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BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

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OBJECTIVES: Gonococcal isolates were differentiated based on susceptibility pattern, penicillinase production (PPNG or non-PPNG), serogroup, auxotype, protein, and plasmid profile. The association between serogroup and auxotype and PPNG was determined. STUDY DESIGN: Women attending tertiary level health centers and the sexually transmitted disease (STD) clinic in Mumbai, India, were screened for Neisseria gonorrhoeae. Minimal inhibitory concentration testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Auxotypes, serogroups, protein profile, and plasmid content were also studied. RESULTS: Of the 33 isolates, 16 (48.5%) were resistant to penicillin, and 28 (84.8%) showed a chromosomally mediated resistance to tetracycline. Five (15.2%) isolates showed resistance to ciprofloxacin, whereas 12 (36.4%) showed a reduced susceptibility. Twenty-seven (81.8%) isolates belonged to the WI serogroup, and 15 (46.7%) were penicillinase producers (PPNG). Seventeen (51.5%) isolates were of the nonrequiring auxotype, whereas seven (21.2%) were proline requiring. Fifteen (55.6%) of the isolates belonged to the nonrequiring-WI auxotype/serogroup (A/S) class. Ten of the PPNG isolates possessed the 4.4 MDa plasmid, whereas four had the 3.2 MDa plasmid. Increases in the molecular weight of the major outer membrane protein were observed. CONCLUSION: A high prevalence of chromosomal resistance to penicillin and tetracycline was observed. The 4.4 MDa plasmid was the most prevalent among the PPNG isolates. We observed ciprofloxacin resistance, which has not been reported in previous studies in India. The nonrequiring auxotype was the most prevalent, followed by the proline requiring auxotype. WI serogroup was the most commonly observed among the isolates studied. The nonrequiring/WI A/S class was the most prevalent among the PPNG.

PIP: This study aims to determine the prevalence of penicillinase-producing Neisseria gonorrhea (PPNG), as well as to differentiate gonococcal isolates based on susceptibility pattern, penicillinase production, serogroup, auxotype, protein and plasmid profile among women attending tertiary level health centers and sexually transmitted disease (STD) clinics in Mumbai (formerly Bombay), India. An association between auxotypes, serogroups and antibiotic susceptibilities of Neisseria gonorrhea was determined. Subjects were screened for Neisseria gonorrhea; the minimal inhibitory concentration testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The antibiotics tested were penicillin, tetracycline, ciprofloxacin, and spectinomycin. The ability of various typing methods to distinguish different isolates was calculated using the discrimination index. Results showed that in the susceptibility testing group 16 (48.5%) were resistant to penicillin and 28 (84.8%) showed chromosomally mediated resistance to tetracycline. 5 isolates (15.2%) showed resistance to ciprofloxacin, while 12 (36.4%) showed reduced susceptibility. 27 (81.8%) isolates belonged to the WI serogroup, and 15 (46.7%) were penicillinase producers. In auxotyping, 17 (51.5%) isolates were of the nonrequiring auxotype, while 7 (21.2%) were proline requiring. 15 (55.6%) of the isolates belonged to the nonrequiring-WI auxotype/serogroup (A/S) class. In plasmid pattern, 10 of the PPNG isolates possessed the 4.4 MDa plasmid, while 4 had the 3.2 MDa plasmid. Increases in the molecular weight of the major outer membrane protein were observed. In conclusion, the combined use of auxotyping and serogrouping offers a good method for discriminating gonococcal isolates. A high prevalence of chromosomal resistance to penicillin and tetracycline was observed. The 4.4 MDa plasmid was the most prevalent among the PPNG isolates. The nonrequiring auxotype was the most prevalent, followed by the proline requiring auxotype. WI serogroup was commonly observed among the isolates, while the nonrequiring/WI A/S class was the most prevalent among PPNG isolates.

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OBJECTIVE: To investigate if there is a difference in response to tuberculosis treatment between HIV seronegative and HIV seropositive patients following two months of intensive phase tuberculosis treatment. DESIGN: Prospective cohort study. SETTING: St. Francis Leprosy Centre, south-east Uganda. SUBJECTS: Four hundred fifty seven patients with never previously treated sputum smear-positive tuberculosis admitted during a two-year period in 1991/1993. INTERVENTION: Intensive phase treatment with streptomycin, isoniazid, rifampicin and pyrazinamide. MAIN OUTCOME MEASURES: Sputum conversion from a positive to a negative smear at eight weeks of treatment. RESULTS: HIV seropositivity prevalence was 28%. Among HIV seronegative patients, conversion to a negative smear status occurred in 76% persons compared to 78% in HIV seropositive patients. This difference was not statistically significant (OR = 0.9; 95% CI, 0.6-1.5). HIV seropositive patients, however, were more likely to die (p = 0.017). A high prevalence of resistance to isoniazid and streptomycin was found. Isoniazid resistance was more likely in HIV seronegative patients with M. tuberculosis strains compared to HIV seropositive persons (p < 0.005). Initial resistance to antituberculosis drugs did not have a significant effect on smear conversion. CONCLUSION: This study demonstrates that HIV-seropositive status is not a principal factor in delaying sputum conversion among patients receiving intensive phase tuberculosis treatment.

