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This study is a process evaluation of the school component of the adolescent sexual health programme MEMA kwa Vijana (MkV), which was implemented in 62 primary schools in rural Mwanza, Tanzania from 1999 to 2001. The MkV curriculum was a teacher-led and peer-assisted programme based on the Social Learning Theory. Process evaluation included observation of training sessions, monitoring and supervision, annual surveys of implementers, group discussions and 158 person-weeks of participant observation. Most teachers taught curriculum content well, but sometimes had difficulty adopting new teaching styles. Peer educators performed scripted dramas well, but were limited as informal educators and behavioural models. The intervention appeared successful in addressing some cognitions, e.g. knowledge of risks and benefits of behaviours, but not others, e.g. perceived susceptibility to risk. MkV shared the characteristics of other African school-based programmes found to be successful, and similarly found significant improvements in self-reported behaviour in surveys. However, a substantial proportion of MkV survey self-reports were inconsistent, there was no consistent impact on biological markers and extensive process evaluation found little impact on several key theoretical determinants of behaviour. Improvements in self-reported survey data alone may provide only a very limited-and perhaps invalid-indication of adolescent sexual health programme success.

Community-randomized trials in Mwanza, Tanzania, and Rakai and Masaka, Uganda, suggested that population characteristics were an important determinant of the impact of sexually transmitted infection (STI) treatment interventions on incidence of human immunodeficiency virus (HIV) infection. We performed simulation modeling of HIV and STI transmission, which confirmed that the low trial impact in Rakai and Masaka could be explained by low prevalences of curable STI resulting from lower-risk sexual behavior in Uganda. The mature HIV epidemics in Uganda, with most HIV transmission occurring outside core groups with high STI rates, also contributed to the low impact on HIV incidence. Simulated impact on HIV was much greater in Mwanza, although the observed impact was larger than predicted from STI reductions, suggesting that random error also may have played some role. Of proposed alternative explanations, increasing herpetic ulceration due to HIV-related immunosuppression contributed little to the diminishing impact of antibiotic treatment during the Ugandan epidemics. The strategy of STI treatment also was unimportant, since syndromic treatment and annual mass treatment showed similar effectiveness in simulations of each trial population. In conclusion, lower-risk behavior and the mature HIV epidemic explain the limited impact of STI treatment on HIV incidence in Uganda in the 1990s. In populations with high-risk sexual behavior and high STI rates, STIs treatment interventions may contribute substantially to prevention of HIV infection.

Sexually transmitted diseases (STDs) are cofactors for human immunodeficiency virus (HIV) transmission, but the specific role of herpes simplex virus type 2 (HSV-2) is unclear. This study aimed to examine the in vivo relationships between HSV-2 and HIV-1 in 300 women in Bangui, Central African Republic. Sera were tested for syphilis, HIV-1, HSV-2 antibody, and levels of vitamins A and E. Genital specimens were tested for other STDs. HSV-2 DNA and HIV-1 RNA were quantified in cervicovaginal lavage. The prevalences of HSV-2 antibody (91% vs. 78%, P=.02), HSV-2 shedding (43% vs. 22%, P=. 003), and levels of HSV-2 DNA (P=.01) were all significantly higher among HIV-1-seropositive than among HIV-1-seronegative women. There was a significant correlation between genital HIV-1 RNA and HSV-2 DNA levels (P=.02) among the 23 women who were shedding HSV-2 DNA. If confirmed, such associations highlight the urgent need for HSV-2 control measures in populations at high risk of both infections.

Background: Cluster-randomized trials, in which health interventions are allocated randomly to intact clusters or communities rather than to individual subjects, are increasingly being used to evaluate disease control strategies both in industrialized and in developing countries. Sample size computations for such trials need to take into account between-cluster variation, but field epidemiologists find it difficult to obtain simple guidance on such procedures., Methods: In this paper, we provide simple formulae for sample size determination for both unmatched and pair-matched trials. Outcomes considered include rates per person-year, proportions and means. For simplicity, formulae are expressed in terms of the coefficient of variation (SD/mean) of cluster rates, proportions or means. Guidance is also given on the estimation of this value, with or without the use of prior data on between-cluster variation., Case Studies: The methods are illustrated using two case studies: an unmatched trial of the impact of impregnated bednets on child mortality in Kenya, and a pair-matched trial of improved sexually-transmitted disease (STD) treatment services for HIV prevention in Tanzania.

