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Biomedical subjects

L A Salako

Publications and source records attributed to L A Salako.

At least 19 recordsLinked to original sources

Seasonal and temporal variations in the population and biting habit of mosquitoes on the Atlantic coast of Lagos, Nigeria.

OBJECTIVES: To determine the hourly density of vector mosquitoes in coastal Nigeria, compare seasonal human-biting and sporozoite rates in the vector density, locate breeding sites of mosquitoes, and determine larval population at breeding sites. MATERIALS AND METHODS: Indoor and outdoor mosquitoes of a coastal Nigerian community were caught during early and late wet seasons and in the harmattan period, a time of dusty wind from the Sahara on the western coast of Africa. Larvae were collected from various locations during the study period. The mosquitoes were physically characterized and their salivary glands dissected for sporozoite rate. Larvae density was calculated. Human-biting rate was calculated for Anopheles gambiae complex. RESULTS: Of the 4,317 female A. gambiae complex collected during the night bait catches, 3,543 (82.1%) were from outdoors and 774 (17.9%) from indoors during the three seasons. The maximum human-biting rate approached 25/h and the sporozoite rate was almost 3.0%. These vector mosquitoes were mainly outdoor biting and midnight feeding. Of the 1,269 Anopheles mosquitoes collected with pyrethrum spray catches, 1,245 (98.1%) were A. gambiae complex. There was no significant difference in the entomological inoculation or sporozoite rates during the three seasons of study. There was a preponderance of A. gambiae complex larvae from larval collection. CONCLUSION: Findings from this study should be useful in the implementation of Integrated Vector Management for the control of malaria in coastal and noncoastal areas of Nigeria.

Animals↗

The effects of alpha1-acid glycoprotein on the reversal of chloroquine resistance in Plasmodium falciparum.

An in-vitro model based on the semi-automated microdilution technique has been developed for selecting compounds that might be used clinically for the reversal of chloroquine resistance. This was used initially to test the susceptibility of Plasmodium falciparum clone W2 to chloroquine (CQ). The model was then employed to investigate the effects of each of four resistance-reversing agents (verapamil, desipramine, chlorpheniramine and promethazine, at 1 microM) on this parasite's susceptibility to CQ, with and without alpha(1)-acid glycoprotein (AGP), at a patho-physiological concentration (1.25 g/litre), in the culture medium. In the absence of AGP, each of the resistance-reversing agents reduced the median inhibitory concentrations of CQ by 82%-97%, from a baseline value of about 94 ng/ml. In the presence of AGP, however, most of the resistance-reversing agents had much less effect. There appears to be competitive interaction between CQ, the resistance-reversing agents and AGP. The binding kinetics between CQ, resistance-reversing agents, AGP and other plasma proteins will clearly need to elucidated if clinically effective resistance-reversing agents are to be selected in vitro.

Animals↗

Knowledge and practices of traditional birth attendants in prenatal services in Lagos State, Nigeria.

A questionnaire-based study was conducted on 189 Traditional Birth Attendants (TBAs) on their knowledge and practices in prenatal services. Only 86 (45.5%) of them associated cessation of menstrual period with pregnancy while others use mystic power 46 (24.3%), early morning sickness, pallor of conjunctiva and reaction to herbs 56 (29.6%) to detect pregnancy. Fundal height n=76 (40.2%), palpation n=82 (43.4%), special soaps and soups n=52 (27.5%) and special devices n=8 (4.2%) are used to determine stages of pregnancy. Foetal health status is determined by regular foetal movements n=95 (50.3%), mystic power n=15 (8%), soap n=2 (1.1%), special concoction 9 (4.8%), health status of mother n=67 (35.4%) and foetal heart beat n=24 (12.7%). Ninety seven (51.3%) of them used herbal treatment, 77 (40.7%) used incantations, 189 (100%) used special soaps as their main methods of delivery, while only 18 (9.5%) of respondents refer difficult cases to hospitals. Instruments used for separating cord were blade 123 (65.1%) and scissors 40 (21.1%). Symptoms recognized by the TBAs as signs of complications in pregnancy were dizziness, swollen feet, pallor, tiredness, absent foetal movement, loss of appetite, heaviness, pain in back/stomach/side, weight loss, vomiting, bleeding, fever/malaria, head ache, bad dream, premature or delayed labour. Although some of them recognized some danger signs in pregnancy and labour, only very few would refer difficult cases for emergency obstetric interventions. Clear protocols for management and referral, which are necessary for improved maternal survival, should be provided through regular training of the TBAs.

