Use and effectiveness of commercial flit-spray insecticides in control of mosquito population in Sagamu, Southwest Nigeria.

INTRODUCTION: Control of mosquito vector is crucial to reducing the burden of malaria in endemic region. In the present study, we investigated the use of commercial insecticides in families and their effectiveness in control of mosquito population in Sagamu, southwest Nigeria. MATERIALS AND METHODS: A pretested structured questionnaire was used to determine mosquito adulticides techniques employed in the community and most commonly used adulticides were evaluated for effectiveness by exposing adult mosquitoes to varying concentrations of the insecticides and responses monitored. RESULTS: Families differ in methods adopted to prevent mosquito and use of flit-spray insecticide was commoner. Although parents constitute 64% of those applying the insecticide, 22.2% were children. Household pyrethroid insecticide products of Baygon (Imiprothrin, Prallethrin plus Cyfluthrin), Mobil (Neopynamin, Prallethrin plus Cyphenothrin) and Raid (Pynamin forte, Neopynamin plus Deltimethrin) were three commonly used in the community. The exposure tie interval for eath of osquitoes was shorter with Raid (100% at 8 minutes) when compared with Mobil (80%) and Baygon (85%) at 10 minutes (p = 0.005). Kaplan-Meier survival curve of cumulative probability of surviving exposure to insecticide was lowest with Raid (log rank 2 = 14.56, P = 0.001). CONCLUSION: Although flit-spray insecticides are affordable with simple application tool, inexplicit use-instruction on labels may cause discrepancies in application. Monitoring responses of mosquitoes to commercial flit-spray insecticide may support effective control technique and prevention of vector resistance in poor resource communities.

Akara Ogbomoso: microbiological examination and identification of hazards and critical control points.

Akara Ogbomoso was examined toward the establishment of hazard analysis and critical control point (HACCP). The akara was produced in residential buildings with the attendant consequence of contamination. There was ample growth of aerobes, coliforms, staphylococci, Shigella and yeast/mold from the samples, water and cowpea pastes. Microbial contaminations occur through the processing, which can be corrected through education by adopting good hygienic and manufacturing practices. The critical control points were identified as frying, storage and refrying. It may be heated in the microwave for 10 s before consumption. Akara, prepared in the laboratory through the implementation of HACCP was not contaminated. Several bacterial isolates, namely; Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Citrobacter freundii, Serratia marcescens, Proteus vulgaris, Bacillus cereus, Streptococcus pyogenes, Bacillus sp. and Shigella sp., showed multiple resistance to antibiotics ranging from two to nine. Seven strains were not resistant to the antibiotics, while five were resistant to one type of antibiotic.

Predictors of the failure of treatment with pyrimethamine-sulfadoxine in children with uncomplicated falciparum malaria.

The prevalence of pyrimethamine-sulfadoxine (PS)-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa or other parts of the world in the last one or two decades. The factors that identify children at risk of treatment failure after being given PS were evaluated in 291 children with acute, symptomatic, uncomplicated, P. falciparum malaria. The children took part in four antimalarial drug trials between July 1996 and July 2004 in a hyperendemic area of southwestern Nigeria. Following treatment, 64 (22%) of 291 children failed treatment by day 7 or 14. In a multivariate analysis, an age < or = 1.5 years (AOR=2.9, 95% CI 1.3-6.4, P = 0.009) and presence of fever (AOR = 3.3, 95% CI 1.28-7.14, P = 0.01) were independent predictors of the failure of treatment with PS at presentation. Following treatment, delay in parasite clearance >3 days (AOR = 2.56, CI 1.19-5.56, P = 0.016) was an independent predictor of the failure of treatment with PS. In addition, compared with the children who had no fever then, children with fever three or more days after starting treatment were more likely to be treatment failures. These findings may have implications for malaria control efforts in some sub-Saharan African countries where treatment of malaria disease depends almost entirely on PS monotherapy, and for programmes employing PS or PS-based combination therapy.

