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Background: Few studies have evaluated the acceptability of self-collected vaginal swabs among young women in sub-Saharan Africa, including in school settings. We evaluated the acceptability of 2 conditions for the self-collection of swabs in secondary schools in Entebbe, Uganda., Methods: Assenting girls with parental consent from 3 secondary schools were provided instructions for sampling, and randomly allocated to self-collection of vaginal swabs with or without nurse assistance to help with correct placement of the swab. Swabs were tested for bacterial vaginosis by Gram stain. Participants were followed up after 1 to 2 days and 1 to 2 weeks and invited for a qualitative interview., Results: Overall 96 girls were enrolled (median age, 16 years; interquartile range, 15-17 years). At the first follow-up visit, participants in both arms reported that instructions for sample collection were easy to understand, and they felt comfortable with self-collection. Girls in the nurse assistance arm reported feeling less relaxed (27% vs. 50%, P = 0.02) than those in the arm without nurse assistance, but more confident that they collected the sample correctly (96% vs. 83%, P = 0.04). About half (47%) of participants agreed that self-sampling was painful, but almost all (94%) would participate in a similar study again. Qualitative data showed that participants preferred self-collection without nurse assistance to preserve privacy. Bacterial vaginosis prevalence was 14% (95% confidence interval, 8-22)., Conclusions: In this setting, self-collection of vaginal swabs in secondary schools was acceptable and feasible, and girls preferred self-collection without nurse assistance. Self-collection of swabs is an important tool for the detection, treatment and control of reproductive tract infections in girls and young women.

Background: Besides use of insecticide-treated mosquito nets (ITNs) and indoor residual spraying (IRS), other complimentary measures including suitable housing structures, and environmental management that reduce breeding of malaria vectors, can be implemented at households to prevent the disease. However, most studies on malaria prevention have focused mainly on ITNs and IRS. The aim of this study was therefore to assess malaria prevention practices beyond ITNs and IRS, and associated environmental risk factors including housing structure in rural Wakiso district, Uganda., Methods: A clustered cross-sectional survey was conducted among 727 households in Wakiso district. Data were collected using an interviewer-administered questionnaire and observational checklist. The questionnaire assessed participants' household practices on malaria prevention, whereas the checklist recorded environmental risk factors for malaria transmission, and structural condition of houses. Poisson regression modeling was used to identify factors associated with use of mosquito nets by households., Results: Of the 727 households, 471 (64.8%) owned at least one mosquito net. Use of mosquito nets by households was higher with increasing education level of participants-primary (aPR = 1.27 [95% CI: 1.00-1.60]), secondary (ordinary level) (aPR = 1.47 [95% CI: 1.16-1.85]) and advanced level / tertiary (aPR = 1.55 [95% CI: 1.19-2.01]), and higher household income (aPR = 1.09 [95% CI: 1.00-1.20]). Additionally, participants who were not employed were less likely to have mosquito nets used in their households (aPR = 0.83 [95% CI: 0.70-0.98]). Houses that had undergone IRS in the previous 12 months were 42 (5.8%), while 220 (43.2%) households closed their windows before 6.00 pm. Environmental risk factors found at households included presence of vessels that could potentially hold water for mosquito breeding 414 (56.9%), and stagnant water in compounds 144 (19.8%). Several structural deficiencies on houses that could promote entry of mosquitoes were found such as lack of screening in ventilators 645 (94.7%), and external doors not fitting perfectly into walls hence potential for mosquito entry 305 (42.0%)., Conclusion: There is need to increase coverage and utilisation of ITNs and IRS for malaria prevention in Wakiso district, Uganda. In addition, other malaria prevention strategies such as environmental management, and improving structural condition of houses are required to strengthen existing malaria prevention approaches., Competing Interests: The authors have declared that no competing interests exist.