Clinical Competence↗

Management of childhood febrile illness prior to clinic attendance in urban Nigeria.

Parents and caregivers often try various treatment modalities for their sick children before bringing them to clinic. Many community-based studies have documented home and self-treatment practices, often with the aid of patent medicine vendors, but less is known about prior treatment behaviour of caregivers who actually reach a government clinic. This study, therefore, aimed at documenting the treatment provided by caregivers prior to their attendance at a public hospital. Beginning in April 1996, a year-long study was conducted among 1,943 sick children and their caregivers who attended the largest government-owned paediatric hospital in Lagos, Nigeria. The major complaints mentioned by the caregivers included fever, cough, and diarrhoea. Most (89%) caregivers had administered some form of medicine to the child prior to the clinic visit, and on average, 2.5 medications had been given. Associations were found between major complaint and type of medicine given: fevers were associated with antimalarial drugs and analgesics (antipyretics), cough was associated with cough syrup and analgesics, while diarrhoea was associated with antidiarrhoeal drugs. Although one-fifth of the children had received an antibiotic, provision of antibiotics was not associated with a particular complaint/illness. Since caregivers appeared to use perceived complaints/illnesses as a treatment guide, this can form the basis of safer and more appropriate recognition of illness and home management. In addition, the information obtained in this study can be used for training clinicians to inquire about home management and, thus, for making more informed decisions about their own treatment and prescribing practices.

Child Care↗

Efficacy and safety of enoxaparin, a low molecular weight heparin in the prevention of deep vein thrombosis in Nigerian patients after orthopaedic surgery.

The objective was to determine the efficacy and safety of Enoxaparin as an antithrombotic agent in orthopaedic patients at risk for thromboembolism. 49 patients who had lower limb orthopaedic surgery were studied. They received subcutaneous Enoxaparin 40mg 12 hours before surgery and subsequently, daily for one week. Blood specimens were drawn at 2 and 12 hours after the first injection, and 24 hours after the fourth injection for anti Factor Xa assay. Specimens were also taken preoperatively, 1st, 5th and 7th post operative days (POD) for determination of Packed Cell Volume (PCV), Haemoglobin level, White Blood Cell (WBC) and Platelet Counts. The mean pre-treatment, 2, 12 and 24 hours anti Factor Xa clotting times were 14.5 +/- 0.8, 36.2 +/- 5.6, 30.6 +/- 9.8 and 25.8 +/- 9.3 seconds respectively. The changes were significant, P = 8.2 x 10(-12). The 2 and 24 hours clotting times corresponded to plasma heparin concentration level of 0.12 - 0.22U/ml read off from prepared Enoxaparin standardisation curve. Significant changes were observed in haemoglobin level, PCV, WBC and Platelet Counts when preoperative, 1st, 5th and 7th POD mean values were compared by Analysis of Variance--P < 0.01 in all cases. The study showed that Enoxaparin 40 mg daily caused hypocoagulation within prophylactic range of 0.12 - 0.22U/ml of heparin in the plasma. Changes in blood counts were within the limits expected post surgery.

Adult↗

Treatment of childhood fevers and other illnesses in three rural Nigerian communities.

The seeking of healthcare for childhood illnesses was studied in three rural Nigerian communities of approximately 10,000 population each. The aim was to provide a baseline understanding of illness behaviour on which to build a programme for the promotion of prepackaged chloroquine and cotrimoxazole for early and appropriate treatment of childhood fevers at the community level. A total of 3117 parents of children who had been ill during the 2 weeks prior to interview responded to questions about the nature of the illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illness and the actions taken. Local illness terms were elicited, and the most prevalent recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per cent), and cough (7.4 per cent). The most common form of first-line treatment was drugs from a patent medicine vendor or drug hawker (49.6 per cent). Only 3.6 per cent did nothing. Most who sought care (77.5 per cent) were satisfied with their first line of action, and did not seek further treatment. The average cost of an illness episode was less than US$2.00 with a median of US$1.00. Specifically, chloroquine tablets cost an average of US 29 cents per course. Analysis found a configuration of signs and symptoms associated with chloroquine use, to include perception of the child having malaria, high temperature and loss of appetite. The configuration positively associated with antibiotic use consisted of cough and difficult breathing. The ability of the child's care-givers, both parental and professional, to make these distinctions in medication use will provide the foundation for health education in the promotion of appropriate early treatment of childhood fevers in the three study sites.

