Jim Todd

Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.

CONTEXT Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment. OBJECTIVE To determine the most effective antibiotic treatment for invasive S. pyogenes infection in humans. DESIGN AND SETTING We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Childrens Hospital. PATIENTS Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections. MAIN OUTCOME MEASURE Lack of progression of disease (or improvement) after at least 24 h of treatment. RESULTS The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a beta-lactam antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14). CONCLUSIONS This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.

Biological and behavioural impact of an adolescent sexual health intervention in Tanzania : a community-randomized trial

Objective:The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania. Design:A community-randomized trial. Methods:Twenty communities were randomly allocated to receive either a specially designed programme of interventions (intervention group) or standard activities (comparison group). The intervention had four components: community activities; teacher-led, peer-assisted sexual health education in years 5–7 of primary school; training and supervision of health workers to provide ‘youth-friendly’ sexual health services; and peer condom social marketing. Impacts on HIV incidence, herpes simplex virus 2 (HSV2) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5, 6 or 7 of primary school. Results:The intervention had a significant impact on knowledge and reported attitudes, reported sexually transmitted infection symptoms, and several behavioural outcomes. Only five HIV seroconversions occurred in boys, whereas in girls the adjusted rate ratio (intervention versus comparison) was 0.75 [95% confidence interval (CI) 0.34, 1.66]. Overall HSV2 prevalences at follow-up were 11.9% in male and 21.1% in female participants, with adjusted prevalence ratios of 0.92 (CI 0.69, 1.22) and 1.05 (CI 0.83, 1.32), respectively. There was no consistent beneficial or adverse impact on other biological outcomes. The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002. Conclusion:The intervention substantially improved knowledge, reported attitudes and some reported sexual behaviours, especially in boys, but had no consistent impact on biological outcomes within the 3-year trial period.

Absolute Levels and Ratios of Proinflammatory and Anti-inflammatory Cytokine Production In Vitro Predict Clinical Immunity to Plasmodium falciparum Malaria

The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.

Syphilis in Pregnancy in Tanzania. I. Impact of Maternal Syphilis on Outcome of Pregnancy

To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.

A bit more truthful: the validity of adolescent sexual behaviour data collected in rural northern Tanzania using five methods.

Objective: To assess the validity of sexual behaviour data collected from African adolescents using five methods. Methods: 9280 Tanzanian adolescents participated in a biological marker and face to face questionnaire survey and 6079 in an assisted self-completion questionnaire survey; 74 participated in in-depth interviews and 56 person weeks of participant observation were conducted. Results: 38% of males and 59% of females reporting sexual activity did so in only one of the two 1998 questionnaires. Only 58% of males and 29% of females with biological markers consistently reported sexual activity in both questionnaires. Nine of 11 (82%) in-depth interview respondents who had had biological markers provided an invalid series of responses about sex in the survey and in-depth interview series. Only one of six female in-depth interview respondents with an STI reported sex in any of the four surveys, but five reported it in the in-depth interviews. Conclusion: In this low prevalence population, biological markers on their own revealed that a few adolescents had had sex, but in combination with in-depth interviews they may be useful in identifying risk factors for STIs. Self-reported sexual behaviour data were fraught with inconsistencies. In-depth interviews seem to be more effective than assisted self-completion questionnaires and face to face questionnaires in promoting honest responses among females with STIs. Participant observation was the most useful method for understanding the nature, complexity, and extent of sexual behaviour.

Overlap in the clinical features of pneumonia and malaria in African children

Pneumonia and malaria are common causes of childhood morbidity and mortality in many developing countries and simple guidelines have been proposed to facilitate their diagnosis by relatively unskilled health workers. We have studied children in The Gambia attending out-patient and under-five clinics with clinically suspected pneumonia (cough or difficulty in breathing and a raised respiratory rate) during periods of high or low malaria transmission. During a period of high malaria transmission, 33% of these children had radiological evidence of pneumonia (with or without malaria parasitaemia) compared to 38% who had malaria parasitaemia, no radiological evidence of pneumonia and no other obvious cause of fever. Corresponding figures during a period of low malaria transmission were 48% and 6% respectively. The clinical overlap between pneumonia and malaria has important implications for case management strategies and evaluation of disease-specific interventions in regions in which both pneumonia and malaria are prevalent.

Incidence of HIV infection in stable sexual partnerships: A retrospective cohort study of 1802 couples in Mwanza region Tanzania.

