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Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. Methods and findings Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 [mu]g/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were [greater than or equal to]5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. Conclusions In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. Trial registration Clinicaltrials.gov registration number: NCT02899936, Author(s): Gary J. Weil 1,*, Joshua Bogus 1, Michael Christian 2, Christine Dubray 3, Yenny Djuardi 2, Peter U. Fischer 1, Charles W. Goss 1, Myra Hardy 4, Purushothaman Jambulingam [...]

The study attempts to determine the epidemiologic features of the Zika virus outbreak on Yap Island, Federated States of Micronesia and to also describe the clinical manifestations of the disease. The results indicate that the outbreak represents a transmission of the virus outside Asia and Africa and the need to create public awareness to avoid further expansion of the virus.

Background: Lymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission. Methodology/Principle findings: Nippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4–2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%). Conclusions/Significance: Overall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance. Author summary: Lymphatic filariasis (LF) is a debilitating parasitic disease that has been targeted for global elimination. The transmission assessment survey (TAS) is a tool used to determine if LF transmission has reached low enough levels that prevention activities can be stopped. This study aimed to identify methods to investigate positive LF cases found during TAS. The investigation was conducted in Nippes Department, Haiti, where 8 positive cases were found in TAS in 2017. Participants were recruited through two methods: purposive selection of the closest 50 households to the positive case, and random selection of 20 households in the census enumeration area of the case. Participants completed a survey and were tested for LF antigen, indicative of current infection, and parasite-specific antibody, indicative of current or past infection. A total of 1,927 people participated in the study; 1.5% of these were antigen-positive, and 4.5% were antibody-positive. Purposive sampling found a higher number of antigen-positive individuals, and random sampling found a higher percent positive. Both sampling methods were feasible to use in this setting, and both methods identified signs of ongoing transmission in a large urban area. Additional research is needed to help standardize guidance for post-TAS surveillance to best identify ongoing transmission. [ABSTRACT FROM AUTHOR]

Background: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). Methodology/Principal findings: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9–36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1–34.3); Papua New Guinea 32.9 (95% CI: 31.9–33.8); Indonesia 30.6 (95% CI: 29.8–31.3); Haiti 28.6 (95% CI: 27.8–29.4); India 26.8 (95% CI: 25.6–28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. Conclusions/Significance: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted. Author summary: The acceptability of a new combination treatment regimen for lymphatic filariasis (ivermectin, plus DEC and albendazole, or IDA) was assessed as part of a larger community-based safety study in Fiji, Haiti, India, Indonesia and Papua New Guinea. To understand how trial participants and communities felt about the new treatment, a survey was carried out with people who had participated in the safety study receiving either the standard treatment [DEC plus albendazole (DA)] or the new treatment regimen (IDA). Focus group discussions and in-depth interviews were performed in the same communities. Results showed that there was no difference in acceptability between the DA and IDA. Adverse events and presence of filarial infection did not affect acceptability. The most important indicator associated with acceptability was country. All countries accepted the treatment regimens. Fiji had the highest acceptability scores, followed by Papua New Guinea, Indonesia, Haiti and India. Results from the qualitative research showed that study participants appreciated the professionalism of the drug delivery team and the support offered for the management of any adverse events. [ABSTRACT FROM AUTHOR]

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti. Author summary: Lymphatic filariasis (LF) also known as "elephantiasis" is caused by infection with filarial worms that are transmitted by mosquitoes. The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through annual rounds of mass drug administration (MDA). Several studies have shown that a single dose of a triple-drug therapy (ivermectin, diethylcarbamazine and albendazole or IDA) was superior to a single dose of the standard double-drug therapy (diethylcarbamazine and albendazole or DA) and might accelerate LF elimination. In Northern Haiti, we performed a large community treatment study to compare the safety and efficacy of three-drug and two-drug therapies. Almost 6,000 participants were treated with IDA or DA and tested for LF. Each participant was assessed for adverse events (AE) and participants who tested positive for LF at enrollment were retested one year after treatment. Less participants who received IDA (11.0%) experienced AEs compared to participants who received DA (17.3%). IDA was also more effective to eliminate microfilariae (adult worm offspring) from the blood compare to DA. Results from this study showed that IDA was well tolerated in Haiti and has the potential to accelerate LF elimination in countries that currently use DA if high MDA coverage can be achieved. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios. Methodology/Principal findings: Age, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the “gold standard” for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing. Conclusions/Significance: Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing. [ABSTRACT FROM AUTHOR]

