Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos,Peru

Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru.     

Results of chromosomal studies in 270 couples with reproductive problems]

Cytogenetic study in couples with recurrent reproductive failure allows the detection of structural chromosome anomalies which don't have a phenotypic effect in carriers, but permit the explanation of the production of genetically unbalanced gametes. We present the investigation performed in 270 couples which demonstrated a chromosomal alteration in 9.2% of them. This allows genetic counselling in respect of the importance of the finding, recurrence risk and reproductive alternatives. In 8.6% we found some cellular lines with aneuploidies in sexual chromosomes, which don't represent a such concrete risk.     

Association between Mycoplasma genitalium and acute endometritis

Up to 70% of cases of pelvic inflammatory disease do not have a known cause. We recruited 115 women who had presented to a clinic for sexually transmitted diseases in Nairobi, Kenya with pelvic pain that had persisted for 14 days or less, to look for an association between Mycoplasma genitalium and endometritis. With PCR, we detected M genitalium in the cervix, endometrium, or both in nine (16%) of 58 women with histologically confirmed endometritis and in one (2%) of 57 women without endometritis (p=0.02). Our results suggest that infection with M genitalium is strongly associated with acute endometritis in this population.     

No association between Helicobacter pylori and Mycobacterium tuberculosis infections among gastrointestinal clinic attendees in Lima,Peru

Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for Mycobacterium tuberculosis (MTB) infection. This study examined the association between HP and MTB infections among persons attending the Policlinico Peruano Japonés Gastrointestinal Clinic in Lima, Peru. From 23 June 2000 to 18 August 2000, consenting 18-55 year olds who attended the clinic for gastric biopsy gave blood for HP serologic testing, underwent tuberculin skin testing (TST) and completed a social and medical history. Of 128 participating patients, 78 (61%) were TST positive for MTB, and 107 (84%) were infected with HP by serology. Of the patients who were HP positive, 67 (63%) developed positive TST reactions compared to 11 (52%) of 21 HP-seronegative subjects (OR 1.29; 95% CI 0.54-3.11; P = 0.6). There was no association after adjusting for covariates of H. pylori infection (OR 0.78; 95% CI 0.23-2.71; P = 0.7). However, study power was limited by high prevalence of the two infections.     

Sampling considerations for designing Aedes aegypti (Diptera:Culicidae) oviposition studies in Iquitos, Peru: substrate preference, diurnal periodicity, and gonotrophic cycle length

When devising methods to sample Aedes aegypti (L.) eggs from naturally-occurring containers to investigate selective oviposition, failure to take into account certain aspects of Ae. aegypti behavior can bias study inferences. In Iquitos, Peru, we tested three assumptions related to designing Ae. aegypti oviposition field studies, as follows: 1) lining containers with paper as an oviposition substrate does not affect oviposition; 2) diurnal egg-laying activity peaks in the late afternoon or early evening, and there is little oviposition during midday; and 3) the gonotrophic cycle length of wild females averages from 3 to 4 d. When wild females were presented with containers lined and unlined with paper toweling, the presence of paper increased oviposition in plastic and metal containers, but had no effect in cement containers. Recording the number of eggs laid by Ae. aegypti every 2 h throughout the day delineated a bimodal diurnal oviposition pattern, with a small morning peak, decreased activity during midday, and a predominant peak in the late afternoon and evening from 16:00 to 20:00 h. Daily monitoring of captive individual Fo females revealed that the gonotrophic cycle length was typically 3-4 d for the Iquitos population. These findings will be used to adjust field study design to 1) account for sampling eggs using paper toweling, and 2) determine the time of day and number of days over which to sample Ae. aegypti eggs. We explored how failure to consider these behaviors could potentially bias field assessments of oviposition preferences.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

Epidemiology of Spotted Fever Group and Typhus Group Rickettsial Infection in the Amazon Basin of Peru

A seroprevalence study for IgG antibodies against spotted fever group (SFGR) and typhus group (TGR) Rickettsia among humans and domestic pets was conducted in the city of Iquitos, located in the Amazon basin of Peru. Of 1,195 human sera analyzed, 521 (43.6%) and 123 (10.3%) were positive for SFGR and TGR antibodies, respectively. District of residence and participant age were associated with antibody positivity for both groups, whereas rodent sightings in the home were associated with TGR antibody positivity. Of the 71 canines tested, 42 (59.2%) were positive for SFGR antibodies, and two (2.8%) were positive for TGR antibodies; one active SFGR infection was detected by polymerase chain reaction. An uncharacterized SFGR species was detected in 95.9% (71/74) of Ctenocephalides felis pools collected from domestic pets. These data suggest that rickettsial transmission is widespread in Iquitos. Rickettsia species should be further explored as potential causes of acute febrile illnesses in the region.     

Synthesis and characterization of PLGA nanoparticles

Poly(lactide-co-glycolide) (PLGA) nanoparticles of different physical characteristics (size, size distribution, morphology, zeta potential) can be synthesized by controlling the parameters specific to the synthesis method employed. The aim of this review is to clearly, quantitatively and comprehensively describe the top-down synthesis techniques available for PLGA nanoparticle formation, as well as the techniques commonly used for nanoparticle characterization. Many examples are discussed in detail to provide the reader with an extensive knowledge base on the important parameters specific to the synthesis method described and ways in which these parameters can be manipulated to control the nanoparticle physical characteristics.