Cotrimoxazole in the treatment of acute uncomplicated falciparum malaria in nigerian children : a controlled clinical trial.

OBJECTIVES: To evaluate the efficacy of cotrimoxazole in the treatment of Plasmodium falciparum malaria and to compare the efficacy of cotrimoxazole with that of pyrimethamine-sulfadoxine, a second-line antimalarial drug, in an area of high malaria transmission. PATIENTS AND METHODS: Children aged between 10 months and 10 years with clinical and parasitological evidence of P. falciparum malaria were randomised to receive either cotrimoxazole or pyrimethamine-sulfadoxine. 145 children (73 and 72, respectively, in the cotrimoxazole and pyrimethamine-sulfadoxine groups) completed the study per protocol and were evaluated. RESULTS: Pretreatment clinical and parasitological parameters were similar in the two treatment groups. The time to clear fever and other symptoms was similar in the two groups: 1.94 +/- 1.10 days versus 2.20 +/- 0.96 days, p > 0.05. Parasite clearance times were also similar: 2.62 +/- 0.91 days versus 2.94 +/- 1.17 days, respectively, for cotrimoxazole and pyrimethamine-sulfadoxine; p > 0.05. The cure rates on days 14, 21 and 28 were, respectively, 84.9, 75.3 and 74.0% for the cotrimoxazole group and 84.7, 80.5 and 75.0% for the pyrimethamine-sulfadoxine group. Both drugs were well tolerated. CONCLUSIONS: These results indicate that cotrimoxazole has similar efficacy to pyrimethamine-sulfadoxine in the treatment of acute uncomplicated P. falciparum malaria in children resident in an endemic area of Southwest Nigeria.

Comparative efficacy of chloroquine and cotrimoxazole in the treatment of acute uncomplicated falciparum malaria in Nigerian children.

OBJECTIVES: To evaluate the efficacy of two dosing regimens of cotrimoxazole in the treatment of falciparum malaria and compare the efficacy with that of chloroquine, the first-line antimalaria drug in the area of study. DESIGN: A prospective cross sectional study. SETTINGS: Department of Clinical Pharmacology, University College Hospital, Ibadan, Nigeria. SUBJECTS: Ninety eight children with acute symptomatic uncomplicated falciparum malaria. MAIN OUTCOME MEASURES: Fever and other symptoms clearance times, parasite clearance times and the cure rates for chloroquine, three day and five day cotrimoxazole. RESULTS: Ninety eight children with acute symptomatic uncomplicated falciparum malaria were randomised to receive three doses of oral chloroquine and two regimens of cotrimoxazole. Pre-treatment clinical and parasitological parameters were similar in the three treatment groups. The fever and other symptoms clearance times were comparable in all the treatment groups: 1.83 +/- 1.3, 1.9 +/- 1.0 and 2.4 +/- 1.3 days for chloroquine, three day cotrimoxazole and five day cotrimoxazole, respectively p = 0.24. Parasite clearance times for the three treatment groups were also similar; 3.0 +/- 1.0, 3.1 +/- 0.7, and 3.0 +/- 1.0 days respectively for chloroquine, three day- and five day- cotrimoxazole; p = 0.96. The cure rates for chloroquine, three day and five day cotrimoxazole were 74.2%, 88.2% and 84.8%, respectively (x2 = 2.40, p = 0.30). The three treatment regimens were well tolerated. CONCLUSION: These results indicate that cotrimoxazole is as effective as chloroquine in treatment of acute symptomatic uncomplicated falciparum malaria in children resident in an endemic area of southwest Nigeria. It is an added advantage when malaria coexists with respiratory tract infections for which cotrimoxazole is the recommended drug.

Plasmodium falciparum hyperparasitaemia in children. Risk factors, treatment outcomes, and gametocytaemia following treatment.

