Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon.

BACKGROUND: The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. METHODS: We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. FINDINGS: Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. INTERPRETATION: This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts.

The Effects of Plasmodium vivax Gestational Malaria on the Clinical and Immune Status of Pregnant Women in Northwestern Colombia.

OBJECTIVE: The study explored the effects of Plasmodium vivax infection on the balance of pro- versus anti- inflammatory cytokines and chemokines and their relationship with some clinical and epidemiology outcomes. METHODS: Thirty-five pregnant women were recruited. Of these, 15 subjects had malaria at delivery (GM+), and 20 had no exposition to infection throughout the pregnancy (GM-) and at delivery. Epidemiological and clinical data were recorded after reviewing the clinical records. At delivery, whole blood from the mother as well as placental tissue was collected. Diagnosis of infection was performed by thick smear and a polymerase chain reaction (PCR). Expression of pro-inflammatory and anti-inflammatory cytokines and chemokines was measured by a real time PCR. RESULTS: The clinical and epidemiological variables explored were similar in both groups, with the exception of gestational age. When comparing the GM+ group with the GM- group, it is clear that although the differences generally are not significant, pro- inflammatory cytokines are elevated in both maternal blood and placental; anti-inflammatory ones are elevated in the mother and reduced in the placenta, and the chemokines are reduced in both compartments, except for MCP-1 which is elevated in all. CONCLUSION: The results appear to be strongly affected by the small number of women with GM by P. vivax at childbirth. Additional studies are needed with larger groups in this and other regions of the country.

OBJETIVO: En este estudio se determinó el efecto de la infección por Plasmodium vivax en el balance de citoquinas pro-inflamatorias/anti-inflamatorias y quemoquinas y su relación con algunas variables epidemiológicas y clínicas. MÉTODOS: Se reclutaron 35 gestantes, 15 con malaria en el momento del parto (GM+) y 20 sin malaria en ningún momento de la gestación (GM-) Los datos epidemiológicos y clínicos fueron colectados a partir de la historia clínica. En el momento del parto fueron tomadas muestras de sangre periférica materna y tejido placentario. El diagnóstico fue realizado mediante gota gruesa y reaccion en cadena de la polimerasa (PCR). La expresión de citoquinas pro-inflamatorias/anti-inflamatorias y quimioquinas, fueron medidas por PCR en tiempo real. La expresión de citoquinas pro-inflamatorias/anti-inflamatorias y quemoquinas, fueron medidas por PCR en tiempo real. RESULTADOS: En las variables epidemiológicas y clínicas, los datos fueron similares en ambos grupos. Al comparar el grupo GM+ con el grupo GM-, resulta claro que, aunque las diferencias, en general, no son significativas, las citoquinas proinflamatorias están elevadas tanto en sangre materna como placentaria, las antiinflamatorias están elevadas en la madre y reducidas en la placenta, y las quimioquinas están reducidas en ambos compartimentos, excepto la MCP-1 que está elevada en ambos. CONCLUSIÓN: Los resultados parecen estar fuertemente afectados por la cantidad pequeña de mujeres con MG por P. vivax en el parto. Es necesario adelantar estudios adicionales con más mujeres tanto en esta región como en otros lugares.

Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults.

Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between IL12B polymorphisms [i.e. IL12Bpro (rs17860508) and IL12B 3' UTR T/G (rs3212227)], severe malaria and cytokine production was examined in patients with Plasmodium falciparum infections (n = 355) recruited from malaria endemic areas along the Thai-Myanmar border in northwest Thailand. Circulating IL-12p40 (p = 0.049) and IFN-gamma (p = 0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients with hyperparasitaemia (p = 0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94-5.81; p = 0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17-9.87; p = 0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p = 0.002) and the highest IFN-gamma (p = 0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3' UTR-T haplotype was associated with protection against severe malaria (OR, 0.51; 95% CI, 0.29-0.90; p = 0.020) and reduced circulating IFN-gamma (p = 0.06). Thus, genotypic and haplotypic variation at IL12Bpro and IL12B 3' UTR in this population influences susceptibility to severe malaria and functional changes in circulating IL-12p40 and IFN-gamma levels. Results presented here suggest that protection against severe malaria in Thai adults is associated with genotypic variants that condition enhanced IL-12p40 and reduced IFN-gamma levels.