Anti-Bacterial Agents↗

Malaria in the first 6 months of life in urban African infants with anemia.

A total of 446 infants in the first 6 months of life who presented at an urban children's hospital with complaints of any illness whatsoever were recruited into a study with the aim of determining the contribution of malaria to infant morbidity in a malaria-endemic urban area in Nigeria. Sixty-eight of the infants were in their first month of life and 79, 77, 61, 97, and 64 were in their second, third, fourth, fifth and sixth month of life, respectively. Overall, 107 (24.0%) infants were clinically diagnosed as having malaria. This included 3 who were in the first month of life, 12 in the second, 15 in the third, 17 in the fourth, 33 in the fifth, and 27 in the sixth months of life (4.4, 15.2, 19.5, 27.9, 34.0, and 42.1%, respectively). Laboratory investigations confirmed 35 (32.7%) of those clinically diagnosed and 86 (25.4%) of those not clinically diagnosed (n = 339) as having malaria parasitemia, giving an overall malaria parasite rate of 27.1% among the infants. Acute respiratory infection was the major diagnosis (41.3%) among those that were not initially diagnosed as malaria but turned out to have malaria parasitemia followed by gastroenteritis (11.8%) and failure to growth (1.5%). Overall geometric mean parasite density was 202.5 parasites/microL of blood (range, 12-65,317 parasites/microL of blood). The mean hematocrit of infants with parasites (33.0%) was significantly lower (P < 0.005) than that of infants without parasites (35.1%). The mean hematocrit of infants with malaria parasites in each age group was lower than that of infants without malaria parasites in the corresponding age group. Among the infants with malaria parasites, those aged 2 to 2.9 months recorded the lowest mean hematocrit (30.1%), and those aged < 1 month recorded the highest mean hematocrit (42.7%). Axillary temperature increased and hematocrit decreased with increase in parasite density. The percentage of infants with anemia likewise increased as the parasite density increased. Plasmodium falciparum was present in all infected infants, but mixed infection with P. malariae was present in only 2.5% of infections. Analysis of our data suggests an urgent need for health education of caretakers and for training of clinicians for increased awareness of malaria as an important cause of illness and anemia in infants aged < 6 months so as to reduce children's wasting due to an easily preventable and treatable disease.

Age Distribution↗

Serum ferritin and other haematological measurements in apparently healthy adults with malaria parasitaemia in Lagos, Nigeria.

We studied 300 apparently healthy residents of Lagos aged 16-57 years. Their mean ferritin levels were 99.6 +/- 50.5 microg/l (men aged 20-57) and 66.5 +/- 44 microg/l (women aged 20-53) in aparasitaemic individuals. In parasitaemic subjects, mean ferritin levels were 133.1 +/- 48.3 microg/l (men aged 20-56) and 114.8 +/- 51.1 microg/l (women aged 16-50). Mean haematocrit values for aparasitaemic males were 45.7 +/- 5.6% and 37.9 +/- 5% for females, while mean haemoglobin levels were 153.2 +/- 1.5 microg/l and 124 +/- 3 microg/l, respectively. The mean values for MCV (mean corpuscular volume), MCH (mean corpuscular haemoglobin), MCHC (mean corpuscular haemoglobin concentration) were 101.7 +/- 8fl, 30.6 +/- 2.2 pg, 335 +/- 0.4 g/l and 99.8 +/- 10.1fl, 29.1 +/- 6.5 pg, 335 +/- 6 g/l. Serum iron levels were 34.2 +/- 5 micromol/l and 29.5 +/- 77 micromol/l. All haematological parameters measured were similar in both malaria parasitaemia positive and negative subjects, except ferritin level which was significantly higher in parasitaemic individuals (P < 0.05). Ferritin concentration and malaria density (r = 0.76 in males, r = 0.74 in females, P < 0.05) were positively correlated. Ferritin levels of subjects infected with Plasmodium falciparum were significantly higher than of those infected with P. malariae (P < 0.05). Hence ferritin estimation without examination for malaria parasitaemia in a malaria-endemic region such as Nigeria is not reliable. Asymptomatic malaria parasitaemia increases the ferritin level. Considering the mean ferritin level we found in normal subjects on a balanced diet, routine iron supplementation may not be necessary in the treatment of malaria-induced anaemia in Nigeria.