Several malariometric studies have examined the impact on human-vector contact of house construction, demographics, bed net and insect repellent use. However, few studies have documented the significance of these proximate determinants on the risks of clinical disease. We undertook a matched case-control study of the risks of both mild clinical malaria and severe life-threatening malaria according to a range of putative factors which would influence the frequency of child-vector encounters in Kilifi district on the Kenyan coast. Among 394 severe disease cases, 380 age-matched mild disease cases, and their respective location and age-matched community controls, we were unable to demonstrate any statistically significant effect upon disease outcome of house construction, presence of domestic animals, or bed net use. Higher population density within a 250 m radius of the homes conferred significant protection from the risks of developing severe malaria compared to community controls. The risks of developing severe malaria compared to the community controls and the transition from mild to severe disease were statistically significantly lower in those who reported use of mosquito coils, local repellents or aerosol insecticides. We concluded that it is likely that the impact of household features on disease outcome is dependent upon both the density of infecting mosquitoes and acquired immunity within a given locality.

Background: Although malaria is known to be a major cause of child mortality and morbidity throughout sub-Saharan Africa there are few detailed studies of malaria mortality rates and incidence of severe malarial disease in defined communities. We have studied the geographical pattern of admissions to hospital with severe malaria and the stability of this pattern over time in Kilifi District on the Kenyan Coast., Methods: Over a 2-year period all children under 5 years of age with severe malaria admitted to the district hospital and living in a rural study population of about 50,000 people were identified. Annual censuses were carried out in the study area, and all households were mapped using a hand-held satellite navigation system. The resulting databases were linked using a geographical information system (GIS)., Results: Using methods originally developed for the study of the geographical distribution of childhood leukaemia we assessed the spatial pattern of hospital admission rates for severe malaria. As expected, admission rates were significantly higher in children with easier access to the hospital. For example, those living more than 25 km from the hospital had admission rates which were about one-fifth of those for children living within 5 km of the hospital. Those living more than 2.5 km from the nearest road had admission rates that were about half of those for children living within 0.5 km of a road. We also investigated short-term local fluctuations in severe malaria and found evidence of space-time clustering of severe malaria., Conclusions: Hospital admission rates for severe malaria are higher in households with better access to hospital than in those further away. The finding of space-time clusters of severe malaria suggests that it would be of value to conduct case-control studies of environmental, genetic and human behavioural factors involved in the aetiology of the disease.

Background: Unprotected heterosexual contact in the presence of other sexually transmitted diseases (STD) enhances the probability of HIV transmission. The objective of this study was to estimate the proportion of HIV infections attributable to STD in rural Uganda., Methods: Simulation modelling scenarios of the transmission dynamics of HIV infection and of ulcerative and non-ulcerative STD were employed to address this objective, drawing on data from a specific rural population cohort of 10,000 in south-west Uganda., Results: In simulations of the initial 10-year period of the HIV epidemic (1980-1990), over 90% of HIV infections were attributed to STD. Even given conservative assumptions about the prevalence of STD and about their enhancing effects on HIV transmission, STD played a critical role in the rapid and extensive spread of HIV infection. The role of STD decreased with progression of the HIV epidemic., Conclusions: In developing countries, control of the spread of HIV infection may benefit substantially from successful STD intervention programmes, and particularly in areas where HIV infection is not already well established.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

A cross-sectional study to estimate the prevalence of latent tuberculosis (TB) in a group of Zambians at high risk of human immunodeficiency virus type 1 (HIV-1) infection and to examine the effect of HIV-1 infection on the tuberculin response was conducted in the University Teaching Hospital in Lusaka, Zambia during July to September 1990. Patients were selected from those presenting to the out-patient clinic for first referral with either sexually transmitted or skin disease. 268 adults were included in the study; 158 (59%; 95% confidence interval [CI] = 53-65%) were HIV-1 antibody positive. Of 82 HIV-1 negative participants who returned for Mantoux skin test reading, 51 (62%; 95% CI = 57-67%) had a positive test reaction (diameter > or = 10 mm) after receiving 2 units of RT-23 tuberculin. Of 106 HIV-1 positive participants who returned, only 32 (30%; 95% CI = 26-34%) had a diameter > or = 10 mm. Nine (28%) of the HIV-1 positive and Mantoux positive participants had large reactions > or = 30 mm, compared to 4 (8%) of the HIV-1 negative, Mantoux positive participants (P = 0.03). Results in the HIV-1 negative group indicated a prevalence of latent TB of 62% in this population. HIV-1 infection was associated with a much higher frequency of negative response to tuberculin and with a few large skin test responses. Thus, in populations where HIV seropositivity is high, Mantoux skin tests cannot be used to assess those with latent TB who might benefit from chemoprophylaxis.

