3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Insecticide resistance and vector status of Anopheles funestus and An. gambiae populations at a sugar estate in Mozambique(2010-04-12T09:55:50Z) Kloke, Ronald GrahamMalaria is on the increase in Mozambique since 2001 and impacts primarily on children < 5 years of age. Insecticide resistance in the malaria vector mosquitoes is on the increase in Mozambique and Africa and is cause for serious concern. Maragra sugar estate is situated in close proximity to the nKomati river floodplain in a rural area in Mozambique and requires intense irrigation for cane growing and as a result provides extensive breeding sites for An. funestus and other mosquitoes. In the areas surrounding the estate there are two important vectors of malaria, Anopheles funestus group and An. gambiae complex. There is intense malaria transmission in the areas surrounding the sugar estate and the last entomological study on the vectors in the Manhica area was done in 1998. It was becoming increasingly urgent to identify to species level the vectors in this area and to monitor the insecticide resistance status of these vectors. Due to leakage (theft) of insecticides and a change by the National Malaria Control Programme (NMCP) to an insecticide to which the predominant vector is resistant, an entomological survey was carried out in this area from January 2009 to March 2009 to ascertain by Polymerase chain reaction (PCR) what species of malaria vectors were present inside and outside of the Maragra vector control area, their population levels and their vectorial status in these two areas. Insecticide resistance studies by insecticide exposure and the synergist piperonyl butoxide (pbo) were carried out using the World Health Organisation (WHO) bioassay method on collected An. funestus mosquitoes. This was done to establish this species resistance status to the four classes of insecticides recommended by the WHO for malaria vector control. The collections of An. arabiensis and An. merus that were identified were too few to carry out insecticide resistance tests on these two species. Enzyme linked v immuno-sorbent assay (ELISA) tests were undertaken to establish the vectorial capacity of Anopheles funestus and An. gambiae complex in this area. The predominant malaria vector species in this area is An. funestus s.s., with the secondary vector being An. arabiensis. An. funestus has a high vectorial capacity in this area and found to have a Plasmodium falciparum sporozoite rate of 6.02%. This is an increase in the sporozoite rate of 1.2% from 1998 when the last survey in this regard was carried out. Coupled with this increase is an increase in the An. funestus populations in this area since this time. One An. gambiae complex sample was found to be positive but the species is not known as this particular sample did not amplify on PCR. Anopheles funestus is highly resistant to synthetic pyrethroids and exhibits a lower level of resistance to bendiocarb, a carbamate insecticide in use at Maragra sugar estate. The synergist pbo mediates the resistance mechanism in both these insecticides indicating that the metabolic resistance mechanism present in this mosquito is strongly mediated by monooxygenase detoxification. The role of the medical entomologist is increasingly necessary and important in the monitoring of this resistance phenomenon in malaria vector mosquitoes, as is the role of the vector control programme manager in implementing and managing vector control programmes. The implication of cane sugar farming and its impact on vector production and malaria transmission is discussed. Insecticide resistance and the change by the NMCP to a synthetic pyrethroid to which the predominant vector of malaria is resistant is discussed.Item Home management of malaria in children under 5 years in Kassena-Nankana District of upper-east region of Ghana: knowledge, attitude and practices of home caregivers(2009-05-04T09:15:30Z) Ameh, Soter SundayABSTRACT INTRODUCTION : Malaria remains a serious health burden among children in sub- Saharan Africa. The Home Management of Malaria (HMM) programme was adopted by African heads of states in 2000 as a strategy to achieve high coverage of prompt and effective anti malarial treatment within 24 hours of the onset of symptoms by home caregivers in areas with poor access to facility based health care. Strategic components of the programme include communication for behavioural change, training of community based public-private health service providers and making antimalarials available in communities[1]. AIM: To determine the impact of HMM strategy in the home treatment of uncomplicated malaria in children in Kassena-Nankana District (KND) of upper-east region of