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1.  Imported malaria and high risk groups: observational study using UK surveillance data 1987-2006 
BMJ : British Medical Journal  2008;337(7661):103-106.
Objective To examine temporal, geographic, and sociodemographic trends in case reporting and case fatality of malaria in the United Kingdom.
Setting National malaria reference laboratory surveillance data in the UK.
Design Observational study using prospectively gathered surveillance data and data on destinations from the international passenger survey.
Participants 39 300 cases of proved malaria in the UK between 1987 and 2006.
Main outcome measures Plasmodium species; sociodemographic details (including age, sex, and country of birth and residence); mortality; destination, duration, and purpose of international travel; and use of chemoprophylaxis.
Results Reported cases of imported malaria increased significantly over the 20 years of the study; an increasing proportion was attributable to Plasmodium falciparum (P falciparum/P vivax reporting ratio 1.3:1 in 1987-91 and 5.4:1 in 2002-6). P vivax reports declined from 3954 in 1987-91 to 1244 in 2002-6. Case fatality of reported P falciparum malaria did not change over this period (7.4 deaths per 1000 reported cases). Travellers visiting friends and relatives, usually in a country in Africa or Asia from which members of their family migrated, accounted for 13 215/20 488 (64.5%) of all malaria reported, and reports were geographically concentrated in areas where migrants from Africa and South Asia to the UK have settled. People travelling for this purpose were at significantly higher risk of malaria than other travellers and were less likely to report the use of any chemoprophylaxis (odds ratio of reported chemoprophylaxis use 0.23, 95% confidence interval 0.21 to 0.25).
Conclusions Despite the availability of highly effective preventive measures, the preventable burden from falciparum malaria has steadily increased in the UK while vivax malaria has decreased. Provision of targeted and appropriately delivered preventive messages and services for travellers from migrant families visiting friends and relatives should be a priority.
doi:10.1136/bmj.a120
PMCID: PMC2453297  PMID: 18599471
2.  Risk of malaria in British residents returning from malarious areas. 
BMJ : British Medical Journal  1990;300(6723):499-503.
OBJECTIVES--To identify which British residents travelling abroad are at greatest risk of malaria infection, and to determine the efficacy of malaria chemoprophylaxis for preventing P falciparum infections in tropical Africa. DESIGN--Prospective cohort study (case-base linkage) with routine national surveillance systems. Denominators (base population) were obtained from monitoring a random sample of returning British travellers with the international passenger survey. Numerators (cases) were obtained from reports of malaria infections in British residents, through the Malaria Reference Laboratory network. SETTING--International passenger survey conducted at passport control of international airports in Britain. Malaria reports received nationally were collated centrally in London. SUBJECTS--2948 British residents (0.2%) returning to Britain in 1987 randomly selected and questioned and 1052 British residents with microscopically confirmed malaria infections in 1987, whose case reports were reviewed and on whom additional data were collected by postal survey. MAIN OUTCOME MEASURES--Annual incidence subdivided by categories of risk. Chemoprophylactic efficacy for east and west Africa by principal regimens and compliance. RESULTS--Annual rates of reported infection per 100,000 travellers to Oceania were 4100; to west and east Africa were 375 and 172 respectively; to Latin America, the Far East, and the Middle East were 12, 2, and 1 respectively. Immigrants visiting friends and relatives in Ghana and Nigeria were at greatest risk (1303 and 952 per 100,000 respectively) in west Africa. Business travellers to Kenya experienced the highest attack rates in east Africa (465 per 100,000). Age-sex specific attack rates varied by region. No prophylaxis was reported to have been used by 23% of British visitors to west Africa, 17% to east Africa, 46% to central or southern Africa, and 58% visiting south Asia. The efficacy of chloroquine plus proguanil against P falciparum infection was 73% and 54% in west and east Africa respectively. Lower values were obtained for chloroquine alone and proguanil alone. The efficacy of Maloprim (pyrimethamine-dapsone) was 61% in west Africa, but only 9% in east Africa. Visitors to west Africa who did not comply with their chemoprophylactic regimen were at a 2.5-fold higher risk of infection than fully compliant users. Non-compliant visitors to east Africa had similar rates of infection as non-drug users. CONCLUSIONS--In 1987 chloroquine plus proguanil was the preferred chemoprophylactic regimen for P falciparum infection in Africa; antimalarial drugs must be taken regularly to be effective.