Background: Management of menstruation can present substantial challenges to girls in low-income settings. In preparation for a menstrual hygiene intervention to reduce school absenteeism in Uganda, this study aimed to investigate menstruation management practices, barriers and facilitators, and the influence of menstruation on school absenteeism among secondary school students in a peri-urban district of Uganda., Methods: Qualitative and quantitative studies were conducted among consenting girls and boys aged 14-17 years in four secondary schools in Entebbe sub-District, Uganda. Methods included group and in-depth interviews with students, a quantitative cross-sectional questionnaire, a prospectively self-completed menstrual diary, key informant interviews with policy makers, and observations of school water, sanitation and hygiene facilities. Multiple logistic regression was used to assess factors associated with school absenteeism during the most recent menstrual period., Results: Girls reported substantial embarrassment and fear of teasing related to menstruation in the qualitative interviews, and said that this, together with menstrual pain and lack of effective materials for menstrual hygiene management, led to school absenteeism. All policy makers interviewed reported poverty and menstruation as the key factors associated with school attendance. The 352 girls with questionnaire data had a median age of 16 (inter-quartile range (IQR) = 15,16) years, with median age at menarche of 13 (IQR = 13,14) years. Of these, 64 girls (18.7%) reported having stained their clothes and 69 (19.7%) reported missing at least 1 day of school, during their most recent period. Missing school during the most recent period was associated with physical symptoms (headache (odds ratio (OR) = 2.15, 95%CI:1.20, 3.86), stomach pain (OR = 1.89, 95%CI:0.89, 4.04), back pain (OR = 1.75, 95%CI:0.97, 3.14), and with changing protection 4 or more times per 24 h period (OR = 2.08, 95%CI:1.06, 4.10). In the diary sub-study among 40 girls, school absence was reported on 28% of period-days, compared with 7% of non-period days (adjusted odds ratio = 5.99, 95%CI:4.4, 8.2; p < 0.001)., Conclusion: In this peri-urban Ugandan population, menstruation was strongly associated with school attendance. Evaluation of a menstrual management intervention that address both psychosocial (e.g. self-confidence, attitudes) and physical (e.g. management of pain, use of adequate menstrual hygiene materials, improved water and sanitation facilities) aspects of menstruation are needed.

The Ugandan government is committed to scaling-up proven HIV prevention strategies including safe male circumcision, and innovative strategies are needed to increase circumcision uptake. The aim of this study was to assess the acceptability and feasibility of implementing a soccer-based intervention ("Make The Cut") among schoolboys in a peri-urban district of Uganda. The intervention was led by trained, recently circumcised "coaches" who facilitated a 60-minute session delivered in schools, including an interactive penalty shoot-out game using metaphors for HIV prevention, sharing of the coaches' circumcision story, group discussion and ongoing engagement from the coach to facilitate linkage to male circumcision. The study took place in four secondary schools in Entebbe sub-district, Uganda. Acceptability of safe male circumcision was assessed through a cross-sectional quantitative survey. The feasibility of implementing the intervention was assessed by piloting the intervention in one school, modifying it, and implementing the modified version in a second school. Perceptions of the intervention were assessed with in-depth interviews with participants. Of the 210 boys in the cross-sectional survey, 59% reported being circumcised. Findings showed high levels of knowledge and generally favourable perceptions of circumcision. The initial implementation of Make The Cut resulted in 6/58 uncircumcised boys (10.3%) becoming circumcised. Changes made included increasing engagement with parents and improved liaison with schools regarding the timing of the intervention. Following this, uptake improved to 18/69 (26.1%) in the second school. In-depth interviews highlighted the important role of family and peer support and the coach in facilitating the decision to circumcise. This study showed that the modified Make The Cut intervention may be effective to increase uptake of safe male circumcision in this population. However, the intervention is time-intensive, and further work is needed to assess the cost-effectiveness of the intervention conducted at scale.

Background: The malaria burden in sub-Saharan Africa (SSA) has fallen substantially. Nevertheless, malaria remains a serious health concern, and Uganda ranks third in SSA in total malaria burden. Epidemiological studies of adult malaria in Uganda are scarce and little is known about rates of malaria in non-pregnant adult women. This pilot study assessed malaria prevalence among adult women from Wakiso district, historically a highly malaria endemic region., Methods: Adult women using public health services were screened for malaria, HIV and pregnancy. A physician-selected subset of women presenting to the Outpatient Department of Entebbe General Hospital (EGH) with current fever (axillary temperature ≥37.5 °C) or self-reporting fever during the previous 24 h, and a positive thick smear for malaria in the EGH laboratory were enrolled (n = 86). Women who self-identified as pregnant or HIV-positive were excluded from screening. Malaria infection was then assessed using HRP2/pLDH rapid diagnostic tests (RDTs) in all participants. Repeat microscopy and PCR were performed at a research laboratory for a subset of participants. In addition, 104 women without a history of fever were assessed for asymptomatic parasitaemia using RDT, and a subset of these women screened for parasitaemia using microscopy (40 women) and PCR (40 women)., Results: Of 86 women diagnosed with malaria by EGH, only two (2.3%) had malaria confirmed using RDT, subsequently identified as a Plasmodium falciparum infection by research microscopy and PCR. Subset analysis of hospital diagnosed RDT-negative participants detected one sub-microscopic infection with Plasmodium ovale. Compared to RDT, sensitivity, specificity and PPV of hospital microscopy were 100% (CI 19.8-100), 0% (CI 0-5.32) and 2.33% (CI 0.403-8.94) respectively. Compared to PCR, sensitivity, specificity and PPV of hospital microscopy were 100% (CI 31.0-100), 0% (CI 0-34.5) and 23.1% (CI 6.16-54.0), respectively. No malaria was detected among asymptomatic women using RDT, research microscopy or PCR., Conclusions: Malaria prevalence among adult women appears to be low in Wakiso, but is masked by high rates of malaria overdiagnosis. More accurate malaria testing is urgently needed in public hospitals in this region to identify true causes of febrile illness and reduce unnecessary provision of anti-malarial therapy.