PIP: A prospective cohort study was undertaken to investigate the response of HIV-seropositive and -seronegative patients at St. Francis Leprosy Center, southeastern Uganda, to tuberculosis chemotherapy. The study population included 457 patients without a history of prior tuberculosis therapy between 1991 and 1993. The subjects were exposed to an intensive phase therapy of rifampicin, streptomycin, isoniazid, and pyrazinamide. After the treatment, sputum culture and sensitivity tests were conducted. Findings showed that 77% of the patients who never received tuberculosis treatment in the past converted to a negative smear status after the 8-week treatment. There was no significant difference in sputum conversion rates between HIV-seropositive and -seronegative patients. The study also revealed that HIV seropositivity prevalence was 28%. Among HIV-seronegative patients, conversion to a negative smear status occurred in 76% compared to 78% HIV-seropositive patients. Moreover, a significant number of HIV-seronegative patients died during the initial course of the therapy. Also, a high prevalence of isoniazid and streptomycin resistance was noted; however, this result never affected the conversions of smears. In conclusion, the study clearly demonstrates that other factors outside the seropositive status may be the principal causes of the delay in sputum conversion among patients receiving intensive tuberculosis chemotherapy.

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OBJECTIVE: To determine the susceptibility pattern of local strains of Neisseria gonorrhoeae from Dar es salaam, Tanzania to locally used antibiotics. METHOD: Out of 429 Neisseria gonorrhoeae strains isolated between 1993 and 1995, one hundred and ninety nine were recovered and tested. Minimum inhibitory concentrations (MIC) of penicillin, doxycycline, erythromycin, cefuroxime and ciprofloxacin were determined by the E-test method while that of spectinomycin was measured by the agar dilution method. Penicillinase producing N. gonorrhoeae were identified by the chromogenic cephalosporin method. RESULTS: Of the 199 strains tested 128 (64%) were found to be penicillinase producing Neisseria gonorrhoeae (PPNG). Only 19 (10%) were penicillin sensitive while all penicillin resistant strains were found to be PPNG. One hundred and seventy five (88%), 11(5%) and 13 (7%) of the tested isolates were resistant, less susceptible and fully susceptible to doxycycline respectively. Resistance to cotrimoxazole, cefuroxime and ciprofloxacin was 36 (18%), 11 (6%), and 3 (2%) respectively. The trend of antibiotic susceptibility rates over the three year period of study showed a significant increase in the proportion of susceptible strains to cotrimoxazole. All of the 75 strains tested against spectinomycin were susceptible. There was a statistically significant difference between the susceptibility patterns of non-PPNG and PPNG. Non-PPNG isolates were more susceptible to doxycycline (chi 2 = 78.2, df 2, p = < 0.0001). CONCLUSION: These findings have shown that spectinomycin, ciprofloxacin and cefuroxime could continue to be used to treat gonorrhoea in our settings. Continuous surveillance of susceptibility to the commonly used antibiotics is important in order to detect emergence of resistance early and control the possible wide spread of resistant strains.

PIP: This article presents a study on the susceptibility pattern of local strains of Neisseria gonorrheae (NG) to antimicrobial agents (penicillin, doxycyline, erythromycin, cefuroxime, ciprofloxacin, cotrimoxazole, and spectinomycin) in Dar Es Salaam, Tanzania. Out of the 429 isolated strains of NG in 1993-95, 199 were included in the study. Susceptibility patterns to the six antimicrobials was determined through the E-test method, a test that measures their minimum inhibitory concentrations (MICs). On the other hand, the spectinomycin MIC was determined through the antibiotic agar dilution method. Results revealed the following patterns of susceptibility of isolates: spectinomycin (100%), ciprofloxacin (97%), Cefuroxime (89%), erythromycin (57%), cotrimoxazole (40%), doxycycline (7%), and penicillin (10%). It was also noted that NG strains are highly resistant to penicillin (64%) and doxycycline (88%). The study concludes that three drugs--spectinomycin, ciprofloxacin, and spectinomycin--could be effective in treating gonorrhea. However, a continued surveillance of common antibiotics against gonococcus is necessary for the early detection and control of strain resistance.

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BACKGROUND: Previous case-control studies of neonatal tetanus (NNT), a leading cause of infant mortality in developing countries, have suggested that antimicrobials applied after delivery to the umbilical cord stump may protect against this disease. However, assessment of their protective effect has been limited by the low prevalence of antimicrobial use in developing countries. METHODS: We conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh. We studied 359 cases (infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT), each matched to three living controls for gender, residence, and date of birth. RESULTS: In univariate analyses, the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants were protective against NNT. The application of antibiotics at delivery (odds ratio [OR] = 0.21, P = 0.019), hand washing by the delivery attendant (OR = 0.64, P = 0.005), and prior maternal immunization with tetanus toxoid (OR = 0.50, P < 0.001) remained protective in conditional logistic-regression analyses. Application of animal dung to the umbilical stump (OR = 2.31, P = 0.047) was hazardous. CONCLUSIONS: Effective and inexpensive topical antimicrobials provide a new prevention opportunity that could be used by traditional birth attendants and mothers to provide additional benefits to NNT control programmes based on maternal immunization with tetanus toxoid. Promotion of hygienic delivery and cord-care practices and increasing tetanus toxoid coverage remain cornerstones for the prevention of NNT deaths.

PIP: Neonatal tetanus (NNT) is a leading cause of infant mortality in developing countries. Findings from previous case-control studies of NNT have suggested that antimicrobials applied following delivery to the umbilical cord stump may protect against the disease. However, assessment of their protective effect has been hampered by the low prevalence of antimicrobial use in developing countries. The authors conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh. 359 cases were studied, infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT. Each case was matched to 3 living controls for gender, residence, and date of birth. Univariate analyses found the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants to protect against NNT. The application of antibiotics at delivery, hand washing by the delivery attendant, and prior maternal immunization with tetanus toxoid remained protective in conditional logistic-regression analyses. The application of animal dung to the umbilical stump was hazardous.

