Central Nervous System Malformations Research Articles

Cavernous malformations of central nervous system in pediatric patients: our single-centered experience in 50 patients and review of literature.

Cavernous malformations (CMs) are rare developmental cerebrovascular malformations of the central nervous system with a childhood prevalence of 0.3 to 0.53%. Our purpose was to assess the clinical features and microsurgical outcome in pediatric central nervous system (CNS) CMs. We retrospectively enrolled all the CM patients admitted to our institute from 1 January 2001 to 31 December 2014. Data was analyzed for their clinical features and surgical outcome. A total of 50 patients with CMs (30 supratentorial, 14 infratentorial, and 6 spinal) with a mean age of 14years (3-18years, SD ±4.64) were enrolled into the study. Most of these patients (78%) were male. Size varied from 1.2 to 6cm. Three patients had multiple CMs. Symptoms of CMs were site specific. Seizure was the most common symptom (63.3%) of CMs at supratentorial location followed by headache (46%) and neurodeficiency (26%), while all brainstem and spinal CMs presented with neurodeficiencies. History of clinically significant acute hemorrhage was present in 19.2% of supratentorial (ST) superficial CMs, 50% of ST deep CMs, 25% of cerebellar CMs, 44.4% of brainstem CMs, and 50% of spinal CMs. Forty-five CMs in 44 patients were surgically excised. Their follow-up ranged from 6 to 162months (mean 47.2months, SD ±53). All supratentorial CM patients showed improvement in their symptoms. Patients with preoperative seizure showed good seizure control with Engel scale I in 16 (94.1%) and Engel scale II in 1 (5.9%). In infratentorial (IT) and spinal CM patients, 92.3 and 66.7% had improvement in their neurodeficiencies, respectively. There was no mortality in our series. Microsurgical excision of CNS CM results in excellent neurological outcome in pediatric patients. Early intervention is necessary in spinal CMs for better outcome.

Different clinical picture of cytomegalovirus neuroinfection – diagnostic and treatment results

Objective: Presentation of different clinical cases of human cytomegalovirus (HCMV) neuroinfection in children Methods: In 42 children (25 females, 17 males) at the age of from one month to 14 years with different clinical symptoms and signs, DNA cytomegalovirus was found in cerebrospinal fluid (CSF) by PCR method. Serological tests as well as quantitative PCR method were used to establish number of viral copies in blood and urine. Antiviral treatment with intravenous ganciclovir (GCV) and also oral valganciclovir (VGC) were administered. Results: Symptomatic epilepsy was the most frequent (37 children) clinical diagnosis in HCMV neuroinfecion. Central nervous system malformations (pachygyria/polimicrogyria) were diagnosed in six patients with epilepsy. Three infants with HCMV neuroinfection and epileptic seizures had severe sensorineural hearing loss. Five infants with drug resistant West syndrome were treated antivirally (ganciclovir) before simultaneous regimen with GCV and synthetic ACTH. One male adolescent had optic neuritis, one 12 year old girl had ADEM. Both were successfully (full recovery) treated with intravenous ganciclovir. In all infants, GCV regimen for at least three weeks was effective and control CSF examination was negative for HCMV DNA. The elimination of HCMV DNA from CSF was also achieved in one patient with congenital cytomegalovirus neuroinfection and persistent neutropenia treated with oral 3-week, valganciclovir course. The elimination was achieved later than in other patients. After the antiviral treatment, this girl, who, at the age of 7 months, had the highest number of HCMV viral copies excreted in urine (10 000 000/1ml), at the age of one year, had no neurological signs. Her psychomotor development is normal. In 14 (29.7%) children, antiepileptic drugs were withdrawn without recurrence of epileptic seizures during ten year follow-up period. Conclusion: Cytomegalovirus neuroinfection in immunocompetent children at different ages has various, severe neurological symptoms and signs, but could be treated efficiently.

Factors Associated with Postoperative Complications in Hydrocephalic Infants Diagnosed at Bernard Mevs Hospital in Port-au-Prince, Haiti, from 2011 to 2013.

