Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin-Piperaquine for Uncomplicated Malaria.

This prospective trial investigated the population pharmacokinetics of piperaquine given with dihydroartemisinin to treat uncomplicated malaria in 107 Ugandan children 6 months to 2 years old, an age group previously unstudied. Current weight-based dosing does not adequately address physiological changes in early childhood. Patients were administered standard 3-day oral doses and provided 1,282 capillary plasma concentrations from 218 malaria episodes. Less than 30% of treatments achieved 57 ng/mL on day 7. A three-compartment model with first-order absorption described the data well. Age had a statistically significant effect (P < 0.005) on clearance/bioavailability in a model that accounts for allometric scaling. Simulations demonstrated that higher doses in all children, but especially in those with lower weight for age, are required for adequate piperaquine exposure, although safety and tolerance will need to be established. These findings support other evidence that both weight- and age-specific guidelines for piperaquine dosing in children are urgently needed.

Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.

Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Etiology of pulmonary infections in predominantly HIV-infected adults with suspected tuberculosis, Botswana.

SETTING: In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important. OBJECTIVE: To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence. DESIGN: Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997. RESULTS: Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%. CONCLUSIONS: Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.

Impact of enhanced notification of tuberculosis laboratory results to minimise treatment delay, Chiang Rai Hospital, Northern Thailand.

SETTING: A provincial referral hospital in northern Thailand, where a cross-sectional study from 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission. OBJECTIVE: To assess the impact of acid-fast bacilli sputum smear-positive results notification to improve tuberculosis (TB) services by documenting the location of sputum collection, completing the TB register immediately, and minimising delays between hospital admission and treatment initiation. DESIGN: The cohort of smear-positive TB patients identified through laboratory microscopy record reviews from 1994-1999. Time from admission to hospital, laboratory diagnosis of TB, registration for treatment, and initiation of therapy were determined during the implementation of enhancing the laboratory results notification system. RESULTS: The number of unregistered TB patients fell from 44 cases in 1994 to none in 1999. The time elapsed from admission to treatment initiation decreased from a mean of 5.6 days in 1997 (n = 162) to 3.1 days in 1999 (n = 136) (P < 0.001). This decrease was attributed to a reduction in time between laboratory diagnosis and treatment from 2.7 days in 1997 to 0.6 days in 1999 (P < 0.001). CONCLUSION: Prompt identification, isolation and treatment of TB patients occurred through an enhanced laboratory notification system. Such systems are inexpensive, improve TB care services and may reduce nosocomial transmission of M. tuberculosis.

Risk of Mycobacterium tuberculosis infection and disease among health care workers, Chiang Rai, Thailand.

SETTING: A provincial referral hospital in northern Thailand, where a cross-sectional study during 1995-1996 reported on the occupational risk of Mycobacterium tuberculosis transmission. OBJECTIVE: To describe the effectiveness of prevention strategies for nosocomial tuberculosis (TB). DESIGN: A prospective study among health care workers (HCW) including annual tuberculin skin test (TST) screening and active TB surveillance. Following a comprehensive risk assessment, preventive interventions were implemented targeting HCWs, hospitalised patients, and the hospital environment. RESULTS: The number of pulmonary TB cases diagnosed increased steadily from 102 in 1990 to 356 in 1999. The TST conversion rate was 9.3 (95% CI 3.3-15) per 100 person-years (py) in 1995-1997, but declined steadily to 2.2 (95% CI 0.0-5.1) in 1999. HCWs first screened within 12 months of employment had higher TST conversion rates (adjusted RR = 9.5, 95% CI 1.8-49.5) compared to those employed for longer than 12 months. The annual rate of active TB per 100 000 HCWs was 536 in 1995-1999. CONCLUSION: These HCWs were exposed to active TB patients and were at risk for M. tuberculosis infection, particularly during their first 12 months of employment. Implementation of nosocomial TB control measures in 1996 was followed by declining TST conversion rates, despite increasing exposure to active TB patients.

Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997-1998.

BACKGROUND: Little is known about causes of death in countries of southern Africa seriously affected by the HIV/AIDS epidemic. METHODS: After obtaining informed consent, autopsies were performed on 128 mainly hospitalised adults in Francistown, Botswana, between July 1997 and June 1998. Criteria for case selection included those who died before a diagnosis could be established, those whose condition deteriorated unexpectedly during hospitalization, and those who had respiratory disease. This represented 14% of adult medical patients who died in hospital during the study period. RESULTS: Of the 128 patients, 104 (81%) were HIV-positive. Among HIV-positive patients, the most common pathologic findings were tuberculosis (TB) (40%), bacterial pneumonia (23%), Pneumocystis carinii pneumonia (11%), and Kaposi's sarcoma (11%); these conditions were the cause of death in 38%, 14%, 11%, and 6%, respectively. Of the 40 pulmonary TB cases, 90% also had disseminated extra-pulmonary TB. Chest radiology could not reliably distinguish the pathologies pre-mortem. CONCLUSIONS: TB was the leading cause of death in our series of HIV-positive adults in Botswana, selected towards those with chest disease; in most, it was widely disseminated. Bacterial pneumonia also played an important role in mortality. Pneumocystis carinii pneumonia was present, but relatively uncommon.

