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PubMed2005

B cell memory to 3 Plasmodium falciparum blood-stage antigens in a malaria-endemic area.

To gain insight into why antibody responses to malarial antigens tend to be short lived, we studied antigen-specific memory B cells from donors in an area where malaria is endemic. We compared antibody and memory B cell responses to tetanus toxoid with those to 3 Plasmodium falciparum candidate vaccine antigens: the C-terminal portion of merozoite surface protein 1 (MSP1(19)), apical membrane antigen 1 (AMA1), and the cysteine-rich interdomain region 1 alpha (CIDR1 alpha ) of a protein from the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. These data are the first to be generated on memory B cells in children who are in the process of acquiring antimalarial immunity, and they reveal defects in B cell memory to P. falciparum antigens. Compared with the results for tetanus toxoid, more donors who were positive for antibody to AMA1 and CIDR1 alpha were negative for memory B cells. These data imply that some exposures to malaria do not result in the establishment of stable populations of circulating antigen-specific memory B cells, suggesting possible mechanisms for the short-lived nature of many anti-malarial antibody responses.

Adult↗
PubMed1996

Analysis of infection control surveillance data in a long-term-care facility: use of threshold testing.

OBJECTIVE: To describe long-term trends in nosocomial infection rates and the threshold testing method for evaluating nosocomial surveillance data in a long-term-care facility (LTCF). DESIGN: Descriptive epidemiology of prospectively collected infection control surveillance data and application of threshold testing for detecting possible outbreaks. Threshold testing uses the binomial distribution to calculate probabilities of infection frequency at selected endemic levels (mean number of infections per month) and compares these probabilities to observed infection frequency. SETTING: One hundred twenty-bed LTCF located within a public, university-affiliated hospital. PATIENTS AND METHODS: The study period was 1987 through 1994. Yearly endemic levels of specific types of infection were calculated and threshold levels were determined using a previously published method. In this study, a probability of P = .01 was chosen to determine the threshold at a specific endemic level; if the observed number of infections in a month reached or exceeded the threshold level, the likelihood that this occurred by chance alone was 1% or less. INTERVENTIONS: None. RESULTS: The overall mean nosocomial infection rate ranged from three to five episodes per 1,000 resident care days per year; mean yearly rates from 1990 onward were higher and more stable than those from 1987 to 1989. The most common infections identified were lower respiratory tract, skin and soft tissue, urinary tract, and conjunctivitis. For each of these infections, threshold levels were calculated periodically, using only the monthly frequency of infection. Despite variations in the yearly mean endemic level of various infections, threshold levels were stable except for skin and soft-tissue infection. CONCLUSIONS: Threshold testing for analysis of infection control surveillance data in the LTCF setting is straightforward and does not require knowledge of statistics, special computer software, or calculation of rates; given the stable population in the typical LTCF, threshold testing can be based on variations in the monthly count of infections and provides an objective evaluation of surveillance data and a method to identify when outbreaks may be occurring.

Analysis of Variance↗
PubMed2004

Postmenopausal hormone use in women with acute coronary syndromes.

BACKGROUND: Recent trials reveal no benefit and possible harm from chronic hormone replacement therapy (HRT). Less is known about intermediate-term outcomes associated with HRT use in the setting of acute coronary syndromes (ACS). METHODS: To examine the prevalence of HRT use and relationships with intermediate-term outcomes among women with ACS, we classified as HRT users or nonusers 4029 postmenopausal women (age > 50 years or postmenopausal by case report form) randomized in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Outcomes included 90-day and 1-year death and 90-day stroke, death, or myocardial infarction (MI); death, MI, or stroke; and death, MI, or severe recurrent ischemia (SRI). RESULTS: HRT use was 13% overall and varied by region (Asia, 0%; Eastern Europe, 0.2%; Latin America, 0.8%; Western Europe, 4%; Australia/New Zealand, 12%; Canada, 14%; United States, 24%); estrogen-only regimens were most common (90%). HRT users were younger, had higher estimated creatinine clearance, more frequently were smokers and had prior revascularization, but less frequently had diabetes, prior angina, or heart failure. Unadjusted 90-day and 1-year mortality rates were lower among HRT users (hazard ratios [95% CI] 0.48 [0.23-0.98] and 0.35 [0.18-0.68], respectively) but after multivariable adjustment, were not significantly different. Ninety-day stroke and composite end points did not differ between HRT users and nonusers. CONCLUSIONS: HRT use (predominantly estrogen-only) was low among patients with ACS but varied by region and was not associated with improved intermediate-term outcomes. These results are consistent with the absence of benefit from HRT use (combination or estrogen only) in previous studies in more stable populations.