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We aimed to determine if the clinical and histological features of chancroid are altered by HIV infection. Male patients presenting to the Nairobi special treatment clinic with a clinical diagnosis of chancroid were eligible for the study. A detailed history, physical examination, swabs for Haemophilus ducreyi culture and blood for HIV serology, syphilis serology and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees C. Patients were treated with erythromycin and followed for 3 weeks. Chi-square and Student's t-test were used to determine if the clinical and laboratory features of chancroid differed between HIV-seropositive and seronegative individuals. Cox regression survival analysis was used to determine if HIV infection altered cure rates of chancroid at 21 days. Immunohistochemical staining was performed using lymphocytic and macrophage markers and tissue sections were analysed by 2 pathologists in a blinded manner. Between February and November 1994, 109 HIV-seropositive and 211 HIV-seronegative individuals were enrolled in the study. HIV patients had ulcers of longer duration than HIV-seronegative patients (P=0.03). Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%, P=0.002). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. This consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and negative patients. HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. This clinical difference cannot be attributed to an altered histopathological response to HIV infection. Additional studies are needed to elucidate the mechanisms responsible for this finding.

PIP: Chancroid is caused by infection with Hemophilus ducreyi, and is associated with an increased risk for the sexual transmission of HIV-1. The authors assessed whether the clinical and histological features of chancroid are changed by HIV infection, using 320 male patients who presented during February-November 1994 to the City of Nairobi Special Treatment Clinic with a clinical diagnosis of chancroid. 109 subjects were HIV seropositive and 211 were HIV seronegative. A detailed history, physical examination, swabs for Hemophilus ducreyi culture and blood for HIV serology, syphilis serology, and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees Celsius. Patients were treated with erythromycin and followed for 3 weeks. HIV patients had ulcers of longer duration than did HIV-seronegative patients. Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% vs. 54%). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. The infiltrate consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and HIV-negative patients. Study findings therefore indicate that HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. The clinical difference cannot be attributed to an altered histopathological response to HIV infection.

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PIP: The findings of a large, multicenter US study indicate that women who are screened for infection risks before IUD insertion are at low risk of such complications, regardless of whether prophylactic antibiotics are administered. More than 300 clinicians at 11 clinics in Los Angeles County, California, provided 1867 women with either 500 mcg of azithromycin or placebo capsules before insertion of a Copper T 380A IUD. The risk of sexually transmitted infection was assessed before IUD insertion through both self-reported medical history and screening for chlamydia and gonorrhea. At least 90 days of postinsertion follow-up was accumulated for about 98% of women in both groups. At 90 days, 92.7% of women who received the antibiotic and 93.2% of those who received a placebo still had their IUD in place. Only 1 woman in each group developed salpingitis. The rate of IUD removal for any reason other than spontaneous partial expulsion was 3.8% in the antibiotic group and 3.4% in the placebo group. At 12 months, approximately 80% of women still had their IUDs in place, indicating a high level of satisfaction with the device. Researchers have expressed hope that these findings will help counteract concerns about IUD safety.^ieng

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BACKGROUND: Primary prevention of acute rheumatic fever requires antibiotic treatment of acute streptococcal pharyngitis. In developing countries, clinicians must rely on clinical guidelines for presumptive treatment of streptococcal pharyngitis since bacterial culture and rapid diagnostic tests are not feasible. We evaluated the WHO Acute Respiratory Infection guideline in a large urban paediatric clinic in Egypt. METHODS: Children between 2 and 13 years of age who had a sore throat and pharyngeal erythema were enrolled in the study. Clinical, historical, and demographic information was recorded and a throat culture for group A beta-haemolytic streptococci was done. Sensitivity (% of true-positive throat cultures) and specificity (% of true-negative throat cultures) were calculated for each clinical feature. The effect of various guidelines on correct presumptive treatment for throat-culture status was calculated. FINDINGS: Of 451 children with pharyngitis, 107 (24%) had group A beta-haemolytic streptococci on throat culture. A purulent exudate was seen in 22% (99/450) of these children and this sign was 31% sensitive and 81% specific for a positive culture. The WHO Acute Respiratory Infections (ARI) guidelines, which suggest treatment for pharyngeal exudate plus enlarged and tender cervical node, were 12% sensitive and 94% specific; 13/107 children with a positive throat culture would correctly receive antibiotics and 323/344 with a negative throat culture would, correctly, not receive antibiotics. Based on our data we propose a modified guideline whereby exudate or large cervical nodes would indicate antibiotic treatment, and this guideline would be 84% sensitive and 40% specific; 90/107 children with a positive throat culture would correctly receive antibiotics and 138/344 with a negative throat culture would, correctly, not receive antibiotics. INTERPRETATION: The WHO ARI clinical guideline has a high specificity but low sensitivity that limits the unnecessary use of antibiotics, but does not treat 88% of children with a positive streptococcal throat culture who are at risk of acute rheumatic fever. A modified guideline may be more useful in this population. Prospective studies of treatment guidelines from many regions are needed to assess their use since the frequency of pharyngitis varies.

