Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics.

BACKGROUND: Previous case-control studies have paradoxically suggested that circumcisions protect against neonatal tetanus (NNT), but these observations have not been adjusted for differences in the length of survival of cases and controls. METHODS: Boy cases (n = 133) and their sex-matched controls (n = 399) were extracted from a population-based study of NNT undertaken in Punjab Province, Pakistan. In the resulting file, circumcisions were censored such that analysis was restricted to only those that occurred before onset in cases or before age of onset in the matched case for controls. The effect of topical antibiotics in circumcision wounds was then evaluated. RESULTS: After adjusting for confounders, circumcision before onset posed a significant risk for NNT (matched odds ratio [OR] = 3.1, 95% CI: 1.2-8.0). The risk of NNT in those circumcised before onset and treated with topical antibiotics did not differ significantly from the referent group who had not been circumcised before onset (matched OR = 1.1, 95% CI: 0.2-6.8), whereas the lack of topical use was associated with significant risk (matched OR = 4.2, 95% CI: 1.4-12.6). This suggests that topical antibiotics are likely to be highly effective in preventing NNT from circumcision wounds. We estimated an overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds that were not protected by topical antibiotics, and that circumcision and umbilical wounds each accounted for about half of this overall risk in these boys. CONCLUSIONS: Topical antibiotics should be routinely applied to all wounds created by traditional circumcisions, to prevent NNT and sepsis from these frequently unsterile procedures.

PIP: The results of previous case-control studies have suggested that circumcisions protect against neonatal tetanus (NNT). Those observations, however, were not adjusted for differences in the length of survival of cases and controls. The authors analyzed 133 boy cases and 399 sex-matched controls extracted from a population-based study of NNT conducted in Punjab Province, Pakistan. After adjusting for confounders, circumcision before the onset of illness or NNT was a significant risk factor for NNT. The risk of NNT among those circumcised before onset and treated with topical antibiotics did not differ significantly from the control group which had not been circumcised before onset, while the lack of topical antibiotic use was associated with a considerable and significant risk, suggesting that the application of topical antibiotics is highly effective in preventing NNT arising from circumcision wounds. There was an estimated overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds which were not protected by topical antibiotics, with circumcision and umbilical wounds each accounting for about half of the overall risk among these boys.

Neonatal tetanus associated with topical umbilical ghee: covert role of cow dung.

BACKGROUND: Previous studies in Pakistan have shown that ghee (clarified butter) is commonly applied to umbilical wounds of neonates, and have documented that such applications are a risk factor for neonatal tetanus (NNT). In-use contamination of ghee with Clostridium tetani has been demonstrated, but mechanisms underlying the risk of ghee have been incompletely evaluated epidemiologically. METHODS: Detailed information on ghee usage, including fuels used to heat it, was obtained from cases of NNT (n = 229) and their matched controls (n = 687) from a population-based study of NNT in Punjab Province, Pakistan. Design variables were created to evaluate the impact of different fuel sources on risk of ghee applications. RESULTS: Nearly one-third of all infants had ghee applied, and it was nearly always heated before application to umbilical wounds of newborns. After controlling for all factors found to be significantly associated with NNT in conditional logistic regression, only ghee that had always been heated with dried cow dung fuel was significantly associated with NNT. Topical antimicrobials and ghee were never applied together. CONCLUSIONS: Ghee applications to umbilical wounds, when heated with 'clean' fuels, appear to pose no increased risk of NNT, although handling practices undoubtedly result in hazardous microbial contamination. In contrast, ghee heated with dung fuel was significantly associated with NNT. The effective promotion of topical antimicrobials might help reduce ghee use, since the intended purpose of each is to enhance healing.

PIP: Ghee, a clarified butter used for cooking, is also applied to neonate umbilical wounds in India and Pakistan and is prepared using dried cow dung as fuel. It has been documented that the application of ghee increases the risk for neonatal tetanus (NNT), which results from contamination of the umbilical wound with spores of Clostridium tetani found in soil and cattle droppings. This population-based study examined ghee preparation and use, and other known NNT risk factors in rural areas of Punjab, Pakistan, in 1990. Detailed information on ghee usage and preparation was gathered among 229 cases and 687 matched controls. Evaluation of the ghee application risk factors in relation to fuel sources utilized four design variables. Results reveal that one-third of infants received umbilical wound applications of ghee, which was often heated beforehand. Using a logistic regression to control all factors significantly associated with NNT, ghee heated with dried cow dung was found to be significantly associated with NNT. In addition, simultaneous application of ghee and topical antimicrobials was found to be rare among the populace. In conclusion, ghee heated with clean fuels appears to pose an insignificant risk when applied to umbilical wounds, although unhygienic handling practices would eventually result in microbial infection. The authors suggest effective promotion and use of topical umbilical antimicrobials to control NNT and eradicate ghee use.

