Development, environmental degradation, and disease spread in the Brazilian Amazon.

The Amazon is Brazil's greatest natural resource and invaluable to the rest of the world as a buffer against climate change. The recent election of Brazil's president brought disputes over development plans for the region back into the spotlight. Historically, the development model for the Amazon has focused on exploitation of natural resources, resulting in environmental degradation, particularly deforestation. Although considerable attention has focused on the long-term global cost of "losing the Amazon," too little attention has focused on the emergence and reemergence of vector-borne diseases that directly impact the local population, with spillover effects to other neighboring areas. We discuss the impact of Amazon development models on human health, with a focus on vector-borne disease risk. We outline policy actions that could mitigate these negative impacts while creating opportunities for environmentally sensitive economic activities.

Estimating the SARS-CoV2 infections detection rate and cumulative incidence in the World Health Organization African Region 10 months into the pandemic.

As of 03 January 2021, the WHO African region is the least affected by the coronavirus disease-2019 (COVID-19) pandemic, accounting for only 2.4% of cases and deaths reported globally. However, concerns abound about whether the number of cases and deaths reported from the region reflect the true burden of the disease and how the monitoring of the pandemic trajectory can inform response measures.We retrospectively estimated four key epidemiological parameters (the total number of cases, the number of missed cases, the detection rate and the cumulative incidence) using the COVID-19 prevalence calculator tool developed by Resolve to Save Lives. We used cumulative cases and deaths reported during the period 25 February to 31 December 2020 for each WHO Member State in the region as well as population data to estimate the four parameters of interest. The estimated number of confirmed cases in 42 countries out of 47 of the WHO African region included in this study was 13 947 631 [95% confidence interval (CI): 13 334 620-14 635 502] against 1 889 512 cases reported, representing 13.5% of overall detection rate (range: 4.2% in Chad, 43.9% in Guinea). The cumulative incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated at 1.38% (95% CI: 1.31%-1.44%), with South Africa the highest [14.5% (95% CI: 13.9%-15.2%)] and Mauritius [0.1% (95% CI: 0.099%-0.11%)] the lowest. The low detection rate found in most countries of the WHO African region suggests the need to strengthen SARS-CoV-2 testing capacities and adjusting testing strategies.

COVID-19 in the WHO African region: using risk assessment to inform decisions on public health and social measures.

Successive waves of COVID-19 transmission have led to exponential increases in new infections globally. In this study, we have applied a decision-making tool to assess the risk of continuing transmission to inform decisions on tailored public health and social measures (PHSM) using data on cases and deaths reported by Member States to the WHO Regional Office for Africa as of 31 December 2020. Transmission classification and health system capacity were used to assess the risk level of each country to guide implementation and adjustments to PHSM. Two countries out of 46 assessed met the criteria for sporadic transmission, one for clusters of cases, and 43 (93.5%) for community transmission (CT) including three with uncontrolled disease incidence (Eswatini, Namibia and South Africa). Health system response's capacities were assessed as adequate in two countries (4.3%), moderate in 13 countries (28.3%) and limited in 31 countries (64.4%). The risk level, calculated as a combination of transmission classification and health system response's capacities, was assessed at level 0 in one country (2.1%), level 1 in two countries (4.3%), level 2 in 11 countries (23.9%) and level 3 in 32 (69.6%) countries. The scale of severity ranged from 0 to 4, with 0 the lowest. CT coupled with limited response capacity resulted in a level 3 risk assessment in most countries. Countries at level 3 should be considered as priority focus for additional assistance, in order to prevent the risk rising to level 4, which may necessitate enforcing hard and costly lockdown measures. The large number of countries at level 3 indicates the need for an effective risk management system to be used as a basis for adjusting PHSM at national and sub-national levels.

Measuring Timeliness of Outbreak Response in the World Health Organization African Region, 2017-2019.

Large-scale protracted outbreaks can be prevented through early detection, notification, and rapid control. We assessed trends in timeliness of detecting and responding to outbreaks in the African Region reported to the World Health Organization during 2017-2019. We computed the median time to each outbreak milestone and assessed the rates of change over time using univariable and multivariable Cox proportional hazard regression analyses. We selected 296 outbreaks from 348 public reported health events and evaluated 184 for time to detection, 232 for time to notification, and 201 for time to end. Time to detection and end decreased over time, whereas time to notification increased. Multiple factors can account for these findings, including scaling up support to member states after the World Health Organization established its Health Emergencies Programme and support given to countries from donors and partners to strengthen their core capacities for meeting International Health Regulations.

