Plasmodium falciparum Incidence Relative to Entomologic Inoculation Rates at a Site Proposed for Testing Malaria Vaccines in Western Kenya

Beier, John C.; Oster, Charles N.; Onyango, Fred K.; Bales, James D.; Sherwood, James A.; Perkins, Peter V.; Chumo, David K.; Koech, Davy V.; Whitmire, Richard E.; Roberts, Clifford R.; Diggs, Carter L.; Hoffman, Stephen L.

doi:10.4269/ajtmh.1994.50.529

Cited by 220 publications

(203 citation statements)

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“…Siaya District is a holoendemic P. falciparum transmission area where residents receive up to 300 infective bites per annum [33]. SMA is the primary clinical manifestation of severe malaria in children under the age of 5 years in this region, with the peak incidence of malarial anemia occurring in children 7-24 months of age [5,34].…”

Section: Study Areamentioning

confidence: 99%

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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Severe malarial anemia (SMA) is a leading cause of mortality among children in sub-Saharan Africa. Although the novel cytokine, interleukin (IL)-23, promotes anemia in chronic inflammatory diseases, the role of IL-23 in SMA remains undefined. Since IL-23 and IL-12 share the IL-12p40 subunit and IL-12Rβ1 receptor, and are down-regulated by IL-10, relationships among these cytokines were explored in Kenyan children with varying severities of malarial anemia. Children with malarial anemia had increased circulating IL-23 and IL-10, and decreased IL-12 relative to healthy controls. Enhanced anemia severity and elevated parasitemia were associated with increased IL-10 relative to IL-23 and IL-12. Further exploration of the relationships among the cytokines using an in vitro model in which peripheral blood mononuclear cells were treated with synthetic hemozoin (sHz, malarial pigment) revealed that IL-12p35 and IL-23p19 transcripts had a sustained induction over 72 hrs, while IL-12p40 and IL-10 message peaked at 24 hrs, and rapidly declined thereafter. Taken together, results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria.

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Section: Study Areamentioning

confidence: 99%

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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“…In the synthetic cohort study, ~5% of infectious bites produced an infection (that is, 1 in 20), but efficiency varied from ~20% down to 1.4% (that is, from 1 in 5 to 1 in 70), and there was a nonlinear association with the EIR 16 . Highly variable estimates were found when the FOI was estimated using cross-sectional parasite surveys.…”

Section: Literature Searchmentioning

confidence: 99%

“…A preliminary literature search identified five kinds of studies that estimated transmission efficiency either directly by exposing people to the bites of infectious mosquitoes, or indirectly as the ratio of the FOI and the EIR, the number of infections per infectious bite: (1) human subjects were challenged by exposing them to the bites of infectious mosquitoes [28][29][30][31] ; (2) synthetic cohorts of uninfected people were created by curing infections with antimalarial drugs, and the cohorts were followed over time to estimate the attack rate: the proportion of the cohort that was infected 16,32,33 ; (3) cross-sectional parasite surveys were used to estimate the FOI by fitting models to the rise in malaria prevalence with age, after accounting for infections that were cleared [12][13][14] ; (4) cross-sectional serological surveys were used to estimate the SCR by fitting models to the rise in seroprevalence with age, after accounting for waning immunity (or sero-reconversion) 34,35 ; and (5) longitudinal studies were used to estimate the FOI by following individuals over time as they naturally acquired infections, and several study designs and methods were used to infer the attack rates from a sequence of parasite positive or negative observations 15,36,37 . These studies were reanalysed and the results assembled to evaluate the functional relationship between the FOI (denoted h in equations, which Ross called the 'happenings' rate 1 ) and the EIR (denoted E in equations).…”

Section: Literature Searchmentioning

confidence: 99%

“…A third measure of transmission is the sero-conversion rate (SCR), the rate that humans develop serological responses to the products of parasite infections; the SCR is analogous to the FOI and would be very similar if serological responses were highly predictive of previous infection. Several studies that have estimated transmission efficiency have shown that malaria transmission is extremely inefficient in high-intensity settings 10,[12][13][14][15][16][17][18] , and there has been a long-standing debate about why [17][18][19][20][21][22] . Low transmission efficiency gave rise to the challenges about the quantitative validity of using entomological measures as a basis for measuring transmission and planning control.…”

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confidence: 99%

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A quantitative analysis of transmission efficiency versus intensity for malaria

et al. 2010

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The relationship between malaria transmission intensity and efficiency is important for malaria epidemiology, for the design of randomized control trials that measure transmission or incidence as end points, and for measuring and modelling malaria transmission and control. Five kinds of studies published over the past century were assembled and reanalysed to quantify malaria transmission efficiency and describe its relation to transmission intensity, to understand the causes of inefficient transmission and to identify functions suitable for modelling mosquitoborne disease transmission. In this study, we show that these studies trace a strongly nonlinear relationship between malaria transmission intensity and efficiency that is parsimoniously described by a model of heterogeneous biting. When many infectious bites are concentrated on a few people, infections and parasite population structure will be highly aggregated affecting the immunoepidemiology of malaria, the evolutionary ecology of parasite life history traits and the measurement and stratification of transmission for control using entomological and epidemiological data.

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“…Full details of the trial can be found in John et al [11]. In brief, the population of Kanyawegi is approximately 3500 and is located in a malaria-endemic region with an approximate entomological inoculation rate (EIR) of 120 infectious bites per person per year [21]. Individuals agreeing to participate were given quinine for 5 days and doxycycline for 7 days to clear parasitaemia, and then followed for malaria infection by microscopic inspection of blood smears obtained weekly for 14 weeks.…”

Section: (A) Datamentioning

confidence: 99%

Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

et al. 2010

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Antibodies to the pre-erythrocytic antigens, circumsporozoite protein (CSP), thrombospondin-related adhesive protein (TRAP) and liver-stage antigen 1, have been measured in field studies of semiimmune adults and shown to correlate with protection from Plasmodium falciparum infection. A mathematical model is formulated to estimate the probability of sporozoite infection as a function of antibody titres to multiple pre-erythrocytic antigens. The variation in antibody titres from field data was used to estimate the relationship between the probability of P. falciparum infection per infectious mosquito bite and antibody titre. Using this relationship, we predict the effect of vaccinations that boost baseline CSP or TRAP antibody titres. Assuming the estimated relationship applies to vaccineinduced antibody titres, then single-component CSP or TRAP antibody-mediated pre-erythrocytic vaccines are likely to provide partial protection from infection, with vaccine efficacy of approximately 50 per cent depending on the magnitude of the vaccine-induced boost to antibody titres. It is possible that the addition of a TRAP component to a CSP-based vaccine such as RTS,S would provide an increase in infection-blocking efficacy of approximately 25 per cent should the problem of immunological interference between antigens be overcome.

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Plasmodium falciparum Incidence Relative to Entomologic Inoculation Rates at a Site Proposed for Testing Malaria Vaccines in Western Kenya

Cited by 220 publications

References 0 publications

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

A quantitative analysis of transmission efficiency versus intensity for malaria

Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

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