Aged↗
PubMed1996

Childhood generalized and mesial temporal epilepsies demonstrate different amounts and patterns of hippocampal neuron loss and mossy fibre synaptic reorganization.

In this study, we determined whether childhood seizures were associated with hippocampal neuron loss and mossy fibre synaptic reorganization and if hippocampal sclerosis evolved from longer seizure histories. Children undergoing surgical treatment for catastrophic epilepsy were grouped into the following pathology categories: (i) those with generalized seizures and extra-hippocampal congenital pathologies (i.e. prenatal cortical dysplasia; n = 17); (ii) cases of generalized seizures and extra-hippocampal acquired lesions. (i.e. postnatal ischaemic injuries and encephalitis; n = 7); (iii) children with complex partial hippocampal epilepsy (n = 4). Further, to determine whether the epileptogenic location influenced hippocampal pathology, the seizure focus was classified as (i) hippocampal, (ii) temporal (n = 13) or (iii) extra-temporal (n = 11). Surgical and autopsy (n = 23) hippocampi were studied for (i) fascia-dentata (FD) and Ammon's horn (AH) neuron densities; (ii) thickness; height or length of the FD molecular layer, stratum granulosum (SG) and stratum pyramidale; and (iii) grey value (GV) densities of supragranular neo-Timm's staining. Statistically significant results (P < 0.05) showed the following. (i) Autopsy hippocampal neuron densities for the hilus (H), AH and prosubiculum (Pro) decreased logarithmically at the same time as the thickness of the stratum pyramidale and Pro increased. By contrast, autopsy granule cell densities and thickness did not significantly change with age; however, the SG lengthened-expanding around the enlarging H. Further, the supragranular molecular layer height increased logarithmically, and took longer than the increase in stratum pyramidale thickness. (ii) Compared with age-matched autopsies, young children with a history of hippocampal seizures showed decreased granule cell, hilar and regio superior neuron densities similar to adults with hippocampal sclerosis (average loss 70%). By contrast, children with extra-hippocampal congenital or acquired pathologies showed only decreased granule cell densities, along with a thinner and shorter SG. Compared with extra-temporal locations, those with temporal lobe lesions showed decreased hilar and AH neuron densities, but averaged 20-30% less than autopsies and not in the pattern typical of hippocampal sclerosis. (iii) The neo-Timm's GV densities, when compared with autopsies, showed supragranular mossy fibre sprouting in children with congenital pathologies and temporal lobe lesions; however, the greatest GVs were in children with hippocampal seizures. (iv) Of the children with extra-hippocampal congenital or acquired pathologies there were no statistical correlations between longer duration of seizures with changes in neuron densities, hippocampal heights, or mossy fibre sprouting. These results indicate the following. (i) In the human there is anatomical evidence for postnatal maturation of the hippocampus and our results are consistent with the notion that AH pyramids are a stable population; however, there are probably increases in granule cell numbers. Further, compared with the AH, dendritic maturation of the FD granule cells appears to take longer. (ii) Extra-hippocampal childhood seizures whether from prenatal or postnatal aetiologies are associated with moderate FD and minimal AH neuron losses and signs of aberrant mossy fibre sprouting. (iii) By contrast, young children with the syndrome of mesial temporal epilepsy show patterns of neuron loss and mossy fibre sprouting, typical of hippocampal sclerosis. (iv) Repeated extra-hippocampal childhood seizures are not associated with progressive evolution of hippocampal damage or mossy fibre sprouting. These findings support the hypothesis that childhood seizures can damage or alter the postnatally developing granule cells of the human hippocampus, and that early neuron loss and aberrant axon circuits may contribute to chronic hippocampal seizures. However, repeated childhood generalized seiz

Adolescent↗
PubMedDate not supplied

Some observations on poliomyelitis lameness surveys.

