The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data.

BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.

Human rabies post exposure prophylaxis at the Pasteur Institute of Dakar, Senegal: trends and risk factors.

BACKGROUND: Rabies remains a major public health problem in developing countries. Most fatal rabies cases, especially in children, result from dog bites and occur in low-income countries, such as those in Sub-Saharan Africa. Rabies can be controlled through mass dog vaccination and human deaths prevented through timely and appropriate post-exposure prophylaxis (PEP). As access to appropriate PEP remains a serious challenge for bite-victims, the aim of this study was to understand the use of PEP, to evaluate the knowledge, attitudes and practices with respect to rabies and to identify risk factors related to non-compliance with PEP to define recommendations for improving PEP in Senegal. METHODS: This study included patients with suspicion of rabies exposure who sought PEP at the Pasteur Institute of Dakar from April 2013 to March 2014. Patients with rabies clinical symptoms, those who had already started PEP and those with exposure outside Senegal or for more than 3 months were excluded. Data on risk factors and propensity to seek and complete PEP were collected using questionnaires and phone interviews. The association between acceptability and compliance with PEP and other independent variables were evaluated using multivariate regression analysis. RESULTS: Among the 905 patients enrolled into the study, 67% were male (sex ratio M/F, 2) and 46%, children under 15 years of age. Exposures by animal bites represented 87%, whereas the remainder were due to scratches or contact; 76% were classified as WHO category III and 88% were due to dogs. Among these patients, 7% refused to start PEP and 54.5% completed the full schedule. Main factors reported by non-compliant patients were vaccine costs and affordability, and knowledge on status of biting animal. CONCLUSION: This study shows that despite the awareness about rabies dangers and prevention, only half of the patients completed the full PEP schedule. The following recommendations, such as free of charge prophylaxis or intradermal regimens as an alternative to intramuscular regimens, should be considered to increase the adherence to PEP at the Pasteur Institute of Dakar and in Senegal.

The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

BACKGROUND: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. METHODS: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. RESULTS: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. CONCLUSIONS: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.

Landscape review of active vaccine safety surveillance activities for COVID-19 vaccines globally.

Background: Evidence of COVID-19 vaccine safety relied upon the global vaccine monitoring infrastructure due to shortened clinical development timelines and emergency use licensure. Differences in AVSS capacity between high-income countries (HICs) versus low- and middle-income countries (LMICs) were known prior to the pandemic. Objective: To assess the global landscape of COVID-19 vaccine AVSS activities to identify gaps in safety evidence generation across vaccine products and populations with a focus on LMICs. Methods: A cross-sectional survey was conducted in January 2022 on AVSS activities evaluating adverse events following immunization (AEFI). Data collected included country, targeted population, COVID-19 vaccine product(s), design of surveillance/monitoring activities or study, and AEFIs to be monitored.To supplement these findings, we conducted a literature review of COVID-19 vaccine safety activities published in PubMed through January 2023. Observational activities assessing AEFI, specifically adverse events of special interest (AESI), following routine use of COVID-19 vaccines in medical practice were included; systematic reviews, benefit/risk assessments, clinical trials, and case reports/series were excluded. Results: The survey, completed by 34 respondents and compiled with reviews of 7 publicly available Risk Management Plans from five vaccine manufacturers, identified 79 monitoring activities in HICs, 24 in LMICs, and 9 in multiple regions. Most activities in LMICs were planned cohort event monitoring (CEM) studies (n = 18); two multi-national hospital-based sentinel surveillance studies for AESI were ongoing. Activities in LMICs evaluated multiple COVID-19 vaccine products simultaneously and were sponsored by health authorities. The literature review identified 1245 unique citations, of which 379 met inclusion criteria. The majority evaluated vaccines primarily used in high-income countries: Pfizer BioNTech (Comirnaty; n = 303), Moderna (mRNA-1273; n = 164), AstraZeneca (AZD1222; n = 126), and Janssen (Ad26.COV2.S); n = 62); 14 citations assessed vaccines used exclusively in LMICs: Sinovac (CoronaVac), Beijing CNBG (BBIBP-Corv), Bharat (Covaxin), SII (Covashield), and Gamaleya (Gam-Covid-Vac) vaccines. Conclusions: Robust safety evidence for input into benefit/risk assessments is likely unavailable for most COVID-19 vaccines used primarily in LMICs due to emphasis on cohort event monitoring methods. Goals for equitable vaccine access should be coupled with investment and support for building infrastructure and capacity for safety evidence generation to inform policy and regulatory decisions at local levels.

