France
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  • Kevin C. Kain MD,

    1. Centre for Travel and Tropical Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Kitty Smith FRCP, PhD,

    1. Brownlee Centre for Infectious & Communicable Diseases, Glasgow, Scotland
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  • Karin Leder MD, PhD,

    1. Victorian Infectious Disease Service, Royal Melbourne Hospital and Department of Epidemiology and Preventive Medicine, Monash University, Clayton, Victoria, Australia
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  • Mogens Jensenius MD, PhD,

    1. Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway
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  • Christina M. Coyle MD, MS,

    1. Division of Infectious Disease, Albert Einstein College of Medicine, Bronx, NY, USA
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  • Francesco Castelli MD, FRCP,

    1. University Division of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy
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  • Alberto Matteelli MD

    1. University Division of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy
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Abstract

Background

According to WHO, 1.5 million cases of malaria are reported annually in Pakistan. Malaria distribution in Pakistan is heterogeneous, and some areas, including Punjab, are considered at low risk for malaria. The aim of this study is to describe the trend of imported malaria cases from Pakistan reported to the international surveillance systems from 2005 to 2012.

Methods

Clinics reporting malaria cases acquired after a stay in Pakistan between January 1, 2005, and December 31, 2012, were identified from the GeoSentinel (http://www.geosentinel.org) and EuroTravNet (http://www.Eurotravnet.eu) networks. Demographic and travel-related information was retrieved from the database and further information such as areas of destination within Pakistan was obtained directly from the reporting sites. Standard linear regression models were used to assess the statistical significance of the time trend.

Results

From January 2005 to December 2012, a total of 63 cases of malaria acquired in Pakistan were retrieved in six countries over three continents. A statistically significant increasing trend in imported Plasmodium vivax malaria cases acquired in Pakistan, particularly for those exposed in Punjab, was observed over time (p = 0.006).

Conclusions

Our observation may herald a variation in malaria incidence in the Punjab province of Pakistan. This is in contrast with the previously described decreasing incidence of malaria in travelers to the Indian subcontinent, and with reports that describe Punjab as a low risk area for malaria. Nevertheless, this event is considered plausible by international organizations. This has potential implications for changes in chemoprophylaxis options and reinforces the need for increased surveillance, also considering the risk of introduction of autochthonous P. vivax malaria in areas where competent vectors are present, such as Europe.

WHO estimates the annual incidence of malaria at 1.5 million cases and categorizes Pakistan in the Group 3 countries of the WHO Eastern Mediterranean Region, which account for 95% of the total regional malaria burden.[1] Malaria distribution in Pakistan is heterogeneous, with high incidence rates in less prosperous districts that have suboptimal heath care service delivery, such as those near the international borders with Afghanistan and the Islamic Republic of Iran.[1] In contrast, other areas including Punjab are considered at low risk for malaria.[2] Plasmodium vivax malaria has been infrequently reported in travelers returning from Pakistan. We describe the trend of imported malaria cases from Pakistan reported to the international surveillance systems from 2005 to 2012.

Methods

Clinics reporting malaria cases acquired after a stay in Pakistan between January 1, 2005, and December 31, 2012, were identified from the GeoSentinel (http://www.geosentinel.org) and EuroTravNet (http://www.Eurotravnet.eu) networks. Demographic and travel-related information was retrieved from the database as described in detail elsewhere,[3] and further information such as areas of destination within Pakistan was obtained directly from the reporting sites.

Data were analyzed with Epi Info 3.5. Standard linear regression models were used to assess the statistical significance of the time trend. Owing to the absence of a true denominator, no incidence rates or risk estimates could be calculated.

Results

From January 2005 to December 2012, a total of 63 cases of malaria acquired in Pakistan were retrieved. Only two cases of Plasmodium falciparum malaria were reported, one in 2008 and the other in 2011, with all the remaining cases being due to P. vivax. The temporal distribution of cases is presented in Figure 1. A statistically significant increasing trend was observed over time (p = 0.006).

Figure 1.

Imported Plasmodium vivax malaria cases from Pakistan by year (n = 63).

