Acute haemolytic anaemia in typhoid fever

Summary Two G-6-PD deficient children with typhoid fever complicated by acute haemolytic anaemia are reported. One of them had the rare complication of haemoglobinuria. The role of typhoid infection versus chloramphenicol treatment in causing haemolysis in G-6-PD deficiency is discussed. From the Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh.     

Update on the treatment of tuberculosis and latent tuberculosis infection

Henry M. Blumberg, MD; Michael K. Leonard, Jr, MD; Robert M. Jasmer, MD

JAMA. 2005;293:2776-2784.

Tuberculosis (TB) has emerged as a global public health epidemic. Despite decreasing numbers of cases in the United States since 1992, TB remains a serious public health problem among certain patient populations and is highly prevalent in many urban areas. The responsibility for prescribing an appropriate drug regimen and ensuring that treatment is completed is assigned to the public health program or the clinician not to the patient. The initial prescribed regimen for the treatment of TB usually consists of 4 drugs: isoniazid, rifampin, pyrazinamide, and ethambutol. The minimum length for the treatment of drug-susceptible TB with a rifampin-based regimen is 6 to 9 months. Providing medications directly to the patient and watching him/her swallow the anti-TB drugs, which is termed directly observed therapy, is recommended for all patients diagnosed with TB and can help ensure higher completion rates, prevent the emergence of drug resistant TB, and enhance TB control. There has been renewed interest in the treatment of those with latent TB infection as a TB-control strategy in the United States for eliminating the large reservoir of individuals at risk for progression to TB. The 2 broad categories of persons who should be tested for latent TB infection are those who are likely to have been recently infected (such as contacts to infectious TB cases) and persons who are at increased risk of progression to TB disease following infection with Mycobacterium tuberculosis (eg, human immunodeficiency virus infection and selected medical conditions; recent immigrants to the United States from high TB-burden countries). The preferred regimen for the treatment of latent TB infection is 9 months of isoniazid. There is now renewed interest in and great need for the development of new drugs to treat TB and latent TB infection.

     

Gene discovery in the adenophorean nematode Trichinella spiralis: an analysis of transcription from three life cycle stages

Expressed sequence tags (ESTs) were produced from cDNA libraries for immature L1, mature muscle larva and adult stages of the adenophorean nematode Trichinella spiralis. 10,130 ESTs were grouped into 3454 gene clusters. The clusters represent a conservative estimate of 3262 unique genes. Interspecific comparisons of the predicted proteins support an ancient divergence of clade I nematodes from other nematodes in the phylum Nematoda. Furthermore, apparent clade I or Trichocephalida-specific proteins were identified, which may include molecular determinants important in the evolution of these species. Similarity matches identified 463 C. elegans genes homologs that confer phenotypes by RNA interference. Classification of predicted proteins suggested diverse cellular, metabolic and extracellular functions, significantly expanding the dataset of T. spiralis proteins with prospective, and potentially critical, functions. Several lines of evidence suggested stage-specific expression of certain genes beyond those previously identified. Evidence was obtained for the existence of large gene families encoding isoforms of known secreted proteins, such as p43 and TspE1. Unexpectedly, diverse isoforms of the muscle larva p43 gene appear to be expressed by immature L1. Proteinases, kinases, antioxidant proteins and enzymes involved in glycan synthesis are implicated in T. spiralis interactions with its hosts. Numerous genes were identified that encode predicted proteins in these categories. The genes discovered, when put into context of functional classification, stage of expression, and biology of the parasite, should substantially enhance experimental potential for research on this parasite.     

Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons

BACKGROUND: Recently, a short-course treatment using 60 daily doses of rifampin and pyrazinamide was recommended for latent tuberculosis (TB) infection (LTBI). STUDY OBJECTIVES: To determine the acceptability, tolerability, and completion of treatment. DESIGN: Observational cohort study. SETTING: Five county jails and TB outreach clinics for homeless populations in three cities. PATIENTS: Study staff enrolled 1,211 patients (844 inmates and 367 homeless persons). INTERVENTIONS: Sites used 60 daily doses of rifampin and pyrazinamide, an approved treatment regimen for LTBI. MEASUREMENTS: Types and frequency of drug-related adverse events and outcomes of treatment. RESULTS: Prior to treatment, 25 of 1,178 patients (2.1%) had a serum aminotransferase measurement at least 2.5 times the upper limit of normal. Patients who reported excess alcohol use in the past 12 months were more likely than other patients to have an elevated pretreatment serum aminotransferase level (odds ratio, 2.1; 95% confidence interval, 1.1 to 6.1; p = 0.03). Treatment was stopped in 66 of 162 patients (13.4%) who had a drug-related adverse event. Among 715 patients who had serum aminotransferase measured during treatment, 43 patients (6.0%) had an elevation > 5 times the upper limits of normal, including one patient who died of liver failure attributed to treatment. In multivariate analyses, increasing age, an abnormal baseline aspartate aminotransferase level, and unemployment within the past 24 months were independent risk factors for hepatotoxicity. Completion rates were similar in jail inmates (47.5%) and homeless persons (43.6%). CONCLUSIONS: This study detected the first treatment-associated fatality with the rifampin and pyrazinamide regimen, prompting surveillance that detected unacceptable levels of hepatotoxicity and retraction of recommendations for its routine use. Completion rates for LTBI treatment using a short-course regimen exceeds historical rates using isoniazid. Efforts to identify an effective short-course treatment for LTBI should be given a high priority.     

Neutralization-sensitive merozoite surface antigens of Babesia bovis encoded by members of a polymorphic gene family.

Monospecific antibodies against native and recombinant versions of the major merozoite surface antigen (MSA-1) of Babesia bovis neutralize the infectivity of merozoites from Texas and Mexico strains in vitro. Sequence analysis shows that MSA-1 and a related, co-expressed 44 kDa merozoite surface protein (MSA-2) are encoded by members of a multigene family previously designated BabR. BabR genes, originally described in Australia strains of B. bovis, are notable because their marked polymorphism is apparently mediated by chromosomal rearrangements, but protein products of BabR genes have not previously been identified. The 3' terminal 173 nucleotides of the MSA-1 gene, including 60 nucleotides of untranslated sequence, are highly similar to the 3' terminal sequences of BabR 0.8 (84% identity) and MSA-2 (94% identity). Alignment of the predicted protein sequences demonstrates significant overall homology between MSA-1 and MSA-2, and between both proteins and the amino terminal BabR sequence. MSA-1 nucleic acid probes also hybridize weakly to genomic DNA from the Australia 'L' strain, even though this strain does not express merozoite surface epitopes cross-reactive with MSA-1 or MSA-2. Hybridization of these same probes to genomic DNA from the cloned Mexico strain reveals a pattern of bands compatible with two copies each of MSA-1 and MSA-2. Proteins encoded by this B. bovis gene family have been designated variable merozoite surface antigens (VMSA). The extent and mechanism of VMSA polymorphism among strains will be important when evaluating the role these surface proteins have in the host-parasite interaction, including immunity to blood stages.     

Postpartum follow-up of a positive purified protein derivative (PPD) among an indigent population

OBJECTIVE: This study was undertaken to investigate the rates and predictors of follow-up and treatment for postpartum patients with a positive purified protein derivative (PPD). STUDY DESIGN: Retrospective cohort study of all women delivered at San Francisco General Hospital in 2000. All patients with a positive PPD were identified and their demographic and PPD follow-up and treatment data were collected and analyzed. RESULTS: Among the 1331 patients delivered, the prevalence of a positive PPD was 32% (n = 425). Of the 393 patients who had not been previously treated, 42% (n = 167) attended a follow-up visit with 42% of these (n = 71) actually completing 6 months of therapy. Among different ethnicities, Asian patients were more likely to follow-up at a rate of 52% (P = .03). Patients who received care from the same physician both antepartum and postpartum were more likely to attend and complete therapy at rates of 67% (P < .001) and 62% (P = .01), respectively. CONCLUSION: We found that despite the opportunity given by the interaction with the medical system during pregnancy, only 18% of patients with a positive PPD actually completed therapy.