Asymptomatic plasmodial infection in pregnant women: A global scenario.

Though asymptomatic plasmodial infection (API) is well known phenomenon and play an important role in different populations and malaria transmission settings, it has received less attention in malaria intervention strategies. This review was aimed to estimate the prevalence of API in pregnant women across the world. The bibliography records relevant to the study were searched on PubMed and Lilacs, till August 15, 2016, without restriction of language. A total of 78 references were identified, of which 29 met the inclusion criteria. The study of the identified reports revealed that the mean prevalence of API in pregnant women was 10.8% (3382/31186), with wide variation among countries and transmission settings. The reports showed that APIs are very common even in low malaria transmission areas, and most of the APIs are due to submicroscopic plasmodial infection (SPI). More sensitive diagnostic tools are required to address API and SPI in such areas. Every malaria endemic region/country should carry out systematic studies for accurate estimation of frequency for both these events (API and SPI) in different populations for planning appropriate intervention measures.

Functional antibodies against VAR2CSA in nonpregnant populations from colombia exposed to Plasmodium falciparum and Plasmodium vivax.

In pregnancy, parity-dependent immunity is observed in response to placental infection with Plasmodium falciparum. Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most settings of malaria endemicity, antibodies against VAR2CSA are predominantly observed in multigravid women and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute P. falciparum and Plasmodium vivax infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5ε, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed only in pregnant women, men, and children exposed either to P. falciparum or to P. vivax. Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulfate A in vitro, suggesting that they are specific and functional. These unexpected results suggest that there may be genotypic or phenotypic differences in the parasites of this region or in the host response to either P. falciparum or P. vivax infection outside pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region.

Genotype comparison of Plasmodium vivax and Plasmodium falciparum clones from pregnant and non-pregnant populations in North-west Colombia.

BACKGROUND: Placental malaria is the predominant pathology secondary to malaria in pregnancy, causing substantial maternal and infant morbidity and mortality in tropical areas. While it is clear that placental parasites are phenotypically different from those in the peripheral circulation, it is not known whether unique genotypes are associated specifically with placental infection or perhaps more generally with pregnancy. In this study, genetic analysis was performed on Plasmodium vivax and Plasmodium falciparum parasites isolated from peripheral and placental blood in pregnant women living in North-west Colombia, and compared with parasites causing acute malaria in non-pregnant populations. METHODS: A total of 57 pregnant women at delivery with malaria infection confirmed by real-time PCR in peripheral or placental blood were included, as well as 50 pregnant women in antenatal care and 80 men or non-pregnant women with acute malaria confirmed by a positive thick smear for P. vivax or P. falciparum. Five molecular markers per species were genotyped by nested PCR and capillary electrophoresis. Genetic diversity and the fixation index FST per species and study group were calculated and compared. RESULTS: Almost all infections at delivery were asymptomatic with significantly lower levels of infection compared with the groups with acute malaria. Expected heterozygosity for P. vivax molecular markers ranged from 0.765 to 0.928 and for P. falciparum markers ranged from 0.331 to 0.604. For P. vivax infections, the genetic diversity was similar amongst the four study groups and the fixation index from each pairwise comparison failed to show significant genetic differentiation. For P. falciparum, no genetic differentiation was observed between placental and peripheral parasites from the same woman at delivery, but the parasites isolated at delivery showed significant genetic differentiation compared with parasites isolated from subjects with acute malaria. CONCLUSIONS: In North-west Colombia, P. vivax parasites have high genetic diversity that is equivalent in pregnant and non-pregnant populations as well as in symptomatic and asymptomatic infections. For P. falciparum, the overall genetic diversity is lower, with specific genotypes associated with asymptomatic infections at delivery.

Asymptomatic plasmodial infection in Colombian pregnant women.

