Publications by authors named "Neal Alexander"

153 Publications

High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection.

PLoS Negl Trop Dis 2021 Mar 18;15(3):e0009283. Epub 2021 Mar 18.

Department for Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk.

Methods/principal Findings: We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermediate (1.0 to 2.9), and high (≥3.0). OD was also modelled as a continuous variable (cubic spline). Median age of cases was 41 years (range 0-85), with 37% having severe infection. Compared to the low category, the age-adjusted risk of severe infection was 1.5 times higher in the intermediate category (95%CI 1.2, 1.9), and 1.3 times higher in the high category (95%CI 1.0, 1.7). The effect was stronger in cases <40 years, doubling the risk in the intermediate and high categories compared to the low category. The effect was more pronounced in cases tested within 7 days of fever onset when IgG ODs are more likely to reflect pre-infection levels.

Conclusions/significance: Intermediate and high IgG antibody levels at the time of diagnosis are associated with a higher risk of severe scrub typhus infection. The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes.
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http://dx.doi.org/10.1371/journal.pntd.0009283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009433PMC
March 2021

Estimating force of infection from serologic surveys with imperfect tests.

PLoS One 2021 4;16(3):e0247255. Epub 2021 Mar 4.

Global Dengue and Aedes-transmitted Diseases Consortium (GDAC), International Vaccine Institute, Seoul, Korea.

Background: The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs.

Methods And Findings: We present Bayesian methods for estimating force of infection using serological surveys of infections which produce a lasting immune response, accounting for imperfections of the test, and uncertainty in such imperfections. In this estimation, the sensitivity and specificity can either be fixed, or belief distributions of their values can be elicited to allow for uncertainty. We analyse data from two published serological studies of dengue, one in Colombo, Sri Lanka, with a single survey and one in Medellin, Colombia, with repeated surveys in the same individuals. For the Colombo study, we illustrate how the inferred force of infection increases as the sensitivity decreases, and the reverse for specificity. When 100% sensitivity and specificity are assumed, the results are very similar to those from a standard analysis with binomial regression. For the Medellin study, the elicited distribution for sensitivity had a lower mean and higher variance than the one for specificity. Consequently, taking uncertainty in sensitivity into account resulted in a wide credible interval for the force of infection.

Conclusions: These methods can make more realistic estimates of force of infection, and help inform the choice of serological tests for future serosurveys.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247255PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932155PMC
March 2021

Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis.

PLoS Negl Trop Dis 2021 Feb 11;15(2):e0008989. Epub 2021 Feb 11.

University of California, San Diego, California, United States of America.

Background: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce.

Methods: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician.

Results: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel.

Conclusions: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.
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http://dx.doi.org/10.1371/journal.pntd.0008989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904137PMC
February 2021

Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings.

PLoS Negl Trop Dis 2021 Feb 10;15(2):e0008861. Epub 2021 Feb 10.

Centre de Recherches Médicales de Lambaréné, Campus CERMEL, Lambaréné, Gabon.

Background: In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon.

Methods: Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR.

Results: Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases.

Conclusion: Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians' diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.
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http://dx.doi.org/10.1371/journal.pntd.0008861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875424PMC
February 2021

Clinical features and natural history of the first 2073 suspected COVID-19 cases in the Corona São Caetano primary care programme: a prospective cohort study.

BMJ Open 2021 01 12;11(1):e042745. Epub 2021 Jan 12.

Instituto de Medicina Tropical (LIM-52, LIM-46, LIM-49) and Departamento de Moléstias Infecciosas e Parasitarias, Universidade de São Paulo, São Paulo, Brazil.

Background: Despite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19.

Methods: The Corona São Caetano programme is a primary care initiative providing care to all residents with COVID-19 in São Caetano do Sul, Brazil. It was designed to capture standardised clinical data on community COVID-19 cases. After triage of potentially severe cases, consecutive patients presenting to a multimedia screening platform between 13 April and 13 May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days with phone calls every 2 days. RT-PCR-negative patients were offered additional SARS-CoV-2 serology testing to establish their infection status. We describe the clinical, virological and natural history features of this prospective population-based cohort.

Findings: Of 2073 suspected COVID-19 cases, 1583 (76.4%) were tested by RT-PCR, of whom 444 (28.0%, 95% CI 25.9 to 30.3) were positive; 604/1136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8.6%) tested SARS-CoV-2 seropositive. The most common symptoms of confirmed COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever (OR 3.0, 95% CI 2.4 to 3.9), anosmia (OR 3.3, 95% CI 2.6 to 4.4) and ageusia (OR 2.9, 95% CI 2.3 to 3.8) were most strongly associated with a positive COVID-19 diagnosis by RT-PCR or serology. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia and closer to symptom onset. The rates of hospitalisation and death among 444 RT-PCR-positive cases were 6.7% and 0.7%, respectively, with older age and obesity more frequent in the hospitalised group.

