Specificity of dysuria and discharge complaints and presence of urethritis in male patients attending an STD clinic in Malawi.

OBJECTIVE: This study evaluated the specificity of discharge and dysuria for laboratory confirmed urethritis in symptomatic men presenting to an urban STD clinic in Malawi for treatment and returning for follow up evaluation. METHODS: Clinical treatment trial where consecutive consenting men with urethritis were enrolled and administered a questionnaire, examined, tested, and given one of five urethritis treatments with an efficacy range of 33-95%. Men returning for follow up were questioned, examined, and tested. RESULTS: The presence of both discharge and dysuria were highly specific for laboratory confirmed urethritis (over 90%). Compared with men who had complaints of both discharge and dysuria, men with complaints of dysuria alone were more likely to have reported prior treatment, 72% v 48% (p = 0.003), and less likely to have had gonorrhoea, 64% v 83% (p = 0.04). Men with complaints of discharge or dysuria without evidence of discharge were rare but half of them had documented urethritis. Among men who returned for follow up, 72% had no symptoms of either discharge or dysuria. However, among the 238 men with no symptoms at follow up, laboratory documented gonorrhoea occurred in 9% and non-gonococcal urethritis in 21%. DISCUSSION: In this population of men discharge or dysuria were specific symptoms for urethritis. The symptom of dysuria should be added as an entry criterion for evaluation for urethritis in the World Health Organisation's treatment recommendations. The high prevalence of asymptomatic infection at follow up in a population of men who received suboptimal antimicrobial therapy suggests that the most effective therapy available should be given at the first visit.

Validation of the WHO diagnostic algorithm and development of an alternative scoring system for the management of women presenting with vaginal discharge in Malawi.

OBJECTIVE: To evaluate the performance of the WHO algorithm for the detection of cervical infection in women presenting with vaginal discharge and modify the risk assessment score for optimum effectiveness in Malawi. METHODS: 550 consecutive women presenting with non-ulcerative genitourinary complaints were interviewed and examined. Cervical infection was defined as presence of Neisseria gonorrhoeae on culture and/or Chlamydia trachomatis by EIA. Other laboratory investigations included wet mount microscopy, serology for syphilis and HIV, LED testing of cervical and vaginal secretions, and pH testing of vaginal fluid. Sensitivity, specificity, and positive predictive values (PPV) of different algorithms were determined in the analysis. RESULTS: Cervical infection was identified in 19.5% of women (17.1% gonorrhoea, 3.7% chlamydial infection). The sensitivity/specificity/PPV of the WHO risk assessment were 43%/73%/28%, respectively by history and 62%/61%/27% with the addition of speculum examination. Using Malawi results to modify the risk assessment improved the performance to 61%/68%/31% respectively by history alone, which increased to 73%/64%/33% with bimanual examination and 72%/56%/29% with speculum examination. CONCLUSION: The sensitivity of the WHO risk assessment is low for the detection of cervical infection in Malawi. Although the Malawi risk assessment performed somewhat better on history alone, this study identified external and bimanual examination variables that improved the diagnostic performance of the algorithm in settings where speculum examination is not possible. Although the PPVs of the algorithms are low, country specific risk assessments can provide a framework for management until simple, affordable diagnostic tests for the definitive diagnosis of cervical infection are available.

Sustained growth but non-sustainable urbanisation in Penang, Malaysia.

PIP: Penang, Malaysia, has been a city characterized by urban growth and rapid industrialization for the past 25 years. Foreign capital, especially from the transnational electronics industry, has spurred the process of urban growth in the city. While the state government is clearly trying to copy and adapt some form of a Singapore model of development and growth in Penang, the quantitative and qualitative demands for labor exceed the available supply from the country's northern states. Local and national labor policies are decided without the involvement of trade unions, which lack the strength to substantially improve wages or influence the institutions of the labor market. Therefore, an energized labor market attempts to balance the upgrading of skills and the control of wages. Focus upon sustainable urbanization will renew the debate on urban, export-oriented industrialization in southeast Asia.^ieng

Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi.

