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1.
Background
African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed.Methods
Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1–15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed.Results
Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%–57.1%) in children 1–15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%–27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%–77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR) = 0.6; 95%CI: 0.4–0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3–0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5–0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0–1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1–4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3–2.4) versus other roofing materials and bigger household size (8–15 people: OR = 1.6; 95%CI: 1.3–2.1) versus small households (1–4 persons).Conclusion
Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs. 相似文献2.
Dicko A Barry A Dicko M Diallo AI Tembine I Dicko Y Dara N Sidibe Y Santara G Conaré T Chandramohan D Cousens S Milligan PJ Diallo DA Doumbo OK Greenwood B 《PloS one》2011,6(8):e23390
Background
Intermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by >80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.Methods
Morbidity from malaria and the prevalence of malaria parasitaemia and anaemia were measured in children who had previously received IPTc with SP and AQ using similar surveillance methods to those employed during the previous intervention period.Results
1396 of 1508 children (93%) who had previously received IPTc and 1406 of 1508 children (93%) who had previously received placebos were followed up during the high malaria transmission season of the year following the intervention. Incidence rates of clinical malaria during the post-intervention transmission season (July –November 2009) were 1.87 (95% CI 1.76 –1.99) and 1.73 (95% CI; 1.62–1.85) episodes per child year in the previous intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09 (95% CI 0.99 –1.21) (P = 0.08). The prevalence of malaria infection was similar in the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73–1.33) (P = 0.95). At the end of post-intervention malaria transmission season, the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91 – 1.12]) (P = 0.84).Conclusion
IPTc with SP+AQ was not associated with an increase in incidence of malaria episodes, prevalence of malaria infection or anaemia in the subsequent malaria transmission season.Trial Registration
ClinicalTrials.gov NCT00738946 相似文献3.
Boel M Carrara VI Rijken M Proux S Nacher M Pimanpanarak M Paw MK Moo O Gay H Bailey W Singhasivanon P White NJ Nosten F McGready R 《PLoS neglected tropical diseases》2010,4(11):e887
Background
Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.Methodology
Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed.Principal Findings
Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23–0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11–0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06–2.60) and anaemia (AOR: 2.41, 95% CI: 1.18–4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02–3.23).Conclusion/Significance
A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy. 相似文献4.
Konaté AT Yaro JB Ouédraogo AZ Diarra A Gansané A Soulama I Kangoyé DT Kaboré Y Ouédraogo E Ouédraogo A Tiono AB Ouédraogo IN Chandramohan D Cousens S Milligan PJ Sirima SB Greenwood BM Diallo DA 《PloS one》2011,6(8):e23391
Background
Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention.Methods
An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3–59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted.Results
On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67–4.02) and 3.45 (95%CI; 3.29–3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04–1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79–0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb<8 g/dL), wasting, stunting, or of being underweight in children differed between treatment arms.Conclusion
IPT with SP+AQ was associated with a small increase in the incidence of clinical malaria in the subsequent malaria transmission season.Trial Registration
ClinicalTrials.gov NCT00738946 相似文献5.
van den Bogaart E Berkhout MM Adams ER Mens PF Sentongo E Mbulamberi DB Straetemans M Schallig HD Chappuis F 《PLoS neglected tropical diseases》2012,6(4):e1617
Background and methodology
Due to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000–2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients'' characteristics and the occurrence of the co-infection.Results
Of 2414 patients with confirmed VL, 450 (19%) were positively diagnosed with concomitant malaria. Most co-infected patients were males, residing in Kenya (69%). While young age was identified by multivariate analysis as a risk factor for concurrent VL and malaria, particularly the age groups 0–4 (odds ratio (OR): 2.44; 95% confidence interval (CI): 1.52–3.92) and 5–9 years (OR: 2.23, 95% CI: 1.45-3-45), mild (OR: 0.53; 95% CI: 0.32–0.88) and moderate (OR: 0.45; 95% CI: 0.27–0.77) anemia negatively correlated with the co-morbidity. VL patients harboring skin infections were nearly three times less likely to have the co-infection (OR: 0.35; 95% CI: 0.17–0.72), as highlighted by the multivariate model. Anorexia was slightly more frequent among co-infected patients (OR: 1.71; 95% CI: 0.96–3.03). The in-hospital case-fatality rate did not significantly differ between cases and controls, being 2.7% and 3.1% respectively (OR: 0.87; 95% CI: 0.46–1.63).Conclusions
Concurrent malaria represents a common condition among young VL patients living in the Pokot region of Kenya and Uganda. Although these co-morbidities did not result in a poorer prognosis, possibly due to early detection of malaria, a positive trend towards more severe symptoms was identified, indicating that routine screening of VL patients living in malaria endemic-areas and close monitoring of co-infected patients should be implemented. 相似文献6.
