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Biomedical subjects

A Nicoll

Publications and source records attributed to A Nicoll.

At least 109 records · Page 6Linked to original sources

The impact of HIV-1 infection on mortality in children under 5 years of age in sub-Saharan Africa: a demographic and epidemiologic analysis.

OBJECTIVE: To estimate the effects of the HIV-1 epidemic on mortality in children under 5 years of age in urban and rural populations in eastern and central, and southern Africa. METHODS: A lifetable method that allows for the effects of competing causes (i.e., mortality due to HIV and other causes) was used to estimate mortality. Our calculations used published and unpublished data on HIV-1 infection in African adults and children (incidence and prevalence, vertical transmissions, transmission by blood transfusion and natural history), and typical baseline fertility and child mortality data. The results were applied to model rural and urban populations to explore the effects of parameters such as mortality in HIV-1-infected children, fertility in infected mothers and overall population growth. RESULTS: We estimate that child mortality will rise substantially because of the prevalence of HIV-1 in urban areas. There will be little difference in the absolute levels of increase in mortality between areas in eastern and central, and southern Africa with similar levels of HIV infection; however, in relative terms the effect will be more noticeable in southern Africa because of the lower baseline mortality. Towns with severe epidemics (30% adult seroprevalence) might experience a rise in child mortality of one-third in eastern and central Africa and three-quarters in southern Africa. This will cancel or reverse existing advantages in urban over rural levels of child mortality and this effect will be more pronounced in southern Africa. The exact impact of HIV-1 will vary according to mortality among HIV-1-infected children and to fertility among infected women. However, changes in age structure and population growth have relatively little impact on mortality. CONCLUSIONS: There are likely to be substantial increases in child mortality in sub-Saharan Africa as a result of HIV-1 infection. The main determinant of childhood infection is the scale of the epidemic among adults. Increases in mortality will depend on local adult seroprevalence but are hard to predict precisely because of possible variation in death rates among HIV-1-infected children. In rural areas with low seroprevalence other diseases will remain the main cause of mortality. However, in urban areas families and health services will have to face considerably increased demands from ill and dying children.

Adolescent↗

Lay health beliefs concerning HIV and AIDS--a barrier for control programmes.

Work in AIDS control in East Africa revealed widespread lay health beliefs concerning HIV infection and AIDS amongst health workers and members of the general population at both lower and higher risk of infection. The beliefs were often factually incorrect and undermining to AIDS control in the field of information, education and communication (IEC). The beliefs were conveyed informally but their origins could often be traced. Local media were important sources. The beliefs were powerful, persistent and resistant to conventional educational methods. Their prevalence and type changed with time in different groups. A model of how the beliefs came to be generated is proposed and reasons suggested for their persistence and strength. A current programme for countering the beliefs is described. An additional important group of policy and scientific beliefs were also identified amongst policy makers and scientists. It is noted that these phenomenon are international and not confined to Africa.

Acquired Immunodeficiency Syndrome↗

Single-fibre EPSPs in layer 5 of rat visual cortex in vitro.

Simultaneous intracellular recordings were made from pairs of synaptically connected layer 5 pyramidal neurones less than 150 microns apart, in slices of rat visual cortex. Action potentials were evoked in one cell of a pair by depolarizing current pulses, while spike-triggered averaging was employed to reveal connections in the other cell and vice versa. Only 4 excitatory postsynaptic potentials (EPSPs) (0.7-1.2 mV) were recorded out of 270 cell pairs tested, equivalent to a connection probability of less than 0.02. Therefore, single-fibre EPSPs between pyramidal cells in layer 5 are less frequent, but individually larger in amplitude, than those found previously between pyramidal cells in layer 2/3 of rat visual cortex.

Animals↗

Sentinel surveillance for HIV-1 among pregnant women in a developing country: 3 years' experience and comparison with a population serosurvey.