Measuring the contribution of human mobility to malaria persistence.

BACKGROUND: To achieve malaria elimination, it is important to determine the role of human mobility in parasite transmission maintenance. The Alto Juruá basin (Brazil) exhibits one of the largest vivax and falciparum malaria prevalence in the Amazon. The goal of this study was to estimate the contribution of human commutes to malaria persistence in this region, using data from an origin-destination survey. METHODS: Data from an origin-destination survey were used to describe the intensity and motivation for commutations between rural and urban areas in two Alto Juruá basin (Brazil) municipalities, Mâncio Lima and Rodrigues Alves. The relative time-person spent in each locality per household was estimated. A logistic model was developed to estimate the effect of commuting on the probability of contracting malaria for a certain residence zone inhabitant commuting to another zone. RESULTS: The main results suggest that the assessed population is not very mobile. A total of [Formula: see text] households reported spending over [Formula: see text] of their annual person-hour in areas within the same residence zone. Study and work were the most prevalent commuting motivations, calculated at [Formula: see text] and [Formula: see text] respectively. Spending person-hours in urban Rodrigues Alves conferred relative protection to urban Mâncio Lima residents. The opposite effect was observed for those spending time in rural areas of both municipalities. CONCLUSION: Residence area is a stronger determinant for contracting malaria than commuting zones in the Alto Juruá region. As these municipalities are a hotspot for Plasmodium transmission, understanding the main local human fluxes is essential for planning control strategies, since the probability of contracting malaria is dependent on the transmission intensity of both the origin and the displacement area. The natural conditions for the circulation of certain pathogens, such as Plasmodium spp., combined with the Amazon human mobility pattern indicate the need for disease control perspective changes. Therefore, intersectoral public policies should become the basis for health mitigation actions.

A modelling approach for correcting reporting delays in disease surveillance data.

One difficulty for real-time tracking of epidemics is related to reporting delay. The reporting delay may be due to laboratory confirmation, logistical problems, infrastructure difficulties, and so on. The ability to correct the available information as quickly as possible is crucial, in terms of decision making such as issuing warnings to the public and local authorities. A Bayesian hierarchical modelling approach is proposed as a flexible way of correcting the reporting delays and to quantify the associated uncertainty. Implementation of the model is fast due to the use of the integrated nested Laplace approximation. The approach is illustrated on dengue fever incidence data in Rio de Janeiro, and severe acute respiratory infection data in the state of Paraná, Brazil.

Correction to: Seasonal dynamics of influenza in Brazil: the latitude effect.

Following publication.

Seasonal dynamics of influenza in Brazil: the latitude effect.

BACKGROUND: Influenza is a global transmissible disease. Its dynamics is far better understood in temperate climates than in the tropics. We aim to close this knowledge gap between tropical and temperate regions by showing how the influenza seasonality evolves in Brazil, a tropical country that encompasses a wide range of latitudes and six climatic sub-types. METHODS: We analyzed a state-level, weekly Syndrome of Acute Respiratory Disease (SARI) incidence data ranging from 2010 to 2016. We combined two techniques hierarchically: first the wavelet decomposition technique to detect annual periodicity and then circular statistics to describe seasonal measures of the periodic states. RESULTS: We found significant annual periodicity in 44% of the states. For these, we calculated several seasonal measures such as the center of gravity or mean timing of activity. The relationship between the seasonal signatures and latitude was clear and statistically significant. States with seasonal signature are clustered along the coast. Most Amazonian and Central West states exhibit no seasonal behavior. Among the seasonal states, influenza starts in Northeast region, spreading southbound. CONCLUSIONS: Our study advances the comprehension of influenza seasonality in tropical areas and could be used to design more effective prevention and control strategies.

Canine visceral leishmaniasis in Araçatuba, state of São Paulo, Brazil, and its relationship with characteristics of dogs and their owners: a cross-sectional and spatial analysis using a geostatistical approach.