Since 1974, greater than 100 different surveys have been carried out throughout the developing world to estimate the prevalence of lameness due to poliomyelitis. Reported prevalence rates have ranged from less than 1 to a high of 25 per 1,000 children surveyed and have prompted many countries to undertake polio vaccination programs. A review of surveys conducted to date reveals considerable variation in both the choice and use of survey methods and in the assumptions made in the analysis and interpretation of findings. More precise and comparable data about the risk of poliomyelitis could be obtained in future surveys by incorporating a standard case definition, by using house-to-house case-finding methods in representative community-based samples, by analyzing and presenting rates in more clearly defined ways, and by selecting stable populations for study.

Adolescent↗
PubMed1991

Analysis of coyote mitochondrial DNA genotype frequencies: estimation of the effective number of alleles.

A restriction-site survey of 327 coyotes (Canis latrans) from most parts of their North American range reveals 32 mitochondrial DNA (mtDNA) genotypes. The genotypes are not strongly partitioned in space, suggesting that there is high gene flow among coyote subpopulations. Consequently, each new geographic location added to the study has a decreasing probability of containing a mtDNA genotype that had not been previously discovered. This being the case, by using Monte Carlo sampling experiments, we can estimate the total number of genotypes that would be found if all possible localities were surveyed. This estimate of total genotypic variability agrees qualitatively with estimates based on theoretical considerations of the expected number of alleles in a stable population. We also predict effective population sizes from genotype data. The accuracy of these estimates is thought to be dependent on the fact that coyotes are not highly genetically structured, a situation which may apply to highly mobile species.

Alleles↗
PubMed2002

Exploring the envelope. Systematic alteration in the sex-determination system of the nematode caenorhabditis elegans.

The natural sexes of the nematode Caenorhabditis elegans are the self-fertilizing hermaphrodite (XX) and the male (XO). The underlying genetic pathway controlling sexual phenotype has been extensively investigated. Mutations in key regulatory genes have been used to create a series of stable populations in which sex is determined not by X chromosome dosage, but in a variety of other ways, many of which mimic the diverse sex-determination systems found in different animal species. Most of these artificial strains have male and female sexes. Each of seven autosomal genes can be made to adopt a role as the primary determinant of sex, and each of the five autosomes can carry the primary determinant, thereby becoming a sex chromosome. Strains with sex determination by fragment chromosomes, episomes, compound chromosomes, or environmental factors have also been constructed. The creation of these strains demonstrates the ease with which one sex-determination system can be transformed into another.

Animals↗
PubMed1983

Control of systemic spread of Candida albicans with ketoconazole in the stomachs of mice treated with cytarabine.

Attempts were made to colonize the gastrointestinal tract of outbred CD-1 mice with Candida albicans or Candida tropicalis before assessing the effects of cytarabine and ketoconazole on colonization. Stable populations of C. albicans but not C. tropicalis could be maintained in the stomachs of mice infected as adults if they were maintained on penicillin and tetracycline, or in untreated mice if the fungus was administered while they were infants. Treatment with cytarabine of mice colonized with C. albicans resulted in increased levels of yeast in the stomach, and small numbers of yeasts were recovered from the livers, kidneys, and spleens. Ketoconazole limited the multiplication of the yeast in the stomachs of colonized mice, although the effect was somewhat variable. Systemic spread of the fungus was essentially eliminated in animals receiving both ketoconazole and cytarabine, suggesting that ketoconazole may be an appropriate prophylactic agent for individuals undergoing therapy with cytarabine.

Animals↗
PubMed2005

Evidence of vancomycin resistance gene transfer between enterococci of human origin in the gut of mice harbouring human microbiota.

