Biomedical subjects

Simon K Kariuki

Publications and source records attributed to Simon K Kariuki.

At least 19 recordsLinked to original sources

PubMed2006

A comparative study of the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 in Plasmodium falciparum and P. vivax.

We investigated the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 (MSP-1) antigen in Plasmodium falciparum and P. vivax, as well as in non-human primate malarial parasites. This fragment undergoes a proteolytic cleavage generating two fragments of 19kDa (MSP-1(19)) and 33kDa (MSP-1(33)) that are critical in erythrocyte invasion. We found that overall the MSP-1(33) fragment exhibits greater genetic diversity than the MSP-1(19) regardless of the species. We have found evidence for positive natural selection only in the human malaria parasites by comparing the rate of non-synonymous versus synonymous substitutions. In addition, we found clear differences between the two major human malaria parasites. In the case of P. falciparum, positive natural selection is acting on the MSP-1(19) region while the MSP-1(33) is neutral or under purifying selection. The opposite pattern was observed in P. vivax. Our results suggest different roles of this antigen in the host-parasite immune interaction in each of the major human malarial parasites.

Amino Acid Motifs↗

PubMed2005

Relationship of measles vaccination with anaemia and malaria in western Kenya.

OBJECTIVE: Mild viral illness, including that following immunization with live attenuated measles virus (LAMV), has been associated with transient decreases in haemoglobin (Hb) and cellular immune response that may persist for several weeks. In areas of intense malaria transmission, such as western Kenya, infants experience a progressive drop in Hb until age 9-10 months and one-third may have Hb < 8 g/dl. These children may be at risk of developing severe anaemia with further haematological insult. The objective of this paper was to determine if immunization with LAMV was associated with increased risk of transient anaemia and malaria infection. METHODS: Data from previous cross-sectional surveys (n = 5970) and one cohort study (n = 546) conducted among pre-school children were analyzed retrospectively. RESULTS: Measles vaccination coverage between 12 and 23 months of age ranged from 44.8% to 62.7%. Hb concentrations in children aged 6-23 months with documented measles immunization within the previous 14 or 30 days (n = 103) were similar to those with no history of measles immunization in the previous 90 days (n = 996); mean differences [95% confidence interval (CI)] by 30 days were: in cross-sectional surveys, -0.49 g/dl (-1.12, 0.14); in the cohort study, -0.032 g/dl (-0.52, 0.46). Similarly, the risk of malaria parasitemia or severe to moderate anaemia did not differ. CONCLUSION: These data do not suggest that the transient decrease in Hb and cellular immune response after immunization with LAMV results in clinically significant changes in the risk of subsequent severe to moderate anaemia or malaria in young children living in malaria-endemic regions.

Anemia↗

PubMed2005

Factors associated with hemoglobin concentrations in pre-school children in Western Kenya: cross-sectional studies.

In sub-Saharan Africa, the etiology of anemia in early childhood is complex and multifactorial. Three community-based cross-sectional surveys were used to determine the prevalence and severity of anemia. Regression methods were used to compare mean hemoglobin (Hb) concentrations across covariate levels to identify children at risk of low Hb levels in an area with intense malaria transmission. In a random sample of 2,774 children < 36 months old, the prevalence of anemia (Hb < 11g/dL) was 76.1% and 71%, respectively, in villages without and with insecticide-treated bed nets (ITNs); severe-moderate anemia (Hb < 7 g/dL) was observed in 11% (non-ITN) and 8.3% (ITN). The prevalence of anemia, high-density malaria parasitemia (21.7%), microcytosis (34.9%), underweight (21.9%), and diarrhea (54.8%) increased rapidly from age three months onwards and remained high until 35 months of age. Multivariate analyses showed that family size, history of fever, pale body, general body weakness, diarrhea, soil-eating, concurrent fever, stunting, and malaria parasitemia were associated with mean Hb levels. Prevention of severe anemia should start early in infancy and include a combination of micronutrient supplementation, malaria control, and possibly interventions against diarrheal illness.

Anemia↗

PubMed2005

Malaria and nutritional status among pre-school children: results from cross-sectional surveys in western Kenya.