BACKGROUND: The incidence of visceral leishmaniasis (VL), one of the most important neglected diseases worldwide, is increasing in Brazil. The objectives of this study were to determine the canine VL (CanL) seroprevalence in an urban area of Araçatuba municipality and to evaluate its relationship with the characteristics of dogs and their owners. RESULTS: The CanL seroprevalence in the study area was 0.081 (95% credible interval [CI]: 0.068-0.096). The following covariates/categories were positively associated with the occurrence of a seropositive dog: more than 10 dogs that had lived in the house (odds ratio [OR] = 2.36; 95% CI: 1.03-5.43) (baseline: 0-10 dogs); house with dogs that previously died of VL (OR = 4.85; 95% CI: 2.65-8.86) or died of causes other than old age (OR = 2.26; 95% CI: 1.12-4.46) (baseline: natural or no deaths); dogs that spent the day in a sheltered backyard (OR = 2.14; 95% CI: 1.05-4.40); dogs that spent the day in an unsheltered backyard or the street (OR = 2.67; 95% CI: 1.28-5.57) (baseline: inside home). Spatial dependence among observations occurred within about 45.7 m. CONCLUSIONS: The number of dogs that had lived in the house, previous deaths by VL or other cause, and the place the dog stayed during the day were associated with the occurrence of a VL seropositive dog. The short-distance spatial dependence could be related to the vector characteristics, producing a local neighbourhood VL transmission pattern. The geostatistical approach in a Bayesian context using integrated nested Laplace approximation (INLA) allowed to identify the covariates associated with VL, including its spatially dependent transmission pattern.

Correction to: Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

After publication of the article [1], it has been brought to our attention that the y-axis of Fig. 6 has been labeled incorrectly. It should read "linear predictor". This has now been corrected in the original article.

Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

BACKGROUND: In the process of geographical retraction of malaria, some important endemicity pockets remain. Here, we report results from a study developed to obtain detailed community data from an important malaria hotspot in Latin America (Alto Juruá, Acre, Brazil), to investigate the association of malaria with socioeconomic, demographic and living conditions. METHODS: A household survey was conducted in 40 localities (n = 520) of Mâncio Lima and Rodrigues Alves municipalities, Acre state. Information on previous malaria, schooling, age, gender, income, occupation, household structure, habits and behaviors related to malaria exposure was collected. Multiple correspondence analysis (MCA) was applied to characterize similarities between households and identify gradients. The association of these gradients with malaria was assessed using regression. RESULTS: The first three dimensions of MCA accounted for almost 50% of the variability between households. The first dimension defined an urban/rurality gradient, where urbanization was associated with the presence of roads, basic services as garbage collection, water treatment, power grid energy, and less contact with the forest. There is a significant association between this axis and the probability of malaria at the household level, OR = 1.92 (1.23-3.02). The second dimension described a gradient from rural settlements in agricultural areas to those in forested areas. Access via dirt road or river, access to electricity power-grid services and aquaculture were important variables. Malaria was at lower risk at the forested area, OR = 0.55 (1.23-1.12). The third axis detected intraurban differences and did not correlate with malaria. CONCLUSIONS: Living conditions in the study area are strongly geographically structured. Although malaria is found throughout all the landscapes, household traits can explain part of the variation found in the odds of having malaria. It is expected these results stimulate further discussions on modelling approaches targeting a more systemic and multi-level view of malaria dynamics.

Prenatal care and childbirth assistance in Amazonian women before and after the Pacific Highway Construction (2003-2011): a cross-sectional study.

