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Biomedical subjects

K Marsh

Publications and source records attributed to K Marsh.

At least 127 records · Page 7Linked to original sources
PubMed1995

Perceptions of symptoms of severe childhood malaria among Mijikenda and Luo residents of coastal Kenya.

Effective community based malaria control programmes require an understanding of current perceptions of malaria as a disease and its severe manifestations. Quantitative and qualitative surveys of mothers on the Kenyan Coast suggest that fever is conceptualised in biomedical terms whereas the aetiology of severe malaria is perceived to be of more complex cultural origin. This is reflected in the treatments sought for convulsions. The results are discussed in the context of ethnographic factors. To be effective, future health information programmes must take cultural beliefs into account.

Adolescent↗
PubMed1995

Halofantrine pharmacokinetics in Kenyan children with non-severe and severe malaria.

1. Kenyan children with uncomplicated malaria given oral halofantrine (HF; non-micronised suspension; 8 mg base kg-1 body weight 6 hourly for three doses) showed wide variation in the disposition of HF and desbutylhalofantrine (HFm). 2. Eight Kenyan children with severe (prostrate) falciparum malaria who were receiving intravenous quinine, were given the same HF regimen by nasogastric tube. One patient had undetectable HF and two had undetectable HFm at all times after drug administration. 3. The mean AUC(0,24 h) of HF in prostrate children was half (7.54 compared with 13.10 micrograms ml-1 h) (P = 0.06), and that for HFm one-third (0.84 compared with 2.51 micrograms ml-1 h) (P < 0.05) of the value in children with uncomplicated malaria. 4. Oral HF may be appropriate for some cases of uncomplicated falciparum malaria in Africa, but in patients with severe malaria, the bioavailability of HF and HFm may be inadequate.

Administration, Oral↗
PubMed1995

Inter-observer agreement of the assessment of coma scales and brainstem signs in non-traumatic coma.

The authors evaluated the inter-observer agreement between two experienced clinicians examining 19 unconscious children who were not paralysed or ventilated. Inter-observer reliability was assessed by proportion of agreement, disagreement rate and kappa statistics. Corneal reflexes, pupillary responses to light and motor responses were the most reliably elicited. Reduction of the number of categories improved inter-observer agreement. Some of the disagreement may be attributed to changes in the child's condition during the period of assessment. There was more agreement about the five-category 0-IV scale than the summated Adelaide (10-category) and Jacobi (13-category) scales. The ability of these scales to follow changes in the patient's condition and to predict outcome needs to be evaluated in a prospective trial.

Brain Stem↗
PubMed1995

Plasmodium falciparum rosetting is associated with malaria severity in Kenya.

Rosette formation in 154 fresh Plasmodium falciparum isolates from Kenyan children with mild (n = 54), moderate (n = 64), or severe (n = 36) malaria was studied to determine whether the ability to form rosettes in vitro is correlated with malaria severity. There was a wide distribution of rosette frequencies within each clinical category; however, a clear trend towards higher rosette frequency with increasing severity of disease was seen, with the median rosette frequency of the mild-malaria group (1%; range, 0 to 82%) being significantly lower than those of the moderate-malaria group (5%; range, 0 to 45%; Mann-Whitney U test, P < 0.02) and the severe-malaria group (7%; range, 0 to 97%; Mann-Whitney U test, P < 0.003). Within the severe-malaria category there was no difference in rosetting among isolates from cerebral malaria patients or those with other forms of severe malaria. We also examined the ABO blood groups of the patients from whom isolates were obtained and found that isolates from group O patients (median rosette frequency, 2%; range 0 to 45%) rosetted less well than those from group A (median, 7%; range 0 to 82%; Mann-Whitney U test, P < 0.01) or group AB (median, 11%; range 0 to 94%; Mann-Whitney U test, P < 0.03). We therefore confirm that rosetting is associated with severe malaria and provide further evidence that rosetting is influenced by ABO blood group type. Whether rosetting itself plays a direct role in the pathogenesis of severe malaria or is a marker for some other causal factor remains unknown.

ABO Blood-Group System↗
PubMed1995

Interobserver variation in respiratory signs of severe malaria.