Complications worsen the prognosis of hydrocephalic children who undergo surgery. The main objective of this study was to determine factors associated with postoperative complications in Haitian infants with hydrocephaly. This was a cross-sectional study conducted on hydrocephalic infants diagnosed in a Haitian hospital from 2011 to 2013. Records were consulted to gather key variables that were evaluated in relation to the occurrence of postoperative complications. Any variable whose P value was less than 0.05 for the Mantel-Haenszel χ2 test was considered a factor associated with postoperative complications. The prevalence of hydrocephalus in our sample was 6.6%. Of the 131 cases of hydrocephalus surveyed, 75 were selected. The sex ratio was 1.02, and the age group from 1 to 6 months old was the most affected (52% of cases). The increase in head circumference (96% of cases) was the most common clinical sign. A total of 70.7% of the infants underwent imaging work-up, and 26.7% had central nervous system malformations. A total of 84% received surgical treatment, and one third of the operated infants presented with complications, the most common being infection (8%). Postoperative mortality was 6.7%, and 40% of operated infants had no postoperative care after medical discharge. Ventriculoperitoneal shunt was more significantly associated with complications than endoscopic third ventriculostomy (odds ratio 3.25, P= 0.03). Hydrocephalus in Haitian infants is diagnosed late and inadequately investigated, treated, and monitored. Ventriculoperitoneal shunts are significantly related to more postoperative complications than endoscopic third ventriculostomy.

Fetal central nervous system malformations: a ten year review of prenatal consultations at a tertiary care center (P4.150)

Fetal central nervous system malformations: a ten year review of prenatal consultations at a tertiary care center (P4.150)

Congenital malformations, palliative care and postnatal redirection to more intensive treatment – a review at a Swiss tertiary center

Purpose: The so-called lethal malformations pose ethical challenges. Most affected fetuses die before or at birth. Live-born neonates commonly receive palliative care. If the postnatal course is better than expected, redirection towards more treatment may occur. We aimed to analyze this in a Swiss patient cohort. Materials and methods: Over 6 years, fetal malformation was suspected in 1113 cases. We identified patients prenatally assigned to palliative care, assessed pre- and postnatal diagnoses, and outcomes. Results: Fourteen neonates received palliative care. Eleven patients received palliative care following late termination of pregnancy, for three, palliative care was planned and the fetus died during delivery, for two, the outcome was unknown (incomplete documentation). Genetic testing was performed in 50%. The predominant diagnostic group was central nervous system malformations (33%), followed by chromosomal aberrations (20%) and renal anomalies (17%). One child assigned to palliative care was resuscitated. Antenatal findings were anhydramnios and pulmonary hypoplasia. Postnatally, respiration was better than expected. The neonate was admitted to intensive care, died on day one. Conclusions: Nervous system malformations seem to be a major criterion for foregoing life-sustaining interventions. Redirection towards more treatment is rare. This may reflect precise prenatal prognostication; a degree of self-fulfilling prophecy cannot be excluded.

Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review.

BackgroundZika virus (ZIKV) infection is an emerging mosquito-borne disease, which is associated with an increase in central nervous system malformations and newborn microcephaly cases. This review investigated evidence of breastfeeding transmission from ZIKV-infected mothers to their children and the presence of ZIKV infection in breastfeeding-related fluids.Methodology/Principal findingsWe conducted a systematic review of observational studies, case studies, and surveillance reports involving breastfeeding women with ZIKV infection in several international databases. Data extraction and analysis were conducted following a PROSPERO-registered protocol. From 472 non-duplicate records, two case reports met criteria for inclusion. We reviewed three cases of ZIKV infection among lactating mothers near the time of delivery. Two of the three (2/3) associated newborns had evidence of ZIKV infection. ZIKV was detected in breast milk of all three mothers. Breast milk detection results were positive in all mothers (3/3) by RT-PCR, one was positive by culture (1/3), and none was tested for ZIKV-specific antibodies. Serum samples were ZIKV positive in all mothers (3/3), and sweat was not tested for ZIKV.Conclusions/SignificanceWe describe three cases of ZIKV-infected breastfeeding mothers who were symptomatic within three days of delivery, and two cases with ZIKV-infected newborns. While ZIKV was detected in the breast milk of all three mothers, the data are not sufficient to conclude ZIKV transmission via breastfeeding. More evidence is needed to distinguish breastfeeding transmission from other perinatal transmission routes.