Conclusion: COVID-19 presents in a similar way to other mild community-acquired respiratory diseases, but the presence of fever, anosmia and ageusia can assist the specific diagnosis. Most patients recovered without requiring hospitalisation with a low fatality rate compared with other hospital-based studies.
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http://dx.doi.org/10.1136/bmjopen-2020-042745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805372PMC
January 2021

Estimating the Force of Infection for Dengue Virus Using Repeated Serosurveys, Ouagadougou, Burkina Faso.

Emerg Infect Dis 2021 Jan;27(1):130-139

Because of limited data on dengue virus in Burkina Faso, we conducted 4 consecutive age-stratified longitudinal serologic surveys, ≈6 months apart, among persons 1-55 years of age, during June 2015-March 2017, which included a 2016 outbreak. The seroconversion rate before the serosurvey enrollment was estimated by binomial regression, taking age as the duration of exposure, and assuming constant force of infection (FOI) over age and calendar time. We calculated FOI between consecutive surveys and rate ratios for potentially associated characteristics based on seroconversion using the duration of intervals. Among 2,897 persons at enrollment, 66.3% were IgG-positive, and estimated annual FOI was 5.95%. Of 1,269 enrollees participating in all 4 serosurveys, 438 were IgG-negative at enrollment. The annualized FOI ranged from 10% to 20% (during the 2016 outbreak). Overall, we observed high FOI for dengue. These results could support decision-making about control and preventive measures for dengue.
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http://dx.doi.org/10.3201/eid2701.191650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774580PMC
January 2021

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.

BMJ Open 2020 12 15;10(12):e035307. Epub 2020 Dec 15.

Centro Nacional de Enfermedades Tropicales, Santa Cruz de la Sierra, Santa Cruz de la Sierra, Bolivia.

Introduction: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean.

Methods And Analysis: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach.

Ethics And Dissemination: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.
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http://dx.doi.org/10.1136/bmjopen-2019-035307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745317PMC
December 2020

Complex relationships between Aedes vectors, socio-economics and dengue transmission-Lessons learned from a case-control study in northeastern Thailand.

PLoS Negl Trop Dis 2020 10 1;14(10):e0008703. Epub 2020 Oct 1.

Norwegian University of Life Sciences, Ås, Norway.

Background/objectives: Dengue fever is an important public health concern in most tropical and subtropical countries, and its prevention and control rest on vector surveillance and control. However, many aspects of dengue epidemiology remain unclear; in particular, the relationship between Aedes vector abundance and dengue transmission risk. This study aims to identify entomological and immunological indices capable of discriminating between dengue case and control (non-case) houses, based on the assessment of candidate indices, as well as individual and household characteristics, as potential risk factors for acquiring dengue infection.

Methods: This prospective, hospital-based, case-control study was conducted in northeastern Thailand between June 2016 and August 2019. Immature and adult stage Aedes were collected at the houses of case and control patients, recruited from district hospitals, and at patients' neighboring houses. Blood samples were tested by RDT and PCR to detect dengue cases, and were processed with the Nterm-34 kDa salivary peptide to measure the human immune response to Aedes bites. Socioeconomic status, and other individual and household characteristics were analyzed as potential risk factors for dengue.

Results: Study findings showed complex relationships between entomological indices and dengue risk. The presence of DENV-infected Aedes at the patient house was associated with 4.2-fold higher odds of dengue. On the other hand, Aedes presence (irrespective of infectious status) in the patient's house was negatively associated with dengue. In addition, the human immune response to Aedes bites, was higher in control than in case patients and Aedes adult abundance and immature indices were higher in control than in case houses at the household and the neighboring level. Multivariable analysis showed that children aged 10-14 years old and those aged 15-25 years old had respectively 4.5-fold and 2.9-fold higher odds of dengue infection than those older than 25 years.

Conclusion: DENV infection in female Aedes at the house level was positively associated with dengue infection, while adult Aedes presence in the household was negatively associated. This study highlights the potential benefit of monitoring dengue viruses in Aedes vectors. Our findings suggest that monitoring the presence of DENV-infected Aedes mosquitoes could be a better indicator of dengue risk than the traditional immature entomological indices.
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http://dx.doi.org/10.1371/journal.pntd.0008703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553337PMC
October 2020

Clinical and epidemiologic characteristics associated with dengue fever in Mombasa, Kenya.

Int J Infect Dis 2020 Nov 3;100:207-215. Epub 2020 Sep 3.

Eastern and Southern Africa Centre of International Parasite Control (ESACIPAC), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.

Objectives: Information on dengue in Africa is limited. To estimate the proportion of dengue-positive cases among febrile patients and describe clinical indicators of dengue, we conducted passive health facility-based fever surveillance in Mombasa, Kenya.

Methods: Non-malarial febrile patients between one and 55 years were enrolled at three health facilities between March 2016 and May 2017. Acute and convalescent blood samples were collected with an interval of 10-21 days. Acute samples were tested with dengue RDT and a selected subset with RT-PCR, and acute/convalescent samples with IgM/IgG ELISA.

