Biomedical subjects

Allen W Hightower

Publications and source records attributed to Allen W Hightower.

At least 19 recordsLinked to original sources

PubMed2006

Correlation between eosinophils and protection against reinfection with Schistosoma mansoni and the effect of human immunodeficiency virus type 1 coinfection in humans.

Longitudinal investigations of an adult male population of Kenyan car washers who have heavy and quantifiable occupational exposure to Schistosoma mansoni cercariae revealed that some individuals develop resistance to reinfection while others remain highly susceptible. We sought to characterize immune correlates associated with host protection in this population. Previous studies have demonstrated an association of peripheral eosinophilia with resistance to reinfection with schistosomes. Thus, we investigated the relationship between the percentage of circulating eosinophils and the effect of human immunodeficiency virus type 1 (HIV-1) coinfection on the susceptibility of the car washers to reinfection with schistosomes. Elevated percentages of circulating eosinophils were associated with resistance to reinfection by S. mansoni in HIV-1-seronegative persons. In the HIV-1-seropositive cohort, low CD4+-T-cell counts were associated with a less intense eosinophilia. Moreover, eosinophils from the car washers expressed high levels of FcepsilonRI beta chain, a molecule important in immunoglobulin E (IgE)-mediated immunity. Levels of FcepsilonRI beta chain expression correlated with serum levels of total and antigen-specific IgE for HIV-1-negative car washers, but this was not the case for individuals coinfected with HIV-1. Overall, these data further implicate eosinophils as having a potential role in development of protective immunity against schistosomes and suggest that changes associated with HIV-1 coinfection increase susceptibility to reinfection.

Adolescent↗

PubMed2006

Burden of malaria at community level in children less than 5 years of age in Togo.

A community-based baseline cross-sectional survey was conducted in three districts in Togo in September 2004 as part of a multidisciplinary evaluation of the impact of the Togo National Integrated Child Health Campaign. During this campaign, long-lasting-insecticide-treated bed nets (LLITNs) were distributed to households with children between 9 months and 5 years of age throughout the country in December 2004. The pre-intervention survey provided baseline malaria and anemia prevalence in children < 5 years of age during peak malaria transmission. Of 2,532 enrolled children from 1,740 households, 62.2% (1,352/2,172) were parasitemic and 84.4% (2,129/2,524) were anemic (hemoglobin < 11 g/dL). Moderate-to-severe anemia (< 8.0 g/dL) was found in 21.7% (543/2,524), with a peak prevalence in children 6-17 months of age and was strongly correlated with parasitemia (OR = 2.3, 95% CI: 1.8-2.5). Net ownership (mainly untreated) was 225/2,532 (8.9%). Subsequent nation-wide introduction of LLITNs and the introduction of artemisinin-based combination therapy have the potential to markedly reduce this burden of malaria.

Anemia↗

PubMed2006

Higher percentages of circulating mast cell precursors correlate with susceptibility to reinfection with Schistosoma mansoni.

A high level of serum IgE is generally associated with human resistance to schistosomes, though the protective mechanisms of IgE remain undefined. We recently reported that whereas some individuals who are occupationally hyperexposed to Schistosoma mansoni display resistance to reinfection, others remain highly susceptible, in some cases due to HIV-1 co-infection. As IgE functions, in part, through FcepsilonRI on mast cells, we characterized circulating CD117(+) FcepsilonRI(+) mast cell precursors in this population. Surprisingly, a higher percentage of CD117(+) cells correlated with a susceptible phenotype in HIV-1 seronegative participants with schistosomiasis. There was no association between percentages of peripheral CD117(+) cells and susceptibility to reinfection in persons with HIV-1. Serum levels of polyclonal IgE were inversely correlated with percentages of CD117(+) cells regardless of HIV-1 status. Thus, immature mast cells may affect IgE availability, or IgE may affect immature mast cells, altering the balance of host susceptibility and resistance to schistosomes.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Epidemiology and spatial analysis of malaria in the Northern Peruvian Amazon.

A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.

Cluster Analysis↗

PubMed2005

Risk factors for kala-azar in Bangladesh.

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3-45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15-44 within household; OR 3.2 95% CI 1.7-6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53-0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70-0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar.

Adolescent↗

PubMed2005

Virgin soil: the spread of visceral leishmaniasis into Uttar Pradesh, India.

We conducted a cross-sectional study to determine the incidence of visceral leishmaniasis (VL) and risk factors in two villages in Uttar Pradesh, India reported to have had a recent outbreak. In 245 households with 2,203 people, we detected 3 current VL cases, 32 past cases, and 8 VL deaths since 2001 (annual incidence = 6 per 1,000). Risk factors included living in the same household as a VL case (odds ratio [OR] = 76, P < 0.0005 in one village and OR = 22, P < 0.0005 in the other village), sleeping downstairs and outside in the summer (OR = 4.7, P = 0.004), and an age > or = 15 years old (OR = 2.9, P = 0.024). Increasing cattle density was a risk factor in one village but not the other. We were not able to determine the route by which VL entered the villages. Our data demonstrate a new spread of VL in previously unaffected areas. We recommend carefully supervised spraying with DDT, surveillance to pinpoint other affected villages, and efforts to increase availability of diagnostic and treatment facilities.

Adolescent↗

PubMed2004

Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence.

BACKGROUND: In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. METHODS: Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1st annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. RESULTS: After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). DISCUSSION: Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having one's neighbors receive treatment with antifilarial drugs.

Journal Article↗

PubMed2004

SARS surveillance during emergency public health response, United States, March-July 2003.

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.

Adolescent↗

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 I. Development of infrastructure and description of study site.

Randomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it.