PMCID: PMC1662322  PMID: 2107927
3.  Declining incidence of malaria imported into the UK from West Africa 
Malaria Journal  2008;7:235.
Background
Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006.
Methods and Results
Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p < 0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually.
Discussion
The reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and/or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa.
Conclusion
With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in chemoprophylaxis policy for UK travelers over the next 5–10 years.
doi:10.1186/1475-2875-7-235
PMCID: PMC2613412  PMID: 19000299
4.  Validation of malaria surveillance case reports: implications for studies of malaria risk. 
STUDY OBJECTIVE--The aim of the study was to investigate the quality of national malaria surveillance reports in the United Kingdom. DESIGN--Persons with malaria reported to the Malaria Reference Laboratory (MRL) in 1987 were contacted by post to verify existing records with respect to key variables. The MRL data set was then analysed for inaccuracies. SETTING--The study was confined to UK residents. PARTICIPANTS--602 persons with malaria in 1987 responded (53%). MEASUREMENTS AND MAIN RESULTS--Review of case reports showed few missing data except for duration of residence in the UK, detailed chemoprophylactic regimens, and compliance. There were more missing surveillance data in reports of ethnic minority groups, principally in dates of travel (p = 0.008) and chemoprophylaxis use (p less than 0.0001). Patient recall in the survey was at variance with the surveillance reports in dates of travel and onset of infection, chemoprophylaxis use, and in compliance. Surveillance reports overestimated the number of days between leaving a malarious area and onset of symptoms (by 9 d for P falciparum and by 24 d for P vivax), and underestimated the delay between onset and diagnosis of P falciparum by 3 d. Over 50% of patients who had recalled the use of chloroquine, proguanil, pyrimethamine/dapsone, and pyrimethamine had not been recorded as having taken these drugs on the surveillance reports. Reported compliance also differed between the two data sets. CONCLUSIONS--It is recommended that research units test the quality of their surveillance data before embarking on analytical studies used to generate health policy guidelines.
PMCID: PMC1060626  PMID: 2370506
5.  Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: an observational study 
Objectives To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers.
Design Observational study based on 20 years of UK national data.
Setting National register of malaria cases.
Participants 25 054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006.
Main outcome measures Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used.
Results Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18–35 year olds. There were no deaths in the ≤5 year age group. Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001). Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the Gambia. There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R2=0.72, P<0.001). Most delay in fatal cases was in seeking care.
Conclusions Most travellers acquiring malaria are of African heritage visiting friends and relatives. In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen. Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice.
doi:10.1136/bmj.e2116
PMCID: PMC3314185  PMID: 22454091
6.  The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator? 
Malaria Journal  2010;9:266.
Background
The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers.
Methods
Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries.
Results
In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years.
Conclusion
The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.
doi:10.1186/1475-2875-9-266
PMCID: PMC2959067  PMID: 20920352
7.  Declining incidence of imported malaria in the Netherlands, 2000-2007 
Malaria Journal  2010;9:300.
Background
To describe the epidemiology and trends of imported malaria in the Netherlands from 2000 through 2007.
Methods
Based on national surveillance data regarding all reported infections of imported malaria, diagnosed 2000 through 2007, incidence and trends of imported malaria in the Netherlands were estimated. Travellers statistics were used to estimate incidence, and data on malaria chemoprophylaxis prescriptions were used to estimate the number of unprotected travellers.
Results
Importation of malaria to the Netherlands is declining even as more travellers visit malaria-endemic countries. On average, 82% were acquired in sub-Saharan Africa, and 75% were caused by Plasmodium falciparum. The overall incidence in imported falciparum malaria fell from 21.5 to 6.6/10,000 of unprotected travellers. The percentage of unprotected travellers rose from 47% to 52% of all travellers. The incidence of imported falciparum infections is greatest from Middle and West Africa, and decreased from 121.3 to 36.5/10,000 travellers. The import of malaria from this region by immigrants visiting friends and relatives (VFR) decreased from 138 infections in 2000, to 69 infections in 2007.