Results: Among 482 enrollees, 295 (61.2%) were dengue-positive based on laboratory results. The surveillance covered the beginning of a dengue outbreak in April-May 2017, during which 73.9% of enrollees were dengue-positive. By contrast, during the non-outbreak period, 54.6% were dengue-positive. Dengue case status was positively associated with rash, fatigue, headache, retro-orbital pain, nausea/vomiting, nose bleeding, gum bleeding, loss of appetite, myalgia, and arthralgia. Dengue-positive cases in our study had mostly mild disease, with only two requiring observation, and no DHF.

Conclusions: The clinical response was generally mild relative to what was observed in SE Asia and the Americas. Given the high level of DENV transmission in Mombasa, more data would be needed to further understand the disease burden and improve case detection for surveillance/monitoring of outbreaks.
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http://dx.doi.org/10.1016/j.ijid.2020.08.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670221PMC
November 2020

Spatial spillover analysis of a cluster-randomized trial against dengue vectors in Trujillo, Venezuela.

PLoS Negl Trop Dis 2020 09 3;14(9):e0008576. Epub 2020 Sep 3.

MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: The ability of cluster-randomized trials to capture mass or indirect effects is one reason for their increasing use to test interventions against vector-borne diseases such as malaria and dengue. For the same reason, however, the independence of clusters may be compromised if the distances between clusters is too small to ensure independence. In other words they may be subject to spillover effects.

Methods: We distinguish two types of spatial spillover effect: between-cluster dependence in outcomes, or spillover dependence; and modification of the intervention effect according to distance to the intervention arm, or spillover indirect effect. We estimate these effects in trial of insecticide-treated materials against the dengue mosquito vector, Aedes aegypti, in Venezuela, the endpoint being the Breteau index. We use a novel random effects Poisson spatial regression model. Spillover dependence is incorporated via an orthogonalized intrinsic conditional autoregression (ICAR) model. Spillover indirect effects are incorporated via the number of locations within a certain radius, set at 200m, that are in the intervention arm.

Results: From the model with ICAR spatial dependence, and the degree of surroundedness, the intervention effect is estimated as 0.74-favouring the intervention-with a 95% credible interval of 0.34 to 1.69. The point estimates are stronger with increasing surroundedness within intervention locations.

Conclusion: In this trial there is some evidence of a spillover indirect effect of the intervention, with the Breteau index tending to be lower in locations which are more surrounded by locations in the intervention arm.
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http://dx.doi.org/10.1371/journal.pntd.0008576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494074PMC
September 2020

Immuno-pharmacokinetics of meglumine antimoniate in patients with cutaneous leishmaniasis caused by Leishmania Viannia.

Clin Infect Dis 2020 Aug 20. Epub 2020 Aug 20.

Centro Internacional de Entrenamiento e Investigaciones Médicas-CIDEIM, Cali-Colombia.

Introduction: Control of cutaneous leishmaniasis (CL) relies on chemotherapy, yet gaps in our understanding of the determinants of therapeutic outcome impede optimization of antileishmanial drug regimens. Pharmacodynamic (PD) parameters of antimicrobials are based on the relationship between drug concentrations/exposure and microbial kill. However, viable Leishmania persist in a high proportion of individuals despite clinical resolution, indicating that determinants other than parasite clearance are involved in drug efficacy.

Methods: In this study, the profiles of expression of neutrophil, monocyte, Th1 and Th17 gene signatures were characterized in peripheral blood mononuclear cells (PBMCs) during treatment with meglumine antimoniate (MA) and clinical cure of human CL caused by L. Viannia. We explored relationships of immune gene expression, with plasma and intracellular antimony (Sb) concentrations.

Results: Our findings show a rapid and orchestrated modulation of gene expression networks upon exposure to MA. We report non-linear pharmacokinetic/pharmacodynamic (PK/PD) relationships of Sb and gene expression dynamics in PBMCs, concurring with a time-lag in the detection of intracellular drug concentrations, and with PK evidence of intracellular Sb accumulation.

Discussion: Our results provide the knowledge base for optimization of antimonial drug treatments guiding the selection and/or design of targeted drug delivery systems that mediate intracellular drug accumulation and quantitatively portray the immune dynamics of therapeutic healing.
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http://dx.doi.org/10.1093/cid/ciaa1206DOI Listing
August 2020

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

Nat Hum Behav 2020 08 31;4(8):856-865. Epub 2020 Jul 31.

Secretariat of Health Surveillance, Department of Immunization and Communicable Diseases, Brazilian Ministry of Health, Brasília, Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.
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http://dx.doi.org/10.1038/s41562-020-0928-4DOI Listing
August 2020

Interepidemic Detection of Chikungunya Virus Infection and Transmission in Northeastern Thailand.

Am J Trop Med Hyg 2020 10;103(4):1660-1669

Department of Microbiology, Khon Kaen University, Khon Kaen, Thailand.