PIP: Malaria and human immunodeficiency virus (HIV) infection are major health problems in many areas in Sub-Saharan Africa. An interaction between malaria and HIV infection has been postulated, since both produce similar cellular immune responses, with a lowering of the CD4/CD8 lymphocyte ratio. The frequency of malaria parasitemia was examined in children born to HIV-seropositive and seronegative mothers attending regular postnatal visits. A prospective study on mother-to-infant transmission of HIV had been underway since 1989 in Queen Elizabeth Central Hospital, Blantyre, a major hospital in urban Malawi. Standard HIV serology was performed on pregnant women, after obtaining consent. To reduce the effect of selection bias and seasonality, HIV seropositive (case) and seronegative (control) mothers and their infants were enrolled at delivery. Children included in the study were 503 born to 494 HIV-seropositive mothers and 540 born to 536 HIV-seronegative mothers. At each 3-monthly postpartum visit a Giemsa-stained thick blood film from the child was examined for malaria parasites. Children born to HIV-seropositive mothers were tested for HIV antibodies at 12 and 18 months of age. Of the 353 children born to HIV-seropositive mothers, 82 children (23.2%) were found to be HIV seropositive by enzyme-linked immunosorbent assay and Western blotting at 12 and 18 months. No statistically significant difference was found in frequency of malaria parasitemia by maternal or infant HIV serostatus after controlling for child's age. There was, however, a significant trend of increase in high parasitemia with age, irrespective of the HIV serostatus of the mother or the child. The frequency of parasitemia was higher in the wet season than in the dry season. This study suggests that maternal or infant HIV infection does not alter susceptibility to, or the clinical course of, malaria in infants.^ieng

Hypothyroidism and anti-endothelial cell antibodies.

Because of our previous demonstration of anti-endothelial cell antibodies (AECA) in patients with insulin-dependent diabetes mellitus and their association, in this condition, with thyroid disease, we sought these antibodies in patients with suspected thyroid dysfunction using an enzyme immunoassay with human umbilical vein endothelial cells as the substrate. AECA were found in 5/120 (4.2%) patients with normal and 15/97 (15.4%) with abnormal thyroid function. The increased prevalence in the latter group was due to a highly significant association between the presence of AECA and raised levels of TSH. We conclude that a highly significant correlation exists between the levels of AECA and TSH, but not between those of AECA and fT4. Patients with hypothyroidism as defined by high levels of TSH have AECA significantly more often than patients with low or normal TSH (22.2% versus 2.8% and 5.8%).

Anti-endothelial cell antibodies in nephropathia epidemica and other viral diseases.

Increased capillary permeability is a central feature of the severe forms of haemorrhagic fever with renal syndrome (HFRS) and occurs also, though less frequently, in nephropathia epidemica (NE), one of the milder forms of this syndrome, caused by Puumala virus. We therefore searched for antiendothelial cell antibodies (AECA) in patients with NE and in those with other presumed or serologically proven acute viral illnesses. By enzyme immunoassay, using human umbilical vein endothelial cells (HUVEC) as the substrate, IgG class AECA were detected significantly more frequently in patients with NE and with influenza A than in Red Cross blood donors. A lesser degree of reactivity could be shown with a human alveolar cell carcinoma line and with human and mouse embryonic fibroblasts. Pretreatment of HUVEC with interferon-gamma (IFN-gamma), but not with IL-1 or tumour necrosis factor-alpha (TNF-alpha), increased their ability to bind IgG of sera from patients with NE and acute febrile illnesses. We conclude that, although AECA can be demonstrated in NE, they occur also in other acute viral illnesses and, unless cytopathic by a mechanism not shared by the AECA of these other illnesses, are unlikely to be casually related to the capillary leak in HFRS.

Anti-endothelial cell antibodies in insulin-dependent diabetes mellitus.

