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IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure.

The U.S. COVID-19 vaccination program launched on December 14, 2020. The Advisory Committee on Immunization Practices recommended prioritizing COVID-19 vaccination for specific groups of the U.S. population who were at highest risk for COVID-19 hospitalization and death, including adults aged ≥75 years*; implementation varied by state, and eligibility was gradually expanded to persons aged ≥65 years beginning in January 2021. By April 19, 2021, eligibility was expanded to all adults aged ≥18 years nationwide.† To assess patterns of COVID-19 vaccination coverage among U.S. adults, CDC analyzed data submitted on vaccinations administered during December 14, 2020-May 22, 2021, by age, sex, and community-level characteristics. By May 22, 2021, 57.0% of persons aged ≥18 years had received ≥1 COVID-19 vaccine dose; coverage was highest among persons aged ≥65 years (80.0%) and lowest among persons aged 18-29 years (38.3%). During the week beginning February 7, 2021, vaccination initiation among adults aged ≥65 years peaked at 8.2%, whereas weekly initiation among other age groups peaked later and at lower levels. During April 19-May 22, 2021, the period following expanded eligibility to all adults, weekly initiation remained

Background Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA) have been recently reported in the United States. Methods We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011 to February 2020 to identify IMD cases caused by strains with blaROB-1- or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. Results Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1- containing US isolates with wild-type gyrA were identified from 2013 to 2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from 6 other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to 6 CCs and contained 10 unique gyrA alleles; 7 were similar or identical to alleles from Neisseria lactamica or Neisseria gonorrhoeae. Conclusions Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the United States. The emerging dual resistance is due to acquisition of ciprofloxacin resistance by β-lactamase–containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.

Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the “Defeating Meningitis by 2030” roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs.

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.

In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of “Defeating Meningitis by 2030,” MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa.

International audience; Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.

Background Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic corynebacteria (eg, Corynebacterium pseudodiphtheriticum) rarely causes diphtheria-like illness. Recently, global diphtheria outbreaks have resulted from breakdown of health care infrastructures, particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among forcibly displaced Myanmar nationals in Bangladesh. Methods Specimens and clinical information were collected from patients presenting at diphtheria treatment centers. Swabs were tested for toxin gene (tox)-bearing C. diphtheriae by real-time polymerase chain reaction (RT-PCR) and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. Results Among 382 patients, 153 (40%) tested tox positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. Conclusions We report confirmation of a diphtheria outbreak and identification of a cocirculating Corynebacterium species. The high proportion of C. pseudodiphtheriticum codetection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.

Background: Historically, the major cause of meningococcal epidemics in the meningitis belt of sub-Saharan Africa has been Neisseria meningitidis serogroup A (NmA), but the incidence has been substantially reduced since the introduction of a serogroup A conjugate vaccine starting in 2010. We performed whole-genome sequencing on isolates collected post-2010 to assess their phylogenetic relationships and inter-country transmission. Methods: A total of 716 invasive meningococcal isolates collected between 2011 and 2016 from 11 meningitis belt countries were whole-genome sequenced for molecular characterization by the three WHO Collaborating Centers for Meningitis. Findings: We identified three previously-reported clonal complexes (CC): CC11 (n = 434), CC181 (n = 62) and CC5 (n = 90) primarily associated with NmW, NmX, and NmA, respectively, and an emerging CC10217 (n = 126) associated with NmC. CC11 expanded throughout the meningitis belt independent of the 2000 Hajj outbreak strain, with isolates from Central African countries forming a distinct sub-lineage within this expansion. Two major sub-lineages were identified for CC181 isolates, one mainly expanding in West African countries and the other found in Chad. CC10217 isolates from the large outbreaks in Nigeria and Niger were more closely related than those from the few cases in Mali and Burkina Faso. Interpretations: Whole-genome based phylogenies revealed geographically distinct strain circulation as well as inter-country transmission events. Our results stress the importance of continued meningococcal molecular surveillance in the region, as well as the development of an affordable vaccine targeting these strains. Fund: Meningitis Research Foundation; CDC's Office of Advanced Molecular Detection; GAVI, the Vaccine Alliance. Keywords: Meningitis, Meningitis belt, Invasive meningococcal disease, Phylogenetics, Neisseria meningitidis