Chikungunya fever is a viral mosquito-borne, acute febrile illness associated with rash, joint pain, and occasionally prolonged polyarthritis. Chikungunya outbreaks have been reported worldwide including many provinces of Thailand. Although chikungunya virus (CHIKV) occurs in Thailand, details on its epidemiology are lacking compared with dengue, a common mosquito-borne disease in the country. Therefore, study on CHIKV and its epidemiology in both humans and mosquitoes is required to better understand its importance clinically and dynamics in community settings. So a prospective examination of virus circulation in human and mosquito populations in northeastern Thailand using serological and molecular methods, including the genetic characterization of the virus, was undertaken. The study was conducted among febrile patients in eight district hospitals in northeastern Thailand from June 2016 to October 2017. Using real-time PCR on the conserved region of nonstructural protein 1 gene, CHIKV was detected in eight (4.9%) of 161 plasma samples. Only one strain yielded a sequence of sufficient size allowing for phylogenetic analysis. In addition, anti-CHIKV IgM and IgG were detected in six (3.7%) and 17 (10.6%) patient plasma samples. The single sequenced sample belonged to the East/Central/South Africa (ECSA) genotype and was phylogenetically similar to the Indian Ocean sub-lineage. Adult mosquitoes were collected indoors and within a 100-m radius from the index case house and four neighboring houses. CHIKV was detected in two of 70 (2.9%) female mosquito pools. This study clearly demonstrated the presence and local transmission of the ECSA genotype of CHIKV in the northeastern region of Thailand.
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http://dx.doi.org/10.4269/ajtmh.20-0293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543817PMC
October 2020

Spatial regression and spillover effects in cluster randomized trials with count outcomes.

Biometrics 2020 Jun 18. Epub 2020 Jun 18.

MRC Tropical Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

This paper describes methodology for analyzing data from cluster randomized trials with count outcomes, taking indirect effects as well spatial effects into account. Indirect effects are modeled using a novel application of a measure of depth within the intervention arm. Both direct and indirect effects can be estimated accurately even when the proposed model is misspecified. We use spatial regression models with Gaussian random effects, where the individual outcomes have distributions overdispersed with respect to the Poisson, and the corresponding direct and indirect effects have a marginal interpretation. To avoid spatial confounding, we use orthogonal regression, in which random effects represent spatial dependence using a homoscedastic and dimensionally reduced modification of the intrinsic conditional autoregression model. We illustrate the methodology using spatial data from a pair-matched cluster randomized trial against the dengue mosquito vector Aedes aegypti, done in Trujillo, Venezuela.
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http://dx.doi.org/10.1111/biom.13316DOI Listing
June 2020

Use of pyriproxyfen in control of Aedes mosquitoes: A systematic review.

PLoS Negl Trop Dis 2020 06 12;14(6):e0008205. Epub 2020 Jun 12.

MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Dengue is the most rapidly spreading arboviral disease in the world. The current lack of fully protective vaccines and clinical therapeutics creates an urgent need to identify more effective means of controlling Aedes mosquitos, principally Aedes aegypti, as the main vector of dengue. Pyriproxyfen (PPF) is an increasingly used hormone analogue that prevents juvenile Aedes mosquitoes from becoming adults and being incapable of transmitting dengue. The objectives of the review were to (1) Determine the effect of PPF on endpoints including percentage inhibition of emergence to adulthood, larval mortality, and resistance ratios; and (2) Determine the different uses, strengths, and limitations of PPF in control of Aedes. A systematic search was applied to Pubmed, EMBASE, Web of Science, LILACS, Global Health, and the Cochrane database of Systematic Reviews. Out of 1,369 records, 90 studies met the inclusion criteria. Nearly all fit in one of the following four categories 1) Efficacy of granules, 2) Auto-dissemination/horizontal transfer, 3) use of ultra-low volume thermal fogging (ULV), thermal fogging (TF), or fumigant technologies, and 4) assessing mosquito resistance. PPF granules had consistently efficacious results of 90-100% inhibition of emergence for up to 90 days. The evidence is less robust but promising regarding PPF dust for auto-dissemination and the use of PPF in ULV, TF and fumigants. Several studies also found that while mosquito populations were still susceptible to PPF, the lethal concentrations increased among temephos-resistant mosquitoes compared to reference strains. The evidence is strong that PPF does increase immature mortality and adult inhibition in settings represented in the included studies, however future research should focus on areas where there is less evidence (e.g. auto-dissemination, sprays) and new use cases for PPF. A better understanding of the biological mechanisms of cross-resistance between PPF, temephos, and other insecticides will allow control programs to make better informed decisions.
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http://dx.doi.org/10.1371/journal.pntd.0008205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314096PMC
June 2020

Risks of Adverse Childhood Outcomes According to Prenatal Time of Exposure to Zika Virus: Assessment in a Cohort Exposed to Zika During an Outbreak in Colombia.