Collaboration within the global vaccine safety surveillance ecosystem during the COVID-19 pandemic: lessons learnt and key recommendations from the COVAX Vaccine Safety Working Group.

This analysis describes the successes, challenges and opportunities to improve global vaccine safety surveillance as observed by the Vaccine Safety Working Group from its role as a platform of exchange for stakeholders responsible for monitoring the safety of vaccines distributed through the COVAX mechanism. Three key elements considered to be essential for ongoing and future pandemic preparedness for vaccine developers in their interaction with other members of the vaccine safety ecosystem are (1) the availability of infrastructure and capacity for active vaccine safety surveillance in low-income and middle-income countries (LMICs), including the advancement of concepts of safety surveillance and risk management to vaccine developers and manufacturers from LMICs; (2) more comprehensive mechanisms to ensure timely exchange of vaccine safety data and/or knowledge gaps between public health authorities and vaccine developers and manufacturers; and (3) further implementation of the concept of regulatory reliance in pharmacovigilance. These aims would both conserve valuable resources and allow for more equitable access to vaccine safety information and for benefit/risk decision-making.

Community-acquired diarrhea among children and adults in urban settings in Senegal: clinical, epidemiological and microbiological aspects.

BACKGROUND: Only limited data are available relating to the etiology of diarrhea in children and adults in Senegal. The aim of this prospective study was to describe the epidemiology and etiology of community-acquired diarrheal infections in children and adults living in urban settings. METHODS: A prospective study was carried out from March 2009 to December 2010, in the urban region of Dakar, Senegal. Patients with acute diarrhea were enrolled, interviewed to collect their clinical history, and their stools were tested for bacteria, virus and parasites. RESULTS: A total of 223 patients (including 112 children younger than five years old) with diarrhea were included. At least one enteropathogen was detected in 81% (180/223) of the patients: 29% (64/223) had bacterial infections (mainly diarrheagenic E. coli and Shigella spp), 21% (39/185) viral infections (mainly rotavirus) and 14% (31/223) parasitic infections. Co-infection was identified in 17.8% (32/180) of the patients. Viral infection was significantly more frequent in children under five years old during the dry season. Bacteria and parasites were equally frequent in all age groups. There was a seasonal variation of bacterial infections during the study period, with a higher proportion of infections being bacterial, and due to Salmonella spp. in particular, during the rainy season. CONCLUSION: Our study suggests that in urban settings in Senegal, rotavirus is the principal cause of pediatric diarrhea during the dry season and that the proportion of bacterial infections seems to be higher during the rainy season. Further work is needed to document the burden of diarrheal diseases in sub-Saharan urban communities and to identify risk factors, including those linked to the rapid and unplanned urbanization in Africa.

Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial.

BACKGROUND: In 2005, the Democratic Republic of Congo (DRC) adopted artesunate and amodiaquine (ASAQ) as first-line anti-malarial treatment. In order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL), a randomized, non-inferiority open-label trial was conducted in Katanga. METHODS: Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolled and randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. RESULTS: Between April 2008 and March 2009, 301 children were included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131) in the ASAQ group and 15.2% (19/125) in the AL group). After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8) in the ASAQ group and 99.1% (95%CI, 94.9-99.9) in the AL group (difference -0.7%, one sided 95% CI -3.1). Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. CONCLUSION: Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country, such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces. TRIAL REGISTRATION: The protocol was registered with the clinicaltrials.gov, open clinical trial registry under the identifier number NCT01567423.

A Bayesian evidence synthesis for estimating campylobacteriosis prevalence.

