Landscape epidemiology modeling using an agent-based model and a geographic information system

A landscape epidemiology modeling framework is presented which integrates the simulation outputs from an established spatial agent-based model (ABM) of malaria with a geographic information system (GIS). For a study area in Kenya, five landscape scenarios are constructed with varying coverage levels of two mosquito-control interventions. For each scenario, maps are presented to show the average distributions of three output indices obtained from the results of 750 simulation runs. Hot spot analysis is performed to detect statistically significant hot spots and cold spots. Additional spatial analysis is conducted using ordinary kriging with circular semivariograms for all scenarios. The integration of epidemiological simulation-based results with spatial analyses techniques within a single modeling framework can be a valuable tool for conducting a variety of disease control activities such as exploring new biological insights, monitoring epidemiological landscape changes, and guiding resource allocation for further investigation

Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa

OBJECTIVE To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS All methods require a plausibility argument - i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added

Differential Association of Gene Content Polymorphisms of Killer Cell Immunoglobulin-Like Receptors with Placental Malaria in HIV− and HIV+ Mothers

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes

Assessment of molecular markers for anti-malarial drug resistance after the introduction and scale-up of malaria control interventions in western Kenya

Background Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively. Methods Smear-positive samples (N = 253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001. Results In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K 76 Y 86 I 51 R 59 N 108 G 437 E 540 , from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1. Conclusions Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers

Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated bed nets (ITNs) reduce malaria transmission and are an important prevention tool. However, there are still information gaps on how the reduction in malaria transmission by ITNs affects parasite genetics population structure. This study examined the relationship between transmission reduction from ITN use and the population genetic diversity of <it>Plasmodium falciparum </it>in an area of high ITN coverage in western Kenya.</p> <p>Methods</p> <p>Parasite genetic diversity was assessed by scoring eight single copy neutral multilocus microsatellite (MS) markers in samples collected from <it>P. falciparum-</it>infected children (< five years) before introduction of ITNs (1996, baseline, n = 69) and five years after intervention (2001, follow-up, n = 74).</p> <p>Results</p> <p>There were no significant changes in overall high mixed infections and unbiased expected heterozygosity between baseline (%M_A= 94% and H_e= 0.75) and follow up (%M_A= 95% and H_e= 0.79) years. However, locus specific analysis detected significant differences for some individual loci between the two time points. Pfg377 loci, a gametocyte-specific MS marker showed significant increase in mixed infections and H_ein the follow up survey (%M_A= 53% and H_e= 0.57) compared to the baseline (%M_A= 30% and H_e= 0.29). An opposite trend was observed in the erythrocyte binding protein (EBP) MS marker. There was moderate genetic differentiation at the Pfg377 and TAA60 loci (F_ST= 0.117 and 0.137 respectively) between the baseline and post-ITN parasite populations. Further analysis revealed linkage disequilibrium (LD) of the microsatellites in the baseline (14 significant pair-wise tests and <it>I^S_A</it>= 0.016) that was broken in the follow up parasite population (6 significant pairs and <it>I^S_A</it>= 0.0003). The locus specific change in H_e, the moderate population differentiation and break in LD between the baseline and follow up years suggest an underlying change in population sub-structure despite the stability in the overall genetic diversity and multiple infection levels.</p> <p>Conclusions</p> <p>The results from this study suggest that although <it>P. falciparum </it>population maintained an overall stability in genetic diversity after five years of high ITN coverage, there was significant locus specific change associated with gametocytes, marking these for further investigation.</p

Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated bed nets (ITNs) reduce malaria transmission and are an important prevention tool. However, there are still information gaps on how the reduction in malaria transmission by ITNs affects parasite genetics population structure. This study examined the relationship between transmission reduction from ITN use and the population genetic diversity of <it>Plasmodium falciparum </it>in an area of high ITN coverage in western Kenya.</p> <p>Methods</p> <p>Parasite genetic diversity was assessed by scoring eight single copy neutral multilocus microsatellite (MS) markers in samples collected from <it>P. falciparum-</it>infected children (< five years) before introduction of ITNs (1996, baseline, n = 69) and five years after intervention (2001, follow-up, n = 74).</p> <p>Results</p> <p>There were no significant changes in overall high mixed infections and unbiased expected heterozygosity between baseline (%M_A= 94% and H_e= 0.75) and follow up (%M_A= 95% and H_e= 0.79) years. However, locus specific analysis detected significant differences for some individual loci between the two time points. Pfg377 loci, a gametocyte-specific MS marker showed significant increase in mixed infections and H_ein the follow up survey (%M_A= 53% and H_e= 0.57) compared to the baseline (%M_A= 30% and H_e= 0.29). An opposite trend was observed in the erythrocyte binding protein (EBP) MS marker. There was moderate genetic differentiation at the Pfg377 and TAA60 loci (F_ST= 0.117 and 0.137 respectively) between the baseline and post-ITN parasite populations. Further analysis revealed linkage disequilibrium (LD) of the microsatellites in the baseline (14 significant pair-wise tests and <it>I^S_A</it>= 0.016) that was broken in the follow up parasite population (6 significant pairs and <it>I^S_A</it>= 0.0003). The locus specific change in H_e, the moderate population differentiation and break in LD between the baseline and follow up years suggest an underlying change in population sub-structure despite the stability in the overall genetic diversity and multiple infection levels.</p> <p>Conclusions</p> <p>The results from this study suggest that although <it>P. falciparum </it>population maintained an overall stability in genetic diversity after five years of high ITN coverage, there was significant locus specific change associated with gametocytes, marking these for further investigation.</p