Background: Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) as a public health problem has been stopped. During the post-MDA period, transmission assessment surveys (TAS) are recommended by the World Health Organization to monitor the presence of the parasite in humans. Molecular xenomonitoring (MX), a method by which parasite infection in the mosquito population is monitored, has also been proposed as a sensitive method to determine whether the parasite is still present in the human population. The aim of this study was to conduct an MX evaluation in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded. Methodology/Principal findings: Mosquitoes were systematically collected from 180 trap sites per district and mosquito pools were tested for W. bancrofti using real-time PCR. A total of 23,436 intact mosquitoes, representing 31 species, were collected from the two districts, of which 10,344 (41%) were Culex quinquefasciatus, the vector of W. bancrofti in Bangladesh. All of the 594 pools of Cx. quinquefasciatus tested by real-time PCR were negative for the presence of W. bancrofti DNA. Conclusions/Significance: This study suggested the absence of W. bancrofti in these districts. MX could be a sensitive tool to confirm interruption of LF transmission in areas considered at higher risk of recrudescence, particularly in countries like Bangladesh where entomological and laboratory capacity to perform MX is available. [ABSTRACT FROM AUTHOR]

In Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5–9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas. [ABSTRACT FROM AUTHOR]

Background: Scabies, a highly pruritic and contagious mite infestation of the skin, is endemic among tropical regions and causes a substantial proportion of skin disease among lower-income countries. Delayed treatment can lead to bacterial superinfection, and treatment of close contacts is necessary to prevent reinfestation. We describe scabies incidence and superinfection among children in American Samoa (AS) to support scabies control recommendations. Methodology/Principal Findings: We reviewed 2011–2012 pharmacy records from the only AS pharmacy to identify children aged ≤14 years with filled prescriptions for permethrin, the only scabicide available in AS. Medical records of identified children were reviewed for physician-diagnosed scabies during January 1, 2011–December 31, 2012. We calculated scabies incidence, bacterial superinfection prevalence, and reinfestation prevalence during 14–365 days after first diagnosis. We used log binomial regression to calculate incidence ratios for scabies by age, sex, and county. Medical record review identified 1,139 children with scabies (incidence 29.3/1,000 children aged ≤14 years); 604 (53%) had a bacterial superinfection. Of 613 children who received a scabies diagnosis during 2011, 94 (15.3%) had one or more reinfestation. Scabies incidence varied significantly among the nine counties (range 14.8–48.9/1,000 children). Children aged <1 year had the highest incidence (99.9/1,000 children). Children aged 0–4 years were 4.9 times more likely and those aged 5–9 years were 2.2 times more likely to have received a scabies diagnosis than children aged 10–14 years. Conclusions/Significance: Scabies and its sequelae cause substantial morbidity among AS children. Bacterial superinfection prevalence and frequent reinfestations highlight the importance of diagnosing scabies and early treatment of patients and close contacts. Investigating why certain AS counties have a lower scabies incidence might help guide recommendations for improving scabies control among counties with a higher incidence. We recommend interventions targeting infants and young children who have frequent close family contact. [ABSTRACT FROM AUTHOR]

The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1e7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. Published by Elsevier Ltd. [ABSTRACT FROM AUTHOR]