PIP: In developing country settings without access to bacterial culture and rapid diagnostic tests, the prevention of acute rheumatic fever depends on clinicians' presumptive treatment of streptococcal pharyngitis. This study evaluated the effectiveness of World Health Organization (WHO) acute respiratory infection guidelines in a large pediatric clinic (Abu Reesh Children's Hospital) in Cairo, Egypt. 451 children 2-13 years of age with sore throat and pharyngeal erythema were enrolled, 107 (24%) of whom had group A beta-hemolytic streptococci on throat culture. Purulent exudate, present in 99 (22%) of these children, was 31% sensitive and 81% specific for a positive culture. The WHO guidelines, which recommend treatment for pharyngeal exudate plus enlarged and tender cervical node, were 12% sensitive and 94% specific. Based on these guidelines, 13 of 107 children with a positive throat culture would correctly receive antibiotics and 323 of 344 with a negative culture would not receive antibiotics. A modified guideline in which exudate or large cervical nodes would indicate antibiotic treatment would be 84% sensitive and 40% specific. With this modification, 90 of 107 children with a positive throat culture would correctly receive antibiotics and 138 out of 344 with a negative culture would not receive treatment. However, additional prospective studies from other regions of Egypt are necessary before modified guidelines are implemented.

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BACKGROUND AND OBJECTIVES: The antimicrobial susceptibility pattern of Neisseria gonorrhoeae varies from one country to another and may also change with time. To monitor these variations and changes, it is desirable to have a method that is simple and reproducible. This study was undertaken to determine the in vitro susceptibility of N. gonorrhoeae to azithromycin and to assess the reliability of results obtained using E-test methodology for determination of the minimum inhibitory concentration (MIC) of azithromycin. STUDY DESIGN: The MICs for 135 clinical isolates of N. gonorrhoeae were determined by a modified Kirby-Bauer method recommended by the National Committee for Clinical Laboratory Standards against penicillin, cefuroxime, ceftriaxone, norfloxacin, tetracycline, kanamycin, spectinomycin, and azithromycin. The MIC of azithromycin was determined by both the E-test and agar dilution method. All tests were done simultaneously. RESULTS: The MIC of azithromycin to all 135 isolates ranged from 0.078 to 0.25 microgram/ml with the agar dilution method and from 0.016 to 0.50 microgram/ml with the E-test. The MIC50 and MIC90 of azithromycin were 0.064 microgram/ml and 0.125 microgram/ml, respectively, by the agar dilution method, whereas they are slightly higher by the E-test method. Seventy-six of the isolates were beta-lactamase producers and 69 were high-level tetracycline-resistant N. gonorrhoeae. There was no difference in the MIC50 and MIC90 of azithromycin in these groups of isolates. The percentage agreement within the acceptable +/-1 log2 dilution difference between MICs obtained by E-test and those obtained by the agar dilution method was 97.8%. CONCLUSIONS: Azithromycin has a very good in vitro antigonococcal activity, and the E-test is a reliable method to determine the MIC of azithromycin against N. gonorrhoeae.

PIP: A single dose of a new antibiotic, azithromycin, has been shown to be effective in the treatment of uncomplicated Neisseria gonorrhoeae. A clinical study was conducted to assess the in vitro susceptibility of N gonorrhoeae to azithromycin and compare the reliability of results obtained using the new E-test methodology for determination of the minimum inhibitory concentration (MIC) of antibiotic with those obtained through the standard agar dilution method. 135 clinical isolates of N gonorrhoeae were obtained from patients attending hospital-based sexually transmitted disease clinics in five geographic locations in Malaysia. 76 of the isolates were penicillinase-producing N gonorrhoeae and 69 were high-level tetracycline-resistant N gonorrhoeae. All isolates were susceptible to azithromycin based on the susceptible MIC breakpoint of 2.0 mcg/ml. The MICs ranged from 0.0078-0.25 mcg/ml by agar dilution method and from 0.016-0.50 mcg/ml by E-test. Agreement between these two methods was 97.8%. The single-dose regime and good antigonococcal and antichlamydial activity of azithromycin make this antibiotic a suitable treatment choice. Moreover, the findings of this study suggest that the simpler, faster E-test is as reliable as the agar dilution method. Given the tendency of the antimicrobial susceptibility pattern of N gonorrhoeae to change rapidly, it is important to monitor MICs to detect the emergence of resistance.

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BACKGROUND: Syphilis remains a major cause of premature birth, fetal and perinatal death, and congenital syphilis in South Africa, despite systematic antenatal screening by rapid plasma reagin and treatment with 2.4 million U of benzathine penicillin G. GOAL: To determine whether one injection of 2.4 million of U of benzathine penicillin G, as recommended by the 1993 Centers for Disease Control and Prevention guidelines, is sufficient treatment for early syphilis during pregnancy. STUDY DESIGN: Outcome of pregnancy was prospectively analyzed after zero to three weekly intramuscular injections of benzathine penicillin G in 180 of 212 human immunodeficiency virus-seronegative black urban women with syphilis in Pretoria, South Africa. RESULTS: One hundred eight women receiving two or three weekly intra-gluteal injections of benzathine penicillin G had a favorable pregnancy outcome. However, after only one injection, lower birth weight, increased immaturity, prematurity, and total preterm birth rate resulted. Total pregnancy loss and perinatal mortality were also increased. After exclusion of patients treated with oral penicillin derivatives and adjustment for the estimated duration of treponemicidal levels at 3 weeks after injection, the perinatal outcome was reanalyzed. Treponemicidal coverage of 3 weeks or less resulted in decreased birth weight (2,748 vs. 3,130 g, P = 0.004) compared with treponemicidal coverage lasting longer than 3 weeks. In addition, the relative risks for prematurity (relative risk [RR], 8.5; 95% confidence interval [CI95], 2.5-28), perinatal mortality (RR, 20.5; CI95, 2.3-184), and congenital syphilis (RR 2.0; CI95-0.6-6.8) were increased when coverage was less then 3 weeks. These results were comparable to those obtained when no treatment was given. Most of the incompletely treated women delivered at less than 4 weeks after they received their injection. These also had the worst neonatal outcome. Impaired outcome due to short treatment clustered in early attenders of prenatal care (before the 28th week of gestation) and when the initial rapid plasma reagin titer was higher than 16. Although numbers were small for a firm conclusion, incompletely treated and untreated women who had taken intercurrent oral ampicillin had an improved birth weight, lower prematurity rate, and lower fetal rate. CONCLUSIONS: One intramuscular injection of 2.4 million U benzathine penicillin G or treponemicidal concentrations lasting 3 weeks or less is not sufficient therapy for pregnant women with syphilis. Although fetal outcome is clearly improved at birth with more than one injection, without follow-up of the neonates, complete cure cannot be predicted from these data. To obtain treponemicidal activity for longer than 3 weeks, the authors recommend administration of two injections of 2.4 million U benzathine penicillin at least 1 week apart, if possible at 4 weeks or more before delivery. This therapy is especially important for patients who attend prenatal care before 28 weeks of pregnancy or when the rapid plasma reagin titer is higher than 16.