Microscopy is the gold standard for malaria epidemiology, but laboratory and point-of-care (POC) tests detecting parasite antigen, DNA, and human antibodies against malaria have expanded this capacity. The island nation of Haiti is endemic for Plasmodium falciparum (Pf) malaria, though at a low national prevalence and heterogenous geospatial distribution. In 2015 and 2016, serosurveys were performed of children (ages 6–7 years) sampled in schools in Saut d’Eau commune (n = 1,230) and Grand Anse department (n = 1,664) of Haiti. Children received malaria antigen rapid diagnostic test and provided a filter paper blood sample for further laboratory analysis of the Pf histidine-rich protein 2 (HRP2) antigen, Pf DNA, and anti-Pf IgG antibodies. Prevalence of Pf infection ranged from 0.0–16.7% in 53 Saut d’Eau schools, and 0.0–23.8% in 56 Grand Anse schools. Anti-Pf antibody carriage exceeded 80% of students in some schools from both study sites. Geospatial prediction ellipses were created to indicate clustering of positive tests within the survey areas and overlay of all prediction ellipses for the different types of data revealed regions with high likelihood of active and ongoing Pf malaria transmission. The geospatial utilization of different types of Pf data can provide high confidence for spatial epidemiology of the parasite.

Toxocariasis, one of a group of parasitic diseases known as neglected parasitic infections, is a disease caused by the larvae of two species of Toxocara roundworms, Toxocara canis, from dogs, and less commonly Toxocara cati, from cats. Although most infected individuals are asymptomatic, clinical manifestations may include fever, fatigue, coughing, wheezing, or abdominal pain (visceral toxocariasis) or vision loss, retina damage, or eye inflammation (ocular toxocariasis). To assess U.S. pediatrician knowledge of toxocariasis, we conducted an electronic survey of American Academy of Pediatrics members. Of the 2,684 respondents, 1,120 (47%) pediatricians correctly selected toxocariasis as the diagnosis in an unknown case presentation with findings typical for toxocariasis; overall 1,695 (85%) stated they were not confident that their knowledge of toxocariasis was current. This knowledge gap suggests a need for improved toxocariasis awareness and education for U.S. pediatricians, especially those caring for children at risk for infection.

Use of eculizumab (Soliris, Alexion Pharmaceuticals), a terminal complement inhibitor, is associated with a 1,000-fold to 2,000-fold increased incidence of meningococcal disease (1). Administration of meningococcal vaccines is recommended for patients receiving eculizumab before beginning treatment (2,3). Sixteen cases of meningococcal disease were identified in eculizumab recipients in the United States during 2008-2016; among these, 11 were caused by nongroupable Neisseria meningitidis. Fourteen patients had documentation of receipt of at least 1 dose of meningococcal vaccine before disease onset. Because eculizumab recipients remain at risk for meningococcal disease even after receipt of meningococcal vaccines, some health care providers in the United States as well as public health agencies in other countries recommend antimicrobial prophylaxis for the duration of eculizumab treatment; a lifelong course of treatment is expected for many patients. Heightened awareness, early care seeking, and rapid treatment of any symptoms consistent with meningococcal disease are essential for all patients receiving eculizumab treatment, regardless of meningococcal vaccination or antimicrobial prophylaxis status.

Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa’s meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization’s updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa’s meningitis belt, will enhance meningococcal disease prevention across the belt.

