Epidemiological and cost analysis of multidrug-resistant tuberculosis in Oman.

We conducted an epidemiological and cost analysis for all 13 patients diagnosed with multaidrug-resistant tuberculosis (11 pulmonary, 2 extrapulmonary) in Oman from January 2000 to October 2005. The disease was secondary, or acquired, in 12 of 13 patients. A total of 140 contacts were screened (mean 10.8 persons per patient), but contact tracing revealed no secondary cases. The mean number of drugs that TB isolates were resistant to was 2.8 (range 2-5). A mean of 4.7 drugs were given to patients, the mean length of therapy was 8 months and all patients were cured. The cost of medications for these multidrug-resistant cases was 14 to 29 times higher than that for the standard drug-sensitive TB regimen.

Endemic nosocomial Acinetobacter calcoaceticus bacteremia. Clinical significance, treatment, and prognosis.

The medical records of 27 patients with blood cultures positive for Acinetobacter calcoaceticus over a recent five-year period (0.7% of all positive blood cultures) were reviewed retrospectively to determine the epidemiologic and clinical significance of these isolates. Eighteen isolates represented true bacteremias, 16 of which were hospital acquired. Patients most frequently were located in an intensive care unit or on a surgical ward. A seasonal July-to-September peak incidence was noted. The most common site of primary infection was the respiratory tract. Aminoglycosides, alone or in combination with a second agent, were used to treat all but one infection. Bacteriologic cure was achieved in 15 cases (88%); six patients had polymicrobial sepsis that carried a higher mortality than pure A calcoaceticus bacteremia (50% vs 0%). Acinetobacter, a low-virulence opportunistic pathogen, may be an infrequent but potentially serious endemic agent of nosocomial bacteremia in some institutions. The prognosis of bacteremia, when appropriately treated, appears to be good.

The neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) comprises hyperpyrexia, altered consciousness, muscular rigidity, and autonomic dysfunction. It is a rare idiosyncratic reaction to major tranquilizers, including the phenothiazines, butyrophenones, and thioxanthenes; haloperidol and fluphenazine enanthate or fluphenazine decanoate are the drugs most commonly incriminated. The syndrome occurs after therapeutic rather than toxic doses of neuroleptic drugs and is unrelated to the duration of therapy. The NMS is attributed to a disturbance of dopaminergic systems within the basal ganglia and hypothalamus. Associated laboratory abnormalities include leukocytosis, with elevated serum creatine phosphokinase (CPK) and liver enzyme concentrations. The NMS, which is known to some psychiatrists and neurologists but to few internists, probably is underdiagnosed; therefore, its true incidence is unknown. The NMS should be included in the differential diagnosis of any febrile patient with a history of neuroleptic treatment. Because the mortality of NMS is about 20%, early diagnosis and withdrawal of the neuroleptic drug therapy is crucial. Supportive treatment in a medical intensive care unit may be required.

A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia.

OBJECTIVE: To determine the relative efficacies of alternative antipneumocystis agents in human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia unresponsive to primary drug treatment with a combination product of trimethoprim and sulfamethoxazole or parenteral pentamidine. METHODS: Meta-analysis of 27 published clinical drug trials, case series, and case reports involving P carinii pneumonia. Data extracted included underlying disease, primary antipneumocystis treatment, days of failed primary treatment, salvage regimen, use of systemic corticosteroids and antiretroviral drugs, and clinical outcome. RESULTS: In 497 patients with microbiologically confirmed P carinii pneumonia (456 with HIV or acquired immunodeficiency syndrome), initial antipneumocystis treatment failed and they therefore required alternative drug therapy. Failed regimens included trimethoprim-sulfamethoxazole (160 patients), intravenous pentamidine (63 patients), trimethoprim-sulfamethoxazole and/or pentamidine (258 patients), aerosolized pentamidine (6 patients), atovaquone (3 patients), dapsone (3 patients), a combination product of trimethoprim and dapsone (2 patients), and trimethoprim-sulfamethoxazole followed by a combination of clindamycin and primaquine phosphate (2 patients). Efficacies of salvage regimens were as follows: clindamycin-primaquine (42 to 44 [88%-92%] of 48 patients; P<10(-8)), atovaquone (4 [80%] of 5), eflornithine hydrochloride (40 [57%] of 70; P<.01), trimethoprim-sulfamethoxazole (27 [53%] of 51; P<.08), pentamidine (64 [39%] of 164), and trimetrexate (47 [30%] of 159). CONCLUSION: The combination of clindamycin plus primaquine appears to be the most effective alternative treatment for patients with P carinii pneumonia who are unresponsive to conventional antipneumocystis agents.

