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Biomedical subjects

J Lines

Publications and source records attributed to J Lines.

At least 19 recordsLinked to original sources
PubMed2001

Specific proliferative T cell responses and antibodies elicited by vaccination with simian immunodeficiency virus Nef do not confer protection against virus challenge.

The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated. Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef. Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein. This immunization protocol elicited anti-Nef antibodies in all of the vaccinates as well as specific proliferative responses. However, specific cytotoxic T cell responses were not detected before virus challenge. All vaccinates were challenged intravenously with 10 MID(50) of SIVmacJ5 along with four controls. All eight subjects became infected after SIV challenge and there were no group-specific differences in virus load as measured by virus titration and vRNA analysis. The results of this study support indirectly the report from Gallimore and colleagues (Nat Med 1995;1:1667) suggesting that CD8(+) T lymphocyte responses are required for Nef-based vaccines to restrict SIV infection. If Nef-based vaccines are to be beneficial in controlling infection with immunodeficiency viruses, then it will be necessary to develop more effective immunization protocols that elicit potent CD8(+) cell responses reproducibly.

Animals↗
PubMed2001

Risk assessment of the use of deltamethrin on bednets for the prevention of malaria.

Risk assessments covering the use of the pyrethroid, deltamethrin, on bednets for the prevention of malaria have been conducted The toxicity of deltamethrin in humans and animals is reviewed following both dermal and oral exposure. The no-adverse-effect level (NOEL) for exposure via the dermal route was 1000 mg/kg body weight/day. From this an acceptable exposure level (AEL) of 10 mg/kg body weight/day has been derived. The NOEL for exposure via the oral route was 1 mg/kg body weight/day, with exposures above this causing neurotoxic effects in animals. This NOEL has been used to derive margins of safety compared with predicted exposures. While direct skin contact does not seem to cause systemic toxicity in humans, it can cause burning, numbness and tingling of the skin, which is a local effect. This too is taken into account in the risk assessments. The risk assessments cover those treating bednets, on an intermittent or regular basis, the washing of treated nets, sleeping under treated nets (infants, children and adults). Worst case scenarios for each of these situations show that dermal exposures are low (one-tenth or less of the AEL) and the margins of safety for systemic exposure derived from oral data are acceptable, ranging from 10 to 3300. The benefits of the use of treated bednets in reducing morbidity and mortality from malaria are considerable and it can be concluded that the risk:benefit ratio is very favourable.

Administration, Oral↗
PubMed1999

A new strategy for treating nets. Part 2: users' perceptions of efficacy and washing practices and their implications for insecticide dosage.

The conventional way to treat a mosquito net with pyrethroid insecticide is to apply a standard dosage every 6-12 months, and to avoid washing the net until just before retreatment. In some places, nets are normally washed much more often than this, and it may then be more appropriate to apply smaller amounts of insecticide after each wash. The choice of strategy must take into account not only biological effectiveness, but also users' perceptions of this effectiveness and their net-washing habits. We used focus groups to compare users' responses to nets treated with different dosages and chemicals. One hundred current net users in urban Dares-Salaam were each given a net that had been pretreated either with permethrin (200 or 500 mg/m2), or with lambdacyhalothrin (3 or 15 mg/m2), or with water. Neither participants nor investigators knew which group had received which treatment. Focus group discussions were held after 2, 8 and 12 weeks. Participants greatly preferred treated nets. Low doses were perceived to be less effective, especially after 8 and 12 weeks. After 12 weeks most participants had washed their nets, despite requests to the contrary Dirty nets were regarded as unhealthy and socially unacceptable. Few participants experienced side-effects or expressed fears about the safety of treatment. We conclude that asking people to refrain from washing their nets is unrealistic. A 'low-dose frequent-treatment' strategy of insecticide application may be more appropriate in the long run. At first, however, low doses give perceptibly inferior protection. An initial high (loading) dose, followed by frequent lower (maintenance) dosages, might solve this problem.

Adolescent↗
PubMed1998

Mechanisms of protection induced by attenuated simian immunodeficiency virus. II. Lymphocyte depletion does not abrogate protection.

