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| 2. |
- Bhattarai, Achuyt, et al.
(author)
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Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar
- 2007
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 4:11, s. e309-
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Journal article (peer-reviewed)abstract
- BackgroundThe Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.Methods and FindingsCross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.ConclusionsFollowing deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.
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- Fernando Chaves, Luis, et al.
(author)
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Spleen rates in children : an old and new surveillance tool for malaria elimination initiatives in island settings
- 2011
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In: Transactions of the Royal Society of Tropical Medicine and Hygiene. - : Oxford University Press (OUP). - 0035-9203 .- 1878-3503. ; 105:4, s. 226-231
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Journal article (peer-reviewed)abstract
- Spleen rates (SR) have been traditionally used to estimate the burden of malaria transmission. Results are presented from 51 surveys, which measured SR and parasite rates (PR) in 29 962 individuals in the archipelago of Vanuatu. Indices for spleen size computed with multivariate statistical tools outperformed the WHO average spleen index and showed that spleen sizes in a population can track shifts in malaria transmission. In general, a positive linear relationship between Plasmodium spp. PR and SR was found for the archipelago. In the context of malaria elimination and for the specific setting of this study we found that spleen examination is a useful tool in post-malaria elimination surveillance. Finally, results highlight the value of measuring spleen sizes to rapidly assess the impact of intervention packages aimed at malaria elimination or control.
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- Friberg Hietala, Sofia, 1973, et al.
(author)
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Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria
- 2007
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In: JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 12, s. 222-222
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Journal article (peer-reviewed)abstract
- The study aimed to characterize the population pharmacokinetics of amodiaquine (AQ) and its major metabolite N-desethylamodiaquine (N-DEAQ), and to assess the correlation between exposure to N-DEAQ and treatment outcome. Blood samples from children in two studies in Zanzibar and one in Papua New Guinea were included in the pharmacokinetic analysis (n = 86). The children had been treated with AQ in combination with artesunate or sulphadoxine-pyrimethamine. The population pharmacokinetics of AQ and N-DEAQ were modeled using the non-linear mixed effects approach as implemented in NONMEM. Bayesian post-hoc estimates of individual pharmacokinetic parameters were used to generate individual profiles of N-DEAQ exposure. The correlation between N-DEAQ exposure and effect was studied in 212 patients and modeled with logistic regression in NONMEM. The pharmacokinetics of AQ and N-DEAQ were best described by two parallel two-compartment models with a central and a peripheral compartment for each compound. The systemic exposure to AQ was low in comparison to N-DEAQ. The t (1/2lambda) of N-DEAQ ranged from 3 days to 12 days. There was a statistically significant, yet weak, association between N-DEAQ concentration on day 7 and treatment outcome. The age-based dosing schedule currently recommended in Zanzibar appeared to result in inadequate exposure to N-DEAQ in many patients.
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- Kaneko, Akira
(author)
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A community-directed strategy for sustainable malaria elimination on islands : Short-term MDA integrated with ITNs and robust surveillance
- 2010
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In: Acta Tropica. - : Elsevier BV. - 0001-706X .- 1873-6254. ; 114:3, s. 177-183
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Journal article (peer-reviewed)abstract
- In the Asia Pacific sites with low and unstable transmission, elimination should be feasible with existing tools. On Aneityum island, Vanuatu both Plasmodium falciparum and Plasmodium vivax malaria were eliminated in 1991 after implementation of a combined intervention package, including mass drug administration (MDA) and insecticide-treated bed nets (ITNs), with high degree of community involvement. Subsequently, community-based surveillance and vector control measures have kept. By reviewing the experiences of the Aneityum project, I intended to examine the roles of community in malaria elimination. To be successful, the program should transfer major intervention components from the external donor-directed initiative to the community-directed approach. Scaling up of community involvement from simple participation to social participation, where communities involve in health planning functions is necessary from malaria control to malaria elimination.
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| 6. |
- Kaneko, Akira, et al.
(author)
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Characteristic Age Distribution of Plasmodium vivax Infections after Malaria Elimination on Aneityum Island, Vanuatu
- 2014
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 82:1, s. 243-252
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Journal article (peer-reviewed)abstract
- Resurgence is a major concern after malaria elimination. After the initiation of the elimination program on Aneityum Island in 1991, microscopy showed that Plasmodium falciparum disappeared immediately, whereas P. vivax disappeared from 1996 onward, until P. vivax cases were reported in January 2002. By conducting malariometric surveys of the entire population of Aneityum, we investigated the age distribution of individuals with parasites during this epidemic in the context of antimalarial antibody levels and parasite antigen diversity. In July 2002, P. vivax infections were detected by microscopy in 22/759 individuals: 20/298 born after the beginning of the elimination program in 1991, 2/126 born between 1982 and 1991, and none of 335 born before 1982. PCR increased the number of infections detected to 77, distributed among all age groups. Prevalences were 12.1%, 16.7%, and 6.0%, respectively (P<0.001). In November, a similar age pattern was found, but with fewer infections: 6/746 and 39/741 individuals were found to be infected by microscopy and PCR, respectively. The frequencies of antibody responses to P. vivax were significantly higher in individuals born before 1991 than in younger age groups and were similar to those on Malakula Island, an area of endemicity. Remarkably low antigen diversity (h, 0.15) of P. vivax infections was observed on Aneityum compared with the other islands (h, 0.89 to 1.0). A P. vivax resurgence was observed among children and teenagers on Aneityum, an age distribution similar to those before elimination and on islands where P. vivax is endemic, suggesting that in the absence of significant exposure, immunity may persist, limiting infection levels in adults. The limited parasite gene pool on islands may contribute to this protection.
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| 7. |
- Kaneko, Akira
(author)
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Malaria on islands : human and parasite diversities and implications for malaria control in Vanuatu
- 1999
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Doctoral thesis (other academic/artistic)abstract
- The genetic diversities displayed by human and malaria parasites at different frequencies in different geographical areas represent a major obstacle for the development of malaria control strategies including malaria chemotherapy and malaria vaccine. We investigated some genetic diversities on Vanuatu islands with various malaria endemicities. Malaria in Vanuatu is unstable, mainly hypo- to mesoendemic and seasonal with occasional epidemics. Our data suggested that malaria transmission has remained significant over many centuries especially on northern and central islands and that this has selected for high glucose 6-phosphate dehydrogenase deficiency rates in the populations. The frequencies of the cytochrome P450 (CYP) 2C19 mutant alleles were uniformly greater in Vanuatu. However, there were differences between populations from different islands. Comparisons of genetic, linguistic and geographic patterns suggested that short range gene flow is largely responsible for the current distribution of CYP2C19 alleles in Vanuatu. Our data in malaria patients demonstrated an association between CYP2C19 mutations and poor metabolism of proguanil to cycloguanil, a strong dihydrofolate reductase (DHFR) inhibitor, and an apparent gene dose effect relationship. Restricted diversity in the dhfr gene was shown in a total of 140 P. falciparum cases on 4 isolated islands of Vanuatu. All isolates had the same Asn-108 mutation, and all, except 3 in Gaua, also had Arg-59 mutation, normally associated with moderate resistance to DHFR-inhibiting drugs. The 3 remaining isolates in Gaua had His-51, a change not previously reported in the literature. Despite these partly resistant variants, pyrimethamine and sulfadoxine treatment was still highly effective. The restricted diversity of the dhfr gene in unstable malaria endemicity on Vanuatu islands may be at least partly explained by a loss in heterozygosity of the parasite populations derived from periodically interrupted transmission and isolation with limited gene flows between islands. Mutations in human CYP2C19 and parasite dhfr genes, related to poor metabolism of proguanil and resistance to cycloguanil respectively, have both been assumed to be associated with poor antimalarial effect by proguanil. We however observed high antimalarial efficacy of proguanil also in patients with CYP2C19-related poor metabolizer genotype and the common dhfr genotype (Arg-59 and Asn- 108). This suggested that the parent compound proguanil has an intrinsic efficacy independent of the metabolite cycloguanil and the dhfr mutation. By combining mass drug administration with impregnated bed nets, we have most probably interrupted malaria transmission on Aneityum island with unstable endemicity and achieved sustained and significant gains over 7 years. The seroepidemiological results indicate that without antigenic stimulation, immunologic memory still remains for many years in adults previously repeatedly exposed to malaria.
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| 10. |
- Stepniewska, Kasia, et al.
(author)
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Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide : a systematic review and meta-analysis of individual patient data
- 2022
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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Research review (peer-reviewed)abstract
- BackgroundIn 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.MethodsA systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.ResultsData comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.ConclusionsOur results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.
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