Malaria-free Area Research Articles

Updated Anopheles mosquitos abundance and distribution in north-eastern malaria-free area of Argentina.

Malaria is the most important parasitic disease worldwide. In 2019, more than 679,441 cases of malaria were reported in the American region. During this study, Argentina was in malaria pre-elimination autochthonous transmission phase with the aim of being declared as malaria-free country. The aim of this work was to assess the influence of remote sensing spectral indices (NDVI, NDWI) and climatic variables (temperature, relative humidity and precipitation) on the distribution and abundance of Anopheles mosquitoes, in four localities with different degrees of anthropogenic disturbance and with previous malaria cases records located , in a historical malarious area in northeastern of Argentina. Between June 2012 and July 2014, mosquitoes were collected. We collected 535 Anopheles adult mosquitoes. Anopheles strodei s.l. was the most abundant species. The greatest richness, diversity and abundance of species were registered in wild and semi-urban environments. The abundance of Anopheles presented a negative association with relative humidity and mean temperature, but positive with mean maximum temperature. The most important variables determining Anopheles total abundance and distribution were NDWI Index and distance to vegetation. The abundance of An. strodei s.l., was positive associated with water areas whereas the NDVI Index was negatively associated.

Updated Anopheles Mosquitos Abundance and Distribution in North-Eastern Malaria-Free Area of Argentina

Updated Anopheles Mosquitos Abundance and Distribution in North-Eastern Malaria-Free Area of Argentina

The changing risk patterns of Plasmodium vivax malaria in Greece due to climate change

ABSTRACT It has great importance to study the potential effects of climate change on Plasmodium vivax malaria in Greece because the country can be the origin of the spread of vivax malaria to the northern areas. The potential lengths of the transmission seasons of Plasmodium vivax malaria were forecasted for 2041–2060 and 2061–2080 and were combined. The potential ranges were predicted by Climate Envelope Modelling Method. The models show moderate areal increase and altitudinal shift in the malaria-endemic areas in Greece in the future. The length of the transmission season is predicted to increase by 1 to 2 months, mainly in the mid-elevation regions and the Aegean Archipelago. The combined factors also predict the decrease of vivax malaria-free area in Greece. It can be concluded that rather the elongation of the transmission season will lead to an increase of the malaria risk in Greece than the increase in the suitability values.

Genetic diversity of the Plasmodium vivax multidrug resistance 1 gene in Thai parasite populations

Plasmodium vivax resistance to chloroquine (CQ) was first reported over 60 years ago. Here we analyzed sequence variations in the multidrug resistance 1 gene (Pvmdr1), a putative molecular marker for P. vivax CQ resistance, in field isolates collected from three sites in Thailand during 2013-2016. Several single nucleotide polymorphisms previously implicated in reduced CQ sensitivity were found. These genetic variations encode amino acids in the two nucleotide-binding domains as well as the transmembrane domains of the protein. The high level of genetic diversity of Pvmdr1 provides insights into the evolutionary history of this gene. Specifically, there was little evidence of positive selection at amino acid F1076L in global isolates to be promoted as a possible marker for CQ resistance. Population genetic analysis clearly divided the parasites into eastern and western populations, which is consistent with their geographical separation by the central malaria-free area of Thailand. With CQ-primaquine remaining as the frontline treatment for vivax malaria in all regions of Thailand, such a population subdivision could be shaped and affected by the current drugs for P. falciparum since mixed P. falciparum/P. vivax infections often occur in this region.

Impact of Irrigation Extension on Malaria Transmission in Simret, Tigray, Ethiopia.

Poor subsistence farmers who live in a semi-arid area of northern Ethiopia build irrigation systems to overcome water shortages. However, there is a high risk of malaria transmission when increased standing water provides more favorable habitats for mosquito breeding. This is a serious problem because there are many barriers to malaria control measures and health care systems in the area. Using a causal loop diagram and computer simulations, the author attempted to visually illustrate positive and negative feedbacks between mosquito and human populations in the context of Simret, which is a small village located in northern Ethiopia and is generally considered a malaria-free area. The simulation results show that the number of infectious mosquitos increases to 17,215 at its peak, accounting for 3.5% of potentially dangerous mosquitos. At the same time, the number of sick people increases to 574 at its peak, accounting for 15% of local population. The malaria outbreak is controlled largely because of a fixed number of vulnerable people or local population that acts as an intermediate host.

Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection.