To determine the role that cellular immune responses play in the protection conferred by vaccination with attenuated SIVmac32H (pC8), we have attempted to deplete macaques of their CD8+ cells prior to challenge with wild-type SIVmac32H (pJ5). In two of four pC8-infected macaques, N109 and N112, a transient partial depletion of CD8+ cells by antibody treatment was achieved. On the day of challenge peripheral CD2+CD4-CD8+ cell counts were reduced by 92 and 95%, respectively, in animals N109 and N112 and their lymph nodes revealed a 46 and 58% reduction, respectively, in CD2+CD4-CD8+ cells. Two other pC8-immunized macaques, N110 and N111, treated in the same way, did not show significant depletion of CD8+ cells. None of these four pC8-immunized animals became infected when challenged with 50 MID50 of pJ5. Treatment of a further four pC8-infected and protected macaques and two naive control animals with Campath-1H antibody successfully depleted peripheral CD3+ cell counts by >99% in all treated animals. Campath-1H depletion resulted in enhanced, longer lasting lymphoid depletion. Yet subsequent challenge with 20 MID50 of pJ5 still failed to infect the pC8-immunized animals. All eight of the naive controls, including two Campath-1H-treated animals, became infected following challenge. In summary, partial depletion of circulating CD8+ cells or total lymphocytes prior to challenge failed to abrogate the protection conferred by vaccination with pC8.

Animals↗
PubMed1998

Evaluation of a candidate human immunodeficiency virus type 1 (HIV-1) vaccine in macaques: effect of vaccination with HIV-1 gp120 on subsequent challenge with heterologous simian immunodeficiency virus-HIV-1 chimeric virus.

Human immunodeficiency virus type 1 (HIV-1) envelope vaccines can now be evaluated for efficacy in macaques by challenging with chimeric viruses in which the env, tat and rev genes of simian immunodeficiency virus (SIV) have been replaced by those of HIV-1. Most experiments have so far been conducted using gp120 molecules derived from T-cell-adapted LAI or MN strains of HIV-1, which predominantly use the CXCR-4 co-receptor. These vaccines protect against infection by apathogenic chimeric virus carrying the same envelope sequences. In the experiment described here, four macaques were vaccinated with W61D gp120 derived from a low passage Dutch isolate and capable of inhibiting the binding of MIP1beta to the co-receptor CCR-5. This vaccine was potent, inducing high titres of binding and neutralizing antibodies against the homologous HIV-1 and tenfold lower titres against a heterologous challenge virus (SHIV(SF33)) in which the env, tat and rev genes of SIV had been replaced by those of a San Francisco isolate, HIV-1(SF33). Despite strong immune responses to the vaccine there was no evidence that it protected against challenge with this chimeric virus. The antigenic divergence between vaccine and challenge virus or the increased virulence of the challenge virus may be responsible for the inability of this vaccine to protect against infection by SHIV(SF33).

AIDS Vaccines↗
PubMed1998

A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone.

A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria.

Anti-Infective Agents↗
PubMed1998

Entomological and epidemiological investigations of malaria transmission in relation to population movements in forest areas of north-west Thailand.

Transmission of forest-related malaria was observed entomologically and epidemiologically for 2 transmission seasons in 1990 and 1991 in 5 villages of Mae Sariang district, Mae Hong Son Province, north-west Thailand. The entomological study included collections of mosquitos and determination of infection rate by using enzyme-linked immunosorbent assay in the residential villages and the farm huts. The epidemiological study included fortnightly visits to 30% of the households to interview and record movement activities and illness of villagers. Circumsporozoite proteins, in most cases of Plasmodium falciparum, were detected in Anopheles minimus species A, An. dirus s.l., An. maculatus s.s. and An. sawadwongporni in residential villages and/or farm huts, suggesting transmission could occur there. Movement of people away from their residences occurred throughout the year for several reasons with a sharp peak in July for agricultural activity, mainly ploughing and planting for rice cultivation. The relative risk of infection for people engaged in agricultural activity was 3 times that of people living in the residential villages. Although a higher biting density of vectors was generally evident at the farm huts, the estimated inoculation rates in the 2 settings were similar. Movement for forest activity increased after harvesting rice in the cool dry season and carried the highest malaria risk, suggesting different epidemiological and probably entomological conditions which need further investigation. The significance is discussed of discrepancies between the case classification system used by this study and that used by malaria sector staff.

Animals↗
PubMed1997

Population structure of Plasmodium falciparum in villages with different malaria endemicity in east Africa.

We have compared allelic polymorphism of two merozoite surface protein genes, MSP-1 and MSP-2, of Plasmodium falciparum and the parasite load in infected individuals in two villages in east Africa. In Michenga village in Tanzania, malaria is holoendemic and transmission is perennial; in Asar village in Sudan, malaria is mesoendemic and transmission is markedly seasonal. The numbers of alleles of both genes were found to be much greater in Michenga than in Asar. More parasite clones exhibiting higher allelic polymorphisms of the genes studied were carried by infected inhabitants in Michenga than those in Asar. The high mean number of clones in Michenga is associated with a very high frequency of out-crossing compared with that estimated in Asar.