Bedding and Linens↗

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

Impact of permethrin-treated bed nets on entomologic indices in an area of intense year-round malaria transmission.

The effect of permethrin-treated bed nets (ITNs) on malaria vectors was studied as part of a large-scale, randomized, controlled trial in western Kenya. Indoor resting densities of fed Anopheles gambiae s.l. and An. funestus in intervention houses were 58.5% (P = 0.010) and 94.5% (P = 0.001) lower, respectively, compared with control houses. The sporozoite infection rate in An. gambiae s.l. was 0.8% in intervention areas compared with 3.4% (P = 0.026) in control areas, while the sporozoite infection rates in An. funestus were not significantly different between the two areas. We estimated the overall transmission of Plasmodium falciparum in intervention areas to be 90% lower than in control areas. Permethrin resistance was not detected during the study period. As measured by densities of An. gambiae s.l., the efficacy of bed nets decreased if one or more residents did not sleep under a net or if bed nets had not been re-treated within six months. These results indicate that ITNs are optimally effective if used every night and if permethrin is reapplied at least biannually.

Animals↗

PubMed2003

Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya.

A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.

Bedding and Linens↗

PubMed2003

Effect of permethrin-treated bed nets on the spatial distribution of malaria vectors in western Kenya.

The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya. There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before (P = 0.027) and after (P = 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P = 0.05). For An. funestus, no pre-intervention trend was observed (P = 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P = 0.027). Reduction in mosquito populations in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages. Sporozoite infection rates decreased in control areas following the introduction of ITNs (P < 0.001 for both species), but no spatial association was detected between sporozoite rates and distance to nearest intervention village. We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito populations that is detectable in neighboring villages lacking ITNs, thereby affording individuals residing in these villages some protection against malaria.

Animals↗

PubMed2003

Community-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western Kenya.

Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby households both with and without ITNs was performed in the context of a large-scale, group-randomized, controlled mortality trial in Asembo, western Kenya. Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels. This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs. This implies that in areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting. The strength of the community effect depended upon the proportion of nearby compounds with treated nets. To maximize their public health impact, high coverage with treated nets is essential.

Bedding and Linens↗

PubMed2003

Implications of the western Kenya permethrin-treated bed net study for policy, program implementation, and future research.

The fifth, and probably last, large-scale, group-randomized, controlled trial of insecticide (permethrin)-treated bed nets (ITNs) showed that ITNs are efficacious in reducing all-cause post-neonatal mortality in an area of intense, perennial malaria transmission. The trial helped to define pregnant women and infants as target groups for this intervention in high transmission settings. High population coverage with ITNs in both target and non-target groups may be critical to enhance health and survival in pregnant women and infants. The proportion of households with ITNs (coverage), the proportion of individuals properly deploying ITNs each night (adherence), and the proportion of nets properly treated with insecticide (treatment) are the three key determinants of effectiveness of large-scale ITN programs. These three simple outcomes should serve as the basis for program objectives and monitoring and evaluation efforts. Coverage effects and economic analysis support the proposition that ITNs may be viewed as a public good, worthy of public support. Research should continue to improve the intervention tools (the net, the insecticide, and methods for durable treatment and re-treatment) and their deployment.

Animals↗

PubMed2003

Geographic distribution of schistosomiasis and soil-transmitted helminths in Western Kenya: implications for anthelminthic mass treatment.

A survey of 1,246 children 10-12 years old in 32 primary schools in Kenya near Lake Victoria was conducted to determine prevalence and distribution of schistosome and geohelminth infections. Stool and urine samples were collected and examined for eggs of Schistosoma mansoni, S. haematobium, and intestinal helminths. A questionnaire was used to obtain demographic information and to quantify exposure to surface waters. Houses, schools, and water sources were mapped using a geographic information system. The mean school prevalence of S. mansoni infection was 16.3% (range = 0-80%). Proximity to the lake (r = 0.89, P < 0.001) and contact with lake water were associated with infection, as were specific water-related activities including swimming, fishing, and collecting water. Sixty-three percent of students were infected with one or more other geohelminths and these infections were more homogenously distributed. The separate distributions of schistosome and geohelminth infections have important implications for combined mass-treatment programs.

Animals↗

PubMed2002

Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study.

BACKGROUND: Previous studies have reported age-dependent development of resistance to reinfection by schistosomes and identified immunological correlates of this resistance. However, whether resistance exists that is independent of age effects has been questioned. We did a longitudinal investigation of reinfection by Schistosoma mansoni in an adult population with high occupational exposure. METHODS: We monitored a cohort of 96 male car washers working along the shores of Lake Victoria, Kenya during 349.7 person-years for frequency of water contact and infection with S mansoni. Patients were treated with praziquantel upon study entry and after reinfection with S mansoni. Bivariate analyses and a multivariate proportional hazards model were used to assess the effects of water contact, previous infections, and HIV-1 on S mansoni reinfection rates. FINDINGS: 13 car washers did not get reinfected or only became reinfected after an extended time (91 weeks). 47 initially had a short time to reinfection (15 weeks) but on subsequent treatments showed increased time to reinfection (29-38 weeks). 36 consistently displayed short times to reinfection (<15 weeks) despite multiple reinfection and treatment cycles. Decreased CD4 T-cell counts in HIV-1-positive individuals corresponded to increased susceptibility to S mansoni reinfection. INTERPRETATION: Adults similarly exposed to schistosomiasis are either resistant to reinfection; susceptible, but develop resistance to reinfection after multiple treatments; or remain susceptible to reinfection. Thus, immunological resistance to reinfection with S mansoni exists or can develop independent of age effects. The consequence of HIV-1 co-infection suggests that CD4 T cells contribute to this resistance.

Adult↗