J Pediatric Infect Dis Soc 2021 Apr;10(3):337-340

Department of Health, Valle del Cauca, Cali, Colombia.

Late gestational exposure to Zika increases the odds of delay in the Bayley-II mental developmental index (MDI) in children with normal baseline neurologic assessments; 9-fold when comparing third and first trimester exposure. Risk of MDI developmental delay increases by 8% for each week of gestational age at time of exposure.
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http://dx.doi.org/10.1093/jpids/piaa042DOI Listing
April 2021

Targeted outdoor residual spraying, autodissemination devices and their combination against mosquitoes: field implementation in a Malaysian urban setting.

Bull Entomol Res 2020 Dec 15;110(6):700-707. Epub 2020 May 15.

Service d'Hygiène, Epidémiologie et Prévention, Hospices Civils de Lyon, F-69437Lyon, France and Laboratoire des Pathogènes Emergents - Fondation Mérieux, Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Centre National de la Recherche Scientifique, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 21, Avenue Tony Garnier, 69007Lyon, France.

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia. The study included one control site (three buildings) and three intervention sites which were treated as follows: targeted outdoor residual spraying only (TORS site, two buildings); deployment of autodissemination devices only (ADD site, four buildings); and the previous two treatments combined (TORS + ADD site, three buildings). The primary entomological measurement was per cent of positive ovitraps-ovitrap index (OI). The effect of each intervention on OI was analyzed by a modified ordinary least squares regression model. Relative to the control site, the TORS and ADD sites showed a reduction in the Aedes OI (-6.5%, P = 0.04 and -8.3%, P = 0.10, respectively). Analysis by species showed that, relative to control, the Ae. aegypti OI was lower in ADD (-8.9%, P = 0.03) and in TORS (-10.4%, P = 0.02). No such effect was evident in the TORS + ADD site. The present study provides insights into the methods to be used for the main trial. The combination of multiple insecticides with different modes of action in one package is innovative, although we could not demonstrate the additive effect of TORS + ADD. Further work is required to strengthen our understanding of how these interventions impact dengue vector populations and dengue transmission.
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http://dx.doi.org/10.1017/S0007485320000188DOI Listing
December 2020

The impact of insecticide treated curtains on dengue virus transmission: A cluster randomized trial in Iquitos, Peru.

PLoS Negl Trop Dis 2020 04 10;14(4):e0008097. Epub 2020 Apr 10.

Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9-71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2-51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.
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http://dx.doi.org/10.1371/journal.pntd.0008097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176142PMC
April 2020

Ability of the Premise Condition Index to Identify Premises with Adult and Immature Mosquitoes in Kampong Cham, Cambodia.

Am J Trop Med Hyg 2020 06;102(6):1432-1439

Malaria Consortium, Phnom Penh Center, Phnom Penh, Cambodia.

-transmitted diseases, especially dengue, are increasing throughout the world and the main preventive methods include vector control and the avoidance of mosquito bites. A simple Premise Condition Index (PCI) categorizing shade, house, and yard conditions was previously developed to help prioritize households or geographical areas where resources are limited. However, evidence about the accuracy of the PCI is mixed. The current study aimed to contribute to a better understanding of the relevance by collecting data from 2,400 premises at four time points over 1 year in Kampong Cham, Cambodia. Regression models were then used to identify associations between PCI and adult female mosquitoes and pupae. In addition, receiver operating characteristic curves were used to measure the ability of PCI to identify premises in the top quartile of mosquito abundance. The density of adult females was positively associated with PCI at the household (ratio of means = 1.16 per point on the PCI scale) and cluster level (ratio of means = 1.54). However, the number of pupae was negatively associated with PCI at the household level (rate ratio = 0.74) and did not have a statistically significant association at the cluster level. Receiver operating characteristic curves suggest the PCI score had "rather low accuracy" (area under the ROC curve = 0.52 and 0.54) at identifying top-quartile premises in terms of adult female and pupae, respectively. These results suggest that caution is warranted in the programmatic use of PCI in areas of similar geography and mosquito abundance.
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http://dx.doi.org/10.4269/ajtmh.19-0453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253129PMC
June 2020

Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients.

PLoS Negl Trop Dis 2020 03 4;14(3):e0008076. Epub 2020 Mar 4.

Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.

Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.
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http://dx.doi.org/10.1371/journal.pntd.0008076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055818PMC
March 2020

Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazil.

Int J Environ Res Public Health 2020 01 21;17(3). Epub 2020 Jan 21.

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife PE, 50740-465, Brazil.