OBJECTIVES: Potential intra- and inter-species transfers of vancomycin resistance genes (vanA gene cluster) between Enterococcus strains were evaluated in the gut of heteroxenic mice harbouring a human microbiota. METHODS: Mice colonized with a stable population of E. faecium 64/3 or E. faecalis JH2-2 recipient strain and harbouring an enterococci-free human microbiota were obtained. Donor strain E. faecium HC-VI2 of clinical origin was administered orogastrically to these mice and transfers were evaluated over time in faecal samples. RESULTS: Only intraspecies transfers were detected in the digestive tract (DT) of mice harbouring a human microbiota. E. faecium 64/3 transconjugants were detected at several sampling times over the 60 day experiment to levels up to 10(3) cfu/g of faeces, but they did not steadily colonize the DT. CONCLUSIONS: Here, we show for the first time that transfer of the vanA gene cluster can occur between Enterococcus strains in the DT colonized with a human microbiota and in the absence of selective pressure. The colonization properties of other enterococci transconjugants and the influence of vancomycin intake should be further investigated since transfers in the DT of animals and humans might contribute to emergence and dissemination of new vancomycin-resistant bacteria.

Animals↗
PubMed2004

Effects of azadirachtin/Neemazal on different stages and adult life table parameters of Trichogramma cacoeciae (Hymenoptera: Trichogrammatidae).

The effects of azadirachtin/Neemazal on adults, emergence, and life table parameters of Trichogramma cacoeciae Marchal were studied. The adults were exposed to fresh residues of the insecticide applied on glass plates. Based on the dose-response study, the LC50 value was 1330 ppm or 13.3 microg (AI)/ml. The effect of Neemazal on three developmental stages of the parasitoid was tested by dipping parasitized Sitotroga cerealella (Olivier) and Cydia pomonella (L.) eggs at the field-recommended concentration 3, 6, and 9 d after parasitization corresponding to larval, prepupal, and pupal stages. The emergence of adult parasitoids was adversely affected in both hosts, but the adverse effect was more in S. cerealella eggs compared with C. pomonella. The adult emergence was reduced by 73.3 and 33.76% in Sitotroga and Cydia eggs compared with controls, respectively. Longevity and progeny production of the emergent adults did not differ significantly from control. Neemazal affected stable population parameters (r(m), T, and DT) significantly. The intrinsic rate of increase for the control and Neemazal-exposed populations was 0.340 and 0.335 female offspring per female per day, respectively. Because some of postemergence life table parameters of adults were significantly reduced by the insecticide treatment, emergence rate of the parasitoid from treated eggs is not an adequate measure of ecological selectivity, and field studies are needed to determine the actual impact of neem on T. cacoeciae.

Animals↗
PubMed1992

First report of Ixodes (Ixodes) minor Neumann (Acari: Ixodidae) from South Carolina.

Previous reports from the literature have indicated the northernmost range of extension of Ixodes minor Neumann to be southern Georgia with the greatest number of collections having been made in the coastal regions of that state. An unpublished record in the U.S. National Tick Collection indicated that I. minor had been collected as far north as South Island, Georgetown County, S.C., as early as 1933. I. minor was collected on three separate occasions in Charleston County, S.C., between October 1990 and February 1991, thus verifying the northern extension of this tick's range and the probable existence of a stable population on the coast of South Carolina. The roof rat (Rattus rattus) is reported for the first time serving as a host for I. minor.

Animals↗
PubMed2006

Catching a 'hopeful monster': shepherd's purse (Capsella bursa-pastoris) as a model system to study the evolution of flower development.

Capsella is a small genus within the mustard family (Brassicaceae). Its three species, however, show many evolutionary trends also observed in other Brassicaceae (including Arabidopsis) and far beyond, including transitions from a diploid, self-incompatible, obligatory outcrossing species with comparatively large and attractive flowers but a restricted distribution to a polyploid, self-compatible, predominantly selfing, invasive species with floral reductions. All these evolutionary transitions may have contributed to the fact that Capsella bursa-pastoris (shepherd's purse) has become one of the most widely distributed flowering plants on our planet. In addition, Capsella bursa-pastoris shows a phenomenon that, although rare, could be of great evolutionary importance, specifically the occurrence of a homeotic variety found in relatively stable populations in the wild. Several lines of evidence suggest that homeotic changes played a considerable role in floral evolution, but how floral homeotic varieties are established in natural populations has remained a highly controversial topic among evolutionary biologists. Due to its close relationship with the model plant Arabidopsis thaliana, numerous experimental tools are available for studying the genus Capsella, and further tools are currently being developed. Hence, Capsella provides great opportunities to investigate the evolution of flower development from molecular developmental genetics to field ecology and biogeography, and from morphological refinements to major structural transitions.

