Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial

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 {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946 Please see later in the article for the Editors'' Summary     

Malaria morbidity in children in the year after they had received intermittent preventive treatment of malaria in Mali: a randomized control trial

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 {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Morbidity from malaria in children in the year after they had received intermittent preventive treatment of malaria: a randomised trial

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 {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial

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 {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946 Please see later in the article for the Editors'' Summary     

HIV incidence among men who have sex with men in China: a meta-analysis of published studies

Background

Men who have sex with men (MSM) have now become one of the priority populations for prevention and control of HIV pandemic in China. Information of HIV incidence among MSM is important to describe the spreading of the infection and predict its trends in this population. We reviewed the published literature on the incidence of HIV infection among MSM in China.

Methods

We identified relevant studies by use of a comprehensive strategy including searches of Medline and two Chinese electronic publication databases from January 2005 to September 2010. Point estimate of random effects incidence with corresponding 95% confidence intervals (CI) of HIV infection was carried out using the Comprehensive Meta-Analysis software. Subgroup analyses were examined separately, stratified by study design and geographic location.

Results

Twelve studies were identified, including three cohort studies and nine cross-sectional studies. The subgroup analyses revealed that the sub-overall incidence estimates were 3.5% (95% CI, 1.7%–5.3%) and 6.7% (95% CI, 4.8%–8.6%) for cohort and cross-sectional studies, respectively (difference between the sub-overalls, Q = 5.54, p = 0.02); and 8.3% (95% CI, 6.9%–9.7%) and 4.6% (95% CI, 2.4%–6.9%) for studies in Chongqing and other areas, respectively (difference between the sub-overalls, Q = 7.58, p<0.01). Syphilis infection (RR = 3.33, p<0.001), multiple sex partnerships (RR = 2.81, p<0.001), and unprotected receptive anal intercourse in the past six months (RR = 3.88, p = 0.007) represented significant risk for HIV seroconversion.

Conclusions

Findings from this meta-analysis indicate that HIV incidence is substantial in MSM in China. High incidence of HIV infection and unique patterns of sexual risk behaviors in this population serve as a call for action that should be answered with the innovative social and public health intervention strategies, and development of biological prevention strategies.     

High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS versus increased risks due to pig-keeping and house construction

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.     

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic

Background

Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use.

Methods

1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.

Findings

Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN''s use was more than 90% in both groups.

Conclusions

Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

Differing burden and epidemiology of non-Typhi Salmonella bacteremia in rural and urban Kenya, 2006-2009

Background

The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change.

Methods

As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006–2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured.

Results

NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman''s correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy.

Conclusions

NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa.     

Renal Function Declines More in Tenofovir- than Abacavir-Based Antiretroviral Therapy in Low-Body Weight Treatment-Na?ve Patients with HIV Infection

Objective

To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART) in low-body weight treatment-naïve patients with HIV infection.

Design

We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART.

Methods

The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR) from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model.

Results

The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152–2.648; p = 0.009) (adjusted HR = 2.080; 95% CI, 1.339–3.232; p<0.001). In subgroup analysis of the patients stratified by intertertile baseline body weight, the effect of tenofovir on renal dysfunction was more evident in patients with lower baseline body weight by multivariate analysis (≤60 kg: adjusted HR = 2.771; 95%CI, 1.494–5.139; p = 0.001) (61–68 kg: adjusted HR = 1.908; 95%CI, 0.764–4.768; p = 0.167) (>68 kg: adjusted HR = 0.997; 95%CI, 0.318–3.121; p = 0.995). The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003).

Conclusion

The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight <60 kg treated with tenofovir.     

Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015

Objective

The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.

Design

Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.

Results

Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.

Conclusion

Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.     

Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast

Background

The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies.

Methods

On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995)

Results

The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005–2006 to 87% in 2007–2008 (odds ratio, 5.4, 95%CI, 2.7–11.1; P<0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7–9.9; P = 0.002) in the DHA-PPQ and AM-LM groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005–2006 and 2007–2008 (OR body temperature >37.5°C, 2.8, 1.9–4.1; P<0.001). Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof.