Since an outbreak in Brazil, which started in 2015, Zika has been recognized as an important cause of microcephaly. The highest burden of this outbreak was in northeast Brazil, including the state of Pernambuco. The prevalence of congenital microcephaly in Pernambuco state was estimated from the RESP (Registro de Eventos em Saúde Pública) surveillance system, from August 2015 to August 2016 inclusive. The denominators were estimated at the municipality level from official demographic data. Microcephaly was defined as a neonatal head circumference below the 3rd percentile of the Intergrowth standards. Smoothed maps of the prevalence of microcephaly were obtained from a Bayesian model which was conditional autoregressive (CAR) in space, and first order autoregressive in time. A total of 742 cases were identified. Additionally, high and early occurrences were identified in the Recife Metropolitan Region, on the coast, and in a north-south band about 300 km inland. Over a substantial part of the state, the overall prevalence, aggregating over the study period, was above 0.5%. The reasons for the high occurrence in the inland area remain unclear.
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http://dx.doi.org/10.3390/ijerph17030700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037094PMC
January 2020

An investigation into the knowledge, perceptions and role of personal protective technologies in Zika prevention in Colombia.

PLoS Negl Trop Dis 2020 01 21;14(1):e0007970. Epub 2020 Jan 21.

Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Arboviruses transmitted by day-biting Aedes mosquitoes are a major public health concern. With the challenges inherent in arbovirus vaccine and therapeutics development, vector control and bite prevention strategies are among the limited options available for immediate intervention. Bite prevention through personal protective technologies (PPT), such as topical mosquito repellents or repellent-impregnated clothing, may help to decrease biting rates and, therefore, the risk of disease in groups most susceptible to adverse outcomes from Zika virus. However, achieving high uptake and compliance with PPT can be challenging.

Methodology/principal Findings: To gain an insight into the knowledge and concerns of pregnant women surrounding Zika and their opinions regarding PPT, particularly repellent clothing, a focus group study was carried out with pregnant women, women of reproductive age, and semi-structured interviews with their male partners in two cities in Colombia. The discussions revealed shortfalls in basic knowledge of Zika virus, with several pregnant participants reporting being unaware of the potential for Zika-related congenital malformations. Although participants generally considered Zika to be a significant personal threat, most rated it as less of a concern than dengue or diarrheal diseases. Overall, repellent clothing and other forms of PPT were viewed as effective, although some participants expressed concerns over the high costs of repellents, and safety fears of regular contact with repellent chemicals, which they perceived as potentially harmful. Plant-derived repellents were considered to be safer than synthetic chemical repellents. Discussions also highlighted that health centers were the preferred source of information on bite-reduction.

Conclusions/significance: Achieving high uptake and compliance with PPT in populations most at risk of adverse outcomes from Zika infection requires engaging key users in open dialogue to identify and address any practical issues regarding PPT use, and concerns over safety. The findings presented here suggest that educational campaigns should strongly emphasize the risks associated with Zika during pregnancy, and discuss safety profiles of approved synthetic repellents and the availability of EPA-approved plant-based repellents. In addition, the economic and political context should be a major consideration when evaluating personal mosquito-repellent strategies.
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http://dx.doi.org/10.1371/journal.pntd.0007970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010294PMC
January 2020

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BMC Infect Dis 2019 Dec 26;19(1):1081. Epub 2019 Dec 26.

Aix-Marseille University, Marseille, France.

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic.

Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies.

Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.
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http://dx.doi.org/10.1186/s12879-019-4685-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933915PMC
December 2019

Land use in relation to composition and abundance of phlebotomines (Diptera: Psychodidae) in five foci of domiciliary transmission of cutaneous leishmaniasis in the Andean region of Colombia.

Acta Trop 2020 Mar 19;203:105315. Epub 2019 Dec 19.

Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM, Carrera 125 # 19-225, Cali, Valle del Cauca 760031, Colombia; Universidad ICESI, Cali, Colombia. Electronic address:

American cutaneous leishmaniasis is a public health concern in Colombia, its incidence being sustained or focally increased principally by the emergence of domestic transmission concomitantly with the adaptation of the phlebotomine vectors to habitat transformation around households. The objective of the study is to scale up a rapid characterization methodology for evaluating the relationship of land use around the house to the composition and abundance of phlebotomines. Five sites with a history of domestic leishmaniasis transmission in the Andean area of Colombia were selected. The peri-domestic habitat was evaluated at 10 m intervals along eight radial transects, centered on each house, at 45° intervals using a web pattern. Phlebotomines were captured by placing three CDC light traps over two nights both indoors and outdoors (10 m from the house). Blood source and infection were determined by PCR. Spearman rank correlation coefficients and negative binomial regression were used to quantify associations between the phlebotomine abundance and habitat categories. The study demonstrated that the vectors were largely anthropophagic (62% of 79 were human blood) and that a single species in each site was favored by the pertaining agriculture monoculture. Specifically, Pintomyia (Pifanomyia) quasitownsendi was associated with sugar cane in Novillero and La Esmeralda; while Pi. (Pif.) longiflocosa was associated with coffee plantations in Agua Bonita and El Cucal. Honda Alta had a more diverse array of land use and forest coverage with a lower number of specimens but higher species diversity. In terms of distance from the house to an area of a given land use, the abundance of Pi. (Pif.) quasitownsendi was inversely related to the distance to sugar cane plantation (Spearman correlation coefficient, ρ = -0.56, p < 0.001 for outdoor catches, and ρ = -0.50, p < 0.001 indoors). A similar inverse relationship was observed for Pi. (Pif.) longiflocosa with regard to technified coffee (ρ = -0.51, p < 0.001 outdoors, and ρ = -0.48, p < 0.001 indoors). This rapid characterization methodology could guide public heath decision makers in identifying those houses at higher risk of domestic transmission, and also educate farmers to increase the distance between their crops and any neighboring houses.
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http://dx.doi.org/10.1016/j.actatropica.2019.105315DOI Listing
March 2020