BACKGROUND: Attention to prenatal care and child delivery is important for the health of women and children, but in the Amazon these indicators tend to be historically unfavorable, in part by geographical and political isolation. In 2003 both Brazilian and Peru governments have finished paving an international road connecting remotes areas in the Brazilian Amazon to the Pacific coast in Peru. METHODS: The situation of prenatal care and child delivery with mothers of children under 5 years old living in the urban area of Assis Brasil, Acre was assessed in two cross-sectional studies performed in 2003 and 2011, corresponding to the period before and after the Pacific highway construction. RESULTS: In 2003, most mothers were of black/Afro-American ethnicity, or "pardos" (the offspring of a Caucasian with a African descendant) (77.69 %), had more than 4 years of schooling (73.40 %) and had a mean age of 22.18 years. In 2011, the number of as a migration of indigenous women increased from 0 to 14.40 % of the respondents, because of migration from communities along the rivers to urban areas, with no other significant changes in maternal characteristics. No significant improvement in childbirth assistance was noticed between 1997 and 2011; only the percentage of in-hospital vaginal deliveries performed by doctors increased from 17.89 to 66.26 % (p <0.001) during this period. Access to prenatal care was associated with white ethnicity in 2003, and higher socioeconomic level and white ethnicity in 2011, while the higher number of prenatal visits was associated with higher maternal education and higher socioeconomic levels in 2011. Vaginal child delivery at a hospital facility was associated with maternal age in 2003, and year of birth, being of white ethnicity and higher level of education in 2011. CONCLUSIONS: The indicators of prenatal care and child delivery were below the national average, showing that geographical isolation still affects women's health care in the Amazon, despite the construction of the highway and governmental health protocols adopted during this period.

Zika is not a reason for missing the Olympic Games in Rio de Janeiro: response to the open letter of Dr Attaran and colleagues to Dr Margaret Chan, Director - General, WHO, on the Zika threat to the Olympic and Paralympic Games.

Attaran and colleagues in an open letter to WHO expressed their concern about the upcoming Olympic and Paralympic Games in Rio de Janeiro and the threat posed by the Zika epidemic (Attaran 2016). We agree that Zika virus is of great public health concern and much remains to be known about this disease. Care should be taken to reduce the risk of infection, especially to pregnant women. However, we argue that this is not sufficient reason for changing the original plans for the Games, in particular because of the time of the year when they will take place. The present article outlines several scientific results related to Zika and mosquito-borne infectious diseases dynamics that we believe ratify the current position of WHO in not endorsing the postponing or relocation of the 2016 Olympic and Paralympic Games (WHO 2016).

Unveiling time in dose-response models to infer host susceptibility to pathogens.

The biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. As much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. Here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (Drosophila melanogaster) with a range of pathogen (Drosophila C Virus) doses and recording survival over time. The experiment was replicated for flies carrying the Wolbachia symbiont, which is known to reduce host susceptibility to viral infections. The entire dataset is fitted by a novel quantitative framework that significantly extends classical methods for microbial risk assessment and provides accurate distributions of symbiont-induced protection. More generally, our data-driven modeling procedure provides novel insights for study design and analyses to assess interventions.

Contribution of fish farming ponds to the production of immature Anopheles spp. in a malaria-endemic Amazonian town.

BACKGROUND: In the past decade fish farming has become an important economic activity in the Occidental Brazilian Amazon, where the number of new fish farms is rapidly increasing. One of the primary concerns with this phenomenon is the contribution of fishponds to the maintenance and increase of the anopheline mosquito population, and the subsequent increase in human malaria burden. This study reports the results of a 2-year anopheline abundance survey in fishponds and natural water bodies in a malaria-endemic area in northwest Brazil. The objective of this study was to investigate the contribution of natural water bodies (rivers, streams, creeks, ponds, and puddles) and artificial fishponds as breeding sites for Anopheles spp. in Mâncio Lima, Acre and to investigate the effect of limnological and environmental variables on Anopheles spp. larval abundance. METHODS: Natural water bodies and fishponds were sampled at eight different times over 2 years (early, mid and late rainy season, dry season) in the Amazonian town of Mâncio Lima, Acre. Anopheline larvae were collected with an entomological dipper, and physical, chemical and ecological characteristics of each water body were measured. Management practices of fishpond owners were ascertained with a systematic questionnaire. RESULTS: Fishponds were four times more infested with anopheline larvae than natural water bodies. Electrical conductivity and the distance to the nearest house were both significant inverse predictors of larval abundance in natural water bodies. The density of larvae in fishponds raised with increasing border vegetation. Fishponds owned by different farmers varied in the extent of anopheline larval infestation but ponds owned by the same individual had similar infestation patterns over time. Commercial fishponds were 1.7-times more infested with anopheline larvae compared to fishponds for family use. CONCLUSIONS: These results suggest that fishponds are important breeding sites for anopheline larvae, and that adequate management activities, such as removal of border vegetation could reduce the abundance of mosquito larvae, most importantly Anopheles darlingi.