OBJECTIVES: To establish unlinked, anonymous sentinel surveillance for HIV-1 among pregnant women attending an antenatal clinic, to determine age-specific seroprevalences, to monitor trends and to compare seroprevalence with that detected by a population serosurvey. To establish the sustainability and costs of surveillance. DESIGN: Sentinel surveillance for HIV through serial collection of unlinked, anonymous seroprevalence data from antenatal care; comparison of sentinel data with those from a population serosurvey; financial and general audit of the sentinel surveillance. SETTING: A community antenatal clinic in a large urban centre, Mwanza Municipality, Tanzania, eastern Africa, between October 1988 and September 1991. PATIENTS: Pregnant women attending for antenatal care. MAIN OUTCOME MEASURE: Age-specific HIV-1 seroprevalences, trends over time, difference from age-specific population seroprevalences, sustainability and costs. RESULTS: Overall HIV-1 seroprevalence was 11.5% (95% confidence interval, 10.5-12.4); differences in age-specific prevalences were not significant. There was no clear evidence of change in seroprevalence over the study period in any age group, although there was some indication of a rise in some age groups in 1988-1989. Sentinel surveillance among pregnant women may have significantly underestimated population HIV-1 seroprevalence for women under the age of 35 years. HIV-1 surveillance proved feasible and sustainable. Additional recurrent costs were US$1.7 per specimen for unlinked anonymous testing and US$0.57 per woman for syphilis screening. CONCLUSIONS: HIV-1 seroprevalence did not change significantly over 3 years, probably implying a substantial incidence of HIV-1 infection. In this setting seroprevalence in pregnant women may have underestimated population seroprevalence in women aged under 35 years. With modest inputs and good organization unlinked anonymous HIV-1 sentinel surveillance of pregnant women can be introduced and sustained in an African setting. This may usefully be carried out in conjunction with syphilis screening.

AIDS Serodiagnosis↗

Immunizations in children.

In 1992, there was a setback in measles vaccination for developing countries as high-titre vaccines were withdrawn following reports of excess mortality in vaccine recipients. The importance of continuing polio vaccination in industrialized countries was emphasized by an outbreak of paralytic polio among an unimmunized community in the Netherlands. Immunization programs are now increasingly using the Jeryl Lynn strain of mumps vaccine following reports of meningoencephalitis associated with the Urabe strain. A hepatitis A vaccine has become generally available and hepatitis B vaccine is being introduced into more childhood programs in countries where the disease is highly prevalent. Trials of group B meningococcal meningitis vaccines have yielded disappointing estimates of efficacy, particularly in younger children. Earlier reports of invasive bacterial infections after pertussis immunization have not been confirmed.

Bacterial Infections↗

Modulation of EPSP shape and efficacy by intrinsic membrane conductances in rat neocortical pyramidal neurons in vitro.

1. Intracellular recordings were made from pyramidal neurons in layers II/III and V of rat visual cortical slices. Distal and proximal excitatory postsynaptic potentials (EPSPs) were evoked using extracellular bipolar electrodes placed on the slice horizontal to each cell, near the apical and basal dendrites respectively. Experiments were conducted in the presence of 2-amino-5-phosphonopentanoate, picrotoxin and, in most cases, 2-hydroxy-saclofen. 2. For layer II/III pyramidal neurons, voltage undershoots following distal and proximal EPSPs (n = 7 pairs) and injected somatic pulses were rarely apparent. In layer V pyramidal neurons substantial voltage undershoots were recorded following distal and proximal EPSPs (n = 27 pairs) and injected somatic pulses, with undershoot being greatest for apical inputs (P = 0.001). The greater undershoots following apical EPSPs were also apparent in semilogarithmic plots of voltage decay where the slope of decay for apical EPSPs was quicker than the voltage decay following pulses of current injected at the soma. There was no significant difference in the shapes of distal and proximal EPSPs in layer II/III or layer V pyramidal cells under control conditions. 3. Pharmacological agents were used to reduce voltage undershoots. The most successful of these was alinidine, a putative blocker of the slow inward rectifier (IH) conductance. In the presence of bath-applied 100 microM alinidine, undershoots were significantly reduced and it became possible to distinguish the relative origins of EPSPs on the basis of their shape. Distally generated EPSPs (n = 14) had rise times and half-widths that were 2.8 and 1.5 times longer respectively than those evoked proximally (n = 10; P = 0.001 for both parameters). 4. These results confirm previous theoretical simulations of somatic recordings in passive model neurons where distal EPSPs display slower rise times and longer half-widths than proximal EPSPs. The present results suggest that, at least in pyramidal neurons of layer V, distal synaptic inputs can be specifically modulated by intrinsic membrane conductances.

Animals↗

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 1. Prevalence and incidence.

OBJECTIVE: To determine the prevalence of syphilis and the prevalence and incidence of self-reported STD syndromes in the population of Mwanza Region, North-Western Tanzania. METHODS: A population-based random cluster sample survey, stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54 years was performed in 1990-91. The seroprevalence of syphilis (using TPHA and RPR) and the prevalence and incidence of self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS) were determined. RESULTS: Active syphilis was detected in 9% of the adult population, while 15% had serological evidence of past or current infection. Seroprevalence was significantly lower in the rural than in the roadside and urban populations, but there was little difference between men and women. Amongst men, a history of GDS was reported by 28%, and a history of GUS by 14%, with point prevalences of 2.3% and 1.3% respectively. Annual incidence among men were 6.8% for GDS and 3.6% for GUS. Women reported these conditions less frequently. There was little difference between the strata in the prevalence or incidence of reported STD syndromes. CONCLUSION: Sexually transmitted diseases represent a major public health problem in both the rural and urban populations of Mwanza Region.