Infection by the rat lungworm Angiostrongylus cantonensis represents the most common cause of infectious eosinophilic meningitis in humans, causing central nervous system (CNS) angiostrongyliasis. Most of CNS angiostrongyliasis cases were described in Asia, Pacific Basin, Australia, and some limited parts of Africa and America. CNS angiostrongyliasis has been reported in the Caribbean but never in the Lesser Antilles. The primary objectives of this study were to depict the first case of CNS angiostrongyliasis in the Lesser Antilles and investigate the environmental presence of A. cantonensis in Guadeloupe, Lesser Antilles. In December 2013, a suspected case of CNS angiostrongyliasis in an 8-month-old infant in Guadeloupe was investigated by real-time polymerase chain reaction (PCR) testing on cerebral spinal fluid (CSF). The environmental investigation was performed by collecting Achatina fulica molluscs from different parts of Guadeloupe and testing the occurrence of A. cantonensis by real-time PCR. CSF from the suspected case of angiostrongyliasis was positive for A. cantonensis by real-time PCR. Among 34 collected snails for environmental investigation, 32.4% were positive for A. cantonensis. In conclusion, we report the first laboratory-confirmed case of CNS-angiostrongyliasis in the Lesser Antilles. We identified the presence and high prevalence of A. cantonensis in A. fulica in Guadeloupe. These results highlight the need to increase awareness of this disease and implement public health programs in the region to prevent human cases of angiostrongyliasis and improve management of eosinophilic meningitis patients.

Lymphatic filariasis afflicts 68 million people in 73 countries, including 17 million persons living with chronic lymphedema. The Global Programme to Eliminate Lymphatic Filariasis aims to stop new infections and to provide care for persons already affected, but morbidity management programs have been initiated in only 24 endemic countries. We examine the economic costs and benefits of alleviating chronic lymphedema and its effects through a simple limb-care program. For Khurda District, Odisha State, India, we estimated lifetime medical costs and earnings losses due to chronic lymphedema and acute dermatolymphangioadenitis (ADLA) with and without a community-based limb-care program. The program would reduce economic costs of lymphedema and ADLA over 60 years by 55%. Savings of US$1,648 for each affected person in the workforce are equivalent to 1,258 days of labor. Per-person savings are more than 130 times the per-person cost of the program. Chronic lymphedema and ADLA impose a substantial physical and economic burden on the population in filariasis-endemic areas. Low-cost programs for lymphedema management based on limb washing and topical medication for infection are effective in reducing the number of ADLA episodes and stopping progression of disabling and disfiguring lymphedema. With reduced disability, people are able to work longer hours, more days per year, and in more strenuous, higher-paying jobs, resulting in an important economic benefit to themselves, their families, and their communities. Mitigating the severity of lymphedema and ADLA also reduces out-of-pocket medical expense.

Summary Background On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. Methods We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. Findings 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. Interpretation This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. Funding US Global Health Security.

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Soil-transmitted helminths (STHs) are controlled by regular mass drug administration. Current practice targets school-age children (SAC) preferentially over pre-school age children (PSAC) and treats large areas as having uniform prevalence. We assessed infection prevalence in SAC and PSAC and spatial infection heterogeneity, using a cross-sectional study in two slum villages in Kibera, Nairobi. Nairobi has low reported STH prevalence. The SAC and PSAC were randomly selected from the International Emerging Infections Program's surveillance platform. Data included residence location and three stools tested by Kato-Katz for STHs. Prevalences among 692 analyzable children were any STH: PSAC 40.5%, SAC 40.7%; Ascaris: PSAC 24.1%, SAC 22.7%; Trichuris: PSAC 24.0%, SAC 28.8%; hookworm < 0.1%. The STH infection prevalence ranged from 22% to 71% between sub-village sectors. The PSAC have similar STH prevalences to SAC and should receive deworming. Small areas can contain heterogeneous prevalences; determinants of STH infection should be characterized and slums should be assessed separately in STH mapping.

To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (prevalence ratio [PR] = 2.2, 95% confidence interval = 1.1–4.6) and ID (PR = 3.3, 95% confidence interval = 1.6–6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population.