Ghana. Specific objectives described the knowledge, attitude and practice and tested the association between knowledge, attitude and other factors and accurate HMM. METHOD: Secondary data from a survey on the role of health information recipients in access and utilization of treatment for malaria management in children under 5 years (U5s) conducted among 818 women in KND from 2005 to 2006 were analyzed using a cross sectional study design. A total of 708 Home caregivers (HCGs) aged 15-49 years who responded to knowledge of the treatment of uncomplicated malaria was obtained after data cleaning. Knowledge of the treatment of uncomplicated malaria was used as a proxy for accurate HMM (correct dosage and correct duration of antimalarial) in U5s because the questionnaire did not contain information on the actual treatment given by the HCGs. Data analysis was done in STATA 10 using Chi squared test for categorical variables. Logistic regression models were used to quantify the associations and adjust for potential confounders and effect modification. RESULTS: The study found that 59% of the women had good knowledge of the symptoms of uncomplicated malaria and 25% knew that only mosquitoes transmit malaria. On treatment seeking attitude (advice and autonomy), the majority (91%) of the home caregivers received various forms of advice from the older women. Such advice included: using herbs (77%), buying drugs (41%), visiting Health Clinic (24%), and visiting the Community Health Officers (19%). On receiving advice, only 15% would utilize the services of the Community Health Officers (CHOs) who are the main source of treatment information for the communities. Thirty percent (30%) of the HCGs had autonomy of health care decision-making in the households. Accurate HMM in children was 28%. Knowledge of malaria and treatment seeking attitude were not significantly associated with accurate HMM (p>0.05). In the multivariate model, the HCGs were more likely to do accurate HMM in children if they had secondary education (OR = 2.54, 95% CI 1.18 ; 5.60), were of Nankani ethnicity (OR = 3.00, 95% CI 2.08 ; 4.35) and belonged to the very poor socio-economic status (OR = 2.31, 95% CI 1.25 ; 4.30). A Chi squared analysis to further identify the differences between the women who gave drugs and those who did not showed that the women differed significantly in their ethnicity (p<0.001), occupation (p<0.001) and relationship as the biological mothers to the children (p=0.008). The major limitation of this study was that knowledge of the treatment of uncomplicated malaria was used as a proxy for accurate HMM hence the finding is not a true reflection of the actual malaria treatment practice HCGs give to U5s. Another limitation is that the study could not measure the promptness of initiating malaria treatment within 24 hours of the onset of symptoms in children because of the absence of such variable in the data. CONCLUSION: Although HCGs had good knowledge of the symptoms of uncomplicated malaria, it did not translate to accurate HMM. The study identified poor dosage of treatment with Chloroquine (the first line antimalarial at the time of the study) was responsible for inaccurate HMM. Therefore, HCGs need to receive adequate information on the dosage of the current first line Artemesinin Combination Therapy drugs which have replaced Chloroquine in the treatment of malaria. Home caregivers need to be encouraged to utilize the services of the CHOs as the main source of malaria related information in the HMM programme. Specific groups to be targeted include the older women and the HCGs at risk of inaccurate HMM. Further research on the actual treatment given to children is recommended with particular emphasis on qualitative technique to unpack culturally related ethnic beliefs associated with HMM in children.Item Clustering of mortality among children under five years due to malaria at the Ifakara demographic surveillance site in Tanzania(2009-04-28T13:20:00Z) Kamara, Mohamed KobloABSTRACT Introduction Under-five mortality is still a major cause of concern in Sub Saharan Africa and among the highest in the world. This is also exacerbated by the high prevalence and episodes of malaria in this age group, which accounts for 90% of all under-five deaths estimated in the region annually. The effect of detecting clustering of all cause and cause specific mortality and underlying factors is crucial for timely public health interventions. This is especially important for health authorities in Tanzania where under-five malaria attributable deaths accounts for 45% of the annual estimated mortality of 100, 000. Study objectives To estimate under-five mortality and analyze clustering of all cause and malaria specific mortality among under five