BackgroundThe Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.Methods and FindingsCross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.ConclusionsFollowing deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

Key Points• Early introduction of cyclosporine did not improve HLH outcome in patients treated with the HLH-94 etoposide-dexamethasone backbone (P 5 .06).• HLH-2004 may be improved by risk-group stratification, less therapy reduction weeks 7 to 8 for verified FHL patients, and earlier HSCT.Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n 5 168) and without (n 5 201) family history/ genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n 5 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P 5 .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P 5 .020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL,(70)(71)(72)(73)(74)(75)(76)(77)(78)). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly. (Blood. 2017;130(25):2728-2738 Medscape Continuing Medical Education onlineIn support of improving patient care, this activity has been planned and

Background: Small intestinal biopsy with villous atrophy (VA) is the gold standard for the diagnosis of celiac disease (CD). We validated VA (Marsh 3) and small intestinal inflammation without VA (Marsh 1+2) in Swedish regional biopsy registers.

Context Studies of mortality in celiac disease have not taken small-intestinal pathology into account. Objective To examine mortality in celiac disease according to small-intestinal histopathology. Design, Setting, and Patients Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n=29 096 individuals) and inflammation (Marsh stage 1-2; n=13 306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n=3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age-and sex-matched controls from the general population. Main Outcome Measure All-cause mortality.

Background-Impaired fetal growth may be a risk factor for asthma although evidence in children is conflicting and there are few data in adults. Little is known about risk factors which may influence asthma in late childhood or early adult life. Whilst there are clues that fatness may be important, this has been little studied in young adults. The relations between birth weight and childhood and adult anthropometry and asthma, wheeze, hayfever, and eczema were investigated in a nationally representative sample of young British adults. Methods-A total of 8960 individuals from the 1970 British Cohort Study (BCS70) were studied. They had recently responded to a questionnaire at 26 years of age in which they were asked whether they had suVered from asthma, wheeze, hayfever, and eczema in the previous 12 months. Adult body mass index (BMI) was calculated from reported height and weight. Results-The prevalence of asthma at 26 years fell with increasing birth weight. After controlling for potential confounding factors, the odds ratio comparing the lowest birth weight group (<2 kg) with the modal group (3-3.5 kg) was 1.99 (95% CI 0.96 to 4.12). The prevalence of asthma increased with increasing adult BMI. After controlling for birth weight and other confounders, the odds ratio comparing highest with lowest quintile was 1.72 (95% CI 1.29 to 2.29). The association between fatness and asthma was stronger in women; odds ratios comparing overweight women (BMI 25-29.99) and obese women (BMI >30) with those of normal weight (BMI <25) were 1.51 (95% CI 1.11 to 2.06) and 1.84 (95% CI 1.19 to 2.84), respectively. The BMI at 10 years was not related to adult asthma. Similar associations with birth weight and adult BMI were present for wheeze but not for hayfever or eczema. Conclusions-Impaired fetal growth and adult fatness are risk factors for adult asthma.

Summary Haemophagocytic lymphohistiocytosis (HLH) poses major therapeutic challenges, and the primary inherited form, familial haemophagocytic lymphohistiocytosis (FHL), is usually fatal. We evaluated, including Cox regression analysis, survival in 86 children (29 familial) that received HLH‐94‐therapy (etoposide, dexamethasone, ciclosporin) followed by allogeneic stem cell transplantation (SCT) between 1995 and 2000. The overall estimated 3‐year‐survival post‐SCT was 64% [confidence interval (CI) = ±10%] (n = 86); 71 ± 18% in those patients with a matched related donor (MRD, n = 24), 70 ± 16% with a matched unrelated donor (MUD, n = 33), 50 ± 24% with a family haploidentical donor (haploidentical, n = 16), and 54 ± 27% with a mismatched unrelated donor (MMUD, n = 13). After adjustment for potential confounding factors, estimated odds ratios (OR) for mortality were 1·93 (CI =0·61–6·19) for MUD, 3·31 (1·02–10·76) for haploidentical, and 3·01 (0·91–9·97) for MMUD, compared with MRD. In children with active disease after 2‐months of therapy (n = 43) the OR was 2·75 (1·26–5·99), compared with inactive disease (n = 43). In children with active disease at SCT (n = 37), the OR was 1·80 (0·80–4·06) compared with inactive disease (n = 49), after adjustment for disease activity at 2‐months. Mortality was predominantly transplant‐related. Most HLH patients survived SCT using MRD or MUD, and survival with partially mismatched donors was also acceptable. Patients that responded well to initial pretransplant‐induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT.

Both treatments were highly efficacious, but AL provided stronger prevention against reinfection. The high proportion of recrudescences found after day 28 and the genetic selection by the long-acting partner drug underlines the importance of long follow-up periods in clinical trials. A long follow-up duration and performance of PCR genotyping should be implemented in programmatic surveillance of antimalarial drugs.

Overall results indicate that policies that offer access to protection and help minimize adversity exposure where possible will promote resilience.