Background: The verbal autopsy appears to be an attractive technique for the assessment of causes of adult death in settings where the proportion of people who die while under medical care is low. Verbal autopsies have been used extensively to assess causes of childhood deaths. The existing experience in verbal autopsies for adult deaths is limited mainly to maternal deaths. This paper aims to highlight the critical issues in verbal autopsies to assess causes of adult death which need further research., Methods: This paper reviews the methods of verbal autopsy used in 35 published studies and discusses issues in the development of verbal autopsies, including mortality classification, design of questionnaires, interviewers, respondents, recall periods, procedures for deriving a diagnosis and the recording of single versus multiple causes of death. It also discusses issues in the validation of verbal autopsies, including the choice of reference diagnosis and the required sample size., Results: The methodological approaches used in verbal autopsy studies have varied widely. Very few studies of the validity of verbal autopsies have been conducted. In these studies, the reported sensitivity and specificity varied widely between different causes of death and between studies., Conclusions: The information available is inadequate to draw firm conclusions on preferred methodological approaches for verbal autopsies for adult deaths. Before these tools are used more widely for adult deaths, further research is required to compare alternative methods and to evaluate the validity of this tool in a range of settings.

The performance of antibody detection for the diagnosis of schistosomiasis has been evaluated in Kenya. Approximately 1500 blood samples from 3 areas with endemic schistosomiasis (Schistosoma mansoni only, S. haematobium only, and a mixed infection area), and from a non-endemic control area, were tested for their antibody reactivity in an enzyme-linked immunosorbent assay (ELISA). The results were compared with infection status determined by parasitological examination. Two test antigens were used: unfractionated S. mansoni egg homogenate (SEA), and CEF6, a previously described, partially purified fraction of SEA containing 2 cationic antigens. The antigens prepared from eggs of Kenya and Puerto Rico S. mansoni isolates gave very similar results. Bloods from patients with S. haematobium infection cross-reacted significantly with the two S. mansoni antigen preparations, but reactivity against CEF6 appeared more specifically indicative of S. mansoni infection. Of 254 blood samples from schoolchildren in the non-endemic area, 100% gave ELISA optical density readings at 492 nm (OD492) < 0.20 against SEA, and 98% were < 0.20 against CEF6. With 887 blood samples from subjects of all ages in the area endemic for S. mansoni alone, using an ELISA OD492 cut-off point of 0.20, SEA and CEF6 had sensitivities of 94% and 97% respectively, and specificities of 64% and 59% respectively. Increasing the OD492 cut-off value reduced the sensitivity and increased the specificity of both test antigens. Specificity of both antigens was poor with samples from 234 children in an area endemic for both S. mansoni and S. haematobium (< 20% for both antigens at an OD492 cut-off value of 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroids are beneficial in the treatment of some forms of tuberculosis, but their role in TB affecting HIV-positive patients is not clear. During a cohort study of tuberculosis patients in Lusaka, Zambia, prednisolone was prescribed for specific indications. Six of 47 (13 per cent) of patients who received prednisolone early in treatment developed herpes zoster, compared with 2 of 118 (2 per cent) of those who did not. Three patients who received prednisolone developed Kaposi's sarcoma, compared with none who did not. At 2 months patients who had received prednisolone showed a greater improvement in generalized lymphadenopathy and cough. Controlled studies of the risks and benefits of administration of corticosteroids to HIV-positive TB patients are urgently needed.

Mortality and morbidity from malaria were measured in children for a one-year period in a rural area of The Gambia 3-4 years after the introduction of a primary health care programme into some villages in the study area. Among children resident in primary health care villages who received treatment for febrile illnesses from a village health worker resident in their village there was no reduction in overall mortality or in morbidity from malaria compared with levels found in villages without a primary health care worker. However, among children aged 3-59 months who received malaria chemoprophylaxis from a village health worker in addition to treatment there was a 49% reduction in mortality and a 73% reduction in attacks of clinical malaria. The level of protection against malaria achieved by chemoprophylaxis given by village health workers 3-4 years after the chemoprophylaxis programme was started was as high as that obtained shortly after the introduction of the primary health care programme.