PIP: To determine whether the US Centers for Disease Control guideline of 1 injection of 2.4 million U of benzathine penicillin G is sufficient treatment for early syphilis in pregnant women, this regimen was tested in 180 human immunodeficiency virus-negative urban Black women with syphilis presenting to Kalafong Hospital in Pretoria, South Africa, during 1988-90. A favorable pregnancy outcome was recorded in 108 women who received 2 or 3 weekly intragluteal injections. On the other hand, 1 injection was associated with lower birth weight, increased prematurity and total preterm birth rate, and increased total pregnancy loss and neonatal mortality. These outcomes were reanalyzed after exclusion of women treated with oral penicillin derivatives and adjusted for the estimated duration of treponemicidal levels at 3 weeks post-injection. Birth weight was significantly lower for treponemicidal coverage of 3 weeks or less compared to coverage lasting more than 3 weeks (2748 and 3130 grams, respectively). Also increased when coverage was less than 3 weeks were the relative risks for prematurity (8.5), perinatal mortality (20.5), and congenital syphilis (2.0). Impaired outcome associated with short treatment was clustered in women who attended prenatal care before the 28th week of gestation and those whose initial rapid plasma reagin titer exceeded 16. These findings indicate that the standard protocol is not adequate in areas where syphilis is endemic. Recommended is administration of 2 injections of 2.4 million U benzathine penicillin at least 1 week apart, preferably 4 weeks or more before delivery.

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The emergence of antibiotic-resistant Streptococcus pneumoniae is an international health problem. Apart from South Africa few data on pneumococcal resistance are available for sub-Saharan Africa. This study examines the nasopharyngeal carriage and prevalence of antibiotic resistance in pneumococci isolated from 260 Zambian children aged < 6 years. Pneumococci were isolated from 71.9% of the children; the odds of carrying organisms were twice as high among children < 2 years of age compared with older children. Antibacterial resistance was found in 34.1% of the isolates; resistance to tetracycline, penicillin, sulfamethoxazole + trimethoprim, and chloramphenicol occurred in 23.0%, 14.3%, 12.7%, and 3.9% of the isolates, respectively. Only 4% of the isolates were resistant to three drugs. High-level resistance was found in all isolates resistant to tetracycline; but only intermediate level penicillin resistance was found. A total of 11.1% of the isolates demonstrated intermediate resistance to sulfamethoxazole + trimethoprim. Children aged < 6 months were less likely to carry antibiotic-resistant organisms. Antibiotic resistance in S. pneumoniae appears to be an emerging public health problem in Zambia, and the national policy for the empirical treatment of pneumococcal meningitis and acute respiratory tract infections may need to be re-evaluated. The establishment of ongoing surveillance to monitor trends in pneumococcal resistance should be considered.

PIP: Pneumococcal pneumonia accounts for up to 25% of deaths in children under 5 years of age in sub-Saharan Africa. This study investigated the nasopharyngeal carriage rate of Streptococcus pneumoniae in a Zambian pediatric population and the prevalence of antibiotic resistance. Enrolled were 260 children under 6 years of age (mean age, 20 months) treated at the University Teaching Hospital in Lusaka, Zambia, in 1994. S. pneumoniae was isolated from the nasopharynx of 187 children (71.9%). The odds of carrying pneumococci were twice as high among children under 2 years of age (76.2%) than older children (59.7%). Overall, 83 (65.9%) of the 126 isolates available for antibiotic resistance profiles were sensitive to the drugs. Resistance to tetracycline, penicillin, sulfamethoxazole plus trimethoprim, and chloramphenicol was found in 23.0%, 14.3%, 12.7%, and 3.9%, respectively, of the isolates. The highest level of resistance was recorded in all isolates resistant to tetracycline. All but one of the multidrug-resistant isolates were serotype 14. Children under 6 months old were least likely to carry antibiotic-resistant organisms. In an anonymous questionnaire completed by 160 mothers, 38% reported they obtained antibiotics without a prescription and 49.4% acknowledged feeling dissatisfied when not given antibiotics to treat their sick child. Ongoing surveillance is recommended in Zambia to ensure that recommended treatment regimens keep pace with trends in antibiotic resistance.