Leptospirosis mimicking acute cholecystitis among athletes participating in a triathlon.

Leptospirosis, a disease acquired by exposure to contaminated water, is characterized by fever accompanied by various symptoms, including abdominal pain. An acute febrile illness occurred in athletes who participated in an Illinois triathlon in which the swimming event took place in a freshwater lake. Of 876 athletes, 120 sought medical care and 22 were hospitalized. Two of the athletes had their gallbladders removed because of abdominal pain and clinical suspicion of acute cholecystitis. We applied an immunohistochemical test for leptospirosis to these gallbladders and demonstrated bacterial antigens staining (granular and filamentous patterns) around blood vessels of the serosa and muscle layer. Rare intact bacteria were seen in 1 case. These results show that leptospirosis can mimic the clinical symptoms of acute cholecystitis. If a cholecystectomy is performed in febrile patients with suspicious environmental or animal exposure, pathologic studies for leptospirosis on formalin-fixed, paraffin-embedded tissues may be of great value.

Meningococcal vaccines.

Global control and prevention of meningococcal disease depends on the further development of vaccines that overcome the limitations of the current polysaccharide vaccines. Protein-polysaccharide conjugate vaccines likely will address the marginal protective antibody responses and short duration of immunity in young children derived from the A, C, Y, and W-135 capsular polysaccharides, but they will be expensive to produce and purchase, and may not offer a practical solution to the countries with greatest need. In addition, OMP vaccines have been tested extensively in humans and hold some promise in the development of a serogroup B vaccine, but are limited by the antigenic variability of these subcapsular antigens and the resulting strain-specific protection. Elimination of meningococcal disease likely will require a novel approach to vaccine development, ideally incorporating a safe and effective antigen or antigens common to all meningoccocal serogroups. As a solely human pathogen, however, N. meningitidis has developed many tools with which to evade the human immune system, and likely will pose a formidable challenge for years to come.

Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

Genetic and immunologic characterization of a novel serotype 4, 15 strain of Neisseria meningitidis.

The porin proteins of Neisseria meningitidis are important components of outer membrane protein (OMP) vaccines. The class 3 porin gene, porB, of a novel serogroup B, serotype 4, 15 isolate from Chile (Ch501) was found to be VR1-4, VR2-15, VR3-15 and VR4-15 by porB variable region (VR) typing. Rabbit immunization studies using outer membrane vesicles revealed immunodominance of individual PorB (class 3) VR epitopes. The predominant anti-Ch501 PorB response was directed to the VR1 epitope. Anti-PorB VR1 mediated killing was suggested by the bactericidal activity of Ch501 anti-sera against a type 4 strain not expressing PorA or class 5 OMPs. Studies that examine the molecular epidemiology of individual porB VRs, and the immune responses to PorB epitopes, may contribute to the development of broadly protective group B meningococcal vaccines.

Completeness and timeliness of treatment initiation after laboratory diagnosis of tuberculosis in Gaborone, Botswana.

SETTING: Gaborone, the capital of Botswana. OBJECTIVE: To determine the time from positive sputum smear microscopy for acid-fast bacilli (AFB) to initiation of therapy, and to identify risk factors for delays. DESIGN: Retrospective cohort study of medical records and surveillance data for patients with positive smear microscopy and newly diagnosed tuberculosis (TB) from January to May 1997. Treatment delay was defined as more than 2 weeks from the first positive sputum smear to the initiation of TB treatment. RESULTS: Of 127 patients identified, 15 (11.8%) had treatment delay, 13 (10.2%) had an incomplete workup (only one smear performed) and were not registered for TB treatment, and six (4.5%) had two or more positive smears but were not registered for TB treatment. Risk factors for treatment delay or non-registration included TB patients who had been diagnosed in a hospital outpatient setting vs. a clinic (RR 2.9, 95% CI 1.2-3.6, P = 0.02), or in a high volume vs. low volume clinic (RR 2.2, 95% CI 1.2-5.3, P = 0.01). CONCLUSION: More than a quarter of the smear-positive TB patients identified had treatment delay or no evidence of treatment initiation. Proper monitoring of laboratory sputum results and suspect TB patient registers could potentially reduce treatment delays and patient loss.

DNA fingerprinting of a national sample of Mycobacterium tuberculosis isolates, Botswana, 1995-1996.