OBJECTIVE A recent randomized clinical trial demonstrated home-based treatment of WHO-defined severe pneumonia with oral amoxicillin was equivalent to hospital-based therapy and parenteral antibiotics. We aimed to determine whether this finding is generalizable across four countries. METHODS Multicentre observational study in Bangladesh, Egypt, Ghana and Vietnam between November 2005 and May 2008. Children aged 3-59 months with WHO-defined severe pneumonia were enrolled at participating health centres and managed at home with oral amoxicillin (80-90 mg/kg per day) for 5 days. Children were followed up at home on days 1, 2, 3 and 6 and at a facility on day 14 to look for cumulative treatment failure through day 6 and relapse between days 6 and 14. RESULTS Of 6582 children screened, 873 were included, of whom 823 had an outcome ascertained. There was substantial variation in presenting characteristics by site. Bangladesh and Ghana had fever (97%) as a more common symptom than Egypt (74%) and Vietnam (66%), while in Vietnam, audible wheeze was more common (49%) than at other sites (range 2-16%). Treatment failure by day 6 was 9.2% (95% CI: 7.3-11.2%) across all sites, varying from 6.4% (95% CI: 3.1-9.8%) in Ghana to 13.2% (95% CI: 8.4-18.0%) in Vietnam; 2.7% (95% CI: 1.5-3.9%) of the 733 children well on day 6 relapsed by day 14. The most common causes of treatment failure were persistence of lower chest wall indrawing (LCI) at day 6 (3.8%; 95% CI: 2.6-5.2%), abnormally sleepy or difficult to wake (1.3%; 95% CI: 0.7-2.3%) and central cyanosis (1.3%; 95% CI: 0.7-2.3%). All children survived and only one adverse drug reaction occurred. Treatment failure was more frequent in young infants and those presenting with rapid respiratory rates. CONCLUSIONS Clinical treatment failure and adverse event rates among children with severe pneumonia treated at home with oral amoxicillin did not substantially differ across geographic areas. Thus, home-based therapy of severe pneumonia can be applied to a wide variety of settings.

OBJECTIVES To assess the performance of an educational campaign to increase adherence to a mass-administered DEC regimen against lymphatic filariasis (LF) in Orissa, and to identify factors that could enhance future campaigns. METHOD Randomized cluster survey, comparing areas that did and did not receive the educational campaign, using a household coverage survey and knowledge, attitudes and practices (KAP) survey. RESULTS LF MDA coverage for the entire population (n = 3449) was 56% (95% CI: 50.0-61.9). There was no statistical difference between the areas that did and did not receive the educational campaign. The most common barriers to adherence were fear of medication side effects (47.4%) and lack of recognition of one's risk for LF (15.8%). Modifiable, statistically significant, multivariable predictors of adherence were knowing that DEC prevents LF (aOR = 2.6, 95% CI: 1.4-5.1), knowing that mosquitoes transmit LF (aOR = 1.9, 95% CI: 1.1-3.2), and knowing both about the mass drug administration (MDA) in advance and that mosquitoes transmit LF (aOR = 5.4, 95% CI: 2.8-10.4). CONCLUSIONS India needs to increase compliance with MDA programmes to reach its goal of interrupting LF transmission. Promoting a simple public health message before MDA distribution, which takes into account barriers to and predictors of adherence, could raise compliance with the LF MDA programme.

Soil-transmitted helminth (STH) infections affect persons living in areas with poor water, sanitation, and hygiene (WASH). Preschool-aged children (PSAC) and school-aged children (SAC) are disproportionately affected by STH infections. We aimed to identify WASH factors associated with STH infection among PSAC and SAC in Kibera, Kenya. In 2012, households containing a PSAC or SAC were randomly selected from those enrolled in the International Emerging Infections Program, a population-based surveillance system. We administered a household questionnaire, conducted environmental assessments for WASH, and tested three stools from each child for STH eggs using the Kato-Katz method. WASH factors were evaluated for associations with STH infection using univariable and multivariable Poisson regression. Any-STH prevalence was 40.8% among 201 PSAC and 40.0% among 475 SAC enrolled. Using the Joint Monitoring Programme water and sanitation classifications, 1.5% of households reported piped water on premises versus 98.5% another improved water source; 1.3% reported improved sanitation facilities, while 81.7% used shared sanitation facilities, 13.9% had unimproved facilities, and 3.1% reported no facilities (open defecation). On univariable analysis, STH infection was significantly associated with a household toilet located off-premises (prevalence ratio (PR) = 1.33; p = 0.047), while always treating water (PR = 0.81; p = 0.04), covering drinking water containers (PR = 0.75; p = 0.02), using clean towels during hand drying (PR = 0.58; p

