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Biomedical subjects

John C Beier

Publications and source records attributed to John C Beier.

14 recordsLinked to original sources

Low recovery rates stabilize malaria endemicity in areas of low transmission in coastal Kenya.

The prevalence of Plasmodium falciparum malaria in African communities can be high and stable even in areas of relatively low transmission where people expose to only a few infectious bites per year. We show in this field study conducted in 30 sites along the coastal Kenya that prevalence in school children was consistently high, although there were many sites where transmission intensity measured by exposure to infectious bites was less than 10 per year. Statistical analyses revealed that prevalence was significantly correlated with the infectious exposure occurring 10-11 months previously, suggesting that long-lived infections were commonplace and one of the major contributors for the stability of malaria in these sites. Using mechanistic models of malaria transmission, we found that the association of high prevalence and low transmission could be due to low recovery rates. Therefore, significant reductions of malaria prevalence and burden require substantial reductions of the duration of acquired infections, even in areas that have quite low transmission intensities by the standards of sub-Saharan Africa. Infection control featured by active detection and drug treatment as well as vector control is critical to combat malaria in areas of relatively low transmission intensity.

Animals↗

Malaria transmission in urban sub-Saharan Africa.

The rapid increase in the world's urban population has major implications for the epidemiology of malaria. A review of malaria transmission in sub-Saharan African cities shows the strong likelihood of transmission occurring within these sprawling cities, whatever the size or characteristics of their bioecologic environment. A meta-analysis of results from studies of malaria transmission in sub-Saharan Africa shows a loose linear negative relationship between mean annual entomologic inoculation rates (EIR) and the level of urbanicity. Few studies have failed to find entomologic evidence of some transmission. Our results show mean annual EIRs of 7.1 in the city centers, 45.8 in periurban areas, and 167.7 in rural areas. The impact of urbanization in reducing transmission is more marked in areas where the mean rainfall is low and seasonal. Considerable variation in the level of transmission exists among cities and within different districts in the same city. This article presents evidence from past literature to build a conceptual framework to begin to explain this heterogeneity. The potential for malaria epidemics owing to decreasing levels of natural immunity may be offset by negative impacts of urbanization on the larval ecology of anopheline mosquitoes. Malaria control in urban environments may be simpler as a result of urbanization; however, much of what we know about malaria transmission in rural environments might not hold in the urban context.

Africa South of the Sahara↗

A geographic sampling strategy for studying relationships between human activity and malaria vectors in urban Africa.

This paper describes a geographic sampling strategy for ecologic studies and describes the relationship between human activities and anopheline larval ecology in urban areas. Kisumu and Malindi, Kenya were mapped using global positioning systems, and a geographic information system was used to overlay a measured grid, which served as a sampling frame. Grid cells were stratified and randomly selected according to levels of planning and drainage. A cross-sectional survey was conducted in April and May 2001 to collect entomologic and human ecologic data. Multivariate regression analysis was used to test the relationship between the abundance of potential larval habitats, and house density, socioeconomic status, and planning and drainage. In Kisumu, 98 aquatic habitats were identified, 65% of which were human made and 39% were positive for anopheline larvae. In Malindi, 91 aquatic habitats were identified, of which, 93% were human made and 65% were harboring anopheline larvae. The regression model explains 82% of the variance associated with the abundance of potential larval habitats in Kisumu. In Malindi, 59% of the variance was explained. As the number of households increased, the number of larval habitats increased correspondingly to a point. Beyond a critical threshold, the density of households appeared to suppress the development of aquatic habitats. The proportion of high-income households and the planning and drainage variables tested insignificant in both locations. The integration of social and biologic sciences will allow local mosquito and malaria control groups an opportunity to assess the risk of encountering potentially infectious mosquitoes in a given area, and concentrate resources accordingly.

Africa↗

Determination of Anopheles gambiae larval DNA in the gut of insectivorous dragonfly (Libellulidae) nymphs by polymerase chain reaction.

We examined the predator-prey relationship between larvae of the malaria mosquito Anopheles gambiae and nymphs of the dragonfly (Libellulidae). Studies were conducted to determine whether polymerase chain reaction (PCR) can be used to detect DNA of An. gambiae in the gut of libellulid nymphs, and to determine how long after feeding on An. gambiae that mosquito DNA remains detectable by PCR. Total DNA was extracted from the gut contents of libellulid nymphs by using 2 types of DNA extraction methods. The target sequence for the diagnostic PCR was the intergenic spacer regions of the ribosomal DNA gene locus. These sequences were analyzed by using An. gambiae complex-specific primers. After analyzing nymphal gut contents with PCR at regular postfeed intervals, a 390-base pair product could be amplified. The presence of mosquito larvae was visually confirmed for up to 40 min after feeding. Regardless of the number of mosquito larvae ingested, libellulid gut contents could be amplified or visually seen up to 1 h of digestion. This result indicates the nymphs have a high rate of digestion and that PCR with An. gambiae complex primers will be best utilized within 1 h after feeding as a detection system. This study confirmed that dragonfly nymphs feed well on anopheline larvae, and that mosquito DNA, although rapidly digested, can be successfully recovered and detected from within nymphal digestive tracts.

Animals↗

Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast.

The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.

Animals↗

MalariaSphere: a greenhouse-enclosed simulation of a natural Anopheles gambiae (Diptera: Culicidae) ecosystem in western Kenya.

BACKGROUND: The development and implementation of innovative vector control strategies for malaria control in Africa requires in-depth ecological studies in contained semi-field environments. This particularly applies to the development and release of genetically-engineered vectors that are refractory to Plasmodium infection. Here we describe a modified greenhouse, designed to simulate a natural Anopheles gambiae Giles ecosystem, and the first successful trials to complete the life-cycle of this mosquito vector therein. METHODS: We constructed a local house, planted crops and created breeding sites to simulate the natural ecosystem of this vector in a screen-walled greenhouse, exposed to ambient climate conditions, in western Kenya. Using three different starting points for release (blood-fed females, virgin females and males, or eggs), we allowed subsequent stages of the life-cycle to proceed under close observation until one cycle was completed. RESULTS: Completion of the life-cycle was observed in all three trials, indicating that the major life-history behaviours (mating, sugar feeding, oviposition and host seeking) occurred successfully. CONCLUSION: The system described can be used to study the behavioural ecology of laboratory-reared and wild mosquitoes, and lends itself to contained studies on the stability of transgenes, fitness effects and phenotypic characteristics of genetically-engineered disease vectors. The extension of this approach, to enable continuous maintenance of successive and overlapping insect generations, should be prioritized. Semi-field systems represent a promising means to significantly enhance our understanding of the behavioural and evolutionary ecology of African malaria vectors and our ability to develop and evaluate innovative control strategies. With regard to genetically-modified mosquitoes, development of such systems is an essential prerequisite to full field releases.

Animals↗

Examining the determinants of mosquito-avoidance practices in two Kenyan cities.

BACKGROUND: This study assesses the behavioural and socio-economic factors associated with avoiding mosquitoes and preventing malaria in urban environments in Kenya. METHODS: Data from two cities in Kenya were gathered using a household survey and a two-stage cluster sample design. The cities were stratified based on planning and drainage observed across the urban areas. This helped control for the strong environmental and topographical variation that we assumed influences mosquito ecology. Individual interviews given to each household included questions on socio-economic status, education, housing type, water source, rubbish disposal, mosquito-prevention practices and knowledge of mosquitoes. In multivariate regression, factors measuring wealth, education level, and the communities' level of planning and drainage were used to estimate the probability that a household engages in multiple mosquito-avoidance activities, or has all members sleeping under a bed net. RESULTS: Our analysis shows that people from wealthier, more educated households were more likely to sleep under a net, in Kisumu (OR = 6.88; 95% CI = 2.56,18.49) and Malindi (OR = 3.80; 95% CI = 1.91,7.55). Similarly, the probability that households use several mosquito-prevention activities was highest among the wealthiest, best-educated households in Kisumu (OR = 5.15; 95% CI = 2.04,12.98), while in Malindi household wealth alone is the major determinant. CONCLUSION: We demonstrate the importance of examining human-mosquito interaction in terms of how access to resources may enhance human activities. The findings illustrate that the poorest segments of society are already doing many things to protect themselves from being bitten, but they are doing less than their richer neighbours.

Animals↗

Characterization of a unique human single-chain antibody isolated by phage-display selection on membrane-bound mosquito midgut antigens.