Conclusions

The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better understanding of the mechanisms underlying reduced parasite clearance rates.

Trial Registration

Controlled-Trials.com ISRCTN88705995     

Iron deficiency and acute seizures: results from children living in rural Kenya and a meta-analysis

Background

There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area.

Methods

We recruited 133 children, aged 3–156 months, who presented to a district hospital on the Kenyan coast with acute seizures and frequency-matched these to children of similar ages but without seizures. We defined iron deficiency according to the presence of malarial infection and evidence of inflammation. In patients with malaria, we defined iron deficiency as plasma ferritin<30µg/ml if plasma C-reactive protein (CRP) was<50mg/ml or ferritin<273µg/ml if CRP≥50mg/ml, and in those without malaria, as ferritin<12µg/ml if CRP<10mg/ml or ferritin<30µg/ml if CRP≥10mg/ml. In addition, we performed a meta-analysis of case-control studies published in English between January 1966 and December 2009 and available through PUBMED that have examined the relationship between iron deficiency and febrile seizures in children.

Results

In our Kenyan case control study, cases and controls were similar, except more cases reported past seizures. Malaria was associated with two-thirds of all seizures. Eighty one (30.5%) children had iron deficiency. Iron deficiency was neither associated with an increased risk of acute seizures (45/133[33.8%] cases were iron deficient compared to 36/133[27.1%] controls, p = 0.230) nor status epilepticus and it did not affect seizure semiology. Similar results were obtained when children with malaria, known to cause acute symptomatic seizures in addition to febrile seizures were excluded. However, in a meta-analysis that combined all eight case-control studies that have examined the association between iron deficiency and acute/febrile seizures to-date, iron deficiency, described in 310/1,018(30.5%) cases and in 230/1,049(21.9%) controls, was associated with a significantly increased risk of seizures, weighted OR 1.79(95%CI 1.03–3.09).

Conclusions

Iron deficiency is not associated with an increased risk of all acute seizures in children but of febrile seizures. Further studies should examine mechanisms involved and the implications for public health.     

Epidemiology of malaria, schistosomiasis, geohelminths, anemia and malnutrition in the context of a demographic surveillance system in northern Angola

Background

Malaria, schistosomiasis and geohelminth infection are linked to maternal and child morbidity and mortality in sub-Saharan Africa. Knowing the prevalence levels of these infections is vital to guide governments towards the implementation of successful and cost-effective disease control initiatives.

Methodology/Principal Findings

A cross-sectional study of 1,237 preschool children (0–5 year olds), 1,142 school-aged children (6–15 year olds) and 960 women (>15 year olds) was conducted to understand the distribution of malnutrition, anemia, malaria, schistosomiasis (intestinal and urinary) and geohelminths in a north-western province of Angola. We used a recent demographic surveillance system (DSS) database to select and recruit suitable households. Malnutrition was common among children (23.3% under-weight, 9.9% wasting and 32.2% stunting), and anemia was found to be a severe public health problem (i.e., >40%). Malaria prevalence was highest among preschool children reaching 20.2%. Micro-hematuria prevalence levels reached 10.0% of preschool children, 16.6% of school-aged children and 21.7% of mothers. Geohelminth infections were common, affecting 22.3% of preschool children, 31.6% of school-aged children and 28.0% of mothers.

Conclusions

Here we report prevalence levels of malaria, schistosomiasis and geohelminths; all endemic in this poorly described area where a DSS has been recently established. Furthermore we found evidence that the studied infections are associated with the observed levels of anemia and malnutrition, which can justify the implementation of integrated interventions for the control of these diseases and morbidities.     

Gender differences in traditional Chinese medicine use among adults in Taiwan

Objectives

The increasing use of complementary, alternative medicine (CAM) and traditional Chinese medicine (TCM) has attracted attention. We report on the gender difference in TCM use among the general population in Taiwan in a population-based, cross-sectional study.

Methods

We collected data on socio-demographic factors, lifestyle and health behavior from the 2001 Taiwan National Health Interview Survey. The medical records of interviewees aged 20–69 years were obtained from National Health Insurance claims data with informed consent. The prevalence of TCM use and the average frequency of TCM use were compared between women and men.

Results

Among 14,064 eligible participants, the one-year prevalence of TCM use for women and men was 31.8% and 22.4%, respectively. Compared with men, women had a higher average TCM use frequency (1.55 visits vs. 1.04 visits, p<0.001). This significant difference remained evident after excluding gender-specific diseases (1.43 visits vs. 1.03 visits, p<0.001). The average TCM use frequency was significantly higher in women than in men across all age groups. TCM use correlates differed for women and men. Marital status (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.30–1.85), family income and unhealthy lifestyle (OR = 1.50, 95% CI = 1.30–1.74) were factors associated with TCM use in men but not in women.

Conclusions

In Taiwan, women used more TCM services than men and the gender differences in the TCM use profile persisted across age groups.     

Net benefits: a multicountry analysis of observational data examining associations between insecticide-treated mosquito nets and health outcomes

Background

Several sub-Saharan African countries have rapidly scaled up the number of households that own insecticide-treated mosquito nets (ITNs). Although the efficacy of ITNs in trials has been shown, evidence on their impact under routine conditions is limited to a few countries and the extent to which the scale-up of ITNs has improved population health remains uncertain.

Methods and Findings

We used matched logistic regression to assess the individual-level association between household ITN ownership or use in children under 5 years of age and the prevalence of parasitemia among children using six malaria indicator surveys (MIS) and one demographic and health survey. We used Cox proportional hazards models to assess the relationship between ITN household ownership and child mortality using 29 demographic and health surveys. The pooled relative reduction in parasitemia prevalence from random effects meta-analysis associated with household ownership of at least one ITN was 20% (95% confidence interval [CI] 3%–35%; I ² = 73.5%, p<0.01 for I ² value). Sleeping under an ITN was associated with a pooled relative reduction in parasitemia prevalence in children of 24% (95% CI 1%–42%; I ² = 79.5%, p<0.001 for I ² value). Ownership of at least one ITN was associated with a pooled relative reduction in mortality between 1 month and 5 years of age of 23% (95% CI 13–31%; I ² = 25.6%, p>0.05 for I ² value).

Conclusions

Our findings across a number of sub-Saharan African countries were highly consistent with results from previous clinical trials. These findings suggest that the recent scale-up in ITN coverage has likely been accompanied by significant reductions in child mortality and that additional health gains could be achieved with further increases in ITN coverage in populations at risk of malaria. Please see later in the article for the Editors'' Summary     

Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults

Background

Antibodies that impair Plasmodium falciparum merozoite invasion and intraerythrocytic development are one of several mechanisms that mediate naturally acquired immunity to malaria. Attempts to correlate anti-malaria antibodies with risk of infection and morbidity have yielded inconsistent results. Growth inhibition assays (GIA) offer a convenient method to quantify functional antibody activity against blood stage malaria.

Methods

A treatment-time-to-infection study was conducted over 12-weeks in a malaria holoendemic area of Kenya. Plasma collected from healthy individuals (98 children and 99 adults) before artemether-lumefantrine treatment was tested by GIA in three separate laboratories.

Results

Median GIA levels varied with P. falciparum line (D10, 8.8%; 3D7, 34.9%; FVO, 51.4% inhibition). The magnitude of growth inhibition decreased with age in all P. falciparum lines tested with the highest median levels among children <4 years compared to adults (e.g. 3D7, 45.4% vs. 30.0% respectively, p = 0.0003). Time-to-infection measured by weekly blood smears was significantly associated with level of GIA controlling for age. Upper quartile inhibition activity was associated with less risk of infection compared to individuals with lower levels (e.g. 3D7, hazard ratio = 1.535, 95% CI = 1.012–2.329; p = 0.0438). Various GIA methodologies had little effect on measured parasite growth inhibition.

Conclusion

Plasma antibody-mediated growth inhibition of blood stage P. falciparum decreases with age in residents of a malaria holoendemic area. Growth inhibition assay may be a useful surrogate of protection against infection when outcome is controlled for age.     