The current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. However, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. Previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. Here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and probucol to modify the host plasma alpha-tocopherol concentration. The drugs were mixed with diet and fed to C57BL/6J mice for 2 weeks. Although all drugs reduced plasma alpha-tocopherol concentration after 2 weeks of feeding, probucol-treated mice showed 90 % reduction and it was the lowest alpha-tocopherol concentration among the four drugs. Ezetimibe, berberine, and combination of ezetimibe and berberine pretreatment for 2 weeks were not effective against infection of Plasmodium yoelii XL17, a lethal strain, for survival and parasitemia in mice. Two-week pretreatment and 1-week treatment after infection of cholestyramine had also no effect on malaria infection. Survival rates of cholestyramine, ezetimibe, and/or berberine treated mice were 0-22 %. However, probucol caused significant decrease in parasitemia and increased in mice survival following 2-week pretreatment and 1-week treatment after infection. All control mice died while all probucol treated mice survived during the course of infection. Thus, probucol which reduced plasma alpha-tocopherol concentration was effective in enhancing the host to resist malaria infection in mice. Our finding indicates that plasma alpha-tocopherol reducing drugs like probucol might be a candidate for beneficial prevention strategy for travelers from malaria-free area.

The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections.

Recent studies in paleopathology have shown promise in associating some skeletal lesions with malarial infection. However, malaria's skeletal manifestation has never been confirmed using a large clinical reference sample from an endemic area for malaria with known individual causes of death. To pinpoint evidence of malaria infection on ancient skeletal remains, this study uses an epidemiological approach to compare skeletal lesions in a modern reference sample of 98 individuals from Uganda, where malaria is holoendemic, to a similar modern sample of 106 individuals from a malaria-free area. Five porous skeletal lesions are identified that appear more frequently in the endemic area population, especially in anemic individuals. These appear on the cranium, vertebral column, and humeral and femoral necks. Periostitis also associates strongly with individuals in the endemic population; however, linear enamel hypoplasias show an inverse association. The identified lesions are tested for their association with each other, and then tested individually for their diagnostic power through measures of sensitivity and specificity. A diagnostic outcome algorithm is formed from the remaining skeletal lesions and their inter-lesion associations. Several etiological explanations for the characteristic malarial skeletal lesions are explored, including severe malarial anemia, an imbalance in bone remodeling, and extramedullary erythropoiesis. The importance of careful differential diagnoses between other infectious and noninfectious causes of these lesions is discussed, including the potential for coinfection of malaria with other infectious diseases. The findings of this study are pivotal in establishing diagnostic criteria by which we can identify the prevalence and impact of malaria on past populations.

First case of a naturally acquired human infection with Plasmodium cynomolgi

Since 1960, a total of seven species of monkey malaria have been reported as transmissible to man by mosquito bite: Plasmodium cynomolgi, Plasmodium brasilianum, Plasmodium eylesi, Plasmodium knowlesi, Plasmodium inui, Plasmodium schwetzi and Plasmodium simium. With the exception of P. knowlesi, none of the other species has been found to infect humans in nature. In this report, it is described the first known case of a naturally acquired P. cynomolgi malaria in humans.The patient was a 39-year-old woman from a malaria-free area with no previous history of malaria or travel to endemic areas. Initially, malaria was diagnosed and identified as Plasmodium malariae/P. knowlesi by microscopy in the Terengganu State Health Department. Thick and thin blood films stained with 10% Giemsa were performed for microscopy examination. Molecular species identification was performed at the Institute for Medical Research (IMR, Malaysia) and in the Malaria & Emerging Parasitic Diseases Laboratory (MAPELAB, Spain) using different nested PCR methods.Microscopic re-examination in the IMR showed characteristics of Plasmodium vivax and was confirmed by a nested PCR assay developed by Snounou et al. Instead, a different PCR assay plus sequencing performed at the MAPELAB confirmed that the patient was infected with P. cynomolgi and not with P. vivax.This is the first report of human P. cynomolgi infection acquired in a natural way, but there might be more undiagnosed or misdiagnosed cases, since P. cynomolgi is morphologically indistinguishable from P. vivax, and one of the most used PCR methods for malaria infection detection may identify a P. cynomolgi infection as P. vivax.Simian Plasmodium species may routinely infect humans in Southeast Asia. New diagnostic methods are necessary to distinguish between the human and monkey malaria species. Further epidemiological studies, incriminating also the mosquito vector(s), must be performed to know the relevance of cynomolgi malaria and its implication on human public health and in the control of human malaria.The zoonotic malaria cannot be ignored in view of increasing interactions between man and wild animals in the process of urbanization.