Genetic diversity of Plasmodium falciparum parasite by microsatellite markers after scale-up of insecticide-treated bed nets in western Kenya

Background: An initial study of genetic diversity of Plasmodium falciparum in Asembo, western Kenya showed that the parasite maintained overall genetic stability 5 years after insecticide-treated bed net (ITN) introduction in 1997. This study investigates further the genetic diversity of P. falciparum 10 years after initial ITN introduction in the same study area and compares this with two other neighbouring areas, where ITNs were introduced in 1998 (Gem) and 2004 (Karemo). Methods: From a cross-sectional survey conducted in 2007, 235 smear-positive blood samples collected from children ≤15-year-old in the original study area and two comparison areas were genotyped employing eight neutral microsatellites. Differences in multiple infections, allele frequency, parasite genetic diversity and parasite population structure between the three areas were assessed. Further, molecular data reported previously (1996 and 2001) were compared to the 2007 results in the original study area Asembo. Results: Overall proportion of multiple infections (M A ) declined with time in the original study area Asembo (from 95.9 %-2001 to 87.7 %-2007). In the neighbouring areas, M A was lower in the site where ITNs were introduced in 1998 (Gem 83.7 %) compared to where they were introduced in 2004 (Karemo 96.7 %) in 2007. Overall mean allele count (M AC ~ 2.65) and overall unbiased heterozygosity (H e ~ 0.77) remained unchanged in 1996, 2001 and 2007 in Asembo and was the same level across the two neighbouring areas in 2007. Overall parasite population differentiation remained low over time and in the three areas at F ST < 0.04. Both pairwise and multilocus linkage disequilibrium showed limited to no significant association between alleles in Asembo (1996, 2001 and 2007) and between three areas. Conclusions: This study showed the P. falciparum high genetic diversity and parasite population resilience on samples collected 10 years apart and in different areas in western Kenya. The results highlight the need for long-term molecular monitoring after implementation and use of combined and intensive prevention and intervention measures in the region

Utilisation of malaria preventive measures during pregnancy and birth outcomes in Ibadan, Nigeria

<p>Abstract</p> <p>Background</p> <p>Malaria remains a major public health problem in sub Saharan Africa and the extent of utilisation of malaria preventive measures may impact on the burden of malaria in pregnancy. This study sought to determine the association between malaria preventive measures utilized during pregnancy and the birth outcomes of birth weight and preterm delivery.</p> <p>Methods</p> <p>This cross sectional survey involved 800 mothers who delivered at the University College Hospital, and Adeoyo Maternity Hospital, Ibadan. Data obtained included obstetric information, gestational age, birth weight and self reported use of malaria prevention strategies in index pregnancy.</p> <p>Results</p> <p>Most (95.6%) mothers used one or more malaria control measures. The most commonly used vector control measures were window net (84.0%), insecticide spray (71.5%) and insecticide treated bed nets (20.1%), while chemoprophylactic agents were pyrimethamine (23.5%), Intermittent Preventive Treatments with Sulphadoxine-Pyrimethamine (IPTsp) (18.5%) and intermittent chloroquine (9.5%) and 21.7% used herbal medications. The mean ± SD birthweight and gestational age of the babies were 3.02 kg ± 0.56 and 37.9 weeks ± 2.5 respectively. Preterm delivery rate was 19.4% and 9% had low birth weight.</p> <p>Comparing babies whose mothers had IPTsp with those who did not, mean birth weight was 3.13 kg ± 0.52 versus 3.0 kg ± 0.56 (p = 0.016) and mean gestational age was 38.5 weeks ± 2.1 versus 37.8 weeks ± 2.5 (p = 0.002).</p> <p>The non-use of IPTsp was associated with increased risk of having low birth weight babies (AOR: 2.27, 95% CI: 0.98; 5.28) and preterm birth (AOR: 1.93, 95% CI: 1.08, 3.44). The non use of herbal preparations (AOR: 0.55, 95% CI: 0.36, 0.85) was associated with reduced risk of preterm birth. The mean ± SD birth weight and gestational ages of babies born to mothers who slept under ITNs were not significantly different from those who did not (p = 0.07 and 0.09 respectively).</p> <p>Conclusions</p> <p>There is a need for improved utilisation of IPTsp as well as discouraging the use of herbal medications in pregnancy in order to reduce pregnancy outcome measures of low birth weight and preterm deliveries in this environment.</p