ABSTRACT
Isoniazid (INH) and rifampicin (RMP) resistance in Mycobacterium tuberculosis complex (MTC) isolates are mainly based on mutations in a limited number of genes. However, mutation frequencies vary in different mycobacterial populations. In this work, we analyzed the distribution of resistance-associated mutations in M. tuberculosis and M. africanum strains from Ghana, West Africa. The distribution of mutations in katG, fabG1-inhA, ahpC, and rpoB was determined by DNA sequencing in 217 INH-resistant (INH(r)) and 45 multidrug-resistant (MDR) MTC strains isolated in Ghana from 2001 to 2004. A total of 247 out of 262 strains investigated (94.3%) carried a mutation in katG (72.5%), fabG1-inhA (25.1%), or ahpC (6.5%), respectively. M. tuberculosis strains mainly had katG 315 mutations (80.1%), whereas this proportion was significantly lower in M. africanum West-African 1 (WA1) strains (43.1%; p<0.05). In contrast, WA1 strains showed more mutations in the fabG1-inhA region (39.2%, p<0.05) compared to M. tuberculosis strains (20.9%). In 44 of 45 MDR strains (97.8%) mutations in the 81-bp core region of the rpoB gene could be verified. Additionally, DNA sequencing revealed that 5 RMP-susceptible strains also showed mutations in the rpoB hotspot region. In conclusion, although principally the same genes were affected in INH(r)M. tuberculosis and M. africanum strains, disequilibrium in the distribution of mutations conferring resistance was verified that might influence the efficiency of molecular tests for determination of resistance.
Subject(s)
Antitubercular Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Bacterial , Mutation , Mycobacterium/drug effects , Mycobacterium/genetics , Tuberculosis/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Ghana , Humans , Isoniazid/pharmacology , Mycobacterium/isolation & purification , Rifampin/pharmacology , Sequence Analysis, DNASubject(s)
Genetic Linkage , Membrane Glycoproteins/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin-1/genetics , Tuberculosis, Pulmonary/genetics , Case-Control Studies , DNA Mutational Analysis , Gene Frequency , Ghana , Humans , Indonesia , Leucine/genetics , Russia , Serine/geneticsABSTRACT
OBJECTIVE: We assessed the feasibility and acceptability of and the willingness to use artemether-lumefantrine (Coartem) during early, appropriate treatment of malaria/fever in children aged 6-59 months at the community and household level in a rural malaria-endemic area in Ghana. METHOD: In this descriptive study with a pre- post-evaluation of an intervention, community perceptions of fever, health-seeking behaviour and current treatment practices for children aged 6-59 months were ascertained through qualitative research and surveys. The children were counted in a household census and given identification cards. Community-based agents (who were supervised monthly) dispensed a 6-dose-treatment formulation of Coartem over a 4 months period and counseled caregivers on case management and referral. Caregivers who consulted were followed up after 4 days to determine adherence to the treatment regimen. Blister packs of the drugs were inspected where available. The performance of the agents in terms of counselling, advising on referral and reporting was evaluated. Community satisfaction was also assessed qualitatively through focus group discussions and interviews. RESULTS: Three hundred and sixty-three children sought care during the intervention period. All 235 children aged 6-35 months were correctly provided the one tablet per dose per treatment package compared with 119 of 125 children 36-59 months (95.2%). Only 5 of 17 children were referred appropriately. All 334 caregivers followed the correct drug administration schedule, i.e. twice a day for 3 days. Validation of drugs received indicates that all 204 children aged 6-35 months and 103/118 (87.3%) children aged 36-59 months received the correct drug dose. Adherence of agents and caregivers to the treatment was 308/334 (92.5%). Delay in seeking care was reduced from 3 to 2 days. No serious adverse drug reactions were reported. Community members were enthusiastic about the performance of the agents. CONCLUSION: A Home Management of Malaria (HMM) strategy with Coartem using trained community-based agents supervised monthly is feasible, acceptable, and can achieve high levels of compliance within Dangme, West District of Ghana. However, if the intervention is to be sustainable, the agents need to be paid.