Background Globally 68 million people are infected with lymphatic filariasis (LF), 17 million of whom have lymphedema. This study explores the effects of a lymphedema management program in Odisha State, India on morbidity and psychosocial effects associated with lymphedema. Methodology/Principal Findings Focus groups were held with patients (eight groups, separated by gender), their family members (eight groups), community members (four groups) and program volunteers (four groups) who had participated in a lymphedema management program for the past three years. Significant social, physical, and economic difficulties were described by patients and family members, including marriageability, social stigma, and lost workdays. However, the positive impact of the lymphedema management program was also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the etiology of the disease. Program volunteers and community members stressed the role that the program had played in educating people, though interestingly, local explanations and treatments appear to coexist with knowledge of biomedical treatments and the mosquito vector. Conclusions/Significance Local and biomedical understandings of disease can co-exist and do not preclude individuals from participating in biomedical interventions, specifically lymphedema management for those with lymphatic filariasis. There is a continued need for gender-specific psychosocial support groups to address issues particular to men and women as well as a continued need for improved economic opportunities for LF-affected patients. There is an urgent need to scale up LF-related morbidity management programs to reduce the suffering of people affected by LF., Author Summary Around the world 68 million people are infected with lymphatic filariasis (LF), a mosquito-borne disease caused by filarial worms. The parasite can damage patients’ lymphatic systems causing pain, infections and swollen limbs, known as lymphedema or, in more advanced stages, elephantiasis. Lymphedema management programs can help patients to deal with the physical and emotional effects of lymphedema and elephantiasis. We held a total of 24 focus groups to discuss the experiences of people with lymphedema in Odisha State, India who participate in such a program. Discussions were held with patients, family members of patients, community members and program volunteers. Significant social, physical and economic difficulties were described by patients and family members, including marriage-related issues, social stigma, and lost workdays. However, the positive impacts of the lymphedema management program were also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the cause of the disease. People were able to hold both a ‘scientific’ and a ‘traditional’ understanding of LF at the same time. The financial hardships that people described highlight the need for improved economic opportunities for lymphedema-affected patients. Support programs based in the community also have clear social and emotional benefits. There is an urgent need to scale up LF management programs to reduce the suffering of people affected by LF.

Schistosoma mansoni infection is a major cause of organomegaly and ultimately liver fibrosis in adults. Morbidity in pre-school-aged children is less defined, and they are currently not included in mass drug administration (MDA) programs for schistosomiasis control. We report results of a study of the association of schistosomiasis with organomegaly in a convenience sample of 201 children under 7 years old in Rusinga, Kenya on two cross-sectional visits, before and after praziquantel treatment. Data included stool examination and serology for schistosomiasis, the Niamey ultrasound protocol to stage hepatosplenic morbidity including organomegaly, and potential confounders including malaria. Unadjusted and adjusted Poisson regressions were performed. The baseline prevalence of schistosomiasis by antibody and/or stool was 80.3%. Schistomiasis was associated with hepatomegaly (adjusted prevalence ratio [aPR] = 1.4; 95% confidence interval [CI]: 1.0-2.1) and splenomegaly (aPR = 2.1; 95% CI: 1.2-3.7). The association with hepatomegaly persisted posttreatment (aPR = 1.4; 95% CI: 1.1-1.6). Schistosomiasis was associated with morbidity in this cohort. Efforts to include young children in mass treatment campaigns should intensify.

To assess clinical findings associated with Wuchereria bancrofti infection, 192 school children in a filariasis-endemic area of Haiti underwent physical and ultrasonographic examinations and testing for circulating filarial antigen (CFA). The CFA-positive children were more likely than CFA-negative children to have severe interdigital lesions (> or = 1 macerated lesion with involvement of > or = 4 toe web spaces) (P < 0.0001) and inguinal (P = 0.003) or crural (P = 0.004) lymph node pathology. In multivariate analysis, CFA positivity remained a significant predictor for severe interdigital lesions (P = 0.006) and inguinal lymph node pathology (P = 0.05). Ultrasound detected adult worms and lymphangectasia (diameter = 2.0-4.0 mm) in 11 (10.8%) CFA-positive children. Among CFA-positive children, ultrasonographic detection of adult worms was associated with inguinal (P = 0.01) and crural (P = 0.004) lymph node pathology and advanced pubertal stage (sexual maturity rating = 3-5) (P = 0.02). This is the first study to associate interdigital lesions with filarial infection in children.