Stakeholders making decisions in public health and world trade need improved estimations of the burden-of-illness of foodborne infectious diseases. In this article, we propose a Bayesian meta-analysis or more precisely a Bayesian evidence synthesis to assess the burden-of-illness of campylobacteriosis in France. Using this case study, we investigate campylobacteriosis prevalence, as well as the probabilities of different events that guide the disease pathway, by (i) employing a Bayesian approach on French and foreign human studies (from active surveillance systems, laboratory surveys, physician surveys, epidemiological surveys, and so on) through the chain of events that occur during an episode of illness and (ii) including expert knowledge about this chain of events. We split the target population using an exhaustive and exclusive partition based on health status and the level of disease investigation. We assume an approximate multinomial model over this population partition. Thereby, each observed data set related to the partition brings information on the parameters of the multinomial model, improving burden-of-illness parameter estimates that can be deduced from the parameters of the basic multinomial model. This multinomial model serves as a core model to perform a Bayesian evidence synthesis. Expert knowledge is introduced by way of pseudo-data. The result is a global estimation of the burden-of-illness parameters with their accompanying uncertainty.

Against the odds: psychomotor development of children under 2 years in a Sudanese orphanage.

Providing abandoned children the necessary medical and psychological care as possible after their institutionalization may minimize developmental delays. We describe psychomotor development in infants admitted to an orphanage in Khartoum, Sudan, assessed at admission and over an 18-month follow-up. Psychological state and psychomotor quotients were determined using a simplified Neonatal Behavior Assessment Scale (NBAS), the Brunet-Lezine and Alarm distress baby (ADBB) scale. From May-September 2005, 151 children were evaluated 2, 4, 9, 12 and 18 months after inclusion. At admission, ~15% of children ≤1 month had a regulation impairment according to the NBAS, and 33.8% presented a distress state (ADBB score >5). More than 85% (129/151) recovered normal psychomotor development. The results of the program reinforce the importance of early detection of psychological disorders followed by rapid implementation of psychological case management to improve the development of young children in similar institutions and circumstances.

Acute malnutrition and under-5 mortality, northeastern part of India.

We assessed the prevalence of childhood acute malnutrition and under-five mortality rate (U5MR) in Darbhanga district, India, using a two-stage 49-cluster household survey. A total of 1379 households comprising 8473 people were interviewed. During a 90-day recall period, U5MR was 0.5 [95% confidence interval (CI), 0.2-1.4] per 10,000 per day. The prevalence of global acute malnutrition among 1405 children aged 6-59 months was 15.4% (NCHS) and 19.4% (2006 WHO references). This survey suggests that in Darbhanga district, the population is in a borderline food crisis with few food resources. Appropriate strategies should be developed to improve the overall nutritional and health status of children.

Cryptococcal meningitis in HIV-infected patients: a longitudinal study in Cambodia.

OBJECTIVE: To describe the frequency of diagnosis of cryptococcosis among HIV-infected patients in Phnom Penh, Cambodia, at programme entry, to investigate associated risk factors, and to determine the incidence of cryptococcal meningitis. METHODS: We analysed individual monitoring data from 11,970 HIV-infected adults enrolled between 1999 and 2008. We used Kaplan-Meier naïve methods to estimate survival and retention in care and multiple logistic regression to investigate associations with individual-level factors. RESULTS: Cryptococcal meningitis was diagnosed in 12.0% of the patients: 1066 at inclusion and 374 during follow-up. Incidence was 20.3 per 1000 person-years and decreased over time. At diagnosis, median age was 33 years, median CD4 cell count was 8 cells/µl, and 2.4% of patients were receiving combined antiretroviral therapy; 38.7% died and 34.6% were lost to follow-up. Of 750 patients alive and in care after 3 months of diagnosis, 85.9% received secondary cryptococcal meningitis prophylaxis and 13.7% relapsed in median 5.7 months [interquartile range 4.1-8.8] after cryptococcal meningitis diagnosis (relapse incidence=5.7 per 100 person-years; 95%CI 4.7-6.9). Cryptococcal meningitis was more common in men at programme entry (adjusted OR=2.24, 95% CI 1.67-3.00) and fell with higher levels of CD4 cell counts (P<0.0001). CONCLUSIONS: Cryptococcal meningitis remains an important cause of morbidity and mortality in Cambodian HIV-infected patients. Our findings highlight the importance of increasing early access to HIV care and cryptococcal meningitis prophylaxis and of improving its diagnosis in resource-limited settings.