Trimethoprim-sulfamethoxazole therapy for Nocardia infections.

The optimal therapy for infections due to Nocardia species has not been established. To assess the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX), we reviewed the records of 19 patients with Nocardia infections seen at Duke University Medical Center, Durham, NC, who were treated with this drug, either alone or in combination with other antibiotics or a surgical procedure. Underlying diseases or therapy causing immunosuppression were present in all but five cases. Sites of involvement were lung (ten of 19), wound (two of 19), and brain (two of 19); five of 19 patients had disseminated disease. The mean duration of therapy was 7.2 months. Overall cure or improvement was achieved in 89% (17/19) of cases; 80% of patients with disseminated disease and 60% of those with CNS involvement recovered. This experience, and accumulated clinical evidence in the literature, indicates that TMP-SMX should be considered the therapeutic drug of choice in infections due to Nocardia species.

Concurrent malaria and enteric fever in Pakistan.

INTRODUCTION: The precise incidence of concurrent malaria and enteric fever in most geographical areas is largely unknown, and no data on such an association exists in Asia. Because both malaria and enteric fever are hyperendemic in Pakistan, we sought to determine the frequency, epidemiology, and clinical and laboratory features of dual malaria and enteric fever in a tertiary care setting. METHODS: We conducted a retrospective case-control study of 1,891 patients hospitalised with malaria over a ten-year period and identified 21 patients with concurrent culture-proven enteric fever. RESULTS: Cases with dual infection had significantly more gastrointestinal symptoms at the time of admission, including nausea, vomiting, abdominal pain, and/or diarrhoea compared to matched control subjects with uncomplicated malaria (p-value is less than 0.006). Cases were more likely to have a continuous rather than intermittent fever (p-value is less than 0.0001), delayed defervescence in response to antimalarial treatment (p-value is less than 0.006), normal or low white blood cell counts (p-value is less than 0.04), relatively higher platelet counts among cases versus control (p-value is less than 0.05) and serum haemoglobin (p-value is less than 0.06), elevated alanine aminotransferase levels (p-value is less than 0.02), and a prolonged hospital stay (p-value is less than 0.03). The negative predictive values for gastrointestinal symptoms, continuous fever pattern and delayed defervescence were 80 percent, 72 percent and 74 percent, respectively. CONCLUSION: Patients with malaria who have marked gastrointestinal symptoms, continuous pattern of fever and persistence of fever for more than 24 hours after appropriate antimalarial therapy, should be investigated or empirically treated for concurrent enteric fever. The absence of the above clinical features in patients with uncomplicated malaria should reassure physicians that there is no concurrent typhoid fever.

Rapid immunochromatography-based detection of mixed-species malaria infection in Pakistan.