The prevalence of IgG class antibodies to endothelial cells (AECA) was studied in 136 young patients with insulin-dependent diabetes mellitus by an enzyme immunoassay using human umbilical cord vein endothelial cells. The patients were divided into four groups according to the time between diagnosis and study and their results were compared with those in control children and blood donors. AECA became progressively more frequent with the duration of diabetes, being 4% in diabetics tested within 2 weeks of diagnosis and reaching 34% after an average disease duration of 11.2 years. They were not more common in patients with neuropathy, retinopathy or nephropathy than in patients without these complications, but were associated with co-existing thyroid disease and IgA deficiency. The results suggest that in insulin-dependent diabetes mellitus AECA are associated with co-existing autoimmune disorders but not with diabetic microvascular disease.

Endothelial cell activation in vasculitis of peripheral nerve and skeletal muscle.

To clarify the role of endothelial cells in the pathogenesis of vasculitis affecting peripheral nerve and skeletal muscle, the endothelial expression of adhesion molecules and major histocompatibility antigens (MHC) in different vasculitic syndromes were studied, and related to the presence of anti-endothelial cell antibodies (AECA). Increased expression of the intercellular adhesion molecule ICAM-1 in vasculitic lesions in nerve and muscle was shown, and this was associated with increased expression of MHC class I and II antigens. AECA were detected in low titre in only a minority of patients. The findings suggest that endothelial cells have a critical role in mediating the tissue injury in vasculitis affecting nerve and muscle and that the process is triggered by cellular and not antibody-mediated mechanism in the majority of patients.

Subclasses of IgG anticardiolipin antibodies in patients with systemic lupus erythematosus.

Antibodies directed to a co-factor associated with negatively charged phospholipids, such as cardiolipin, occur in patients with systemic lupus erythematosus (SLE), and possibly more often in those with venous or arterial thrombosis, thrombocytopenia or recurrent fetal loss. They are also found in patients without any of these manifestations and their biological effect, if any, might thus be related to their IgG subclass. To investigate this possibility, we determined anticardiolipin antibodies (ACA) by enzyme immunoassay (EIA) using monoclonal antibodies (MoAb) against human IgG subclasses. A net absorbance of x +3 SD of the value of 30 blood donors was taken as the cut-off point. The specificity of the assay was verified through inhibition experiments using cardiolipin micelles. Thirty-three patients with SLE were studied, all of whom had been shown to have ACA by a point dilution screening assay. IgG1 ACA were found in 85% of the patients, and ACA of the IgG2, IgG3 and IgG4 subclasses in 42%, 39% and 15%. There was a significant correlation between the presence of IgG3 ACA and of anti-DNA antibodies but none between subclass distribution and major clinical manifestations of SLE.

Polyclonal B-cell activation after intravenous immunoglobulin therapy in idiopathic thrombocytopenic purpura--an anti-idiotype response?

Polyclonal B cell activation occurred in 3 patients following treatment with intravenous immunoglobulin (i.v. Ig) for idiopathic thrombocytopenic purpura (ITP). The possibility that this may represent an anti-idiotype response and the hypothesis that prolonged remission of ITP may be induced by this mechanism are discussed.

Suppression of in vivo antibody responses by suppressor factors induced by human myeloma proteins.

Suppressor factors induced in vitro, using purified human IgG and IgA myeloma proteins, were shown to efficiently suppress murine antibody production in vivo. The suppression was not isotype specific, viz. IgG and IgA suppressor factors suppressed the production of IgM and IgG antibody. Neither the suppressor factors (SF) nor the inducing proteins suppressed the proliferative responses to concanavalin A and purified protein derivative (PPD). The results are compared to the in vitro findings and discussed in the context of isotype regulation, hypogammaglobulinemia and immunotherapy.

Effects of a human urinary mitogen on subpopulations of peripheral blood mononuclear leukocytes.

