Mass administrations of antimalarial drugs.

Administration of antimalarial drugs to whole populations has been used as a malaria-control measure for more than 70 years. Drugs have been administered either directly as a full therapeutic course of treatment or indirectly through the fortification of salt. Mass drug administrations (MDAs) were generally unsuccessful in interrupting transmission but, in some cases, had a marked effect on parasite prevalence and on the incidence of clinical malaria. MDAs are likely to encourage the spread of drug-resistant parasites and so have only a limited role in malaria control. They could have a part to play in the management of epidemics and in the control of malaria in areas with a short transmission season. To reduce the risk of spreading drug resistance, MDAs should use more than one drug and, preferably include a drug, such as an artemisinin, which has a gametocidal effect

Mortality after fluid bolus in children with shock due to sepsis or severe infection: a systematic review and meta-analysis.

Sepsis is one of the leading causes of childhood mortality, yet controversy surrounds the current treatment approach. We conducted a systematic review to assess the evidence base for fluid resuscitation in the treatment of children with shock due to sepsis or severe infection

The Failure of Screening and Treating as a Malaria Elimination Strategy.

Lorenz von Seidlein discusses the study by Katherine Halliday and colleagues and explores the reasons why a school-based screening and treatment strategy for malaria might have failed. Please see later in the article for the Editors' Summary

The Future of the RTS,S/AS01 Malaria Vaccine: An Alternative Development Plan.

Roly Gosling and Lorenz von Seidlein consider a potential future development plan for the RTS,S/AS01 malaria vaccine

Gametocytaemia after Drug Treatment of Asymptomatic Plasmodium falciparum

OBJECTIVES: Treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) is followed by a sharp rise in the prevalence and density of gametocytes. We did a randomized trial to determine the effect of treatment of asymptomatic infections with SP or SP plus one dose of artesunate (SP+AS) on gametocyte carriage. DESIGN: The study was a three-arm open-label randomized trial. We randomized asymptomatic carriers of P. falciparum to receive antimalarial treatment or placebo, and recorded the prevalence and density of gametocytes over the next 2 mo. SETTING: The trial was conducted during the dry (low malaria transmission) season in four rural villages in Gambia. PARTICIPANTS: Participants were adults and children aged over 6 mo with asexual P. falciparum infection and confirmed free of clinical symptoms of malaria over a 2-d screening period. INTERVENTIONS: Participants were randomized to receive a single dose of SP or SP+AS or placebo. OUTCOME MEASURES: The outcome measures were the presence of gametocytes 7 and 56 d after treatment, and the duration and density of gametocytaemia over 2 mo. RESULTS: In total, 372 asymptomatic carriers were randomized. Gametocyte prevalence on day 7 was 10.5% in the placebo group, 11.2% in the SP group (risk difference to placebo 0.7%, 95% confidence interval −7.4% to 8.7%, p = 0.87), and 7.1% in the SP+AS group (risk difference to placebo 4.1%, 95% confidence interval −3.3% to 12%, p = 0.28). By day 56, gametocyte prevalence was 13% in the placebo group and 2% in both drug-treated groups. Gametocyte carriage (the area under the curve of gametocyte density versus time), was reduced by 71% in the SP group, and by 74% in the SP+AS group, compared to placebo. Gametocyte carriage varied with age and was greater among children under 15 than among adults. CONCLUSIONS: Treatment of asymptomatic carriers of P. falciparum with SP does not increase gametocyte carriage or density. Effective treatment of asexual parasitaemia in the dry season reduces gametocyte carriage to very low levels after 4 wk

Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae.

Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections. Lowering transmission by reducing gametocyte infectivity would be an additional benefit. To examine the effect of such therapy on transmission, Gambian children with Plasmodium falciparum malaria were treated with standard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate. The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment. Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density. The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate, and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone. Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely. The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria

Differences in perception of dysentery and enteric fever and willingness to receive vaccines among rural residents in China.

BACKGROUND: Enteric diseases including dysentery and enteric fever remain significant public health problems in China. While vaccines offer great potential in controlling these diseases, greater understanding of factors influencing acceptance of vaccines is needed to create effective enteric disease control programs in rural China. DESIGN: Cross-sectional quantitative study with randomly sampled households from two sites in China, one experiencing high rates of shigellosis (Zengding) and the other of typhoid/paratyphoid (Lingchuan). METHODS: Sociobehavioral survey data were collected through face-to-face interviews from 501 respondents (56% female) in Zhengding regarding dysentery and 624 in Lingchuan (51% female) regarding enteric fever. Vaccine acceptability was measured by expressed need for vaccination and willingness to pay. Comparative and associative analyses were conducted to assess disease perception, vaccination service satisfaction, likelihood of improvements in water and sanitation, and vaccine acceptability. RESULTS: Nearly all respondents in Lingchuan considered enteric fever to be prevalent in the community, while only one half of the respondents in Zhengding considered dysentery to be problematic (p < 0.01). Nevertheless, more respondents in Zhengding were fearful that a household member would acquire dysentery than were Lingchuan respondents worried that a household member would acquire enteric fever (p < 0.01). Perceived vulnerability of specific subgroups (odds ratios ranging from 1.6 to 8.1), knowing someone who died of the disease (odds ratio reached infinity) and satisfaction with past vaccination services (odds ratios reached infinity) were consistently associated with perceived need for vaccines of target populations of all age groups while the association between perception of sanitary improvement and vaccine need was limited. Perceived need for a vaccine was associated with willingness to pay for the vaccine. CONCLUSIONS: Perceptions of enhanced vulnerability of specific subgroups to a disease and satisfactory experiences with vaccination services may increase the perceived need for a vaccine, leading to increased willingness to pay for vaccine. Vaccines are not perceived as important for the elderly

Recent atmospheric neutrino results from Soudan 2

An updated measurement of the atmospheric nu_mu/nu_e ratio-of-ratios, 0.68+-0.11+-0.06, has been obtained using a 4.6-kty exposure of the Soudan-2 iron tracking calorimeter. The L/E distributions have been analyzed for effects of nu_mu -> nu_x oscillations, and an allowed region in the Delta m^2 vs. sin^2 2 theta plane has been determined.Comment: 3 pages, 4 figures; presented at TAUP99, the 6th Int. Workshop on Topics in Astroparticle and Underground Physics, Sept. 6-10, 1999, College de France, Paris, Franc

Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment.

Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials

Efficacy of chloroquine, sulphadoxine-pyrimethamine and amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in Kajo Keji county, Sudan.

To provide advice on the rational use of antimalarial drugs, Médecins Sans Frontières conducted a randomized, an open label efficacy study in Kajo Keji, an area of high transmission of malaria in southern Sudan. The efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) were measured in a 28-day in vivo study, with results corrected by PCR genotyping. Of 2010 children screened, 115 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were randomized into each group to receive a supervised course of treatment. Of these, 114, 103 and 111 were analysed in the CQ, SP and AQ groups, respectively. The overall parasitological failure rates at day 28 were 93.9% [95% confidence interval (CI) 87.3-97.3] for CQ, 69.9% (95% CI 60.0-78.3) for SP, and 25.2% (95% CI 17.7-34.5) for AQ. These results provide important missing data on antimalarial drug efficacy in southern Sudan. They indicate that none of the drugs could be used in monotherapy and suggest that even in combination with artemisinin, cure rates might not be efficacious enough. We recommend a combination of artemether and lumefantrine as first-line treatment for uncomplicated P. falciparum malaria cases in Kajo Keji county