Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon

Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range.     

Mitochondrial genome sequences support ancient population expansion in Plasmodium vivax

Examination of nucleotide diversity in 106 mitochondrial genomes of the most geographically widespread human malaria parasite, Plasmodium vivax, revealed a level of diversity similar to, but slightly higher than, that seen in the virulent human malaria parasite Plasmodium falciparum. The pairwise distribution of nucleotide differences among mitochondrial genome sequences supported the hypothesis that both these parasites underwent ancient population expansions. We estimated the age of the most recent common ancestor (MRCA) of the mitochondrial genomes of both P. vivax and P. falciparum at around 200,000-300,000 years ago. This is close to the previous estimates of the time of the human mitochondrial MRCA and the origin of modern Homo sapiens, consistent with the hypothesis that both these Plasmodium species were parasites of the hominid lineage before the origin of modern H. sapiens and that their population expansion coincided with the population expansion of their host.     

Meiotic recombination, cross-reactivity, and persistence in Plasmodium falciparum

We incorporate a representation of Plasmodium falciparum recombination within a discrete-event model of malaria transmission. We simulate the introduction of a new parasite genotype into a human population in which another genotype has reached equilibrium prevalence and compare the emergence and persistence of the novel recombinant forms under differing cross-reactivity relationships between the genotypes. Cross-reactivity between the parental (initial and introduced) genotypes reduces the frequency of appearance of recombinants within three years of introduction from 100% to 14%, and delays their appearance by more than a year, on average. Cross-reactivity between parental and recombinant genotypes reduces the frequency of appearance to 36% and increases the probability of recombinant extinction following appearance from 0% to 83%. When a recombinant is cross-reactive with its parental types, its probability of extinction is influenced by cross-reactivity between the parental types in the opposite manner; that is, its probability of extinction after appearance decreases. Frequencies of P. falciparum outcrossing are mediated by frequencies of mixed-genotype infections in the host population, which are in turn mediated by the structure of cross-reactivity between parasite genotypes. The three leading hypotheses about how meiosis relates to oocyst production lead to quantitative, but no qualitative, differences in these results.     

First published record of urban malaria in Puerto Gaitán, Meta,Colombia

Patterns of malaria cases were compared between the department of Meta and themunicipality of Puerto Gaitán, Colombia, to examine temporal change in malaria from2005-2010. During this time frame in Meta the mean ratio was 2.53; in contrast, inPuerto Gaitán it was 1.41, meaning that a surprisingly high proportion ofPlasmodium falciparum cases were reported from this municipality.A detailed analysis of data from Puerto Gaitán for 2009 and 2010 detected asignificant difference (χ2, p < 0.001) in the distribution of plasmodia, withPlasmodium vivax more prevalent in 2009 and P.falciparum in 2010. Males had the highest number of cases but there wasno difference in the distribution of cases between sexes and years. In both years,for both sexes, people 16-40 accounted for the majority of cases (58.9% in 2009;60.4% in 2010). There were significant differences in the distribution of bothP. vivax (χ2, p < 0.01) and P. falciparumcases (χ2, p < 0.05) by geographic setting (urban vs. non-urban) between years.Urban cases of both P. vivax and P. falciparum arerecorded in this study for the first time in Puerto Gaitán, possibly the result ofarea wide displacement and migration due to armed conflict.     

The assessment of antimalarial drug efficacy

Antimalarial drug efficacy in uncomplicated malaria should be assessed parasitologically in large, community-based trials, enrolling the age groups most affected by clinical disease. For rapidly eliminated drugs, a 28-day follow-up is needed, but, for slowly eliminated drugs, up to nine weeks could be required to document all recrudescences, and, when possible, the drug levels should also be measured. The WHO 14-day assessments are neither sensitive nor specific. In tropical Plasmodium vivax and Plasmodium ovale infections treated with chloroquine, the first relapse is usually suppressed by residual drug levels. A relapse cannot be distinguished confidently from a recrudescence. Host immunity is a major contributor to the therapeutic response, and can make failing drugs appear effective.     

A historical perspective on malaria control in Brazil

Malaria has always been an important public health problem in Brazil. The earlyhistory of Brazilian malaria and its control was powered by colonisation by Europeansand the forced relocation of Africans as slaves. Internal migration brought malariato many regions in Brazil where, given suitableAnopheles mosquitovectors, it thrived. Almost from the start, officials recognised the problem malariapresented to economic development, but early control efforts were hampered by stilldeveloping public health control and ignorance of the underlying biology and ecologyof malaria. Multiple regional and national malaria control efforts have beenattempted with varying success. At present, the Amazon Basin accounts for 99% ofBrazil’s reported malaria cases with regional increases in incidence often associatedwith large scale public works or migration. Here, we provide an exhaustive summary ofprimary literature in English, Spanish and Portuguese regarding Brazilian malariacontrol. Our goal was not to interpret the history of Brazilian malaria control froma particular political or theoretical perspective, but rather to provide astraightforward, chronological narrative of the events that have transpired in Brazilover the past 200 years and identify common themes.     

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.     

Surveillance of vivax malaria vectors and civilian patients for malaria high-risk areas in northern Gyeonggi and Gangwon Provinces near the demilitarized zone,Republic of Korea, 2003–2006

After re-emergence of malaria in 1993, a continued increase in Plasmodium vivax cases was observed from 1993 to 2006 in northern Gyeonggi and Gangwon Provinces adjacent to the demilitarized zone separating North from South Korea. Annual parasite incidence per 1000 people ranged from 0.33 in 2004 to 0.89 in 2006. While malaria case rates declined (22.6%) in 2004, they increased 75.1% in 2005 and 51.7% in 2006 from the previous years. An initial incorrect diagnosis of 46.8% of malaria cases as common cold resulted in a mean delay of 1.3 days for the detection malarial parasites. Of the total cases, 10.2% from December to May were due to latent intrinsic incubation infections acquired the previous malaria season and the rest of the cases from June to November were either latent or short incubation infections. Overall, the peak anopheline population occurred from July to September, resulting in a similar peak in malaria cases. While malaria cases increased during 2005–2006, anopheline populations, based on trap indices, were not significantly different during 4 years of surveillance. To decrease the malaria patient infective period to mosquitoes, public health centers in Paju and Cheorwon in 2006 prescribed chloroquine + primaquine at days 0–3 after initial malaria diagnosis followed by an additional 11 days of primaquine (early primaquine treatment), rather than chloroquine on days 0–3 and primaquine on days 4–17 (delayed primaquine treatment). A reduction in the malaria parasite incidence during 2007 was recorded for the two locations offering the early primaquine treatment relative to other locations using the delayed primaquine treatment.     

Review: Natural Antimalarial Agents (1995-2001)

Malaria is one of the diseases for which even today not many suitable drugs are available. The rapid spread of resistance toward current drugs encourages the study for new active molecules. Ethnobotanical research can be of help to find new leads. Traditional remedies have always been a source of important antimalarial drugs and continue to provide novel and effective treatments, both where pharmaceuticals are not available and also where the disease is highly resistant to commonly prescribed drugs. This article provides a comparative compilation of various studies reported between 1995 and 2001 on natural compounds with antiplasmodial activity, with the goal of providing a basis for further in vitro and in vivo studies, as well as for clinical trials for the development of new antimalarial medicines. Referee: Dr. Robert Verpoorte, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, PO Box 9502, 2300 RA Leiden, The Netherlands     

Malaria in Brazil: what happens outside the Amazonian endemic region

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.     

Membrane proteins involved in the adherence of Plasmodium falciparum-infected erythrocytes to the endothelium.

Plasmodium falciparum (human malaria) infections are characterized by the attachment of erythrocytes infected with mature stage parasites to endothelial cells lining the post-capillary venules, a phenomenon known as sequestration. In the human body, the microvessels of the heart, lungs, kidneys, small intestine, and liver are the principal sites of sequestration. Sequestered cells that clog the brain capillaries may reduce blood flow sufficiently so that there is confusion, lethargy, and unarousable coma--cerebral malaria. This review considers what is known about the molecular characteristics of the surface proteins, that is, the red cell receptors and the endothelial cell ligands, involved in sequestration. Recent work from our laboratory on the characterization of the adhesive proteins on the surface of the P falciparum-infected red cell, and the ligands to which they bind on human brain endothelial cells is also discussed. Finally, consideration is given to the multifactor processes involved in sequestration and cerebral malaria, as well as the possible role of 'anti-adhesion therapy' in the management of severe malaria.