We report the identification of mixed Plasmodium infections in four recent patients with malaria clinically refractory to empiric chloroquine therapy using the rapid antigen detection kit, NOW ICT Malaria Pf/Pv. A rapid in vitro immunodiagnostic test, the NOW ICT Malaria Pf/Pv test kit was used for the detection of circulating Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) antigens in whole blood. Peripheral blood microscopy confirmed mixed-species infection in all the cases. Thick and thin peripheral blood films were made and stained with Giemsa stain and examined by both hospital laboratory staff and an experienced parasitologist who was blinded to the results of the rapid malarial antigen tests. Four recent patients (all male; mean age, 24 years) with mixed malarial infection were identified. All the subjects were males working for an oil company in a coastal area of Pakistan, and all had been diagnosed presumptively with malaria based on clinical grounds (without microbiologic confirmation), and were treated empirically with chloroquine without clinical response. Semiquantitative malaria counts via microscopy were as follows: P. vivax, scanty (2 patients) and moderate (2 patients); for P. falciparum--scanty (1 patient), moderate (2 patients), and heavy (1 patient). The present case series, although limited by the small number of patients with proven mixed P. falciparum-P. vivax infection, highlights the usefulness of the rapid antigen test in a highly malarious region of Pakistan where chloroquine resistance is prevalent. Although there was full concordance between the results of blood smear microscopy and rapid antigen testing, these techniques are potentially most useful when there is a discrepancy with microscopy findings. Accurate and rapid diagnosis of parasites, particularly in cases of mixed P. falciparum and P. vivax infection, is of immense importance for individual patient management and in reducing the burden of disease, especially in regions of chloroquine resistance.

Lymphocutaneous syndrome. A review of non-sporothrix causes.

The lymphocutaneous syndrome can be caused by a number of diverse microorganisms requiring very different antimicrobial therapy for resolution. The epidemiology and geographic occurrence of the infection often can provide important first clues to the microbiologic etiology. Accurate diagnosis can be accomplished usually by punch or wedge biopsy of a primary lesion or proximal subcutaneous nodule submitted for histopathologic examination and culture. The microbiology laboratory staff should be alerted to the diagnostic possibilities so that appropriate cultural and incubation techniques, procedures, and precautions can be initiated. Provision of a correct microbiologic diagnosis and institution of appropriate antimicrobial therapy will result in a complete cure in almost all instances. Adjunctive surgical debridement may be required for certain organisms such as Nocardia or Mycobacterium chelonae.

Use of acyclovir for varicella pneumonia during pregnancy.

Twenty-one cases (five new and 16 literature) of varicella pneumonia of pregnancy were retrospectively reviewed to evaluate the benefits and risks of intravenous acyclovir on maternal and fetal outcomes. All women were in their second (12 cases) or third (nine cases) trimester. Mean gestational ages at the onset of pneumonia and time of delivery were 27 and 36 weeks, respectively. Twelve patients required mechanical ventilation. The mean duration of treatment was 7 days. No definite adverse drug effects were noted. Three women (14%) died of uncontrolled infection or complications. Two infants died (whose mothers also died): One was stillborn at 34 weeks' gestation, and the other died from prematurity shortly after birth at 26 weeks. No child was born with features of congenital varicella syndrome, and none developed active perinatal varicella infection. Onset of pneumonia during the third trimester was a risk factor associated with fatal maternal outcome. Intravenous acyclovir may reduce maternal morbidity and mortality associated with varicella pneumonia occurring during pregnancy, and appears to be safe for the developing fetus when given during the latter trimesters.

Epidemic non-A non-B hepatitis in urban Karachi, Pakistan.

An outbreak of icteric non-A non-B (NANB) hepatitis occurred in a residential community of urban Karachi, Pakistan, from August 1986 through October 1986. Of the 114 cases reported from this community during the 1986 calendar year, a clustering of 85 cases was seen during the above period. Twenty-seven percent of 226 households and 9% of 1,250 individuals were affected. Five persons were hospitalized and 1 death occurred in a young pregnant woman. Cases occurred predominantly in the less than or equal to 29-year-old age group (72%), with a male:female ratio of 1.8:1. Thirty-four cases occurred singly within households, while in 28 households multiple cases were seen. Analysis of the epidemic curve and intervals of onset of multiple cases within households suggested prolonged common source exposure rather than secondary person-to-person transmission. No single water source was implicated but a contaminated municipal supply was presumed. Information collected from several other communities and from a university hepatitis reference laboratory suggested that the outbreak was part of a larger urban epidemic of NANB hepatitis. Based upon this investigation and data from recently published reports, it is concluded that NANB hepatitis is endemic in Pakistan.

