Pathology of the swine-origin influenza A (H1N1) flu.

Pathological studies would aid in finding the real causes of death and in outlining adequate strategies for treatment regarding patients with poor clinical outcome of influenza A H1N1 swine flu. We describe the autopsy findings of six cases of influenza A H1N1 swine flu. The lungs in these cases had an alveolitis with hyaline membranes. Immunohistochemistry for influenza was positive only in lungs (in pneumocytes, in macrophages, in some multinucleate cells in alveoli, and in blood vessel walls) of two cases. Disseminated petechial brain hemorrhage was observed in four of the cases and focally in one case. Focal myocarditis was observed in one case. Coagulation infarcts (ischemic) were observed in the pancreas of two cases and in the spleen of two cases. Our results indicate that there was marked replication of the virus in alveoli in the more recently infected cases, which could explain the extensive diffuse alveolar damage. In our cases, there were important vascular phenomena that resulted in hemorrhage and thrombosis, but without marked decrease of platelet count and coagulation cascade disruptions. This would be attributed to hemodynamic disruption. However, it is possible that the hemorrhagic petechial lesions in the brain are due to vascular lesions or to an increase of endothelial permeability.

Barriers to treatment of hepatitis C in HIV/HCV coinfected adults in Brazil.

UNLABELLED: The objective of this study was to assess the prevalence of barriers to interferon treatment in a population of HIV/HCV coinfected patients. A cross-sectional study was conducted at two AIDS Outpatient Clinics in Brazil. The study included all HIV infected patients followed at these institutions from January 2005 to November 2007. Medical records of 2,024 HIV-infected patients were evaluated. The prevalence of anti-HCV positive patients among them was 16.7%. Medical records of HCV/HIV coinfected patients were analyzed. 189 patients with the following characteristics were included in our study: mean age 43 years; male gender 65%; former IDUs (52%); HCV genotype 1 (66.4%); HCV genotype 3 (30.5%); median CD4+ T cell count was 340 cells/mm³. Among 189 patients included in the analyses, only 75 (39.6%) were considered eligible for HCV treatment. The most frequent reasons for non-treatment were: non-compliance during clinical follow-up (31.4%), advanced HIV disease (21.9%), excessive alcohol consumption or active drug use (18.7%), and psychiatric disorders (10.1%). CONCLUSIONS: In Brazil, as in elsewhere, more than half of HIV/HCV coinfected patients (60.4%) have been considered not candidates to received anti-HCV treatment. The main reasons may be deemed questionable: non-adherence, drug abuse, and psychiatric disease. Our results highlight the importance of multidisciplinary teams to optimize the access of coinfected patients to HCV treatment.

High frequency of lamivudine resistance mutations in Brazilian patients co-infected with HIV and hepatitis B.

This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co-infected with HIV and hepatitis B virus (HBV). A cross-sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an "in-house" real-time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty-eight patients with co-infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF.

Barriers to treatment of hepatitis C in HIV/HCV coinfected adults in Brazil

The objective of this study was to assess the prevalence of barriers to interferon treatment in a population of HIV/HCV coinfected patients. A cross-sectional study was conducted at two AIDS Outpatient Clinics in Brazil. The study included all HIV infected patients followed at these institutions from January 2005 to November 2007. Medical records of 2,024 HIV-infected patients were evaluated. The prevalence of anti-HCV positive patients among them was 16.7 percent. Medical records of HCV/HIV coinfected patients were analyzed. 189 patients with the following characteristics were included in our study: mean age 43 years; male gender 65 percent; former IDUs (52 percent); HCV genotype 1 (66.4 percent); HCV genotype 3 (30.5 percent); median CD4+ T cell count was 340 cells/mm³. Among 189 patients included in the analyses, only 75 (39.6 percent) were considered eligible for HCV treatment. The most frequent reasons for non-treatment were: non-compliance during clinical follow-up (31.4 percent), advanced HIV disease (21.9 percent), excessive alcohol consumption or active drug use (18.7 percent), and psychiatric disorders (10.1 percent). CONCLUSIONS: In Brazil, as in elsewhere, more than half of HIV/HCV coinfected patients (60.4 percent) have been considered not candidates to received anti-HCV treatment. The main reasons may be deemed questionable: non-adherence, drug abuse, and psychiatric disease. Our results highlight the importance of multidisciplinary teams to optimize the access of coinfected patients to HCV treatment.