Protein-energy malnutrition (PEM) affects millions of children in the developing world. The relationship between malaria and PEM is controversial. The goal of this study was to evaluate whether undernutrition is associated with increased or decreased malaria attributable morbidity. Three cross-sectional surveys were conducted using insecticide-treated bed nets (ITNs) among children aged 0-36 months living in an area with intense malaria transmission. Data were collected on nutritional status, recent history of clinical illness, socioeconomic status, current malaria infection status, and hemoglobin. In multivariate models, stunted children had more malaria parasitemia (odds ratio [OR] 1.98, P < 0.0001), high-density parasitemia (OR 1.84; P < 0.0001), clinical malaria (OR 1.77; P < 0.06), and severe malarial anemia (OR 2.65; P < 0.0001) than nonstunted children. The association was evident in children with mild-to-moderate (-3 < height-for-age Z-score [HAZ] < -2) and severe stunting (HAZ < -3). The cross-sectional nature of the study limits the interpretation of causality, but the data provide further observational support that the presence of undernutrition, in particular chronic undernutrition, places children at higher, not lower risk of malaria-related morbidity.

Bedding and Linens↗

PubMed2004

Relation between the response to iron supplementation and sickle cell hemoglobin phenotype in preschool children in western Kenya.

BACKGROUND: Iron supplementation has been associated with greater susceptibility to malaria and lower hematologic responses in pregnant Gambian women with sickle cell trait (HbAS) than in similar women with the normal (HbAA) phenotype. It is not known whether a similar interaction exists in children. OBJECTIVE: Our aim was to determine the influence of the HbAS phenotype on hematologic responses and malaria after iron supplementation in anemic (hemoglobin: 70-109 g/L) children aged 2-35 mo. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial (HbAS, n = 115; HbAA, n = 408) of intermittent preventive treatment with sulfadoxine pyrimethamine (IPT-SP) at 4 and 8 wk and daily supervised iron for 12 wk. RESULTS: The mean difference in hemoglobin concentrations at 12 wk between children assigned iron and placebo iron, after adjustment for the effect of IPT-SP, was 9.1 g/L (95% CI: 6.4, 11.8) and 8.2 g/L (4.0, 12.4) in HbAA and HbAS children, respectively (P for interaction = 0.68). Although malaria parasitemia and clinical malaria occurred more often in HbAS children in the iron group than in those in the placebo iron group, this difference was not significant; incidence rate ratios were 1.23 (95% CI: 0.64, 2.34) and 1.41 (0.39, 5.00), respectively. The corresponding incidence rate ratios in HbAA children in the same groups were 1.07 (95% CI: 0.77, 1.48) and 0.59 (0.35, 1.01), respectively. The corresponding interactions between the effects of iron and hemoglobin phenotype were not significant. CONCLUSIONS: There was no evidence for a clinically relevant modification by the hemoglobin S phenotype of the effects of iron supplementation in the treatment of mild anemia. The benefits of iron supplementation are likely to outweigh possible risks associated with malaria in children with the HbAA or HbAS phenotype.

Anemia↗

PubMed2004

Daily iron supplementation is more efficacious than twice weekly iron supplementation for the treatment of childhood anemia in western Kenya.

A recent meta-analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation resulted in significantly greater hematological improvement in pregnant women. No such definitive beneficial effect was demonstrated in preschool children. We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [hemoglobin (Hb) 50-109 g/L] in children aged 2-59 mo living in a malaria-endemic area of western Kenya. The study was a cluster-randomized trial using a factorial design; participants were aware of the treatment assigned. All children (n = 1049) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [3-6 mg/(kg.d)], twice weekly supervised iron supplementation [6-12 mg/(kg.wk)], daily unsupervised iron supplementation, or twice weekly unsupervised iron supplementation. In the supervised groups, Hb concentrations at 6 and 12 wk (6 wk postsupplementation) were significantly higher in children given iron daily rather than twice weekly [mean (95% CI) difference at 6-wk: 4.2 g/L (2.1, 6.4); 12-wk: 4.4 g/L (1.8, 7.0)]. Among the unsupervised groups, Hb concentrations were not different at 6 wk [mean (95% CI) difference: 0.86 g/L (-1.4, 3.1)], but significantly higher at 12 wk for those assigned daily iron [mean (95% CI) difference: 3.4 g/L (0.79, 6.0), P = 0.02]. In this malarious area and after initial antimalarial treatment, 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children, regardless of whether adherence can be ensured.

Anemia↗

PubMed2003

Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya.

In areas where Plasmodium falciparum malaria is endemic, parasite density, morbidity, and mortality decrease with increasing age, which supports the view that years of cumulative exposure are necessary for the expression of maximal protective immunity. Developmental changes in the host also have been implicated in the expression of maximal resistance. To further evaluate the contribution of host developmental factors in malaria resistance, we examined the relationship between P. falciparum parasitemia and pubertal development in a cross-sectional sample of 12-18-year-old schoolgirls from an area of intense transmission in western Kenya. Among pubertal girls, dehydroepiandrosterone sulfate (DHEAS) levels were significantly associated with decreased parasite density, even after adjustment for age. DHEAS levels also were related to increased hemoglobin levels, even after accounting for age and other determinants of hemoglobin level. These findings support the hypothesis that host pubertal development, independent of age and, by proxy, cumulative exposure, is necessary for maximal expression of resistance to malarial infection and morbidity, as assessed by hemoglobin level.