Vivax malaria in an Amazonian child with dilated cardiomyopathy

A child living in the Brazilian Amazon region who had had vivax malaria at the age of 11 months was admitted three months later with a history of progressive dyspnoea and fever, which culminated in respiratory distress and severe dilated cardiomyopathy at hospital admission in a malaria-free area. She received treatment for cardiac insufficiency and was tested for malaria with two thick blood smears, which were negative. There was general improvement of cardiorespiratory function in the next two weeks, but in the third week of hospital admission, there was re-appearance of fever, severe anaemia, severe plaquetopaenia, and respiratory distress. A third thick blood smear was positive for Plasmodium vivax mono-infection, which was confirmed by molecular methods. A serological panel with the most prevalent infectious agents known to cause myocarditis was performed, and specific anti-cytomegalovirus (CMV) IgM and elevated levels of anti-CMV IgG were also detected in the serum. After treatment for malaria, there was improvement of respiratory distress, although cardiac function did not recover. She was discharged home with drugs for cardiac insufficiency and is currently under follow-up with a paediatric cardiologist as an outpatient. This report presents a young child with several episodes of vivax malaria who suffers from cardiac insufficiency, probably related to CMV-induced myocarditis.

Visiting Friends and Relatives (VFRs) travelers and imported malaria in the Palermo district (Sicily).

Although Italy has been malaria-free since 1970, the infection is commonly introduced into the country by travelers and immigrants from endemic areas. The term VFRs refers to immigrants from malaria-endemic countries who are regularly resident in a malaria-free area, and who travel to their countries of origin to visit friends and relatives (VFRs). This group is at special risk of malaria as they are unaware of having lost their transitory immunity to the disease. We conducted a retrospective study at the International Travelers Department of Palermo (Italy), examining records of malaria cases (67) reported over the period from 1998 to 2013. VFRs represent the highest number of cases (77.6%), followed by workers (16.4%) and tourists (6.0%). All female patients and patients under the age of 18 were VFRs. Plasmodium falciparum was the most frequently-identified species. In all cases, chemoprophylaxis was not taken or was incomplete. VFRs are at high risk of contracting malaria. This is probably related to an inequality in health care available to immigrants, as well as to ethnic and cultural conditions.

Activation of minority-variant Plasmodium vivax hypnozoites following artesunate + amodiaquine treatment in a 23-year old man with relapsing malaria in Antananarivo, Madagascar

In endemic areas, Plasmodium vivax relapses are difficult to distinguish from new infections. Genotyping of patients who experience relapse after returning to a malaria-free area can be used to explore the nature of hypnozoite activation and relapse. This paper describes a person who developed P. vivax malaria for the first time after travelling to Boriziny in the malaria endemic coastal area of Madagascar, then suffered two P. vivax relapses 11 weeks and 21 weeks later despite remaining in Antananarivo in the malaria-free central highlands area. He was treated with the combination artesunate + amodiaquine according to the national malaria policy in Madagascar. Genotyping by PCR-RFLP at pvmsp-3α as well as pvmsp1 heteroduplex tracking assay (HTA) showed the same dominant genotype at each relapse. Multiple recurring minority variants were also detected at each relapse, highlighting the propensity for multiple hypnozoite clones to activate simultaneously to cause relapse.

Analysis of the B cell responsiveness to the TLR9 agonist CPG in malaria semi-immune versus malaria na�ve individuals

