Malaria In Non-endemic Area Research Articles

Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

BackgroundThe current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. MethodsA cohort study of patients managed for malaria in a non-endemic setting (2005–2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2–10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. ResultsAmong 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). ConclusionsSeverity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.

Falciparum malaria case acquired by wound exposed to the blood of infected malaria patient

Malaria is a serious Anopheles mosquito-borne disease. It is not endemic in Egypt but continues to be imported by travelers returning from endemic areas. The transmission of malaria in non-endemic areas is an extremely unusual event, but it is possible under certain conditions.Herein, we report a case of prolonged fever in a patient living in the countryside of Egypt with no reported travel history following accidental blood exposure to a malaria patient. The purpose is to shed light on this rare mode of malaria transmission and also to alert physicians and infectious disease specialists to consider malaria in the differential diagnosis in case of contact history to the blood of a malaria patient.

Diagnostic challenges of recurrent malaria in non-endemic areas†.

In Spain, a patient’s unexpected relapse with Plasmodium falciparum raises questions about genetic influences on treatment efficacy. Meanwhile, in a separate case, a recurrence of Plasmodium malariae prompts speculation on latent reservoirs and treatment strategies. Here, we delve into these complex cases that underscore the evolving landscape of malaria.

Airport Malaria in Non-Endemic Areas: New Insights into Mosquito Vectors, Case Management and Major Challenges.

Despite the implementation of preventive measures in airports and aircrafts, the risk of importing Plasmodium spp. infected mosquitoes is still present in malaria-free countries. Evidence suggests that mosquitoes have found a new alliance with the globalization of trade and climate change, leading to an upsurge of malaria parasite transmission around airports. The resulting locally acquired form of malaria is called Airport malaria. However, piecemeal information is available, regarding its epidemiological and entomological patterns, as well as the challenges in the diagnosis, treatment, and prevention. Understanding these issues is a critical step towards a better implementation of control strategies. To cross reference this information, we conducted a systematic review on 135 research articles published between 1969 (when the first cases of malaria in airports were reported) and 2020 (i.e., 51 years later). It appears that the risk of malaria transmission by local mosquito vectors in so called malaria-free countries is not zero; this risk is more likely to be fostered by infected vectors coming from endemic countries by air or by sea. Furthermore, there is ample evidence that airport malaria is increasing in these countries. From 2010 to 2020, the number of cases in Europe was 7.4 times higher than that recorded during the 2000–2009 decade. This increase may be associated with climate change, increased international trade, the decline of aircraft disinsection, as well as delays in case diagnosis and treatment. More critically, current interventions are weakened by biological and operational challenges, such as drug resistance in malaria parasites and vector resistance to insecticides, and logistic constraints. Therefore, there is a need to strengthen malaria prevention and treatment for people at risk of airport malaria, and implement a rigorous routine entomological and epidemiological surveillance in and around airports.

Increasing proportions of relapsing parasite species among imported malaria in China's Guangxi Province from Western and Central Africa

BackgroundTravel-related malaria in non-endemic areas returning from endemic areas presents important challenges to diagnosis and treatment. Imported malaria to newly malaria-free countries poses further threats of malaria re-introduction and potential resurgence. For those traveling to places with high Plasmodium falciparum prevalence, prophylaxis against this parasite is recommended, whereas causal prophylaxis against relapsing malaria is often overlooked. MethodsWe analyzed a cluster of imported malaria among febrile patients in Shanglin County, Guangxi Province, China, who had recent travel histories to Western and Central Africa. Malaria was diagnosed by microscopy and subsequently confirmed by species- and subspecies-specific PCR. Plasmodium vivax was genotyped using a barcode consisting of 42 single nucleotide polymorphisms. ResultsInvestigations of 344 PCR-confirmed malaria cases revealed that in addition to Plasmodium falciparum being the major parasite species, the relapsing parasites Plasmodium ovale and P. vivax accounted for ~40% of these imported cases. Of the 114 P. ovale infections, 65.8% and 34.2% were P. ovale curtisi and P. ovale wallikeri, respectively, with the two subspecies having a ~2:1 ratio in both Western and Central Africa. Phylogenetic analysis of 14 P. vivax isolates using a genetic barcode demonstrated that 11 formed a distinct clade from P. vivax populations from Eastern Africa. ConclusionThis study provides support for active P. vivax transmission in areas with the predominant Duffy-negative blood group. With relapsing malaria making a substantial proportion of the imported malaria, causal prophylaxis should be advocated to travelers with a travel destination to Western and Central Africa.