Biological Evolution↗
PubMed1993

Relation between blood lead and urinary biogenic amines in community-exposed men.

The cross-sectional relation between levels of urinary biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) and levels of blood lead was examined in a study of 645 male participants from a longitudinal study of aging. This stable population of men had initially been recruited from communities in and around Boston, Massachusetts, and had not been selected with regard to lead exposure. Blood lead samples and 24-hour and 2-hour urine specimens were collected during regularly scheduled clinic visits. In multivariate linear regression step-forward models, 24-hour epinephrine excretion was significantly and positively associated with blood lead (beta = 0.101 microgram(microgram/dl)-1 blood lead, SE (standard error) (beta) = 0.045, p = 0.026). Twenty-four-hour norepinephrine excretion was positively associated with blood lead (beta = 0.023 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.029, p = 0.425), and both 24-hour dopamine (beta = -4.35 microgram(microgram/dl)-1 blood lead, SE(beta) = 6.90, p = 0.529) and 2-hour serotonin (beta = -0.348 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.277, p = 0.210) excretion were negatively associated with blood lead; however, these relations did not achieve statistical significance. An increase of 10 micrograms/dl in blood lead was associated with an increase in epinephrine excretion of 11 micrograms/24 hours. These results support the hypothesis that epinephrine metabolism is influenced by low levels of lead exposure.

Adult↗
PubMed2004

Use of radiotracking techniques to study a summer repopulation with Red-Legged partridge (Alectoris rufa) chicks.

On a private property with a stable population of wild Red-Legged partridge (Alectoris rufa) and an appropriate habitat for the survival of the species, reinforcement repopulations were carried out using 54 birds that were 2 to 3 mo old and reared on a commercial game farm. This study aimed to evaluate the effectiveness of repopulations, the behavior in the wild of released partridges, and the possible causes of success or failure of reinforcement population operations. The releases were carried out during August and September of 2 consecutive years. All birds were equipped with radio transmitter collars to determine their behavior after release. Two release methods were used in yr 1: an acclimatization cage (AC) method and a direct release method on the day of the birds arrival (DR). The aim of the release in yr 2 was to collect data to determine the influence of year conditions using the DR method. Of the 54 released birds, none remained alive by the time of the reproductive period in the following spring. The mean survival time was 16.79 d for the AC method and was 11.89 and 5 d for the DR method in yr 1 and 2, respectively. Of the recorded mortalities, we assigned 81.13% to predation, 7.55% to hunting, and 11.32% to unknown causes of death, accidents, or starvation. Repopulation was not successful at providing a long-term increase in partridge numbers, with most birds falling victim to predation within 1 mo of release. Dispersion is the maximum distance from the release point at which each bird was located. The postrelease mean dispersion was 437.65 m for the AC method and was 647.57 and 266.07 m for the DR method in yr 1 and 2, respectively.

Animal Identification Systems↗
PubMed1996

Wegener's granulomatosis--increased incidence or increased recognition?

We aimed to calculate the annual incidence of Wegener's granulomatosis (WG) in Norfolk (UK) and to compare the clinical spectrum of disease to that seen in tertiary centres in both the UK and USA. We also aimed to examine the seasonal onset of symptoms. This was a prospective study of all patients presenting with WG to a district hospital with a well-defined stable population (515,000) during the period 1988-1993. The annual incidence for WG in the adult population is 8.5/million (95% CI 5.2-12.9). These are the first incidence figures for a well-defined population and are higher than previously published. The clinical spectrum of disease in Norfolk was similar to that seen in tertiary centres and there is supportive evidence for a seasonal variation in the onset of symptoms (highest in winter).

Adult↗
PubMed1999

Photoperiodic effects on gonadotropin-releasing hormone (GnRH) content and the GnRH-immunoreactive neuronal system of male Siberian hamsters.

Despite profound photoperiodic differences in circulating gonadotropin levels, consistent differences in the GnRH system have not been observed in Siberian hamsters (Phodopus sungorus) housed chronically in short or long days. During the transition from short to long days, however, male hamsters exhibit a transient increase in the number of cells expressing prepro-GnRH mRNA on the morning of the second long day. Here, we present two experiments designed to examine whether or not this change in mRNA level is associated with changes in GnRH protein synthesis. In the first experiment, we used RIA to measure GnRH content in preoptic area-mediobasal hypothalamic homogenates. We observed a significant increase in GnRH protein levels on the morning of the second long day relative to short- and long-day controls. The latter two groups did not differ from one another. In the second experiment, we used immunocytochemistry to quantify GnRH cell number in the various treatment groups. GnRH-immunoreactive (-ir) cell number did not increase significantly after long-day transfer relative to that in short-day controls; however, both of these groups had significantly more GnRH-ir neurons than long-day controls. We hypothesize that during the transition from short to long days, male Siberian hamsters experience a transient increase in GnRH production in a stable population of neurons. When GnRH secretion subsequently increases on long days, peptide content within neuronal cell bodies declines, leading to a decrease in the number of immunoreactive neurons detected. The rapid response of the hypothalamo-pituitary-gonadal axis in Siberian hamsters to a change in day length defines a narrow temporal window in which to identify the physiological, cellular, and molecular mechanisms mediating the photoperiodic regulation of reproduction.

Animals↗
PubMed2001

Distribution of Bcl-2 and Bax in embryonic and fetal human skin: antiapoptotic and proapoptotic proteins are differentially expressed in developing skin.

The Bcl-2 protein is involved in the regulation of apoptosis. Bax has an antagonistic effect and enhances cell death. We report that in early gestation, Bcl-2 and Bax colocalize to the epidermal portion of the hair follicle. In the more advanced stages, Bax is located in the compartments where a hair canal is excavated and keratinization and holocrine secretion are initiated, in contrast to Bcl-2, which is expressed in the follicular papilla, preventing apoptosis and underscoring its role as a permanent and stable population of specialized fibroblasts. Scattered dendritic cells located in the basal and immediate suprabasal interfollicular epidermis as well as in the outer root sheath of the developing hair follicle, including the bulge, strongly express Bcl-2 and label for HMB-45, identifying them as melanocytes. The spatial and temporal expression pattern of Bcl-2 and Bax during human hair follicle development underscores their importance for hair biology and most likely is disturbed in the evolution of follicular tumors.

Apoptosis↗
PubMed1996

Incidence and spectrum of severe medical complications among hospitalized HIV-seronegative and HIV-seropositive narcotic drug users.

OBJECTIVE: To examine differences in the incidence and spectrum of diseases, as well as duration of inpatient stay, between HIV-seronegative and HIV-seropositive narcotic drug, users (NDU). DESIGN: Retrospective analysis of 9 years of experience. Data collection by chart review using preset criteria for diagnoses. Estimation of hospital admission densities by assuming a dynamic but stable population of 2000 NDU (with a mean HIV-seroprevalence of 25%) throughout the study period. PATIENTS: Comprising 314 HIV-seronegative NDU. 217 HIV-seropositive NDU, and 10 NDU with admissions registered in either group (from a total of 1011 admissions). RESULTS: The overall admission incidence density was 35 and 120 per 1000 person-years among HIV-seronegative NDU and HIV-seropositive NDU, respectively [risk ratio (RR) 3.5, 95% confidence interval (CI) 3.2-3.7]. Compared with seronegative NDU, HIV-seropositive NDU were more frequently admitted for various non-opportunistic infections (RR 7.2, 95% CI 6.1-8.4), including pneumonia (RR 10.9, 95% CI 7.6-16.6), tuberculosis (RR 30.0, 95% CI 3.6-233.8), soft-tissue infections (RR 3.5, 95% CI 1.7-7.2), osteoarticular infections (RR 6.0, 95% CI 1.5-23.9), endocarditis (RR 5.3, 95% CI 1.5-17.9), and various other infections (RR 5.8, 95% CI 3.2-10.5). HIV-seropositive NDU were also more frequently admitted for non-infectious medical complications (RR 2.3, 95% CI 1.8-3.0). Seronegative NDU had a shorter median inpatient stay (2 versus 9 days, P < 0.00001). HIV infection accounted for an estimated excess burden of at least 2700 inpatient care days in 9 years among the 500 local HIV-seropositive NDU. CONCLUSIONS: Among NDU, HIV infection adds considerable excess burden in terms of severe complications needing inpatient care.

AIDS-Related Opportunistic Infections↗