Information about asymptomatic plasmodial infection is scarce in the world, and the current antimalarial program goals (control, elimination, and eradication) demand this evidence to be well documented in different populations and malaria transmission settings. This study aimed to measure the prevalence of API in Colombian pregnant women at delivery. A retrospective prevalence survey was used. Women were recruited at hospital obstetric facility in each of the municipalities of Turbo, Necoclí in Antioquia department, and Puerto Libertador in Córdoba department. Malaria infection was tested by thick blood smear (TBS) and real-time quantitative PCR (qPCR). Ninety-six pregnant women at delivery were studied: 95% were asymptomatic (91/96), 45% had asymptomatic plasmodial infection (API) by qPCR (41/91), and only 8% (7/91) had API by microscopy. The prevalence of submicroscopic infections (TBS negative and qPCR positive) was very high, 37% (34/91) in asymptomatic women and 41% (39/96) in total women studied (91 asymptomatic and 5 symptomatic). The prevalence of API in Colombian pregnant women is much higher than which is expected for a country that does not have the level of malaria transmission as Sub-Saharan African countries.

A high resolution case study of a patient with recurrent Plasmodium vivax infections shows that relapses were caused by meiotic siblings.

Plasmodium vivax infects a hundred million people annually and endangers 40% of the world's population. Unlike Plasmodium falciparum, P. vivax parasites can persist as a dormant stage in the liver, known as the hypnozoite, and these dormant forms can cause malaria relapses months or years after the initial mosquito bite. Here we analyze whole genome sequencing data from parasites in the blood of a patient who experienced consecutive P. vivax relapses over 33 months in a non-endemic country. By analyzing patterns of identity, read coverage, and the presence or absence of minor alleles in the initial polyclonal and subsequent monoclonal infections, we show that the parasites in the three infections are likely meiotic siblings. We infer that these siblings are descended from a single tetrad-like form that developed in the infecting mosquito midgut shortly after fertilization. In this natural cross we find the recombination rate for P. vivax to be 10 kb per centimorgan and we further observe areas of disequilibrium surrounding major drug resistance genes. Our data provide new strategies for studying multiclonal infections, which are common in all types of infectious diseases, and for distinguishing P. vivax relapses from reinfections in malaria endemic regions. This work provides a theoretical foundation for studies that aim to determine if new or existing drugs can provide a radical cure of P. vivax malaria.

Molecular detection of malaria at delivery reveals a high frequency of submicroscopic infections and associated placental damage in pregnant women from northwest Colombia.

Plasmodium infection in pregnancy causes substantial maternal and infant morbidity and mortality. In Colombia, both P. falciparum and P. vivax are endemic, but the impact of either species on pregnancy is largely unknown in this country. A cross-sectional study was carried out with 96 pregnant women who delivered at their local hospital. Maternal, placental, and cord blood were tested for malaria infection by microscopy and real-time quantitative polymerase chain reaction (qPCR). A high frequency of infection was detected by qPCR (45%). These infections had low concentrations of parasite DNA, and 79% were submicroscopic. Submicroscopic infections were associated with placental villitis and intervillitis. In conclusion, the overall frequency of Plasmodium infection at delivery in Colombia is much higher than previously reported. These data prompt a re-examination of the local epidemiology of malaria using molecular diagnostics to establish the clinical relevance of submicroscopic infections during pregnancy as well as their consequences for mothers and newborns.

Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia.

This study compared the efficacy against Plasmodium falciparum gametocytes of four regimens: amodiaquine-sulfadoxine/pyrimethamine (AQ-SP) and mefloquine-artesunate (MQ-AS), with and without primaquine (PQ) administered with the second dose of the schizonticide (AQ-SP; AQ-SP-PQ; MQ-AS; MQ-AS-PQ). Efficacy was determined by thick smear on days 1, 4 and 8 after the beginning of treatment. A total of 82 patients (19-23/group) were recruited. After AQ-SP administration, gametocytemia steadily increased until day 8. With AQ-SP-PQ, a marked decline in gametocytemia was detected on days 4 and 8. MQ-AS treatment resulted in reduced gametocytemia on days 4 and 8, and with MQ-AS-PQ it was reduced even further. None of the treatments cleared gametocytemia by day 8. Currently, artemisinin-based combination therapies plus PQ are the recommended treatment option against falciparum malaria; however, further studies are required to optimize the use of PQ. Issues to be addressed include the optimal time of administration, treatment duration, optimal daily and total dose, and day of evaluation of the gametocytocidal effect. In falciparum malaria, the WHO recommends a maximum of 4days of treatment; consequently, an effective regimen must clear asexual parasites and symptoms within this time frame. The same criteria should be taken into account when evaluating the anti-gametocyte activity.