DNA fingerprinting may be useful to elucidate tuberculosis (TB) transmission in community settings, but its utility is limited if only few fingerprint patterns are observed or band numbers are low. We performed DNA fingerprinting on a national, population-based sample of Mycobacterium tuberculosis isolates from Botswana. During 1995-1996, a random sample of 213 isolates, representing 5% of all smear-positive TB cases, underwent DNA fingerprinting using restriction fragment length polymorphism (RFLP) IS6110 analysis. Eighty-two (38%) of the 213 isolates belonged to one of 18 clusters, with 2-9 isolates/cluster. The median number of bands was 10 (range 1-19); 183 (86%) had six or more bands. Sixty-three (49%) of 128 patients tested were infected with the human immunodeficiency virus (HIV). The degree of RFLP pattern heterogeneity and high band number support the feasibility of a prospective DNA fingerprinting study in Botswana.

Survey of drug resistance of Mycobacterium tuberculosis in 3 Mexican states, 1997.

BACKGROUND: Drug resistance threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Mexico. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Mexico. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in the states of Baja California, Sinaloa, and Oaxaca, Mexico. We performed cultures and drug susceptibility testing on M tuberculosis isolates from patients with newly diagnosed, smear-positive TB from April 1 to October 31, 1997. RESULTS: Mycobacterium tuberculosis was isolated from 460 (75%) of the 614 patients. Levels of resistance in new and retreatment TB cases to 1 or more of the 3 current first-line drugs used in Mexico (isoniazid, rifampin, and pyrazinamide) were 12.9% and 50.5%, respectively; the corresponding levels of multi-drug-resistant TB were 2.4% and 22.4%. Retreatment cases were significantly more likely than new cases to have isolates resistant to 1 or more of the 3 first-line drugs (relative risk [RR], 3.9; 95% confidence interval [CI], 2.8-5.5), to have isoniazid resistance (RR, 3.6; 95% CI, 2.5-5.2), and to have multi-drug-resistant TB (RR, 9.4; 95% CI, 4.3-20.2). CONCLUSIONS: This population-based study of M tuberculosis demonstrates moderately high levels of drug resistance. Important issues to consider in the national strategy to prevent M tuberculosis resistance in Mexico include consideration of the most appropriate initial therapy in patients with TB, the treatment of patients with multiple drug resistance, and surveillance or periodic surveys of resistance among new TB patients to monitor drug resistance trends.

Analysis of the 1998 outbreak of leptospirosis in Missouri in humans exposed to infected swine.

OBJECTIVE: To determine the extent of leptospirosis in persons exposed to infected swine, confirm the source of disease, define risk factors for infection, and identify means for preventing additional infections during an outbreak in Missouri in 1998. DESIGN: Cross-sectional study. SAMPLE POPULATION: 240 people and 1,700 pigs. PROCEDURE: An epidemiologic investigation was conducted of people exposed to infected pigs from the University of Missouri-Columbia swine herd. The investigation included review of health of the pigs, a cross-sectional study of the people handling the pigs, serologic testing of human and porcine sera, and risk-factor analysis for leptospirosis within the human population. RESULTS: Serologic testing of samples collected at the time of the investigation indicated that 59% of the pigs had titers to leptospires, denoting exposure. Of the 240 people in the exposed study population, 163 (68%) were interviewed, and of these, 110 (67%) submitted a blood sample. Nine (8%) cases of leptospirosis were confirmed by serologic testing. Risk factors associated with leptospirosis included smoking (odds ratio [OR], 14.4; 95% confidence interval [CI], 1.39 to 137.74) and drinking beverages (OR, 5.1; 95% CI, 1.04 to 24.30) while working with infected pigs. Washing hands after work was protective (OR, 0.2; 95% CI, 0.03 to 0.81). CONCLUSIONS AND CLINICAL RELEVANCE: Leptospirosis is a risk for swine producers and slaughterhouse workers, and may be prevented through appropriate hygiene, sanitation, and animal husbandry. It is essential to educate people working with animals or animal tissues about measures for reducing the risk of exposure to zoonotic pathogens.

Mycobacterium ulcerans infection.

After tuberculosis and leprosy, Buruli-ulcer disease (caused by infection with Mycobacterium ulcerans) is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been identified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, undermined ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M. ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

PIP: This paper focuses on Buruli-ulcer disease, the third most common mycobacterial disease among immunocompetent people. Buruli-ulcer disease is caused by an infection with Mycobacterium ulcerans, which belongs to the large group of environmental mycobacteria. It is endemic in many countries, usually in areas of tropical rain forest. Transmission of infection is through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation. This disease mostly affects children which manifest from painless nodules to large, undermined ulcerative lesions that heals spontaneously but slowly. Buruli-ulcer disease is accompanied by few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. However, extensive scarring can lead to contractures of the limbs, blindness, and other adverse complications. Management of the disease is still primarily surgical, and includes excision, skin grafting, or both. Although Bacillus Calmette-Guerin vaccine has mild but a significant protective effect, vaccine developments directed at the toxin produced by M. ulcerans are needed.

Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile.

CONTEXT: Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group. OBJECTIVE: To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy. DESIGN: Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994. SETTING: Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993. PARTICIPANTS: Infants younger than 1 year (n = 187), children aged 2 to 4 years (n = 183), and adults aged 17 to 30 years (n = 173). INTERVENTION: Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3. MAIN OUTCOME MEASURE: Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer. RESULTS: Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen. CONCLUSIONS: These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain-specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.

Tuberculin reactivity in a pediatric population with high BCG vaccination coverage.

SETTING: The tuberculin skin test (TST) is often included in diagnostic algorithms for tuberculosis (TB) in children. TST interpretation, however, may be complicated by prior Bacillus Calmette-Guerin (BCG) vaccination. We assessed the prevalence of and risk factors for positive TST reactions in children 3 to 60 months of age in Botswana, a country with high TB rates and BCG coverage of over 90%. METHODS: A multi-stage cluster survey was conducted in one rural and three urban districts. Data collected included demographic characteristics, nutritional indices, vaccination status, and prior TB exposure. Mantoux TSTs were administered and induration measured at 48-72 hours. RESULTS: Of 821 children identified, 783 had TSTs placed and read. Of the 759 children with vaccination cards, 755 (99.5%) had received BCG vaccine. Seventy-nine per cent of children had 0 mm induration, 7% had > or =10 mm induration ('positive' TST), and 2% had > or =15 mm. A positive TST was associated with reported contact with any person with active TB (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.02-3.6), or a mother (OR 5.1; 95% CI 2.1-12.4) or aunt (OR 5.3; 95% CI 2.0-14.0) with active TB. TSTs > or =5 mm (but not > or =10 mm) were associated with presence of a BCG scar. Positive reactions were not associated with age, time since BCG vaccination, clinical signs or symptoms of TB, nutritional status, crowding, or recent measles or polio immunization. CONCLUSION: The TST remains useful in identifying children with tuberculous infection in this setting of high TB prevalence and extensive BCG coverage.

Age-dependent Neisseria meningitidis serogroup C class-specific antibody concentrations and bactericidal titers in sera from young children from Montana immunized with a licensed polysaccharide vaccine.

Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme-linked immunosorbent assay (ELISA) antibody concentrations were measured in sera from 173 children (1 to 5 years old) before and 6 weeks and 7 months following vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune responses of the children were compared with those of 40 adults 6 weeks postvaccination. Both bactericidal titers and ELISA antibody concentrations were significantly higher in the adults than in the children (P < 0.05). In addition, the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a measure of seroconversion, >/=84% of the individuals from each age group responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50 to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that >50% of all children retained >/=2 microg of total antibody per ml at 7 months postimmunization. However, the bactericidal titers suggest that <10% of children <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer (<1:8). Discordant results between bactericidal titers and ELISA antibody concentrations were not explained by the presence of IgA blocking antibody or relative levels of IgG and IgM. The bactericidal results show age-dependent differences in the production and retention of antibody in young children immunized with serogroup C polysaccharide; these differences are not evident with the ELISA data.

Molecular epidemiology of bartonella infections in patients with bacillary angiomatosis-peliosis.

BACKGROUND: Bacillary angiomatosis and bacillary peliosis are vascular proliferative manifestations of infection with species of the genus bartonella that occur predominantly in patients infected with the human immunodeficiency virus. Two species, B. henselae and B. quintana, have been associated with bacillary angiomatosis, but culture and speciation are difficult, and there has been little systematic evaluation of the species-specific disease characteristics. We studied 49 patients seen over eight years who were infected with bartonella species identified by molecular techniques and who had clinical lesions consistent with bacillary angiomatosis-peliosis. METHODS: In this case-control study, a standardized questionnaire about exposures was administered to patients with bacillary angiomatosis-peliosis and to 96 matched controls. The infecting bartonella species were determined by molecular techniques. RESULTS: Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent) were infected with B. henselae and 23 (47 percent) with B. quintana. Subcutaneous and lytic bone lesions were strongly associated with B. quintana, whereas peliosis hepatis was associated exclusively with B. henselae. Patients with B. henselae infection were identified throughout the study period and were epidemiologically linked to cat and flea exposure (P< or =0.004), whereas those with B. quintana were clustered and were characterized by low income (P=0.003), homelessness (P = 0.004), and exposure to lice (P= 0.03). Prior treatment with macrolide antibiotics appeared to be protective against infection with either species. CONCLUSIONS: B. henselae and B. quintana, the organisms that cause bacillary angiomatosis-peliosis, are associated with different epidemiologic risk factors and with predilections for involvement of different organs.