Konaté AT Yaro JB Ouédraogo AZ Diarra A Gansané A Soulama I Kangoyé DT Kaboré Y Ouédraogo E Ouédraogo A Tiono AB Ouédraogo IN Chandramohan D Cousens S Milligan PJ Sirima SB Greenwood B Diallo DA 《PLoS medicine》2011,8(2):e1000408
Background
Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN).Methods and Findings
An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥5,000/µl, was 2.88 (95% confidence interval [CI] 2.70–3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78–0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%–74%) (p<0.001). There was a 69% (95% CI 6%–90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%–69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%–77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%–70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65–1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72–0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3–3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded.Conclusions
IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission.Trial Registration
ClinicalTrials.gov NCT00738946 Please see later in the article for the Editors'' Summary 相似文献7.
Taylor SM Messina JP Hand CC Juliano JJ Muwonga J Tshefu AK Atua B Emch M Meshnick SR 《PloS one》2011,6(1):e16420
Background
Epidemiologic data on malaria are scant in many high-burden countries including the Democratic Republic of the Congo (DRC), which suffers the second-highest global burden of malaria. Malaria control efforts in regions with challenging infrastructure require reproducible and efficient surveillance. We employed new high-throughput molecular testing to characterize the state of malaria control in the DRC and estimate childhood mortality attributable to excess malaria transmission.Methods and Findings
The Demographic and Health Survey was a cross-sectional, population-based cluster household survey of adults aged 15–59 years in 2007 employing structured questionnaires and dried blood spot collection. Parasitemia was detected by real-time PCR, and survey responses measured adoption of malaria control measures and under-5 health indices. The response rate was 99% at the household level, and 8,886 households were surveyed in 300 clusters; from 8,838 respondents molecular results were available. The overall prevalence of parasitemia was 33.5% (95% confidence interval [C.I.] 32–34.9); P. falciparum was the most prevalent species, either as monoinfection (90.4%; 95% C.I. 88.8–92.1) or combined with P. malariae (4.9%; 95% C.I. 3.7–5.9) or P. ovale (0.6%; 95% C.I. 0.1–0.9). Only 7.7% (95% CI 6.8–8.6) of households with children under 5 owned an insecticide-treated bednet (ITN), and only 6.8% (95% CI 6.1–7.5) of under-fives slept under an ITN the preceding night. The overall under-5 mortality rate was 147 deaths per 1,000 live births (95% C.I. 141–153) and between clusters was associated with increased P. falciparum prevalence; based on the population attributable fraction, 26,488 yearly under-5 deaths were attributable to excess malaria transmission.Conclusions
Adult P. falciparum prevalence is substantial in the DRC and is associated with under-5 mortality. Molecular testing offers a new, generalizable, and efficient approach to characterizing malaria endemicity in underserved countries. 相似文献8.
Emerson PM Ngondi J Biru E Graves PM Ejigsemahu Y Gebre T Endeshaw T Genet A Mosher AW Zerihun M Messele A Richards FO 《PLoS neglected tropical diseases》2008,2(3):e197
Background
Amhara Regional State of Ethiopia has a population of approximately 19.6 million, is prone to unstable and epidemic malaria, and is severely affected by trachoma. An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau. To provide baseline data, a survey was conducted during December 2006 to estimate malaria parasite prevalence, malaria indicators, prevalence of trachoma, and trachoma risk factors in households and people of all ages in each of the ten zones of the state, excluding three urban centers (0.4% of the population).Methodology/Principal Findings
The study was designed to provide prevalence estimates at zone and state levels. Using multi-stage cluster random sampling, 16 clusters of 25 households were randomly selected in each of the ten zones. Household heads were interviewed for malaria indicators and trachoma risk factors (N = 4,101). All people were examined for trachoma signs (N = 17,242), and those in even-numbered households provided blood films for malaria parasite detection (N = 7,745); both thick and thin blood films were read.Zonal malaria parasite prevalence ranged from 2.4% to 6.1%, with the overall state-wide prevalence being 4.6% (95% confidence interval (CI): 3.8%–5.6%). The Plasmodium falciparum: Plasmodium vivax ratio ranged from 0.9–2.1 with an overall regional ratio of 1.2. A total of 14.8% of households reported indoor residual spraying in the past year, 34.7% had at least one mosquito net, and 16.1% had one or more long-lasting insecticidal net. Zonal trachoma prevalence (trachomatous inflammation follicular [WHO grade TF] in children aged 1–9 years) ranged from 12.6% to 60.1%, with the overall state-wide prevalence being 32.7% (95% CI: 29.2%–36.5%). State-wide prevalence of trachomatous trichiasis (TT) in persons aged over fifteen was 6.2% (95% CI: 5.3–7.4), and 0.3% (95% CI: 0.2–0.5) in children aged 0–14 years. Overall, an estimated 643,904 persons (lower bound 419,274, upper bound 975,635) have TT and require immediate corrective surgery.Conclusions/Significance
The results provide extensive baseline data to guide planning, implementation, and evaluation of the integrated malaria and trachoma control program in Amhara. The success of the integrated survey is the first step towards demonstration that control of priority neglected tropical diseases can be integrated with one of the “big three” killer diseases. 相似文献9.
Dicko A Diallo AI Tembine I Dicko Y Dara N Sidibe Y Santara G Diawara H Conaré T Djimde A Chandramohan D Cousens S Milligan PJ Diallo DA Doumbo OK Greenwood B 《PLoS medicine》2011,8(2):e1000407
Background
Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established.Methods and Findings
To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p<0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%–99%) (p = 0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%–92%) (p<0.001) during the intervention period and by 46% (95% CI 31%–68%) (p<0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] <8 g/dl) was reduced by 47% (95% CI 15%–67%) (p<0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event.Conclusions
IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions.Trial Registration
ClinicalTrials.gov NCT00738946 Please see later in the article for the Editors'' Summary 相似文献10.
Aims
The main focus of this study is to illustrate the importance of the statistical analysis in the evaluation of the accuracy of malaria diagnostic tests, without admitting a reference test, exploring a dataset (3317) collected in São Tomé and Príncipe.Methods
Bayesian Latent Class Models (without and with constraints) are used to estimate the malaria infection prevalence, together with sensitivities, specificities, and predictive values of three diagnostic tests (RDT, Microscopy and PCR), in four subpopulations simultaneously based on a stratified analysis by age groups (, 5 years old) and fever status (febrile, afebrile).Results
In the afebrile individuals with at least five years old, the posterior mean of the malaria infection prevalence is 3.2% with a highest posterior density interval of [2.3–4.1]. The other three subpopulations (febrile 5 years, afebrile or febrile children less than 5 years) present a higher prevalence around 10.3% [8.8–11.7]. In afebrile children under-five years old, the sensitivity of microscopy is 50.5% [37.7–63.2]. In children under-five, the estimated sensitivities/specificities of RDT are 95.4% [90.3–99.5]/93.8% [91.6–96.0] – afebrile – and 94.1% [87.5–99.4]/97.5% [95.5–99.3] – febrile. In individuals with at least five years old are 96.0% [91.5–99.7]/98.7% [98.1–99.2] – afebrile – and 97.9% [95.3–99.8]/97.7% [96.6–98.6] – febrile. The PCR yields the most reliable results in four subpopulations.Conclusions
The utility of this RDT in the field seems to be relevant. However, in all subpopulations, data provide enough evidence to suggest caution with the positive predictive values of the RDT. Microscopy has poor sensitivity compared to the other tests, particularly, in the afebrile children less than 5 years. This type of findings reveals the danger of statistical analysis based on microscopy as a reference test. Bayesian Latent Class Models provide a powerful tool to evaluate malaria diagnostic tests, taking into account different groups of interest. 相似文献11.
Hsiang MS Hwang J Kunene S Drakeley C Kandula D Novotny J Parizo J Jensen T Tong M Kemere J Dlamini S Moonen B Angov E Dutta S Ockenhouse C Dorsey G Greenhouse B 《PloS one》2012,7(1):e29550
Background
To guide malaria elimination efforts in Swaziland and other countries, accurate assessments of transmission are critical. Pooled-PCR has potential to efficiently improve sensitivity to detect infections; serology may clarify temporal and spatial trends in exposure.Methodology/Principal Findings
Using a stratified two-stage cluster, cross-sectional design, subjects were recruited from the malaria endemic region of Swaziland. Blood was collected for rapid diagnostic testing (RDT), pooled PCR, and ELISA detecting antibodies to Plasmodium falciparum surface antigens. Of 4330 participants tested, three were RDT-positive yet false positives by PCR. Pooled PCR led to the identification of one P. falciparum and one P. malariae infection among RDT-negative participants. The P. falciparum-infected participant reported recent travel to Mozambique. Compared to performing individual testing on thousands of samples, PCR pooling reduced labor and consumable costs by 95.5%. Seropositivity was associated with age ≥20 years (11·7% vs 1·9%, P<0.001), recent travel to Mozambique (OR 4.4 [95% CI 1.0–19.0]) and residence in southeast Swaziland (RR 3.78, P<0.001).Conclusions
The prevalence of malaria infection and recent exposure in Swaziland are extremely low, suggesting elimination is feasible. Future efforts should address imported malaria and target remaining foci of transmission. Pooled PCR and ELISA are valuable surveillance tools for guiding elimination efforts. 相似文献12.
Duncan CJ Sheehy SH Ewer KJ Douglas AD Collins KA Halstead FD Elias SC Lillie PJ Rausch K Aebig J Miura K Edwards NJ Poulton ID Hunt-Cooke A Porter DW Thompson FM Rowland R Draper SJ Gilbert SC Fay MP Long CA Zhu D Wu Y Martin LB Anderson CF Lawrie AM Hill AV Ellis RD 《PloS one》2011,6(7):e22271
Background
Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.Methods
In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.Results
A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = −0.93 [95% CI: −1.0, −0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = −0.93 [95% CI: −0.99, −0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5–9], control group median 9 days [range 7–9]).Conclusions
Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.Trial Registration
ClinicalTrials.gov [NCT00984763] 相似文献13.
14.
Bruneel F Tubach F Corne P Megarbane B Mira JP Peytel E Camus C Schortgen F Azoulay E Cohen Y Georges H Meybeck A Hyvernat H Trouillet JL Frenoy E Nicolet L Roy C Durand R Le Bras J Wolff M;Severe Imported Malaria in Adults 《PloS one》2010,5(10):e13236
Background
Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit.Methodology and Principal Findings
Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000–2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses.Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths). By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28–2.32; P = 0.0004), Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20–1.45; P<0.0001), and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22–1.62; P<0.0001).Conclusions and Significance
In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available. 相似文献15.
Objective
We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period.Methods
A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group.Principal Findings
AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7–38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3–2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01).Conclusions
Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested. 相似文献16.
Wilson AL;IPTc Taskforce 《PloS one》2011,6(2):e16976
Background
Intermittent preventive treatment of malaria in children less than five years of age (IPTc) has been investigated as a measure to control the burden of malaria in the Sahel and sub-Sahelian areas of Africa where malaria transmission is markedly seasonal.Methods and Findings
IPTc studies were identified using a systematic literature search. Meta-analysis was used to assess the protective efficacy of IPTc against clinical episodes of falciparum malaria. The impact of IPTc on all-cause mortality, hospital admissions, severe malaria and the prevalence of parasitaemia and anaemia was investigated. Three aspects of safety were also assessed: adverse reactions to study drugs, development of drug resistance and loss of immunity to malaria. Twelve IPTc studies were identified: seven controlled and five non-controlled trials. Controlled studies demonstrated protective efficacies against clinical malaria of between 31% and 93% and meta-analysis gave an overall protective efficacy of monthly administered IPTc of 82% (95%CI 75%–87%) during the malaria transmission season. Pooling results from twelve studies demonstrated a protective effect of IPTc against all-cause mortality of 57% (95%CI 24%–76%) during the malaria transmission season. No serious adverse events attributable to the drugs used for IPTc were observed in any of the studies. Data from three studies that followed children during the malaria transmission season in the year following IPTc administration showed evidence of a slight increase in the incidence of clinical malaria compared to children who had not received IPTc.Conclusions
IPTc is a safe method of malaria control that has the potential to avert a significant proportion of clinical malaria episodes in areas with markedly seasonal malaria transmission and also appears to have a substantial protective effect against all-cause mortality. These findings indicate that IPTc is a potentially valuable tool that can contribute to the control of malaria in areas with markedly seasonal transmission. 相似文献17.
Philip Bejon Tabitha W. Mwangi Brett Lowe Norbert Peshu Adrian V. S. Hill Kevin Marsh 《PLoS neglected tropical diseases》2008,2(2)
Background
Helminth infection is common in malaria endemic areas, and an interaction between the two would be of considerable public health importance. Animal models suggest that helminth infections may increase susceptibility to malaria, but epidemiological data has been limited and contradictory.Methodology/Principal Findings
In a vaccine trial, we studied 387 one- to six-year-old children for the effect of helminth infections on febrile Plasmodium falciparum malaria episodes. Gastrointestinal helminth infection and eosinophilia were prevalent (25% and 50% respectively), but did not influence susceptibility to malaria. Hazard ratios were 1 for gastrointestinal helminth infection (95% CI 0.6–1.6) and 0.85 and 0.85 for mild and marked eosinophilia, respectively (95% CI 0.56–1.76 and 0.69–1.96). Incident rate ratios for multiple episodes were 0.83 for gastro-intestinal helminth infection (95% CI 0.5–1.33) and 0.86 and 0.98 for mild and marked eosinophilia (95% CI 0.5–1.4 and 0.6–1.5).Conclusions/Significance
There was no evidence that infection with gastrointestinal helminths or urinary schistosomiasis increased susceptibility to Plasmodium falciparum malaria in this study. Larger studies including populations with a greater prevalence of helminth infection should be undertaken. 相似文献18.
Background
Cross-sectional serosurveys using IgG antibody to pertussis toxin (IgG-PT) are increasingly being used to estimate trends in recent infection independent of reporting biases.Methods/Principal Findings
We compared the age-specific seroprevalence of various levels of IgG-PT in cross-sectional surveys using systematic collections of residual sera from Australian diagnostic laboratories in 1997/8, 2002 and 2007 with reference to both changes in the pertussis vaccine schedule and the epidemic cycle, as measured by disease notifications. A progressive decline in high-level (≥62.5 EU/ml) IgG-PT prevalence from 19% (95% CI 16–22%) in 1997/98 to 12% (95% CI 11–14%) in 2002 and 5% (95% CI 4–6%) in 2007 was consistent with patterns of pertussis notifications in the year prior to each collection. Concomitantly, the overall prevalence of undetectable (<5 EU/ml) levels increased from 17% (95% CI 14–20%) in 1997/98 to 38% (95% CI 36–40%) in 2007 but among children aged 1–4 years, from 25% (95% CI 17–34%) in 1997/98 to 62% (95% CI 56–68%) in 2007. This change followed withdrawal of the 18-month booster dose in 2003 and preceded record pertussis notifications from 2008 onwards.Conclusions/Significance
Population seroprevalence of high levels of IgG-PT is accepted as a reliable indicator of pertussis disease activity over time within and between countries with varying diagnostic practices, especially in unimmunised age groups. Our novel findings suggest that increased prevalence of undetectable IgG-PT is an indicator of waning immunity useful for population level monitoring following introduction of acellular vaccines and/or schedule changes. 相似文献19.
Background
Around 8.8 million children under-five die each year, mostly due to infectious diseases, including malaria that accounts for 16% of deaths in Africa, but the impact of international financing of malaria control on under-five mortality in sub-Saharan Africa has not been examined.Methods and Findings
We combined multiple data sources and used panel data regression analysis to study the relationship among investment, service delivery/intervention coverage, and impact on child health by observing changes in 34 sub-Saharan African countries over 2002–2008. We used Lives Saved Tool to estimate the number of lives saved from coverage increase of insecticide-treated nets (ITNs)/indoor residual spraying (IRS). As an indicator of outcome, we also used under-five mortality rate. Global Fund investments comprised more than 70% of the Official Development Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for malaria enabled distribution of 50,478 ITNs [95%CI: 37,774–63,182] in the disbursement year. 1,000 additional ITNs distributed saved 0.625 lives [95%CI: 0.369–0.881]. Cumulatively Global Fund investments that increased ITN/IRS coverage in 2002–2008 prevented an estimated 240,000 deaths. Countries with higher malaria burden received less ODA disbursement per person-at-risk compared to lower-burden countries ($3.90 vs. $7.05). Increased ITN/IRS coverage in high-burden countries led to 3,575 lives saved per 1 million children, as compared with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under-five mortality was significant among major child health interventions such as immunisation showing that 10% increase in households with ITN/IRS would reduce 1.5 [95%CI: 0.3–2.8] child deaths per 1000 live births.Conclusions
Along with other key child survival interventions, increased ITNs/IRS coverage has significantly contributed to child mortality reduction since 2002. ITN/IRS scale-up can be more efficiently prioritized to countries where malaria is a major cause of child deaths to save greater number of lives with available resources. 相似文献20.
Mpimbaza A Filler S Katureebe A Kinara SO Nzabandora E Quick L Ratcliffe A Wabwire-Mangen F Chandramohan D Staedke SG 《PloS one》2011,6(10):e26892