Economic Burden of Malaria: A National Disease

World Health Organization (WHO) stated that Malaria is a life-threatening parasite illness caused by the Genus Plasmodium spreading to human beings through the bites of infected female Anopheles mosquitoes. Malaria disease is curable and preventable. Unawareness of Malaria in non-endemic areas needs specific attention and the need for health awareness through the health care workers should be enhanced usual care in both areas. Despite being aware of the government programs and measures for the control of Malaria and the endless major problem of health disease in India and many other nations. The complexness and the panic preponderance of the disease are governed by multiple limitations as technological, functional, and monetary and therefore go on inflicting heavy socio-economic losses to people.

Molecular surveillance of anti-malarial resistance Pfdhfr and Pfdhps polymorphisms in African and Southeast Asia Plasmodium falciparum imported parasites to Wuhan, China

BackgroundAnti-malarial drug resistance is a severe challenge for eventual control and global elimination of malaria. Resistance to sulfadoxine-pyrimethamine (SP) increases as mutations accumulate in the Pfdhfr and Pfdhps genes. This study aimed to assess the polymorphisms and prevalence of mutation in these genes in the Plasmodium falciparum infecting migrant workers returning to Wuhan, China.MethodsBlood samples were collected for 9 years (2011–2019). Parasite genomic DNA was extracted from blood spots on filter paper. The mutations were evaluated by nested PCR and sequencing. The single-nucleotide polymorphisms (SNPs) and haplotypes of the Pfdhfr and Pfdhps genes were analysed.ResultsPfdhfr codon 108 showed a 94.7% mutation rate, while for Pfdhps, the rate for codon 437 was 79.0%. In total, five unique haplotypes at the Pfdhfr locus and 11 haplotypes at the Pfdhps locus were found while the Pfdhfr-Pfdhps combined loci revealed 28 unique haplotypes. A triple mutant (IRNI) of Pfdhfr was the most prevalent haplotype (84.4%). For Pfdhps, a single mutant (SGKAA) and a double mutant (SGEAA) were detected at frequencies of 37.8 and 22.3%, respectively. Among the combined haplotypes, a quadruple mutant (IRNI-SGKAA) was the most common, with a 30.0% frequency, followed by a quintuplet mutant (IRNI-SGEAA) with a frequency of 20.4%.ConclusionThe high prevalence and saturation of Pfdhfr haplotypes and the medium prevalence of Pfdhps haplotypes demonstrated in the present data will provide support for predicting the status and progression of antifolate resistance in malaria-endemic regions and imported malaria in nonendemic areas. Additional interventions to evaluate and prevent SP resistance should be continuously considered.

Challenging diagnosis of congenital malaria in non-endemic areas

BackgroundCongenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported.Case presentationA 2-month-old male child was admitted to Bambino Gesù Children’s Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks’ gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification.ConclusionsThe maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother’s blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant’s mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.