Background. Systemic antibiotics are routinely prescribed for severe acute malnutrition (SAM). However, there is no consensus regarding the most suitable regimen. In a therapeutic feeding centre in Khartoum, Sudan, a randomised, unblinded, superiority-controlled trial was conducted, comparing once daily intramuscular injection with ceftriaxone for 2 days with oral amoxicillin twice daily for 5 days in children aged 6–59 months with SAM. Methods. Commencing with the first measured weight gain (WG) following admission, the risk difference and 95% confidence interval (95% CI) for children with a WG ≥ 10 g/kg/day were calculated over a 14-day period. The recovery rate and case fatality ratio (CFR) between the two groups were also calculated. Results. In an intention-to-treat analysis of 458 children, 53.5% (123/230) in the amoxicillin group and 55.7% (127/228, difference 2.2%, 95% CI -6.9–11.3) in the ceftriaxone group had a WG ≥ 10 g/kg/day during a 14-day period. Recovery rate was 70% (161/230) in the amoxicillin group and 74.6% (170/228) in the ceftriaxone group (p=0.27). CFR was 3.9% (9/230) and 3.1% (7/228), respectively (p=0.67). Most deaths occurred within the 1st 2 weeks of admission. Conclusion. In the absence of severe complications, either ceftriaxone or amoxicillin is appropriate for malnourished children. However, in ambulatory programmes, especially where there are large numbers of admissions, ceftriaxone should facilitate the work of medical personnel. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and Prevention’s (CDC’s) Global Rapid Response Team (GRRT) was created in 2015 to efficiently deploy multidisciplinary CDC experts outside the United States for public health emergencies. The COVID-19 pandemic dramatically increased the need for domestic public health responders. This study aimed to follow up on previously published data to describe the GRRT surge staffing model during the height of the COVID-19 response. We conducted descriptive analyses to assess GRRT deployment characteristics during April 1, 2019–March 31, 2022, and characteristics of responders rostered in 2021 and 2022. We analyzed data on response events, remote versus in-person work, and international versus domestic deployment location. We also examined the number of responders on call per month, language proficiency, and technical skills. During the study period, 1725 deployments were registered, accounting for 82 058 person-days deployed. Of all person-days deployed during the study period, 82% were related to COVID-19. Eighty-seven percent of all person-days deployed were domestic. Virtual deployments that were not in person accounted for 51% of deployments registered, yet these resulted in 67% of person-days deployed. The median deployment duration was 31 days. We found a median of 79 surge responders on call each month. Among 608 responders rostered in 2021 and 2022, 35% self-reported proficiency in a second language. Epidemiology was the most common technical skill (38%). GRRT transitioned to primarily remote, domestic deployments to support the COVID-19 pandemic response. The GRRT model demonstrates how response structure shifted to address the global health threat of a pandemic. [ABSTRACT FROM AUTHOR]

Highlights: [•] Alternative survey methods that would estimate drug coverage were investigated. [•] The survey methods were compared to the 30-cluster method in three countries. [•] The alternative survey methodologies were logistically feasible. [•] More research is needed to determine the scientific rigor of these survey methods. [Copyright &y& Elsevier]

Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22 † -July 3, 2020 were analyzed. The analysis was limited to 23 states § with >70% complete race/ethnicity information and five or more laboratory-confirmed COVID-19 cases among both AI/AN persons (alone or in combination with other races and ethnicities) and non-Hispanic white (white) persons. Among 424,899 COVID-19 cases reported by these states, 340,059 (80%) had complete race/ethnicity information; among these 340,059 cases, 9,072 (2.7%) occurred among AI/AN persons, and 138,960 (40.9%) among white persons. Among 340,059 cases with complete patient race/ethnicity data, the cumulative incidence among AI/AN persons in these 23 states was 594 per 100,000 AI/AN population (95% confidence interval [CI] = 203-1,740), compared with 169 per 100,000 white population (95% CI = 137-209) (rate ratio [RR] = 3.5; 95% CI = 1.2-10.1). AI/AN persons with COVID-19 were younger (median age = 40 years; interquartile range [IQR] = 26-56 years) than were white persons (median age = 51 years; IQR = 32-67 years). More complete case report data and timely, culturally responsive, and evidence-based public health efforts that leverage the strengths of AI/AN communities are needed to decrease COVID-19 transmission and improve patient outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.