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A prospective study was undertaken to investigate the relative prevalence of Chlamydia trachomatis in asymptomatic pregnant women of 2 socioeconomic groups and those attending the family planning clinics. Group 1 consisted of women attending the antenatal clinics of the Aga Khan University Hospital which caters to the affluent strata of our society (n = 100). Group 2 comprised women attending the antenatal clinics of Lady Dufferin Hospital which provides free obstetric care to women belonging to the lower socioeconomic groups of Karachi (n = 100). Group 3 consisted of sexually active women attending the family planning clinics of Lady Dufferin Hospital (n = 100). Endocervical swabs were taken from women assigned to each group. Chlamydiazyme, an enzyme linked immunoassay, was used to detect chlamydia antigen. The positive samples were retested by using the direct fluorescent monoclonal antibody technique. Chlamydia positive patients and their sexual partners were treated with Erythromycin stearate 500 mg 8-hourly for 7 days. These patients were retested after antibiotic therapy to assess the efficacy of the therapy. In groups 1 and 2, 2% and in Group 3, 12% of the females tested positive. Selective screening of sexually active women for chlamydial infection is advocated as a cost-effective public health measure.

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Pelvic infection complicates up to 12% of induced abortions and has an adverse effect on future reproductive outcome. The presence in the lower genital tract of Neisseria gonorrhoeae, Chlamydia trachomatis or the anaerobic organisms characterizing bacterial vaginosis is associated with an increased risk of post-abortion infective morbidity. Meta-analysis of randomized trials has shown that prophylaxis with antibiotics effective against either C. trachomatis or bacterial vaginosis reduces the risk of post-abortion infective morbidity by around a half. Other strategies which have been advocated for minimizing the risk of infective morbidity are screening for lower genital tract infections, with treatment of positive cases only, and a combined strategy where women are screened for sexually transmitted infections as well as receiving prophylaxis. These strategies provide the opportunity for appropriate follow-up and partner notification of those women found to have sexually transmitted infections. A multicentre study designed to determine the prevalence of genital tract infections among Scottish women seeking induced abortion, and to compare strategies of 'universal prophylaxis' and 'screen and treat' for minimizing infective morbidity in such women has been undertaken. A total of 1672 women were recruited. Prevalence rates of lower genital tract gonorrhoea, chlamydia and bacterial vaginosis were found to be similar to those reported in other UK studies. Women managed by the 'screen and treat' strategy (particularly those whose genital tract swabs were reported negative) had slightly higher rates of infective morbidity in the 8 weeks after abortion than those managed by 'prophylaxis'. Using currently available screening tests and genitourinary medicine services, 'prophylaxis' appears to be the more cost effective of the two strategies studied.

PIP: Reported rates of post-abortion pelvic inflammatory disease (PID) range from 5-29%. The risk of infection has been associated with the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, and anaerobic organisms in the lower genital tract. The present study analyzed the prevalence of genital tract infections in 1672 women undergoing induced abortion at 3 centers in Scotland and evaluated the efficacy of two preventive interventions. Prevalence rates of lower genital tract gonorrhea, chlamydia, and bacterial vaginosis before abortion were similar to those identified in other UK studies. Women were randomly allocated to receive either prophylactic metronidazole (immediately before abortion) and doxycycline (for 7 days after abortion) or received antibiotics only if pre-abortion genital tract swabs were positive for any of the 3 infections. During the 8-week post-abortion follow-up period, women managed by the screen-and-treat protocol had slightly less favorable outcomes in terms of hospital readmissions, general practitioner consultations, antibiotic prescriptions, time off work, and limitations on domestic activities than women who received prophylactic treatment. Differences were statistically significant, however, only for women whose swabs were negative for all 3 infections. The rate of post-abortion PID/endometritis in this groups was 3% among women who received prophylactic antibiotics and 6% in those who were screened and not treated. These findings suggest that universal antibiotic prophylaxis may represent the most cost-effective approach to minimizing the risk of infective morbidity. Advocated for consideration is a third strategy involving prophylaxis at the time of abortion followed by screening for gonorrhea and chlamydia to ensure adequate follow-up of treatment results and partner notification.

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BACKGROUND: HIV infection is common in mothers and their children in Zimbabwe, and HIV-infected children are particularly susceptible to bacterial infections. There is little information on the etiology and outcome of HIV-related bacteremia in African children. METHODS: Blood cultures from 309 hospitalized children in Zimbabwe, of whom 168 were diagnosed as having HIV, were examined for pathogens. The association among significant bacteremia, HIV infection and mortality was assessed in these children. RESULTS: The most common isolates were coagulase-negative staphylococci (31 children, 25 clinically significant), Staphylococcus aureus (22 children) and Streptococcus pneumoniae (20 children). Nontyphoidal Salmonella (10 children), Escherichia coli (4 children) and Klebsiella sp. (4 children) were the most frequent Gram-negative bacteria. Two children had Rhodococcus equi pneumonia. HIV-infected children showed increased risk of bacteremia (odds ratio (OR) = 2.68), especially if younger than 18 months of age (OR = 2.94), and high risk of enterobacteremia (OR = 15.76). There was no significant association of bacteremia with nutritional status. Mortality was 17% overall but was higher in HIV-infected children up to 6 months of age (OR = 2.81) and in bacteremic children of any age (OR = 2.03). CONCLUSIONS: Prompt recognition of pathogens and early administration of appropriate antimicrobials is important in reducing the morbidity and mortality associated with bacteremia in HIV-infected children in Africa.

