Reversible binocular visual loss in temporal association with artesunate-amodiaquine treatment in a child on mefloquine chemoprophylaxis.

A case of an acute reversible visual loss in a 10-year-old child who was on mefloquine prophylaxis, and was treated with artesunate-amodiaquine for an acute febrile illness diagnosed clinically as uncomplicated malaria, is reported. On admission the patient could not perceive light and had bilateral papilloedema. She was treated with dexamethasone and recovered her sight gradually over a 21-day period. There has been no previous report to our knowledge, of an association between acute visual loss and mefloquine, amodiaquine, or artesunate in the published literature, even though mefloquine is associated with blurring of vision, and antimalarials of the quinoline class have been associated with retinopathy (during long term use). While causality is difficult to ascribe in this case, it may be prudent to avoid the use of quinoline-based antimalarials for treating acute malaria in travelers taking mefloquine prophylaxis, because information on the safety of concurrent use of artemisinin combination therapies and mefloquine, or other recommended prophylactic regimens, is limited.

Pharmacogenetics in Ghana: reviewing the evidence.

Different clinical response of different patients to the same medicine has been recognised and documented since the 1950's. Variability in response of individuals to standard doses of drug therapy is important in clinical practice and can lead to therapeutic failures or adverse drug reactions. Pharmacogenetics seeks to identify individual genetic differences (polymorphisms) in drug absorption, metabolism, distribution and excretion that can affect the activity of a particular drug with the view of improving efficacy and reducing toxicity. Although knowledge of pharmacogenetics is being translated into clinical practice in the developed world, its applicability in the developing countries is low. Several factors account for this including the fact that there is very little pharmacogenetic information available in many indigenous African populations including Ghanaians. A number of genes including Cytochrome P450 (CYP) 2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, MDR1 and TPMT have been genotyped in the Ghanaian population since the completion of the Human genome project. There is however, an urgent need to increase pharmacogenetic research in Ghana to increase availability of data. Introducing Pharmacogenetics into the curriculum of Medical and Pharmacy training institutions will influence translating knowledge of pharmacogenetics into clinical practice. This will also equip health professionals with the skill to integrate genetic information into public health decision making.

Parents' perceptions, attitudes and acceptability of treatment of childhood malaria with artemisinin combination therapies in ghana.

BACKGROUND: There is little information on sociocultural and contextual factors that may influence attitudes of patients to new treatments, such as artemisinin combination therapies (ACT). METHODS: Semi-structured questionnaires and focus group discussions were used to assess views of parents of children with uncomplicated malaria treated with ACT in a low socio-economic area in Accra, Ghana. RESULTS: The majority of parents reported a favourable experience, in terms of perceived i) rapidity of symptom resolution, compared to their previous experience of other therapies for childhood malaria, or ii) when their experience was compared that of parents of children treated with monotherapy. The parents of children treated with ACT were more willing to pay for the treatment, or adhere to the full treatment course. The explanations given for adherence were consistent with conventional biomedical explanations. Although care-seeking practices for childhood malaria were considered appropriate, perceived or real barriers to accessible health care were also important factors in the decision to seek treatment. Household dynamics and perceived inequities at the care-provider-patient interface were identified as having potential negative impact on care-seeking practices and adherence. CONCLUSIONS: Health education messages aimed at improving the response to childhood febrile illness should include other strategic stakeholders, such as decision-makers at the household level. The effectiveness and implementation success of the ACT policy could be enhanced by highlighting and reinforcing messages intrinsic to these regimens. Integrating the views of caretakers during the clinical encounter was validated as an empowerment tool that could aid in the appropriate responses to childhood illness.

Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose.

A case of an acute dystonic reaction in a child presumptively treated for malaria with amodiaquine, and a case of persistent asymptomatic bradycardia in another child with mild pulmonary stenosis treated with a standard dose of amodiaquine for parasitologically confirmed uncomplicated malaria, is reported. Both subjects were homozygous for the wild type allele of cytochrome P450 2C8, the main enzyme responsible for amodiaquine metabolism. In both subjects, plasma concentrations of N-desethylamodiaquine and N-bis-desethylamodiaquine, the main metabolites of amodiaquine, were normal. No other drugs were detectable in the plasma of these two subjects after further toxicological screening. These observations, which suggest altered metabolism in the subject with an acute dystonic reaction, support the assertion that amodiaquine-associated dystonia is an idiosyncratic reaction. However, the occurrence of bradycardia after a standard dose of amodiaquine, which coincided with the time of expected peak concentrations of the active metabolite of amodiaquine, suggests a direct drug effect. These less reported adverse effects are likely to increase in parallel with the increased use of amodiaquine as a partner drug for combination therapy of malaria in Ghana. Further studies aimed at elucidating the mechanisms underlying these effects are, therefore, required.