Alleles↗
PubMed1995

Knowledge of mosquitos in relation to public and domestic control activities in the cities of Dar es Salaam and Tanga.

A study of community awareness of mosquitos and related subjects in the residential areas of two Tanzanian cities (Dar es Salaam and Tanga) showed that residents were well aware of mosquitos. Almost all claimed to use some form of domestic mosquito control product for their personal protection, and many spend a significant portion of the household income on this. The problems of nuisance-biting and malaria transmission are usually not separated and are considered to be the result of poor environmental hygiene, for which both residents and local authorities are responsible. Although Culex mosquitos are not a primary target of the Urban Malaria Control Project (UMCP), the persistence of nuisance-biting has made residents sceptical and dissatisfied with insecticide spraying. The residents' priorities are evidently not the same as those of the health authorities, yet mutual cooperation is essential. In order to maintain community support, campaigns aimed at malaria vectors should consider the need for additional measures to control Culex mosquitos, such as those now being tried by the UMCP. Mosquito breeding sites are non-specifically associated with rubbish and standing water of all kinds, and so the actions that the community considers necessary for mosquito source reduction tend to be poorly targeted. Residents do not recognize that some sources produce malaria mosquitos while others produce nuisance mosquitos. The environmental anti-mosquito measures currently promoted by health education and other forms of propaganda are also poorly targeted. While some of them are directed at important Culex breeding sites, others are aimed at sites of little importance for mosquitos of any kind.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

Use of nasopharyngeal tubes as aids to lateral port construction and maintenance of the airway in pharyngeal flap surgery.

We suggest the bilateral placement of nasopharyngeal tubes of appropriate size as a simple aid in constructing lateral ports of the correct size when doing a superiorly-based, lined, pharyngeal flap for velopharyngeal incompetence. If one leaves the tubes in for 24 to 48 hours postoperatively, they are of great help in maintaining a clear airway during that period.

Adolescent↗
PubMedDate not supplied

Entomological evaluation of community-wide use of lambdacyhalothrin-impregnated bed nets against malaria in a border area of north-west Thailand.

This paper reports 2 studies. (i) After a year of baseline data collection, lambdacyhalothrin-treated bed nets were introduced into 3 of 5 villages in north-west Thailand, the remaining 2 being treated with placebo. Human bait collections were carried out in each village on 2 nights per month, for 8 months of each year, and the biting densities were compared between the first year and the second year. The treated bed nets did not have any significant impact on the density or parous rates of Anopheles sawadwongporni and A. maculatus s.s. populations. The results for A. dirus s.l. were not conclusive because of the low number caught. Significant reductions in biting and parous rates of A. minimus species A were observed in only one of the 3 treated villages, and there was no overall difference between treated and control groups. However, the trial suffered from the washing of nets by villagers and the low rate of reimpregnation. (ii) A short-term study involved 4 villages in a cross-over design, and lasted 48 d. For the first 24 d, residents of 2 villages were given new treated nets while the other 2 villages retained their own untreated nets. For the second 24 d, this situation was reversed. Daily light-trapping revealed no significant difference in the indoor densities or parous rates of A. minimus species A between the periods with treated or untreated nets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Permethrin-treated bed nets do not have a 'mass-killing effect' on village populations of Anopheles gambiae s.l. in The Gambia.

In The Gambia, the use of permethrin-treated bed nets has led to a reduction in morbidity and mortality from malaria in children. However, no clear evidence has been found for a 'mass-killing effect' on the mosquito vectors as a result of this intervention. Two further entomological studies to investigate this phenomenon have been carried out. In one study, 20 villages were paired so that bed nets in one member of each pair were treated with permethrin. In the other, a cross-over design was used in which treated and untreated bed nets were exchanged between 2 villages. Longevity, biting rate and resting density of the malaria vector population and sporozoite rates were assessed in both studies. Malaria vectors were equally abundant and long-lived, and as likely to be infective, in villages with treated bed nets as in those with untreated nets. However, a clear reduction in the density of the indoor-resting population of mosquitoes in rooms with treated bed nets was found, probably reflecting the excito-repellency of the insecticide. This study confirmed that, in The Gambia, the protection against death and morbidity from malaria seen in children using treated bed nets must be due primarily to personal protection rather than to a 'mass-killing effect' on the mosquito vector population at a village level.

Animals↗