Adolescent↗

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour.

OBJECTIVE: To determine risk factors for syphilis and sexually transmitted disease (STD) syndromes, and to study health seeking behaviour among those with STD syndromes, in the population of Mwanza Region, North-Western Tanzania. METHODS: A population-based random cluster sample survey, stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54 years was performed in 1990-91. The seroprevalence of syphilis and the prevalence and incidence of self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS) are reported in the accompanying paper. This paper reports on risk factors for these conditions and on health seeking behaviour among those reporting them. RESULTS: In both sexes, the risk of STDs increased with the reported number of sexual partners in the previous five years. Men who were separated, divorced or widowed were at increased risk of STDs, but this was not the case among women. Higher educational status was associated with an increased risk of urethral discharge in males but with a decreased prevalence of syphilis in females. Male circumcision was associated with an increased risk of urethral discharge but a reduced prevalence of syphilis. Nearly all men, and 90% of women, reporting symptoms of genital discharge or ulceration had sought treatment. Of these, approximately 70% of males and 60% of females had sought treatment in the official health sector. CONCLUSIONS: Targetted health education concerning risk reduction for HIV infection and other STDs should be a high priority in this population. Improved case management of STDs in health centres and dispensaries may have a substantial impact on the incidence of these infections.

Adolescent↗

Sentinel surveillance for HIV-1 infection: how representative are blood donors, outpatients with fever, anaemia, or sexually transmitted diseases, and antenatal clinic attenders in Mwanza Region, Tanzania?

OBJECTIVE: To assess the validity of extrapolation from sentinel data by comparing the HIV-1 prevalence of various sentinel groups with that of the general population in Mwanza Region, Tanzania. METHODS: In a population survey, 4161 individuals were selected in a stratified random cluster sample. Sentinel groups (all in the age group 15-54 years) included blood donors (n = 1090); patients examined at district hospitals for the presence of malaria parasites (n = 1488), anaemia (n = 1339), or syphilis (n = 33); and antenatal clinic attenders (n = 1193). The HIV-1 serostatus of individuals selected from the population survey was tested using enzyme-linked immunosorbent assay (ELISA) and Western blot; 51% of the blood donors were tested using HIVCHEK, and all others using ELISA. HIV-1 prevalence was standardized for age, sex, and urban/non-urban location. RESULTS: HIV-1 prevalence (standardized by age, sex, and residence) in Mwanza Region was 4.0% (3.0% in non-urban areas and 11.3% in town). The standardized HIV-1 prevalences in the sentinel groups were: blood donors, 4.5%; patients with fever, 11.6%; patients with anaemia, 8.9%; urban sexually transmitted disease patients, 27.1%; urban antenatal clinic attenders, 11.8%. The crude prevalence in blood donors was 6.0%. CONCLUSION: Blood donors who are related to blood recipients appear to be a representative sentinel group in this region, provided that data are standardized for age, sex, and urban/non-urban location. Patients with fever and antenatal clinic attenders may reflect trends, but data from patients with fever markedly overestimate, and data from antenatal clinic attenders underestimate, population HIV-1 prevalence. Because self-selection of blood donors may become more pronounced, this comparison should be repeated later or elsewhere, should the opportunity arise.

Adolescent↗

EPSPs in rat neocortical pyramidal neurones in vitro are prolonged by NMDA receptor-mediated currents.

We investigated the influence of 2-amino-5-phosphonovalerate (APV), a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the time course of small excitatory postsynaptic potentials (EPSPs) in pyramidal neurones in layer 2/3 of adult rat visual cortex in vitro. Time constants of the voltage decay following the EPSPs (T(s)) and after brief (2 ms) pulses of current injected at the soma (T(p)) were determined from semilogarithmic plots of averages of 100-250 trials. The mean T(s)/T(p) ratio decreased from 1.53 +/- 0.29 (S.D.) to 1.10 +/- 0.08 on addition of 50 microM APV to the bathing medium (P less than 0.001; n = 23), but there was no significant change in EPSP peak amplitude or rise-time. These results suggest that the time course of many small EPSPs, even at negative membrane potentials and in the presence of Mg2+, can be prolonged by NMDA receptor-mediated currents.

