Target-organ damage and cardiovascular complications in hypertensive Nigerian Yoruba adults: a cross-sectional study.

BACKGROUND: Hypertension is a major challenge to public health as it is frequently associated with sudden death due to the silent nature of the condition. By the time of diagnosis, some patients would have developed target-organ damage (TOD) and associated clinical conditions (ACC) due to low levels of detection, treatment and control. TOD and ACC are easy to evaluate in a primary healthcare (PHC) setting and offer valuable information for stratifying cardiovascular risks in the patient. The aim of this study was to evaluate the prevalence and correlates of TOD and established cardiovascular disease (CVD) in hypertensive Nigerian adults. METHODS: A cross-sectional study was conducted on 2 000 healthy Yoruba adults between 18 and 64 years who lived in a rural community in south-western Nigeria. Participants diagnosed to have hypertension were examined for TOD and ACC by the presence of electrocardiographically determined left ventricular hypertrophy (LVH), microalbuminuria or proteinuria, retinopathy, or history of myocardial infarction and stroke. RESULTS: A total of 415 hypertensive participants were examined and of these, 179 (43.1%) had evidence of TOD and 45 (10.8%) had established CVD. TOD was associated with significantly higher systolic (SBP) and diastolic blood pressure (DBP). The prevalence of LVH was 27.9%, atrial fibrillation 16.4%, microalbuminuria 12.3%, proteinuria 15.2%, hypertensive retinopathy 2.2%, stroke 6.3%, congestive heart failure (CHF) 4.6%, ischaemic heart disease 1.7%, and peripheral vascular disease 3.6%. Compared with those with normal blood pressure (BP), the multivariate adjusted odds ratios (95% confidence interval) of developing TOD was 3.61 (0.59-8.73) for those with newly diagnosed hypertension; 4.76 (1.30-13.06) for those with BP ≥ 180/110 mmHg; and 1.85 (0.74-8.59) for those with diabetes mellitus. CONCLUSIONS: This study provides new data on TOD and its correlates in a nationally representative sample of hypertensive adults in Nigeria. In this low-resource setting, attempts should be made to detect hypertensive patients early within the community and manage them appropriately before irreversible organ damage and complications set in. The methods used in this study are simple and adaptable at the primary healthcare level for planning prevention and intervention programmes.

A prevalence of cardiometabolic risk factors among a rural Yoruba south-western Nigerian population: a population-based survey.

BACKGROUND: It has been hypothesised that rural sub-Saharan Africa is at an early stage of epidemiological transition from communicable to non-communicable diseases (NCD). Limited information exists about the prevalence of cardiometabolic risk factors and the burden of cardiovascular disease (CVD) in the adult Nigerian population, especially in the rural setting. OBJECTIVES: The aim of this study was to assess and describe the prevalence of several cardiometabolic risk factors in the sub-Saharan adult population of a rural Yoruba community, living in south-western Nigeria. METHODS: The study was a descriptive, cross-sectional, random-sample survey. Participants were visited at home by trained nurses and community health extension workers (CHEW) who administered a questionnaire, took the relevant history, carried out clinical examinations and measurements and took samples for laboratory tests. They were supervised by primary healthcare physicians serving the community. The variables recorded comprised clinical history, CVD risk factors including blood pressure (BP), body mass index (BMI), waist circumference, blood sugar and serum lipid levels, cigarette use, and dietary habits. The participants included 2 000 healthy adults aged 18 to 64 years who had been living in the area for more than three years. RESULTS: The average age was 42.1 +/- 21.6, with 43.7% (873) being males and 56.3% (1127) females; 20.8% were hypertensive with BP > or = 140/90 mmHg, 42.3% of the men and 36.8% of the women had BP > or = 130/85 mmHg; 2.5% had diabetes, 1.9% had hypertriglycerideaemia, 43.1% had low HDL-C, 3.9% had general obesity, 14.7% had abdominal obesity, 3.2% were physically inactive, and 1.7% smoked cigarettes. Overall, 12.9% of the subjects were found to have at least one CVD risk factor. Using the Adult Treatment Panel (ATP) III criteria, 2.1% of men and 2.7% of women in the study population had at least three of the criteria, the commonest being HDL-C < 40 mg/dl in men or < 50 mg/dl in women, followed by BP >or = 130/85 mmHg, then waist circumference > 88 cm in women or > 102 cm in men, followed by blood glucose > or = 110 mg/dl. CONCLUSION: The results obtained from this study strongly suggest a high prevalence of cardiometabolic risk factors in this rural population and that the epidemiological transition is not restricted to the urban population. This serves as a wake-up call for action in the planning of health services for the management of CVD and other chronic NCDs.

Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria.

The aim of this study was to identify candidate antivenoms with specific activity against the venom of the saw-scaled or carpet viper (Echis ocellatus) in northern Nigeria, where bites by this species cause great morbidity and mortality but where effective antivenoms have become scarce and unaffordable. Selected antivenoms were destined to be compared by randomised controlled clinical trials (RCTs). Standard pre-clinical neutralisation assays were carried out in rodents. We included two licensed antivenoms of established clinical efficacy and 6 candidate antivenoms. Although 6 of the tested antivenoms showed promising efficacy, all but 3 were excluded from further study because of inadequate pre-clinical efficacy or because they were unavailable or unaffordable for the anticipated RCTs. Median effective doses (ED(50)) of the remaining three candidate antivenoms suggested that the following doses might neutralise the maximum observed venom yield of 24.8 mg (dry weight) of venom milked from captive E. ocellatus: 10 ml of MicroPharm "EchiTAb G" (ET-G) antivenom; 30 ml of Instituto Clodomiro Picado "EchiTAb-Plus-ICP" (ET-Plus) antivenom; 50 ml of VacSera, Cairo "EgyVac" antivenom. A preliminary clinical dose-finding and safety study of these three antivenoms was carried out in 24 patients with incoagulable blood after E. ocellatus bites who were not severely envenomed. A 3+3 dose escalation design was employed. Initial doses of 10 ml ET-G and 30 ml ET-Plus restored blood coagulability in groups of 6 patients with early mild reactions (pruritus only) in not more than one third of them. EgyVac antivenom did not fulfil efficacy or safety criteria in 12 patients. On the basis of these results, ET-G and ET-Plus were selected for comparison in a RCT.

Envenoming after carpet viper (Echis ocellatus) bite during pregnancy: timely use of effective antivenom improves maternal and foetal outcomes.

The report describes successful management of 10 women in 2nd and 3rd pregnancy trimesters with EchiTab IgG antivenom after carpet viper (Echis ocellatus) envenoming. All women survived but foetal loss in a victim with delayed presentation and a case of mild hypersensitivity reaction were recorded. Excellent outcomes can be achieved in rural and semi-nomadic populations without specialized care and immediate access and provision of effective antivenoms is paramount in curtailing snakebite maternal morbidity, mortality and foetal loss.

Prevalence of malaria at booking among antenatal clients in a secondary health care facility in Ibadan, Nigeria.

The prevalence of malaria parasitemia at booking was studied in 1,848 pregnant women in a secondary hospital in Ibadan, Nigeria. Main outcome variables were patent parasitemia and fever. 8.4% hadpatent malaria parasitaemia. Most clients (89%) with parasitemia were asymptomatic. Febrile subjects booked at an earlier gestational age [22.7 versus 24.2 weeks] than afebrile patients (p = 0.0052). Anemia was more prevalent among patients with patent parasitemia than those without (58.1% versus 22.6%, p < 0.0001). Malaria parasitaemia was higher among nulliparous women than other parity groups (p < 0.0001). Symptomatic malaria was associated with early booking for antenatal care and malaria parasitemia was a significant determinant of anemia. The prevalence of malaria parasitaemia in this study is much lower than in previous reports.

Prevalence of malaria at booking among antenatal clients in a secondary health care facility in Ibadan, Nigeria

The prevalence of malaria parasitemia at booking was studied in 1,848 pregnant women in a secondary hospital in Ibadan, Nigeria. Main outcome variables were patent parasitemia and fever. 8.4% had patent malaria parasitaemia. Most clients (89%) with parasitemia were asymptomatic. Febrile subjects booked at an earlier gestational age [22.7 versus 24.2 weeks] than afebrile patients (p = 0.0052). Anemia was more prevalent among patients with patent parasitemia than those without (58.1% versus 22.6%, p<0.0001). Malaria parasitaemia was higher among nulliparous women than other parity groups (p<0.0001). Symptomatic malaria was associated with early booking for antenatal care and malaria parasitemia was a significant determinant of anemia. The prevalence of malaria parasitaemia in this study is much lower than in previous reports. (Afr J Reprod Health 2008; 12[2]:141-152)

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.

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.

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.

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.

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.

Tuberculosis masquerading as 'constant malaria'.

Four hundred adults aged 20-60 years, (200 females and 200 males) were studied. All the subjects were residing in the urban areas of Lagos, Nigeria. Thirteen percent claimed they were having "constant malaria" (> 8 times per year), 5% (20) claimed to have cough mostly during the cold period, 2.5% (10) produced mucoid sputum, 2.5% unproductive cough, 13% were AFB smear positive, 1.5% had positive chest X-ray for pulmonary Tuberculosis (PTB), 1.5% were HIV positive and 50% were mantoux positive (> 10 mm induration). All who complained of "constant malaria" were AFB positive. Malaria parasite density was lower in those who complained of "constant malaria" than those who did not complain (P = 0.003). The complaint of frequent malaria attack decreased after Antituberculosis therapy for 6 months. This study revealed that in a malaria and tuberculosis endemic region, early stage of tuberculosis can masquerade as "constant malaria". Therefore any such complaint should be fully investigated.

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

One hundred apparently normal nursery and primary school children aged between 2 to 12 years from private schools, in Lagos Nigeria were studied. From this study the mean ferritin levels for children aged 2-5 years, and 6-12 years were 112 +/- 48 micrograms/l, and 119 +/- 38 micrograms/l respectively. Mean haematocrit values were 37.6 +/- 2.2%, and 37.5 +/- 2.6%, while mean haemoglobin levels were 126 +/- 9 g/l 127 +/- 7.9 g/l (2-5 years and 6-12 years respectively). The mean values for MCV, MCH, MCHC were 92 +/- 8.6 fl, 27.6 +/- 3.0 pg, 338.0 +/- 15.0 g/l and 93.5 +/- 9.0 fl, 28.7 +/- 2.5 pg, 332.0 +/- 17.0 g/l (2-5 years and 6-12 years respectively). All haematological parameters measured were similar in both malaria parasitaemia positive and negative subjects, except ferritin level which was significantly higher in subjects with malaria parasitaemia (p < 0.05). There was positive correlation between ferritin concentration and malaria density (r = 0.85, p < 0.05). From the above findings, it would be concluded that, ferritin estimation without examination for malaria parasitaemia in a malarious region like Nigeria is not reliable. It is also concluded that with the high mean ferritin level obtained in this study for normal children on balanced diet, routine iron supplementation may not be necessary for this group of children in Nigeria.

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.

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.

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.

Increased plasma levels of histidine and histamine in falciparum malaria: relevance to severity of infection.

Severe falciparum malaria, with its associated hyperpyrexia, distorts plasma levels of large neutral amino acids (NAA) and consequently, brain uptake of individual NAA. Since brain levels of NAA determine cerebral synthesis of monoamines (serotonin, histamine, catecholamines), we measured plasma concentrations of NAA, and also plasma histamine (Hm) in children with falciparum malaria and in uninfected controls. Malaria elicited a marked (P < 0.025) increase in plasma histidine (His) with a 5-fold significant (P < 0.001) elevation in histamine, as well as a 2.5-fold increase (P < 0.005) in plasma phenylalanine (Phe), with no changes in the other NAA. Using kinetic parameters of NAA transport at human blood-brain barrier (BBB), we showed that malaria significantly altered calculated brain uptake of His (+30%), Phe (+96%), Trp (-30%) and Ile (-27%), with no change in the other NAA, compared with controls. Our data suggested enhanced cerebral synthesis of Hm with impaired production of serotonin and the catecholamines in the patients, and therefore, the need to evaluate the encephalopathy in severe malaria within the context of abnormalities in metabolism of Hm and other monoamines resulting from imbalance in plasma levels of the large neutral amino acids. Of clinical relevance also is the impaired inactivation of increased brain Hm by antimalarials such as the widely used aminoisoquinolines leading to elevated brain levels of imidazole-4-acetic acid (IAA), a potent inducer of a sleep-like state often accompanied by seizures, analgesia, decreased blood pressure and other effects.

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.

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.