Clinical and epidemiologic characteristics associated with dengue during and outside the 2016 outbreak identified in health facility-based surveillance in Ouagadougou, Burkina Faso.

PLoS Negl Trop Dis 2019 12 6;13(12):e0007882. Epub 2019 Dec 6.

Institute for Research on Sustainable Development (IRD), CEPED, Université de Paris, ERL INSERM SAGESUD, Paris, France.

Background: In Africa, the magnitude of dengue virus (DENV) transmission is largely unknown. In Burkina Faso, several outbreaks have been reported and data are often based on findings from outbreak investigations.

Methods: To better understand dengue epidemiology and clinical characteristics in Burkina Faso, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-malarial febrile illness at five primary healthcare facilities in Ouagadougou, Burkina Faso from December 2014 to February 2017, encompassing a 3-month dengue outbreak in September-November 2016. Acute and convalescent blood samples were collected within an interval of 10-21 days between visits. Acute samples were tested with dengue rapid diagnostic tests (RDT) and a selected subset with RT-PCR, and all acute/convalescent samples with IgM/IgG ELISA.

Results: Among 2929 non-malarial febrile patients, 740 (25%) were dengue-positive based on RT-PCR and/or IgM/IgG ELISA; 428 out of 777 patients (55%) and 312 out of 2152 (14%) were dengue-positive during outbreak and non-outbreak periods, respectively. There were 11% (316/2929) and 4% (129/2929) patients showing positive for NS1 and IgM, on the RDT, respectively. DENV 2 predominated during the outbreak, whereas DENV 3 predominated before the outbreak. Only 25% of dengue-positive cases were clinically diagnosed with suspected dengue. The odds of requiring observation for ≤3 days (versus routine outpatient care) were 11 times higher among dengue-positive cases than non-dengue cases. In adjusted analyses, dengue-positivity was associated with rash and retro-orbital pain (OR = 2.6 and 7.4, respectively) during the outbreak and with rash and nausea/vomiting (OR = 1.5 and 1.4, respectively) during the non-outbreak period.

Conclusion: Dengue virus is an important pathogen in Burkina Faso, accounting for a substantial proportion of non-malarial fevers both during and outside outbreak, but is only infrequently suspected by clinicians. Additional longitudinal data would help to further define characteristics of dengue for improved case detection and surveillance.
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http://dx.doi.org/10.1371/journal.pntd.0007882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897397PMC
December 2019

Frequent inappropriate use of unweighted summary statistics in systematic reviews of pathogen genotypes or genogroups.

J Clin Epidemiol 2020 03 15;119:26-35. Epub 2019 Nov 15.

Evidence Based Medicine Research Group, Ton Duc Thang University, Ho Chi Minh City, 70000, Vietnam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, 70000, Vietnam; Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan. Electronic address:

Objectives: Our study aimed to systematically assess and report the methodological quality used in epidemiological systematic reviews (SRs) and meta-analysis (MA) of pathogen genotypes/genogroups.

Study Design And Setting: Nine electronic databases and manual search of reference lists were used to identify relevant studies. The method types were divided into three groups: 1) with weighted pooling analysis (which we call MA), (2) unweighted analysis of the study-level measures (which we call summary statistics), and (3) without any data pooling (which we call SR only). Characteristics were evaluated using Assessment of Multiple Systematic Reviews (AMSTAR), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Risk Of Bias In Systematic reviews (ROBIS) tools. The protocol was registered in PROSPERO with CRD42017078146.

Results: Among 36 included articles, 5 (14%) studies conducted SR only, 16 (44%) performed MA, and 15 (42%) used summary statistics. The univariable and multivariable linear regression of AMSTAR and PRISMA scores showed that MA had higher quality compared with those with summary statistics. The SR only and summary statistics groups had approximately equal scores among three scales of AMSTAR, PRISMA, and ROBIS. The methodological quality of epidemiological studies has improved from 1999 to 2017.

Conclusion: Despite the frequent use of unweighted summary statistics, MA remains the most suitable method for reaching rational conclusions in epidemiological studies of pathogen genotypes/genogroups.
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http://dx.doi.org/10.1016/j.jclinepi.2019.11.009DOI Listing
March 2020

Implementation of guppy fish (Poecilia reticulata), and a novel larvicide (Pyriproxyfen) product (Sumilarv 2MR) for dengue control in Cambodia: A qualitative study of acceptability, sustainability and community engagement.