Event Abstract Back to Event Analysis of the B cell responsiveness to the TLR9 agonist CPG in malaria semi-immune versus malaria naïve individuals Younoussou Kone1*, Doumbo Safiatou Niare1, Didier Doumtabe1, Kassoum Kayentao1, Aissata Ongoiba1, Silvia Portugal2, Jacqueline Moebius2, Susan K. Pierce2, Ogobara K. Doumbo1, Peter D. Crompton2 and Boubacar Traore1 1 Malaria Research and Craining Center(MRTC)/USTTB, Laboratory of Immunogenetics, Mali 2 NIH, Malaria Infection Biology, Laboratory of Immunogenetics, United States In the context of Phase 1 clinical trials of the malaria vaccine candidate AMA1 we found that the novel vaccine adjuvant CPG, TLR9 agonist that activates memory B cells, enhanced the antibody and memory B cell response to AMA1 in malaria-naïve U.S. adults, but not in malaria-immune Malian adults, suggesting that chronic P. falciparum exposure leads to TLR9 refractoriness. To follow up on this clinical observation we are conducting a systematic ex vivo analysis in which we compare the phenotype and function of memory B cells obtained from malaria-experienced and naïve individuals. In response to CPG stimulation we measure B cell proliferation, immunoglobulin class switching, cytokine production, antibodies secretion and the expression of co- stimulatory molecules. Male and female at age of 18 or greater from malaria endemic village are equally enrolled. Adult from malaria free area are used as control. Our preliminary results showed that both naïve and memory B cells from malaria semi-immune individuals respond less to CPG stimulation compared to malaria naïve individuals. Also malaria semi-immune individuals have a greater expression of the costimulatory molecule CD86. The next step will consist of comparing the above variables among 30 infected individuals, 30 uninfected individuals from Mali and 30 naïve individuals from the USA. The results from this study may highlight the importance of testing the efficacy of novel vaccine adjuvants in the target population and may also provide fundamental insights into how chronic P. falciparum exposure modulates the innate immune response. Acknowledgements Volonteers from Kambila (Mali) Volunteers from USA National Institute of Health (NIH) Malaria Reseach and Training Center (MRTC) Keywords: Malaria, innate immunity, TLR9, B cells, Vaccines Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Kone Y, Niare D, Doumtabe D, Kayentao K, Ongoiba A, Portugal S, Moebius J, Pierce S, Doumbo O, Crompton P and Traore B (2013). Analysis of the B cell responsiveness to the TLR9 agonist CPG in malaria semi-immune versus malaria naïve individuals. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00837 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Younoussou Kone, Malaria Research and Craining Center(MRTC)/USTTB, Laboratory of Immunogenetics, Bamako, 1805, Mali, ykone@icermali.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Younoussou Kone Doumbo Safiatou Niare Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Silvia Portugal Jacqueline Moebius Susan K. Pierce Ogobara K. Doumbo Peter D. Crompton Boubacar Traore Google Younoussou Kone Doumbo Safiatou Niare Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Silvia Portugal Jacqueline Moebius Susan K. Pierce Ogobara K. Doumbo Peter D. Crompton Boubacar Traore Google Scholar Younoussou Kone Doumbo Safiatou Niare Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Silvia Portugal Jacqueline Moebius Susan K. Pierce Ogobara K. Doumbo Peter D. Crompton Boubacar Traore PubMed Younoussou Kone Doumbo Safiatou Niare Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Silvia Portugal Jacqueline Moebius Susan K. Pierce Ogobara K. Doumbo Peter D. Crompton Boubacar Traore Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

In vivo efficacy of mefloquine for the treatment of Falciparum malaria in Brazil.

Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.

Co-infection with malaria and HIV in injecting drug users in Brazil: a new challenge to public health?

To describe AIDS and malaria geography in Brazil, highlighting the role of injecting drug users (IDUs) in malaria outbreaks occurring in malaria-free regions, and the potential clinical and public health implications of malaria/HIV co-infection. Review of the available literature and original analyses using geoprocessing and spatial analysis techniques. Both HIV/AIDS and malaria distribution are currently undergoing profound changes in Brazil, with mutual expansion to intersecting geographical regions and social networks. Very recent reports describe the first clinical case of AIDS in a remote Amazonian ethnic group, as well as malaria cases in Rio de Janeiro state (hitherto a malaria-free area for 20 years); in addition, two outbreaks of both infections occurred at the beginning of the 1990s in the most industrialized Brazilian state (São Paulo), due to the sharing of needles and syringes by drug users. Spatial data point to: (a) the expansion of HIV/AIDS towards malarigenic areas located in the centre-west and north of Brazil, along the main cocaine trafficking routes, with IDU networks apparently playing a core role; and (b) the possibility of new outbreaks of secondary malaria in urban settings where HIV/AIDS is still expanding, through the sharing of needles and syringes. New outbreaks of cases of HIV and malaria are likely to occur among Brazilian IDUs, and might conceivably contribute to the development of treatment-resistant strains of malaria in this population. Health professionals should be alert to this possibility, which could also eventually occur in IDU networks in developed countries.

