Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6-14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis. RESULTS: In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%-99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%-96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%-56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%-60%, P < .0001). CONCLUSIONS: Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting. CLINICAL TRIALS REGISTRATION: NCT01231880

Intermittent preventive treatment with dihydroartemisinin-piperaquine in Ugandan schoolchildren selects for Plasmodium falciparum transporter polymorphisms that modify drug sensitivity.

Dihydroartemisinin-piperaquine (DP) offers prolonged protection against malaria, but its impact on Plasmodium falciparum drug sensitivity is uncertain. In a trial of intermittent preventive treatment in schoolchildren in Tororo, Uganda, in 2011 to 2012, monthly DP for 1 year decreased the incidence of malaria by 96% compared to placebo; DP once per school term offered protection primarily during the first month after therapy. To assess the impact of DP on selection of drug resistance, we compared the prevalence of key polymorphisms in isolates that emerged at different intervals after treatment with DP. Blood obtained monthly and at each episode of fever was assessed for P. falciparum parasitemia by microscopy. Samples from 160 symptomatic and 650 asymptomatic episodes of parasitemia were assessed at 4 loci (N86Y, Y184F, and D1246Y in pfmdr1 and K76T in pfcrt) that modulate sensitivity to aminoquinoline antimalarials, utilizing a ligase detection reaction-fluorescent microsphere assay. For pfmdr1 N86Y and pfcrt K76T, but not the other studied polymorphisms, the prevalences of mutant genotypes were significantly greater in children who had received DP within the past 30 days than in those not treated within 60 days (86Y, 18.0% versus 8.3% [P = 0.03]; 76T, 96.0% versus 86.1% [P = 0.05]), suggesting selective pressure of DP. Full sequencing of pfcrt in a subset of samples did not identify additional polymorphisms selected by DP. In summary, parasites that emerged soon after treatment with DP were more likely than parasites not under drug pressure to harbor pfmdr1 and pfcrt polymorphisms associated with decreased sensitivity to aminoquinoline antimalarials. (This study has been registered at ClinicalTrials.gov under no. NCT01231880.)

Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p>Plants have long been investigated as a source of antibiotics and other bioactives for the treatment of human disease. New Zealand contains a diverse and unique flora, however, few of its endemic plants have been used to treat tuberculosis. One plant, <it>Laurelia novae-zelandiae</it>, was reportedly used by indigenous Maori for the treatment of tubercular lesions.</p> <p>Methods</p> <p><it>Laurelia novae-zelandiae </it>and 44 other native plants were tested for direct anti-bacterial activity. Plants were extracted with different solvents and extracts screened for inhibition of the surrogate species, <it>Mycobacterium smegmatis</it>. Active plant samples were then tested for bacteriostatic activity towards <it>M. tuberculosis </it>and other clinically-important species.</p> <p>Results</p> <p>Extracts of six native plants were active against <it>M. smegmatis</it>. Many of these were also inhibitory towards <it>M. tuberculosis </it>including <it>Laurelia novae-zelandiae </it>(Pukatea). <it>M. excelsa </it>(Pohutukawa) was the only plant extract tested that was active against <it>Staphylococcus aureus</it>.</p> <p>Conclusions</p> <p>Our data provide support for the traditional use of Pukatea in treating tuberculosis. In addition, our analyses indicate that other native plant species possess antibiotic activity.</p

Intestinal parasitic infections in schoolchildren in different settings of Côte d'Ivoire : effect of diagnostic approach and implications for control

BACKGROUND: Social-ecological systems govern parasitic infections in humans. Within the frame of assessing the accuracy of a rapid diagnostic test for Schistosoma mansoni in Cote d'Ivoire, three different endemicity settings had to be identified and schoolchildren's intestinal parasitic infection profiles were characterized. METHODS: In September 2010, a rapid screening was conducted in 11 schools in the Azaguie district, south Cote d'Ivoire. In each school, 25 children were examined for S. mansoni and S. haematobium. Based on predefined schistosome endemicity levels, three settings were selected, where schoolchildren aged 8-12 years were asked to provide three stool and three urine samples for an in-depth appraisal of parasitic infections. Triplicate Kato-Katz thick smears were prepared from each stool sample for S. mansoni and soil-transmitted helminth diagnosis, whereas urine samples were subjected to a filtration method for S. haematobium diagnosis. Additionally, a formol-ether concentration method was employed on one stool sample for the diagnosis of helminths and intestinal protozoa. Multivariable logistic regression models were employed to analyse associations between schoolchildren's parasitic infections, age, sex and study setting. RESULTS: The prevalences of S. mansoni and S. haematobium infections in the initial screening ranged from nil to 88% and from nil to 56%, respectively. The rapid screening in the three selected areas revealed prevalences of S. mansoni of 16%, 33% and 78%. Based on a more rigorous diagnostic approach, the respective prevalences increased to 92%, 53% and 33%. S. haematobium prevalences were 0.8%, 4% and 65%. Prevalence and intensity of Schistosoma spp., soil-transmitted helminths and intestinal protozoan infections showed setting-specific patterns. Infections with two or more species concurrently were most common in the rural setting (84%), followed by the peri-urban (28.3%) and urban setting (18.2%). CONCLUSIONS: More sensitive diagnostic tools or rigorous sampling approaches are needed to select endemicity settings with high fidelity. The observed small-scale heterogeneity of helminths and intestinal protozoan infections has important implications for contro

Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren

BACKGROUND: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT. METHODS: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens. RESULTS: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003). CONCLUSIONS: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00852371

The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination

Background: Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward. Results: This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway. Conclusion: Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial

An update of malaria infection and anaemia in adults in Buea, Cameroon

<p>Abstract</p> <p>Background</p> <p>Anaemia is caused by many factors in developing countries including malaria. We compared anaemia rates in patients with malaria parasitaemia to that of patients without malaria parasitaemia.</p> <p>Findings</p> <p>A cross-sectional study was carried out from November 2007 to July 2008 in health units in Buea, Cameroon. Adult patients with fever or history of fever were included in the study. Information on socio-demographic variables and other variables was collected using a questionnaire. Malaria parasitaemia status was determined by microscopy using Giemsa stained thick blood smears. Haemoglobin levels were determined by the microhaematocrit technique.</p> <p>The study population consisted of 250 adult patients with a mean age of 29.31 years (SD = 10.63) and 59.44% were females. 25.60% of the patients had malaria parasitaemia while 14.80% had anaemia (haemoglobin < 11 g/dl). Logistic regression revealed that those with malaria parasitaemia had more anaemia compared to those without malaria parasitaemia(OR = 4.33, 95%CI = 1.21-15.43, p = 0.02) after adjusting for age, sex, rural residence, socioeconomic status, use of antimalarials, use of insecticide treated nets(ITN) and white blood cell count.</p> <p>Conclusions</p> <p>In adult patients with fever in this setting, malaria parasitaemia contributes to anaemia and is of public health impact. Our results also provide a baseline prevalence for malaria parasitaemia in febrile adults in health units in this setting.</p

Topography-derived wetness indices are associated with household-level malaria risk in two communities in the western Kenyan highlands

<p>Abstract</p> <p>Background</p> <p>Transmission of <it>Plasmodium falciparum </it>generally decreases with increasing elevation, in part because lower temperature slows the development of both parasites and mosquitoes. However, other aspects of the terrain, such as the shape of the land, may affect habitat suitability for <it>Anopheles </it>breeding and thus risk of malaria transmission. Understanding these local topographic effects may permit prediction of regions at high risk of malaria within the highlands at small spatial scales.</p> <p>Methods</p> <p>Hydrologic modelling techniques were adapted to predict the flow of water across the landscape surrounding households in two communities in the western Kenyan highlands. These surface analyses were used to generate indices describing predicted water accumulation in regions surrounding the study area. Households with and without malaria were compared for their proximity to regions of high and low predicted wetness. Predicted wetness and elevation variables were entered into bivariate and multivariate regression models to examine whether significant associations with malaria were observable at small spatial scales.</p> <p>Results</p> <p>On average, malaria case households (n = 423) were located 280 m closer to regions with very high wetness indices than non-malaria "control" households (n = 895) (t = 10.35, p < 0.0001). Distance to high wetness indices remained an independent predictor of risk after controlling for household elevation in multivariate regression (OR = 0.93 [95% confidence interval = 0.89–0.96] for a 100 m increase in distance). For every 10 m increase in household elevation, there was a 12% decrease in the odds of the house having a malaria case (OR = 0.88 [0.85–0.90]). However, after controlling for distance to regions of high predicted wetness and the community in which the house was located, this reduction in malaria risk was not statistically significant (OR = 0.98 [0.94–1.03]).</p> <p>Conclusion</p> <p>Proximity to terrain with high predicted water accumulation was significantly and consistently associated with increased household-level malaria incidence, even at small spatial scales with little variation in elevation variables. These results suggest that high wetness indices are not merely proxies for valley bottoms, and hydrologic flow models may prove valuable for predicting areas of high malaria risk in highland regions. Application in areas where malaria surveillance is limited could identify households at higher risk and help focus interventions.</p