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.

Comparative features and outcomes of malaria at a tertiary care hospital in Karachi, Pakistan.

OBJECTIVES: A comparison of clinical and laboratory features, diagnostic methods, drug treatment, and outcomes for patients hospitalized with malaria by Plasmodium species. METHODS: Records of 521 patients hospitalized during the four and half-year study period were analyzed. RESULTS: Infections were caused by Plasmodium vivax (51.8%), Plasmodium falciparum (46.5%), P. vivax plus P. falciparum (1.3%), and Plasmodium malariae (0.4%). Vomiting (odds ratio (OR)=1.86, p=0.001) and abdominal pain (OR=1.60, p=0.024) occurred more frequently in patients infected with P. falciparum compared to P. vivax; this was also the case for hepatomegaly, splenomegaly and jaundice. Low hemoglobin levels were common but were significantly lower with P. falciparum, and creatinine levels were significantly higher with P. falciparum. Treatment regimens consisted of single drug therapy (61.5%), appropriate combination therapy (15.8%), and inappropriate combination therapy (22.7%). Antimalarials given alone included chloroquine (38.7%), quinine (19%) and doxycycline (1.5%). The overall mortality was 1.7% (n=9) and nearly 56% of patients developed disease complications, most commonly thrombocytopenia (36.4%), anemia (23.4%), and thrombocytopenia plus anemia (32.7%). CONCLUSIONS: Despite resistance, chloroquine was prescribed in patients with malaria requiring hospitalization. We found a high proportion of single antimalarial drug use as well as inappropriate combination therapy (22.7%), and inadequate use of primaquine terminal prophylaxis. Physicians need to be acquainted with malaria treatment guidelines in an endemic zone.

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.

Avoiding laboratory pitfalls in infectious diseases.

In today's medical care environment, clinicians are challenged to order clinically relevant, cost effective laboratory tests and antibiotic therapy. Together, physicians and laboratories must have guidelines and strategies that can provide quality patient care, while minimising costs and preventing further emergence of antimicrobial drug resistance. Five clinical vignettes that demonstrate these principles are presented.

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.

Features distinguishing amoebic from pyogenic liver abscess: a review of 577 adult cases.

Distinguishing amoebic from pyogenic liver abscesses is crucial because their treatments and prognoses differ. We retrospectively reviewed the medical records of 577 adults with liver abscess in order to identify clinical, laboratory, and radiographic factors useful in differentiating these microbial aetiologies. Presumptive diagnoses of amoebic (n = 471; 82%) vs. pyogenic (n = 106; 18%) abscess were based upon amoebic serology, microbiological culture results, and response to therapy. Patients with amoebic abscess were more likely to be young males with a tender, solitary, right lobe abscess (P = 0.012). Univariate analysis found patients with pyogenic abscess more likely to be over 50 years old, with a history of diabetes and jaundice, with pulmonary findings, multiple abscesses, amoebic serology titres <1:256 IU, and lower levels of serum albumin (P < 0.04). Multivariate logistic regression analysis confirmed that age >50 years, pulmonary findings on examination, multiple abscesses, and amebic serology titres <1:256 IU were predictive of pyogenic infection. Several clinical and laboratory parameters can aid in the differentiation of amebic and pyogenic liver abscess. In our setting, amebic abscess is more prevalent and, in most circumstances, can be identified and managed without percutaneous aspiration.

Prognostic indicators in patients with intracranial tuberculoma: a review of 102 cases.

OBJECTIVE: To see the characteristics, course and outcome of patients suffering from intracranial tuberculoma. METHODS: Retrospective review of 102 patients diagnosed as intracranial tuberculoma at a tertiary care center over 10 years. RESULTS: A total of 102 cases were seen with an age range of 1 to 75 years (mean, 30 years). Predisposing factors included Diabetes mellitus (8 patients) and pregnancy or puerperium (7 patients). Five pediatric patients had tuberculoma despite documented BCG vaccination. Fever (59%), headache (57%), meningeal irritation (36%) were the commonest presenting features; one-third of patients were drowsy or comatosed at presentation. Cerebrospinal fluid analysis was performed in 63 patients, of whom 88% had elevated protein, 83% had low glucose, and 84% had pleocytosis (one-third with neutrophilia). Forty-nine (50%) patients had clinical or laboratory evidence of concomitant tuberculous meningitis. Chest radiographs showed active or old tuberculous infection (25%), with a miliary pattern in 20%. Two-thirds of subjects had multiple tuberculomas (mean, 4.5 lesions per patient) on contrast CT or MRI scan. Hydrocephalus was present in 37 (37%) patients of which 21 required shunt surgery. Thirty-nine patients had > 9 months of follow up; 17 patients showed complete recovery, 20 patients had partial recovery, and 2 patients had no response. Coma at presentation and miliary pattern on chest X-ray were predictors of poor prognosis. CONCLUSION: The study demonstrate that fever, headache, signs of meningeal irritation and cranial nerve palsies are common presenting features. Complete recovery was seen in 40% patients. Coma and military TB are predictors of poor prognosis.

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.

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.

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.

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.

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.

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.

Dual pulmonary infection with Mycobacterium tuberculosis and Pneumocystis carinii in patients infected with human immunodeficiency virus.

During a 22-month period, we identified 39 patients with human immunodeficiency virus (HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with pneumonia and who had sputum and/or other specimens that tested concurrently positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most common chest x-ray abnormality was a reticulonodular pattern or bilateral infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17 (85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%]) received both antituberculous and anti-PCP therapy (17 with steroids), and 22 improved. All ten patients who received no treatment for PCP improved and were discharged from the hospital, whereas 4 (80%) of the 5 persons who received no antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with HIV or acquired immune deficiency syndrome may present with both TB and PCP; of the 2, TB seems to account for the most severe features of disease.

Control of an outbreak of vancomycin-resistant Enterococcus faecium in an oncology ward in South Africa: effective use of limited resources.

An outbreak of vancomycin-resistant enterococci (VRE) occurred in an adult oncology ward of a large teaching hospital in Johannesburg, South Africa. The outbreak strain was identified as an Enterococcus faecium carrying the vanA resistance genotype. Macro-restriction analysis showed that the majority of strains were clonally related. Modified infection control interventions were implemented and control of the outbreak was achieved. Although the epidemiology of VRE is well documented in Europe, North America and Australia, this problem has only recently emerged in South Africa. The epidemiology of the outbreak appears similar to that described for outbreaks elsewhere.

Epidemiology of glycopeptide-resistant enterococci colonizing high-risk patients in hospitals in Johannesburg, Republic of South Africa.

Recent cases of infections caused by glycopeptide-resistant enterococci (GRE) have highlighted the emergence of these organisms in the Republic of South Africa. During May 1998 we conducted a prevalence study in four hospitals in Johannesburg and obtained 184 rectal swabs from patients identified as being at high risk for GRE colonization. Twenty enterococcal isolates showing various glycopeptide resistance genotypes were recovered: 3 Enterococcus faecium vanA isolates, 10 E. faecium vanB isolates, 6 E. gallinarum vanC1 isolates, and 1 E. avium vanA isolate. Macrorestriction analysis was used to demonstrate the clonal spread of GRE strains within hospitals. Evidence also demonstrated the likely persistence of the original E. faecium vanA isolate associated with the first confirmed death contributed to by GRE infection in South Africa in March 1997.