A systematic review of transfusion-transmitted malaria in non-endemic areas

BackgroundTransfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient’s bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients.MethodsRelevant articles were retrieved from Pubmed, EMBASE, Scopus, and LILACS. From each selected study the following data were extracted: study area, gender and age of blood donor and recipient, blood component associated with TTM, Plasmodium species, malaria diagnostic method employed, blood donor screening method, incubation period between the infected transfusion and the onset of clinical symptoms in the recipient, time elapsed between the clinical symptoms and the diagnosis of malaria, infection outcome, country of origin of the blood donor and time of the last potential malaria exposure.ResultsPlasmodium species were detected in 100 TTM case reports with a different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16% Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by P. falciparum whilst the other fatalities occurred in individuals infected by P. malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were not attributed directly to malaria. The incubation time for all Plasmodium species TTM case reports was longer than what expected in natural infections. This difference was statistically significant for P. malariae (p = 0.006). A longer incubation time in the recipient together with a chronic infection at low parasite density of the donor makes P. malariae a subtle but not negligible risk for blood safety aside from P. falciparum.ConclusionsTTM risk needs to be taken into account in order to enhance the safety of the blood supply chain from donors to recipients by means of appropriate diagnostic tools.

Blood donors screening for malaria in non-endemic area in the Kingdom of Saudi Arabia: Is it necessary to introduce immunological testing?

IntroductionIn Saudi Arabia, where malaria is not endemic, the incidence is very low. However, malaria transmission cases have been reported, mainly in Asir and Jazan provinces along the Southwestern border with Yemen. Imported cases also have been reported. The aims of this study were to determine the prevalence of malaria in blood donors in a tertiary care hospital in the central area of Saudi Arabia and to assess the effectiveness of malaria screening methods used by transfusion services in Prince Sultan Military Medical City.MethodsThis study was conducted on 180,000 people who donated blood during 2006–2015. All blood smears from blood donors were screened for malaria infection using Giemsa staining, low power and high power microscopic examinations, and using oil immersion lens. The data were analyzed and reported in descriptive statistics and prevalence.ResultsFrom the total of 180,000 blood donors who were screened for malaria, 156,000 (87%) and 23.400 (13%) were Saudi Arabia citizens and non-Saudi residents, respectively. The mean age of the blood donors was 32 (ranging from 18 to 65), 97% and 3% were male and female, respectively. Using our current method for malaria screening, the prevalence of malaria in the study population was zero.ConclusionThe current methods of malaria screening in blood donors is not suitable for screening low-level parasiotemia. Adding the immunoassay and molecular screening methods is suggested.

Awareness and treatment seeking behaviour of malaria in selected endemic and non-endemic rural areas of Kanyakumari district, Tamilnadu, India

Background: Malaria is one of the world’s major public health concerns contributing to 243 million clinical cases and around million deaths annually. India reports the highest malaria burden in the South East Asia region. There is evidence that the availability of services alone may not ensure healthy practices, as they could be influenced by socio cultural barriers and inappropriate understanding of the disease etiology. Understanding of community perceptions and practices are crucial to bring down the burden of malaria. The objectives was to assess the awareness of malaria and treatment seeking behavior in an endemic and non-endemic area and to highlight the differences in the perceptions and treatment seeking behavior between the two areas. Methods: A descriptive study was undertaken in Primary Health Centres of Rajakkamangalamthurai (Endemic) and Chembagaramanputhur (Non endemic) for 2 Months. Patients with fever above the age of 15 years attending the Outpatient department of both the PHCs were chosen as study subjects. 150 patients were included in the study. Responses regarding malaria awareness and treatment seeking behavior were obtained using pre-structured, pre-tested and closed ended questionnaire. Results: Majority of the study subjects from the endemic area gave a correct response to the questions related to the disease terminology, modes of transmission and the usefulness of indoor residual sprays than the subjects from the non-endemic area and the difference was found to be statistically significant (P<.05). Most of the patients from the non-endemic areas were not aware about any information regarding malaria. Among the health seeking behaviour majority of the study subjects from the endemic area visits the health centre in less than 3 days after the onset of fever and also undergo a blood smear examination than that of the patients from the non-endemic area and the difference was found to be statistically significant. Majority of the patients from a non-endemic area opted for private hospital for their treatment whereas majority of them from the endemic area received the treatment from a government hospital. Conclusions: The lack of awareness of malaria in non endemic areas need special attention and the need of health awareness through the health care workers should be enhanced in both the endemic and non-endemic areas.

