A randomized, comparative study of supervised and unsupervised artesunate-amodiaquine, for the treatment of uncomplicated malaria in Ghana.

Although the use of artesunate-amodiaquine treatment is growing in Africa, data on its effectiveness are limited. In only the second published comparison of supervised and unsupervised treatments with this combination, Ghanaian children with uncomplicated malaria have recently been investigated in an open-label, randomized, comparative study. Children aged 6-120 months attending the Navrongo War Memorial hospital between November 2005 and December 2006 were enrolled if they had uncomplicated Plasmodium falciparum malaria and at least one of their parents/guardians gave their informed consent. Overall, 638 patients were screened, 357 were found to have P. falciparum infection, and 308 of these satisfied the other selection criteria and were enrolled. The subjects were divided randomly into two treatment arms. All the children were scheduled to receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154 (the 'supervised') were given all their treatments in hospital, with each dose directly observed. Although the other 154 children (the 'unsupervised') were given their first dose in hospital, under supervision, they were then sent home with the tablets they required to complete treatment. Study participation lasted for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up, axillary temperatures, any emergent signs and symptoms, and concomitant drug consumption were recorded and haemoglobin concentrations and malarial parasitaemias and gametocytaemias were measured. All but seven of the 308 subjects completed the study. At enrolment the subjects had a mean age of 45.0 months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of the children investigated were girls. There were no significant baseline difference between the two treatment arms. Although there was also no difference in the clearance of fever and parasitaemia between the two arms by day 14, a supervised child was significantly more likely to show an adequate clinical and parasitological response, by day 21 (91.3% v. 84.1%; P= 0.05) or day 28 (80.0% v. 64.9%; P<0.01), than an unsupervised child. The reported adverse effects following treatment and the trend in haemoglobin recovery were, however, similar in the two arms. Although artesunate-amodiaquine appeared very effective in the treatment of uncomplicated P. falciparum malaria in children, whether supervised or not, it appears that supervised treatment provided stronger prevention against re-infection and recrudescence. At least in the present study, treatment at home, without medical supervision, probably led to relatively poor compliance.

Experimental control of Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni, by the ampullariid snail Lanistes varicus.

The biological control of the snail hosts of the trematodes that cause human schistosomiasis appears to be a promising method for achieving sustainable reductions in the transmission of the parasites. The possibility of using the Ghanaian strain of an ampullariid snail, Lanistes varicus, for the biological control of the main snail host of Schistosoma mansoni , Biomphalaria pfeifferi, has now been investigated in laboratory-based experiments. Adult and 2-week-old L. varicus were found to feed voraciously on the egg masses and juveniles of B. pfeifferi (from the Tono irrigation canals in northern Ghana). When single L. varicus were exposed to 20-200 egg masses, they consumed all of the masses over 24 h (if adult) or about 50% of them over 4 days (if 2-week-old juveniles). The effect of the secretions of the ampullariid on the reproduction, growth and mortality of B. pfeifferi was also investigated, by maintaining the two snail species in the same aquarium but separated by nylon netting. The presence of L. varicus in the same aquarium reduced the number of egg masses produced by each B. pfeifferi, although, curiously, the presence of a single L. varicus in the aquarium appeared to have more of an impact, on the egg-mass deposition by 20 B. pfeifferi, than the presence of five or more of the ampullariids. It appears that, under laboratory conditions at least, the Ghanaian stain of L. varicus has the potential to limit populations of B. pfeifferi.

The relative susceptibilities of juvenile and adult Bulinus globosus and Bulinus truncatus to the molluscicidal activities in the fruit of Ghanaian Blighia sapida, Blighia unijugata and Balanites aegyptiaca.

