Malaria in Eritrean migrants newly arrived in seven European countries, 2011 to 2016.

Global migration has resulted in a large number of asylum applications in Europe. In 2014, clusters of Plasmodium vivax cases were reported among newly arrived Eritreans. This study aimed to assess malaria among Eritrean migrants in Europe from 2011 to 2016. We reviewed European migration numbers and malaria surveillance data for seven countries (Denmark, Germany, Netherlands, Norway, Sweden, Switzerland and the United Kingdom) which received 44,050 (94.3%) of 46,730 Eritreans seeking asylum in Europe in 2014. The overall number of malaria cases, predominantly P. vivax, increased significantly in 2014 compared to previous years, with the largest increases in Germany (44 P. vivax cases in 2013 vs 294 in 2014, p < 0.001) and Sweden (18 in 2013 vs 205 in 2014, p < 0.001). Overall, malaria incidence in Eritreans increased from 1-5 to 25 cases per 1,000, and was highest in male teenagers (50 cases/1,000). In conclusion, an exceptional increase of malaria cases occurred in Europe in 2014 and 2015, due to rising numbers of Eritreans with high incidence of P. vivax arriving in Europe. Our results demonstrate potential for rapid changes in imported malaria patterns, highlighting the need for improved awareness, surveillance efforts and timely healthcare in migrants.

Hemoglobin E protects against acute Plasmodium vivax infections in a Kachin population at the China-Myanmar border.

OBJECTIVES: Hemoglobin E (HbE, ß26 Glu-Lys) is the most prevalent hemoglobinopathy in Southeast Asia. This study aimed to determine whether HbE protects against clinical Plasmodium vivax malaria in Southeast Asia. METHODS: In a case-control study performed in villages along the China-Myanmar border, we determined the prevalence of HbE in 257 villagers who had acute P. vivax infections and in 157 control healthy villagers. RESULTS: HbE in P. vivax patients (17.4%) was significantly less prevalent than in the healthy villager population (36.3%). Moreover, there was a complete lack of HbEE homozygotes in the vivax patients as compared to 9.5% prevalence in the healthy villagers. Using the HbAA group as the reference, both the HbEA heterozygotes and HbEE homozygotes had significantly lower odds of presenting with acute P. vivax infections. Furthermore, HbEA heterozygotes also had significantly lower P. vivax asexual parasite densities. HbEA did not affect the proportion of P. vivax patients with gametocytemia nor the gametocyte densities. CONCLUSIONS: HbE offers significant protection against the occurrence and parasite density of acute P. vivax infections and provides a renewed perspective on P. vivax malaria as a potentially strong driving force behind the high frequencies of HbE in the Kachin population.

Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial.

BACKGROUND: Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, single-blinded trial was conducted. Duffy positive (Fy+; Pv susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) Pv-infected Anopheles mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (Pv refractory) volunteers was immunized with bites from non-irradiated Pv-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated Pv-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8-13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-PvCS response was associated with protection. CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria. TRIAL REGISTRATION: Identifier: NCT01082341.

Epidemiology and Control of Plasmodium vivax in Afghanistan.

Around half of the population of Afghanistan resides in areas at risk of malaria transmission. Two species of malaria (Plasmodium vivax and Plasmodium falciparum) account for a high burden of disease-in 2011, there were more than 300,000 confirmed cases. Around 80-95% of malaria is P. vivax Transmission is seasonal and focal, below 2,000 m in altitude, and in irrigated areas which allow breeding of anopheline mosquito vectors. Malaria risk is stratified to improve targeting of interventions. Sixty-three of 400 districts account for ∼85% of cases, and are the target of more intense control efforts. Pressure on the disease is maintained through case management, surveillance, and use of long-lasting insecticide-treated nets. Plasmodium vivax treatment is hampered by the inability to safely treat latent hypnozoites with primaquine because G6PD deficiency affects up to 10% of males in some ethnic groups. The risk of vivax malaria recurrence (which may be as a result of reinfection or relapse) is around 30-45% in groups not treated with primaquine but 3-20% in those given 14-day or 8-week courses of primaquine. Greater access to G6PD testing and radical treatment would reduce the number of incident cases, reduce the infectious reservoir in the population, and has the potential to reduce transmission as a result. Alongside the lack of G6PD testing, under-resourcing and poor security hamper the control of malaria. Recent gains in reducing the burden of disease are fragile and at risk of reversal if pressure on the disease is not maintained.

Killer cell immunoglobulin-like receptor (KIR) gene diversity in a population naturally exposed to malaria in Porto Velho, Northern Brazil.

