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

Multidisciplinary Studies of Disease Burden in the Diseases of the Most Impoverished Programme

With limited healthcare resources, rational prioritization of healthcare interventions requires knowledge and analysis of disease burden. In the absence of actual disease-burden data from less-developed countries, various types of morbidity and mortality estimates have been made. Besides having questionable reliability, these estimates do not capture the full burden of a disease since they provide only the number of cases and deaths. The modelling methods that include disability are more comprehensive but are difficult to understand, and their reliability is affected by baseline approximations. To provide policy-makers with information needed for rational decision-making, the Diseases of the Most Impoverished (DOMI) Programme of the International Vaccine Institute has used a multidisciplinary approach to describe the burden of disease due to typhoid fever, shigellosis, and cholera. Recognizing the relative advantages and disadvantages of various methodologies, the programme employs passive clinic-based surveillance in defined communities to provide prospective data. The prospective data are complemented with retrospectively-collected information from existing sources, frequently less accurate and complete but readily available for the whole population over extended periods. To create a more complete picture, economic and qualitative studies specific to each disease are incorporated in these prospective studies. The goal is to achieve a more complete and realistic picture by combining the results of these various methodologies, acknowledging the strengths and limitations of each. These projects also build in-country capacity in terms of treatment, diagnosis, epidemiology, and data management

Healthcare use for diarrhoea and dysentery in actual and hypothetical cases, Nha Trang, Viet Nam.

To better understand healthcare use for diarrhoea and dysentery in Nha Trang, Viet Nam, qualitative interviews with community residents and dysentery case studies were conducted. Findings were supplemented by a quantitative survey which asked respondents which healthcare provider their household members would use for diarrhoea or dysentery. A clear pattern of healthcare-seeking behaviours among 433 respondents emerged. More than half of the respondents self-treated initially. Medication for initial treatment was purchased from a pharmacy or with medication stored at home. Traditional home treatments were also widely used. If no improvement occurred or the symptoms were perceived to be severe, individuals would visit a healthcare facility. Private medical practitioners are playing a steadily increasing role in the Vietnamese healthcare system. Less than a quarter of diarrhoea patients initially used government healthcare providers at commune health centres, polyclinics, and hospitals, which are the only sources of data for routine public-health statistics. Given these healthcare-use patterns, reported rates could significantly underestimate the real disease burden of dysentery and diarrhoea

Reduced Risk of Malaria Parasitemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study

BACKGROUND: In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin-combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross-sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55). CONCLUSIONS/SIGNIFICANCE: Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission

Comparisons of predictors for typhoid and paratyphoid fever in Kolkata, India

BACKGROUND: Exposure of the individual to contaminated food or water correlates closely with the risk for enteric fever. Since public health interventions such as water improvement or vaccination campaigns are implemented for groups of individuals we were interested whether risk factors not only for the individual but for households, neighbourhoods and larger areas can be recognised? METHODS: We conducted a large enteric fever surveillance study and analyzed factors which correlate with enteric fever on an individual level and factors associated with high and low risk areas with enteric fever incidence. Individual level data were linked to a population based geographic information systems. Individual and household level variables were fitted in Generalized Estimating Equations (GEE) with the logit link function to take into account the likelihood that household factors correlated within household members. RESULTS: Over a 12-month period 80 typhoid fever cases and 47 paratyphoid fever cases were detected among 56,946 residents in two bustees (slums) of Kolkata, India. The incidence of paratyphoid fever was lower (0.8/1000/year), and the mean age of paratyphoid patients was older (17.1 years) than for typhoid fever (incidence 1.4/1000/year, mean age 14.7 years). Residents in areas with a high risk for typhoid fever had lower literacy rates and economic status, bigger household size, and resided closer to waterbodies and study treatment centers than residents in low risk areas. CONCLUSION: There was a close correlation between the characteristics detected based on individual cases and characteristics associated with high incidence areas. Because the comparison of risk factors of populations living in high versus low risk areas is statistically very powerful this methodology holds promise to detect risk factors associated with diseases using geographic information systems