Adolescent↗

Hyperphenylalaninaemia in children with falciparum malaria.

Brain monoamine levels may underlie aspects of the cerebral component of falciparum malaria. Since circulating amino acids are the precursors for brain monoamine synthesis, we measured them in malaria patients and controls. Malaria elicited significantly elevated plasma levels of phenylalanine, particularly in comatose patients, with the Tyr/Phe (%) ratio reduced from 83.3 in controls to 39.5 in infected children, suggesting an impaired phenylalanine hydroxylase enzyme system in malaria infection. Malaria significantly increased the apparent K(m) for Trp, Tyr and His, with no effect on K(m)(app) for Phe. Using the kinetic parameters of NAA transport at the human blood-brain barrier, malaria significantly altered brain uptake of Phe (+96%), Trp (-28%) and His (+31%), with no effect on Tyr (-8%), compared with control findings. Our data suggest impaired cerebral synthesis of serotonin, dopamine and norepinephrine, and enhanced production of histamine, in children with severe falciparum malaria.

Adolescent↗

Malaria control priorities and constraints.

The capacity to prioritize correctly actions in malaria control depends on good knowledge not only of the epidemiology of the disease in the area but also of the behaviour of the people. Health policy makers frequently believe that the people already know enough about malaria and there is no need to commit further resources on finding out what the people actually know and do about the disease in order to modify their wrong habits. One of the pressing priorities for malaria control in Africa is therefore changing the attitude of malaria control policy makers. Considering the constraints to malaria control it is stressed that the health budget is usually below a level sufficient to finance an effective health care system. This is further compounded by inequities in the allocation of funds between health care institutions located in the urban areas compared with those located in the rural areas. Another important constraint is lack of manpower suitably trained to undertake the various elements of the global malaria control strategy. Finally, a very well known constraint is the unavailability of effective drugs at the locations where they are needed.

Behavior↗

Enhancement of the antimalarial effect of chloroquine by chloropheniramine in vivo.

The efficacy of chloroquine and chloroquine plus chloropheniramine, a histamine H1 receptor blocker which reverses chloroquine insensitivity in Plasmodium falciparum in vitro, was studied in 96 children with acute symptomatic uncomplicated falciparum malaria. The chloroquine/chloropheniramine combination produced a significantly higher cure rate than chloroquine alone and cured 77% of children with chloroquine treatment failures. Children with chloroquine treatment failure had mean plasma chloroquine concentrations above the minimum therapeutic concentration for the area. Chloroquine concentrations in plasma and red blood cells and ratio of red cell to plasma chloroquine concentrations on days 3 and 7 after initiation of therapy were not significantly different in the two groups. Chloroquine/chloropheniramine produces a higher cure rate than chloroquine alone and reverses chloroquine insensitivity in Plasmodium falciparum in vivo. It may be a useful way of optimising the antimalarial effect of chloroquine.

Antimalarials↗

In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum with promethazine.

The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC50s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Re-treatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/microl of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.

Adult↗

Influence of baseline values. I: Effects on plasma total cholesterol and triglyceride levels during doxazosin treatment for hypertension.

Forty-six African patients with essential hypertension aged 40 to 65 years had plasma total cholesterol and triglyceride levels determined at four different periods during a 12-month treatment with doxazosin. The patients were classified according to their pretreatment (baseline) values into 'low', 'medium' and 'high' baseline value groups. The mean total cholesterol levels significantly decreased in the three baseline groups while mean triglyceride levels reduced only in the patients that belonged to the medium and high baseline value groups. The baseline values of total cholesterol did not influence the beneficial cholesterol changes in all the patients, while the lack of significant favorable triglyceride changes was influenced by the low baseline values of triglyceride of the patients during doxazosin treatment. A similar study involving lipoprotein fractions and sub-fractions is also in progress.

Adult↗

Effect of dose size on the pharmacokinetics of orally administered quinine.