Protective effects of topical antimicrobials against neonatal tetanus.

BACKGROUND: Case-control studies previously conducted in Pakistan suggested that topical antimicrobials might provide protection against neonatal tetanus (NNT) when applied to the umbilical cord wound during the first several days of life. The present case-control study, the largest such study yet reported, was undertaken in Punjab Province, Pakistan and afforded further opportunities to evaluate such effects. METHODS: A population-based, matched, case-control study was undertaken to assess topical antimicrobials and other factors related to NNT risk in rural parts of Punjab Province. RESULTS: Continuous use of antimicrobial agents (antibiotics and antiseptics) at delivery and during the first few days after delivery was highly protective in univariate testing (matched odds ratio 0.2 [95% confidence interval: 0.11-0.64], P = 0.003), and remained significantly protective when other delivery and cord care practices were controlled. In contrast, applying nothing to the wound was risky compared with antimicrobial exposures. Hand washing and delivery by a trained birth attendant appeared protective. Application of animal dung or ash to the umbilical wound was hazardous. Similarly, predelivery cutaneous or intravaginal exposure of mothers to ghee (clarified butter) and delivery on a surface prepared with dried cow dung were risky, with significant interaction noted between them. Mortality and NNT were far more likely among previous births to mothers of cases. CONCLUSIONS: Topical antimicrobials offer a new, effective and inexpensive means to prevent NNT, and could usefully complement maternal immunization with tetanus toxoid in controlling the disease. Special prevention efforts should be directed towards mothers of NNT cases.

PIP: A population-based case-control study in Pakistan's Punjab province evaluated the capability of topical application of antimicrobials to the umbilical cord wound in the first days of life to prevent neonatal tetanus infection. A 1990 cluster survey of 23,670 live births occurring in rural areas of Punjab Province in the preceding year identified 229 neonatal tetanus deaths. Overall, neonatal tetanus accounted for 64% of all neonatal deaths. The 18 cases where circumcision had occurred before tetanus onset were excluded, leaving 211 cases and 211 matched controls who survived the neonatal period for analysis. The greatest protection against neonatal tetanus (odds ratio, 0.27) was found when antimicrobial substances were used continuously. Hand washing and delivery by a trained birth attendant were also protective against neonatal tetanus, while maternal exposure to ghee and delivery on a surface prepared with dried cow dung increased the risk. The risk of neonatal tetanus was increased more than 2-fold (odds ratio, 2.5) for infants with dry cord care compared with those who had non-hazardous substances, including antimicrobials, applied. Efforts to protect the umbilical wound are especially important in villages where animals and animal dung exist in close proximity to living areas. The routine application of topical antimicrobials to the umbilical cord is recommended at all deliveries to complement maternal immunization with tetanus toxoid. The most promising agents for use in developing countries appear to be nitrofurazone, bacitracin, and povidone-iodine ointments.

Bundling, a newly identified risk factor for neonatal tetanus: implications for global control.

BACKGROUND: Bundling, which consists of wrapping an infant for prolonged periods in a sheepskin cover after dried cow dung is applied, is a common and apparently unique practice limited to the rural, mountainous regions of Northern Pakistan. The practice is initiated at various ages during the neonatal period. Its potential contribution to neonatal tetanus (NNT) had not been evaluated. METHODS: A population-based, matched, case-control study was undertaken to assess bundling and other factors potentially related to NNT in rural parts of the Northern Areas, Pakistan. RESULTS: Bundling instituted within the first 3 days of life was a substantial risk factor for NNT (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.3-4.9). Other factors found risky for NNT were delivery on a straw surface and pre-delivery intravaginal application of ghee to the mothers. Handwashing by the delivery attendant and use of a new razor to cut the umbilical cord were protective. CONCLUSIONS: Bundling is a significant risk factor for NNT in the mountainous regions of Northern Pakistan. While this practice is seemingly limited to these remote areas, the findings have broad implications since they indicate that NNT can derive from exposures of the umbilical wound at any time during the first several days of life. Thus, clean cord care at delivery is not itself sufficient to prevent NNT and control programmes need to address post-delivery sources of NNT.

