Successful use of higher-than-recommended dosage of imipenem in Pseudomonas aeruginosa endocarditis.

OBJECTIVE: To report a case of Pseudomonas aeruginosa endocarditis that was successfully treated with high-dose imipenem/cilastatin and to discuss dosage modification based on individual pharmacokinetic parameters. DATA SOURCES: Clinical studies, review articles, and relevant laboratory and pharmacokinetic information. CASE SUMMARY: A 27-year-old man with right-sided P. aeruginosa endocarditis was successfully treated with long-term imipenem/cilastatin and tobramycin. The imipenem dose required to achieve therapeutic serum concentrations and cidal activity was 6 g/d. The manufacturer's recommended maximum dose is 4.0 g/d or 50 mg/kg/d. Because of the patient's large apparent volume of distribution, low serum imipenem concentrations, and lack of serum cidal activity, the clinical decision was made to increase the dose to 6 g/d or 54 mg/kg/d. Treatment was tolerated for seven weeks without any adverse effects. The patient remains free of symptoms 24 months after the diagnosis. CONCLUSIONS: Careful and discriminate use of larger-than-recommended doses of imipenem may be indicated in certain clinical situations. Dosage may need to be adjusted to body size in order to obtain optimal serum concentrations and activity.

Prevalence of antibodies interactive with HTLV-I antigens in selected Solomon Islands populations.

Serum samples obtained in 1986 from healthy individuals in three distinct Solomon Islands populations were screened for antibodies to human lymphotropic virus type I (HTLV-I). One of the populations tested lives on the remote Polynesian outlier atoll, Ontong Java. The other two groups, the Baegu and the Lau, are Melanesians living on Malaita, the most populous of the larger Solomon Islands. Eighty-eight of a total of 601 (14.6%) sera tested were repeatably reactive in an enzyme-linked immunosorbent assay (ELISA) that uses as antigen a lysate of HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I viral particles. The prevalence of antibodies interactive with HTLV-I antigens varied among the three groups, ranging from 8.5% (16/188) in the Baegu, through 13% (7/54) in the Lau, to 18.1% (65/359) among the Ontong Java population. The specificity of the screening ELISA was confirmed by protein immunoblot. No serum samples were obtained from children under 9 years of age. Although 121 of the 601 sera came from children between the ages of 9 and 19, none of these were reactive in the HTLV-I ELISA. Starting in the third decade, the prevalence of HTLV-I seropositivity increased with age, from 8.8% (10/113) between the ages of 20 and 29 to a peak of 25.9% (15/58) and 25% (15/60) in the sixth and seventh decade, respectively. This age-specific prevalence pattern is strikingly similar to that which is seen in populations where HTLV-I infection is endemic.

Hematoma infected with Mycoplasma hominis.

Although mycoplasmas are commonly isolated in the genitourinary and upper respiratory tracts, they are rarely isolated from other sites. We describe a case of a young woman with trauma to her pelvis and genitourinary tract who had a thigh hematoma infected with Mycoplasma hominis. The patient had persistent systemic symptoms that resolved with appropriate antibiotics and surgical drainage. This case as well as other cases of Mycoplasma-infected hematomas point out the need to consider mycoplasma infection in patients with persistent fever unresponsive to conventional antibiotic therapy.

Cultural practices contributing to the transmission of human immunodeficiency virus in Africa.

Differences between the epidemiology of AIDS cases in Africa and that in Western societies have prompted speculation regarding risk factors that may be unique to Africa. Because of the age and sex distribution of AIDS cases in Africa, emphasis has been placed on sexual transmission of human immunodeficiency virus (HIV). Factors thought to influence this sexual transmission include (1) promiscuity, with a high prevalence of sexually transmitted disease; (2) sexual practices that have been associated with increased risk of transmission of AIDS virus (homosexuality and anal intercourse); and (3) cultural practices that are possibly connected with increased virus transmission (female "circumcision" and infibulation). Other nonsexual cultural practices that do not fit the age distribution pattern of AIDS but may expose individuals to HIV include (1) practices resulting in exposure to blood (medicinal bloodletting, rituals establishing "blood brotherhood," and possibly ritual and medicinal enemas); (2) practices involving the use of shared instruments (injection of medicines, ritual scarification, group circumcision, genital tatooing, and shaving of body hair); and (3) contact with nonhuman primates. At the current time promiscuity seems to be the most important cultural factor contributing to the transmission of HIV in Africa.

PIP: Differences between the epidemiology of cases of acquired immunodeficiency syndrome (AIDS) in Africa compared to Western societies have prompted speculation that the risk factors may be unique to Africa. This difference is particularly apparent in terms of the male-to-female ratio of AIDS affectd individuals: 1:1 in Africa versus 19:1 in the US and Europe. Further suggestive of patterns of transmission that differ is the absence of the established risk factors of intravenous drug abuse and homosexuality from the African setting. Specific factors thought to influence AIDS transmission in Africa include: promiscuity, with a high prevalence of sexually transmitted diseases; sexual practices that have been associated with increased risk of human immunodeficiency virus (HIV) such as homosexuality and anal intercourse; and cultural practices, including female circumcision and infibulation. Other nonsexual cultural practices that may expose individuals to AIDS include: medicinal bloodletting, rituals establishing "blood brotherhood," ritual and medicinal enemas, and other practices resulting in exposure to blood; the use of shared instruments, such as in the injection of medicine, ritual scarification, group circumcision, genital tatooing, and shaving of body hair; and contact with nonhuman primates. Overall, however, sexual promiscuity seems to be the most important cultural factor contributing to the spread of AIDS in Africa.

Epidemiology of rotaviral infection in adults.

Although classic rotaviral gastroenteritis occurs in children between the ages of six and 24 months, infection with rotavirus is common in all age groups, including adults. Virtually all adults have been infected, as is demonstrated by the presence of serum antibodies, but previous infection does not protect against new infection with the same or a different serotype. Rotaviral infection of adults is seen in five settings: secondary contacts from pediatric cases, with variable attack rates in adults; waterborne outbreaks, which are often characterized by higher attack rates in adults than in children; travelers' diarrhea; epidemic spread in isolated or closed populations, often in the absence of contact with children; and endemic infections, which may account for 5%-10% of sporadic cases of diarrhea in adults. Frequent asymptomatic infections with rotavirus occur, and they may be important in the epidemiology of the disease. Although rotaviral infections in adults tend to be milder than those in children, death due to rotaviral infection in adults have been reported.

Investigation of genetic interaction between simian rotavirus SA11 and reovirus.

Rotavirus and reovirus are physically and genetically very similar. Their genetic interaction would have important implications for understanding both the epidemiology of rotavirus and the biological basis of rotavirus pathogenicity. A permissive line of rhesus macaque kidney cells, MA104, was infected with the simian rotavirus SA11 and various temperature sensitive mutants of reovirus (type 3 groups A, B, C, D, G, type 1 M79, and type 2 122). The mixed cell infections were carried out at permissive temperature in the presence of absence of proteolytic enzymes, and the progeny were plated at a non-permissive temperature in mouse L cells, which are non-permissive to SA11. The progeny clones were labelled with 32P and analyzed by polyacrylamide gel electrophoresis. There was no evidence for genetic reassortment. Under this heavy selection pressure, such reassortment would have been apparent if it occurred with a frequency greater than 10-5 to 10-3.

Molecular basis of reovirus neurovirulence: role of the M2 gene in avirulence.

A number of field isolates of reovirus 3 were examined to determine their relative neurovirulence after intracerebral inoculation. One isolate was found that had decreased neurovirulence. This "avirulent" strain showed the typical type 3 neural tropism but grew significantly less well in brain tissue than T3 (Dearing) and the other type 3 reoviruses. The avirulent virus was not temperature-sensitive, and its yield in mouse L cells in vitro was similar to that of the laboratory strains. To determine the reason that this clone was avirulent, we isolated a series of reassortant progeny clones from crosses between the avirulent strain and T1 (Lang) and T3 (Dearing). Using these reassortants, we showed that avirulence was a property of the M 2 gene segment. The M2 segment was also responsible for conferring greater sensitivity to chymotryptic digestion on the avirulent strain, compared to more virulent strains. Prior studies have determined that the localization of virus in different cell types in the brain (tropism) is a property of the viral hemagglutinin, the product of the S1 RNA genome segment. Our studies thus indicate that the basis for relative neurovirulence does not reside in the viral hemagglutinin and clearly illustrate the multigenic nature of neurovirulence.

Rotavirus antibodies in hanuman langurs (Presbytis entellus).

Serum samples from wild Hanuman langurs (Presbytis entellus) from Mysore State, India, were compared to samples from a laboratory colony from Davis, Calif., for antibodies to rotavirus, which is an important cause of gastroenteritis in mammals. Animals from the laboratory colony had a higher frequency and higher levels of antibody than wild animals. It is likely that wild populations of langurs have a much lower incidence of rotaviral infection than laboratory populations, which are exposed to both crowded conditions and rotaviruses from other species.

Polymorphism of the migration of double-stranded RNA genome segments of reovirus isolates from humans, cattle, and mice.

A series of 94 isolates of reovirus from humans, cattle, and mice, showed extensive variability in the patterns of migration of the ten double-stranded RNA genome segments. This variation was found in all three serotypes, and involved all ten genome segments, including the segment responsible for serological specificity. Although a single pattern was present among several samples isolated from individuals and collected at a single time and place, there were often multiple genetic variants of a single serotype present in a population. Samples isolated from widely different geographic origins or different mammalian hosts showed different patterns; samples from a single species from the same area over a period of time showed more limited variations. Among most isolates, the migration of the slowest S segment, the segment that encodes the hemagglutinin and is responsible for serological specificity in laboratory strains, was similar to reference strains for type 1 and type 3 isolates. However, the type 2 isolates showed considerable variation in this segment.

Analysis of hair samples of mummies from Semma South (Sudanese Nubia).

Hair samples from 76 burials at Semna South (Sudanese Nubia) were examined using a variety of techniques. Electrophoresis and fluorescence microscopy indicated some oxidation of the cuticule and keratin protein had taken place. However, the cuticular structure and the lack of fluorescence of the cortex indicate that the low humidity and non-alkaline conditions preserved the physical and chemical properties of the hair well. Pigmentation, even allowing for oxidation of melanin, showed a higher proportion of lighter samples than is currently associated with the Nubian area. Hair form analysis showed medium diameter and scale count; the curling variables were intermediate between European and African samples. There was a high ratio of maximum to minimum curvature (a measure of irregularity), approached only by Melanesian samples. Meroitic and X-group burial types were not statistically significantly different (largely due to sample sizes), but the X-group, especially males, showed more African elements than the Meroitic in the curling variables. Principal components analysis showed the Semna sample to be significantly different from seven populations examined earlier.

Frequency of an electrophoretic variant of hair alpha keratin in human populations.

A previously reported electrophoretic variant in hair keratin was looked for in a number of different racial groups. Only Caucasian samples showed the variant with the exception of one American black and one American Indian where Caucasian admixture is likely.

Hierarchical Relations Among Female Hanuman Langurs (Primates: Colobinae, Presbytis entellus).

Female hierarchies are stable over short periods but fluctuate from year to year. In general, young females rise in rank over older and often larger female relatives, even though old females remain active in troop defense. This previously undescribed dominance system can be plausibly explained with reference to inclusive fitness theory and the concept of reproductive value.

Tuberculin and histoplasmin sensitivity in six solomon islands populations.

Skin testing with antigens from Histoplasma capsulatum, Mycobacterium tuberculosis (PPD-S), and atypical mycobacteria (PPD-B, PPD-G, PPD-Y, and PPD-platy) was carried out among six population groups in the Solomon Islands between 1968 and 1972. There was no positive reaction to histoplasmin among any of the groups, suggesting that histoplasmosis is not endemic in the Solomon Islands. There were significant numbers of tuberculin reactors among each group. Largest mean reactions to PPD-S were present among the Lau and Ulawa, in whom reactions to PPD-S were larger than those to any other antigen tested. Thus significant infection with M. tuberculosis appears to occur in these populations. This was corroborated by radiologic survey. Among the Lau, large reactions to PPD-G and PPD-Y were also elicited, raising the possibility of multiple infection. Among the Aita, Baegu, Nagovisi, and Ontong Java, PPD-G elicited the largest reactions. PPD-G produced the second largest reactions among the Lau and Ulawa. PPD-S elicited the largest or second largest reaction among 4 of the 6 groups. A notable exception was the Aita, in whom PPD-S elicited the smallest mean reaction. The Aita also had the lowest prevalence of radiologic findings consistent with tuberculosis. These observations suggest that M. tuberculosis has been introduced into the Solomon Islands from outside sources, a hypothesis which may explain the variability in prevalence of tuberculosis-like disease demonstrated by chest film among the six groups. Genetic differences may also play a role in this variability. The study also demonstrated a high prevalence of "baseline" sensitivity to the atypical mycobacteria among the Solomon Islanders. This sensitivity may confer some immunity to infection with M; tuberculosis, but this protection is far from complete.

Protein polymorphism in the Hanuman langur (Presbytis entellus).

26 specimens of Presbytis entellus were examined for a variety of blood proteins. In contrast to previous studies of other species of leaf monkeys, our P.entellus sample proved to be very heterogeneous. Polymorphisms were found in the third component of complement, group-specific component, glycine-rich beta-glycoprotein, alpha1-antitrypsin, phosphoglucomutase, 6-phosphogluconate dehydrogenase, adenylate kinase, superoxide dismutase, malate dehydrogenase, and phosphohexose isomerase. Variable band strengths that might represent polymorphism were found in acid phosphatase and lactate dehydrogenase. Further analyses of the P. cristatus sample studied by Barnicot and Hewett-Emmett failed to disclose variation. The interpretation of blood protein variability in relation to sample collection and population structure is discussed.