Congenital Zika Syndrome in 2017

Between January 1, 2015, and December 14, 2016, the World Health Organization (WHO) found mosquito-transmitted Zika virus infections in 69 countries or territories and person-to-person Zika virus transmission in 13 of them. Of great concern, in 29 of the 69 countries, Zika virus–associated central nervous system (CNS) malformations (such as microcephaly) were found among infants and fetuses suggestive of congenital infection.1 Although these Zika virus–related CNS abnormalities were first recognized in the Americas in 2015, the earliest known cases occurred in the French Polynesia islands in 2014. Zika virus–related CNS abnormalities also have been seen in Southeast Asia and West Africa.1

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

Background & objectives:Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings.Methods:This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings.Results:Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%).Interpretation & conclusions:Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Clinical Trials of Therapeutics for the Prevention of Congenital Zika Virus Disease: Challenges and Potential Solutions.

Zika virus (ZIKV) infection in pregnancy is associated with adverse fetal outcomes, such as microcephaly and other congenital malformations. No therapeutic options are available to pregnant women with ZIKV infection to prevent these effects. Drug trials in pregnancy raise several scientific, ethical, and logistic challenges, which are compounded further in ZIKV because of limited knowledge of the disease pathophysiology and a product development pipeline in its infancy. We evaluate the major challenges in choosing therapeutics to prevent congenital ZIKV disease and conducting clinical trials of these treatments, with a focus on preventing congenital central nervous system malformations. These challenges must be characterized and planned for now so that clinical trials can progress expediently and effectively in the future.

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

Attenuation of Neuronal Lipid Accumulations and Delayed Myelination in the Brain of Postnatal PEX2 Zellweger Mice

Zellweger syndrome is a peroxisomal biogenesis disorder, characterized by the absence of peroxisomes. Peroxin (PEX) genes, which regulate the import process of peroxisome matrix proteins, are mutated in patients with Zellweger syndrome. The majority of peroxisomal reactions involve lipids, including fatty acid beta-oxidation and ether phospholipid biosynthesis. However, in the absence of peroxisomes, these metabolic pathways are severely disrupted, resulting in toxic accumulations of very long chain fatty acids and many other metabolic disturbances (Wanders and Romeijn, 1998). Previous research on mice with deletion of the PEX2 gene (PEX2-/-) revealed an absence of normal peroxisomes, central nervous system malformations with an abnormality of neuronal migration and neuronal lipid accumulation in embryonic and newborn brain (Faust, 2003; Faust and Hatten, 1997; Faust et al., 2001). Using the PEX2-/- mouse model, we characterized the distribution and time course of abnormal neuronal lipid accumulation in the postnatal mutant brain. Oil red staining in PEX2 mutant mice illustrates persistence of abnormal lipid deposits in postnatal day 3 (P3) brain but their near complete disappearance in P12-P36 PEX2 mutants, with the exceptions of olfactory bulb and ependymal lining. This loss of neuronal lipid accumulation suggests these lipids may be removed by alternate non-peroxisomal mechanisms in the developing brain. Alternatively, changing metabolic requirements in developing versus mature neurons may differentially affect lipid metabolism in the absence of peroxisomes. Lastly, our results show that myelin sheaths are visibly attenuated in the brains of PEX2 mutant mice at P15. This attenuation persists somewhat through P36. The relationship of these myelin abnormalities to specific peroxisomal lipid dysfunctions remains to be investigated.