Conclusion
The annual number of imported malaria shows a continuing declining trend, even with an increasing number of travellers visiting malaria endemic countries. VFR import less malaria than previously, and contribute largely to the declining incidence seen. The decline is not readily explained by increased use of chemoprophylaxis and may reflect a reduced risk of infection due to decreasing local malaria transmission as observed in some malaria endemic areas. Nevertheless, the increasing number of unprotected travellers remains worrisome.
doi:10.1186/1475-2875-9-300
PMCID: PMC2988037  PMID: 21029424
8.  Epidemiology and clinical features of vivax malaria imported to Europe: Sentinel surveillance data from TropNetEurop 
Malaria Journal  2004;3:5.
Background
Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999.
Objectives
To present epidemiological and clinical data on imported P. vivax malaria collected at European level.
Material and methods
Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries.
Results
Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41–158) versus 31 days (inter-quartile range 4–133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries.
Conclusions
TropNetEurop data can contribute to the harmonization of European treatment policies.
doi:10.1186/1475-2875-3-5
PMCID: PMC385246  PMID: 15003128
9.  The spatial and temporal patterns of falciparum and vivax malaria in Perú: 1994–2006 
Malaria Journal  2009;8:142.
Background
Malaria is the direct cause of approximately one million deaths worldwide each year, though it is both preventable and curable. Increasing the understanding of the transmission dynamics of falciparum and vivax malaria and their relationship could suggest improvements for malaria control efforts. Here the weekly number of malaria cases due to Plasmodium falciparum (1994–2006) and Plasmodium vivax (1999–2006) in Perú at different spatial scales in conjunction with associated demographic, geographic and climatological data are analysed.
Methods
Malaria periodicity patterns were analysed through wavelet spectral analysis, studied patterns of persistence as a function of community size and assessed spatial heterogeneity via the Lorenz curve and the summary Gini index.
Results
Wavelet time series analyses identified annual cycles in the incidence of both malaria species as the dominant pattern. However, significant spatial heterogeneity was observed across jungle, mountain and coastal regions with slightly higher levels of spatial heterogeneity for P. vivax than P. falciparum. While the incidence of P. falciparum has been declining in recent years across geographic regions, P. vivax incidence has remained relatively steady in jungle and mountain regions with a slight decline in coastal regions. Factors that may be contributing to this decline are discussed. The time series of both malaria species were significantly synchronized in coastal (ρ = 0.9, P < 0.0001) and jungle regions (ρ = 0.76, P < 0.0001) but not in mountain regions. Community size was significantly associated with malaria persistence due to both species in jungle regions, but not in coastal and mountain regions.
Conclusion
Overall, findings highlight the importance of highly refined spatial and temporal data on malaria incidence together with demographic and geographic information in improving the understanding of malaria persistence patterns associated with multiple malaria species in human populations, impact of interventions, detection of heterogeneity and generation of hypotheses.
doi:10.1186/1475-2875-8-142
PMCID: PMC2714521  PMID: 19558695
10.  Chemoprophylaxis and Malaria Death Rates 
Emerging Infectious Diseases  2006;12(3):447-451.
Malaria chemoprophylaxis increases the survival of nonimmune travelers.
To determine the effect of chemoprophylaxis on the case-fatality rate of malaria, we analyzed all cases of Plasmodium falciparum malaria in nonimmune persons reported from 1993 to 2004 in Germany. In univariate and multivariate logistic regression analysis, we determined the effect of age, sex, chemoprophylaxis, chemoprophylactic regimen, compliance for chemoprophylactic regimen, exposure prophylaxis, country of infection, and year of reporting on the outcome. Of 3,935 case-patients, 116 (3%) died of malaria. Univariate analysis showed significant associations with death for chemoprophylaxis with chloroquine plus proguanil compared to no chemoprophylaxis. The multivariate model showed that patients who had taken chemoprophylaxis were less likely to die compared to those who had not taken chemoprophylaxis, adjusted for patient age and reporting year. The study demonstrated that chemoprophylaxis significantly reduced fatality rates among nonimmune malaria patients and supports the importance of existing guidelines for malaria prevention.
doi:10.3201/eid1203.050736
PMCID: PMC3291437  PMID: 16704783
malaria; chemoprophylaxis; CFR; chloroquine; plasmodium falciparum; research
11.  Temporal trends in severe malaria in Chittagong, Bangladesh 
Malaria Journal  2012;11:323.
Background
Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division.
Methods
Malaria screening data from 22,785 inpatients in CMCH from 1999–2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh.
Results
From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008–2011, remaining steady during this period.