PIP: Researchers compared data on 168 HIV-positive pediatric patients with data on 141 HIV-negative pediatric patients to examine the etiology and outcome of HIV-related bacterial infections in a pediatric population admitted to Harare Hospital in Zimbabwe during June 1993 to December 1994. The age of the children ranged from less than 1 month to 96 months. 72% were less than 12 months old. 54% of all pediatric patients tested were HIV-infected. HIV-infected children were more likely to have a bacterial infection than HIV-negative children (40% vs. 20%; odds ratio [OR] = 2.68; p 0.001). The difference in the bacterial infection rate was only significant for children aged less than 18 months (41% vs. 19%; OR = 2.94; p 0.001), however. 14% of the children suffered from severe malnutrition. Nutritional status was not significantly associated with bacterial infection. In both HIV-positive and HIV-negative children, Staphylococcus aureus was the most frequent bacterial pathogen (29% for HIV-positive and 18% for HIV-negative children). Many Gram-positive and Gram-negative isolates were resistant to the combination therapy of trimethoprim-sulfamethoxazole. Only 1 child, who was HIV-positive, had more than one bacterial infection (both Streptococcus pneumoniae and Actinomyces israelii). HIV-positive children were more likely to have an enterobacterial infection than HIV-negative children (10% vs. 0.7%; p 0.001). Mortality was significantly higher among HIV-infected children aged less than 6 months old than their HIV-negative counterparts (28% vs. 12%; OR = 2.81; p 0.05). Even though it was also higher among HIV-positive children aged more than 6 months (17% vs. 7%), the difference was not significant. Regardless of HIV status, children with bacteremia were more likely to die than those without bacteremia (24% vs. 14%; OR = 2.03; p 0.05). These findings stress the importance of early and effective antibiotic therapy. This therapy will reduce the morbidity and mortality associated with bacteriemia in HIV-infected children in Africa.

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PIP: In Colombia, health workers obtained a nasopharyngeal wash from 103 infants aged less than 12 months hospitalized for acute lower respiratory infection (ALRI) at the General Hospital of Medellin during April 1994 to April 1995 so researchers could determine the frequency of ALRI caused by respiratory syncytial virus (RSV) in hospitalized children. Immunofluorescence detected RSV infection in 43 (41.7%) patients. The presence of the following signs and symptoms allowed a clinical diagnosis of a viral infection: rhinorrhea, prolonged expiration, expiratory wheezing, interstitial infiltrates, and hyperinflation on chest radiographs as well as negative tests for 3 or 4 acute phase reactants. The physicians initiated antibiotic therapy (for 1-3 days) in 12 cases (27.9%) based on acute phase reactant findings who actually had an RSV infection. When the physicians learned that the laboratory confirmed RSV infection, they stopped antibiotic therapy. Antibiotics were continued in 16 (37.2%) other RSV infected infants, all of whom were less than 2 months old, due to mixed pneumonia (viral and bacterial). 39.4% of RSV-infected children whose clinical findings strongly suggested RSV received no antibiotics. None of these children or other ALRI patients with a viral disease suffered complications. They required less hospitalization time--since no further diagnostic tests were needed--than ALRI patients with a bacterial infection. Admissions for both ALRI and RSV infection peaked during November to January. RSV incidence peaked in January (23.3%). The leading reasons for hospitalization were pneumonia and bronchiolitis. These findings show that RSV diagnosis is useful and it lessens the indiscriminate use of antibiotics.^ieng

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OBJECTIVE: To assess the impact of the introduction of new medical methods on the provision of therapeutic abortions at the Royal Infirmary Edinburgh. DESIGN: A review of the total number of abortions performed by medical and surgical means between 1989 and 1995 (inclusive); a prospective survey of the terminations of pregnancy (< or = 9 weeks of gestation) performed over the six-month period of January to June 1994; and a questionnaire of the reasons why women chosen a particular method. SETTING: Large teaching hospital in Scotland. SUBJECTS: One thousand and seven women seeking early pregnancy termination between January and June 1994. MAIN OUTCOME MEASURES: Proportion of pregnancies terminated by medical means; comparison of complete abortion rate, incidence of complications and morbidity following both medical and surgical methods (< or = 9 weeks of gestation); reasons for preference of the method of abortion. RESULTS: Since 1991 there has been a progressive increase in the number of medical abortions performed at the Royal Infirmary of Edinburgh, and by 1994 the majority of women (57%) seeking abortion at < or = 9 weeks chose a medical method. Women who chose medical abortion had more years at full-time education and were less likely to smoke (P < 0.04). Both medical and surgical methods were highly effective (> 96% complete abortion) with a low incidence of complications and morbidity. However, women who had chosen the medical method were less likely to receive antibiotics for suspected endometritis than their surgical counterparts (chi 2, P = 0.0001). CONCLUSIONS: If this trend towards medical methods in Edinburgh is repeated elsewhere, it will inevitably have an impact on gynaecological services by releasing staff and operating time for other purposes.

PIP: Data on 329 medical (drug-induced) abortions were compared with data on 215 vacuum aspiration abortions to determine the impact of new medical methods on therapeutic abortions. Medical abortions were performed at less than 9 weeks' gestation, while vacuum aspirations were performed at less than 12 weeks' gestation. All abortions were performed at the Royal Infirmary of Edinburgh, Scotland, during January-June 1994. The medical abortion method included 200 mg oral mifepristone and 0.5 mg gemeprost (vaginal pessary) or 600 mcg oral misoprostol 36-48 hours after administration of mifepristone. Since 1991, in terms of early pregnancy termination, the number of medical abortions has increased and the number of vacuum aspirations has decreased at the Royal Infirmary. Women who chose the medical method of pregnancy termination were more likely than those who chose vacuum aspiration not to smoke (60% vs. 51%), to have completed at least 19 years of formal education (18.5% vs. 13%), and to have had a previous induced abortion (32.5% vs. 24%) (p 0.04). Complete abortion rates were similar (96.4% for medical abortion and 97.9% for surgical abortion). Complications were rare for both methods. Women who had undergone vacuum aspiration were more likely to receive antibiotics for suspected endometritis than those who opted for medical abortion (9.6% vs. 1.2%; p = 0.0001). Postabortion bleeding was more likely to be perceived as heavier than normal menses in the medical abortion group than in the surgical abortion group (66% vs. 11%; p = 0.001). The two most important sources of information on abortion methods were medical staff (87%) and the information sheet (40%). The reduced demand for vacuum aspirations has released operating room time for other gynecological procedures. If the trend continues in Edinburgh and elsewhere, it will influence the provision of abortion services nationwide.