The risk factors associated with hyperparasitemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 1,048 children enrolled prospectively in seven antimalarial drug trials between July 1996 and September 2003 in a hyperendemic area of southwestern Nigeria. The outcomes of treatment of hyperparasitaemia, and gametocyte carriage following treatment were also evaluated. The children were assigned to one of seven treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only; amodiaquine (AQ) only; CQ plus chlorpheniramine (CQCP); PS combined with CQ or AQ (COM); PS combined with probenecid (PPS); and halofantrine (HF). Hyperparasitaemia was found in 100 (9.5%) of the 1,048 children at enrolment (day 0). Following oral therapy, 1.2% of all patients (i.e. 13 patients) became hyperparasitaemic, which developed in all patients by day 1 of follow-up. In a multiple regression model, age < or = 5 years, and a core temperature (oral or rectal) > or = 39.5 degrees C were found to be independent risk factors for hyperparasitaemia at enrolment. Following therapy, the cure rate on day 14 was significantly lower in those treated with CQ compared to other treatment groups. Severe resistance (RIII) response to treatment occurred significantly more frequently in those with hyperparasitaemia at enrolment than in those without, and was seen in five and one child with hyperparasitaemia who were treated with CQ and CQCP, respectively. Gametocyte carriage was insignificantly lower at enrolment and at all times following treatment in children with hyperparasitaemia than in age- and gender-matched children without hyperparasitaemia who received the same treatment. The results are discussed in the light of management of uncomplicated hyperparasitaemia in children in endemic settings.

Predictors of asymptomatic malaria in pregnancy.

A number of studies have described malaria parasitaemia in pregnancy as mostly an asymptomatic condition, however information about predictors of asymptomatic malaria is largely lacking. We investigated the prevalence of symptoms and potential predictors of asymptomatic malaria in pregnant women attending Ante-Natal Clinic (ANC) of two public maternity hospitals in Ibadan, Southwest-Nigeria. Demographic data, history of previous and present pregnancy were obtained from the subjects and blood smears were examined for malaria diagnosis by light microscopy. Seventy - seven parasitaemic pregnant women attending antenatal clinic were evaluated for presence or absence of symptoms that may be associated with malaria. Thirty-seven women (48%) were asymptomatic whereas 40 (52%) presented with symptoms such as weakness, headache and general body ache and fever. Parasite density was significantly higher in symptomatic patients (P = 0.042), while asymptomatic patients had low level parasitaemia but significantly higher gametocyte carriage (P = 0.035). In conclusion, parasitaemic pregnant women resident in hyper- or holo-endemic malaria region are likely to be symptomatic with increasing density of the parasitaemia.

Asexual and sexual stages of Plasmodium falciparum in Nigerian pregnant women attending antenatal booking clinic.

Susceptibility to infection by Plasmodium falciparum is increased in pregnant women. In sub-Saharan Africa, the consequences of maternal malaria include preterm birth, fetal growth restriction and increased infant mortality. Malaria transmission requires the circulation of viable gametocytes that can be ingested by the female mosquito taking a blood meal. This study was conducted to evaluate the presence of asexual and sexual stages of P. falciparum in pregnant women attending antenatal booking clinics in south-western Nigeria, an area hyper-endemic for malaria. Gametocyte carriage was about 13%, similar to that documented for children symptomatic for malaria in our area of study.

The effects of artemether-lumefantrine vs amodiaquine-sulfalene-pyrimethamine on the hepatomegaly associated with Plasmodium falciparum malaria in children.

An open randomized controlled study of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) for the treatment of uncomplicated Plasmodium falciparum malaria was carried out in 181 children. In 79 children, the hepatomegaly reduction ratios (HRR) and the speed of resolution of hepatomegaly, the hepatomegaly resolution rates (HRSR), were calculated and compared between the two treatment groups. HRR and HRSR were similar in the two treatment groups. HRSR was 71% and 62% in AL- and ASP-treated children, respectively, 14 days after commencing treatment. There was no significant correlation between HRR and parasite reduction ratio in the same patient. In children in whom parasitaemia cleared and hepatomegaly resolved within 14 days, recurrence of parasitaemia was associated with reoccurrence of hepatomegaly, suggesting that the propensity for recurrence of infection drives the malaria-attributable hepatomegaly in children from this endemic area. Combination therapy may provide additional beneficial effects on pathophysiological processes and changes associated with falciparum malaria by rapid clearing of asexual parasitaemia and reducing the propensity for recurrence of infection.

Predictors of the failure of treatment with trimethoprim-sulfamethoxazole in children with uncomplicated, Plasmodium falciparum malaria.

In many African countries, trimethoprim-sulfamethoxazole (TS) is recommended for the treatment of children with malaria and pneumonia - in accordance with the guidelines for the integrated management of childhood illness (IMCI) - and, in some settings, for the home management of febrile illnesses. There have been few studies, however, of the risk of failure of treatment with this drug combination in children with acute, Plasmodium falciparum malaria. The factors that identify children at risk of treatment failure after being given TS were therefore evaluated in 101 children with acute, symptomatic, uncomplicated, P. falciparum malaria, in a hyper-endemic area of south-western Nigeria. Overall, 11% of the children failed treatment by day 14. In a multivariate analysis, two factors were found to be independent predictors of the failure of treatment with TS: an age of <3 years (adjusted odds ratio=0.1; 95% confidence interval=0.02-0.53; P=0.007); and a body temperature of >or=38 degrees C 2 days after the commencement of treatment (adjusted odds ratio=4.9; 95% confidence interval=1.2-21.3; P=0.03). These findings may have implications for control efforts in some sub-Saharan African countries, where TS is recommended for the management of malaria in children, with or without pneumonia.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children.

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per microl blood) of peripheral young gametocyte (PYG), that is, < or = stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Effects of antifolates--co-trimoxazole and pyrimethamine-sulfadoxine--on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria.

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS--but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrollment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in children with acute, uncomplicated, Plasmodium falciparum malaria.

Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P = 0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9; 95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature of > or =38 degrees C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.

Plasmodium falciparum malaria in Nigerian children during high and low transmission seasons: gametocyte carriage and response to oral chloroquine.

Plasmodium falciparum malaria during high and low transmission seasons was evaluated in 1031 children treated with different antimalarial drug in a hyperendemic area of southwestern Nigeria. Seventy-three (10.5%) of 693 and forty (11.8%) of 338 children were gametocyte carriers in the high transmission seasons (HTS) and low transmission seasons (LTS), respectively. In a multiple regression model, two factors were found to be independent risk factors for the presence of gametocytemia at enrolment in the HTS: duration of illness >3 d, and asexual parasite densities less than 10,000/microl. Similarly male gender, duration of illness >4 d and parasite density less than 5000/mul were found independent risk factors for presence of gametocytemia during LTS. The presenting parasitemia, parasite clearance times, intensity of gametocytemia and proportion carrying gametocytes post treatment differ significantly in the 333 (32.3%) of these children that were treated with chloroquine in the two seasons. These findings may be important in our understanding of P. falciparum transmission sustenance, response to chloroquine therapy and contribution of chloroquine to gametocyte carriage as seasonal changes occur.

Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated, Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance.

Resistance to chloroquine (CQ) in Plasmodium falciparum has reached unacceptably high levels in many endemic countries. The pre-treatment factors that identify the children who are at risk of treatment failure after being given CQ were evaluated in 385 children with acute, uncomplicated, Plasmodium falciparum malaria. These children each took part in one of six antimalarial drug trials conducted, between July 1996 and July 2004, in a hyper-endemic area of south-western Nigeria. Following treatment with CQ, 149 (39%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =7 years [giving an adjusted odds ratio (AOR) of 2.17, with a 95% confidence interval (CI) of 1.19-3.85; P = 0.01], an asexual parasitaemia of > or =100,000/microl (AOR = 2.17; CI = 1.08-4.35; P = 0.03), the presence of gametocytaemia (AOR = 2.08; CI = 1.14-3.85; P = 0.02) and enrolment >4 years after commencement of the study (i.e. after 2000; AOR = 2.13; CI = 1.3-4.0; P = 0.003) were found to be independent predictors at presentation of the subsequent failure of treatment with CQ. Compared with the other children, those who failed to clear their parasitaemias within 3 days and those who still had fever 1-2 days after commencing treatment were more likely to be treatment failures. Together, these findings may have implications for malaria-control efforts in all areas of sub-Saharan Africa where treatment of malaria depends almost entirely on antimalarial monotherapy.

