Heterogeneous feeding patterns of the dengue vector, Aedes aegypti, on individual human hosts in rural Thailand.

BACKGROUND: Mosquito biting frequency and how bites are distributed among different people can have significant epidemiologic effects. An improved understanding of mosquito vector-human interactions would refine knowledge of the entomological processes supporting pathogen transmission and could reveal targets for minimizing risk and breaking pathogen transmission cycles. METHODOLOGY AND PRINCIPAL FINDINGS: We used human DNA blood meal profiling of the dengue virus (DENV) vector, Aedes aegypti, to quantify its contact with human hosts and to infer epidemiologic implications of its blood feeding behavior. We determined the number of different people bitten, biting frequency by host age, size, mosquito age, and the number of times each person was bitten. Of 3,677 engorged mosquitoes collected and 1,186 complete DNA profiles, only 420 meals matched people from the study area, indicating that Ae. aegypti feed on people moving transiently through communities to conduct daily business. 10-13% of engorged mosquitoes fed on more than one person. No biting rate differences were detected between high- and low-dengue transmission seasons. We estimate that 43-46% of engorged mosquitoes bit more than one person within each gonotrophic cycle. Most multiple meals were from residents of the mosquito collection house or neighbors. People ≤ 25 years old were bitten less often than older people. Some hosts were fed on frequently, with three hosts bitten nine times. Interaction networks for mosquitoes and humans revealed biologically significant blood feeding hotspots, including community marketplaces. CONCLUSION AND SIGNIFICANCE: High multiple-feeding rates and feeding on community visitors are likely important features in the efficient transmission and rapid spread of DENV. These results help explain why reducing vector populations alone is difficult for dengue prevention and support the argument for additional studies of mosquito feeding behavior, which when integrated with a greater understanding of human behavior will refine estimates of risk and strategies for dengue control.

Mapping the human face: biophysical properties.

BACKGROUND: Facial skin exhibits unique biophysical properties that are distinct from skin belonging to other areas of the body. Small to large regional differences in biophysical properties between facial sites are observed. Technological advances in dermatological research allow a quantitative study of the biophysical qualities of the face and its relation to skin elsewhere. However, comprehensive studies examining inter-regional variations using each of the six standard biophysical parameters have been few. We summarize findings on the biophysical parameters used to explore the human face as well as regional differences in skin reactivity to chemical irritants. METHODS: We performed a literature search using Pubmed, Embase, Science Citations Index, and the UCSF's dermatological library on biophysical parameters and skin physiology pertaining to the human face. RESULTS: Distinct regional differences in transepidermal water loss (TEWL), capacitance, blood flow, sebum, pH, and temperature were demonstrated in facial skin. However, studies cannot be compared with each other because each uses different anatomical sites, skin conditions, and measurement techniques. Intraregional differences in TEWL, sebum, and temperatures were observed on the cheeks and appeared to follow characteristic distribution patterns. Higher blood flow levels and skin temperatures were generally observed in areas with dense networks of blood vessels such as the nose and perioral region. Areas such as the forehead, nose, and chin consistently showed higher sebum casual levels, but variability in sebum levels between sites was also observed. The susceptibility of the face to hexyl nicotinate, sodium lauryl sulfate, and benzoic acid differed depending on location and age. CONCLUSION: Establishing a standardized biophysical profile of the human face will help to improve therapeutics, and further our understanding of differences in chemical reactivity and disease distribution. Future research necessitates standardization of the anatomical sites studied, sample size, and experimental protocols.

Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors.

Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in DNA copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used array-based CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. Overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool.

Lymph node biopsies in HIV-infected and non-infected children with persistent lung disease.

OBJECTIVE: The diagnosis of opportunistic infections in children with persistent lung disease (PLD) who are infected with the human immunodeficiency virus (HIV) is difficult to establish, especially in resource-poor countries. Lymphadenopathy is a frequent associated clinical finding among these children. We evaluated the usefulness of excision lymph node biopsies in determining an aetiological diagnosis in HIV-infected and non-infected children with PLD. METHOD: Forty-five children with PLD and significant lymphadenopathy were subjected to lymph node biopsy. Of these, 27 were HIV-infected. All subjects had excision biopsies; 39 (86.7%) of these cases also underwent fine needle aspiration cytodiagnosis (FNAC) and trucut needle biopsies. RESULTS: Tuberculosis was identified as the final diagnosis in 11 (40.7%) and 12 (66.7%) HIV-infected and noninfected children, respectively. Ancillary investigations (Mantoux, gastric washings) suggested a diagnosis of tuberculosis in eight (72.7%) and eight (66.7%) of the final diagnoses of tuberculosis among HIV-infected and non-infected children, respectively. Lymph node biopsies identified a further three (27.3%) and four (33.3%) more cases of tuberculosis as compared to ancillary investigations among HIV-infected and non-infected groups, respectively. Results of FNAC and trucut biopsy showed good correlation with excision biopsy: 96.4% and 97.4%, respectively. However, adequate samples were obtained in only 23 of 39 FNAC and 33 of 39 trucut biopsies. CONCLUSION: Excision lymph node biopsies form a useful adjunct investigation in children with PLD and generalised lymphadenopathy. The most common disease identified among HIV-infected and non-infected children in Durban, South Africa, is tuberculosis. FNAC and trucut biopsies may also be useful in the evaluation of lymphadenopathy when appropriate specimens are obtained.

Folliculosebaceous cystic hamartoma.

Although folliculosebaceous cystic hamartoma (FCH) is an uncommon cutaneous entity with distinct classical and variant histopathologic features, it lacks distinctive typifying clinical features. Since the original description of five cases of FCH by Kimura et al. in 1991, 12 cases have been documented. We report a further case of FCH presenting as facial lesion in a 35 year old African male. FCH comprises prominent epithelial and mesenchymal components. The epithelial component is characterised by folliculosebaceous proliferation with cyst-like infundibular dilatation, and the mesenchymal component exhibits variable fibroplasia, vascular and neural proliferation and adipocyte metaplasia. Awareness of the lesion is important to avoid confusion with other cystic or cyst-like cutaneous lesions that contain prominent epithelial folliculosebaceous and variable mesenchymal components.

The significance of arterial hypertension at the onset of clinical lupus nephritis.

The prognostic importance of hypertension at the onset of clinical lupus nephritis is not well established. We studied retrospectively 44 patients with lupus nephritis in order to ascertain the prevalence of hypertension at presentation and to investigate a possible association between hypertension and renal functional impairment. A correlation was also sought between hypertension and histological class of lupus nephritis. Hypertension was graded as mild (diastolic 95-99 mmHg), moderate (100-114) or severe (> 115). Impaired renal function (creatinine > 120 mumol/l) was graded as mild (120-200 mumol/l), moderate (200-350 mumol/l), or severe (> 350 mumol/l). Histological class and the presence of hypertensive renal vascular lesions was recorded. The prevalence of hypertension was 38%. There were 17 hypertensives and 27 normotensives. The incidence of renal impairment was greater in the hypertensives, 47% vs 18.5% (p = 0.04). Mean serum creatinine was also higher higher in this group (p = 0.02). The presence of hypertensive renal vascular lesions identified a high-risk subgroup who had a higher incidence of renal functional impairment and worse renal function than the hypertensive group as a whole. Even at an early stage, hypertension and hypertensive renal vascular lesions correlated well with renal functional impairment. Aggressive treatment of hypertension is therefore essential in early lupus nephritis in order to prevent further deterioration of renal function as the disease evolves.

Pneumocystis carinii and cytomegalovirus infections in severely ill, HIV-infected African infants.

Unlike in the industrialized world, in which Pneumocystis carinii and cytomegalovirus (CMV) are major respiratory opportunistic organisms, the causes of severe pneumonia, which accounts for much of the mortality in HIV-infected infants in developing countries, are not known, although tuberculosis has been associated with HIV in adults. We report on post-mortem lung and liver biopsies obtained soon after death from 36 HIV-infected infants and 36 HIV-uninfected matched controls who had been admitted with severe pneumonia to an ICU. Nineteen of the HIV-infected infants were classified by WHO criteria as having AIDS and 17 'symptomatic HIV'. P. carinii and CMV were detected significantly more frequently in lung tissue from the AIDS patients (14 of 18 samples tested, p < 0.01; 14 of 18 samples tested, p < 0.01, respectively) as compared with matched controls. P. carinii was detected in two of 13 lung biopsies from symptomatic HIV infants, but in none of the controls. Lung tissue obtained from AIDS patients had P. carinii and CMV more frequently (p < 0.01, p < 0.01, respectively) than that from symptomatic HIV patients. CMV was also detected in excess in liver tissue from AIDS infants (five of 18 samples) as compared with that from symptomatic HIV (0 of 16; p = 0.03) and matched controls (two of 34; p = 0.04). Ante-mortem investigations revealed more CMV infections in AIDS patients (four of 19) than in matched controls (0 of 36; p < 0.01). Tuberculosis was detected in post-mortem lung tissue from only one patient with symptomatic HIV infection. The finding that pathogens (P. carinii, CMV) most frequently detected in seriously ill African infants with HIV/AIDS are similar to those in their counterparts from industrialized countries has implications for improved management in the former.

PIP: Biopsies were performed on postmortem lung and liver tissue soon after death from 36 HIV-infected infants and 36 HIV-uninfected matched controls who had been admitted with severe pneumonia to an intensive care unit. By World Health Organization criteria, 19 of the HIV-infected infants were classified as having AIDS and 17 as having symptomatic HIV. Pneumocystis carinii and cytomegalovirus (CMV) were detected significantly more frequently in lung tissue from the AIDS patients as compared with matched controls. P. carinii was detected in 2 of 13 lung biopsies from symptomatic HIV infants, but in none of the controls. Lung tissue obtained from AIDS patients had P. carinii and CMV more frequently than that from symptomatic HIV patients. CMV was also detected in 5 of 18 liver tissue samples from AIDS infants, none of 16 samples from cases with symptomatic HIV, and 2 of 34 matched controls. Antemortem investigations identified 4 cases of CMV infection among 19 AIDS patients and no case among 36 matched controls. Tuberculosis was detected in postmortem lung tissue from only one patient with symptomatic HIV infection.

Intralingual cysts of foregut origin.

Intralingual cysts lined by epithelium of foregut origin are rarely reported. We present 16 patients seen over an 8-year period (1983 to 1990) with such lesions. Respiratory and squamous epithelium were the most commonly encountered. These unusual cysts generally presented in the neonatal period with feeding difficulty. Two children had multiple cysts. Histological varieties of epithelia are described and the clinical features are discussed. From our experience we conclude that these cysts are adequately treated by complete surgical excision through a sagittal glossal split. This can be safely done electively in the neonatal period. Cyst aspiration was found to be inadequate definitive treatment.

Gastrointestinal mucormycosis.

Twenty patients with gastrointestinal mucormycosis are reviewed. This often fatal opportunistic fungal infection was diagnosed histologically, and was categorized as colonization (five patients), infiltration (seven patients), or vascular invasion (eight patients). There were no fatalities from colonization. In 10 patients, mucormycosis complicated peptic ulcer disease. Seven of these patients had infiltrative or invasive disease. The presentation and operative findings mimicked malignancy in five of these seven patients, and six had successful surgical intervention. The other patient was cured by medical therapy alone. Ten patients had infection associated with other gastrointestinal diseases: post-traumatic peritonitis (four patients), transmural amoebiasis (two patients), tuberculosis (one patient), gastroenteritis (one patient), gastric carcinoma (one patient) and diabetes (one patient). Eight patients had significant infection and only one survived. In this series, mucormycosis had a less aggressive course when complicating peptic ulcer than when it occurred in association with other gut diseases.

Oncocytic cyst of the larynx. A case report.

Cystic oncocytoma of the larynx is rare, and found mainly in older patients; there is a female preponderance. It arises mainly from the ventricle. These lesions are considered to be metaplastic or hyperplastic rather than neoplastic. Regardless of the pathogenesis, complete excision is associated with a good prognosis. A case is reported.

Usefulness of clinical features and liver biopsy in diagnosis of disseminated herpes simplex infection.

With the advent of effective antiviral treatment for disseminated herpes infection it has become important to be able to make a firm clinical diagnosis of this condition. We undertook a retrospective analysis of 20 patients with disseminated herpes simplex infection diagnosed at necropsy to derive useful clinical pointers to this severe form of the disease. The most useful clinical criteria were malnutrition, post measles state, and local herpes infection in addition to encephalopathy, enlarging hepatomegaly, and deteriorating pneumonia. The liver showed characteristic histological changes in 18 of 19 patients. These clinical criteria combined with liver biopsy were applied in a prospective pilot study of five patients at risk for disseminated herpes infection and the results were encouraging.

Absence of 'true' minimal change nephrotic syndrome in African children in South Africa.

Minimal change nephrotic syndrome (MCNS) which is a well defined clinical, histopathological and therapeutic entity accounts for the majority of childhood nephrosis throughout the world except Africa. We describe 15 (13%) of 115 biopsy-confirmed African children with nephrotic syndrome who had minimal change on light microscopy. These are compared to 42 biopsied Indian children with typical MCNS. The critical differences between African children and children with classical MCNS were the lack of a predictable response in eight of the former to steroids and cyclophosphamide and in a later peak age of presentation (7-8 years). These patients differed in most respects from minimal change seen in the malarial zones of North Africa except for clinical presentation. Minimal change in West and East Africa more closely approximates typical MCNS. Two of the African patients with minimal change had endemic syphilis and responded clinically to penicillin therapy. The clinical presentation in all the African children, the favourable short-term outcome in 12 of these patients, immunofluorescent (13 patients) and electron microscopic (three patients) findings, and selectivity of proteinuria (eight patients) paralleled that of classical MCNS. The implications of this study are that African children in South Africa with MCNS should not be treated with steroids or cyclophosphamide. There is no clear benefit in the use of these drugs in nephrotic children with obvious glomerular lesions and therefore it follows that such therapy should be avoided in all African children in South Africa with this disease.

Melanotic neuro-ectodermal tumour of infancy. A case report.

A case of melanotic neuro-ectodermal tumour of infancy (retinal anlage tumour, melanotic ameloblastoma) is described. Although a well recognized entity, the biological origin of this tumour is still disputed. A confusing array of names has been awarded to this tumour which characteristically occurs in infants under one year of age, commonly arising from the maxilla but also from the mandible, frontal bone, mediastinum, shoulder and cerebellum. While the origin of the tumour remains unclear, the ultra-structural evidence of Haywood et al. (1969) supports a neural crest origin. Consistent with this are the findings by Borello and Gorlin (1966) of high urinary vanillylmandelic acid excretion in one case and the correlation of tumour enzyme patterns with those of paragangliomas, neuroblastomas and phaeochromocytomas.

Extramembranous nephropathy in black South African children.

Membranous nephropathy is the most frequent histological category among black children with nephrotic syndrome. In this study 31 African children with this condition are described. There were more boys than girls and the peak age was four to 11 years. The incidence of this histological category and clinical outcome in the African children were similar to these features in adults with membranous nephropathy. During a follow-up period of up to six years there was spontaneous remission in a third of patients, persistent proteinuria in just over a third (37.5%) and persistent relapse in under a third (29.2%). Hypertension occurred more frequently (19.3%) and spontaneous remission less often (33.3%) than in children with membranous nephropathy elsewhere. Hypertension, the lower remission rate and persistence of proteinuria during the course of the disease were similar to the disease seen in adults. Renal failure was not encountered in any patients. Steroids were of little value in the treatment of these children. Five children (16.2%) had associated infections. HBsAg was present in three of six children tested.