children in Ifakara Demographic Surveillance System from 2002-2005. Methods Data from the Ifakara Health Research and Development Centre (IHRDC) were obtained for all under-five children who lived in 25 villages in the DSS from 2002 – 2005. Analyses for all cause and malaria cause specific under-five mortality were done using data collected from the DSS and verbal autopsy systems. Annual all cause and malaria specific mortality rates were calculated by dividing number of deaths and person years observed. Clustering of deaths for all cause and cause specific (malaria) in the 25 villages were analyzed using SaTScanTM version 7.0 software. A Poisson model was used to detect clusters with high rates in space and in space-time. Household assets and characteristics were used to construct a wealth index using Principal component analysis (PCA) in StataTM version9. The index was used to group households into five equal groups from poorest to least poor. Results Overall infants’ mortality was sixty-three times higher (326 per 1,000 person years) compared to children (5.1 per 1,000 person years) and with mortality rates between girls and boys were very similar, (15.8 and 14.8 per 1,000 person years). Year of death and place of death (village) were found to be significantly associated with malaria deaths. However, socio-economic status of parents in households where deaths occurred was not associated to malaria deaths in the DSS. A number of statistically significant clusters of all cause and cause specific malaria deaths were identified in several locations in the DSS. The located clusters imply that villages within the clusters have an elevated risk of under-five deaths. A space-time cluster of four villages with radius of 15.91 km was discovered with the highest risk (RR 2.71; P-value 0.020) of malaria deaths in 2004. Conclusion These findings demonstrate that there is non-random clustering of both all cause and malaria cause specific mortality in the study area. The high infant mortality results also suggest a careful examination of the data collection procedures in the DSS and require further studies to understand this pattern of mortality among the under-five population. Appropriate health interventions aimed at reducing burden of malaria should be strengthened in this part of rural Tanzania. There is need to replicate this study to other areas in the country.Item A meta-analysis of artesunate plus sulfadoxinepyrimethamine alone for treatment of uncomplicated malaria in children(2006-11-17T08:23:06Z) Benido, ImpoumaStudy objectives The objective of this meta-analysis was to review the comparative efficacy and tolerance of sulfadoxine-pyrimethamine (SP) given alone or in combination with one (SPAS1) or three (SPAS3) doses of artesunate in children with uncomplicated P. falciparum malaria, aged 6 months to 10 years. Specifically, it assessed cure rate, fever and parasite clearance time, gametocyte carriage and tolerability. Methods The methodology used was a systematic review and a meta-analysis of four randomised controlled trials. The primary endpoint was the parasitological cure rate at day 28. Secondary endpoint included the parasitological cure rate at day 14, time to fever and parasite clearance, gametocyte carriage and occurrence of adverse events. Results Cure rate at day 28 corrected by PCR was 2.5 times higher in the combination of SPAS3 than in SP alone (pooled OR=2.55, 95% CI 1.93 to 3.37). There was no difference in cure rate at day 28 corrected by PCR between the combination of SPAS1 and SP alone (pooled OR=1.06 95% CI 0.98 to 1.15). Fever and parasite clearance times were significantly faster in both SPAS1 and SPAS3 compared to SP alone (p<0.001). By day 28 all children on the combination therapy were agametocytaemic as opposed to those on SP alone (p<0.001). All drug regimens were well tolerated and safe. Conclusion The combination of SPAS3 is more efficacious than SP alone in treatment of children with uncomplicated P. falciparum malaria. The combination is recommended for adoption as a replacement for SP alone in areas where malaria is endemic.Item The role of mutations in uncomplicated Plasmodium falciparum malaria and sulfadoxine pyrimethamine efficacy in Mpumalanga Province, South Africa.