PIP: Bundling consists of wrapping an infant for prolonged periods in a sheepskin cover after dried cow dung is applied. This is a common practice among the inhabitants of the rural, mountainous regions of Northern Pakistan which is initiated at various ages during the neonatal period. A population-based, matched, case-control study was conducted to the determine the role of bundling and other factors potentially related to the incidence and prevalence of neonatal tetanus (NT) in rural parts of the Northern Areas, Pakistan. Bundling instituted within the first 3 days of life was found to be a substantial risk factor for NT. Delivery on a straw surface and the pre-delivery intravaginal application of ghee among mothers are also risk factors for NT. Handwashing by the delivery attendant and use of a new razor to cut the umbilical cord were protective. These findings demonstrate that NT can result from exposures of the umbilical wound any time during the first several days of life. Clean cord care at delivery alone is therefore not sufficient to prevent NT. NT prevention and control programs need to take these findings into account and operate accordingly.

Valoración indirecta de la integridad de la membrana celular mediante la redistribución de veinticuatro horas y reinyección de talio 201 para el diagnóstico de viabilidad miocárdica: análisis de costo beneficio y correlación con el vaso afectado / Indirect assessment of membrane integrity with thallium 201 24 hs redistribution and reinjection for diagnosis of myocardial viability: cost-benefit analysis and correlation with the damaged vessel

La perfusión miocárdica con talio 201 ha demostrado ser de gran utilidad en la evaluación de pacientes con enfermedad coronaria. Se ha desarrollado un nuevo campo para tratar de establecer la existencia de territorios con alteraciones de la función contráctil secundarias a coronariopatía, con capacidad de recuperarse cuando son revascularizados ("viabilidad miocárdica"). El objetivo de este estudio es evaluar la información que aporta la reinyección de 1mCi de talio 201 sobre la redistribución de 24 horas para el diagnóstico de segmentos miocárdicos viables. Se incluyeron 25 pacientes con antecedentes de infarto. A todos se les realizó perfusión miocárdica con talio 201, adquiriéndose imágenes planares en el posesfuerzo, a las 4 y 24 horas y a los 15 minutos de la reinyección. La coronariografía mostró: 15 obstrucciones significativas de la arteria descendente anterior, 14 de la coronaria derecha y 7 de la circunfleja. Para el puntaje de extensión hubo diferencias significativas para la redistribución de 24 horas (p<0,002) y la reinyección (p<0,0001) con respecto a la redistribución a las 4 horas. De los 82 segmentos con hipoperfusión en las imágenes de esfuerzo, 25 (30,49 po ciento) mejoraron en la redistribución a las 4 horas, 30 (36,58 por ciento) en la redistribución a las 24 horas y 47 (57,32 por ciento) en la reinyección

Epidemic cholera in Latin America, 1991-1993: implications of case definitions used for public health surveillance.

This report presents the various cholera case definitions used by the affected countries of Latin America, shows the numbers of cholera cases and deaths attributable to cholera (as reported by Latin American countries to PAHO through 1993), and describes some regional trends in cholera incidence. The information about how cholera cases were defined was obtained from an October 1993 PAHO questionnaire. In all, 948429 cholera cases were reported to PAHO by affected Latin American countries from January 1991 through December 1993, the highest annual incidences being registered in Peru (1991 and 1992) and Guatemala (1993). The case-fatality rate over the three-year period, and also in 1993, was 0.8%. A general downward trend in the incidence of cholera was observed in most South American countries, while the incidence increased in most Central American countries. A good deal of variation was noted in the definitions used for reporting cholera cases, hospitalized cholera cases, and cholera-attributable deaths. Because of these variations, broad intercountry comparisons (including disease burden calculations and care quality assessments based on case-fatality rates) are difficult to make, and even reported trends within a single country need to be evaluated with care. The situation is likely to be complicated in the future by the arrival of V. cholerae O139 in Latin America, creating a need to distinguish between it and the prevailing O1 strain. For purposes of simplicity, wide acceptance, and broad dissemination of case data, the following definitions are recommended: Confirmed case of O1 cholera: laboratory-confirmed infection with toxigenic V. cholerae O1 in any person who has diarrhea. Confirmed case of O139 cholera: laboratory-confirmed infection with toxigenic V. cholerae O139 in any person who has diarrhea. Clinical case of cholera: acute watery diarrhea in a person over 5 years old who is seeking treatment. Death attributable to cholera: death within one week of the onset of diarrhea in a person with confirmed or clinically defined cholera. Hospitalized patient with cholera:a person who has confirmed or clinically defined cholera and who remains at least 12 hours in a health care facility for treatment of the disease.

Further observations on ghee as a risk factor for neonatal tetanus.

BACKGROUND: Previous case-control studies of neonatal tetanus (NNT) in the North West Frontier Province of Pakistan indicated that clarified butter (ghee) applied to the umbilical wound of newborns was a significant risk factor for NNT. However, the mechanisms underlying the risk remained undisclosed. METHODS: A hospital-based case-control study was undertaken to evaluate further ghee and other factors possibly associated with risk of NNT. Mothers of several recent ghee-associated cases were visited in their homes, asked to simulate the procedures used in preparing the ghee, and samples of ghee were collected for culture. RESULTS: Topical application of ghee to the umbilical wound was again shown to pose a significant risk for NNT. In-use contamination of ghee was documented as mothers repeatedly heated and manipulated samples of ghee set aside in special containers for this purpose. Ghee was usually applied to the umbilical wound of the baby several times each day for the first few days of life. Mothers of cases were again confirmed to be substantially more likely to report prior NNT cases than mothers of controls. CONCLUSIONS: Educational interventions to reduce umbilical ghee use or to wash hands before each manipulation might reduce the risk of NNT in babies exposed to ghee who are born to non-immunized mothers. Increased efforts to immunize women of childbearing age with tetanus toxoid are also needed, with special priority for mothers known to have been associated with a previous NNT case. Topical antibiotics should be further evaluated for protective effects in non-immunized mothers.

PIP: Previous investigations in Pakistan revealed that the application of ghee (clarified butter) to umbilical wounds is a risk factor for neonatal tetanus (NNT), but the underlying mechanisms remained unknown because multiple cultures of ghee obtained from relevant households failed to culture Clostridium tetani. This study used a case-control approach to continue the evaluation of the risk of ghee applications through within-household observations of patterns of use of ghee and further microbiological tests. 100 physician-diagnosed cases who were hospitalized with NNT from September 1990 to January 1991 were compared with 300 controls matched as nearly as possible in age and sex. Data collected through questionnaires were submitted to descriptive analyses, matched analysis with single variables, stratified analysis, and other tests of statistical significance. Conditional logistic regression and Pearson correlation coefficients were also assessed. The only significant factors discovered were delivery by an academically trained attendant (which had a protective effect against NNT) and use of ghee on the umbilical wound (which was a risk factor for NNT). The household investigations revealed that the ghee for use on the newborn is kept in a separate container than that for general household use. The newborn's ghee is reheated and manipulated frequently by the mother. 25% of the samples from the secondary pots of ghee were contaminated. Heating is likely to activate rather than kill the spore-bearing bacteria which causes NNT. The influence of maternal practices is also seen in the fact that the incidence of NNT among previous births was statistically higher for mothers of cases than for mothers of controls. Since use of ghee is unlikely to be abandoned for sociocultural reasons, the added use of topical antibiotics should be evaluated for their impact on the risk factor posed by ghee. Also, special priority should be paid to the immunization of mothers of NNT cases.

A reassessment of risk factors for neonatal tetanus.

A hospital-based case-control study was conducted to further examine the risk factors for neonatal tetanus (NNT) in the North-west Frontier Province of Pakistan. Three control infants were concurrently evaluated for each of 102 consecutively diagnosed NNT cases hospitalized over an 8-week period. Application of clarified butter (ghee) during the first few days of life was shown to be a significant risk factor, confirming our previously reported finding. However, the risk appeared to be limited to ghee made in the home from cow's milk. The tool used to cut the umbilical cord was again refuted to be a risk factor; application of topical antibiotics conferred significant protection. Multivariate analysis of the matched data showed that delivery by persons with academic training (physicians, nurses, and lady health visitors) was also protective. Mothers with a past history of NNT babies were shown to have a significantly increased risk, and accounted for more than one-third of all cases in the present study. The findings suggest possible ways to augment the effectiveness of NNT elimination programmes.

PIP: A hospital-based case-control study was conducted to further examine the risk factors for neonatal tetanus (NNT) in the Northwest Frontier Province of Pakistan. 3 control infants were concurrently evaluated for each of 102 consecutively diagnosed NNT cases hospitalized for over an 8-week period. Application for clarified butter (ghee) during the 1st few days of life was seen as a significant risk factor, confirming the previously reported finding of the authors. However, the risk appeared to be limited to ghee made in the home from cow's milk. The tool used to cut the umbilical cord was again refuted to be a risk factor; application of topical antibiotics conferred significant protection. Multivariate analysis of the matched data showed that delivery by persons with academic training (physicians, nurses, and lady health visitors) was also protective. Mothers who had a past history of NNT babies were shown to have a significantly increased risk and accounted for more than 1/3 of all cases in the present study. The findings suggest possible ways to augment the effectiveness of NNT elimination programs. (author's)

Ghee applications to the umbilical cord: a risk factor for neonatal tetanus.