A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border.
Conclusions
The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.
doi:10.1186/1475-2875-11-323
PMCID: PMC3544696  PMID: 22970881
Malaria; Bangladesh; Epidemiology; Incidence; Severe; Falciparum; Vivax
12.  Patterns of Plasmodium vivax and Plasmodium falciparum malaria underscore importance of data collection from private health care facilities in India 
Malaria Journal  2009;8:227.
Background
This study describes patterns of falciparum and vivax malaria in a private comprehensive-care, multi-specialty hospital in New Delhi from July 2006 to July 2008.
Methods
Malarial morbidity by Plasmodium species (Plasmodium falciparum, Plasmodium vivax, or Plasmodium sp.) was confirmed using microscopy and antigen tests. The influence of seasonal factors and selected patient demographics on morbidity was evaluated. The proportions of malaria cases caused by P. falciparum at the private facility were compared to data from India's National Vector Borne Disease Control Programme (NVBDCP) during the same period for the Delhi region.
Results
In New Delhi, P. faciparum was the dominant cause of cases requiring treatment in the private hospital during the period examined. The national data reported a smaller proportion of malaria cases caused by P. falciparum in the national capital region than was observed in a private facility within the region. Plasmodium vivax also caused a large proportion of the cases presenting clinically at the private hospital during the summer and monsoon seasons.
Conclusion
The proportion of P. falciparum malaria cases tends to be greatest during the post-monsoon season while the proportion of P. vivax malaria cases tends to be greatest in the monsoon season. Private hospital data demonstrate an under-reporting of malaria case incidences in the data from India's national surveillance programme during the same period for the national capital region.
doi:10.1186/1475-2875-8-227
PMCID: PMC2766385  PMID: 19822005
13.  Malaria in the United Kingdom 
British Medical Journal  1974;2(5921):707-711.
Over the past decade the United Kingdom had the second highest number of cases of imported malaria among European countries. There has been a substantial rise in recorded cases of malaria during the past three years though some of it may be due to improved notification. Fatal cases of malaria in visitors to Africa have averaged 6.5% of reported infections due to Plasmodium falciparum. Attacks of vivax malaria may occur several months after travellers return from a malarious country.
PMCID: PMC1611114  PMID: 4604717
14.  Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil 
Malaria Journal  2012;11:245.
Background
Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions.
Methods
An observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence.
Results
Twenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses.
Conclusions
A known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines.
doi:10.1186/1475-2875-11-245
PMCID: PMC3416703  PMID: 22839416
Plasmodium vivax malaria; Relapse; Therapeutic failure; Weight-based dosing
15.  Characteristics and Spectrum of Disease Among Ill Returned Travelers from Pre- and Post-Earthquake Haiti: The GeoSentinel Experience 
To describe patient characteristics and disease spectrum among foreign visitors to Haiti before and after the 2010 earthquake, we used GeoSentinel Global Surveillance Network data and compared 1 year post-earthquake versus 3 years pre-earthquake. Post-earthquake travelers were younger, predominantly from the United States, more frequently international assistance workers, and more often medically counseled before their trip than pre-earthquake travelers. Work-related stress and upper respiratory tract infections were more frequent post-earthquake; acute diarrhea, dengue, and Plasmodium falciparum malaria were important contributors of morbidity both pre- and post-earthquake. These data highlight the importance of providing destination- and disaster-specific pre-travel counseling and post-travel evaluation and medical management to persons traveling to or returning from a disaster location, and evaluations should include attention to the psychological wellbeing of these travelers. For travel to Haiti, focus should be on mosquito-borne illnesses (dengue and P. falciparum malaria) and travelers' diarrhea.
doi:10.4269/ajtmh.2012.11-0430
PMCID: PMC3247103  PMID: 22232445
16.  Epidemiological and Clinical Features of Plasmodium falciparum Malaria in United Nations Personnel in Western Bahr el Ghazal State, South Sudan 
PLoS ONE  2013;8(1):e55220.