Socioeconomic inequities and hepatitis A virus infection in Western Brazilian Amazonian children: spatial distribution and associated factors.

BACKGROUND: Hepatitis A is still a neglected health problem in the world. The most affected areas are the ones with disadvantaged socioeconomic conditions. In Brazil, seroprevalence studies showed that 64.7 % of the general population has antibodies against HAV (hepatitis A virus), and the Amazon region has the highest seroprevalence in the country. METHODS: In the present study the seroprevalence of total HAV antibodies in children between 1 and 5 years old residing in the urban area of Assis Brasil, Acre was measured and spatial distribution of several socioeconomic inequities was evaluated. RESULTS: In the year of 2011, seroprevalence rate was 16.66 %. Factors associated with having a positive serology identified by multivariate analysis were being of indigenous ethnicity [adjusted Odds Ratio (aOR) = 3.27, CI 1.45-7.28], usage of water from the public system (aOR = 8.18, CI 1.07-62.53), living in a house not located in a street (aOR = 3.48, CI 1.54-7.87), and child age over 4 years old (aOR = 2.43, CI 1.23-4.79). The distribution of seropositive children was clustered in the eastern part of the city, where several socioeconomic inequities (lack of flushed toilets, lack of piped water inside the household and susceptibility of the household to flooding during rain, low maternal education, having wood or ground floor at home, and not owning a house, lack of piped water at home, and type of drinking water) also clustered. CONCLUSIONS: The findings highlight that sanitation and water treatment still need improvement in the Brazilian Amazon, and that socioeconomic development is warranted in order to decrease this and other infectious diseases.

Mass trapping with MosquiTRAPs does not reduce Aedes aegypti abundance.

The objective of this study was to evaluate the effectiveness of Aedes aegypti mass trapping using the sticky trap MosquiTRAP (MQT) by performing a cluster randomised controlled trial in Manaus, state of Amazonas, Brazil. After an initial questionnaire and baseline monitoring of adult Ae. aegypti abundance with BG-Sentinel (BGS) traps in six clusters, three clusters were randomly assigned to the intervention arm where each participating household received three MQTs for mass trapping during 17 months. The remaining three clusters (control arm) did not receive traps. The effect of mass trapping on adult Ae. aegypti abundance was monitored fortnightly with BGS traps. During the last two months of the study, a serological survey was conducted. After the study, a second questionnaire was applied in the intervention arm. Entomological monitoring indicated that MQT mass trapping did not reduce adult Ae. aegypti abundance. The serological survey indicated that recent dengue infections were equally frequent in the intervention and the control arm. Most participants responded positively to questions concerning user satisfaction. According to the results, there is no evidence that mass trapping with MQTs can be used as a part of dengue control programs. The use of this sticky trap is only recommendable for dengue vector monitoring.

Surveillance of dengue vectors using spatio-temporal Bayesian modeling.

BACKGROUND: At present, dengue control focuses on reducing the density of the primary vector for the disease, Aedes aegypti, which is the only vulnerable link in the chain of transmission. The use of new approaches for dengue entomological surveillance is extremely important, since present methods are inefficient. With this in mind, the present study seeks to analyze the spatio-temporal dynamics of A. aegypti infestation with oviposition traps, using efficient computational methods. These methods will allow for the implementation of the proposed model and methodology into surveillance and monitoring systems. METHODS: The study area includes a region in the municipality of Rio de Janeiro, characterized by high population density, precarious domicile construction, and a general lack of infrastructure around it. Two hundred and forty traps were distributed in eight different sentinel areas, in order to continually monitor immature Aedes aegypti and Aedes albopictus mosquitoes. Collections were done weekly between November 2010 and August 2012. The relationship between egg number and climate and environmental variables was considered and evaluated through Bayesian zero-inflated spatio-temporal models. Parametric inference was performed using the Integrated Nested Laplace Approximation (INLA) method. RESULTS: Infestation indexes indicated that ovipositing occurred during the entirety of the study period. The distance between each trap and the nearest boundary of the study area, minimum temperature and accumulated rainfall were all significantly related to the number of eggs present in the traps. Adjusting for the interaction between temperature and rainfall led to a more informative surveillance model, as such thresholds offer empirical information about the favorable climatic conditions for vector reproduction. Data were characterized by moderate time (0.29 - 0.43) and spatial (21.23 - 34.19 m) dependencies. The models also identified spatial patterns consistent with human population density in all sentinel areas. The results suggest the need for weekly surveillance in the study area, using traps allocated between 18 and 24 m, in order to understand the dengue vector dynamics. CONCLUSIONS: Aedes aegypti, due to it short generation time and strong response to climate triggers, tend to show an eruptive dynamics that is difficult to predict and understand through just temporal or spatial models. The proposed methodology allowed for the rapid and efficient implementation of spatio-temporal models that considered zero-inflation and the interaction between climate variables and patterns in oviposition, in such a way that the final model parameters contribute to the identification of priority areas for entomological surveillance.