The insect midgut is the primary site for food digestion, as well as for vector-borne pathogen infection into the invertebrate host. Accordingly, antigens of this critical insect organ are targets for anti-vector vaccines, insecticidal toxins, and transmission-blocking vaccines. We used midgut proteins of the African malaria vector mosquito Anopheles gambiae to select single-chain human antibody fragments (scFv) from a high-diversity, phage-displayed library. Using a phage-display selection method on western-blotted antigens, we selected an unusual truncated scFv clone, consisting of a heavy-chain only, which binds to An. gambiae midgut tissue. This clone binds a spectrum of mosquito antigens from the midgut and other mosquito tissues, as well as various mammalian glycoproteins, but binding was reduced when these glycoproteins were enzymatically deglycosylated. We also observed that this clone preferentially binds the lumenal midgut surface. Furthermore, antigen binding by our selected scFv was limited by competition with increasing concentrations of certain soluble carbohydrates, most dramatically by galactose and N-acetyl glucosamine. Our results show that the cognate epitope of this scFv is a carbohydrate moiety. This paper describes a phage-display selection of antibody fragments on mosquito midgut tissue and it also describes a method for phage-display selection on membrane-immobilized heterogeneous antigens. These selection methods resulted in the isolation of a novel, truncated, carbohydrate-binding human antibody fragment from a naive phage-display library.

Amino Acid Sequence↗

Vector analysis.

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Animals↗

A biologic basis for integrated malaria control.

In a series of models of Plasmodium falciparum dynamics, spontaneous local extinctions of the parasite sometimes occurred under steady, perennial-transmission conditions. These extinctions occurred only with extremely low mosquito densities or when the parameter describing the duration of human infection-blocking immunity was at its maximum value, and, simultaneously, those describing vector survivorship and the duration of human infectivity were at their minimum values. The range and frequency of extinctions increased with seasonal transmission, and decreased with the emergence of recombinant genotypes. Here we extend the immunity parameter up to levels that would describe a successful vaccine, and examine the combined influences of seasonality, genotype cross-reactivity, meiotic recombination, and human population turnover on parasite persistence. As Ross did 90 years ago, we conclude that malaria control programs that encompass several methods and targets of intervention are the most likely to succeed. Success is more likely if programs are cognizant of local circumstances of transmission, and, within that context, aim to reduce vector survivorship and human infectivity as well as augment human immunity.

Animals↗

Fast and slow blood-feeding durations of Aedes aegypti mosquitoes in Trinidad.

The duration of blood feeding by similar-sized Aedes aegypti (L.) was determined under laboratory conditions in Trinidad, West Indies. Ae. aegypti from the F0 generation contained individuals that fed quickly (106.2 seconds) as well as slowly (330.0 seconds). Among the fast feeders (<2 min), the time taken for blood feeding during the first gonotrophic cycle was much shorter than that observed for the 2nd, 3rd and 4th gonotrophic cycles. In contrast, among the slow feeders the time taken was much slower in the first gonotrophic cycle than that observed in subsequent gonotrophic cycles. Similarly, fast and slow feeding rates did not persist among the progeny of the F0 individuals reared to F1, F2, F3 and F4 generations. The size of the egg clutches was not significantly different for fast- and slow-feeding Ae. aegypti mosquitoes, with mean number of eggs being 85.1 +/- 21.6 for fast feeders and 83.8 +/- 17.7 for slow feeders during the first gonotrophic cycle. Similar patterns were observed among F1, F2, F3 and F4 generations with mean number of eggs being 86.4 +/- 14.8 (range 70-179 eggs) and 87.9 +/- 15.7 (range 68-121 eggs) for the fast and slow feeding females, respectively. These results indicate that mosquitoes have the ability to increase or decrease feeding durations as required, which may counter any physical interference during the blood-feeding process and may consequently enhance vector efficiency.

Adaptation, Physiological↗

An individual-based model of Plasmodium falciparum malaria transmission on the coast of Kenya.

Individual-based models provide powerful tools to model complex interactions characterized by individual variability. This paper presents an object-oriented design for individual-based modelling of Plasmodium falciparum malaria transmission. Two kinds of objects, human and mosquito, that exhibit variability among individuals for parameters such as recovery and survival rates are defined. The model tracks the dynamics of human hosts and adult female mosquitoes individually. Immunity, modelled as a function of exposure history, is represented by reduced susceptibility and increased recovery rate. The model was calibrated using epidemiological data collected at 30 sites along the coast of Kenya. The sites were grouped into low, intermediate and high transmission based on mean daily human-biting rates. Simulation results show that malaria transmission was stable even in low transmission areas where the human-biting rate is approximately 0.5 bite per day. The model was used to examine the effect of infection control programmes that aim at interrupting transmission by reducing human-vector contact rates and implementing active case detection and drug treatment of infections. With this intervention, local elimination of malaria is likely with a probability of extinction of approximately 0.8 in low transmission areas. However, a small amount of immigration (> 0.3%) by infected people into the community could prevent local extinction of the parasite. In intermediate and high transmission areas, reduction in prevalence is short-lived and the probability of local elimination is low, even at high coverage levels of the intervention.

Age Distribution↗