Acute renal failure and hypercalcemia in an athletic young man.

Hypercalcemia is a life-threatening disorder and is related primarily to neoplastic diseases and primary and secondary hyperparathyroidism. The association of hypercalcemia and renal failure is frequent in the medical literature, although pathogenetic mechanisms remain to be elucidated. In this article, we present a case of hypercalcemia and acute renal failure secondary to vitamin D and vitamin A intoxication, after an over-the-counter intramuscular use by a young man starting an athletic performance program. A discussion of clinical picture, diagnosis and treatment is made, and we highlight the risk of pathological conditions triggered by inadvertent use of supplementation products and formulas available in health and fitness commercial centers.

Effect of highly active antiretroviral therapy on cytomegalovirus antigenaemia in AIDS patients.

To assess the effect of highly active antiretroviral therapy (HAART) on cytomegalovirus (CMV) antigenaemia in AIDS patients, 70 patients with CD4+ cell counts < or = 50/mm3 and positive anti-(CMV) immunoglobulin G (IgG) were tested at 15-30 day intervals for CMV antigenaemia. We selected those patients who had been followed up for more than 3 months. Three patient profiles were defined: A, followed up before the introduction of HAART; B, followed up before and after the use of HAART; and C, followed up after the use of HAART. Thirty-nine patients were included, 12 in group A, 17 in group B, and 10 in group C. Group A patients presented a lower median CD4+ cell count compared with groups B and C patients (9, 122 and 127 cells/mm3, respectively), with the increase in the last 2 groups being related to the use of HAART (P<0.001). A lower proportion of positive antigenaemia was observed in group B after the introduction of HAART compared with the time before HAART (P=0.02). HAART caused an immunological improvement and was found to be associated with negativity of CMV antigenaemia.

Comparison between antigenemia and a quantitative-competitive polymerase chain reaction for the diagnosis of cytomegalovirus infection after heart transplantation.

BACKGROUND: Antigenemia and quantitative polymerase chain reaction (PCR) are widely used for cytomegalovirus (CMV) diagnosis after heart transplantation due to their enhanced predictive values for disease detection when specific cut-off values are used. The purpose of this study was to compare, in the same patient setting, the predictive values of quantitative PCR and antigenemia for CMV disease detection, using specific cut-off values. METHODS: Thirty heart transplant receptors were ch prospectively monitored for active CMV infection and disease detection, using quantitative PCR and anti- po genemia. Positive and negative predictive values for pr CMV disease detection were calculated using cut-off pr values for both antigenemia (5 and 10 positive cells/300,000 neutrophils) and quantitative-PCR (50,000 and 100,000 copies/10(6) leukocytes). RESULTS: Active CMV infection was diagnosed in 93.3% of patients and CMV disease in 23.3%. The positive and negative predictive (%) values for CMV disease detection were 35/100 and 46.7/100, respectively, for quantitative PCR and antigenemia. Using 5 and 10 positive cells/300,000 neutrophils as cut-off values for antigenemia, the positive and negative predictive values (%) for disease detection were respectively 63.6/100 and 70/100. For quantitative PCR, the positive and th negative predictive values (%) for cut-off values of to 50,000 and 100,000 copies/10(6) leukocytes were 53.8/100 and 60/94.1, respectively. CONCLUSION: In our series, antigenemia and quantitative-PCR had enhanced and similar predictive values for CMV disease detection when specific cut-off values were used. The choice between these two methods for disease detection may rely less on their efficiency and more on the experience and familiarity with them.

Detection of mycobacteria in the bloodstream of patients with acquired immunodeficiency syndrome in a university hospital in Brazil.

This study was done to determine the occurrence of mycobacteria in the bloodstreams of patients with fever and advanced AIDS in a Brazilian hospital. We also verified the capability of an automated method for recovering these bacteria. During a period of 19 months, 254 patients with AIDS were evaluated. Blood cultures were generally submitted in pairs and drawn separately. Blood cultures were processed by the BACTEC 460TB System (Becton Dickinson Microbiology Systems, Sparks, MD), using the Bactec 13A media (Becton Dickinson Microbiology Systems, Sparks, MD). Of the 530 vials submitted, 77 (14.5%) from 41 (16%) patients were positive. Mycobacterium avium complex was recovered from 45 (58.4%) of the 77 positive vials, corresponding to 22 (53.6%) patients with positive blood cultures. The average time to detect Mycobacterium avium complex was 15 days. Mycobacterium tuberculosis was recovered from 26 (33.8%) of the 77 positive vials, corresponding to 15 (36.6%) patients with positive blood cultures, with an average detection time of 24 days. Other species of mycobacteria were recovered from 6 (7.8%) of the 77 vials, corresponding to 4 (9.8%) patients. M.avium complex was fairly prevalent (8.7%) in severely ill patients with AIDS in our hospital. M. tuberculosis was also an important (6.0%) agent of systemic bacterial infections in these patients. The rapid diagnosis of mycobacteremia was possible with the implementation of this automated technology.

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

CMV and transplant-related coronary atherosclerosis: an immunohistochemical, in situ hybridization, and polymerase chain reaction in situ study.

Accelerated graft coronary atherosclerosis is the main obstacle to long-term survival in patients who have had a heart transplant. A possible involvement of the human cytomegalovirus (HCMV) in this type of coronary atherosclerosis has been postulated by many authors but has not been definitively demonstrated. In an attempt to clarify the role of HCMV infection in the pathogenesis of this complication, we looked for in situ antigens or DNA of HCMV in 30 coronary artery segments obtained at necropsy from patients who had undergone orthotopic cardiac transplantation at the São Paulo Heart Institute. We tried to correlate these HCMV markers with the presence of inflammation and/or atherosclerosis in histologic sections. The patients were grouped as follows: GI, less than 170 days of graft survival and absent/mild atherosclerosis; GII, more than 170 days of graft survival and absent/mild atherosclerosis; GIII, more than 170 days of graft survival and severe/moderate atherosclerosis (170 days was the shortest graft survival time associated with atherosclerosis). The search for HCMV genome and antigens in the coronary artery sections was performed using immunohistochemistry, in situ hybridization, and polymerase chain reaction in situ techniques. Immunohistochemistry and in situ hybridization revealed no evidence of HCMV in all 30 cases. Polymerase chain reaction in situ revealed scarce HCMV-positive lymphocytes in two cases (one each from GI and GIII) located in the adventitial layer. These findings preclude a direct role for the HCMV in the pathogenesis of accelerated graft coronary atherosclerosis. However, the possibility of an indirect effect of the virus, such as an immune-mediated inflammatory response by the host that increases the expression of histocompatibility antigens, leading to tissue injury, cannot be excluded.

Use of itraconazole in the treatment of mucocutaneous leishmaniasis: a pilot study.

OBJECTIVE: Mucocutaneous leishmaniasis is widely distributed in Brazil, with Leishmania (Viannia) braziliensis being the major etiologic agent. The currently recommended therapy is limited by its parenteral use, high toxicity, and variable efficacy. A clinical pilot study was conducted to analyze itraconazole as an oral alternative for the treatment of mucocutaneous leishmaniasis. METHODS: Ten patients were enrolled to receive 4 mg/kg per day (up to 400 mg/d) itraconazole for 6 weeks on an outpatient regimen. Diagnosis was based on clinical otorhinolaryngologic examination, followed by a specific serologic reaction, the Montenegro test and pathologic analysis with immunohistochemical reaction. Healing of the lesions was confirmed by clinical otorhinolaryngologic examination. Side effects were monitored by general clinical assessment, hemoglobin determination, leukocyte counts, and liver function tests, all performed before, during, and 1 month after the end of treatment. RESULTS: Six of 10 patients presented healed lesions 3 months after treatment, with a sustained therapeutic response for at least a median period of 14.5 months (range, 12-18 mo). Side effects were not observed. CONCLUSIONS: This pilot study demonstrated that itraconazole can be an effective and well-tolerated alternative for the treatment of mucocutaneous leishmaniasis. Further randomized studies and double blind controlled trials are needed to assess the benefits of this drug in the treatment of mucocutaneous leishmaniasis.

Nosocomial coagulase negative Staphylococci bacteremia: five year prospective data collection.

UNLABELLED: Coagulase-negative Staphylococcus (CoNS) species, as a group, constitute a major component of the normal microflora of the human skin and mucous membranes. Over the last 20 years, there has been an increase in the documentation of infections due to CoNS, especially with S. epidermidis species, the most common cause of nosocomial primary bloodstream infections. OBJECTIVE: To determine the frequency of CoNS isolates in blood cultures, to evaluate the meaning of this isolation (contaminant or pathogen), and to determine their epidemiologic and susceptibility patterns (oxacillin, ciprofloxacin, vancomycin, clindamycin and teicoplanin). METHODS: All strains of CoNS isolated from blood cultures collected from adults and children during 1993 to 1998, were classified as contaminant or pathogenic according to NNISS criteria (1988). Infections were classified as primary or secondary bacteremia, from clinical or surgical patients, and divided by sex and age. Susceptibility patterns were also studied in both groups. RESULTS: From 1993 to 1998, 1,702 positive blood cultures were recorded. CoNS were isolated from 546 samples (32%), with 306 (56%) classified as contaminant and 240 (44%) as true bacteremia. The presence of an intravenous catheter was an important risk factor. Endocarditis (47%) ans pneumonia (32%) were the most common sites leading to secondary bacteremia. CONCLUSION: The results confirm the increasing importance of true CoNS bacteremia and confirm their association with prosthetic valve endocarditis. We emphasize the need for care at the time of blood collection, as well as the need for care in the processing of the material, so that contamination can be reduced. This will allow a more precise description of the infections caused by coagulase-negative Staphylococcus.

An evaluation of clinical, serologic, anatomopathologic and immunohistochemical findings for fifteen patients with mucosal leishmaniasis before and after treatment.

Treatment of mucosal leishmaniasis (ML) can be controlled by clinical examination and by serologic titers by the indirect immunofluorescence serologic reaction (IISR). We studied the correlation between the presence of antigen in tissue determined by immunohistochemistry, the IISR titers and the anatomopathologic findings in fifteen patients with ML before and after healing of the lesions as determined by otorhinolaryngologic evaluation, and evaluated these parameters to determine which of them could be useful during follow-up. Tissue antigens became negative in four patients (group A) after treatment, with a statistically significant reduction or negativity of IISR titers (p < 0.05). This did not occur in patients in whom the antigen persisted after treatment (group B), suggesting that serologic follow-up should be performed together with the search for tissue antigen, a combination which, to our knowledge, has not been used in previous studies. The negativity of tissue antigens and the behavior of IIRS titers in group A patients probably indicate a lower possibility of recurrence. Upon anatomopathologic examination the inflammatory process was found to persist after treatment even in group A, suggesting that the permanence of inflammatory activity even in clinically healed lesions is possibly correlated with the presence of the antigen or of some unknown factor.

Roxithromycin treatment for diarrhoea caused by Cryptosporidium spp. in patients with AIDS.

In view of the action of newer macrolide antibiotics on intracellular protozoa, we have investigated the efficacy of roxithromycin in the treatment of cryptosporidiosis in 26 patients with AIDS. Cryptosporidiosis was confirmed either by faecal examination for parasites (modified Kinyoun method) or by detection of the parasite in biopsy material obtained by colonoscopy. Patients received oral roxithromycin (300 mg bd) for 4 weeks. Twenty-two patients completed the study. At the end of the study, 15 patients (68%) were considered to be cured and six patients (27%) improved, and treatment failed in one patient (5%). We conclude that roxithromycin is a useful treatment for diarrhoea caused by Cryptosporidium spp. associated with AIDS.

[Evaluation of the quality of life in patients with Chagas' disease undergoing a heart transplant]. / Avaliação da qualidade de vida de pacientes com doença de Changas submetidos a transplante de coração.

Quality of life was evaluated in 11 patients with Chagas' disease 26 to 126 months after submission to heart transplantation. There was an objective improvement in their quality of life, after the transplant.

[Cutaneous lesions as the only manifestations of reactions to Trypanosoma cruzi infection in a recipient of a kidney transplant]. / Lesões cutâneas como únicas manifestações de reativação da infecção pelo Trypanosoma cruzi em receptora de rim por transplante.

We report a patient with chronic asymptomatic Chagas' disease that presented Trypanosoma cruzi reactivation after kidney transplantation and immune depression. The only clinical manifestation of the disease was ulcerative skin lesions, which is unusual in Chagas' disease.