Adolescent↗

PubMed2003

The effects of varying exposure to malaria transmission on development of antimalarial antibody responses in preschool children. XVI. Asembo Bay Cohort Project.

In areas of intense malaria transmission, malaria morbidity and mortality is highest in children 3-18 months old. Interventions that reduce malaria exposure early in life reduce morbidity but may also delay development of clinical immunity. We assessed the relationship between intensity of malaria exposure and development of antibody responses. Thirty-nine children were monitored monthly, from birth to > or =2.5 years old (1238 observations), and were divided into 3 exposure categories, on the basis of parasitemic episodes or entomological data. Children with low exposure during the first 2 years of life had higher subsequent levels of antibody to merozoite surface protein-1(19-kDa) (a marker of blood-stage responses) by months 24-35 (P<.05). This inverse relationship decreased as children aged. There was no consistent relationship between exposure early in life and subsequent levels of antibody to circumsporozoite protein (a marker of sporozoite-stage responses). These data suggest that, in areas of intense malaria transmission, during the first 3 years of life, interventions that either reduce the number of asexual parasitemic episodes or lower entomological exposure do not delay the development of antibody responses to blood-stage malarial antigens.

Animals↗

PubMed2003

Randomized, controlled trial of daily iron supplementation and intermittent sulfadoxine-pyrimethamine for the treatment of mild childhood anemia in western Kenya.

A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7-11 g/dL) children aged 2-36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82-1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46-1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, -0.15-0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest.

Anemia↗

PubMed2003

Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing.

Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.

Anti-Infective Agents↗

PubMed2003

Association of interferon-gamma responses to pre-erythrocytic stage vaccine candidate antigens of Plasmodium falciparum in young Kenyan children with improved hemoglobin levels: XV. Asembo Bay Cohort Project.

Previous studies in animal models have revealed an association between interferon-gamma (IFN-gamma), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-gamma can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-gamma and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN-gamma positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN-gamma non-responders, suggesting that IFN-gamma immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN-gamma production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

Anemia↗

PubMed2003

The efficacy of permethrin-treated bed nets on child mortality and morbidity in western Kenya II. Study design and methods.

This paper describes the study design and methods used in a large community-based, group-randomized, controlled trial of permethrin-treated bed nets (ITNs) in an area with intense, perennial malaria transmission in western Kenya conducted between 1996 and 1999. A multi-disciplinary framework was used to explore the efficacy of ITNs in the reduction of all-cause mortality in children less than five years old, the clinical, entomologic, immunologic, and economic impact of ITNs, the social and behavioral determinants of ITN use, and the use of a geographic information system to allow for spatial analyses of these outcomes. Methodologic difficulties encountered in such large-scale field trials are discussed.

Bedding and Linens↗

PubMed2003

Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.

The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17-54%) in the incidence of malaria parasitemia and 47% (95% CI = 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.

Adult↗

PubMed2003

Effects of permethrin-treated bed nets on immunity to malaria in western Kenya I. Antibody responses in pregnant women and cord blood in an area of intense malaria transmission.

As part of a community-based group-randomized trial on the impact of permethrin-treated bed nets (ITNs) on malaria in pregnancy in a holoendemic area of western Kenya, we assessed their effects on antibody responses to Plasmodium falciparum pre-erythrocytic antigens (recombinant circumsporozoite protein [CSP] and peptides complimentary to the repeat region of the liver stage antigen-1 [LSA-1]) and blood stage antigen (recombinant C-terminal domain of the merozoite surface protein-1 [MSP-1(19) kD]) in paired maternal/cord plasma samples obtained from 296 deliveries (157 from ITN villages and 139 control villages). Levels of total IgG and IgG subclasses 1-3 to LSA-1 and total IgG and IgG3 to MSP-1 were lower, whereas those of total IgG to CSP were significantly higher in women from ITN villages than those from control villages. In cord plasma, levels of total IgG and IgG2 to LSA-1 and IgG3 to MSP-1 were lower in ITN villages than in control villages, but antibody responses to CSP were similar. Our results suggest that the use of ITNs decreases antibody responses to LSA-1 and MSP-1 antigens in pregnant women with associated reductions in levels of the same antibodies in cord blood. In contrast, ITN use was found to be associated with increased antibody responses to CSP in pregnant women, but had no effect on antibody levels to CSP in cord blood.