Open randomized study of artesunate-amodiaquine vs. chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children.

BACKGROUND: Artemisinin-based combination antimalarials are currently considered effective alternatives for the treatment of malaria in Africa, but there are few studies of such combinations in Nigerian children. We assessed the safety, treatment efficacy and effects on gametocyte carriage of the combination of artesunate plus amodiaquine and chloroquine plus pyrimethamine-sulfadoxine in children. METHODS: We evaluated 153 children who were aged 12 years or younger who had uncomplicated Plasmodium falciparum malaria. Patients were randomly assigned a combination of artesunate (4 mg/kg of body weight daily for 3 days) plus amodiaquine (30 mg/kg over 3 days), or chloroquine (25 mg/kg over 3 days) plus pyrimethamine-sulfadoxine (25 mg/kg of the sulfadoxine component at presentation). The primary endpoints were the proportions of children with adequate clinical and parasitological response, late parasitological failure, late clinical failure and early treatment failure. The parasitological cure rates on days 14-28 were also used as the primary endpoints. RESULTS: Both regimens were well tolerated; no child was withdrawn because of drug intolerance. All children treated with artesunate plus amodiaquine had adequate clinical and parasitological response (ACPR), while all but five children treated with chloroquine plus pyrimethamine-sulfadoxine had similar response. Fever clearance times were similar in the two treatment groups. However, the proportion of patients whose parasitaemia cleared by day 2 was significantly higher (100 vs. 50%, P = 0.00001) and parasite clearance was significantly faster (1.7 +/- 0.4 vs. 2.5 +/- 0.8 days, P = 0.0001) in children treated with artesunate plus amodiaquine. The cure rates on days 21 (100%vs. 94%, P = 0.03) and 28 (100%vs. 90%, P = 0.003) were also significantly higher in children treated with artesunate plus amodiaquine than in those treated with chloroquine plus pyrimethamine-sulfadoxine. Overall, a significantly higher proportion of children treated with chloroquine plus pyrimethamine-sulfadoxine carried gametocytes at least once during follow-up compared with those treated with artesunate plus amodiaquine [5 of 50 (10%) vs. 1 of 103 (0.97%), P = 0.01]. CONCLUSION: The combination of artesunate plus amodiaquine is therapeutically superior to a combination of chloroquine plus pyrimethamine-sulfadoxine, and significantly reduced gametocyte carriage following treatment.

The effects of chloroquine, amodiaquine and chloroquine plus chlorpheniramine on the disposition kinetics of the hepatomegaly associated with acute, uncomplicated, Plasmodium falciparum malaria in children.

The effects of chloroquine (CQ), amodiaquine (AQ) and CQ plus chlorpheniramine (a histamine H(1) antagonist that reverses CQ resistance in vitro and in vivo) on the disposition of the enlarged liver associated with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria were evaluated. The subjects, 131 children aged 0.6-12 years who lived in an endemic area of Nigeria, were randomly allotted to the three treatment groups. The cumulative proportions of the children with complete resolution of their enlarged livers at 48, 96, 168 or 336 and 504 h after commencement of treatment were significantly higher in those treated with CQ plus chlorpheniramine (CQCP) than in the other two treatment groups (with P-values of 0.02, 0.001, 0.00000 and 0.00002, respectively). Among those with complete resolution, however, the times to resolution of 50% (HR50) or 90% (HR90) of the liver enlargement were similar in all the treatment groups. Complete resolution of the enlarged liver within 168 h was associated with a sensitive response to each treatment. Overall, in children with complete or partial resolution of their enlarged livers, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUC(hp)) and the half-life of the hepatomegaly (t(1/2hp)) were significantly lower in the CQCP group than in the other two groups. The volume of blood completely cleared of the 'hepatic pathological processes' which led to the hepatomegaly (CL(Bhp)) and the fractional reduction of AUC(hp) at 48 and 96 h (i.e. AUC(hpFr148) and AUC(hpFr96)) were significantly higher in the CQCP group than in the other treatment groups. When the children with complete resolution of their liver enlargement were considered separately, t(1/2hp) (P=0.0008) but not AUC(hp) was found to be significantly lower, and AUC(hpFr196) (P=0.01) and CL(Bhl) (P=0.002) were found to be significantly higher in the CQCP group than in the other groups. Among the children with only partial resolution of their enlarged livers, the indices of resolution and the kinetic parameters of disposition were similar in all three groups. The data indicate that the addition of chlorpheniramine to chloroquine had a beneficial effect on both the early and late stages of the resolution of the liver enlargement associated with acute, symptomatic, uncomplicated, P. falciparum malaria.

Live viral vaccine potency: an index for assessing the cold chain system.

This study was carried out in the states of Lagos, Oyo, Osun, Nigeria and was designed to assess the efficiency of the cold chain and the potency of the vaccines from the National Cold Store through to the vaccination centres. Storage equipment was inspected and oral polio, measles and yellow fever vaccines were tested for potency. All 27 centres studied had adequately trained staff and storage was shown to be adequate at the National and State Cold Store Level. However, vaccines were adversely affected at the local Government Area Cold Store and Vaccination Centre Levels. Losses of potency of vaccines were shown: loss of titre of oral polio and yellow fever vaccine (0.03-0.9 log) was less than that of the measles vaccines (0.1-2.7 log). This was ascribed to thawing and refreezing due to equipment failure, to intermittent power supply in the absence of standby generators and mishandling of vaccines in the vaccine centres. This study revealed inadequacies at the Local Government Area and Vaccination Centre level. The cold chain should be examined in the remaining states of Nigeria and the inadequacies corrected.

Risk factors for gametocyte carriage in uncomplicated falciparum malaria in children.

The risk factors associated with gametocytaemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 767 children enrolled prospectively in 5 antimalarial drug trials between July 1996 and December 2002 in a hyperendemic area of southwestern Nigeria. The children were assigned to one of 6 treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only; amodiaquine (AQ) only; CQ combined with chlorpheniramine (CQCP); or PS combined with CQ (CQPS) or AQ (AQPS). At enrolment, 115 (15%) of 767 children were gametocyte carriers. During follow-up, 15.6% of all patients (i.e. 120 patients) developed patent gametocytaemia, which in 85% (102 patients) had developed by day 7 following treatment. In a multiple regression model, 4 factors were found to be independent risk factors for the presence of gametocytaemia at enrolment: male gender (adjusted odds ratio [AOR] = 0.55, 95% confidence interval [CI] 0.36-0.83, P=0.005), absence of fever (AOR = 1.61, 95% CI 1.05-2.5, P=0.03), duration of illness >3 days (AOR=1.57, 95% CI 1.0-2.4, P=0.047), and asexual parasite densities less than 5000/microl (AOR=0.42, 95% CI 0.24-0.73, P=0.002). The presence of patent gametocytaemia at enrolment (AOR=0.04, 95% CI 0.02-0.07, P<0.001) and recrudescence of asexual parasites within 14 days were associated with the presence of gametocytaemia 7 or 14 days after enrolment (AOR=0.5, 95% CI 0.3-0.8, P=0.007). Delay in the time taken to clear the initial parasitaemia (>2 days) was associated with increased risk of subsequent gametocyte carriage. These findings may have implications for malaria control efforts in sub-Saharan Africa where control of the disease depends almost entirely on chemotherapy.