Western Bahr el Ghazal State is located in northwestern South Sudan, which is a tropical area subject to Plasmodium falciparum malaria epidemics. The aim of this study is to explore the epidemiological and clinical features of Plasmodium falciparum malaria in United Nations personnel stationed in this area. From July 2006 to June 2009, epidemiological data and medical records of 678 patients with Plasmodium falciparum malaria at the U.N. level 2 hospital were analyzed. The U.N. personnel were divided into individuals not immune to Plasmodium falciparum and individuals semi-immune to Plasmodium falciparum. The patients were divided into a chemoprophylaxis group (non-immune individuals who complied with the chemoprophylaxis regimen, 582 cases) and a no/incomplete chemoprophylaxis group (non-immune individuals who either did not fully comply with chemoprophylaxis or did not use it at all and semi-immune individuals who did not use chemoprophylaxis, 96 cases). Overall morbidity was about 11.3%. There was a significant difference in the morbidity of semi-immune and non-immune individuals (1.3% vs. 15.1%, P<0.001). Out of the total, 82.9% of cases occurred during the rainy season. The incidence of fever in the chemoprophylaxis group was significantly lower than in the no/incomplete chemoprophylaxis group (36.8% vs. 96.9%, P<0.001). Significant differences were observed between the two groups with respect to all other malaria-like symptoms except gastrointestinal symptoms, serum glucose level, platelet count, and alanine aminotransferase level. The incidence of complications was 1.2% (chemoprophylaxis group) and 44.8% (no/incomplete chemoprophylaxis group).The most common complication was thrombocytopenia, which was seen in 40.6% of the no/incomplete chemoprophylaxis group. In summary, Plasmodium falciparum malaria mainly occurred in rainy season. Gastrointestinal symptoms are an important precursor of malaria. Blood smears and rapid diagnostic tests should be performed after the onset of gastrointestinal symptoms. Appropriate chemoprophylaxis is necessary for reducing the severity of malaria.
doi:10.1371/journal.pone.0055220
PMCID: PMC3555950  PMID: 23372839
17.  Defining the Global Spatial Limits of Malaria Transmission in 2005 
Advances in parasitology  2006;62:157-179.
There is no accurate contemporary global map of the distribution of malaria. We show how guidelines formulated to advise travellers on appropriate chemoprophylaxis for areas of reported Plasmodium falciparum and Plasmodium vivax malaria risk can be used to generate crude spatial limits. We first review and amalgamate information on these guidelines to define malaria risk at national and sub-national administrative boundary levels globally. We then adopt an iterative approach to reduce these extents by applying a series of biological limits imposed by altitude, climate and population density to malaria transmission, specific to the local dominant vector species. Global areas of, and population at risk from, P. falciparum and often-neglected P. vivax malaria are presented for 2005 for all malaria endemic countries. These results reveal that more than 3 billion people were at risk of malaria in 2005.
doi:10.1016/S0065-308X(05)62005-2
PMCID: PMC3145102  PMID: 16647970
18.  Malaria prophylaxis: taking aim at constantly moving targets. 
The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections.
PMCID: PMC2589577  PMID: 1290274
19.  History of malaria control in Tajikistan and rapid malaria appraisal in an agro-ecological setting 
Malaria Journal  2008;7:217.
Background
Reported malaria cases in rice growing areas in western Tajikistan were at the root of a rapid appraisal of the local malaria situation in a selected agro-ecological setting where only scarce information was available. The rapid appraisal was complemented by a review of the epidemiology and control of malaria in Tajikistan and Central Asia from 1920 until today. Following a resurgence in the 1990s, malaria transmission has been reduced considerably in Tajikistan as a result of concerted efforts by the government and international agencies. The goal for 2015 is transmission interruption, with control interventions and surveillance currently concentrated in the South, where foci of Plasmodium vivax and Plasmodium falciparum persist.
Methods
The rapid malaria appraisal was carried out in six communities of irrigated rice cultivation during the peak of malaria transmission (August/September 2007) in western Tajikistan. In a cross-sectional survey, blood samples were taken from 363 schoolchildren and examined for Plasmodium under a light microscope. A total of 56 farmers were interviewed about agricultural activities and malaria. Potential Anopheles breeding sites were characterized using standardized procedures. A literature review on the epidemiology and control of malaria in Tajikistan was conducted.
Results
One case of P. vivax was detected among the 363 schoolchildren examined (0.28%). The interviewees reported to protect themselves against mosquito bites and used their own concepts on fever conditions, which do not distinguish between malaria and other diseases. Three potential malaria vectors were identified, i.e. Anopheles superpictus, Anopheles pulcherrimus and Anopheles hyrcanus in 58 of the 73 breeding sites examined (79.5%). Rice paddies, natural creeks and man-made ponds were the most important Anopheles habitats.
Conclusion
The presence of malaria vectors and parasite reservoirs, low awareness of, and protection against malaria in the face of population movements and inadequate surveillance may render local communities vulnerable to potential epidemics. To attain malaria transmission interruption in Tajikistan by 2015, there is a need for rigorous surveillance along with strengthening of primary health care facilities for effective case management, and possibly a more differentiated vector control strategy based on additional local evidence.
doi:10.1186/1475-2875-7-217
PMCID: PMC2584067  PMID: 18950536
20.  Spatial-temporal analysis of malaria and the effect of environmental factors on its incidence in Yongcheng, China, 2006–2010 
BMC Public Health  2012;12:544.
Background
In 2003, Plasmodium vivax malaria has re-emerged in central eastern China including Yongcheng prefecture, Henan Province, where no case has been reported for eleven years. Our goals were to detect the space-time distribution pattern of malaria and to determine significant environmental variables contributing to malaria incidence in Yongcheng from 2006 to 2010, thus providing scientific basis for further optimizing current malaria surveillance and control programs.
Methods
This study examined the spatial and temporal heterogeneities in the risk of malaria and the influencing factors on malaria incidence using geographical information system (GIS) and time series analysis. Univariate analysis was conducted to estimate the crude correlations between malaria incidence and environmental variables, such as mosquito abundance and climatic factors. Multivariate analysis was implemented to construct predictive models to explore the principal environmental determinants on malaria epidemic using a Generalized Estimating Equation (GEE) approach.
Results
Annual malaria incidence at town-level decreased from the north to south, and monthly incidence at prefecture-level demonstrated a strong seasonal pattern with a peak from July to November. Yearly malaria incidence had a visual spatial association with yearly average temperature. Moreover, the best-fit temporal model (model 2) (QIC = 16.934, P<0.001, R2 = 0.818) indicated that significant factors contributing to malaria incidence were maximum temperature at one month lag, average humidity at one month lag, and malaria incidence of the previous month.
Conclusions
Findings supported the effects of environment factors on malaria incidence and indicated that malaria control targets should vary with intensity of malaria incidence, with more public resource allocated to control the source of infections instead of large scale An. sinensis control when malaria incidence was at a low level, which would benefit for optimizing the malaria surveillance project in China and some other countries with unstable or low malaria transmission.
doi:10.1186/1471-2458-12-544
PMCID: PMC3488337  PMID: 22823998
Malaria; Anopheles; Weather; Geographic information system; Modeling
21.  A Predictive Spatial Model to Quantify the Risk of Air-Travel-Associated Dengue Importation into the United States and Europe 
Journal of Tropical Medicine  2012;2012:103679.
The number of travel-acquired dengue infections has been on a constant rise in the United States and Europe over the past decade. An increased volume of international passenger air traffic originating from regions with endemic dengue contributes to the increasing number of dengue cases. This paper reports results from a network-based regression model which uses international passenger travel volumes, travel distances, predictive species distribution models (for the vector species), and infection data to quantify the relative risk of importing travel-acquired dengue infections into the US and Europe from dengue-endemic regions. Given the necessary data, this model can be used to identify optimal locations (origin cities, destination airports, etc.) for dengue surveillance. The model can be extended to other geographical regions and vector-borne diseases, as well as other network-based processes.
doi:10.1155/2012/103679
PMCID: PMC3317038  PMID: 22523497
22.  Targeting the Lipid Metabolic Pathways for the Treatment of Malaria 
Drug development research  2010;71(1):44-55.
The control and eventual eradication of human malaria is considered one of the most important global public health goals of the 21st Century. Malaria, caused by intraerythrocytic protozoan parasites of the genus Plasmodium, is by far the most lethal and among the most prevalent of the infectious diseases. Four species of Plasmodium (P. falciparum, P. malariae, P. ovale, and P. vivax) are known to be infectious to humans, and more recent cases of infection due to P. knowlesi also have been reported. These species cause approximately 300 million annual cases of clinical malaria resulting in around one million deaths mostly caused by P. falciparum. The rapid emergence of drug-resistant Plasmodium strains has severely reduced the potency of medicines commonly used to treat and block the transmission of malaria and threatens the effectiveness of combination therapy in the field. New drugs that target important parasite functions, which are not the target of current antimalarial drugs, and have the potential to act against multi-drug-resistant Plasmodium strains are urgently needed. Recent studies in P. falciparum have unraveled new metabolic pathways for the synthesis of the parasite phospholipids and fatty acids. The present review summarizes our current understanding of these pathways in Plasmodium development and pathogenesis, and provides an update on the efforts underway to characterize their importance using genetic means and to develop antimalarial therapies targeting lipid metabolic pathways.