The age-specific prevalence of Plasmodium falciparum in migrants to Irian Jaya is not attributable to agglutinating antibody repertoire

Previous observations have shown that individuals migrating from a malaria free area to a malaria endemic region in North Eastern Irian Jaya quickly acquire anti-parasite immunity, in an age-dependent manner. Sera from migrants and long-term residents in this area were examined for their ability to agglutinate a range of Plasmodium falciparum isolates and to disrupt erythrocyte rosettes. Antibody responses to merozoite surface protein 2 (MSP2) and ring-infected erythrocyte surface antigen (RESA) were also determined. The range of isolates agglutinated by sera from the migrants approached that seen in long-term residents. No difference was found between migrant adults and children in the range of agglutinating antibody, size of agglutinates, nor disruption of rosettes. Anti-MSP2 and anti-RESA antibodies were the only factors examined which showed a correlation with age. We conclude that although antibody to parasite neoantigens expressed on the surface of infected erythrocytes may play a role in the acquisition of immunity, the humoral response to other P. falciparum antigens is more likely to account for the age-dependent prevalence of parasitaemia observed.

Lymphocyte responsiveness to a candidate malaria sporozoite vaccine (R32tet32) of individuals with naturally acquired Plasmodium falciparum malaria.

Lymphocyte proliferative responses to the candidate malaria sporozoite vaccine antigen R32tet32 were evaluated in 29 patients with acute Plasmodium falciparum malaria, 20 convalescent patients, 11 nonimmune individuals, and 22 healthy residents of two endemic malarious areas in Thailand. The results indicate that 14 of 20 (70%) convalescent patients and 14 of 22 (64%) residents of endemic areas responded to the R32tet32 antigen. However, only 8 of 29 (28%) patients with acute P. falciparum malaria responded. When 4 of the convalescent patients who remained in a malaria-free area were restudied 5-10 months after the acute infection, they were either not responsive or their responses had greatly diminished. These findings show that sensitization to R32tet32 occurs following a natural P. falciparum infection, but the cellular immune response to sporozoite antigens may be short-lived and may be suppressed during acute P. falciparum malaria.

Antibodies against malaria sporozoites in patients with acute uncomplicated malaria and patients with cerebral malaria.

Serum samples from 95 patients with acute uncomplicated falciparum malaria (AM) and 95 patients with cerebral malaria (CM) were tested by the indirect immunofluorescent assay (IFA) for IgG and IgM antibodies against Plasmodium falciparum and P. vivax sporozoites. Forty-six (48%) CM patients were positive for antibodies against P. falciparum sporozoites whereas only 23 (24%) were positive for antibodies against P. vivax sporozoites (P less than 0.002). A similar result was obtained in AM patients. However, CM patients had significantly lower mean IgG anti-sporozoite titer for P. falciparum than did AM patients (P less than 0.05), especially when only anti-sporozoite antibody-positive CM and AM patients were compared (P less than 0.0005), suggesting that CM patients had relatively less exposure and were probably less immune to malaria than were AM patients. The persistence of anti-sporozoite antibodies also was investigated in paired sera taken 63 days apart from 108 patients with acute falciparum malaria. There were significant decreases in the mean antibody titers in the follow-up sera during the period of stay in the malaria-free area. It was proposed that determination of anti-sporozoite antibody be made as a substitute for, or in addition to, anti-blood stage antibody for seroepidemiological study of malaria, especially in the monitoring of the success of the malaria control program.

Nephrotic syndrome in the Africans and Indians of South Africa. A ten-year study

The frequency of nephrotic syndrome was 0.2% of all medical admission records. A prospective study of 180 nephrotic patients was begun in 1966 and ended in 1976 and the clinical, biochemical and renal histological changes were studied. Unlike other studies of nephrotic syndrome in West and East Africa, in which malaria is believed to play an important aetiological part, this study in Durban was done in a malaria-free area. Most of the patients were between the ages of 12 and 30 years. The aetiology of the nephrotic syndrome was undetermined in 94% of the African patients and in 87% of the Indian patients. The most common histological pattern in both racial groups was proliferative glomerulonephritis, followed by membranous glomerulonephritis. Minimal change on light microscopy was rare. This has important implications from the therapeutic aspect because African patients suffering from nephrotic syndrome will not as a rule respond to steroids or cyclophosphamide therapy. An initial diastolic blood pressure greater than or equal to 110 mm Hg and a low serum complement were more common in proliferative glomerulonephritis. The serum gamma-globulin, though low, was raised compared with the normal serum gamma-globulin, in the white population. A difference in the serum lipoprotein patient between the two races was observed.