Killer cell immunoglobulin-like receptors (KIR) are expressed mainly in natural killer cells and specifically recognize human leukocyte antigen (HLA) class I molecules. The repertoire of KIR genes and KIR-HLA pairs is known to play a key role in the susceptibilities to and the outcomes of several diseases, including malaria. The aim of this study was to investigate the distribution of KIR genes, KIR genotypes and KIR-HLA pair combinations in a population naturally exposed to malaria from Brazilian Amazon. All 16 KIR genes investigated were present in the studied population. Overall, 46 KIR genotypes were defined. The two most common genotypes in the Porto Velho communities, genotypes 1 and 2, were present at similar frequencies as in the Americas. Principal component analysis based on the frequencies of the KIR genes placed the Porto Velho population closer to the Venezuela Mestizos, USA California hispanic and Brazil Paraná Mixed in terms of KIR gene frequencies. This analysis highlights the multi-ethnic profile of the Porto Velho population. Most of the individuals were found to have at least one inhibitory KIR-HLA pair. Seventy-five KIR-HLA pair combinations were identified. The KIR-2DL2/3_HLA-C1, KIR3DL1_HLA-Bw4 and KIR2DL1_HLA-C2 pairs were the most common. There was no association between KIR genes, KIR genotypes or KIR-HLA pair combinations and malaria susceptibility in the studied population. This is the first report on the distribution of KIR and known HLA ligands in the Porto Velho population. Taken together, these results should provide baseline information that will be relevant to population evolutionary history, malaria and other diseases studies in populations of the Brazilian Amazon.

Imported malaria is stable from Africa but declining from Asia.

INTRODUCTION: In this study, we describe patients with imported malaria seen at the Department of Infectious Diseases (DID), Hvidovre Hospital, Denmark. Our aim was to address possible risk factors for contracting malaria and risk factors for developing complicated malaria. MATERIAL AND METHODS: We searched patient databases for all cases of malaria seen at the DID from 1994 to 2012. Various parameters were registered. RESULTS: A total of 320 cases were identified. We found a significant 3.39 % decrease in the incidence of cases per year (p = 0.0008). Plasmodium falciparum infection was predominant (n = 217) followed by P. vivax infection (n = 76). 37% of all cases were Africans visiting relatives and friends (VRF). A total of 12 patients had one or more re-lapses of their P. vivax infection. In all, 53 (17%) cases were defined as severe malaria. 36% (n = 112) reported using some type of chemoprophylaxis. 14% (n = 26) of patients traveling to Africa in 1999-2012 reported taking chemoprophylaxis as recommended in the current guidelines. Complicated malaria was significantly associated with failure to take any chemoprophylaxis (p = 0.0317, χ(2)-test). CONCLUSION: Imported malaria is decreasing at the DID. The patients who carry the highest risk of imported malaria are ethnic Africans who travel as VRF without using chemoprophylaxis. Recrudescence from P. vivax malaria is a substantial risk. Complicated malaria is associated with failure to take any chemoprophylaxis. It is important that travelers receive expedient advice on the use of efficient chemoprophylaxis to bring down the number of imported malaria cases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Efficacy and safety of atovaquone-proguanil in treating imported malaria in Japan: the second report from the research group.

Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use - oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil in 1999, and reported on its excellent antimalarial efficacy and safety for treating non-immune patients with uncomplicated Plasmodium falciparum malaria (20 adult and 3 pediatric cases) in 2006. In the present study, additional cases of malaria were analyzed to confirm the efficacy and safety of this antimalarial drug. Fourteen adult and 2 pediatric cases of P. falciparum malaria and 13 adult cases and 1 pediatric case of P. vivax/ovale malaria were successfully treated with atovaquone-proguanil, including 3 P. falciparum cases in which the antecedent treatment failed. Two patients with P. vivax malaria were treated twice due to primaquine treatment failure as opposed to atovaquone-proguanil treatment failure. Except for 1 patient with P. falciparum malaria who developed a moderate liver function disturbance, no significant adverse effects were observed. Despite the intrinsic limitations of this study, which was not a formal clinical trial, the data showed that atovaquone-proguanil was an effective and well-tolerated therapeutic option; licensure of this drug in Japan could greatly contribute to individually appropriate treatment options.

Eritrean and Sudanese migrants presenting with malaria in Israel.

In Israel, a malaria-free country, we have noticed lately an increase of hospital admissions with malaria, parallel to the rise in the number of Eritrean and Sudanese migrants. Eritrea and Sudan are malaria-endemic countries; Plasmodium falciparum accounts for 85-90% and Plasmodium vivax accounts for 10-15% of malaria species in these areas. We aimed to describe the features of malaria in this migrant population by conducting a retrospective descriptive study of Eritrean and Sudanese migrants admitted with malaria during 1/2009-4/2010. Patient files were reviewed for demographics, clinical data, laboratory tests, treatment and outcome. 101 patients (mean age 24.9 (SD 5.6) years; 86.1% males) with malaria were identified. 87.1% were infected with P. vivax, 6% with P. falciparum, and 6.9% had both. All presented with pyrexia. None had respiratory or cerebral complications. Mean length of hospitalization was 2.49 (SD 1.5) days. No treatment failures or complications were observed. We conclude that in countries with waves of migrants from malaria-endemic areas, onset of fever should raise suspicion of malaria. Contrary to the known dominance of P. falciparum among malaria species in Eritrea and Sudan, the vast majority of migrants presented with P. vivax. The region of P. vivax acquisition remains unclear.

Plasmodium vivax malaria in a Romanian traveller returning from Greece, August 2011.

In August 2011, a Plasmodium vivax malaria infection was diagnosed in a Romanian traveller returning from Greece. This case together with several reports over the past decade of autochthonous cases in Greece highlight that malaria should be considered as differential diagnosis in symptomatic travellers returning from this country. Travellers may serve as sentinels of emerging vector-borne diseases.

Co-infections of Plasmodium knowlesi, P. falciparum, and P. vivax among Humans and Anopheles dirus Mosquitoes, Southern Vietnam.

A single Anopheles dirus mosquito carrying sporozoites of Plasmodium knowlesi, P. falciparum, and P. vivax was recently discovered in Khanh Phu, southern Vietnam. Further sampling of humans and mosquitoes in this area during 2009-2010 showed P. knowlesi infections in 32 (26%) persons with malaria (n = 125) and in 31 (43%) sporozoite-positive An. dirus mosquitoes (n = 73). Co-infections of P. knowlesi and P. vivax were predominant in mosquitoes and humans, while single P. knowlesi infections were found only in mosquitoes. P. knowlesi-co-infected patients were largely asymptomatic and were concentrated among ethnic minority families who commonly spend nights in the forest. P. knowlesi carriers were significantly younger than those infected with other malaria parasite species. These results imply that even if human malaria could be eliminated, forests that harbor An. dirus mosquitoes and macaque monkeys will remain a reservoir for the zoonotic transmission of P. knowlesi.

Malaria endemicity in an Orang Asli community in Pahang, Malaysia.

An epidemiological cross-sectional study was undertaken to determine the endemicity of malaria among the Orang Asli population of Raub, Pahang. Malaria endemicity was measured in terms of the prevalence of parasitaemia and splenomegaly. A total of 520 Orang Asli were examined. The point prevalence of malaria was 24.2% (95% CI 20.7-25.1), with Plasmodium falciparum (67.5%) being the predominant species. Children < 12 years were at least 3.7 times more likely to be parasitaemic compared to those older. The prevalence of malaria among children 2-<10 years was 38.1% (95% CI 31.6-50.0). Spleen rate among children 2-<10 years old was 22.3% (95% CI 17.1-28.3). The average enlarged spleen size was 1.2. These findings classify the study area as being mesoendemic. Malaria control activities among the Orang Asli should focus on protecting vulnerable subgroups like young children. Measuring the level of malaria endemicity at regular intervals is fundamental in evaluating the effectiveness of malaria control programs.

Circumsporozoite protein gene diversity among temperate and tropical Plasmodium vivax isolates from Iran.

To date, there is no information on the genetic diversity of the circumsporozoite protein (CSP), a leading vaccine candidate, in Plasmodium vivax populations circulating in Iran. The gene for this protein, Pvcsp, was amplified from 374 P. vivax isolates collected in the temperate northern, and in the tropical southern endemic areas. PCR-RFLP analysis of the repeated central region revealed that the parasites collected in the northern area were almost exclusively of the VK210 type. Parasites collected in the south-eastern areas were of both VK210 and VK247 types. We detected VK210 parasite in 70.5% of the samples, VK247 parasites in 17.5% and mixed type infections in 12% of the isolates. Sequence analysis of 137 isolates obtained from both areas identified a total of 25 distinct genotypes. The degree of genetic diversity was generally higher for the tropical (21 genotypes) than the temperate (7 genotypes) P. vivax populations, a difference possibly reflecting the high cross-border exchanges between Afghanistan and Pakistan and southern Iran. Interestingly, all but two VK210 type isolates sequenced harboured a 36-bp post-repeat insert previously only observed in North Korea and China. This large-scale survey of parasite diversity in the Eastern Mediterranean Region provides a set of baseline data suitable for future molecular epidemiological studies of P. vivax.

Imported malaria infections diagnosed at the Malaria Referral Laboratory in Riyadh, Saudi Arabia.

OBJECTIVE: To determine epidemiological characteristics of imported malaria infections in Riyadh, Kingdom of Saudi Arabia, based on retrospective analysis of laboratory records within the Central Laboratory. METHODS: Records of the Malaria Referral Laboratory in Riyadh, Kingdom of Saudi Arabia (KSA) were reviewed for the past 6 years: 1416-1421 Hejri inclusive (1996-2001 Gregorian). The dates of blood films were converted to Gregorian calendar in addition to the Hejri dates already used in the records. Data collected included the date of film, age, sex, nationality and parasitological findings in the film. All data was entered and analyzed using statistical package for social sciences computer software. RESULTS: The annual mean number of positive slides was 212 +/- 78. Positive slides were reported at the rate of 18 /100,000 among 137,402 potential blood donors screened during this period. The overall slide positivity was 12.9% among suspected cases referred from hospitals and 9.5% among those referred from health centers and private clinics. Most positive slides were from Saudis (36.6%), Sudanese (30.9%), Indians (13.9%), Pakistanis (8%) and Yemenis (5%). The type of malaria infection varied in the different nationalities, reflecting the pattern of endemicity at the source of infection. Positive cases show a marked seasonality in Saudis, reflection seasonal transmission of the disease in the endemic areas. CONCLUSION: Although there is no active malaria transmission in Riyadh KSA, imported infections still poses a significant health problem. A high index of suspicion should be maintained in those with suggestive travel history. Efforts to reduce the incidence of transfusion malaria should aim at formulation of appropriate policies for selection of blood donors and for screening of blood.

Seasonality of presentation of imported Plasmodium vivax malaria in Birmingham, UK.

Residents of the UK returning from northern Pakistan with Plasmodium vivax infection tend to develop symptoms and present to hospital in the summer months, irrespective of the month of return. Thus, infections acquired in the cooler months of November to April appear to have a longer latency before presentation. Experiments suggest that more hypnozoites arise from the liver when ambient temperatures fall, somehow 'programming' parasites within biting mosquitoes.

Control of malaria: a successful experience from Viet Nam.

OBJECTIVE: To follow malaria prospectively in an ethnic minority commune in the south of Viet Nam with high malaria transmission and seasonal fluctuation, during malaria control interventions using insecticide-treated bednets (ITBNs) and early diagnosis and treatment (EDT) of symptomatic patients. METHODS: From 1994 onwards the following interventions were used: distribution of ITBNs to all households with biannual reimpregnation; construction of a health post and appointment of staff trained in microscopic diagnosis and treatment of malaria; regular supply of materials and drugs; annual cross-sectional malaria surveys with treatment of all parasitaemic subjects, and a programme of community involvement and health education. Surveys were held yearly at the end of the rainy season. During the surveys, demographic data were updated. Diagnosis and treatment of malaria were free of charge. Plasmodium falciparum infection was treated with artesunate and P. vivax infection with chloroquine plus primaquine. FINDINGS: The baseline survey in 1994 recorded 716 inhabitants. Of the children under 2 years of age, 37% were parasitaemic; 56% of children aged 2-10 years, and 35% of the remaining population were parasitaemic. P. falciparum accounted for 73-79% of these infections. The respective splenomegaly rates for the above-mentioned age groups were 20%, 56%, and 32%. In 1999, the proportion of parasitaemic subjects was 4%, 7% and 1%, respectively, of which P.falciparum contributed 56%. The splenomegaly rate was 0%, 5% and 2%, respectively. CONCLUSIONS: A combination of ITBNs and EDT, provided free of charge, complemented by annual diagnosis and treatment during malaria surveys and community involvement with health education successfully brought malaria under control. This approach could be applied to other regions in the south of Viet Nam and provides a sound basis for further studies in other areas with different epidemiological patterns of malaria.

[Malaria. An evaluation of 127 patients treated in Rigshospitalet in 1999 and 2000]. / Malaria. Opgørelse over 127 patienter behandlet på Rigshospitalet i 1999 og 2000.

INTRODUCTION: The incidence of malaria has increased globally to 500 million cases a year. Imported malaria in travellers comprises only a small fraction, but the disease has become a serious problem in Europe and the United States. The aim of the present study was to elucidate the epidemiological and clinical aspects of patients with imported malaria in Denmark. MATERIAL AND METHODS: All patients treated for malaria at the Department of Infectious Diseases, Rigshospitalet, in 1999-2000 were evaluated retrospectively. Age, sex, nationality, destination, chemoprophylaxis, symptoms, duration of symptoms, parasitaemia, treatment, and complications were registered. RESULTS: Seventy per cent of the patients had falciparum malaria. Of these, 95% had been infected in Africa and 46% of these patients were Africans living in Denmark. Only 50% of all patients had been taking chemoprophylaxis and of these only half had been compliant. Chloroquine and proguanile were most commonly used. Seven patients had parasitaemia above 5%, but only one of these developed complicated malaria. DISCUSSION: The risk of complicated malaria in this series was low and seems to be related to lack of chemoprophylaxis, advanced age, and duration of symptoms.

[The factors associated with noncompliance with antimalarial treatment in Ecuadorian patients]. / Factores asociados con el incumplimiento del tratamiento antipalúdico en pacientes ecuatorianos.

A total of 249 persons living in the northwest part of Ecuador with a clinical diagnosis of malaria confirmed by thick blood films were treated with chloroquine and primaquine according to the therapeutical system in force in the National Service for Eradication of Malaria. New clinical assessment and thick blood film were applied after 4 days in P. falciparum (n = 120) cases and after 8 days in P. vivax (n = 129) cases; patients were questioned about the compliance or non-compliance with the treatment, and the reasons for their acting in either way were studied. EPI-INFO 6.04 and SPSS PC 7.0 packages served to process the information: "kind adjustment test" (bondad de ajuste) abd factorial analysis of correspondences were used. The patient who daily took his/her pills for the number of days indicated, at the established intervals and at the right time was defined as a patient complying with the drug therapy. For every 3 patients complying with treatment, there were 2 who did not; non-compliance was not significantly related to age, sex, educational level, ethnic group, urban or rural setting or level of income, but learning about seriousness of the infection did help to compliance with the therapy. The reasons for non-compliance were mainly associated with drugs (side effects/reluctancy to take drugs), with the fact of forgetting to take them and of "getting cured quickly". The profile of the patient who did not comply with treatment corresponded to male, teenager, mixed race, poor and rural setting.

[Increase of malaria among migrants in Amsterdam-Zuidoost]. / Toename van malaria bij migranten in Amsterdam-Zuidoost.

In a general practice in Amsterdam Southeast in 1998 a delayed first attack of Plasmodium ovale infection was diagnosed in a 13-year-old girl from Ghana, malaria tropica with a low parasitaemia index in a 43-year-old Ghanaian man and a 8-year-old Ghanaian girl, and Plasmodium vivax infection in a 44-year-old Surinam woman. The Ghanaian patients had visited their native country, the Surinam woman had contracted the infection during a visit to India. All patients responded well to antimalaria medication. These patients were among a total of 6 patients of non-Dutch origin diagnosed with malaria in 1998 in this general practice. Four patients had not taken any prophylactic drug and two had not used the drugs properly. A relative increase of malaria in immigrants has been seen in the Netherlands and elsewhere in Europe in recent years. Underestimation of the risks and lack of knowledge of malaria and of the changing epidemiology make people of ethnic minorities travel without taking appropriate precautions. New, creative ways of communication and information will have to be explored to reach these migrant communities.

Increase of malaria among migrants in Amsterdam-Zuidoost

In a general practice in Amsterdam SouthEast in 1998 a delayed first attack of Plasmodium ovale infection was diagnosed in a 13-year-old-girl from Ghana, malaria tropica with a low parasitaemia index in a 43-year-old Ghanaian man and a 8-year-old Ghanaian girl, and a Plasmodium vivax infection in a 44-year-old Surinam woman. The Ghanaian patients had visited their native country, the Surinam woman had contracted the infection during a visit to India. All patients responded well to antimalaria medication. These patients were among a total of 6 patients of non-Dutch origin diagnosed with malaria in 1998 in this general practice. Four patients had not taken any prophylactic drug and two had not used the drugs properly. A relative increase of malaria in immigrants has been seen in the Netherlands and elsewhere in Europe in recent years. Underestimation of the risks and lack of knowledge of malaria and of the changing epidemiology make people of ethnic minorities travel without taking appropriate precautions. New, creative ways of communication and information will have to be explored to reach these migrant communities. (AU)