Animals↗

PubMed2003

Impact of permethrin-treated bed nets on malaria, anemia, and growth in infants in an area of intense perennial malaria transmission in western Kenya.

As part of a community-based, group-randomized, controlled trial of insecticide-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, a birth cohort (n = 833) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of reduced malaria exposure during pregnancy and infancy. Malaria transmission and morbidity were comparable pre-intervention. The ITNs reduced malaria attack rates (force of infection) in infancy by 74%, and delayed the median time-to-first parasitemia (4.5 to 10.7 months; P < 0.0001). The incidence of both clinical malaria and moderate-severe anemia (hemoglobin level <7 g/dL) were reduced by 60% (P < 0.001 for both). Protective efficacy was greatest in infants less than three months old and similar in older infants and one-year-old children. Efficacy was lowest in the dry season. Infants from ITN villages experienced better height and weight gain. In areas of intense perennial malaria transmission, ITNs substantially reduce exposure to malaria and subsequent malaria-associated morbidity in children less than 24 months old. Reduced malaria exposure during infancy did not result, with continued ITN use, in increased malaria morbidity in one-year-old children.

Age Factors↗

PubMed2003

Permethrin-treated bed nets in the prevention of malaria and anemia in adolescent schoolgirls in western Kenya.

The impact of insecticide (permethrin)-treated bed nets (ITNs) on the health of adolescent schoolgirls was investigated during a community-based, randomized, controlled trial of ITNs in western Kenya. Two school-based cross-sectional surveys were conducted to determine the prevalence of malaria and anemia in 644 schoolgirls 12-18 years old in a rural area with intense perennial malaria transmission. In 12- and 13-year-old schoolgirls, ITNs were associated with a reduced prevalence of all cause anemia (hemoglobin level <12 g/dL, 16.9% versus 31.4%, adjusted odds ratio [OR] = 0.38, 95% confidence interval [CI] = 0.21, 0.69%) and a 0.34 g/dL (95% CI = 0.02, 0.66) increase in mean hemoglobin concentrations. No beneficial effect on all-cause anemia (adjusted OR = 0.79, 95% CI = 0.43, 1.45) or hemoglobin concentrations (difference in mean = 0.14 g/dL, 95% CI = -0.24, 0.53) was evident in older girls. In all age groups, no effect was found on malaria parasite prevalence or density, clinical malaria, all-cause morbidity, standard measures of nutritional status and growth, or the use of antimalarials and other medications. ITNs approximately halved the prevalence of mild anemia in young, school-attending, non-pregnant, adolescent girls, but had no impact in older girls or on other malaria-associated morbidity or nutritional status.

Adolescent↗

PubMed2003

Impact of permethrin-treated bed nets on malaria and all-cause morbidity in young children in an area of intense perennial malaria transmission in western Kenya: cross-sectional survey.

Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya, we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old. Children in ITN and control villages were comparable pre-intervention, but after the introduction of ITNs, children in intervention villages were less likely to have recently experienced illness requiring treatment (protective efficacy [95% confidence intervals] = 15% [1-26%]), have an enlarged spleen (32% [20-43%]), be parasitemic (19% [11-27%]), have clinical malaria (44% [6-66%]), have moderately severe anemia (hemoglobin level < 7.0 g/dL; 39% [18-54%]), or have a pruritic body rash, presumably from reduced nuisance insect bites (38% [24-50%]). Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences. There was no evidence, however, that ITNs reduced the risk of helminth infections, diarrhea, or upper or lower respiratory tract infections. The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission.

Bedding and Linens↗

PubMed2003

Effects of permethrin-treated bed nets on immunity to malaria in western Kenya II. Antibody responses in young children in an area of intense malaria transmission.

As part of a large community-based trial on the impact of insecticide (permethrin)-treated bed nets (ITNs) on childhood morbidity and mortality in an area of intense perennial malaria transmission in western Kenya, we assessed the effects of ITNs on malaria-specific humoral responses in young children. The IgG responses to Plasmodium falciparum pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen-1 (LSA-1) and the blood stage antigen merozoite surface protein-1 (MSP-1(19) kD) in children less than three years old were investigated during a series of cross-sectional surveys. At 14 and 22 months after the introduction of ITNs, the frequencies and levels of IgG to CSP and LSA-1 were significantly lower in children from ITN villages than in children from control villages (P < 0.001). In contrast, the prevalence of IgG to MSP-1 was significantly higher in children from ITN villages at 14 months (P = 0.0069), but not at 22 months. Our results show that decreased exposure by ITNs reduces IgG responses to pre-erythrocytic antigens, but there was no evidence that two years of ITN use compromises IgG responses to blood stage antigens in these young children in this malaria holoendemic area.

Antibodies, Protozoan↗