The relative susceptibilities of juvenile (2- to 3-week-old) and adult (5- to 7-week-old) Bulinus globosus and Bu. truncatus to the molluscicidal activities of aqueous preparations of the powdered, dried fruits of Blighia sapida, Bl. unijugata and Balanites aegyptiaca were investigated under laboratory conditions. For the extract prepared from the freeze-dried, semi-ripe fruits of Bl. sapida, the concentrations killing 95% of the snails after an exposure for 24 h (LC95) were, respectively, 232.7 and 161.2 ppm for the juveniles and adults of Bu. globosus and 187.6 and 140.2 ppm for the juveniles and adults of Bu. truncatus. The corresponding values for Bl. unijugata were 136.9 and 98.7 ppm for Bu. globosus and 132.2 and 98.5 ppm for Bu. truncatus, respectively. Extracts of the freeze-dried, ripe fruit of Ba. aegyptiaca were much more active, however, giving LC95 of just 16.9 and 19.7 ppm for the juveniles and adults of Bu. globosus, and 14.2 and 12.0 ppm for the juveniles and adults of Bu. truncatus, respectively. In general, similar results were obtained when the fruit were oven-dried rather than freeze-dried but the potency of Balanites extracts produced from oven-dried fruit was relatively low. That the juvenile snails appeared less susceptible than the adults to the molluscicidal activity in each Blighia extract is interesting. This observation may have implications for snail control, in terms of the optimal frequency, timing and concentration of molluscicides applied in a particular habitat.

A randomized, comparative study of two regimens of beta-artemether for the treatment of uncomplicated, Plasmodium falciparum malaria, in northern Ghana.

In Ghana, wide-spread resistance to chloroquine has necessitated the drug's replacement as the first-line treatment for malaria, both to increase the likelihood of cure and to reduce transmission. To see if beta-artemether could be a suitable alternative to chloroquine, 223 adults (aged > or = 15 years) with uncomplicated, Plasmodium falciparum malaria were each given a total dose of 480 mg beta-artemether over 4 or 5 days. The patients were randomly allocated to receive an initial, loading dose of 80 or 160 mg, and were checked on days 1, 2, 3, 4 (or 5), 7 and 14, for fever clearance and any adverse events. Blood samples collected on days 0, 4 (or 5), 7 and 14 were smeared so that levels of parasitaemia could be evaluated. Haemoglobin concentrations on days 0 and 14 were also determined. In terms of the clinical cure 'rates' estimated in the intention-to-treat analysis (92.5% v. 97.4%) and the evaluability analysis (98.9% v. 100%), and of the frequency of parasitological cure by day 14 (97.0% v. 96.5%), the patients given an initial dose of 80 mg were similar to those given 160 mg as the loading dose. The regimen with the 160-mg loading dose appears as safe and as effective as the regimen with an initial dose of 80 mg. Since the regimen with the higher loading dose is shorter and involves fewer treatments than the other regimen, it would probably be associated with better compliance.

Prevalence of unusual human rotavirus strains in Ghanaian children.

Sixty-seven rotavirus-positive fecal samples, collected between January and April 1999, from children with diarrhea in the Upper East Region of Ghana were examined for rotavirus VP7 and VP4 types. Sufficient viral RNA could be obtained from 46 (68.7%) of the samples and all the isolates had short electrophoretic pattern and typed as subgroup I rotaviruses by subgroup ELISA. Three rotavirus strains with G8 specificity were identified for the first time in Ghana. G and P typing by PCR identified two distinct strains, P[6]G2 (50%) and P[6]G8 (4.3%). Eighty-two percent of the isolates (n = 38) were of the "putative" neonatal P[6] genotype. Two of these G8 isolates carried the VP4 P[6] genotype whereas the third could not be assigned a P type. Mixed infections of G1, G2, G3 and G8 were detected amongst the stool samples. The presence of these unusual strains, especially the high incidence of G2 rotavirus strains in Ghana, reinforces the need to put in place a surveillance system for the detection of new and exotic rotavirus strains, that will provide information on the spread of these strains in West Africa as well as useful data for the formulation of the next generation of rotavirus vaccines.

Rotavirus G and P genotypes in rural Ghana.

An epidemiological study of rotavirus infection was conducted on specimens collected from patients with gastroenteritis and domiciled in the rural Upper Eastern Region of Ghana during 1998. Fifty isolates, randomly selected from 165 human group A rotavirus-positive samples, were G and P characterized by a reverse transcription (RT)-PCR assay using a seminested multiplex method. Rotaviruses of the G3 genotype were found to be the predominant strain (78%), followed by G2 (14%) and G1 (2%). Mixed infections, as shown by combinations of G3 and G2 (4%) and G3 and G1 (2%), were also observed. P typing showed P[4] (72.34%) to be the prevalent strain, followed by P[6] (21.3%), P[8] (2.13%), and a combination of P[4] and P[6] (4.3%).