Cerebral involvement in benign tertian malaria.

Although Plasmodium vivax usually causes benign uncomplicated malaria, it can occasionally result in severe disease with life-threatening, end-organ involvement generally seen with falciparum malaria. We report a case of cerebral malaria caused by P. vivax and review the literature on this subject.

A systematic review of the adjunctive use of systemic corticosteroids for pulmonary tuberculosis.

OBJECTIVE: To determine the safety and benefit of adjunctive systemic corticosteroid therapy in the management of pulmonary tuberculosis. METHODS: A systematic review of 11 randomized, comparative clinical trials published from 1959 to 1999 involving the use of prednisone, prednisolone and/or adrenocorticotrophin (ACTH) in conjunction with standard anti-tuberculosis chemotherapy. A total of 1814 steroid-treated patients were analyzed, most of whom had moderate to severe disease and cavitation. Clinical, microbiologic and radiographic outcome measures included time to defervescence, weight gain, normalization of serum albumin level and erythrocyte sedimentation rate, length of hospitalization, rate and rapidity of sputum conversion and radiographic regression of pulmonary infiltrates and cavities. RESULTS: Corticosteroid therapy resulted in broad and significant clinical benefits in almost all of the studies reviewed. More rapid radiographic resolution of pulmonary infiltrates and, to a lesser extent, closure of cavities accompanied steroid use, especially in the first 4 months, but extended up to one year after initiation of treatment. Steroids did not have any appreciable effect on the speed or rate of sputum conversion. No detrimental side-effects attributed to steroid therapy or bacteriologic relapse were observed. CONCLUSION: The adjunctive use of systemic corticosteroid therapy can safely provide significant early and prolonged clinical and radiographic benefits in selected patients with advanced pulmonary tuberculosis.

Paradoxical tuberculous reactions in HIV-infected patients.

OBJECTIVE: To report the occurrence of paradoxical tuberculous reactions in two patients co-infected with HIV/AIDS, and to review the literature on this subject. PATIENTS: Two HIV-infected patients with miliary tuberculosis who developed expansion of tuberculous disease at a new site following initiation of anti-tuberculosis treatment, with or without antiretroviral treatment, and an additional 29 literature cases of HIV infection with paradoxical tuberculous reaction. RESULTS: Index episodes of tuberculosis included pulmonary, nodal, cutaneous and miliary forms. Types of paradoxical reactions included enlargement of lymph nodes or appearance of new lymphadenopathy, radiographic worsening of pulmonary infiltrates or appearance of miliary infiltrates or pleural effusions, peritonitis, tenosynovitis, worsening or development of new soft tissue lesions, and appearance of new contrast-enhancing intracranial tuberculomas. The occurrence of paradoxical reactions appears more temporally related to antiretroviral than to anti-tuberculosis therapy. CONCLUSIONS: It is important for clinicians to recognise paradoxical tuberculous reactions as inflammatory responses to treatment, and to understand that they do not necessarily indicate drug resistance or an inadequate response to therapy. Anti-tuberculosis and antiretroviral drug regimens need not be altered or discontinued, although a short course of corticosteroids may be useful in reducing inflammation.

An academic health center-community partnership: the Morgantown Health Right free clinic.

This article reports the main findings of a descriptive study of the origin, structure, and evolution of the Morgantown Health Right (MHR) free clinic in Morgantown, West Virginia. The study was conducted between 1984 and 1995 to examine the organizational and operational features of this rural academic health center-community partnership. The MHR's longevity and provision of primary care without charge to low-income, uninsured, and underinsured residents of north central West Virginia are a function of its intimate relationship with the Robert C. Byrd Health Sciences Center of West Virginia University. Essential elements of this rural academic health center-community partnership include social commitment and voluntarism, shared community and faculty leadership, joint problem-oriented long-term planning, and interdisciplinary practice and training opportunities for faculty, residents, and students. Financial support for the MHR comes from a variety of public and private sources, and the clinic serves as a prototypic rural free health care provider by virtue of its social and fiscal sustainability. The MHR experience shows that, like inner-city counterparts, academic health center-community partnerships can enhance access to health care for rural underserved populations.

Predictors of childhood immunization completion in a rural population.

Despite the availability of effective vaccines, immunization rates among two-year old children continue to be low in many areas of the United States including rural West Virginia. The goal of this study was to identify barriers to childhood immunization in rural West Virginia and determine factors that were important in the completion of the childhood immunization schedule. A telephone survey was used to collect data from a randomly selected sample of 316 mothers, of two-year olds, from 18 rural counties of West Virginia. Results indicated that two-thirds or 65% of the children in the study sample had completed their recommended immunizations by two years of age. Immunization barriers identified in this study include: living in health professional shortage areas, lack of health insurance, negative beliefs and attitudes regarding childhood immunizations, problems accessing the immunization clinic, and a perception of inadequate support from the immunization clinic. Results of the structural equation modeling, using LISREL-8, indicated that 20% of the variation in immunization completion (R2 = 0.197) was explained by attitude towards immunization and perceived support received from the immunization clinic. Furthermore, 42% of the variation in attitude towards immunization (R2 = 0.419) was explained by immunization-related beliefs, and 28% of the variation in immunization-related beliefs (the R2 = 0.277) was explained by general problems faced during immunization and perceived clinic support. The study concluded that positive immunization-related beliefs and attitudes, support from the immunization clinic, and ease of the immunization seeking process are important factors in the timely completion of the childhood immunization schedule.

Systematic review of combination antiretroviral therapy with didanosine plus hydroxyurea: a partial solution to Africa's HIV/AIDS problem?

Effective antiretroviral therapy remains beyond the reach of most human immunodeficiency virus (HIV)-infected persons living in the third world because of its tremendous cost. The cancer drug, hydroxyurea, inhibits HIV-1 replication in vitro and, when combined with didanosine (ddI), results in significant antiretroviral synergy. In vivo, hydroxyurea specifically targets quiescent lymphocytes and macrophages, important cellular reservoirs for HIV-1, and the combination of ddI plus hydroxyurea effectively reduces plasma HIV-1 RNA levels. Combination ddI-hydroxyurea costs about one-eighth as much as currently recommended triple drug combinations, and several countries in Africa are exploring the feasibility of widescale use of ddI-hydroxyurea for their HIV-infected populations. Intrigued by its potential relevance for Africa, the authors reviewed the literature on the in vitro and clinical efficacy of ddI plus hydroxyurea against HIV. The combination of ddI plus hydroxyurea is an effective and potentially more affordable regimen for HIV-infected persons living in poorer countries.

An experimental model for amoebic abscess production in the cheek pouch of the Syrian golden hamster, Mesocricetus auratus.

A new experimental model was developed in hamsters for amoebic abscess caused by Entamoeba histolytica. E. histolytica trophozoites were cultured in a liquid axenic medium, and then injected intradermally into the cheek pouch of the Syrian golden hamster, Mesocricetus auratus. Inoculation consistently resulted in abscess formation at the site in 20 of 22 (91%) study animals. The amoebic nature of the abscesses was confirmed by light microscopy and histopathologic examination. Abscess formation was maximal at day 12 post-inoculation. Potential applications of this simple and reliable model include further elucidation of the pathogenesis of invasive amoebiasis, studies of the host response to amoebae, and in vivo evaluation of chemotherapeutic agents that show in vitro efficacy against E. histolytica.

The benefits of telephone-access medical consultation.