We have earlier isolated, to apparent homogeneity, a 27-28 kD human basic protein (UM) from the urine of a patient with myelomonocytic leukaemia. UM is a mitogen for resting human peripheral blood mononuclear leukocytes (PBML). We have now further defined the effect of UM on human PBML and their subpopulations in 6-day cultures. Cell proliferation was measured by 3H-thymidine uptake and Ig production by the plaque forming cell (PFC) response. Whole PBML responded to UM with proliferation and an increase in PFC. The PFC response was at best equal to and frequently synergistic with that produced by pokeweed mitogen and occurred in the three major Ig classes. To test the effect of UM on subpopulations of PBML, adherent cells (AC) were isolated by plastic adherence and T and B enriched populations by rosetting with sheep red blood cells. The proliferative response of T cells needed the presence of AC whilst the effect on Ig production by B cells required both T cell help and the presence of AC. Human thymocytes also responded to UM by proliferation. The results show that, in addition to being a T cell mitogen, UM is also a T cell dependent polyclonal B cell activator.

Bone marrow transplantation in the rat. B lymphocyte activation in acute graft-versus-host disease.

We have isolated the white cells from the bone marrow, spleen, and blood of a rat recipient of a bone marrow allograft and the inflammatory leukocytes from the recipient skin, lung, gut, and liver (the parenchymal target organs for acute graft-versus-host disease (aGVHD)) and compared the number of immunoglobulin-synthesizing and releasing cells in these cell populations to corresponding compartments of a syngeneic graft recipient. Bone marrow transplantation was associated in the early phase with marked immunoglobulin production in the cells of bone marrow, spleen, and blood of the allograft recipient; as, however, a similar response occurred in the syngeneic graft recipient we conclude that this is related to reconstitution rather than to aGVHD. Later, during aGVHD, the number of immunoglobulin releasing cells decreased significantly in the spleen and bone marrow of the allografted animal. In clear contrast, in the liver--but not in skin, lung, or gut--very few immunoglobulin-releasing cells were observed in the syngeneic graft recipient, whereas in the allograft recipient a very strong and significantly higher immunoglobulin synthesis and release was seen coinciding with the inflammatory episode of aGVHD in the liver.

Suppressor factors generated from human mononuclear cells by means of purified myeloma proteins.

Peripheral blood mononuclear cells (PBMC) from normal human donors were cultured in Marbrook flasks in the presence of purified IgG or IgA myeloma proteins. The culture supernatants were tested for their ability to suppress pokeweed mitogen (PWM)- or Epstein-Barr virus (EBV)-driven Ig synthesis by normal PBMC. Two supernatants from PBMC cultured with IgG and one from PBMC cultured with IgA were tested and suppressed PWM-driven Ig synthesis as measured by a reverse haemolytic plaque assay and by quantitation of the Ig secreted into the culture medium of the PWM-driven cells. This suppression was not restricted to the Ig isotype of the 'inducing' myeloma protein, but was extended to IgG, IgA, and IgM. The suppressive effect could be absorbed out with human IgG.

Hypophosphatemic rickets, hyperparathyroidism, and hyperthyroidism with hypercalcemia.

We describe a case of hypophosphatemic rickets in which hyperparathyroidism and hypercalcemia developed and were possibly secondary to co-existent hyperthyroidism. During the period of hypercalcemia with high immunoreactive parathyroid hormone levels the serum inorganic phosphorus level became, and remained, normal. This supports the concept that renal tubular phosphate absorption may be sensitive to calcium.

The effect of phenytoin in vitro on normal human mononuclear cells and on human lymphoblastoid B cell lines of different Ig isotype specificities.

The anticonvulsant drug phenytoin, in less than cytotoxic concentrations, caused significant reductions in Ig secretion by unstimulated or EBV-stimulated normal MNC, as measured by PFC or secretion of Ig into the culture medium. Isotype-specific LBL varied in their sensitivity, the secretion of IgA (1 line) and IgG (3 lines) being reduced by phenytoin near therapeutic concentrations, whereas that of IgM (1 line) was resistant. Six-day exposure of MNC to phenytoin caused no selective depletion of or enrichment for B cells, monocytes or T cell subsets. The results suggest that the reduction in serum Ig levels reported in phenytoin-treated epileptic patients is, at least in part, due to a direct effect of the drug on the B lymphocyte. However, among EBV-activated normal MNC, those secreting IgA were no more sensitive to the drug than those secreting IgG or IgM, and other factors may, therefore, operate to cause the preferential reduction in serum IgA in phenytoin-treated patients.