Background: The World Health Organization recommends use of multiple approaches to control malaria. The integrated approach to malaria prevention advocates the use of several malaria prevention methods in a holistic manner. This study assessed perceptions and practices on integrated malaria prevention in Wakiso district, Uganda., Methods: A clustered cross-sectional survey was conducted among 727 households from 29 villages using both quantitative and qualitative methods. Assessment was done on awareness of various malaria prevention methods, potential for use of the methods in a holistic manner, and reasons for dislike of certain methods. Households were classified as using integrated malaria prevention if they used at least two methods. Logistic regression was used to test for factors associated with the use of integrated malaria prevention while adjusting for clustering within villages., Results: Participants knew of the various malaria prevention methods in the integrated approach including use of insecticide treated nets (97.5%), removing mosquito breeding sites (89.1%), clearing overgrown vegetation near houses (97.9%), and closing windows and doors early in the evenings (96.4%). If trained, most participants (68.6%) would use all the suggested malaria prevention methods of the integrated approach. Among those who would not use all methods, the main reasons given were there being too many (70.2%) and cost (32.0%). Only 33.0% households were using the integrated approach to prevent malaria. Use of integrated malaria prevention by households was associated with reading newspapers (AOR 0.34; 95% CI 0.22 -0.53) and ownership of a motorcycle/car (AOR 1.75; 95% CI 1.03 - 2.98)., Conclusion: Although knowledge of malaria prevention methods was high and perceptions on the integrated approach promising, practices on integrated malaria prevention was relatively low. The use of the integrated approach can be improved by promoting use of multiple malaria prevention methods through various communication channels such as mass media.

Objectives: To evaluate and determine the value of monitoring models developed by the Mahidol Oxford Tropical Research Unit and the East African Consortium for Clinical Research, consider how this can be measured and explore monitors' and investigators' experiences of and views about the nature, purpose and practice of monitoring., Research Design: A case study approach was used within the context of participatory action research because one of the aims was to guide and improve practice. 34 interviews, five focus groups and observations of monitoring practice were conducted., Setting and Participants: Fieldwork occurred in the places where the monitoring models are coordinated and applied in Thailand, Cambodia, Uganda and Kenya. Participants included those coordinating the monitoring schemes, monitors, senior investigators and research staff., Analysis: Transcribed textual data from field notes, interviews and focus groups was imported into a qualitative data software program (NVIVO V. 10) and analysed inductively and thematically by a qualitative researcher. The initial coding framework was reviewed internally and two main categories emerged from the subsequent interrogation of the data., Results: The categories that were identified related to the conceptual framing and nature of monitoring, and the practice of monitoring, including relational factors. Particular emphasis was given to the value of a scientific and cooperative style of monitoring as a means of enhancing data quality, trust and transparency. In terms of practice the primary purpose of monitoring was defined as improving the conduct of health research and increasing the capacity of researchers and trial sites., Conclusions: The models studied utilise internal and network wide expertise to improve the ethics and quality of clinical research. They demonstrate how monitoring can be a scientific and constructive exercise rather than a threatening process. The value of cooperative relations needs to be given more emphasis in monitoring activities, which seek to ensure that research protects human rights and produces reliable data.