A major disadvantage of rural medical practice is the limited reserve of consultative options. To determine the perceived clinical utility and educational impact of the West Virginia University Medical Access and Referral System (MARS), a 24-hour prompt telephone-consultation service, a mailed questionnaire was administered to 303 West Virginia clinicians who had used MARS for infectious disease problems. The overall questionnaire response rate was 62 percent. Callers included family practitioners (35%), medical specialists (32%), surgical specialists (13%), pediatricians (11%), obstetricians (5%), and nonphysicians (4%). Major referral questions posed were therapeutic (60%), diagnostic (48%), and epidemiologic (10%) in nature. On a scale of 1 (not useful) to 5 (very useful), survey responders rated the overall clinical usefulness of MARS as either a 4 (22%) or 5 (76%). Callers felt that MARS consultation assisted in accurate case diagnosis in 80 percent of cases, and aided in successful therapeutic management of 96 percent of cases. An educational benefit was reported by 96 percent of responders. Physicians located in more rural, underserved areas tended to use MARS to a greater degree than colleagues in more populated, medically accessible areas (P < 0.005). These findings suggest that an academic telephone-access consultation program can be a clinically relevant and educational consultative tool for practicing clinicians, especially those located in rural areas.

An experimental model for Naegleria fowleri-induced primary amebic meningoencephalitis in rabbits.

A new model was developed in rabbits for primary amebic meningoencephalitis, a rare disease caused by the free-living ameba, Naegleria fowleri. Naegleria fowleri was cultured in a liquid axenic medium, and then injected intracisternally into New Zealand White rabbits. Inocula of 10(3) or 10(5) trophozoites consistently produced a sanguinopurulent meningitis; duration of survival of rabbits was 57 or 45 hr, respectively. Counts of cells in cerebrospinal fluid were proportional to the size of inoculum used; white blood cell counts ranged from 30 to 1,055 cells/mm3, and red blood cell counts from five to 8,640 cells/mm3. Necropsies revealed severe basilar meningoencephalitis with extensive hemorrhagic necrosis and polymorphonuclear cell infiltration. Trophozoites of N. fowleri were seen within the meningeal exudate and the brain parenchyma. Potential applications of this model include studies of the host response to amebae in the CSF, evaluation of the optimal route of administration of amphotericin B, and in vivo studies of other chemotherapeutic agents that show in vitro efficacy.

Lack of benefit of granulocyte macrophage or granulocyte colony stimulating factor in patients with febrile neutropenia.

OBJECTIVES: To compare the clinical benefits of granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) plus standard supportive care to supportive care alone among cancer patients with febrile neutropenia. METHODS: Clinical data were collected retrospectively from 148 consecutive cancer patients with neutropenia and fever. Patients had hematologic (i.e., acute leukemias or lymphoproliferative disorders) or non-hematologic malignancies (i.e., solid tumors including carcinoma of breast, lung, or colon). Clinical variables analyzed included: age and sex; underlying malignancies; chemotherapy regimens; symptoms at time of presentation; duration of fever prior to study enrollment; days from chemotherapy until administration of GM-CSF or G-CSF; number of previous neutropenic episodes; duration of fever and day of defervescence; absolute neutrophil count on day of defervescence; duration of neutropenia; number and types of antibiotics used; day amphotericin B begun; number of culture-documented infective episodes involving bloodstream, lung, pleura, urinary tract, gastrointestinal tract, intravenous cannulae, or skin; types of antimicrobial isolates; cost of cytokine therapy; length of hospital stay and clinical outcome. RESULTS: The use of myeloid growth factors increased the number of circulating peripheral white blood cells, but no significant effect was noted in terms of duration of neutropenia or fever, number of culture-proven infections (except pneumonia; p < 0.04), length of hospital stay, or survival. CONCLUSION: In areas with limited health care resources, expensive treatment with GM-CSF or G-CSF should be reserved for patients with complicated febrile neutropenia where the expected risk of infection is high and the duration of neutropenia is prolonged, or those with documented infections that are refractory to antibiotic treatment.