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A quantitative analysis of transmission efficiency versus intensity for malaria.

ABSTRACT: 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 mosquito-borne 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.

SUBMITTER: Smith DL

PROVIDER: S-EPMC3065713 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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A quantitative analysis of transmission efficiency versus intensity for malaria.

Smith David L DL Drakeley Chris J CJ Chiyaka Christinah C Hay Simon I SI

Nature communications 20101102

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 trans ...[more]

PMID: 21045826

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Project description:BackgroundUnderstanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity.MethodsClinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2-10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models.Results52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2-10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2-10 < 5%), five low-moderate transmission (PfPR2-10 5-9%), 20 moderate transmission (PfPR2-10 10-29%) and 12 high transmission (PfPR2-10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69-85%) and rare among children aged 10-14 years (0.7-5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines.ConclusionsTargeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2-23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.

Project description:Introduction: Plasmodium falciparum induced antibodies are key components of anti-malarial immunity in malaria endemic areas, but their antigen targets can be polymorphic. Induction of a high proportion of strain-specific antibodies will limit the recognition of a broad diversity of parasite strains by these responses. There are indications that circulating parasite diversity varies with malaria transmission intensity, and this may affect the specificity of elicited anti-malarial antibodies. This study therefore assessed the effect of varying malaria transmission patterns on the specificity of elicited antibody responses and to identify possible antibody correlates of naturally acquired immunity to malaria in children in an area of Ghana with seasonal malaria transmission.Methods: This retrospective study utilized plasma samples collected longitudinally at six time points from children aged one to five years. Multiplex assays were used to measure antibody levels against four P. falciparum AMA 1 variants (from the 3D7, FVO, HB3 and CAMP parasite strains) and the 3D7 variant of the EBA 175 region II antigen and the levels compared between symptomatic and asymptomatic children. The relative proportions of cross-reactive and strain-specific antibodies against the four AMA 1 variants per sampling time point were assessed by Bland-Altman plots. The levels of antibodies against allelic AMA1 variants, measured by singleplex and multiplex luminex assays, were also compared.Results: The data show that increased transmission intensity is associated with higher levels of cross-reactive antibody responses, most likely a result of a greater proportion of multiple parasite clone infections during the high transmission period. Anti-AMA1 antibodies were however associated with a history of infection rather than protection in this age group.Conclusion: The data contribute to understanding the underlying mechanism of the acquisition of strain-transcending antibody immunity following repeated exposure to diverse parasite strains.

Project description:BACKGROUND: The precise nature of the relationship between malaria mortality and levels of transmission is unclear. Due to methodological limitations, earlier efforts to assess the linkage have lead to inconclusive results. The malaria transmission intensity and mortality burden across Africa (MTIMBA) project initiated by the INDEPTH Network collected longitudinally entomological data within a number of sites in sub-Saharan Africa to study this relationship. This work linked the MTIMBA entomology database with the routinely collected vital events within the Rufiji Demographic Surveillance System to analyse the transmission-mortality relation in the region. METHODS: Bayesian Bernoulli spatio-temporal Cox proportional hazards models with village clustering, adjusted for age and insecticide-treated nets (ITNs), were fitted to assess the relation between mortality and malaria transmission measured by entomology inoculation rate (EIR). EIR was predicted at household locations using transmission models and it was incorporated in the model as a covariate with measure of uncertainty. Effects of covariates estimated by the model are reported as hazard ratios (HR) with 95% Bayesian confidence interval (BCI) and spatial and temporal parameters are presented. RESULTS: Separate analysis was carried out for neonates, infants and children 1-4 years of age. No significant relation between all-cause mortality and intensity of malaria transmission was indicated at any age in childhood. However, a strong age effect was shown. Comparing effects of ITN and EIR on mortality at different age categories, a decrease in protective efficacy of ITN was observed (i.e. neonates: HR = 0.65; 95% BCI:0.39-1.05; infants: HR = 0.72; 95% BCI:0.48-1.07; children 1-4 years: HR = 0.88; 95% BCI:0.62-1.23) and reduction on the effect of malaria transmission exposure was detected (i.e. neonates: HR = 1.15; 95% BCI:0.95-1.36; infants: HR = 1.13; 95% BCI:0.98-1.25; children 1-4 years: HR = 1.04; 95% BCI:0.89-1.18). A very strong spatial correlation was also observed. CONCLUSION: These results imply that assessing the malaria transmission-mortality relation involves more than the knowledge on the performance of interventions and control measures. This relation depends on the levels of malaria endemicity and transmission intensity, which varies significantly between different settings. Thus, sub-regions analyses are necessary to validate and assess reproducibility of findings.

Project description:BackgroundIn individuals living in malaria-endemic regions, parasitaemia thresholds for the onset of clinical symptoms vary with transmission intensity. The mechanisms that mediate this relationship are however, unclear. Since inflammatory responses to parasite infection contribute to the clinical manifestation of malaria, this study investigated inflammatory cytokine responses in children with malaria from areas of different transmission intensities (ranging from low to high).MethodsBlood samples were obtained from children confirmed with malaria at community hospitals in three areas with differing transmission intensities. Cytokine levels were assessed using the Luminex®-based magnetic bead array system, and levels were compared across sites using appropriate statistical tests. The relative contributions of age, gender, parasitaemia and transmission intensity on cytokine levels were investigated using multivariate regression analysis.ResultsParasite density increased with increasing transmission intensity in children presenting to hospital with symptomatic malaria, indicating that the parasitaemia threshold for clinical malaria increases with increasing transmission intensity. Furthermore, levels of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-6, IL-8, and IL-12, decreased with increasing transmission intensity, and correlated significantly with parasitaemia levels in the low transmission area but not in high transmission areas. Similarly, levels of anti-inflammatory cytokines, including IL-4, IL-7, IL-10 and IL-13, decreased with increasing transmission intensity, with IL-10 showing strong correlation with parasitaemia levels in the low transmission area. Multiple linear regression analyses revealed that transmission intensity was a stronger predictor of cytokine levels than age, gender and parasitaemia.ConclusionTaken together, the data demonstrate a strong relationship between the prevailing transmission intensity, parasitaemia levels and the magnitude of inflammatory responses induced during clinical malaria.

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A quantitative analysis of transmission efficiency versus intensity for malaria.

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A quantitative analysis of transmission efficiency versus intensity for malaria.

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