A Dumbbell-Shaped Extradural Intracanal Cavernous Hemangioma: A Rare Case Report and Review of Literature

Cavernous hemangiomas, first described by Globus in 1929, are one of the uncommon vascular malformations of central nervous system. They seemed to have benign vascular structure with dilated vessel bed. Cavernous hemangiomas encompass nearly ‘five’–12% of all spinal vascular malformations; however, existence in the epidural space without bone involvement is rare. Only ‘four’% of all cavernous hemangiomas are merely epidural cavernous hemangiomas. In this case report, we removed a hemorrhagic thoracic mass by T3-T5 laminectomy presenting with neurological deficits mimicking symptoms of intervertebral disk herniation in a 33-year-old male patient who came to our Clinic. We have chosen this case to be reported due to its rare characteristics and occurrence of this type of cavernous hemangioma in the world.

Retinoic acid embryopathy

Isotretinoin is a retinoid which is derived from Vitamin A. It is indicated for severe cystic acne treatment, but it has been classified as teratogenic. A wide spectrum of birth defects including craniofacial, heart, and nervous system malformations have been described with prenatal exposure to this drug. We report the case of a newborn with a history of prenatal exposure to isotretinoin with craniofacial defects, including left-sided anotia, right-sided microtia, complex congenital heart disease, and central nervous system malformation.

Assessing the knowledge of the consequences of uncontrolled diabetesin pregnancy and its effects on fetal development, among femaleadolescents with type 1 diabetes.

Two forms of diabetes can be distinguished during pregnancy: gestational diabetes and pregestational diabetes, which exists prior to pregnancy. In young women, the most common form of pregestational diabetes is type 1 diabetes (T1D). Regarding the decreasing age of sexual initiation and health risks for the mother and child related to hyperglycemia, it is essential that adolescents with T1D possess proper knowledge of pregnancy planning and diabetes management in case of pregnancy. Preconception counseling in adolescent patients with T1D remains a challenge for the whole therapeutic team. Assessing the awareness of consequences of uncontrolled diabetes on the course of pregnancy and fetal development among patients with T1D. The study was carried out in the group of 70 patients with T1D, aaged 15-18 years. The survey was consisted of 25 questions regarding health status, lifestyle, the knowledge of self-management of diabetes and the impact of diabetes on pregnancy and fetal development. Respondents were asked to indicate the sources of information from which they had gianed knowledge about the aforesaid issues. The data obtained were statistically analyzed. 20% (n=14) of respondents declared sexual activity. In the group of sexually active patients, in 50% (n=7) last HbA1c level, reported by subjects, was between 7.5-9%, and in 21.4% (n=3) >9%. The patients were aware of the consequences of uncontrolled diabetes on fetal development, however their knowledge was unsatisfactory. Surveyed adolescents indicated metabolic disorders (61.4 %, n=43), central nervous system malformations (55.7%, n=39) and heart defects (47.1%, n=33) as the most frequent complications. The respondents gathered knowledge mainly from a diabetologist (40%, n=28) and the Internet (40%, n=28). The majority of patients stated that preconception care should be provided by a diabetologist (88.6%, n=62) or a gynecologist (70%, n=49). In spite of continuous diabetes care, adolescents with T1D do not possess sufficient knowledge regarding the consequences of hyperglycemia during pregnancy. This study has emphasized the need for including reproductive health issues in diabetes education addressed to adolescent patients.

Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans.

Spina bifida is among the phenotypes of the larger condition known as neural tube defects (NTDs). It is the most common central nervous system malformation compatible with life and the second leading cause of birth defects after congenital heart defects. In this review paper, we define spina bifida and discuss the phenotypes seen in humans as described by both surgeons and embryologists in order to compare and ultimately contrast it to the leading animal model, the mouse. Our understanding of spina bifida is currently limited to the observations we make in mouse models, which reflect complete or targeted knockouts of genes, which perturb the whole gene(s) without taking into account the issue of haploinsufficiency, which is most prominent in the human spina bifida condition. We thus conclude that the need to study spina bifida in all its forms, both aperta and occulta, is more indicative of the spina bifida in surviving humans and that the measure of deterioration arising from caudal neural tube defects, more commonly known as spina bifida, must be determined by the level of the lesion both in mouse and in man.