doi:10.1002/ddr.20347
PMCID: PMC2886290  PMID: 20559451
malaria; lipid; metabolism; Plasmodium; therapy
23.  Imported Malaria in Children in Industrialized Countries, 1992–2002 
Emerging Infectious Diseases  2009;15(2):185-191.
Children account for a considerable proportion of cases imported to the United States and Europe.
Children account for an appreciable proportion of total imported malaria cases, yet few studies have quantified these cases, identified trends, or suggested evidence-based prevention strategies for this group of travelers. We therefore sought to identify numbers of cases and deaths, Plasmodium species, place of malaria acquisition, preventive measures used, and national origin of malaria in children. We analyzed retrospective data from Australia, Denmark, France, Germany, Italy, Japan, the Netherlands, Sweden, Switzerland, the United Kingdom, and the United States and data provided by the United Nations World Tourism Organization. During 1992–2002, >17,000 cases of imported malaria in children were reported in 11 countries where malaria is not endemic; most (>70%) had been acquired in Africa. Returning to country of origin to visit friends and relatives was a risk factor. Malaria prevention for children should be a responsibility of healthcare providers and should be subsidized for low-income travelers to high-risk areas.
doi:10.3201/eid1502.080712
PMCID: PMC2657617  PMID: 19193261
pediatric; malaria; children; travel; research
24.  Imported malaria to Northern Ireland: improving surveillance for better intervention 
The Ulster medical journal  2006;75(2):129-135.
Malaria is a preventable disease, which is under notified in the UK. This study sought to evaluate the current surveillance arrangements in Northern Ireland (NI), describe the epidemiology of malaria and make appropriate recommendations.
A case was defined as a resident or visitor to NI with laboratory confirmed malaria, diagnosed by the NI haematology laboratories and/or the Malaria Reference Laboratory (MRL) from 1998–2003. Laboratory data were compared with notifications and hospital admission data.
One hundred and fourteen laboratory cases were identified compared with 63 notifications received by the regional surveillance centre. Six cases were associated with two episodes of malaria reflecting recurrence and or reinfection. P. falciparum was the most common infection with two fatalities reported; this was particularly associated with travel to West Africa. Most cases were associated with short visits to malarious areas. Thirty-three percent of all cases did not take prophylaxis and, of those that did, approximately half were taking a prophylactic regime appropriate to the region visited.
This study highlights the need for improved surveillance of malaria in order to capture risk factors and other relevant information to inform public and professional education. This would facilitate increasing local awareness, enhancing prescription of and compliance with appropriate chemoprophylaxis and enabling early diagnosis and treatment of malaria.
PMCID: PMC1891728  PMID: 16755943
25.  The changing pattern of imported malaria in British visitors to Kenya 1987-1990. 
Following a sudden increase of imported malaria from Kenya in December 1989-January 1990, an investigation was set up to identify risk factors for travellers' malaria. A questionnaire asking for details of travel patterns and compliance with prophylaxis was sent to cases reported over the 6-month Kenyan winter period. Quarterly malaria attack rates between January 1987 and June 1991 were calculated and linked to meteorological conditions in Mombasa. The number of travellers to Kenya has doubled in the 4 years studied and the quarterly rates varied 4-fold over this period. There was no clear seasonal pattern of malaria in travellers, nor was there any clear relation of malaria to coastal rainfall. Compliance with chemoprophylaxis was poor, with only 16% of cases using currently advised regimens. While the annual malaria attack rate per 10,000 travellers decreased by 37% over the study period, the total numbers of malaria cases imported from Kenya rose by 61%, reflecting the increase in the numbers of travellers to the region. As the popularity of East Africa as a tourist destination continues to increase, Kenya will remain an important and significant source of malaria imported into the UK.
PMCID: PMC1293905  PMID: 8459379

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