A detailed analysis was conducted on 45 P. vivax cases, which were seen at six centers globally, each of which observed three or more individual cases. The sociodemographic and epidemiologic characteristics of the patients are presented in Table 1. The largest number of cases came from Italy (27 cases, 60%). For the 45 cases, the mean age of patients was 29.7 years and 73.4% were male. The majority (80.0%) were born in Pakistan. There were 17 (37.8%) first-time immigrants and 24 (53.3%) travelers visiting friends and relatives (VFRs) in their origin country, whereas only two were business travelers, one was a student, and another was a tourist. Information about specific region of exposure was collected for 48.9% of travelers, 72.7% of whom were exposed in Punjab. No cases of complicated malaria were reported.

Table 1. Demographic characteristics of 51 cases of Plasmodium vivax malaria observed at six clinics in Europe, North America, and Australia over the period 2005–2012
Country of current residenceItaly (Brescia)Canada (Toronto)United Kingdom (Glasgow)United States (Bronx)Australia (Melbourne)Norway (Oslo)Total
  • VFRs = visiting friends and relatives.
  • *Not available for eight patients.
n2764333 45 (%)
Gender (%)
Female7/273/60/30/30/32/312/45 (26.6)
Country of birth (%)
Country of residence2/270/60/30/31/31/34/45 (8.9)
Pakistan25/275/62/33/30/31/336/45 (80.0)
Others0/271/60/30/32/31/34/45 (8.9)
Unknown0/270/271/30/30/30/31/45 (2.2)
Travel reason (%)
VFRs13/274/62/32/31/32/324/45 (53.3)
Immigration (first trip)14/271/60/31/31/30/317/45 (37.8)
Business0/270/60/30/31/31/32/45 (4.4)
Tourism0/271/60/30/30/30/31/45 (2.2)
Student0/270/61/30/30/30/31/45 (2.2)
Pretravel advice (excluding those traveling for immigration)
Do not know3/132/53/30/20/22/310/28 (35.7)
No10/133/50/32/21/21/317/28 (60.7)
Yes0/130/50/30/21/20/31/28 (3.6)
Age (years)       
Mean23.938.522.561.54430.329.7
Region of exposure in Pakistan
Punjab12/271/61/30/30/32/316/45 (35.5)
Others2/272/60/30/32/30/3 6/45 (13.3)
Unknown13/273/62/33/31/31/323/45 (51.1)
Mean time lag from return and onset of symptoms *(dd)162188.624.559.6781.3402282
Chemoprophylaxis (excluding those traveling for immigration)
Yes0/130/50/30/20/20/30/28 (0.0)
No13/134/50/32/20/23/322/28 (78.6)
Unknown0/131/53/30/22/20/36/28 (21.46)

Twenty-one cases (46.7%) were diagnosed in the months of September–October and 19 (42.2%) in July–August. Only one case was reported in June (3.7%). The average incubation period was 282 days, with a maximum of 41,123 days and a minimum of 1 day. None of the cases with information available had taken chemoprophylaxis (Table 1).

Discussion

We report a significant rise in P. vivax malaria cases imported from Pakistan to six countries over three continents. Almost 40% of the cases were observed in immigrants, and half of the cases in Pakistani people VFRs in their home country: tourists, businessmen, and other traveler categories were not affected. This observation confirms reports from Europe, where the overall proportion of P. vivax malaria cases reported in travelers seen at EuroTravet sites doubled from 0.5% to 1% from 2008 to 2010, respectively, with most cases in individuals returning from the Indian subcontinent (ISC)[4] and from Germany, where P. vivax malaria imported from Pakistan peaked at 32 cases in 2012 from a yearly average of 8 in previous years.[5] Similarly, in the UK, despite a 5% decrease in imported malaria infections overall reported in 2011 compared with that in 2010, an increasing number of cases from the Indian subcontinent was observed in 2011, particularly due to the doubling of cases of P. vivax malaria acquired in Pakistan.[6]