Parotid enlargement due to adenovirus infection in patient with human immunodeficiency virus infection.

The authors report a case of adenovirus-induced enlargement of the parotid gland involving a patient infected with human immunodeficiency virus (HIV). Physical examination revealed good general condition, no fever and bilateral enlargement of the parotid region, which was of increased consistency and slightly tender to palpation. Histological examination of the parotid gland demonstrated a slight periductal lymphomononuclear inflammatory infiltrate with the presence of focal points of necrosis. Tests to determine the presence of fungi and alcohol-acid resistant bacilli were negative. Immunohistochemistry for cytomegalovirus, herpes simplex, HIV p24 antigen and adenovirus showed positivity only for adenovirus in the epithelial nuclei of numerous gland ducts. This is the third case of this type reported in the literature, indicating the importance of including adenovirus in the differential diagnosis of this condition.

[Infections caused by virus in 100 patients submitted to heart transplantation]. / Infecções causadas por vírus em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: To analyse prevalence, clinical features and organ involvement in viral infections occuring after heart transplantation. METHODS: One hundred consecutive heart transplantation patients were studied. The follow-up was three to 90 (mean 23.32 +/- 25.97) months. Viral infections were diagnosed using the Center for Disease Control criteria. RESULTS: Viral infections were responsible for 51 infections, 19.6% of all infections in this patient population. Herpesvirus infection was the most common etiology: 32 (59.25%) of all viral infections were caused by reactivation of or reinfection by cytomegalovirus. Of those infections 27 (84.37%) occurred in the first three weeks following surgery. Only 4 (12.50%) of those showed clinical signs of cytomegalovirus disease. Other herpesvirus causing infections were herpes simplex and varicella-zoster virus. CONCLUSION: Infections are common after heart transplantation and viral infections of herpesviridae family are important causes of those infections; usually as reactivation in an immune suppressed patient. The most important viral infections were caused by reactivation of or reinfection by cytomegalovirus.

Infecções bacterianas em 100 pacientes submetidos a transplante cardíaco / Bacterial Infections in 100 Patients Submitted to Heart Transplantation

Objetivo - analisar as ocorrências, os agentes etiológicos e a apresentaçäo clínica referentes às infecçöes bacterianas diagnosticadas em grupo de pacientes submetidos a transplante (Tx) cardíaco. Métodos - foram considerados 100 doentes, observados consecutivamente, após Tx cardíaco. O período de seguimento variou de 3 a 90 (média 25,38 + ou - 25,96) meses. O reconhecimento das infecçöes bacterianas levou em conta os critérios estabelecidos pelos Centers for Disease Control. Resultados - as infecçs pulmonares bacterianas comparecem em maior número, havendo dificuldade para diagnosticá-las depois do Tx. Ocorreram comprometimentos motivados por bactérias em pele, mucosas, partes moles, ferida operatória, pericárdio, pleura, loja do marcapasso e vias urinárias, tendo também sido constatadas bacteremias e endocardites. Os agentes etiológicos, quando reconhecidos, ficaram devidamente especificados. Conclusäo - o período pós-operatório inicial é crítico, pois nos 30 dias subsequentes a ele as infecçöe acterianas surgem com maior frequência. Elas também suscitam maior preocupaçäo nas fases de tratamento dos episódios de rejeiçöes. Diagnóstico precoce e rápida adoçäo de medidas coercitivas podem evitar gravidade e evoluçäo para óbito

Purpose - To evaluate clinical findings and etiology of bacterial infections diagnosed in 100 consecutive heart transplantations. Methods - One hundred consecutive heart transplant patients were studied. Follow-up after heart transplantation varied from 3 to 90 (mean 25.38± SD 25.97) months. Etiology of bacterial infection was established using the Centers for Disease Control criteria. Results - Bacterial infection was the most common cause of infection after heart transplantation; diagnosis was difficult. Infection sites were skin, mucous, membranes, soft tissue, surgical scar, pericardial and pleural spaces, soft tissue around heart pacing devices, urinary tract; bacteremias and endocarditis were also found. All bacterial agents recovered were fully identified Conclusion - Bacterial infections are the most common infections in the first month after heart transplantation. They are important and also common after the treatment of the rejection episodes. Rapid diagnosis and adequate treatment are essential to prevent morbidity and death