This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P < or = 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P < or = 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P < or = 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.

To assess the clinical findings associated with detection of adult Wuchereria bancrofti worms on ultrasound, 186 schoolchildren in a filariasis-endemic area of Haiti underwent physical and ultrasonographic examinations. The filaria dance sign (FDS) of adult W. bancrofti was detected in the inguinal and crural lymphatics of 28 (15%) children. FDS detection was more common in older children (P 0.003) and in those with a history of inguinal lymph node inflammation (P 0.002) or crural lymphadenopathy on physical exam (P 0.01). Twenty-five FDS-positive children were reexamined after three annual cycles of mass treatment for lymphatic filariasis (LF). The total number of adult worm nests detected by ultrasound decreased from 29 to 4 (P 0.0001). FDS and lymphangiectasia were detected in the intrascrotal (N 3) and inguinal (N 1) lymphatic vessels of three postpubescent boys. This study demonstrates clinical and subclinical findings of LF in FDS-positive children.

Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. At present, there are no documented drug-drug interactions. Nitazoxanide has been licensed for the treatment of Giardia intestinalis-induced diarrhea in patients >or=1 year of age and Cryptosporidum-induced diarrhea in children aged 1-11 years. At present, it is pending licensure for treatment of infection due to Cryptosporidium species in adults and for use in treating immunocompromised hosts. It represents an important addition to the antiparasitic arsenal.

Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR’s were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.

Background Programs for control of soil-transmitted helminth (STH) infections are increasingly evaluating national mass drug administration (MDA) interventions. However, “unprogrammed deworming” (receipt of deworming drugs outside of nationally-run STH control programs) occurs frequently. Failure to account for these activities may compromise evaluations of MDA effectiveness. Methods We used a cross-sectional study design to evaluate STH infection and unprogrammed deworming among infants (aged 6–11 months), preschool-aged children (PSAC, aged 1–4 years), and school-aged children (SAC, aged 5–14 years) in Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of households with randomly-selected children about past-year receipt and source(s) of deworming drugs. Local non-governmental organizations (NGOs) and school staff participating in school-based deworming were interviewed to collect information on drug coverage. Results Of 679 children (18 infants, 184 PSAC, and 477 SAC) evaluated, 377 (55%) reported receiving at least one unprogrammed deworming treatment during the past year. PSAC primarily received treatments from chemists (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150 schools attended by children in our study area. Past-year deworming was negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC whose most recent deworming medication was sourced from a chemist were more often infected with Trichuris (38.0%) than those who received their most recent treatment from a health center (17.3%) or school (23.1%) (p = 0.05). Conclusion Unprogrammed deworming was received by more than half of children in our study area, from multiple sources. Both individual-level treatment and unprogrammed preventive chemotherapy may serve an important public health function, particularly in the absence of programmed deworming; however, they may also lead to an overestimation of programmed MDA effectiveness. A standardized, validated tool is needed to assess unprogrammed deworming., Author Summary In countries with endemic soil-transmitted helminth infections, deworming medications are widely available from multiple sources, including over the counter. However, in many countries, national programs already provide deworming medications in mass drug administrations to primary school students, as part of World Health Organization recommendations. Evaluations of the effectiveness of such medications at reducing worm burden in children is based solely on the national program’s distribution schedules, primarily because little is known about how frequently deworming medications are obtained from other sources. We investigated sources of deworming medications received by children in a Kenyan slum, finding that more than half of school-aged and preschool-aged children received deworming medications outside of a national school-based deworming program. These drugs were received from multiple sources, including chemists, healthcare centers, and at schools, via the efforts of non-governmental organizations. These data strongly indicate a need to collect data on all sources of deworming medications when evaluating the effectiveness of national school-based deworming programs.