Chromosomal integration of the extended-spectrum beta-lactamase gene blaCTX-M-15 in Salmonella enterica serotype Concord isolates from internationally adopted children.

We report the emergence of Salmonella enterica isolates of serotype Concord (and its monophasic variant 6,7:l,v:-) producing the extended-spectrum beta-lactamases (ESBLs) SHV-12 and CTX-M-15 in France and Norway between 2001 and 2006 (43 in France and 26 in Norway). The majority of these isolates were from adopted children from Ethiopia, most of whom were healthy carriers. Several symptomatic secondary cases were found in the adoptive families and health care facilities in France. Serotype Concord isolates collected before 2003 produced SHV-12 encoded on a 340-kb conjugative plasmid of replicon IncI1. Isolates collected after 2003 produced CTX-M-15. We detected two conjugative plasmids carrying bla(CTX-M-15). One plasmid, approximately 300 kb in size, was positive for the IncHI2 replicon and the plasmid-mediated quinolone resistance gene qnrA1. The other plasmid, from one of the earliest CTX-M-15-producing isolates collected, was a fusion plasmid with IncY and IncA/C(2) replicons and was 200 kb in size. However, we showed, using Southern hybridization of I-CeuI-digested chromosomal DNA and S1 nuclease analysis of plasmid DNA, that most isolates had a bla(CTX-M-15) gene located on chromosomal DNA. Analysis of the flanking regions of the chromosomally located bla(CTX-M-15) gene by cloning revealed an ISEcp1 truncated by an intact IS26 upstream from the bla(CTX-M-15) gene and a truncated orf477 gene downstream from bla(CTX-M-15). We found regions beyond the IS26 and the orf477 genes that were derived from IncA/C(2) plasmids, suggesting the chromosomal integration of part of the bla(CTX-M-15)-carrying IncY and IncA/C(2) fusion plasmid from early CTX-M-15-producing isolates.

The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis.

BACKGROUND: We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. METHODS: A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RESULTS: RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. CONCLUSION: RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.

Ceftriaxone-resistant salmonella enterica serotype Newport, France.

The multidrug-resistant (MDR) Salmonella enterica serotype Newport strain that produces CMY-2 beta-lactamase (Newport MDR-AmpC) was the source of sporadic cases and outbreaks in humans in France during 2000-2005. Because this strain was not detected in food animals, it was most likely introduced into France through imported food products.

Surveillance of hemolytic uremic syndrome in children less than 15 years of age, a system to monitor O157 and non-O157 Shiga toxin-producing Escherichia coli infections in France, 1996-2006.

BACKGROUND: Since the 1980s, Shiga toxin-producing Escherichia coli (STEC), especially E. coli O157:H7, has been an important cause of food borne disease in industrial countries. In France, as there was no routine screening for STEC in clinical laboratories, enhanced surveillance of hemolytic uremic syndrome (HUS) in children less than 15 years of age was established in 1996 to monitor trends in the incidence of STEC infections. METHODS: The surveillance system was based on a voluntary national network of pediatricians of 31 pediatric nephrology units in public hospitals. RESULTS: From 1996 to 2006, the mean annual incidence of HUS was 0.71 cases per 100,000 children less than 15 years of age and 1.87 cases per 100,000 children less than 5 years of age. STEC infections were confirmed in 66% of patients; STEC O157 was the most common serogroup identified in STEC-related HUS (83%). In this 11-year period, 96% of HUS cases were sporadic and only 2 outbreaks caused by STEC O157 and by a dual infection of STEC O26 and O80 were detected. CONCLUSIONS: An evaluation of the surveillance of pediatric HUS showed that it is a simple and useful system for monitoring trends in STEC infections in France. It provides the information needed to measure the impact of new and changing vehicles of STEC transmission, and evaluate the effectiveness of prevention measures.