(2006-11-17T07:55:38Z) Mngomezulu, Nicros MagangeniThe antifolate combination of sulfadoxine and pyrimethamine (SP) is one of few remaining affordable drug combinations available for wide-scale treatment of uncomplicated Plasmodium falciparum malaria in Africa. In vivo studies of SP efficacy conducted during 1998, 2000 and 2002 at the Naas sentinel site in Mpumalanga province, South Africa, demonstrated a gradual non-significant increase in late treatment failure (LTF) and early treatment failure (ETF) resistance to SP, while gametocyte carriage increased significantly between 1998 and 2002 (p < 0.0001). This study aimed to determined and compare the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) resistant haplotypes in P. falciparum parasites from patients treated with SP in three consecutive standardized in vivo therapeutic efficacy studies in Mpumalanga province, since implementation of SP as first line treatment in 1998, and to investigate associations between the presence of mutations and treatment outcomes after SP treatment. Four hundred-and-three samples were studied and 358 yielded polymerase chain reaction products. A novel high throughput sequence-specific oligonucleotide probe-based approach was used to examine the resistance status of the three in vivo P. falciparum populations. Screening for the presence of all known point mutations in dhfr and dhps genes revealed that only five dhfr and three dhps allelic haplotypes were present. In all the samples investigated, point mutations were identified only at codons 108, 51 and 59 of the dhfr gene and at codons 347 and 540 of the dhps gene. The prevalence of dhfr resistant haplotypes was 35.4% in 1998, 38.7% in 2000, and 41.0% in 2002, while the prevalence of dhps resistant haplotypes was 9.7% in 1998, 7.2% in 2000 and 41.6% in 2002, the latter representing a significant increase (p < 0.002). The prevalence in both dhfr and dhps gene resistant haplotypes were selected gradually during the three in vivo studies in Mpumalanga province. Infection with parasites having triple dhfr mutations and double dhps mutations, "the quintuple mutant", was associated with SP treatment failure (p < 0.001). Mutations at both dhfr and dhps loci may be important predictors of SP resistance in Mpumalanga province.Item Efficacy of artemisinin derivatives in treating severe malaria in children: A systematic review and meta-analysis(2006-11-01T11:28:34Z) Praygod, GeorgeBackground Evidence shows that the efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing. Artemisinin derivatives are the potential replacement for quinine. Their efficacy compared to quinine in treating severe malaria in children is not well known. Objective To assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children. Search strategy The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to October 2005), EMBASE (1980 to October 2005), and LILACS (1982 to October 2005) were searched. Malaria researchers and a pharmaceutical company were contacted. In addition, conference proceedings were also searched. Selection criteria Randomised controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children. All trials had to report mortality as an outcome. Data collection After data were extracted, two individuals independently assessed the trial quality. In addition, information on adverse effects from the studies was also collected. Main results Eleven trials were selected (1455 subjects), nine of them from Africa and the rest from Asia. Allocation concealment was adequate in seven trials (1238 subjects). Overall there was no difference in mortality between artemisinin derivatives and quinine (Risk Ratio= 0.89, 95% confidence interval 0.71 to 1.1). There was no difference in mortality between adequately concealed and inadequately concealed /unconcealed trials (Risk Ratio = 0.93, 95% confidence interval 0.74 to 1.16 and Risk Ratio=0.66, 95% confidence interval 0.36 to 1.22). In Parasite Clearance Time (PCT), though there was no statistical difference between the two groups there was a tendency towards favouring the artemisinin derivatives (weighted mean difference among studies which reported PCT as mean was -4.76 with 95% confidence interval -9.68 to 0.17 and all three studies which reported PCT as median showed that artemisinin derivatives cleared parasites faster than quinine, each had p<0.001). However; when only trials with adequate concealment were considered this potential advantage disappeared. In exploring heterogeneity for PCT, it was shown that study settings (Asia versus Africa) might have been a cause for heterogeneity. The artemisinin derivatives resolved coma faster than quinine (weighted mean difference=-5.32, 95%CI: -8.06 to -2.59), but when only trials with adequate concealment were considered this difference disappeared. Other secondary outcomes i.e. Fever clearance time, Incidence of neurological sequelae, and 28th day cure rate showed no significant difference between artemisinin derivatives and quinine. There was no enough data to make meaningful comparison of adverse effects between the two groups. Conclusions The available evidence suggests that parenteral artemisinin derivatives are as efficacious as quinine in preventing mortality from severe malaria in children.