Barriers to insecticide-treated mosquito net possession 2 years after a mass free distribution campaign in Luangwa District, Zambia

Background and Methods

Roll Back Malaria set the goal of 100% of households in malaria endemic countries in Africa owning an insecticide-treated mosquito net (ITN) by 2010. Zambia has used mass free distribution campaigns and distribution through antenatal care (ANC) clinics to achieve high coverage.

Methodology and Principal Findings

We conducted a probability survey of 801 households in 2008 to assess factors associated with households that lacked an ITN after mass distribution. Community perceptions of barriers to ITN access were also obtained from in-depth interviews with household heads that reported not owning an ITN. Nearly 74% of households in Luangwa district reported owning ≥1 ITN. Logistic regression showed households without a child <5 years old during the ITN distribution campaigns were twice as likely to not have an ITN as those with a child <5 during distribution (Adjusted odds ratio (AOR)  = 2.43; 95% confidence interval (CI): 1.67–3.55). Households without a woman who attended an ANC in the past 2 years were more likely to be without ITNs compared to households with a woman who attended an ANC in the past 2 years (AOR  = 1.52; 95% CI: 1.04–2.21). In-depth interviews with heads of households without an ITN revealed that old age was a perceived barrier to receiving an ITN during distribution, and that ITNs wore out before they could be replaced.

Conclusions and Significance

Delivery of a large number of ITNs does not translate directly into 100% household coverage. Due to their design, current ITN distribution strategies may miss households occupied by the elderly and those without children or ANC access. ITN distribution strategies targeting the elderly, those with limited access to distribution points, and others most likely to be missed are necessary if 100% ITN coverage of households is to be achieved.     

Body adiposity in later life and the incidence of dementia: the health in men study

Objective

To determine if adiposity in later life increases dementia hazard.

Methods

Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease.

Results

Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR.

Conclusions

Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.     

Knowledge of Malaria and Its Association with Malaria-Related Behaviors—Results from the Malaria Indicator Survey,Ethiopia, 2007

Background

In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers.

Methods and Findings

A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women''s malaria knowledge on household ITN ownership and women''s ITN use. In addition, we investigated the effect of mothers'' malaria knowledge on their children under 5 years of age''s (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n = 5,949) and mothers of children U5 (n = 3,447) reported some knowledge of malaria. Women''s knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR] = 2.1; 95% confidence interval [CI] 1.6–2.7) and with increased ITN use for themselves (aOR = 1.8; 95% CI 1.3–2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR = 1.6; 95% CI 1.1–2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women''s ITN use (aOR = 2.0; 95% CI 1.1–3.9), their children U5′s ITN use (aOR = 4.4; 95% CI 1.6–12.1), and their children U5 having sought treatment for a fever (aOR = 6.5; 95% CI 1.9–22.9).

Conclusions

Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women.     

High and persistent HIV seroincidence in men who have sex with men across 47 U.S. cities

Objective

To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion.

Methods

From 1998–2002, 4684 high-risk MSM, age 18–60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional hazard model with time-varying covariates.

Results

Overall, HIV incidence was 2.7/100 py and was relatively uniform across study sites and study years. HIV incidence was highest among young men and men reporting unprotected sex, recreational drug use, and a history of a sexually transmitted infection. Independent predictors of HIV seroconversion included: age 18–30 years (aHR = 2.4; 95% CI 1.4,4.0), having >10 partners (aHR = 2.4; 95% CI 1.7,3.3), having a known HIV-positive male sex partner (aHR = 1.6; 95% CI 1.2, 2.0), unprotected anal intercourse with HIV positive/unknown male partners (aHR = 1.7; 95% CI 1.3, 2.3), and amphetamine (aHR = 1.6; 95% CI 1.1, 2.1) and popper (aHR = 1.7; 95% CI 1.3, 2.2) use.

Conclusions

HIV seroincidence was high among MSM despite repeated HIV counseling and reported declines in sexual risk behaviors. Continuing development of new HIV prevention strategies and intensification of existing efforts will be necessary to reduce the rate of new HIV infections, especially among young men.