ANALYSIS OF FUNCTIONS FOR THE EXTRAPOLATION OF RHEOLOGICAL PHENOMENA OF PRESTRESSING STEEL

BACKGROUND: The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context. The article explores how these factors influenced attitudes and behaviours towards TMT in Kayin (Karen) State, Myanmar. METHODS: Semi-structured interviews were conducted with villagers from study villages (N = 31) and TMT project staff (N = 14) between March and July 2015. RESULTS: Community engagement consisted of a range of activities to communicate the local malaria situation (including anti-malarial drug resistance and asymptomatic malaria), the aims of the TMT project, and its potential benefits. Community engagement was seen by staff as integral to the TMT project as a whole and not a sub-set of activities. Attitudes towards TMT (including towards community engagement) showed that developing trusting relationships helped foster participation. After initial wariness, staff received hospitality and acceptance among villagers. Offering healthcare alongside TMT proved mutually beneficial for the study and villagers. A handful of more socially-mobile and wealthy community members were reluctant to participate. The challenges of community engagement included time constraints and the isolation of the community with its limited infrastructure and a history of conflict. CONCLUSIONS: Community engagement had to be responsive to the local community even though staff faced time constraints. Understanding the social context of engagement helped TMT to foster respectful and trusting relationships. The complex relationship between the local context and community engagement complicated evaluation of the community strategy. Nonetheless, the project did record high levels of population coverage.</p

Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to identify and compare factors associated with <it>Plasmodium falciparum </it>gametocyte carriage in three regions of differing malaria endemicity.</p> <p>Methods</p> <p>Retrospective data from Thailand, The Gambia and Tanzania were used. The data came from large prospective field-based clinical trials, which investigated gametocyte carriage after different anti-malarial drug treatments.</p> <p>Results</p> <p>Gametocytaemia was detected during the observation period in 12% of patients (931 out of 7548) in Thailand, 34% (683 out of 2020) in The Gambia, and 31% (430 out of 1400) in Tanzania (p < 0.001). Approximately one third (33%, 680/2044) of the patients with gametocytaemia during the observation period, already had patent gametocytaemia at enrolment (day 0 or day 1): 35% (318/931) in Thailand, 37% (250/683) in The Gambia, 26% (112/430) in Tanzania. Maximum gametocytaemia was usually observed on or before the seventh day after starting treatment (93% in Thailand, 70% in Tanzania and 78% in The Gambia). Lowest gametocyte carriage rates were observed following treatment with artemisinin derivatives, while sulphadoxine-pyrimethamine (SP) was associated with significantly greater development of gametocytaemia than other drug treatments (p < 0.001). The duration of gametocyte carriage was shorter in Thailand by 86% and Tanzania by 65% than in The Gambia. Gametocyte carriage was 27% longer among people presenting with anaemia, and was shorter in duration among patients who received artemisinin derivatives, by 27% in Thailand and by 71% in Tanzania and The Gambia.</p> <p>Conclusion</p> <p>This study confirms the independent association of gametocytaemia with anaemia, and the significantly lower prevalence and duration of gametocyte carriage following treatment with an artemisinin derivative. The large differences in gametocyte carriage rates between regions with different levels of malaria transmission suggest that drug interventions to prevent transmission will have different effects in different places.</p

Recommendations for building out mosquito-transmitted diseases in sub-Saharan Africa: the DELIVER mnemonic

In sub-Saharan Africa, most transmission of mosquito-transmitted diseases, such as malaria or dengue, occurs within or around houses. Preventing mosquito house entry and reducing mosquito production around the home would help reduce the transmission of these diseases. Based on recent research, we make key recommendations for reducing the threat of mosquito-transmitted diseases through changes to the built environment. The mnemonic, DELIVER, recommends the following best practices: (i) Doors should be screened, self-closing and without surrounding gaps; (ii) Eaves, the space between the wall and roof, should be closed or screened; (iii) houses should be Lifted above the ground; (iv) Insecticide-treated nets should be used when sleeping in houses at night; (v) houses should be Ventilated, with at least two large-screened windows to facilitate airflow; (vi) Environmental management should be conducted regularly inside and around the home; and (vii) Roofs should be solid, rather than thatch. DELIVER is a package of interventions to be used in combination for maximum impact. Simple changes to the built environment will reduce exposure to mosquito-transmitted diseases and help keep regions free from these diseases after elimination. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'

Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria.

Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)