Respiratory abnormalities are common presentations of malaria and acute respiratory tract infection, both of which are major causes of childhood mortality and morbidity in sub-Saharan Africa. Appropriate management depends on accurate assessment of disease severity which for the majority of children must be based on clinical signs alone. Choosing which signs best serve this purpose remains a considerable problem particularly in malaria endemic areas. As part of a prospective study to define clinical signs indicative of life threatening malaria video recordings were used to examine the level of agreement between clinicians for potentially important respiratory signs in 51 children. Overall agreement was good for recession, severe recession, and nasal flaring (kappa = 0.57, 0.50, and 0.60 respectively) and substantial for deep breathing and the summary impression of respiratory distress (kappa = 0.70 and 0.69 respectively). However, within this substantial variation in interpretation was apparent between individual observers from slight to almost perfect agreement (kappa values 0.10-0.92). Video is a useful tool to demonstrate interobserver variation and it may also allow training in recognition of signs and a means of standardising clinical signs between centres.

Child↗
PubMed1995

Relationships between Plasmodium falciparum transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast.

The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at nine sites in the Kilifi District in Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s. l., An. funestus, An. coustani, An. squamosus, An. nili, and An. pharoensis. Anopheles gambiae s.l. was the predominant vector, comprising 98.4% of the total anophelines collected. Overall, 3.5% of 2,868 An. gambiae s.l. collected indoors and 0.8% of 261 collected outdoors contained P. falciparum sporozoites. Transmission was detected during 10 months, with peak periods from June to August and December to January. In eight of the nine sites, entomologic inoculation rates (EIRs) averaged only four infective bites per year (range 0-18); an annual EIR of 60 was measured for the site with the highest intensity of transmission. The incidence of severe malaria infections, ranging from 8.6 to 38.1 per 1,000 children (0-4 years), was not associated with EIRs. At these sites on the coast of Kenya, a high incidence of severe disease occurs under conditions of very low levels of transmission by vector populations. With respect to conventional approaches for vector control in Africa, decreases in transmission, even to levels barely detectable by standard approaches, may not yield corresponding long-term reductions in the incidence of severe disease.

Animals↗
PubMed1995

Parasite viability during treatment of severe falciparum malaria: differential effects of artemether and quinine.

The effect of artemether (AR) and quinine (QN) on parasite viability ex vivo was compared in children being treated for severe Plasmodium falciparum malaria. Parasitized blood taken at intervals during treatment was cultured in vitro, and parasite development was assessed microscopically. Parasite viability (defined as the proportion of circulating rings developing to early schizonts) was 56.8% in the AR group (n = 7) 6 hr after the start of treatment, compared with 93.3% for QN (n = 6; P = 0.015). Even after 24 hr of QN treatment, parasite viability was not significantly reduced in five patients. These ex vivo findings, which confirm previous observations of the stage-specific effects of these drugs against P. falciparum, suggest that AR may be superior to QN in the treatment of severe malaria.

Animals↗
PubMed1994

Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773.

Based on the knowledge that glucuronidation was a major route of metabolism of the N-hydroxyurea class of 5-lipoxygenase inhibitors, a simple in vitro glucuronidation assay was established using liver microsomes from various species, including man. Compounds that were potent inhibitors of 5-LO and showed a reduced metabolic liability in vitro were then characterized more extensively in experimental animals. This prudent usage of in vitro glucuronidation proved to be highly efficient and was indispensable in the identification of A-78773, a potent new long-acting 5-LO inhibitor. Further studies with liver microsomes revealed that glucuronidation of A-78773 was stereoselective and that the R(+) enantiomer was considerably more resistant to conjugation than the S(-) stereoisomer. Pharmacokinetic studies in experimental animals and humans confirmed the greater metabolic stability of the R(+) enantiomer. A single 400-mg oral dose of A-78773 inhibited ex vivo leukotriene biosynthesis for more than 24 hours. Since 78% of the drug plasma AUC following A-78773 administration was accounted for by the R(+) enantiomer, it is reasonable to assume that the majority of the leukotriene inhibition caused by the racemate is attributable to the R(+) enantiomer, A-79175, particularly at the later times. The equivalent 5-lipoxygenase inhibitory potency coupled with the superior pharmacokinetic profile of the R(+) enantiomer, A79175, compared to the S(-) enantiomer, A-79176, indicate that the development of this compound may be preferable to the racemate A-78773.

Animals↗
PubMed1994

Plasmodium falciparum: a family of sulphated glycoconjugates disrupts erythrocyte rosettes.