The observed increase in malaria cases may be partly attributable to an increase in the number of immigrants from Pakistan to Italy, which was observed in the period 2008–2011, but the high proportion of malaria cases acquired in Punjab was unexpected. According to national reports, Punjab maintains a very low annual parasite incidence of <1 case/10,000 populations/year.[2] Reportedly, large-scale ecological changes in this province, related to water logging and salinization, are likely to result in a low density of Pakistan's primary vector A. culicifacies.[7] However, Pakistan has a high vulnerability to climate change due to its geographic location, high dependence on agriculture and water resources, and a weak system of emergency preparedness.[8] The recent flooding in Pakistan has been associated with a large increase in malaria incidence.[8] Probably, a combination of climate change, poor vector control, and inadequate health care can justify the increased numbers of malaria cases. Punjab region is known to be one of the most deprived regions in Pakistan in terms of socioeconomic indicators, and as reported by Malik and colleagues, this should sensitize the government to direct its efforts to the socioeconomic uplift of these lagging regions in order to reduce their vulnerability to the adverse effects of climate change.[8] Therefore, our observation may herald a variation in malaria incidence in the Punjab province of Pakistan, an event that is considered plausible by international organizations.[9]

We observed a clear seasonality of P. vivax malaria cases among travelers from Pakistan, with the majority of the cases being diagnosed from July to October. This may be due to travel patterns, but it is also consistent with local epidemiology, as P. vivax prevalence in Pakistan is 60% higher in July–August than in January–June, probably due to the monsoon period and the more intense transmission period for mosquitoes following the floods.[10]

Only two cases of P. falciparum malaria in patients coming from Pakistan were recorded over the reporting period. This is compatible with WHO information that the majority of malaria cases in Pakistan are due to P. vivax,[9] but contrasts with the information from the US Centers for Disease Control and Prevention (CDC), which describes the higher prevalence of P. falciparum malaria (70%) than that of P. vivax (30%) in Pakistan.[11]

In a malariometric population survey conducted in 2011 using blood samples collected from 801 febrile patients of all ages in four provinces and in the capital city of Islamabad, 707 samples were PCR positive, of which 128 (18%) were P. falciparum, 536 (76%) were P. vivax, and 43 (6%) were mixed P. falciparum and P. vivax. No cases of Plasmodium malariae and Plasmodium ovale have been reported. Prevalence of P. vivax ranged from 2.4% in Punjab Province to 10.8% in Sindh Province, and prevalence of P. falciparum ranged from 0.1% in Islamabad to 3.8% in Balochistan. This survey confirmed the predominance of P. vivax in most Pakistan regions and the lower prevalence of malaria in Punjab.[12]

The implication of a rising P. vivax malaria trend from Pakistan for travel medicine clinicians is uncertain, although reports are progressively indicating that P. vivax malaria can be severe[13] and drug resistance might soon become an issue.[14] The relevance for preventive interventions in travelers is also uncertain. The observed decreasing incidence of malaria in travelers to the ISC (India, Pakistan, Bangladesh, and Sri Lanka) has recently prompted a change in guidelines in some European countries advocating the use of standby emergency self-treatment strategies, bite precautions plus awareness of risks instead of chemoprophylaxis.[15] Regional variations in malaria risk are considered irrelevant, given the low numbers of cases from the continent as a whole.[16] Rising malaria risk in travelers due to P. vivax malaria may not change this attitude, as currently available chemoprophylaxis options do not prevent disease from relapsing parasites, but surveillance should nevertheless be strengthened to ensure that P. falciparum malaria does not increase as well.

Conclusions

A statistically significant increase in P. vivax malaria cases imported from Pakistan is reported, particularly in those coming from Punjab. This reinforces the need for attentive surveillance procedures.

Finally, the rise in imported cases of P. vivax malaria should be regarded as a potential hazard for the introduction of autochthonous P. vivax malaria in areas where competent vectors are present, such as Europe,[17] as was recently witnessed in Greece, in link with Pakistani migrants.[18]

Acknowledgments

The authors thank David Freedman and Philippe Parola for their assistance in identifying patients from the GeoSentinel and EuroTravNet databases.

Declaration of Interests

The authors state that they have no conflicts of interest.

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