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PIP: Tuberculosis (TB) probably did not become a problem in sub-Saharan Africa (SSA) until around the 1850s. Poverty, inadequate TB control activities, and the HIV epidemic contribute to SSA having the world's highest TB case notification rate. HIV infection is responsible for a marked increase in TB in 15-45 year olds. In some parts of SSA, up to 70% of TB patients have HIV infection. A healthy immune system controls infection with Mycobacterium tuberculosis and prevents progression to TB but does not rid the body of dormant TB bacilli. HIV infection lowers immunity, therefore increasing susceptibility to TB. 25% of new TB cases each year in SSA are attributable to HIV infection. TB is the leading cause of death in HIV-infected individuals in SSA. The median CD4 count in HIV-infected adult TB patients is 200-250. Many persons in late stage HIV infection with TB are sputum smear negative. HIV-infected persons are more likely to have disseminated and extrapulmonary TB than HIV-negative persons. HIV infection sometimes reduces the skin test response to tuberculin. It is best to avoid anti-TB treatment as a diagnostic test for TB. Clinicians should not treat HIV-infected TB patients with thiacetazone but rather ethambutol. Thiacetazone can induce a severe, and sometimes fatal, skin reaction in HIV-infected persons. Many National TB Programs recommend ethambutol in place of streptomycin due to the problems associated with inadequate sterilization of needles and syringes and the pain associated with streptomycin injections in wasted HIV-infected TB patients. HIV-infected TB patients are more likely to die within 12 months after anti-TB treatment has begun than HIV-negative patients. Active TB may boost HIV replication. The World Health Organization does not yet recommend widespread isoniazid preventive therapy for HIV-positive persons in high TB prevalence countries.^ieng

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BACKGROUND: The outcomes of treatment of chronic suppurative otitis media (CSOM) are disappointing and uncertain, especially in developing countries. Because CSOM is the commonest cause of hearing impairment in children in these countries, an effective method of management that can be implemented on a wide scale is needed. We report a randomised, controlled trial of treatment of CSOM among children in Kenya; unaffected schoolchildren were taught to administer the interventions. METHODS: We enrolled 524 children with CSOM, aged 5-15 years, from 145 primary schools in Kiambu district of Kenya. The schools were randomly assigned treatments in clusters of five in a ratio of two to dry mopping alone (201 children), two to dry mopping with topical and systemic antibiotics and topical steroids (221 children), and one to no specific treatment (102 children). Schools were matched on factors thought to be related to their socioeconomic status. The primary outcome measures were resolution of otorrhoea and healing of tympanic membranes on otoscopy by 8, 12, and 16 weeks after induction. Absence of perforation was confirmed by tympanometry, and hearing levels were assessed by audiometry. 29 children were withdrawn from the trial because they took non-trial antibiotics. There was no evidence of differences in timing of withdrawals between the groups. FINDINGS: By the 16-week follow-up visit, otorrhoea had resolved in a weighted mean proportion of 51% (95% CI 42-59) of children who received dry mopping with antibiotics, compared with 22% (14-31) of those who received dry mopping alone and 22% (9-35) of controls. Similar differences were recorded by the 8-week and 12-week visits. The weighted mean proportions of children with healing of the tympanic membranes by 16 weeks were 15% (10-21) in the dry-mopping plus antibiotics group, 13% (5-20) in the dry-mopping alone group, and 13% (3-23) in the control group. The proportion with resolution in the dry-mopping alone group did not differ significantly from that in the control group at any time. Hearing thresholds were significantly better for children with no otorrhoea at 16 weeks than for those who had otorrhoea, and were also significantly better for those whose ears had healed than for those with otorrhoea at all times. INTERPRETATION: Our finding that dry mopping plus topical and systemic antibiotics is superior to dry mopping alone contrasts with that of the only previous community-based trial in a developing country, though it accords with findings of most other trials in developed countries. The potential role of antibiotics needs further investigation. Further, similar trials are needed to identify the most cost-effective and appropriate treatment regimen for CSOM in children in developing countries.

PIP: 524 children aged 5-15 years with chronic suppurative otitis media (CSOM) were enrolled in a study to determine the effectiveness of different treatment regimens. The subjects were from 145 primary schools in Kenya's Kiambu district. 201 children received dry mopping treatment, 221 received dry mopping with topical and systemic antibiotics and topical steroids, and 102 received no treatment. Participating schools were matched on factors thought to be related to their socioeconomic status. 29 children were withdrawn from the trial for taking non-trial antibiotics, with no evidence observed of differences in the timing of withdrawals between the two groups. At 16 weeks of follow-up, otorrhoea had resolved in a weighted mean proportion of 51% of children who received dry mopping with antibiotics, 22% of children who received dry mopping alone, and 22% of untreated children. Similar differences were observed at 8 and 12 weeks of follow-up. The weighted mean proportions of children with healing of the tympanic membranes by 16 weeks were 15% in the dry-mopping plus antibiotics group, 13% in the dry-mopping alone group, and 13% in the control group. Hearing thresholds were significantly better for children with no otorrhoea at 16 weeks than for those who had otorrhoea, and were also significantly better for those whose ears had healed than for those with otorrhoea at all times.

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