PLoS Negl Trop Dis 2019 11 18;13(11):e0007907. Epub 2019 Nov 18.

Technical Department, Malaria Consortium, Phnom Penh, Cambodia.

Background: In Cambodia dengue vector control activities are focused on larviciding with temephos and pyrethroid based adulticide sprays to which Aedes have been shown to be increasingly resistant. A cluster randomized trial assessed the impact of using biological control tools (guppy fish, pyriproxyfen (PPF), and Communication for Behavioral Impact (COMBI) activities in combination), which would be used in a value comparison to traditional chemical control tools. Given these new intervention methods, a qualitative assessment was designed in order to represent the quality of understanding, acceptance, and implementation by participants.

Methodology/principal Findings: A total of 103 participants in 12 Focus Group Discussions (FGDs) and nine In-Depth Interviews (IDIs) were included in the study. The majority of participants in intervention villages (50 out of 80) preferred guppy fish over other vector control methods due to ease of use and rearing, quick reproduction and propensity to eat larvae. A substantial number of participants (11 out of 40) in intervention villages with PPF favored it due to long-lasting effectiveness, lack of smell and easy maintenance. Participants showed high demand for both interventions and were willing to pay between 100-500 riel (0.03-0.13 USD). Nearly all participants perceived that the interventions resulted in a reduction in Aedes mosquitos (both adults and immatures) and dengue cases. The presence of larvae in the water despite the use of PPF was a source of concern for some participants, although this was overcome in some cases with proper health education through health volunteers. Interpersonal communication through health volunteers was the most favorite method of transmitting prevention messages.

Conclusions/significance: The community led COMBI strategy resulted in high acceptance and perceived effectiveness of the interventions in target villages. Health volunteers are an effective and accepted channel of communication to engage communities, disseminate information and promote behavioral change at the household and community level. If shown effective through corresponding entomological surveys, the interventions should be continued and further strengthened to ensure they are accessible, available and affordable.
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http://dx.doi.org/10.1371/journal.pntd.0007907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886868PMC
November 2019

Antibody response following scrub typhus infection: clinical cohort study.

Trop Med Int Health 2019 12 27;24(12):1455-1464. Epub 2019 Nov 27.

Department of Clinical Microbiology, Christian Medical College, Vellore, India.

Objective: Scrub typhus is a common cause of fever in Asia. The antibody response to infection and its effect on subsequent infection are unclear. We studied the IgM and IgG antibody response after infection, accounting for clinical severity.

Method: We studied 197 scrub typhus patients for up to 2 years post-infection. Overall, 501 blood samples were analysed for scrub typhus antibodies using ELISA. IgM and IgG ELISA optical densities (OD) were analysed using quantile regression. OD values of 1.0 (IgM) and 1.5 (IgG) were used to define seropositivity.

Results: IgM OD values fell rapidly from an initial peak after infection. 50% of cases were IgM seronegative after 82 days. About 2 years after fever onset, 50% of cases had fitted IgG OD values of <1.5. Patients with high initial IgG OD values (≥2.5, used as a proxy for probable previous scrub typhus infection) had a more sustained IgG response than those with a low initial IgG OD, and more often presented with complications (18/36 = 50% vs. 28/91 = 30.8%, risk ratio = 1.63, 95% CI 1.04, 2.55, P = 0.035). This association was robust to adjusting for age (risk ratio 1.50, 95% CI 0.96, 2.33, P = 0.072).

Conclusion: Cross-sectional IgG seroprevalence data substantially underestimate the proportion in a population ever infected with scrub typhus. A high initial IgG as a potential marker for previous scrub typhus infection may be associated with long-term IgG persistence and a higher risk of complicated scrub typhus.
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http://dx.doi.org/10.1111/tmi.13322DOI Listing
December 2019

Local human movement patterns and land use impact exposure to zoonotic malaria in Malaysian Borneo.

Elife 2019 10 22;8. Epub 2019 Oct 22.

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Human movement into insect vector and wildlife reservoir habitats determines zoonotic disease risks; however, few data are available to quantify the impact of land use on pathogen transmission. Here, we utilise GPS tracking devices and novel applications of ecological methods to develop fine-scale models of human space use relative to land cover to assess exposure to the zoonotic malaria in Malaysian Borneo. Combining data with spatially explicit models of mosquito biting rates, we demonstrate the role of individual heterogeneities in local space use in disease exposure. At a community level, our data indicate that areas close to both secondary forest and houses have the highest probability of human exposure, providing quantitative evidence for the importance of ecotones. Despite higher biting rates in forests, incorporating human movement and space use into exposure estimates illustrates the importance of intensified interactions between pathogens, insect vectors and people around habitat edges.
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http://dx.doi.org/10.7554/eLife.47602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814363PMC
October 2019