Difficulties in Diagnosis of Malaria in Non-Endemic Areas: A Case Report of a Child in Brazil

Malaria is a tropical parasitic disease that triggers severe social and economic problems worldwide and causes thousands of deaths each year. Early diagnosis enables proper treatment. People from non-endemic areas who travel to areas of transmission are often exposed to late or incorrect diagnosis because healthcare professionals have great difficulty in conceiving malaria as a diagnostic hypothesis. In addition, technicians skilled in recognizing malaria etiologic agent are not abundant. This paper addresses the case of a child from a non-endemic malaria region in Brazil, with a prior hypothetic diagnosis of visceral leishmaniasis, however bone marrow aspirate revealed Plasmodium instead of Leishmania. A retrospective epidemiological investigation showed a history of a recent trip to a malaria area and the review of blood smears obtained on admission disclosed a large number of trophozoites and gametocytes of Plasmodium falciparum that had been unnoticed, suggesting that diagnosis could have been possible earlier. Malaria clinical picture is easily mistaken for other febrile infectious diseases, thus the possibility of its occurrence cannot be ruled out. There is a need to increasingly train the microscopy technicians, both in endemic and non-endemic areas, so as to minimize the false diagnoses and decrease morbidity and mortality of the disease.

Hematologic Abnormalities Improve The Clinical Suspicion Of Malaria In Non-Endemic Countries

Malaria is one of the most frequent hemoparasitic infections in developing countries, responsible for a high health burden; with increasing world travel, growing numbers of patients present with malaria in non-endemic areas. While the clinical presentation of malaria is well characterized in the literature, it is non-specific, and suspicion is often raised simply by a fever and a report of a recent stay in an endemic area. Due to the connection of Europe with its former colonies, with bilateral migratory patterns, this anamnestic suspicion is frequent. To determine whether the addition of classic malaria hematology findings (thrombocytopenia, anemia and increased serum lactate dehydrogenase – LDH - levels) can improve clinical suspicion in patients presenting in non-endemic countries, We reviewed all malaria testing resulting from emergency room (ER) visits between 01-01-2000 and 06-30-2013. Repeated tests related to the same ER visit were analysed together; patients with more than one unrelated ER visit with suspected malaria were treated as separate subjects. Results 1357 subjects (69.0% male) fulfilled our criteria (median of 96 per year); the percentage of yearly Positive results varied between 2.6 and 17.0%, with no discernible temporal pattern, for an overall average of 9.5% of Positives. The monthly distribution of testing was balanced, with each month accounting for 6.4 to 10.2% of yearly tests; however, the percentage of Positives had a bimodal distribution, with two significant peaks in April (14.3% positivity) and December (16.5%); males were twice as likely to be Positive (11.0 vs 6.2%, p=0.005). There was a significant decrease in the mean haemoglobin of malaria-Positive patients (12.8±2.6 vs 13.5±2.2 g/dL, p&lt;0.001), leading to a higher incidence of anemia (39.8 vs 18.6%, p&lt;0.001). The positivity for malaria in anemic patients was 18.6% (vs the overall 9.5%). Mean platelet counts decreased in Positives (102.2±82.8 vs 227.1±91.8 G/L, p&lt;0.001), leading to an increase in thrombocytopenia from 16.1 to 80.6%, p&lt;0.001. Malaria-positivity in thrombocytopenic patients was 34.9%, rising to 36.6% when anemia was also present. Mean leukocyte counts decreased in Positives (5.5±2.4 vs 8.3±4.2 G/L, p&lt;0.001), affecting all lineages, with overt leukopenia present in 20.9 vs 6.8%, p&lt;0.001. Positivity for malaria in leukopenic patients was 20.9%. Leukocytosis was more frequent in suspicious patients without malaria (38.0 vs 17.8%, p&lt;0.001), as was an elevated erythrocyte sedimentation rate (30.8±38.1 vs 16.5±16.8 mm, p=0.005). Serum LDH increased in Positives from 263±287 to 414±201 U/L, p=0.003, with values over the upper limit of normal being more likely in Positives (78.7 vs 35.8%, p&lt;0.001); however, among Positives, high LDH was as likely to be found in patients with anemia as without (87.5 vs 74.2%, p=NS). Malaria-positivity was 19.5% in the presence of high LDH, rising to 35.9% with concomitant anemia or 53.1% with thrombocytopenia. The simultaneous presence of thrombocytopenia, anemia and high LDH (irrespective of leukopenia) resulted in 62% of Positive results, although only 10% of malaria patients fulfilled these criteria. Only 1.8% of patients who were normal on all three counts had malaria, and only 3% of malaria patients were negative for all three. We found that malaria was suspected more often in males, who were in fact more likely to have a positive result. Although suspicion was spread out across the year, there were two seasonal peaks of positive diagnoses, around Easter and Christmas, temporally coinciding with the migratory movements of expatriates and their families. Compared to patients with a clinical suspicion of malaria but without infection, patients who tested positive were more likely to be anemic, thrombocytopenic or leukopenic and to present with elevated LDH levels (irrespective of anemia). Patients with normal haemoglobin, platelets and LDH had a very low likelihood of malaria. The incorporation of these laboratory findings into the clinical scenario improved on clinical suspicion nearly 6-fold (with the percentage of positivity rising from just under 10% to over 60%), although at a high cost of false-negatives. In patients presenting at the ER in non-endemic countries with a fever and recent travel, the presence of combinations of anemia, thrombocytopenia and high LDH greatly increased the likelihood of malaria, although their absence should not impede testing. Disclosures: No relevant conflicts of interest to declare.

A retrospective review of malaria cases seen in a non-endemic area of South Africa

Malaria is a risk for travelers to endemic areas. We describe the diagnosis and treatment of malaria in Pretoria, a non-endemic area in South Africa. Records of specimens submitted to the medical microbiology laboratory for malaria investigations over 3 years were reviewed with follow up of hospital records for positive specimens for clinical data. The laboratory performs malaria smears and uses HRP2-Ag testing for rapid diagnosis of Plasmodium falciparum. A total of 516 specimens were received, with a 211/516 (41%) malaria smear positive rate. The number of malaria positive specimens has been increasing overtime and this increase was statistically significant in children [p=0.005]. HRP2-Ag testing was done on 430 specimens with124/430 (29%) being positive, of which 10/124 (8%) were smear negative, giving 98% sensitivity. Hospital records for 198/211 (94%) smear positive cases showed that 190/198 (96%) of the patients had a travel history with 170/190 (71%) having traveled to Mozambique, a malaria endemic country. Most patients presented with uncomplicated malaria; the CFR was 4/198 (2%). Treatment mainly followed South African national guidelines. Imported malaria is increasingly being diagnosed in returning travelers, especially from Mozambique. Rapid antigen tests remain useful for the diagnosis of malaria in non-endemic areas.

Severe malaria and intensive care

Malaria is an infective disease caused by sporozoan parasites that are transmitted to humans via the bite of an infected female anopheles mosquito. It is estimated that there are over 300 million acute infections each year and between 1.5–2.7 million deaths. 90% of these deaths occur in children from Sub-Saharan Africa and are due to Plasmodium falciparum (Fig. 1). The trend of P. falciparum infections is on the increase and there is evidence that it is reappearing in previously eradicated areas. There is also evidence of an increasing incidence of P. falciparum resistance to chloroquine and other antimalarials in certain areas. With the increase in travel and business to the third world, imported cases of malaria in nonendemic areas (the developed world) are on the increase and are estimated to be about 10,000 to 30,000 per year.