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The relationship between quantitative Plasmodiumfalciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/microl. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area.
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PMID:Parasite density and malaria morbidity in the Pakistani Punjab. 1058 14

We performed a phase II, Southwest Oncology Group (SWOG) clinical trial of recombinant human interleukin-4 (rhuIL-4) in patients with previously treated non-Hodgkin's lymphoma (NHL). We studied 18 eligible patients with low-grade and 21 patients with intermediate- or high-grade NHL. All patients had received prior chemotherapy. A protocol amendment after the first four patients reduced the frequency of s.c. rhuIL-4 administration from daily to 3 times per week at 3 microg/kg and limited the number of prior chemotherapy regimens allowed. We documented no complete or partial responses in the low-grade NHL group [0%; 95% confidence interval (CI) 0-19%]. One patient in the intermediate/high-grade NHL group developed a partial response lasting longer than 15 months (5%; 95% CI 0-24%). Median survivals for the low- and intermediate/high-grade NHL groups were 15 and 13 months, respectively. Common toxicities included: arhralgia/myalgia, fatigue/malaise/lethargy, fever, headache, nausea and rigors/chills. Cardiac toxicity, gastrointestinal ulceration and nasal congestion due to rhuIL-4 were not prominent toxicities in our patients. Our previously treated NHL patients tolerated s.c. rhuIL-4 at a dose of 3 microg/kg given 3 times per week, but objective response rarely occurred. Further evaluation of rhuIL-4 in these patient populations does not appear warranted.
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PMID:Phase II evaluation of interleukin-4 in patients with non-Hodgkin's lymphoma: a Southwest Oncology Group trial. 1112 30

Japanese-B virus encephalitis (JE) is considered a uniphasic illness with a variable outcome. Biphasic illness patterns have never been reported previously. From an endemic zone in India we observed six patients of JE (from 62 patients treated in 7 years) who had an early relapse resulting in the biphasic clinical course. Five had poor socio-economic status and three had laboratory evidence of nutritional deficiency. Two patients were adults and the other four were children. Fever, rigors, headaches, body aches, altered consciousness, rigidity and tremors predominated the first phase of illness. During the second phase, behavioural changes, dystonia, pen-oral dyskinesia, drooling, mutism and muscle wasting due to anterior horn cell involvement were the important features. Though the serial antibody titres against the JE virus showed a four-fold rise in the initial or late convalescent phases, there was no increase during the second phase of the illness as compared to the first phase. On MRI, fresh lesions appeared during the second phase at the sites known for their involvement in JE, suggesting recrudescence of the virus. One patient survived with major sequelae, two with minor sequelae and the other three had complete recovery. We conclude that some patients with JE may have an early relapse after partial recovery, giving rise to the biphasic illness pattern. A locally prevalent genetic variant of the virus or host factors may be responsible for the altered clinical course of the disease. Biphasic illness does not necessarily mean a bad prognosis.
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PMID:Biphasic illness pattern due to early relapse in Japanese-B virus encephalitis. 1116 88

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.
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PMID:A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease. 1142 20

Brucellosis is hyperendemic in Saudi Arabia. We report infection in a breast implant as an unusual complication of laboratory-acquired brucellosis. A 48-year-old female developed fever, rigors, headache, arthralgia and weight loss. A blood culture for Brucella was positive. A 6-week course of antibiotics effected a clinical and bacteriological cure but the resolution was short-lived. Six weeks later a relapse of her febrile symptoms occurred together with the appearance of a breast abscess. Cultures of the abscess and blood yielded brucella. A second course of antibiotics together with surgical drainage and subsequent reconstruction resulted in a cure.
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PMID:Unusual complication of breast implants: Brucella infection. 1168 12

Meningococcal septicaemia has high mortality, especially when the diagnosis is delayed or missed. Early recognition is not always straightforward, as classic clinical features may be absent or overlooked at initial presentation. Septicaemia without focal infection accounts for 15%-20% of cases of meningococcal disease and is the most worrisome manifestation in terms of diagnosis and outcome; in contrast, meningococcal meningitis is usually straightforward to diagnose, with a relatively good prognosis. Useful early clinical clues to meningococcaemia include: - a haemorrhagic (petechial or purpuric) rash; - blanching macular or maculopapular rash that appears in first 24 hours of illness; - true rigors; - severe pain in extremities, neck or back; vomiting, especially in association with headache or abdominal pain; rapid evolution of the illness; - concern of parents, relatives or friends; - patient age (highest incidence at age 3-12 months, followed by 1-4 and then 15-19 years); and - contact with a patient with meningococcal disease. In addition to specific clues, clinicians should look at the whole pattern of the illness. Timely clinical review is essential if there is doubt about the diagnosis. In any acutely febrile patient, it is prudent to ask "Why is this patient seeking help now?", then "Could this patient have meningococcaemia?".
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PMID:Early clinical clues to meningococcaemia. 1255 87

Several cases of life threatening respiratory disease with no identifiable cause were reported from Guangdong Province, China; these were soon followed by reports from many other countries. The disease was named as severe acute respiratory syndrome (SARS). A novel coronavirus, isolated from the respiratory secretions of patients, has been implicated in the causation of SARS. The modes of transmission include droplet spread, close contact, and Fomites; shedding of virus from respiratory tract is the primary mode of transmission. SARS clinically presents with high-grade fever, chills and rigors, myalgia, headache, cough with or without sputum production, dyspnea, and dizziness. Chest radiographs reveal unilateral or bilateral, predominantly peripheral, areas of consolidation progressing with in a short time of bilateral patchy consolidation. Preliminary reports suggest a milder illness in young children. The case definition of probable SARS cases, laboratory investigations and precautions for prevention of spread are discussed.
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PMID:Severe acute respiratory syndrome (SARS). 1284 1

Rat bite fever is a rarely reported acute febrile bacterial illness caused by Streptobacillus moniliformis or Spirillum minus following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.
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PMID:Rat bite fever without fever. 1292 66

Availability of a drug regimen that eradicates the hepatitis C virus (HCV) in more than half of treated patients provides the medical community with a powerful new weapon to diminish the anticipated future wave of HCV-related liver disease and cancer. Clinicians must understand the benefits, risks, and costs associated with the combination of peginterferon alfa and ribavirin. Major clinical trials with this new standard of HCV therapy have demonstrated sustained virologic responses of 54% and 56% with 48 weeks of combination therapy. Response is highest in those with genotype 2/3, with early virologic response by week 12, in patients with high adherence, and in patients receiving weight-appropriate ribavirin dosages. The most common side effects are manageable and include fatigue, headache, myalgia, rigors, fever, nausea, insomnia, and depression. Neutropenia associated with interferon and anemia associated with ribavirin are more serious side effects that can cause discontinuation or dose reduction. Clinicians can maximize results and reduce costs with a regimen of peginterferon alfa plus ribavirin by choosing patients carefully, educating patients thoroughly, stopping therapy early in those patients who do not respond by week 12 of therapy, and enhancing adherence by managing side effects with appropriate dose reductions and/or selective use of antidepressants or hematopoietic colony stimulators.
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PMID:Managing hepatitis C. 1508 65

Intravenous immunoglobulins (IVIgs) exert a variety of immunomodulating activities and are, therefore, increasingly being used for the treatment of immune-mediated as well as autoimmune diseases. There is also accumulating evidence that high-dose IVIg (hdIVIg) is highly efficacious in the treatment of skin diseases, despite the lack of evidence from randomized, double-blind, placebo-controlled trials. A major advantage of hdIVIg in comparison with other commonly used immunomodulating therapeutic strategies is the excellent safety profile. Accordingly, IVIgs have been used successfully for the treatment of bullous autoimmune diseases such as pemphigus and bullous pemphigoid, dermatomyositis, scleroderma, cutaneous lupus erythematosus, toxic epidermal necrolysis, and erythema exudativum multiforme. In most cases, hdIVIg is effective only in combination with other immunomodulating strategies and allows for the reduction of adjuvants. Adverse effects of hdIVIg are generally mild and self-limiting. These include headache, myalgia, flush, fever, nausea or vomiting, chills, lower backache, changes in blood pressure, and tachycardia. To avoid infusion-related rigors, headaches, and other adverse events, pre-treatment with analgesics, NSAIDs, antihistamines, or low-dose intravenous corticosteroids may be beneficial. Controlled, double-blind, long-term clinical trials and a better understanding of the complex immunomodulating mechanism of IVIg are required to ultimately optimize dose, frequency, duration, and mode of IVIg administration.
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PMID:Efficacy and safety of intravenous immunoglobulin for immune-mediated skin disease: current view. 1518 94


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