Cross-sectional and longitudinal studies were performed in a rural population living in The Gambia to examine the relationship between several in vitro assays of the host immune response to asexual stages of Plasmodium falciparum and protection from malaria in vivo. Assays included an enzyme-linked immunosorbent assay for antibodies to schizont antigens; an indirect immunofluorescence assay for total antiblood-stage antibodies; an immunofluorescence assay on glutaraldehyde-fixed parasites to detect antibodies to antigen Pf 155; an assay for serum inhibition of red blood cell invasion; a micro-agglutination assay to detect antibodies to neo-antigens on the surface of infected red blood cells; and an assay using polymorphonuclear leucocytes to detect antibodies capable of opsonizing schizont infected red blood cells. There were marked differences in the age-related pattern of response for different assays performed on sera obtained at a cross-sectional survey of 280 individuals. Examination of the correlation between the various immune responses and malariometric indices at the population level and at the individual level provided no evidence that any of the in vitro assays were related to protective immunity. The relationship between in vitro measurements of the anti-malarial immune response and protection from clinical episodes of malaria was examined in a group of 134 children aged 11 years and under who were monitored weekly throughout an entire malaria transmission season. The only immune factor to show a consistent protective effect against clinical malaria was the titre of antibodies to neo-antigens on the infected erythrocyte surface (P = 0.01). The same longitudinal techniques were used to examine the effect of two non-immunological factors, sickle cell trait and mosquito net usage, both of which showed significant protection against clinical episodes and malaria.

The relationship between reinfection with Schistosoma haematobium and immunological parameters was studied in a group of Gambian children aged from 8 to 13 years. Each individual's exposure to infection was assessed from observations of water contact, cercarial densities and infected snail densities at water contact sites. Eosinophil counts were made and responses to egg antigen (SEA) and adult worm antigen (WWH) measured by ELISA. Low levels of reinfection were associated with a high eosinophil count, high levels of antibodies against WWH and SEA, increased age and low exposure. In a multiple regression analysis of the association of reinfection with eosinophil count, antibody levels, exposure, age and sex, the effects of eosinophil count and exposure were still very significant after allowing for all the other variables. The effects of the antibody levels were close to significance after allowance for exposure and eosinophil count (for WWH: P = 0.09; for SEA: P = 0.07), although the evidence was less clear after additional allowance was made for age and sex. The ability of sera from the children to recognize different parasite antigens was also examined by immunoprecipitation of labelled schistosomulum surface, WWH, SEA and S. haematobium adult worm mRNA in vitro translation products. Schistosomulum surface antigens were recognized by all the sera and there was little variation in this response. There was more variation in their responses to SEA and WWH and a marked heterogeneity in the response to in vitro translation products. However, the pattern of antigen recognition appeared unrelated to susceptibility to reinfection.

The process of reinfection after treatment was studied in a cohort of subjects in a focus of intense Schistosoma haematobium infection. Detailed observations were made at water contact sites of cercarial densities and of water contact by members of the cohort. Individual values of a cumulative index of exposure to infection were calculated using these observations and assumptions which were made about the effect of different water contact activities on the entry of cercariae into the skin. Among groups of subjects with an apparently similar intensity of exposure to infection, reinfection tended to be much heavier in children under 10 years of age than in 10 to 14-year-olds, while only light infections were found in the few adults who became reinfected. This trend for reinfection to decrease with increasing age, after an allowance for variation in exposure, was highly significant (p less than 0.001). These observations suggest that subjects in this area slowly acquire an increasing degree of immunity to the acquisition of S. haematobium infection which is effective in the absence of a mature egg laying infection.

Diarrhoeal morbidity was studied during a 15-week period of the rainy season in 244 children aged 6 to 35 months in an urban Gambian community. The average prevalence of diarrhoea was 12.0% and the mean number of episodes per child varied between 2.4 and 2.9 depending on the definition of an episode. The number of chronic episodes lasting 14 d or more was tripled when 7 rather than one diarrhoea-free days were required to define a new episode. Neither prevalence nor the number of episodes varied significantly with age or sex. There was little association between the social and environmental characteristics of the children and diarrhoeal morbidity. The implications of using differing measures of diarrhoeal morbidity are discussed.

