Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study
Gichohi-Wainaina, W.N. ; Boonstra, A. ; Feskens, E.J.M. ; Demir, A.Y. ; Veenemans, J. ; Verhoef, H. - \ 2015
Malaria Journal 14 (2015). - ISSN 1475-2875 - 11 p.
plasmodium-falciparum malaria - tnf-alpha promoter - cerebral malaria - linkage disequilibrium - rheumatoid-arthritis - diabetes-mellitus - polymorphisms - gene - disease - hla
Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. Methods Data from a placebo-controlled trial in which 612 Tanzanian children aged 6–60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature =37.5°C or whole blood C-reactive protein concentration =8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. Results Genotyping of 94.9% (581/612) children for TNF-1031 (TNF-1031 T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF-308 G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF-1031 CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01¿1.97] and 1.31 [0.97¿1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF-308 AA genotype (corresponding HR: 0.13 [0.02¿0.63] and 0.16 [0.04¿0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF-1031 and TNF-308 affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed.
Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
Murray, C.J. ; Ortblad, K.F. ; Guinovart, C. ; Lim, S.S. ; Wolock, T.M. ; Roberts, D.A. ; Dansereau, E.A. ; Geleijnse, J.M. - \ 2014
The Lancet 384 (2014)9947. - ISSN 0140-6736 - p. 1005 - 1070.
middle-income countries - female sex workers - plasmodium-falciparum malaria - active antiretroviral therapy - millennium development goals - severe febrile illness - prospective cohort - verbal autopsy - projection package - cost-effectiveness
Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Findings Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Interpretation Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. Incidence rates for HIV, tuberculosis, and malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
Effect of a+ -thalassaemia on episodes of fever due to malaria and other causes: a communitybased cohort study in Tanzania
Veenemans, J. ; Jansen, E.J.S. ; Baidjoe, A.Y. ; Mbugi, E.V. ; Demir, A.Y. ; Kraaijenhagen, R.J. ; Savelkoul, H.F.J. ; Verhoef, H. - \ 2011
Malaria Journal 10 (2011). - ISSN 1475-2875 - 10 p.
plasmodium-falciparum malaria - c-reactive protein - alpha-thalassemia - clinical malaria - case definitions - endemic areas - children - morbidity - anemia - disease
Background It is controversial to what degree a+-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium. Methods In Tanzania, in children aged 6-60 months and height-for-age z-score <-1.5 SD (n = 612), rates of fevers due to malaria and other causes were compared between those with heterozygous or homozygotes a+-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child. Results The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with a+-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, a+-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes. Conclusions In this population, the association between a+-thalassaemia and malaria depends on age. Our data suggest that protection by a+-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity
Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors
Russell, T.L. ; Lwetoijera, D.W. ; Knols, B.G.J. ; Takken, W. ; Killeen, G.F. ; Ferguson, H.M. - \ 2011
Proceedings of the Royal Society. B: Biological Sciences 278 (2011)1721. - ISSN 0962-8452 - p. 3142 - 3151.
plasmodium-falciparum malaria - anopheles-gambiae - multimodel inference - culicidae - diptera - transmission - arabiensis - mosquitos - fecundity - abundance
Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in phenotypic traits predict the dynamics of Anopheles gambiae sensu lato mosquitoes, the most important vectors of human malaria. Anopheles gambiae dynamics were monitored over a six-month period of seasonal growth and decline. The population exhibited density-dependent feedback, with the carrying capacity being modified by rainfall (97% wAICc support). The individual phenotypic expression of the maternal (p = 0.0001) and current (p = 0.040) body size positively influenced population growth. Our field-based evidence uniquely demonstrates that individual fitness can have population-level impacts and, furthermore, can mitigate the impact of exogenous drivers (e.g. rainfall) in species whose reproduction depends upon it. Once frontline interventions have suppressed mosquito densities, attempts to eliminate malaria with supplementary vector control tools may be attenuated by increased population growth and individual fitness
Climate Change and Highland Malaria: Fresh Air for a Hot Debate
Chaves, L.F. ; Koenraadt, C.J.M. - \ 2010
Quarterly Review of Biology 85 (2010)1. - ISSN 0033-5770 - p. 27 - 55.
anopheles-gambiae s.s. - western kenya highlands - east-african highlands - entomological inoculation rates - plasmodium-falciparum malaria - nino southern-oscillation - mosquito-borne disease - medium-sized town - mm-x traps - risk-factors
In recent decades, malaria has become established in zones at the margin of its previous distribution, especially in the highlands of East Africa. Studies in this region have sparked a heated debate over the importance of climate change in the territorial expansion of malaria, where positions range from its neglect to the reification of correlations as causes. Here, we review studies supporting and rebutting the role of climatic change as a driving force for highland invasion by malaria. We assessed the conclusions from both sides of the argument and found that evidence for the role of climate in these dynamics is robust. However, we also argue that over-emphasizing the importance of climate is misleading for setting a research agenda, even one which attempts to understand climate change impacts on emerging malaria patterns. We review alternative drivers for the emergence of this disease and highlight the problems still calling for research if the multidimensional nature of malaria is to be adequately tackled. We also contextualize highland malaria as an ongoing evolutionary process. Finally, we present Schmalhausen's law, which explains the lack of resilience in stressed systems, as a biological principle that unifies the importance of climatic and other environmental factors in driving malaria patterns across different spatio-temporal scales.
Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection
Mast, Q. de; Nadjm, B. ; Reyburn, H. ; Kemna, E.H.J.M. ; Amos, B. ; Laarakkers, C.M.M. ; Silalye, S. ; Verhoef, H. ; Sauerwein, R.W. ; Swinkels, D.W. ; Ven, A.J.A.M. van der - \ 2009
The Journal of Infectious Diseases 199 (2009)2. - ISSN 0022-1899 - p. 253 - 262.
plasmodium-falciparum malaria - soluble transferrin receptor - mass-spectrometry - anemia - serum - erythropoietin - ferroportin - expression - children - inflammation
Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone hepcidin in anemic Tanzanian children with febrile Plasmodium falciparum malaria. Before initiation of antimalarial treatment, urinary concentrations of hepcidin were strongly elevated and were associated with iron maldistribution, as was suggested by the presence of hypoferremia and high serum concentrations of ferritin. Antimalarial treatment resulted in a rapid decrease in urinary concentrations of hepcidin and reversal of the hypoferremia. Exploration of regulatory pathways of hepcidin production by analysis of iron, erythropoietic, and inflammatory indices suggested that reduced erythropoietic activity and inflammation stimulated hepcidin production. We conclude that high concentrations of hepcidin explain the observed disturbances in host iron homeostasis associated with malaria and may contribute to malarial anemia and an impaired erythropoietic response to iron supplementation
Efficacy of iron-fortified whole maize flour on iron status of schoolchildren in Kenya: a randomised controlled trial
Andang'o, P.E.A. ; Osendarp, S.J.M. ; Ayah, R. ; West, C.E. ; Mwaniki, D. ; Wolf, C.A. de; Kraaijenhagen, R. ; Kok, F.J. ; Verhoef, H. - \ 2007
The Lancet 369 (2007)9575. - ISSN 0140-6736 - p. 1799 - 1806.
plasmodium-falciparum malaria - edta nafe(iii)edta - food fortificant - missing values - elemental iron - curry powder - rapid tests - absorption - women - wheat
Background Sodium iron edetic acid (NaFeEDTA) might be a more bioavailable source of iron than electrolytic iron, when added to maize flour. We aimed to assess the effect, on children's iron status, of consumption of whole maize flour fortified with iron as NaFeEDTA or electrolytic iron. Methods 516 children, aged 3-8 years, from four schools in Marafa, Kenya, were randomly assigned to four groups. All were given the same amount of porridge five times a week. The porridge for one group was made from unfortified whole maize flour; for the other three groups it was fortified with either high-dose NaFeEDTA (56 mg/kg), low-dose NaFeEDTA (28 mg/kg), or electrolytic iron (56 mg/kg). Concentrations of haemoglobin, plasma ferritin, and transferrin receptor were analysed in samples taken at baseline and at the end of the 5-month intervention. The primary outcome was iron-deficiency anaemia. We analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00386074. Findings The prevalence of iron-deficiency anaemia in children given unfortified flour was 10%. Compared with placebo, the prevalence of iron-deficiency anaemia in children given flour fortified with high-dose NaFeEDTA, low-dose NaFeEDTA, and electrolytic iron changed by -89% (95% CI -97% to -49%), -48% (-77% to 20%), and 59% (-18% to 209%), respectively. Consumption of high-dose NaFeEDTA improved all measured iron-status indicators. Low-dose NaFeEDTA decreased the prevalence of iron deficiency but did not noticeably change the prevalence of anaemia. Electrolytic iron did not improve any of these iron-status indicators. Children who were iron-deficient at baseline benefited more from high-dose and low-dose NaFeEDTA than those with sufficient iron at baseline. Interpretation Consumption of whole maize flour fortified with NaFeEDTA caused modest, dose-dependent improvements in children's iron status. Fortification with electrolytic iron did not improve their iron status. Therefore, in high-phytate flours, NaFeEDTA is more suitable than electrolytic iron for supplementation of iron in the diet.
Taking malaria transmission out of the bottle: implications of mosquito dispersal for vector-control interventions
Killeen, G.F. ; Knols, B.G.J. ; Gu, W.D. - \ 2003
The Lancet Infectious Diseases 3 (2003)5. - ISSN 1473-3099 - p. 297 - 303.
insecticide-treated nets - impregnated bed nets - entomologic inoculation rates - plasmodium-falciparum malaria - anopheles-gambiae complex - child-mortality - burkina-faso - kenyan coast - tanzania - bednets
Most malaria transmission models assume enclosed systems of people, parasites, and vectors in which neither emigration nor immigration of mosquitoes is considered. This simplification has facilitated insightful analyses but has substantial limitations for evaluating control measures in the field. Here we show that mosquito dispersal can confound conventional approaches to evaluating malaria vector-control interventions, and explore this association with a model of two villages between which mosquito subpopulation exchange occurs. Exchange of mosquitoes between such subpopulations can readily explain the discrepancy between experimental efficacy measurements for insecticide-treated nets and their much lower apparent effectiveness when in use. Our results indicate that current approaches to assessing malaria interventions that confer community-level protection may be severely compromised by mosquito dispersal in many endemic settings. The true effectiveness of many vector-control methods may be much greater than previously appreciated and the application of such interventions should be consolidated into larger contiguous spatial units so that more effective local suppression of malaria can be achieved. Spatially explicit modelling formats that consider vector dispersal as a determinant of malaria transmission and control are needed urgently for rational planning and evaluation of efforts to roll back malaria