Plasma concentrations of quinine were measured by high-performance liquid chromatography (HPLC) after oral administration of 250, 500 and 1000 mg base to seven healthy adults. The doses were administered after an overnight fast. A washout period of at least 21 days was allowed between the doses. Area under the plasma concentration-time curve (AUC) for quinine increased in approximate proportion to the dose from 250 to 1000 mg. There was also a linear relationship between dose and maximum plasma concentration and dose and AUC in individual subjects. Time to reach peak plasma concentration remained unchanged over the dose range. There was no significant difference in elimination half-life, volume of distribution and systemic clearance over the dose range. The occurrence of adverse effects was dose and plasma quinine concentration dependent; central nervous system side effects increased as dose and plasma concentrations increased. These data suggest that after oral administration of quinine, linear pharmacokinetics occur in the dose range of 250-1000 mg.

Administration, Oral↗

Open comparison of artemether and mefloquine in uncomplicated Plasmodium falciparum hyperparasitaemia in children.

The efficacy of intramuscular artemether given for 5 days and a single oral dose of mefloquine, 25 mg/kg/body-weight, was evaluated in 84 children with uncomplicated Plasmodium falciparum hyperparasitaemia ( > 5% parasitized erythrocytes). Follow-up was for 14 days in the artemether group and 28 days in the mefloquine group. Artemether produced a significantly higher parasite reduction at 24 hours [mean 90.6 vs 63.3%, 95% confidence interval 10.7-43.9] and significantly shorter parasite clearance time [mean 38.4 vs 49.3 hours, 95% confidence interval 5.5-16.3] than mefloquine. Fever clearance times were similar, presumably because of the use of an antipyretic in both treatment groups. Cure rate was 98% with artemether on day 14 and 100% with mefloquine on day 28. One child in the artemether group who had recurrence of parasitaemia on day 14 responded promptly to mefloquine with clearance of parasitaemia and fever at 24 hours. Although both drugs were well tolerated, mefloquine produced more episodes of abdominal pain with or without diarrhoea and vomiting. These results suggest that both drugs are effective in uncomplicated Plasmodium falciparum hyperparasitaemia in children from an endemic area of south-west Nigeria.

Administration, Oral↗

Amlodipine as monotherapy in hypertensive Africans: clinical efficacy and safety studies.

Amlodipine as a monotherapy was evaluated in 20 patients with mild, moderate, and severe hypertension over a 10 week period. After a washout period of 4 weeks, Amlodipine was administered at a dose of 5 mg once daily for 2 weeks and increased to 10 mg once daily if diastolic blood pressure did not fall to below 90 mmHg. At the end of the trial, diastolic blood pressure was reduced to below 90 mmHg in all but four patients. However, these four patients had greater than 20 mmHg reduction in diastolic blood pressure. There was a slight, but insignificant increase in heart rate. Dizziness and weakness occurred in one patient, otherwise, the drug was well tolerated. Laboratory tests, including plasma lipids done at the start and end of the trial, remained unchanged.

Aged↗

Biochemical changes during a cross-over treatment of doxazosin, moduretic and amlodipine in hypertensive patients.

A cross-over study was done to compare the effects of doxazosin, moduretic and amlodipine on biochemical values in 9 hypertensive Nigerians aged 35 to 65 years. Doxazosin therapy was characterized by significant increase in the levels of mean plasma total protein and albumin, while moduretic therapy showed significant reduction in the mean values of plasma creatinine and calcium. All other parameters did not show any significant variation during doxazosin and moduretic treatment phases; and amlodipine therapy did not have any effect on the biochemical values of the hypertensive patients.

Adult↗

Open trial of doxazosin in hypertensive Africans: dose finding, efficacy and safety studies.

Doxazosin, as a mono-therapy, was studied in 28 patients with mild to severe hypertension over a period of 8 weeks. After a wash-out period of 2 weeks, doxazosin was started at a dose of 1 mg daily and increased gradually until the diastolic blood pressure fell to below 90 mm Hg or a maximum dose of 16 mg daily was reduced. Forty-three percent of the patients had good response with diastolic blood pressure falling to normal (< 90 mm Hg) or by more than 10 mm Hg whilst 68% of the patients had a reduction of greater than 5 mm Hg. Doxazosin reduced blood pressure without significant increase in heart rate and was, overall, well tolerated producing mild side effects not requiring withdrawal, or reduction in dosage of the drug in 6 cases. The effect of doxazosin on lipids showed a trend towards reduction of total cholesterol and increase in HDL, but these data need confirmation in a longer study in a larger population sample.

Adult↗