Impact of Pregnancy-Associated Malaria on Infant Malaria Infection in Southern Benin

Background

Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life.

Methodology/ Principal Findings

To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother’s age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively.

Conclusions/ Significance

This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers.     

Spatial Biodiversity Patterns of Madagascar's Amphibians and Reptiles

Madagascar has become a model region for testing hypotheses of species diversification and biogeography, and many studies have focused on its diverse and highly endemic herpetofauna. Here we combine species distribution models of a near-complete set of species of reptiles and amphibians known from the island with body size data and a tabulation of herpetofaunal communities from field surveys, compiled up to 2008. Though taxonomic revisions and novel distributional records arose since compilation, we are confident that the data are appropriate for inferring and comparing biogeographic patterns among these groups of organisms. We observed species richness of both amphibians and reptiles was highest in the humid rainforest biome of eastern Madagascar, but reptiles also show areas of high richness in the dry and subarid western biomes. In several amphibian subclades, especially within the Mantellidae, species richness peaks in the central eastern geographic regions while in reptiles different subclades differ distinctly in their richness centers. A high proportion of clades and subclades of both amphibians and reptiles have a peak of local endemism in the topographically and bioclimatically diverse northern geographic regions. This northern area is roughly delimited by a diagonal spanning from 15.5°S on the east coast to ca. 15.0°S on the west coast. Amphibian diversity is highest at altitudes between 800–1200 m above sea-level whereas reptiles have their highest richness at low elevations, probably reflecting the comparatively large number of species specialized to the extended low-elevation areas in the dry and subarid biomes. We found that the range sizes of both amphibians and reptiles strongly correlated with body size, and differences between the two groups are explained by the larger body sizes of reptiles. However, snakes have larger range sizes than lizards which cannot be readily explained by their larger body sizes alone. Range filling, i.e., the amount of suitable habitat occupied by a species, is less expressed in amphibians than in reptiles, possibly reflecting their lower dispersal capacity. Taxonomic composition of communities assessed by field surveys is largely explained by bioclimatic regions, with communities from the dry and especially subarid biomes distinctly differing from humid and subhumid biomes.     

Plasmodium falciparum produce lower infection intensities in local versus foreign Anopheles gambiae populations

Both Plasmodium falciparum and Anopheles gambiae show great diversity in Africa, in their own genetic makeup and population dynamics. The genetics of the individual mosquito and parasite are known to play a role in determining the outcome of infection in the vector, but whether differences in infection phenotype vary between populations remains to be investigated. Here we established two A. gambiae s.s. M molecular form colonies from Cameroon and Burkina Faso, representing a local and a foreign population for each of the geographical sites. Experimental infections of both colonies were conducted in Cameroon and Burkina Faso using local wild P. falciparum, giving a sympatric and allopatric vector-parasite combination in each site. Infection phenotype was determined in terms of oocyst prevalence and intensity for at least nine infections for each vector-parasite combination. Sympatric infections were found to produce 25% fewer oocysts per midgut than allopatric infections, while prevalence was not affected by local/foreign interactions. The reduction in oocyst numbers in sympatric couples may be the result of evolutionary processes where the mosquito populations have locally adapted to their parasite populations. Future research on vector-parasite interactions must take into account the geographic scale of adaptation revealed here by conducting experiments in natural sympatric populations to give epidemiologically meaningful results.     

Midgut Microbiota of the Malaria Mosquito Vector Anopheles gambiae and Interactions with Plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.     

Anopheles and Plasmodium: from laboratory models to natural systems in the field

Parasites that cause malaria must complete a complex life cycle in Anopheles vector mosquitoes in order to be transmitted from human to human. Previous gene-silencing studies have shown the influence of mosquito immunity in controlling the development of Plasmodium. Thus, parasite survival to the oocyst stage increased when the parasite antagonist gene LRIM1 (leucine-rich repeat immune protein 1) of the mosquito was silenced, but decreased when the C-type lectin agonist gene CTL4 or CTLMA2 (CTL mannose binding 2) was silenced. However, such effects were shown for infections of the human mosquito vector Anopheles gambiae with the rodent parasite Plasmodium berghei. Here, we report the first results of A. gambiae gene silencing on infection by sympatric field isolates of the principal human pathogen P. falciparum. In contrast with the results obtained with the rodent parasite, silencing of the same three genes had no effect on human parasite development. These results highlight the importance of following up discoveries in laboratory model systems with studies on natural parasite-mosquito interactions.     

Nicotinamide adenine dinucleotides permeate through mitochondrial membranes in human Epstein-Barr virus-transformed lymphocytes

Human cultured cells are widely used for the investigation of respiratory chain disorders. Oxidative properties are generally investigated by means of polarographic studies carried out on detergent-permeabilized cells. By studying the oxidative properties of Epstein-Barr virus-transformed B lymphocytes, we found that the respiration was significantly decreased after 3–4 days of cell culture. Simultaneously, we observed that NAD⁺-dependent oxidations (malate, glutamate, pyruvate) became dependent upon the addition of exogenous NAD⁺. The effect of NAD⁺ was shown to be related to an influx of catalytic amount of NAD⁺ into the mitochondrial matrix. A full ability to oxidize NAD⁺-dependent substrates was restored less than 2 h after a change of the culture medium.These observations suggested: (a) the occurrence of fluxes of catalytic amounts of NAD⁺ through the mitochondrial inner membrane in human cells; (b) an early control of mitochondrial metabolism by matrix NAD⁺ content in cells grown under limiting growth conditions; (c) the possible confusion between complex I deficiency and a decrease content of matrix NAD⁺ when using human cultured cells. (Mol Cell Biochem 115–119, 1997)     

Monitoring Great Ape and Elephant Abundance at Large Spatial Scales: Measuring Effectiveness of a Conservation Landscape

Protected areas are fundamental to biodiversity conservation, but there is growing recognition of the need to extend beyond protected areas to meet the ecological requirements of species at larger scales. Landscape-scale conservation requires an evaluation of management impact on biodiversity under different land-use strategies; this is challenging and there exist few empirical studies. In a conservation landscape in northern Republic of Congo we demonstrate the application of a large-scale monitoring program designed to evaluate the impact of conservation interventions on three globally threatened species: western gorillas, chimpanzees and forest elephants, under three land-use types: integral protection, commercial logging, and community-based natural resource management. We applied distance-sampling methods to examine species abundance across different land-use types under varying degrees of management and human disturbance. We found no clear trends in abundance between land-use types. However, units with interventions designed to reduce poaching and protect habitats - irrespective of land-use type - harboured all three species at consistently higher abundance than a neighbouring logging concession undergoing no wildlife management. We applied Generalized-Additive Models to evaluate a priori predictions of species response to different landscape processes. Our results indicate that, given adequate protection from poaching, elephants and gorillas can profit from herbaceous vegetation in recently logged forests and maintain access to ecologically important resources located outside of protected areas. However, proximity to the single integrally protected area in the landscape maintained an overriding positive influence on elephant abundance, and logging roads – even subject to anti-poaching controls - were exploited by elephant poachers and had a major negative influence on elephant distribution. Chimpanzees show a clear preference for unlogged or more mature forests and human disturbance had a negative influence on chimpanzee abundance, in spite of anti-poaching interventions. We caution against the pitfalls of missing and confounded co-variables in model-based estimation approaches and highlight the importance of spatial scale in the response of different species to landscape processes. We stress the importance of a stratified design-based approach to monitoring species status in response to conservation interventions and advocate a holistic framework for landscape-scale monitoring that includes smaller-scale targeted research and punctual assessment of threats.