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Background: Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects., Method: This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS)., Results: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%)., Conclusion: Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity., (© The Author(s) 2023. Published by Oxford University Press.)

Mosquitoes transmit a variety of pathogens that have devastating consequences for global public and veterinary health. Despite their capacity to serve as vectors, these insects have a robust capacity to respond to invading organisms with strong cellular and humoral immune responses. In Egypt, Aedes caspius (Pallas, 1771) has been suspected to act as a bridge vector of Rift Valley Fever virus between animals and humans. Microscopic analysis of Ae. caspius hemolymph revealed the presence of phagocytic cells called granulocytes. We further evaluated cellular immune responses produced by Ae. caspius as a result of exposure to a Gram-negative, and Gram-positive bacterium, and to latex beads. After challenge, a rapid and strong phagocytic response against either a natural or synthetic invader was evident. Hemocyte integrity in bacteria-inoculated mosquitoes was not morphologically affected. The number of circulating granulocytes decreased with age, reducing the overall phagocytic capacity of mosquitoes over time. The magnitude and speed of the phagocytic response suggested that granulocytes act as an important force in the battle against foreign invaders, as has been characterized in other important mosquito vector species.

The identification of the members of the Culex pipiens L. complex in arbovirus surveillance programs relies heavily on the use of morphology. In this work, we studied Cx. pipiens complex male mosquitoes collected from nine different locations, from northern, southern, and the hybrid zone sites in North America; Cairo, Egypt; and Nairobi, Kenya. Specimens were identified using DV/D ratio and also using amplification of the acetylcholinesterase (ACE.2) gene by both conventional and real-time polymerase chain reaction, and examination of the CQ11 locus. Consistent with previous findings, the morphological and molecular identifications did not always agree, particularly in regions of extensive introgression. There was an increased frequency of hybrid forms in late summer and early fall in Champaign Co., IL, that is north of the previously described Cx. pipiens complex hybrid zone. This represents an expansion of the North American hybrid zone. The biological and epidemiological relevance of the high degree of introgression and the late season increase in the proportion of intermediate forms is discussed.

As part of an evaluation of potential vectors of arboviruses during a Rift Valley fever (RVF) outbreak in the Nile Valley of Egypt in August 1993, we collected mosquitoes in villages with known RVF viral activity. Mosquitoes were sorted to species, pooled, and processed for virus isolation both by intracerebral inoculation into suckling mice and by inoculation into cell culture. A total of 33 virus isolates was made from 36,024 mosquitoes. Viruses were initially identified by indirect fluorescent antibody testing and consisted of 30 flaviviruses (all members of the Japanese encephalitis complex, most probably West Nile [WN] virus) and three alphaviruses (all members of western equine encephalitis complex, most probably Sindbis). The identity of selected viruses was confirmed by reverse transcriptase-polymerase chain reaction and sequencing. Culex antennatus (Becker) and Culex perexiguus Theobald accounted for five (17%) and 23 (77%) of the WN virus isolations, respectively. Despite isolation of viruses from 32 pools of mosquitoes (both WN and Sindbis viruses were isolated from a single pool), RVF virus was not isolated from these mosquitoes, even though most of them are known competent vectors collected during an ongoing RVF outbreak. Thus, it should be remembered, that even during a known arbovirus outbreak, other arboviruses may still be circulating and causing disease.

In 1993, Rift Valley fever (RVF) virus reappeared in Egypt. We determined the prevalence and feeding patterns of mosquitoes in 5 villages where the virus was active. Of 10 species recovered, Aedes caspius (Pallas), Culex pipiens L., Cx. antennatus (Becker), and Cx. perexiguus Theobald constituted 99% of > 35,000 mosquitoes captured in dry ice-baited CDC light traps. Ae. caspius was most prevalent, except at Nag' El Hagar where it was replaced by Cx. perexiguus. Cx. pipiens ranked 2nd, except at Nag' El Ghuneimiya, where it was replaced by Cx. antennatus. Most blood meals analyzed by an enzyme-linked immunosorbent assay reacted to > or = 1 antiserum. Cx. pipiens was mainly anthropophagic, and therefore may have been the main vector of RVF virus among humans. Ae. caspius feeds were chiefly from humans, bovines, and equines. Cx. antennatus and Cx. perexiguus fed generally on bovines. Mixed blood meals from humans and RVF virus susceptible animals were identified in the predominant mosquitoes. Prevalence and host selection, as well as predicted probability for a blood meal being interrupted, indicated that Ae. caspius may have served as a bridge vector between humans and bovines in 4 of the villages. Cx. perexiguus may have played this role at Nag' El Hagar. Because potential vectors are abundant, susceptible domestic animals are associated closely with humans, and surveillance of imported livestock is not systematic, we conclude that RVF virus sporadically will recur in Egypt.

Human blood samples and indoor-resting Culex pipiens were collected in 33 randomly selected houses from different sectors of a village in the Nile Delta of Egypt which was endemic for Wuchereria bancrofti. Blood was also collected from subjects with no history of living in filarial endemic areas. Human blood samples were divided and assessed by both membrane filtration and polymerase chain reaction (PCR). Similarly, mosquito samples were assessed by both dissection and PCR. Blood pools representing each household were tested by PCR. If a pool gave a positive result, then individual blood specimens were also tested by PCR. Of the 33 houses tested, both membrane filtration and blood pools assayed by PCR identified 14 (42.4%) 'infected houses'. PCR detected parasite deoxyribonucleic acid (DNA) in blood pools from an additional 3 households that gave negative results by membrane filtration. Of 178 endemic blood samples tested by membrane filtration, 22 (12.3%) had microfilariae and all were individually positive by PCR. Although microfilaria counts were lower in blood collected during the day than in night-collected blood, the PCR results were consistent, regardless of time of collection. All non-endemic blood samples were negative by PCR. Among the 33 houses rested, mosquito pools assayed by PCR identified 17 (51.5%) as 'infected households'. Of these, 8 houses (47%) contained at least one microfilaraemic resident. One 'infected household' was identified by mosquito dissection. We concluded that PCR is a powerful epidemiological tool for screening villages for the prevalence of W. bancrofti. PCR detection of W. bancrofti DNA in blood-fed mosquitoes could be used initially to locate endemic areas with transmission of bancroftian filariasis. PCR detection of W. bancrofti DNA in blood collected during the day could then be used to assess W. bancrofti infection rates.

Host-selection patterns of mosquitoes were determined over a 1-yr period at Abu Heif, a village in Sharqiya Governorate, Egypt, that has had a history of Rift Valley fever virus (RVFV) transmission. Culex pipiens L. and Cx. antennatus Becker were the most common mosquito species collected, and 8,252 blood meals from both species were analyzed by a precipitin technique. Host availability was estimated by a monthly census of human and animal populations. Both mosquito species exhibited opportunistic endophagic behavior. In bedrooms, 79% of Cx. pipiens fed on humans, compared with 53% of the Cx. antennatus. In animal sheds, 35% of Cx. pipiens and 68% of Cx. antennatus fed on sheep or goats. Cx. pipiens was primarily anthropophilic (forage ratio = 2.7) whereas Cx. antennatus was mainly an ovine feeder (forage ratio = 2.4). These findings indicated that both species probably were involved in the transmission of RVFV in Sharqiya Governorate during the epidemics of 1977 and 1978, Cx. pipiens being mainly responsible for transmission to humans, and Cx. antennatus for transmission among domestic animals. The persistent custom of keeping sheep and goats inside human dwellings, combined with the opportunistic host selection by the local mosquitoes, continues to make this area receptive to RVFV transmission.

Autogenous ovarian development was investigated in pupal and adult stages of Culex pusillus Macquart from Egypt. Vitellogenesis was initiated synchronously in > 90% of 1-d-old pupae, and primary follicles of all pupae reached stages III and IV 1 d later. All adult females oviposited their initial autogenous egg batches within 1-4 d after emergence. Females were capable of ovipositing up to four successive autogenous egg batches. The expression of repeated autogeny was confirmed by the presence of an equivalent number of dilatations and the concurrent existence of mature primary follicles and maturing secondary follicles in the same ovarioles. In addition, the total fecundity of 33% of the females that oviposited repeatedly exceeded the ovariole number of the two ovaries. This species failed to ingest a blood meal when offered a variety of hosts. Therefore, Cx. pusillus from Egypt expressed autogenous ovarian development throughout life, a characteristic apparently unique among the genus Culex.

We have previously reported that a monoclonal antibody-based antigen detection assay (AD12) is sensitive and specific for Bancroftian filariasis in Egypt. The purpose of the present study was to demonstrate the use of this assay in a sentinel population as a means of efficiently screening for filariasis endemicity. Antigen testing was performed with finger-prick blood collected during the day from 743 schoolchildren (ages 11-16 years). The school draws students from 5 villages in Qalubia Governorate, 35 km north-east of Cairo, Egypt. The prevalence of filarial antigenaemia in the school was 17.2%. Antigenaemia rates in children from the 5 villages were 29, 20, 18, 17, and 10% (non-uniformity significant by chi 2 analysis, P = 0.02). These data agree with Ministry of Health rankings of relative endemicity for these villages based on prior night blood surveys. The village with the highest antigen prevalence in children was surveyed one year before the present study. Prevalence rates of antigenaemia and microfilaraemia at that time for a different sample of children aged 11-16 years were 33% and 22%, respectively. We conclude that antigen detection in schoolchildren of this age group is an efficient means of assessing filariasis endemicity in Egypt.

The objective of this study was to find the best tests for efficiently estimating the true prevalence of Bancroftian filariasis in endemic areas. The study population comprised 427 people over 10 years of age in an endemic village in Egypt. Four tests were evaluated; a standardized clinical examination, night blood examinations for microfilariae (50 microL thick films and 1 mL membrane filtration), and a test for circulating filarial antigen. 191 subjects (44.75%) had at least one positive test and were considered to have filariasis. The sensitivities of clinical examination, thick films, membrane filtration and antigen testing for filariasis were 16%, 50%, 64%, and 88%, respectively. Relative to membrane filtration of night blood, the filarial antigen test had a sensitivity of 97.5%, a positive predictive power of 71%, and a negative predictive power of 99%. None of the blood tests was a sensitive indicator of clinical filariasis; 69% of clinical cases were negative in all 3 blood tests and would have been missed if clinical examinations had not been done. Therefore, we recommend a combination of clinical examination and the filarial antigen test (with optional examination for microfilariae of those with positive antigen tests) for community diagnosis of Bancroftian filariasis in endemic areas.

Geographic variation among Culex pipiens L. populations was studied along a north-south transect across Egypt. Horizontal starch gel electrophoresis of 10 enzyme loci permitted estimates of adult polymorphism for 10 demes of Cx. pipiens. Levels of genetic variability, as indicated by a mean of 1.25 alleles per locus, a mean expected heterozygosity of 0.023, and a proportion of 0.25 of the loci being polymorphic, indicated limited genetic heterogeneity within and among demes. Nei's estimates of genetic divergence indicated considerable genetic exchange among demes (average genetic distance, 0.013). Thus, Cx. pipiens in Egypt was not differentiated into genetically isolated demes but, rather, seemed to consist of a single panmictic population.

4 Egyptian mosquito species were tested for their ability to transmit the Egyptian ZH-501 strain of Rift Valley fever virus (RVFV) to golden Syrian hamsters. Culex (Cx.) antennatus was the most efficient vector, showing a 37.5% transmission rate following a hamster blood meal containing 10 suckling mouse intracerebral 50% lethal doses (SMILD50) per ml. Fully engorged mosquitoes of this species showed an infection rate of 85% with the mean viral titres of transmitting mosquitoes 100-fold higher than non-transmitters. Autogenous and anautogenous populations of Aedes (Ae.) caspius were tested separately, and the transmission rates were 23.1% and 9.7% respectively, following feeding on hamsters with similar levels of viraemia. Two anopheline species, Anopheles (An.) multicolor and An. pharoensis, showed 12.5% and 3.5% transmission rates under similar conditions. In these 3 species infection rates exceeded 75% and mosquitoes transmitting had a higher average titre than those not transmitting.