Schistosomiasis mansoni incidence data in Rwanda can improve prevalence assessments, by providing high-resolution hotspot and risk factors identification.

BACKGROUND: Schistosomiasis mansoni constitutes a significant public health problem in Rwanda. The nationwide prevalence mapping conducted in 2007-2008 revealed that prevalence per district ranges from 0 to 69.5% among school children. In response, mass drug administration campaigns were initiated. However, a few years later some additional small-scale studies revealed the existence of areas of high transmission in districts formerly classified as low endemic suggesting the need for a more accurate methodology for identification of hotspots. This study investigated if confirmed cases of schistosomiasis recorded at health facility level can be used to, next to existing prevalence data, detect geographically more accurate hotspots of the disease and its associated risk factors. METHODS: A GIS-based spatial and statistical analysis was carried out. Confirmed cases, recorded at primary health facilities level, were combined with demographic data to calculate incidence rates for each of 367 health facility service area. Empirical Bayesian smoothing was used to deal with rate instability. Incidence rates were compared with prevalence data to identify their level of agreement. Spatial autocorrelation of the incidence rates was analyzed using Moran's Index, to check if spatial clustering occurs. Finally, the spatial relationship between schistosomiasis distribution and potential risk factors was assessed using multiple regression. RESULTS: Incidence rates for 2007-2008 were highly correlated with prevalence values (R2 = 0.79), indicating that in the case of Rwanda incidence data can be used as a proxy for prevalence data. We observed a focal distribution of schistosomiasis with a significant spatial autocorrelation (Moran's I > 0: 0,05-0.20 and p ≤ 0,05), indicating the occurrence of hotspots. Regarding risk factors, it was identified that the spatial pattern of schistosomiasis is significantly associated with wetland conditions and rice cultivation. CONCLUSION: In Rwanda the high density of health facilities and the standardized microscopic laboratory diagnostic allow the derived data to be used to complement prevalence studies to identify hotspots of schistosomiasis and its associated risk factors. This type of information, in turn, can support disease control interventions and monitoring.

A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone + artesunate for the treatment of uncomplicated Plasmodium falciparum malaria.

We tested the efficacy and safety of chlorproguanil/dapsone co-administered with artesunate (CD+A) for the treatment of uncomplicated Plasmodium falciparum malaria in children compared with amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) at two different sites in Rwanda. The trial was open label and 800 patients were randomly assigned to AQ+SP (n=400) or CD+A (n=400). Patients were hospitalised for 3 days and then followed-up weekly until Day 28 after treatment. Clinical and parasitological outcomes were recorded. Results showed that neither treatment was adequately efficacious. At one site, the adequate clinical and parasitological response (ACPR), PCR-adjusted, was 73.3% in the CD+A arm and 87.8% in the AQ+SP arm (P<0.001), and at the second site the ACPR, PCR-adjusted, was 70.5% in the CD+A arm and 38.1% in the AQ+SP arm (P<0.001). The combination CD+A is considered an alternative to, or replacement for, SP in Africa because CD has been shown to be effective in patients for whom SP treatment has failed and, with its short half-life, it is expected to exert less selection pressure for resistant parasites than SP. However, the results of this trial indicate that in an area of high SP resistance, CD+A may not be the best choice.

A randomised trial to assess the safety and efficacy of artemether-lumefantrine (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda.

Coartem is a fixed-dose combination of artemether-lumefantrine that, given in six doses, provides effective treatment for children with uncomplicated Plasmodium falciparum infection in areas with highly endemic and multidrug-resistant malaria. In Rwanda since 2001, amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) has been the first-line treatment, but resistance to this combination has rapidly emerged and spread. Coartem was considered as a possible alternative, and a randomised, open-label, clinical trial to test its safety, tolerability and efficacy was carried out in 2004-2005. Five hundred children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to AQ+SP or Coartem. Patients were followed up until day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Adequate clinical and parasitological response (ACPR) was significantly higher in children treated with Coartem than in those treated with AQ+SP: the PCR-adjusted 28-day ACPR was 96.68% for Coartem and 79.35% for AQ+SP. Both treatments rapidly cleared parasitaemia and fever, although parasite clearance was significantly faster in children treated with Coartem. Mean packed cell volume increased in all patients, with no significant differences between treatments. Coartem proved to be more efficacious than AQ+SP, with a good safety and tolerability profile.

Taste-masked quinine pamoate tablets for treatment of children with uncomplicated Plasmodium falciparum malaria.

UNLABELLED: Children with uncomplicated malaria are generally treated with oral medication, except those unable to take oral drugs. Even though quinine has shown to be effective in treatment of African children with uncomplicated malaria its high bitterness limited the paediatric use. This study aimed to develop taste-masked quinine tablets suitable for children and offering dosing flexibility to adjust the quinine dose in function of body weight. METHODS: Insoluble quinine pamoate was used to formulate fast-disintegrating tablets, using a specific tablet design (rectangular tablet which can be divided into 8 subunits) to allow dosing flexibility. The physical properties of tablets were evaluated in vitro, as well as the quinine bioavailability in healthy adults (n=18) and the efficacy for treatment of children with uncomplicated Plasmodium falciparum malaria (n=56) using a 7-day regimen of 8 mg quinine/kg. RESULTS: Quinine pamoate tablets complied with the pharmacopoeial requirements for mass uniformity, friability, content uniformity, breakability, disintegration and dissolution. The quinine pharmacokinetic parameters after single administration of a quinine pamoate tablet were similar to a commercially available quinine sulfate tablet. The fast decline in parasitemia (28.6%/24h), the reduction rate of fever (all children were apyretic after 72 h) and the steady state quinine plasma concentration (5.7-15.8 microg/ml) proved the efficacy of the quinine pamoate tablets against P. falciparum. CONCLUSION: Fast-dispersible and taste-masked quinine pamoate tablets improved dosing accuracy, allowed easy administration and resulted in a high efficacy during the treatment of children with uncomplicated malaria.