Dandy–Walker malformation is a rare cause of syringomyelia in adults

Neural tube defects are the most common central nervous system malformation. Dandy–Walker malformation (DWM) is a rare abnormality of the posterior cranial fossa, which is generally diagnosed in the prenatal period or early infancy. The paper describes a case of the late clinical manifestation of DWM, which has caused syringomyelia. All variants of pathological changes within the Dandy–Walker complex very rarely become a cause of syringomyelia. Only four cases of DWM, in which syringomyelia was found in adults, are known. The authors believe that formation of syringomyelia cysts in these patients is associated with the impaired circulation of normal cerebrospinal fluid between the superior cistern and the subarachnoid spaces of the spinal cord due to the caudal dislocation of the cyst formed in the fourth ventricle. Decompression of the craniovertebral junction, by resecting the caudal portion of the cyst in the foramen magnum, and repair of the free communication between the superior cistern and the cerebrospinal fluid spaces of the spinal cord, which is complemented by duroplasty, are pointed out to be an optimal treatment in these patients.

Zika Virus Infection in Pregnant Women in Rio de Janeiro

BackgroundZika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.MethodsWe enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes.ResultsA total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester).ConclusionsDespite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.)

Partial corpus callosum agenesis and colpocephaly: a case report

Callosal abnormalities are mostly described as central nervous system malformations and can be symptomatic or asymptomatic. Herein, we report an autopsy case of a 50-year-old Syrian immigrant male with poor academic performance, presented with partial agenesis of the corpus callosum and colpocephaly. He was evidently asymptomatic until death.The cause of death was determined to be hypothermia. Autosy revealed a corpus callosum of 3 cm only in the anterior part. Posterior part of the corpus callosum, anterior, posterior and hippocampal commissures were absent. On coronal sections, inferior horn of the lateral ventricle was dilated. Histopathological examination showed petechial microhemorrhagic areas and congestion in the brain. This case report was presented to demonstrate a good example of corpus callosum agenesis in asymptomatic individuals except for poor academic performance. Furthermore, this is the first corpus callosum agenesis in medical literature encountered during medicolegal autopsy in an adult case.

Congenital optic nerve anomalies

Abstract Objective To update the current knowledge about congenital optic disk anomalies. Methods A comprehensive literature search was performed in the major biomedical databases. Results Patients with these anomalies usually have poor vision in infancy. Refractive errors are common, and serous retinal detachment may develop in some of these anomalies. It is critically important to clinically differentiate between these congenital optic disk anomalies, as central nervous system malformations are common in some, whereas others may be associated with systemic anomalies. Conclusions Congenital optic disk anomalies are a heterogeneous group of pathologies with characteristic fundus appearance and systemic associations. We should always try to make a correct diagnosis, in order to ask for specific tests, as well as to provide an adequate follow-up.

The sterile insect technique as a tool for control of insect vectors and vector-borne diseases

The mosquito species Aedes aegypti and Ae. albopictus are responsible for the transmission of human pathogenic viruses including yellow fever, dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV). According to the World Health Organization (WHO), dengue and chikungunya are still causing significant human health problems in over 100 countries, while Zika has recently spread to over 70 countries and territories, and has been associated with microcephaly and other central nervous system (CNS) malformations, and Guillain-Barré syndrome (GBS). Efficient, safe and low-cost drugs and vaccines to combat these diseases are yet to be discovered and therefore population control of the insect vector is considered as the most effective way of managing these diseases. Current vector control programmes are largely based on insecticides; however, concerns over the growing resistance to all major groups of insecticides, lack of sustainability and the impact on environment and human health calls for alternative, sustainable and environment-friendly approaches for controlling populations of Aedes mosquitoes. We propose the use of the combined sterile insect technique (SIT) and incompatible insect technique (IIT)-approach, as a component of a stakeholder-driven integrated vector management (IVM) strategy, to suppress Aedes mosquito populations below the threshold required for disease transmission. We will present recent advances in the development and application of the combined SIT/IIT package as an effective, safe and efficient approach to suppress populations of Aedes species, including proof-of-concept data.