2-Amino-5-phosphonovalerate↗

Heterosexually acquired HIV-1 infection: cases reported in England, Wales and Northern Ireland, 1985 to 1991.

By the end of 1991, there had been 417 reports of AIDS and 1620 reports of HIV-1 infection in persons in England, Wales and Northern Ireland who probably acquired their infection through sexual intercourse between men and women. Between 1986 and 1991, the proportion of AIDS cases attributable to heterosexual transmission increased from 2% to 14% and of diagnosed HIV-1 infections from 4% to 23%. Reported HIV-1 infections inadequately reflect the extent of infection as only individuals choosing to be tested can be reported. HIV-1 infection acquired during heterosexual intercourse may be the result of transmission from partners who were infected by routes other than heterosexual transmission (first generation transmission) or of transmission from infected partners who were themselves infected through heterosexual intercourse (second generation transmission). Of the 417 cases in which AIDS was acquired through heterosexual intercourse, 42 (10%) were categorised as due to first generation transmission, 328 (79%) as second generation transmission--abroad, and 47 (11%) as second generation transmission--UK. Transmission categories could be allocated to 1438 of the 1620 reports of HIV infection: 17% were categorised as first generation, 74% as second generation--abroad, and 9% as second generation--UK. Heterosexual transmission of HIV infection is increasing, both in individuals acquiring their infection abroad as well as those who become infected in the United Kingdom.

Acquired Immunodeficiency Syndrome↗

The epidemiology of HIV-1 infection in urban areas, roadside settlements and rural villages in Mwanza Region, Tanzania.

OBJECTIVE: To determine the prevalence of HIV-1 infection and to identify the most important risk factors for infection. DESIGN: A cross-sectional population survey carried out in 1990 and 1991 in Mwanza Region, Tanzania. METHODS: Adults aged 15-54 years were selected from the region (population, 2 million) by stratified random cluster sampling: 2434 from 20 rural villages, 1157 from 20 roadside settlements and 1554 from 20 urban wards. Risk factor information was obtained from interviews. All sera were tested for HIV-1 antibodies using enzyme-linked immunosorbent assay (ELISA); sera non-negative on ELISA were also tested by Western blot. RESULTS: The response rate was 81%. HIV-1 infection was 1.5 times more common in women than in men; 2.5% of the adult population in rural villages, 7.3% in roadside settlements and 11.8% in town were infected. HIV-1 infection occurred mostly in women aged 15-34 years and men aged 25-44 years. It was associated with being separated or widowed, multiple sex partners, presence of syphilis antibodies, history of genital discharge or genital ulcer, travel to Mwanza town, and receiving injections during the previous 12 months, but not with male circumcision. CONCLUSION: This study confirms that HIV-1 infection in this region in East Africa is more common in women than in men. The results are consistent with the spread of HIV-1 infection along the main roads. There is no evidence that lack of circumcision is a risk factor in this population.

Adolescent↗

Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro.

Synaptic transmission between pairs of neurons in layer 2/3 of in vitro slices from the rat visual cortex was studied by dual intracellular recording. The intrinsic electrophysiological properties of these neurons suggested that they were pyramidal cells. More than 1/3 of the total number of synaptically connected neurons were stained by intracellular iontophoresis of biocytin, and all had pyramidal morphology. Postsynaptic potentials (PSPs) were evoked by single action potentials (elicited by current injection) in presynaptic cells. Measurements of PSP latency, amplitude, and shape were made on spike-triggered averages. Forty-eight synaptic connections were found out of a possible total of 549, equivalent to a probability of about 0.09. For these 48 connections, the distance between the 2 impalement sites ranged from 50 to 340 microns. All PSPs were depolarizing at rest (-74 +/- 5 mV, mean +/- SD), and all 14 of the PSPs that were also recorded with the postsynaptic cell depolarized to around action potential threshold (about -55 mV) remained depolarizing. PSPs had short latencies (1.2 +/- 0.6 msec, mean +/- SD), suggesting that they were mediated by monosynaptic pathways. Peak amplitudes of the averaged PSPs varied widely (range, 0.05-2.08 mV), but the majority were less than 0.5 mV. PSPs decayed exponentially with time constants that were correlated with, but slightly longer than, the membrane time constants of the postsynaptic cells measured using injected current pulses. Four cell pairs were connected reciprocally, and 6 examples of convergent input were found in which a single cell was postsynaptic to more than 1 presynaptic cell. Trial-to-trial fluctuations in PSP amplitude were analyzed for 16 synaptic connections. The amplitude of the PSP evoked by a presynaptic action potential fluctuated more than could be accounted for by the background noise.

Action Potentials↗