A case-control study was done to elucidate risk factors for neonatal tetanus (NNT) in rural Pakistan; three controls were selected for each of the 69 cases. Factors commonly believed to be associated with NNT, such as the tool used to cut the umbilical cord and the method of preparing the tool, were not confirmed as risk factors. However, applying ghee to the wound stump was. New prevention opportunities deriving from the finding should be pursued aggressively while efforts to develop effective delivery systems to immunise mothers against tetanus continue, a task made difficult by sociocultural factors.

Clinical efficacy of a new, enhanced-potency, inactivated poliovirus vaccine.

The 1986-87 outbreak of paralytic poliomyelitis in Senegal, with 676 reported cases, provided an opportunity to evaluate the efficacy of an enhanced-potency inactivated poliovirus vaccine (N-IPV) in the Kolda region, where this vaccine has been used since 1980. 89 cases, confirmed to have poliomyelitis with residual paralysis, were enrolled in a case-control study, up to 5 matched controls being obtained for each case. The clinical efficacy for one dose of N-IPV was 36% (95% confidence interval 0%, 67%) and for two doses was 89% (95% CI 62%, 97%).

[External intestinal fistulae. Clinical treatment. Surgical treatment]. / Fistulas intestinales externas. Tratamiento médico.

There are 105 cases shown, all of them as a consequence of surgical operations or external traumatisms or surgery in the duodenum, jejunum, ileum and colon. These 105 cases were divided into two major groups: 1) simple and 2) multiple. 76 of the first group and 29 of the second group were treated. An equal therapeutic criterion was followed independently of the etiology. In the first stage the surgical cleaning of the wound was made and it was washed and vacuum cleaned with a solution of lactic acid. The surgery is only used in the complicated cases. The nutrition intravenous therapeutic of hidroelectrolitic and blood volume replacement was installed, besides, this system is used for the antibiotheraphy. The success of the parenteral nutrition depends upon the control of the sepsis. In cases where it is possible, the enteral nutrition is started only after 10 days of treatment. Before surgery on the fistula, the medical treatment is maintained, at least, during 4 weeks, which in some cases could be extended up to a maximum of six months. The fistula reappears again when the surgery is performed too soon. When the process is restrained, the nutritive condition is improved and the sepsis is controlled, the surgery takes place to reestablish the intestinal passage. The 47,7% of the cases recovered with only medical treatment. It is evident that late surgery improves the results, since of 22 cases, where surgery was performed, 86,3% cured, and which in turn represents 18% of the total cases.

Vitamin K-dependent gamma-carboxyglutamic acid formation by mouse renal adenocarcinoma cells (RAG).

Previous studies have identified gamma-carboxyglutamic acid as a constituent of one or more protein(s) synthesized by rat and chicken kidney microsomes in vitro in a vitamin K-dependent post-translational reaction [1]. Incubation of microsomes from a mouse kidney cell line (RAG) with [14C]NaHCO3 results in formation of protein-bound [14C]gamma-carboxylglutamic acid. Incorporation is stimulated threefold by addition of the active vitamin K compound 2-methyl, 3-farnesyl, 1,4-naphthoquinone. At least 90% of incorporated, nondialyzable [14C] is situated in the gamma-carboxyl group of gamma-carboxyglutamic acid residues.

Isolation, purification, and cross-linking profiles of elastin from lung and aorta.

Elastin from anatomically defined regions of young calf lung and dog aorta was isolated and purified by a procedure which sequentially removed lipids, collagen, structural glycoproteins, and the microfibrillar proteins without apparent damage to the cross-linking residues, which have been shown to be sensitive to autoclaving and hot alkali treatment. One of the methods described was effective in obtaining pure elastin from lung parenchyma. Visceral pleura was found to be the richest source (25% dry weight) of elastin in the lung tissues examined. The amino acid compositions of the elastins purified by different methods were compared for purity and for the detection of possible damage to cross-linking compounds. Cross-linking profiles were obtained by column chromatography either after reduction with 3[H]NaBH4 or after reaction with 14[C]NaCN and NH3. The 3[H]NaBH4 method, under carefully controlled conditions, proved not to be quantitatively reproducible. The reaction of elastin with 14[C]NaCN and NH3 appeared preferable due to its reproducibility; this procedure required one type of hydrolysis for the analysis of all the cross-linking compounds. Examination of the cross-linking profiles of the elastins from various tissue regions revealed differences in the type, distribution, and quality of cross-links.