Burden of herpes zoster in 16 selected immunocompromised populations in England: a cohort study in the Clinical Practice Research Datalink 2000-2012.

OBJECTIVES: Herpes zoster (HZ) is caused by reactivation of varicella-zoster virus which remains latent in individuals after a varicella infection. It is expected that HZ will be more frequent in immunocompromised (IC) individuals than in immunocompetent (IC-free). This study assessed the incidence rate (IR) of HZ in individuals with a wide set of IC conditions and in IC-free individuals. SETTING: A retrospective cohort study was conducted in England using data (January 2000 to March 2012) from the Clinical Practice Research Datalink with linkage to the Hospital Episodes Statistics. PARTICIPANTS: A cohort of 621 588 individuals with 16 selected IC conditions and a gender/age-matched cohort of IC-free individuals were identified. The IC conditions included haematopoietic stem cell transplant (HSCT), solid organ transplant, malignancies, autoimmune diseases and users of immunosuppressive medications. OUTCOMES: IR of HZ per 1000 person-years (PY) was estimated. Proportions of postherpetic neuralgia (PHN) and other HZ complications within 90 days of HZ onset were also estimated among patients with HZ. Risk factors for PHN in IC individuals with HZ were assessed by a multivariate regression model. RESULTS: The overall IR of HZ in the IC cohort was 7.8/1000 PY (95% CI 7.7 to 7.9), increasing with age from 3.5/1000 PY (3.4-3.7) in individuals aged 18-49 years to 12.6/1000 PY (12.2-13.0) in individuals aged ≥80 years. This IR in the IC-free cohort was 6.2/1000 PY (6.1-6.3). The overall IR of HZ varied across IC conditions, ranging from 5.3 (5.1-5.5) in psoriasis to 41.7/1000 PY (35.7-48.4) in HSCT. The proportions of PHN and other HZ complications were 10.7% (10.2-11.1) and 2.9% (2.7-3.2) in the IC cohort, but 9.1% (8.7-9.5) and 2.3% (2.1-2.6) in the IC-free cohort, respectively. CONCLUSION: IC population contributes to the public health burden of HZ in England. Vaccination might be the most preferable HZ preventive measure for the IC population.

Incidence and costs of herpes zoster and postherpetic neuralgia in German adults aged ≥50 years: A prospective study.

OBJECTIVES: Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden. METHODS: From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. RESULTS: HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective. CONCLUSIONS: The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN.

Two consecutive large outbreaks of Salmonella enterica serotype Agona infections in infants linked to the consumption of powdered infant formula.

BACKGROUND: An increase of isolation of Salmonella Agona was observed in January through February 2005 among infants in France. METHODS: Case-control study, food trace-back and microbiologic investigations were promptly carried out. RESULTS: A total of 141 confirmed cases <12 months of age were identified. Most had diarrhea (99%; bloody 56%) and fever (75%) and 36% were hospitalized for 5 days on average and none died. In the case-control analysis, all 23 cases and none of the 23 controls had consumed powdered formula of brand A (P < 10(-5)). Active follow up of all cases showed that after the withdrawal of formula A, cases that had consumed formula A decreased rapidly, but new cases had consumed another formula (brand B). The trace-back found that 5 batches of formula B had been manufactured on the same production line as formula A. Forty-four cases were linked to formula A and 92 to formula B. All routine controls performed by the producers were negative for Salmonella. However, enhanced microbiologic investigations yielded S. Agona in one of 176 samples of formula A, in 4 of 27 tins of formula B consumed by cases and in 6 of 420 environmental swabs from the production line. All clinical, food and environmental isolates were of the same pulsed-field gel electrophoresis profile. CONCLUSIONS: Powdered infant formulas are not sterile products and may contain low levels of Salmonella. Routine microbiologic controls are insufficient to detect a low-grade contamination, which may cause serious illness and outbreaks among infants.

Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old, Health District of Sokone, Senegal, 2010-2013.

INTRODUCTION: Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal. METHODS: Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature ≥ 37.5°C, a Rapid Diagnostic Test (RDT) was performed. RESULTS: From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season. CONCLUSION: This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity.