Quantification of microbial risks to human health caused by waterborne viruses and bacteria in an urban slum.

AIMS: To determine the magnitude of microbial risks from waterborne viruses and bacteria in Bwaise III in Kampala (Uganda), a typical slum in Sub-Saharan Africa. METHODS AND RESULTS: A quantitative microbial risk assessment (QMRA) was carried out to determine the magnitude of microbial risks from waterborne pathogens through various exposure pathways in Bwaise III in Kampala (Uganda). This was based on the concentration of Escherichia coli O157:H7, Salmonella spp., rotavirus (RV) and human adenoviruses F and G (HAdV) in spring water, tap water, surface water, grey water and contaminated soil samples. The total disease burden was 680 disability-adjusted life years (DALYs) per 1000 persons per year. The highest disease burden contribution was caused by exposure to surface water open drainage channels (39%) followed by exposure to grey water in tertiary drains (24%), storage containers (22%), unprotected springs (8%), contaminated soil (7%) and tap water (0.02%). The highest percentage of the mean estimated infections was caused by E. coli O157:H7 (41%) followed by HAdV (32%), RV (20%) and Salmonella spp. (7%). In addition, the highest infection risk was 1 caused by HAdV in surface water at the slum outlet, while the lowest infection risk was 2.71 × 10(-6) caused by E. coli O157:H7 in tap water. CONCLUSIONS: The results show that the slum environment is polluted, and the disease burden from each of the exposure routes in Bwaise III slum, with the exception of tap water, was much higher than the WHO reference level of tolerable risk of 1 × 10(-6) DALYs per person per year. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study provide guidance to governments, local authorities and nongovernment organizations in making decisions on measures to reduce infection risk and the disease burden by 10(2) to 10(5) depending on the source of exposure to achieve the desired health impacts. The infection risk may be reduced by sustainable management of human excreta and grey water, coupled with risk communication during hygiene awareness campaigns at household and community level. The data also provide a basis to make strategic investments to improve sanitary conditions in urban slums.

Modelling anaerobic digestion acclimatisation to a biodegradable toxicant: application to cyanide.

The observed acclimatisation to biodegradable toxicants in anaerobic cassava wastewater treatment is explained by modelling anaerobic cyanide degradation. A complete degradation pathway is proposed for cyanide. Cyanide degradation is modelled as enzymatic hydrolysis to formate and ammonia. Ammonia is added to the inorganic nitrogen content of the digester while formate is degraded by the hydrogenotrophic methanogens. Cyanide irreversible enzyme inhibition is modelled as an inhibition factor to acetate uptake processes. Cyanide irreversible toxicity is modelled as a decay factor to the acetate degraders. Cyanide as well as added phosphorus buffer solution were considered in the chemical equilibrium calculations of pH. The observed reversible effect after acclimatisation of sludge is modelled by a population shift between two aceticlastic methanogens that have different tolerance to cyanide toxicity. The proposed pathway is added to the IWA Anaerobic Digestion Model no.1 (ADM1). The ADM1 model with the designed extension is validated by an experiment using three lab-scale upflow anaerobic sludge bed reactors which were exposed to different cyanide loadings.

Palmar papillomatous lesions reminiscent of epidermal nevus in a case of focal dermal hypoplasia: a nosological consideration.

A 40-year-old woman with focal dermal hypoplasia had a palmar papillomatous lesion showing a linear arrangement and histopathological features compatible with a diagnosis of epidermal nevus. This unusual manifestation of focal dermal hypoplasia is difficult to categorize. Undoubtedly the lesion reflects functional X-chromosome mosaicism. Although the mechanism of lyonization may give rise to true epidermal nevi such as CHILD nevus, we prefer to classify the present skin lesion as a nevoid disorder and not as an epidermal nevus.

Growth factor mRNA levels in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

The early immune response in alopecia areata is characterized by a Th1 T helper cell cytokine pattern and an aberrant expression of ICAM-1 and HLA-DR molecules on lesional hair bulbs. A counteracting cytokine pattern induced by a therapeutic contact dermatitis is supposed to mediate the hair regrowth. In addition to cytokines, growth factors have been shown to influence immune responses, and we therefore investigated the expression levels for a panel of growth factors in untreated versus alopecia areata after treatment with the contact sensitizer diphenylcyclopropenone. Using semiquantitative reverse transcriptase polymerase chain reaction we detected a striking overexpression of transforming growth factor beta 1 mRNA in successfully treated patients. This cytokine has been shown to be a potent immune response modifier, which can suppress Th1 immune responses. The way in which topical immunotherapy induces hair regrowth in alopecia areata is unknown, but a lesional increased expression of transforming growth factor beta 1 may be a possible mechanism.

Cytokine mRNA levels in Alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

Although the nature of the noxious signal and the anatomical target in alopecia areata (AA) are still unknown, it has been assumed that CD4+ T lymphocytes surrounding and infiltrating the hair bulb might trigger the hair loss. As these T lymphocytes do not promote cytotoxic activity we hypothesize that AA is triggered by cytokines. Topical immunotherapy with diphenylcyclopropenone (DCP) is at present the most effective approach. If it is true that AA results from a distinct cytokine pattern, we can hypothesize that the beneficial effect of DCP should be mediated by locally secreted cytokines during the contact allergy. Using semiquantitative reverse transcription-polymerase chain reaction with RNA extracted from scalp biopsies from patients with AA before and after successful treatment with DCP, and from healthy controls we detected a T-cell response with increased steady state mRNA levels for interferon (IFN)-gamma, interleukin (IL)-1 beta, and IL-2 in untreated AA of the totalis type. After DCP treatment, the IFN-gamma expression was reduced but still above the constitutive level found in controls, whereas mRNA expression of IL-2, IL-8, IL-10, and tumor necrosis factor-alpha was increased. Our results point towards cytokines involved in the pathogenesis in AA. A TH1 type cytokine pattern is present in untreated AA, and this is modified by cytokines secreted during DCP treatment. IL-10 has recently been described as an immunomodulator of the TH1 response and, therefore, we hypothesize that basal keratinocytes or lesional T cells secrete bioactive IL-10 after DCP application, resulting in an inhibitory effect on lesional T lymphocytes. This hypothesis would explain the effectiveness of DCP and implies the theoretical possibility of a response to topical or intralesional application of recombinant IL-10.

Topical immunotherapy of alopecia areata.

Topical immunotherapy has proven to be a highly rewarding treatment modality for extensive forms of AA. The method should be considered at this time to be in an experimental stage, and therefore hesitation to adopt it is understandable. However, other acceptable and effective modes of treatment are thus far lacking. Extensive AA is not merely a cosmetic problem. Affected individuals often experience a considerable subjective loss of quality of life, and in such cases topical immunotherapy should be considered.

The genetic risk for alopecia areata in first degree relatives of severely affected patients. An estimate.

Substantial evidence indicates that genetic factors may have a role in the etiology of alopecia areata (AA). Most studies, however, provide only general information on the familial incidence but fail to specify family relationships. We therefore obtained information on the incidence of AA in first degree relatives of 348 severely affected patients. In 7% one of the parents was affected. Among the siblings of the patients 3% had developed AA, while AA was present in 2% of the children. Taking into account the age of the children, their lifetime risk was calculated to approach 6%. However, a severe type of AA is to be expected only in about 2% of the children. The degree of involvement observed in the patients did not influence the frequency and type of AA present in their first degree relatives.

Epidermal proliferation and keratinization following standardized elicitation with diphenylcyclopropenone.

Diphenylcyclopropenone (DCP) was applied to the upper arms of five alopecia areata patients using 10% of the concentration that had been applied previously to the scalp during topical immunotherapy. DCP applied in this concentration evoked a mild eczematous reaction. Biopsies were taken before DCP application and after 24, 48 and 96 h. A large increase in T-lymphocytes and CD14-positive cells in the dermis was seen after 24 h. Migration of these cells into the epidermis was mainly observed during the first 48 h. This was followed by epidermal proliferation as assessed by the number of Ki-67-positive nuclei and the degree of Ks8.12-binding. Both showed their main increase after 48 h; but after 24 h the increase of Ki-67-positive nuclei was significant (P < 0.04). Involucrin and filaggrin showed a gradual increase which became substantial after 96 h (both P < 0.04). As the invasion of inflammatory cells into the epidermis preceded the main increase in epidermal proliferation, cytokines are suggested as possible mediators for the initial phase of the proliferative response after DCP application.

Can alopecia areata be triggered by emotional stress? An uncontrolled evaluation of 178 patients with extensive hair loss.

One hundred and seventy-eight patients with severe alopecia areata were asked at interview whether they attributed their first attack of hair loss to an emotional trauma. Twelve patients (6.7%) reported a severely disturbing event during the 6 months preceding the first symptoms of their disease. No patient reported that episodes of hair loss coincided with stressful life events. Emotional triggers were not especially correlated with any particular type of alopecia areata. The present study does not therefore provide evidence of a significant role of emotional stress in the pathogenesis of alopecia areata.

'Dyschromia in confetti' as a side effect of topical immunotherapy with diphenylcyclopropenone.

"Dyschromia in confetti" is a pigmentary disturbance that so far has not been reported to have occurred during topical immunotherapy. In a group of 243 patients treated with diphenylcyclopropenone for alopecia areata, four patients showed a similar pattern of hyperpigmentation and hypopigmentation. In one patient the pigmentary disturbance was confined to the site of diphenylcyclopropenone application on the scalp. Besides dyschromic skin changes on her scalp, one patient had development of a hyperpigmentation on her forearms. In the remaining two patients, dyschromia in confetti became manifest exclusively in areas other than the scalp. This type of pigmentary disturbance appeared 4 to 14 months after the start of treatment, and it has remained unchanged in three patients during a follow-up period of 3 to 10 months. In one patient, the pigmentary changes disappeared when therapy was discontinued but recurred, albeit to a lesser extent, after treatment had been resumed. We conclude that dyschromia in confetti should be regarded as a possible, but probably rare, side effect of topical immunotherapy with diphenylcyclopropenone, especially in individuals with a rather dark complexion.

Topical immunotherapy for alopecia areata: re-evaluation of 139 cases after an additional follow-up period of 19 months.

Within a group of 139 patients previously studied during treatment for alopecia areata with diphenylcyclopropenone (DCP), hair growth was re-evaluated after a period of 19 months following completion of our previous study. Fifty-four patients treated with DCP had total and 6 had partial but cosmetically acceptable regrowth. Twenty-five patients with total regrowth had stopped DCP treatment for a mean period of 15 months and had not relapsed. Nineteen of 28 patients who still applied DCP were in the process of stepwise discontinuation of treatment. Fifteen patients had subsequently been treated with squaric acid dibutylester (SADBE) after having acquired 'tolerance' to DCP; at the time of re-evaluation 3 of these patients had complete regrowth, and 4 patients had partial but cosmetically acceptable regrowth. Topical immunotherapy with DCP and SADBE had resulted in total regrowth in 57/139 patients (41.0%) and in partial but cosmetically satisfactory regrowth in 10/139 patients (7.2%). The type of involvement and duration of alopecia areata were factors of prognostic significance.

Clinical and immunohistochemical responses of plantar warts to topical immunotherapy with diphenylcyclopropenone.

A 30-year-old man with bilateral plantar warts of the mosaic type which had been resistant to standard treatment modalities was treated with diphenylcyclopropenone. After 10 weeks, the treated warts had disappeared; the untreated warts, although showing some involution, still persisted. The untreated warts, serving as a control to prove the effectiveness of topical immunotherapy, responded likewise to subsequent treatment with diphenylcyclopropenone. Wart regression was reflected histopathologically by decreases in acanthosis, papillomatosis, granular vacuolation, and hyperkeratosis. Immunohistochemically, Ki-67 expression was markedly reduced, and a reversal of the CD4/CD8 ratio was seen. These findings suggest a major role of a cell-mediated immune response in the spontaneous resolution of warts.

Prognostic factors in the treatment of alopecia areata with diphenylcyclopropenone.

One hundred thirty-nine patients with alopecia areata were treated with diphenylcyclopropenone. Before treatment, 85 patients had subtotal or total hair loss (greater than 90% bald area) and in the remaining patients scalp involvement was between 40% and 90%. The following three factors were found to be of prognostic significance: type of alopecia areata as documented before treatment, duration of the disease before therapy, and presence of nail changes. Other factors such as age at onset, sex, presence of atopic features, the extent of variation in the range of diphenylcyclopropenone concentrations during treatment, and sleep disturbances caused by pruritus did not influence the prognosis significantly.

Treatment of alopecia areata with diphenylcyclopropenone.

One hundred thirty-nine patients with severe alopecia areata (the majority with the subtotal, total, or universalis type) were treated with topical immunotherapy (diphenylcyclopropenone). Patients were initially treated unilaterally; the other side of the scalp served as a control. In 50.4% of the patients the response was either excellent (total regrowth) or satisfactory (subtotal regrowth with only a few remaining bald patches). The most frequent side effects were eczematous reactions with blistering, spreading of the induced contact eczema, and sleep disturbances.

The captopril test in the detection of renovascular disease in hypertensive patients.

A number of reports share the conclusion that the captopril test is an adequate screening procedure for the detection of renovascular disease among hypertensive patients. Therefore, we prospectively studied the value of this test in 149 consecutive hypertensive patients. The test was considered positive if plasma renin activity, after an oral dose of 25 mg of captopril, rose by more then 4.44 ng.L-1.s-1 (16.0 ng/mL per hour). The sensitivity of the test was 39%, the specificity was 96%, the positive predictive value was 81%, and the negative predictive value was 79%. No clinically important cutoff point identifying patients with renal artery stenosis could be detected in the values of baseline and stimulated plasma renin activity nor in baseline blood pressure or changes after captopril testing. The low sensitivity makes the captopril test unfit to be used as a screening procedure in an unselected hypertensive population.