Socioeconomic inequalities are still a barrier to full child vaccine coverage in the Brazilian Amazon: a cross-sectional study in Assis Brasil, Acre, Brazil.

INTRODUCTION: Vaccines are very important to reduce morbidity and mortality by preventable infectious diseases, especially during childhood. Optimal coverage is not always achieved, for several reasons. Here we assessed vaccine coverage for the first 12 months of age in children between 12 and 59 months old, residing in the urban area of a small Amazonian city, and factors associated with incomplete vaccination. METHODS: A census was performed in the urban area of Assis Brasil, in the Brazilian Amazon, in January 2010, with mothers of 282 children aged 12 to 59 months old, using structured interviews and data from vaccination cards. Mixed logistic regression was used to determine factors associated with incomplete vaccination schemes. RESULTS: Only 82.6% of all children had a completed the basic vaccine scheme for the first year of life. Vaccine coverage ranged from 52.7% coverage (oral rotavirus vaccine) to 99.7% coverage (for Bacille Calmette-Guérin). The major deficiencies occurred in doses administered after the first six months of life. Incomplete vaccination was associated with not having enough income to buy a house (aOR = 2.12, 95% CI 1.06-4.21), low maternal schooling (aOR = 2.60, 95% CI 1.28 - 5.29) , and time of residence of the child in the urban area of the city (aOR = 0.73, 95% CI 0.55 - 0.95). CONCLUSIONS: This study showed that vaccine coverage in the first twelve months of life in Assis Brasil is similar to other areas in the Amazon and it is below the coverage postulated by the Brazilian Ministry of Health. Low vaccine coverage was associated with socioeconomic inequities that still prevail in the Brazilian Amazon. Short and long-term strategies must be taken to update child vaccines and increase vaccine coverage in the Amazon.

She's a femme fatale: low-density larval development produces good disease vectors.

Two hypotheses for how conditions for larval mosquitoes affect vectorial capacity make opposite predictions about the relationship of adult size and frequency of infection with vector-borne pathogens. Competition among larvae produces small adult females. The competition-susceptibility hypothesis postulates that small females are more susceptible to infection and predicts frequency of infection should decrease with size. The competition-longevity hypothesis postulates that small females have lower longevity and lower probability of becoming competent to transmit the pathogen and thus predicts frequency of infection should increase with size. We tested these hypotheses for Aedes aegypti in Rio de Janeiro, Brazil, during a dengue outbreak. In the laboratory, longevity increases with size, then decreases at the largest sizes. For field-collected females, generalised linear mixed model comparisons showed that a model with a linear increase of frequency of dengue with size produced the best Akaike's information criterion with a correction for small sample sizes (AICc). Consensus prediction of three competing models indicated that frequency of infection increases monotonically with female size, consistent with the competition-longevity hypothesis. Site frequency of infection was not significantly related to site mean size of females. Thus, our data indicate that uncrowded, low competition conditions for larvae produce the females that are most likely to be important vectors of dengue. More generally, ecological conditions, particularly crowding and intraspecific competition among larvae, are likely to affect vector-borne pathogen transmission in nature, in this case via effects on longevity of resulting adults. Heterogeneity among individual vectors in likelihood of infection is a generally important outcome of ecological conditions impacting vectors as larvae.