Objective: To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting., Methods: A cohort of HIV-1-infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6-monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 °C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random-effects Poisson regression for the effect of HAART at the population level., Results: A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person-years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrollment (CD4+ T-cell counts and WHO stage) and time since enrollment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART., Conclusions: HAART availability in a resource-poor setting substantially reduced the trends of bacteraemia among HIV-infected adults. This may further impact on future morbidity and healthcare costs of HIV-infected people., (© 2011 Blackwell Publishing Ltd.)

The development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01&#95;AE, that could identify top-ranking samples with 50% inhibitory concentration (IC(50)) neutralization titers of >or=100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC(50) titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.

Objective: To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility., Methods: Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients' characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel-Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole., Results: A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g/dl and median CD4+ 131 cells/microl) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g/dl and median CD4+ 130 cells/microl) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12-0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45-0.94)., Conclusion: These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.

Background: Cotrimoxazole is recommended for prevention of opportunistic infections in symptomatic HIV patients in sub-Saharan Africa., Methods: We examined the feasibility and effectiveness of daily cotrimoxazole prophylaxis in a well-established cohort of HIV-infected adults attending clinics in Entebbe, Uganda. We compared mortality and morbidity rates for 12 months before and after the introduction of cotrimoxazole., Results: Between August 2000 and February 2002, 94% of cohort members were enrolled onto cotrimoxazole prophylaxis. Revisits were scheduled every 4 weeks to replenish pills; patients attended 61% of revisits. The main reasons for nonenrollment and defaulting were lack of transport, being away from home, and sickness. Drug-related adverse events, mainly itching and rash, were seen in 4% of participants. Although bacterial resistance rate to cotrimoxazole was high, the adjusted mortality incidence rate ratio was significantly reduced after the introduction of cotrimoxazole (0.76; 95% confidence interval, 0.60-0.96; P = 0.020). Overall febrile events and morbidity rates were unchanged after the introduction of cotrimoxazole, but the incidence of malaria was reduced (incidence rate ratio, 0.31; 95% confidence interval, 0.13-0.72)., Conclusions: Cotrimoxazole prophylaxis can be introduced into routine HIV clinic activities and is associated with a reduction in overall mortality and malaria morbidity, even in an area with high bacterial resistance. These results reinforce the need for large-scale provision of cotrimoxazole prophylaxis for all HIV-positive patients in developing countries.

Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans.

We investigated the immunogenicity of a 7-valent conjugate pneumococcal vaccine (CPV) in human immunodeficiency virus-infected Ugandan adults and measured the effect of past pneumococcal polysaccharide vaccine (PPV) receipt given as part of a controlled trial. Two doses of CPV, 4 weeks apart, were given to 54 past PPV recipients and 55 past placebo recipients (84% female; median CD4 cell count, 251 cells/ microL [range, 1-936 cells/ microL]). Postvaccination anticapsular immunoglobulin G (IgG) concentrations were directly correlated with CD4 cell count (P < .01 for all serotypes). There were significant increases in anticapsular IgG concentrations for all serotypes after the first dose (P < .01) and for all serotypes except 14 and 9V after the second dose. Past receipt of PPV did not affect vaccine response.

23-Valent pneumococcal polysaccharide vaccine was previously reported to be ineffective in HIV-infected Ugandan adults. Prolonged follow-up of trial participants confirmed persistent excess of all-cause pneumonia in vaccine recipients [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.0-2.4], but surprisingly a survival advantage favouring vaccination (HR 0.84; CI 0.7-1.0). An explanation for the improvement in survival in the face of excess morbid events is lacking; a role for vaccine in HIV care in Africa remains unlikely.

Objective: To determine whether tuberculin skin testing (TST) is associated with an increase in human immunodeficiency virus (HIV) viral load, and to examine the effect of TST on anti-mycobacterial immune responses., Design: A nested cohort study of HIV-1-infected adults., Method: Forty-two participants (21 TST-positive and 21 TST-negative) from a larger cohort were recruited to the study. Blood was collected for CD4+ T-cell count, whole blood was cultured, and plasma saved for viral load. These measurements were taken before, 3 days after, 3 months after, and 3 months plus 3 days after TST. Cytokine responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis and phytohaemagglutinin (PHA) were examined in the whole blood assay., Results: Twenty-nine participants attended all four visits. No statistically significant change in viral load, CD4+ T-cell count, or cytokine response to PHA was observed at any visit. However, TST was associated with a transient increase in the interferon-gamma response to CFP and a lasting increase in the interleukin-5 response to CFP., Conclusion: There appeared to be a systemic effect of TST on the anti-tuberculosis immune response.