Pyriproxyfen and the microcephaly epidemic in Brazil - an ecological approach to explore the hypothesis of their association

Albuquerque, Maria de Fátima Pessoa Militão de; Souza, Wayner Vieira de; Mendes, Antônio da Cruz Gouveia; Lyra, Tereza Maciel; Ximenes, Ricardo A. A.; Araújo, Thália Velho Barreto de; Braga, Cynthia; Miranda-Filho, Demócrito Barros; Martelli, Celina Maria Turchi; Rodrigues, Laura C.

doi:10.1590/0074-02760160291

Cited by 36 publications

(22 citation statements)

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“…However, as is the case with surveillance in the United States, for example [27], the majority of cases did not have a documented cause and, in the current study, individual etiological investigation is only partially available. Suggestions that maternal vaccination, or the insecticide pyriproxyfen, could be risk factors for microcephaly have not been borne out [25,29,30].…”

Section: Discussionmentioning

confidence: 99%

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

Alexander

Souza

Rodrigues

et al. 2020

IJERPH

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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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Section: Discussionmentioning

confidence: 99%

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

Alexander

Souza

Rodrigues

et al. 2020

IJERPH

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“…Urban hospitals attract populations from a large area [73] and official reporting of cases is not broken down by municipality but rather by state, so that a direct analysis of geographical distribution of exposure to pyriproxyfen is difficult in these particular cases. A recent paper studied the association of microcephaly with the areas of claimed pyriproxyfen use and reports a lack of correlation [74]. If the geographic distribution of use and the reported residences of mothers are confirmed, this study would provide strong evidence against pyriproxyfen as a cause.…”

Section: Use Of Pyriproxyfen In Water Supply In Brazilmentioning

confidence: 74%

A Possible Link Between Pyriproxyfen and Microcephaly

Bar‐Yam

Nijhout

Parens

et al. 2017

Preprint

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The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. However its role is not confirmed despite individual cases in which viral infections were found in neural tissue. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus's role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses.Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly-incomplete formation of the anterior cerebral hemispheres-in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedentedit has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further. I. OVERVIEWIn 2015 and early 2016 over 6,000 suspected [1] cases of microcephaly and other neurodevelomental disorders were reported in Brazil, primarily in the northeast, a dramatic increase over . CC-BY-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/115279 doi: bioRxiv preprint first posted online Mar. 10, 2017; 2 expected numbers. By September 2016, over 2,000 were confirmed [2]. The cause of these developmental disorders has been widely attributed to a Zika virus epidemic first detected in May, 2015 [3]. While evidence exists, particularly in neurological infections of a few microcephalic cases [4,5], only 12 − 16% of confirmed microcephaly cases have also been confirmed as having Zika infections [1,6], preventing health authorities from determining a conclusive causal link [7,8]. T...

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“…However, smoking was found to be associated with microcephaly . Similarly, an ecological study found no correlation between the use of the larvicide pyriproxyfen in stored water and microcephaly among municipalities of the metropolitan region of Pernambuco, the epicenter of the Brazilian microcephaly epidemic (Albuquerque et al 2016). Interestingly, experiments in mouse models suggested that maternal diet protein restriction (Barbeito-Andrés et al 2020) and exposure to cyanobacterial saxitoxin through water intake (Pedrosa et al 2019) exacerbate brain malformations induced by ZIKV.…”

Section: Fig 2 Machine Learning Approach and Genetic Czs/microcephamentioning

confidence: 99%

Hypothetical Human Immune Genome Complex Gradient May Help to Explain the Congenital Zika Symdrome Catastrophe in Brazil: A New Theory

Oliveira

Bresani-Salvi

Morais

et al. 2020

Preprint

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There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas.We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others.Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297SNVs. We employed a two-step approach. In the first step, decision trees (DTs) were used to extract the most discriminating SNVs among populations. In the second step, machine learning algorithms were used to evaluate the quality of the SNV pool identified in step one for discriminating between individuals from sub-Saharan African and Latin-American populations.Our results suggest that 10 SNVs from 10 genes (CLEC4M, CD58, OAS2, CD80, VEPH1, CTLA4, CD274, CD209, PLAAT4, CREB3L1) were able to discriminate sub-Saharan Africans from Latin American populations using only immune genome data, with an accuracy close to 100%.Moreover, we found that these SNVs form a genome gradient across the three main continental populations. These SNVs are important elements of the innate immune system and in the response against viruses. Our data support the Human Immune Genome Complex Gradient hypothesis as a new theory that may help to explain the CZS catastrophe in Brazil.

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Pyriproxyfen and the microcephaly epidemic in Brazil - an ecological approach to explore the hypothesis of their association

Cited by 36 publications

References 5 publications

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

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

A Possible Link Between Pyriproxyfen and Microcephaly

Hypothetical Human Immune Genome Complex Gradient May Help to Explain the Congenital Zika Symdrome Catastrophe in Brazil: A New Theory

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