The ability of Plasmodium falciparum-infected erythrocytes to form spontaneous rosettes with uninfected red cells is a parasite adhesion property which has been associated with severe malaria. The mechanism of rosetting remains unknown, but the ability of heparin to disrupt rosettes has been recognised previously. In this paper we show that a group of sulphated glycoconjugates including sulphatide, dextran sulphate, and fucoidan are more effective rosette reversing agents than heparin and are active against both laboratory strains and wild isolates. Other related anionic glycosaminoglycans such as the chondroitin sulphates A, B, and C and hyaluronic acid have no effect on rosette formation. This family of sulphated glycoconjugates which are active against rosettes is also known to inhibit sporozoite invasion of hepatocytes and merozoite reinvasion of erythrocytes, suggesting that sulphated glycoconjugate interaction may be an important process in cell adhesion at different stages in the plasmodial life cycle.

Animals↗
PubMed1994

Severe childhood malaria in two areas of markedly different falciparum transmission in east Africa.

Malaria remains a major public health challenge in sub-Saharan Africa, yet our knowledge of the epidemiology of malaria in terms of patterns of mortality and morbidity is limited. We have examined the presentation of severe, potentially life-threatening malaria to district hospitals in two very different transmission settings: Kilifi, Kenya with low seasonal transmission and Ifakara, Tanzania with high seasonal transmission. The minimum annual rates of severe disease in children below five years in both populations were similar (46 per 1000 children in Kilifi and 51 per 1000 children in Ifakara). However, there were important differences in the age and clinical patterns of severe disease; twice as many patients were under one year of age in Ifakara compared with Kilifi and there was a four fold higher rate of cerebral malaria and three fold lower rate of malaria anaemia among malaria patients at Kilifi compared with Ifakara. Reducing malaria transmission in Ifakara by 95%, for example with insecticide-treated bed nets, would result in a transmission setting comparable to that of Kilifi and although this reduction may yield early successes in reducing severe malaria morbidity and mortality in young, immunologically naive children, place these same children at increased risk at older ages of developing severe and potentially different manifestations of malaria infection hence producing no net cohort gain in survivorship from potentially fatal malaria.

Anemia↗
PubMed1994

Efficacy of A-73209, a potent orally active agent against VZV and HSV infections.

A-73209 is a novel oxetanocin derivative with potent in vitro and in vivo activity against VZV, HSV-1, and HSV-2. A-73209 was two logs more potent than acyclovir against five thymidine kinase positive (TK+) strains of VZV in vitro (mean EC50 0.01 vs. 1.22 micrograms/ml). The activity of A-73209 was one log more potent than acyclovir against TK+ HSV-1 strains in vitro (EC50 = 0.03 vs. 0.32 micrograms/ml). A-73209 yielded a mean EC50 of 2.2 micrograms/ml compared to a mean EC50 of 0.37 micrograms/ml for acyclovir against a panel of TK+ HSV-2 strains in vitro. The in vitro activity of A-73209 against thymidine kinase negative or deficient strains of VZV, HSV-1 and HSV-2 was much lower than for the corresponding TK+ strains. A-73209 produced efficacy superior to acyclovir against lethal systemic or intracerebral HSV-1 infections in mice. The greater efficacy of A-73209 relative to acyclovir was especially apparent with oral dosing. Against HSV-2 infections in mice, the efficacy of A-73209 ranged from equal to 1.7 times less active relative to acyclovir with oral dosing. A-73209 was orally bioavailable in mice, with maximal serum concentrations well in excess of in vitro inhibitory concentrations. A-73209 appears to be a potent and selective agent against varicella-zoster virus and herpes simplex virus infections.

Acyclovir↗
PubMed1994

The prevalence and morbidity of snake bite and treatment-seeking behaviour among a rural Kenyan population.

Snake-bite mortality among a rural population in Kenya was estimated to be 6.7/100,000 people each year, representing 0.7% of all deaths. A community-based retrospective survey of 4712 households provided estimates of the incidence of snake bite in this population. Although 151/100,000 people are bitten each year, only 19% of these are bitten by potentially venomous snakes. When those who had been bitten were shown photographs of a range of locally prevalent snakes, most indicated that both venomous and non-venomous snakes were capable of causing death. Most (68%) of bite cases sought treatment from a traditional healer who invariably used local herbal preparations applied to the bite site and/or in a ring around the bitten limb. Local skin incisions were also commonly practised. The use of traditional medicine for snake bite is a feature of most areas of the developing world where venomous snakes are prevalent. Improvements in early referral and appropriate care will only occur when traditional healers are integrated into primary health care and hospital-based health systems.

Adolescent↗
PubMed1994

Factors influencing admission to hospital during terminal childhood illnesses in Kenya.

BACKGROUND: Access to essential clinical services offered by district hospitals or health centres forms an important component of primary health care activities in the developing world. Utilization of hospital facilities during life-threatening childhood illnesses will affect survivorship. METHODS: We have examined clinical, geographical, social, economic and demographic features of families of 49 children who consulted a hospital facility during a terminal illness and 88 who did not during a 1-year prospective demographic and hospital-based surveillance of a rural community on the Kenyan Coast. RESULTS: Of children who died without admission, 15% had symptoms which lasted only 1 day compared to no children who were admitted (P = 0.004). Furthermore, those who died without admission tended to live further away from the nearest bus stage (P = 0.01) and had made greater use of traditional healers (P = 0.08). Mothers' education or household socioeconomic status did not influence admission to hospital. CONCLUSION: Health education is required to improve early recognition of clinical signs warranting hospital care and traditional healers should be included in any community-based education programmes.

Child↗
PubMed1994

Treatment of experimental Pneumocystis carinii infection by combination of clarithromycin and sulphamethoxazole.

The efficacy of clarithomycin and sulphamethoxazole for treatment of experimental Pneumocystis carinii infection was investigated. Rats were immunosuppressed with dexamethasone and inoculated intratracheally with 5 x 10(6) P. carinii cysts. After 2 weeks, the lung tissues were assayed for P. carinii cyst burden. The combination of clarithromycin and sulphamethoxazole caused a significantly greater reduction in cyst burden than either drug alone. Up to 50% of the rats treated with the combination of clarithromycin and sulphamethoxazole were negative for P. carinii cysts. Equivalent doses of the individual drugs given alone did not produce cures. The combination of clarithromycin and sulphamethoxazole was more than twice as effective as either drug alone. Clarithromycin combined with sulphamethoxazole in treatment of P. carinii infection could be especially useful since clarithromycin monotherapy provides safe and effective treatment against many other pathogens, including several that are associated with AIDS.

Animals↗
PubMed1994

Brain swelling and ischaemia in Kenyans with cerebral malaria.

Computed tomography was performed on 14 unconscious Kenyan children recovering from cerebral malaria (seven of whom had another scan 12-120 days later) to elucidate the cause of intracranial hypertension and neurological sequelae. Brain swelling, defined as a loss of cerebrospinal fluid spaces, was documented in six children, while a further two had conspicuously small ventricles only. There was severe intracranial hypertension in the two children with definite brain swelling in whom intracranial pressure was monitored. There was no evidence of acute hydrocephalus or vasogenic oedema. Four children with brain swelling also had widespread low density areas suggestive of ischaemic damage. The patterns of damage were not uniform but were consistent with a critical reduction in cerebral perfusion pressure (which was documented in the two in whom this was monitored), hypoglycaemia, or status epilepticus. All four had serious neurological sequelae. These data suggest that brain injury in cerebral malaria may be due in part to secondary systemic and intracranial factors as well as to the direct effect of intravascular sequestration.

Brain↗
PubMed1993

Plasmodium falciparum: a method for the amplification of S antigens and its application to laboratory and field samples.

Polymerase chain reaction amplification of several polymorphic genes has been used to study the population biology of Plasmodium falciparum. S antigen is particularly suitable for such studies, but difficulties in the amplification of this gene have precluded its use. Here we describe a simple method for the amplification of S antigen and show why previous attempts may have been unsuccessful. Data are presented from both laboratory and field isolates.

Animals↗
PubMed1993

Maternal recall of symptoms associated with childhood deaths in rural east Africa.

Verbal autopsies (VA) are frequently used to determine causes of death for individuals for whom there is no reliable clinical information regarding the terminal illness. VA interviews are used to note key symptoms and signs recalled by relatives of the deceased and diagnoses ascribed according to the symptom complexes. The VA technique assumes that individual disease entities have discrete symptom complexes and that these can be accurately recognized and recalled by the interviewees. We have examined the accuracy with which specific symptoms are recalled over time by mothers or normal guardians of 491 children who died on the paediatric wards of two district hospitals in East Africa. Kwashiorkor, measles, trauma, generalized convulsions and neonatal tetanus were all reported with a high degree of accuracy for children who died of these conditions and had low false positive rates for children without these conditions. Recall was similar within 1 month of death compared to recall after 6 months for most symptoms and signs except neonatal tetanus where false positive reports by mothers increased with time since death. Symptoms and signs commonly used to describe malaria, respiratory tract and diarrhoea-related deaths were reported by mothers to have been present during the terminal illness in 43% of cases where these features were absent. Recall abilities differed between the two communities studied for some symptoms and signs highlighting the importance of such studies in every setting where VA are applied.

Bereavement↗