Objective: To describe the dynamics of HIV transmission in stable sexual partnerships in rural Tanzania. Design: Retrospective cohort study nested within community‐randomized trial to investigate the impact of a sexually transmitted disease treatment program. Methods: A cohort of 1802 couples was followed up for 2 years, with the HIV status of each couple assessed at baseline and follow‐up. Results: At baseline, 96.7% of couples were concordant‐negative, 0.9% were concordant‐positive, 1.2% were discordant with the male partner being HIV‐positive, and 1.2% were discordant with the female partner being HIV‐positive. Individuals living with an HIV‐positive partner were more likely to be HIV‐positive at baseline (women: odds ratio [OR] = 75.7, 95% confidence interval [CI]: 33.4‐172; men: OR = 62.4, CI: 28.5‐137). Seroincidence rates in discordant couples were 10 per 100 person‐years (py) and 5 per 100 py for women and men, respectively (rate ratio [RR] = 2.0, CI: 0.28‐22.1). In concordant‐negative couples, seroincidence rates were 0.17 per 100 py in women and 0.45 per 100 py in men (RR = 0.38, CI: 0.12‐1.04). Individuals living in discordant couples were at a greatly increased risk of infection compared with individuals in concordant‐negative couples (RR = 57.9, CI: 12.0‐244 for women; RR = 11.0, CI: 1.2‐47.5 for men). Conclusion: Men were more likely than women to introduce HIV infection in concordant‐negative partnerships. In discordant couples, incidence in HIV‐negative women was twice as high as in men. HIV‐negative individuals in discordant partnerships are at high risk of infection, and preventive interventions targeted at such individuals are urgently needed.

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 1. Design.

ObjectiveTo describe the rationale, and design of a randomized trial of the impact of improved services for the treatment of sexually transmitted diseases (STD) on the incidence of HIV infection in Mwanza Region, Tanzania. MethodsThe likely impact of improved STD treatment services on HIV incidence, and the need for empirical information on the effectiveness of this intervention strategy, are discussed. The rationale, and design of such an intervention programme in Mwanza Region, and of a community-randomized trial to measure the impact of the programme on HIV, and other STD, are presented. Problems in the design, and interpretation of the trial are reviewed. ResultsResults of the baseline survey of the cohort of over 12000 adults in 12 communities are presented in a companion paper. ConclusionThere is an urgent need for effective preventive measures against the HIV epidemic in sub-Saharan Africa, and other developing regions. Improved STD treatment has been promoted as a potentially effective strategy, but there is little empirical information on its impact. The trial in Mwanza Region is the first randomized study of this intervention, and should provide valuable data for health policy makers.

Antibody to Herpes Simplex Virus Type 2 as a Marker of Sexual Risk Behavior in Rural Tanzania

A serosurvey was conducted in a random sample of 259 women and 231 men in 12 rural communities in Mwanza Region, Tanzania, using a type-specific ELISA for Herpes simplex virus type 2 (HSV-2) infection. Seroprevalence rose steeply with age to approximately 75% in women >=25 years old and 60% in men >=30. After adjusting for age and residence, HSV-2 prevalence was higher in women who were married, in a polygamous marriage, Treponema pallidum hemagglutination assay (TPHA)-positive, had more lifetime sex partners, or who had not traveled. Prevalence was higher in men who were married, had lived elsewhere, had more lifetime partners, had used condoms, or were TPHA-positive. HSV-2 infection was significantly associated with recent history of genital ulcer. The association between HSV-2 infection and lifetime sex partners was strongest in those <25 years old in both sexes. This association supports the use of HSV-2 serology as a marker of risk behavior in this population, particularly among young people.

Cause-specific mortality rates in sub-Saharan Africa and Bangladesh.

OBJECTIVE To provide internationally comparable data on the frequencies of different causes of death. METHODS We analysed verbal autopsies obtained during 1999 -2002 from 12 demographic surveillance sites in sub-Saharan Africa and Bangladesh to find cause-specific and age-specific mortality rates. The cause-of-death codes used by the sites were harmonized to conform to the ICD-10 system, and summarized with the classification system of the Global Burden of Disease 2000 (Version 2). FINDINGS Causes of death in the African sites differ strongly from those in Bangladesh, where there is some evidence of a health transition from communicable to noncommunicable diseases, and little malaria. HIV dominates in causes of mortality in the South African sites, which contrast with those in highly malaria endemic sites elsewhere in sub-Saharan Africa (even in neighbouring Mozambique). The contributions of measles and diarrhoeal diseases to mortality in sub-Saharan Africa are lower than has been previously suggested, while malaria is of relatively greater importance. CONCLUSION The different patterns of mortality we identified may be a result of recent changes in the availability and effectiveness of health interventions against childhood cluster diseases.