Bacterial beta-glucuronidase (gus) and neomycin phosphotransferase (neo) genes were introduced into coat protein replacement vectors based on DNA A of tomato golden mosaic virus (TGMV). Recombinant gus and neo vectors up to 1.1 kbp larger than DNA A were shown to replicate stably in transgenic plants containing partial dimers (master copies) of the vectors integrated into their chromosomal DNA in the absence of DNA B. Beta-glucuronidase and neomycin phosphotransferase activities in independently transformed plants were proportional to the copy number of the double-stranded forms of the vector. Deletion analysis has shown that an essential part of the TGMV coat protein promoter, including a TATA box, lies within 76 nt upstream of the initiation codon of the gene. An increase in expression of a neo gene was obtained by replacing this 76 nt sequence by an 800 nt sequence containing a cauliflower mosaic virus 35S RNA promoter with no effect on the ability of the vector to replicate or on its stability in transgenic plants. Systemic infection of plants by agroinoculation with TGMV vectors larger than DNA A in the presence of DNA B resulted in deletions in the vector DNA in some, but not all, plants. Possible reasons for vector instability in systemically infected plants, and vector stability in transgenic plants containing master copies of the vector, are discussed.

A prospective study of the relationship between anthropometric indices and subsequent morbidity was conducted during 2 seasons in young children in an urban Gambian community. Children with low height-for-age at the beginning of the rainy season had a significantly higher prevalence of diarrhoea and fever during the next 4 months, even after controlling for the possible confounding effects of a range of social, economic and environmental factors. The association was weaker in the dry season. This indicates that the increased prevalence of symptoms among stunted children is not solely attributable to environmental factors, and suggests that impaired growth is associated with impaired host response to infection.

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.

A survey for leptospiral antibodies was made of 1,375 persons in northern Trinidad between mid-1977 and mid-1978. The subjects were employees in seven occupational categories thought to entail a high risk of exposure to leptospires, and members of the general population of three rural and two urban communities. They were questioned inter alia about their leisure and occupational activities, household water supply and effluent, and contact with animals. Leptospiral infection was found to be widespread in the general population but not primarily associated with employment. Among the occupational groups the highest prevalence of antibodies was found in sugar-cane workers (45% infected), while among the communities prevalence was highest in the rural village of Cacandee (37%) and lowest in Woodbrook (Port-of-Spain) (5%). Keeping cattle, hunting and walking barefoot in the countryside were significantly associated with leptospiral serology. Over-all, serogroups Icterohaemorrhagiae and Autumnalis each accounted for about 25% of the seropositives in the general population. Among the occupational groups Autumnalis was the most commonly found (36%). It accounted for 42% of the seropositive sugar-cane workers and 57% of the seropositive rice farmers.

A group of 479 children born in a peri-urban West African community during a two-year period was studied in an attempt to identify social and environmental factors associated with the risk of dying in early childhood. Comparison of the characteristics of the 17 children that had died with those of the 462 survivors suggested an increased risk among the children of self-employed women, and among children living in compounds in which animals were kept. Of 500 mothers who were studied (including some whose children were born elsewhere), 145 had experienced at least one child death. When these 145 women were compared with the remaining 355, several factors related to living conditions, maternal education and health knowledge were found to be associated with the risk of child mortality.

Tomato golden mosaic geminivirus has a genome of two single-stranded (ss) DNA components, A and B. An almost identical 'common' region in DNA A and DNA B is thought to contain sequence elements controlling replication and transcription. Hence investigation of sequences important for DNA replication by in vitro mutagenesis is complicated by possible effects on the transcription of genes for replication proteins. To overcome this problem, transgenic plants expressing open reading frames (ORFs) of DNA A from an enhanced cauliflower mosaic virus 35S RNA promoter were constructed and tested for their ability to support the replication of DNA B and DNA B mutants. The results show that plants transgenic for ORF AL1 are able to support the replication of the double-stranded (ds) forms of DNA B, but that ORF AL2 is required in addition to produce ssDNA B. ORFs AL3, BL1 or BR1 were not required for replication of ds or ssDNA B. To the best of our knowledge this is the first time that essential replication proteins of a geminivirus have been expressed constitutively from a plant genome without giving rise to replicating DNA A molecules, thereby allowing DNA B to replicate alone. Such transgenic plants should enable not only the mutational analysis of sequence elements within the replication origin region, but also the construction of a new generation of vectors for gene amplification in plants, based on a minimal virus replicon.

The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge.