Showing papers by "Makerere University published in 2014"

Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges.

Abstract: Summary Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities.

Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis

Abstract: Supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID; U01AI089244, K23AI073192, T32AI055433, and K24AI096925), the Wellcome Trust (081667 and 098316 and the Veterans Affairs Research Service

Findings from the SASA! Study: a cluster randomized controlled trial to assess the impact of a community mobilization intervention to prevent violence against women and reduce HIV risk in Kampala, Uganda

Abstract: Background: Intimate partner violence (IPV) and HIV are important and interconnected public health concerns. While it is recognized that they share common social drivers, there is limited evidence surrounding the potential of community interventions to reduce violence and HIV risk at the community level. The SASA! study assessed the community-level impact of SASA!, a community mobilization intervention to prevent violence and reduce HIV-risk behaviors. Methods: From 2007 to 2012 a pair-matched cluster randomized controlled trial (CRT) was conducted in eight communities (four intervention and four control) in Kampala, Uganda. Cross-sectional surveys of a random sample of community members, 18- to 49-years old, were undertaken at baseline (n = 1,583) and four years post intervention implementation (n = 2,532). Six violence and HIV-related primary outcomes were defined ap riori .A n adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up. Results: The intervention was associated with significantly lower social acceptance of IPV among women (adjusted risk ratio 0.54, 95% confidence interval (CI) 0.38 to 0.79) and lower acceptance among men (0.13, 95% CI 0.01 to 1.15); significantly greater acceptance that a woman can refuse sex among women (1.28, 95% CI 1.07 to 1.52) and men (1.31, 95% CI 1.00 to 1.70); 52% lower past year experience of physical IPV among women (0.48, 95% CI 0.16 to 1.39); and lower levels of past year experience of sexual IPV (0.76, 95% CI 0.33 to 1.72). Women experiencing violence in intervention communities were more likely to receive supportive community responses. Reported past year sexual concurrency by men was signi ficantly lower in intervention compared to control communities (0.57, 95% CI 0.36 to 0.91). Conclusions: This is the first CRT in sub-Saharan Africa to assess the community impact of a mobilization program on the social acceptability of IPV, the past year prevalence of IPV and levels of sexual concurrency. SASA! achieved important community impacts, and is now being delivered in control communities and replicated in 15 countries. Trial registration: ClinicalTrials.gov #NCT00790959, Study protocol available at http://www.trialsjournal.com/content/13/1/96

Research capacity. Enabling the genomic revolution in Africa

Abstract: H3Africa is developing capacity for health-related genomics research in Africa Our understanding of genome biology, genomics, and disease, and even human history, has advanced tremendously with the completion of the Human Genome Project. Technological advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiology, diagnosis, and therapy for some of the world's most intractable and devastating diseases—including malaria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, despite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only participated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on African participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants (www.genome.gov/gwastudies/). As discussed in 2011 (www.h3africa.org), if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent.

Lethal aggression in Pan is better explained by adaptive strategies than human impacts

Abstract: Observations of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) provide valuable comparative data for understanding the significance of conspecific killing. Two kinds of hypothesis have been proposed. Lethal violence is sometimes concluded to be the result of adaptive strategies, such that killers ultimately gain fitness benefits by increasing their access to resources such as food or mates. Alternatively, it could be a non-adaptive result of human impacts, such as habitat change or food provisioning. To discriminate between these hypotheses we compiled information from 18 chimpanzee communities and 4 bonobo communities studied over five decades. Our data include 152 killings (n = 58 observed, 41 inferred, and 53 suspected killings) by chimpanzees in 15 communities and one suspected killing by bonobos. We found that males were the most frequent attackers (92% of participants) and victims (73%); most killings (66%) involved intercommunity attacks; and attackers greatly outnumbered their victims (median 8:1 ratio). Variation in killing rates was unrelated to measures of human impacts. Our results are compatible with previously proposed adaptive explanations for killing by chimpanzees, whereas the human impact hypothesis is not supported.

Barriers to male involvement in contraceptive uptake and reproductive health services: a qualitative study of men and women’s perceptions in two rural districts in Uganda

Abstract: Background: Spousal communication can improve family planning use and continuation. Yet, in countries with high fertility rates and unmet need, men have often been regarded as unsupportive of their partner’s use of family planning methods. This study examines men and women’s perceptions regarding obstacles to men’s support and uptake of modern contraceptives. Methods: A qualitative study using 18 focus group discussions (FGDs) with purposively selected men aged 15–54 and women aged 15–49 as well as eight key informant interviews (KIIs) with government and community leaders was conducted in 2012 in Bugiri and Mpigi Districts, Uganda. Open-ended question guides were used to explore men and women’s perceptions regarding barriers to men’s involvement in reproductive health. All FGDs and KIIs were recorded, translated, and transcribed verbatim. Transcripts were coded and analyzed thematically using ATLAS.ti. Results: Five themes were identified as rationale for men’s limited involvement: (i) perceived side effects of female contraceptive methods which disrupt sexual activity, (ii) limited choices of available male contraceptives, including fear and concerns relating to vasectomy, (iii) perceptions that reproductive health was a woman’s domain due to gender norms and traditional family planning communication geared towards women, (iv) preference for large family sizes which are uninhibited by prolonged birth spacing; and (v) concerns that women’s use of contraceptives will lead to extramarital sexual relations. In general, knowledge of effective contraceptive methods was high. However, lack of time and overall limited awareness regarding the specific role of men in reproductive health was also thought to deter men’s meaningful involvement in issues related to fertility regulation. Conclusion: Decision-making on contraceptive use is the shared responsibility of men and women. Effective development and implementation of male-involvement family planning initiatives should address barriers to men’s supportive participation in reproductive health, including addressing men's negative beliefs regarding contraceptive services.

Genome sequence of the tsetse fly (Glossina morsitans ): Vector of African trypanosomiasis

Abstract: Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein–encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast.

Abstract: Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006–2009 (n = 299) in Uganda and during 2010–2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 μL, 94.2% for 100 μL). CRAG latex agglutination test sensitivity (97.0%–97.8%) and specificity (85.9%–100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings.

Polymorphisms in Plasmodium falciparum chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors That Affect Treatment Outcomes for P. falciparum Malaria After Artemether-Lumefantrine and Artesunate-Amodiaquine

Abstract: Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

A value proposition: resource recovery from faecal sludge—can it be the driver for improved sanitation?

Abstract: There is currently a lack of access to affordable sanitation in urban areas of Sub-Saharan Africa. This study evaluated the potential for resource recovery from innovative faecal sludge treatment processes to generate a profit that could help sustain the sanitation service chain. A total of 242 interviews were conducted in Accra, Ghana; Dakar, Senegal; and Kampala, Uganda to compare markets in different cultural and regional contexts. Products identified to have potential market value include dry sludge as a fuel for combustion, biogas from anaerobic digestion, protein derived from sludge processing as animal feed, sludge as a component in building materials, and sludge as a soil conditioner. The market demand and potential revenue varied from city to city based on factors such as sludge characteristics, existing markets, local and regional industrial sectors, subsidies, and locally available materials. Use as a soil conditioner, which has been the most common end use of treated sludge, was not as profitable as other end uses. These findings should help policy and decision makers of sanitation service provision to design financially viable management systems based on resource recovery options.

Estimating the annual entomological inoculation rate for Plasmodium falciparum transmitted by Anopheles gambiae s.l. using three sampling methods in three sites in Uganda

Abstract: The Plasmodium falciparum entomological inoculation rate (Pf EIR) is a measure of exposure to infectious mosquitoes. It is usually interpreted as the number of P. falciparum infective bites received by an individual during a season or annually (aPf EIR). In an area of perennial transmission, the accuracy, precision and seasonal distribution (i.e., month by month) of aPf EIR were investigated. Data were drawn from three sites in Uganda with differing levels of transmission where falciparum malaria is transmitted mainly by Anopheles gambiae s.l. Estimates of aPf EIR derived from human-landing catches – the classic method for estimating biting rates – were compared with data from CDC light traps, and with catches of knock down and exit traps separately and combined. Entomological surveillance was carried out over one year in 2011/12 in three settings: Jinja, a peri-urban area with low transmission; Kanungu, a rural area with moderate transmission; and Nagongera, Tororo District, a rural area with exceptionally high malaria transmission. Three sampling approaches were used from randomly selected houses with collections occurring once a month: human-landing collections (eight houses), CDC light traps (100 houses) and paired knock-down and exit traps each month (ten houses) for each setting. Up to 50 mosquitoes per month from each household were tested for sporozoites with P. falciparum by ELISA. Human biting rate (HBR) data were estimated month by month. P. falciparum Sporozoite rate (Pf SR) for yearly and monthly data and confidence intervals were estimated using the binomial exact test. Monthly and yearly estimates of the HBR, the Pf SR, and the Pf EIR were estimated and compared. The estimated aPf EIR values using human-landing catch data were 3.8 (95% Confidence Intervals, CI 0-11.4) for Jinja, 26.6 (95% CI 7.6-49.4) for Kanungu, and 125 (95% CI 72.2-183.0) for Tororo. In general, the monthly Pf EIR values showed strong seasonal signals with two peaks from May-June and October-December, although the precise timing of the peaks differed between sites. Estimated HBRs using human-landing catches were strongly correlated with those made using CDC light traps (r2 = 0.67, p < 0.001), and with either knock-down catches (r2 = 0.56, p < 0.001) and exit traps (r2 = 0.82, p < 0.001) or the combined catches (r2 = 0.73, p < 0.001). Using CDC light trap catch data, the Pf SR in Tororo was strongly negatively correlated with monthly HBR (r2 = 0.44, p = 0.01). In other sites, no patterns in the Pf SR were discernible because either the number P. falciparum of sporozoite positive mosquitoes or the total number of mosquitoes caught was too low. In these settings, light traps provide an alternative method for sampling indoor-resting mosquitoes to human-landing catches and have the advantage that they protect individuals from being bitten during collection, are easy to use and are not subject to collector bias. Knock-down catches and exit traps could also be used to replace human-landing catches. Although these are cheaper, they are subject to collector bias.

A multicountry evaluation of careHPV testing, visual inspection with acetic acid, and papanicolaou testing for the detection of cervical cancer.

Abstract: Globally, cervical cancer is the third leading cancer and fourth cause of cancer-related mortality in women.1 There is a high disparity for cervical cancer between higher-income and lower-income regions, with more than 85% of cervical cancer occurring in low- and middle-income countries.1 This difference is primarily due to the difficulty in implementing Papanicolaou test–based screening programs because of their complexity, need for highly trained providers for reading the samples, need for close quality control, and mediocre sensitivity of the test even in optimal conditions.2 Based on the absolute etiologic link between carcinogenic human papillomavirus (HPV) and cervical cancer, 2 new approaches for the prevention of cervical cancer have emerged, these are as follows: (1) HPV vaccination for preventing incident HPV infection in younger women3,4 and (2) carcinogenic HPV detection for screening for cervical precancer and cancer.5–11 Both vaccine and screening have demonstrated high degrees of efficacy in prevention of HPV infection or detection at a treatable stage, with maximum effectiveness when guided by an understanding of the causal model and applied in an age-appropriate manner.12 Although prophylactic HPV vaccination may be the ultimate prevention strategy, these vaccines do not treat preexisting HPV infections and precancerous conditions.13–15 Therefore, there are millions of at-risk women who will not benefit from HPV vaccination, and robust screening and management programs developed for low- and middle-income countries are needed to reduce the burden of cervical cancer. Additionally, because the HPV vaccines do not protect against all the oncogenic genotypes of the virus, screening is still required even among vaccinated cohorts. Several new screening strategies have emerged as options for areas with limited resources. Visual inspection with acetic acid (VIA) is a method based on the use of 5% acetic acid (vinegar) that, when applied to the cervix, makes the dysplastic epithelium turn white (acetowhitening), becoming visible on evaluation by the unaided eye. The sensitivity of VIA is variable; 2 recent meta-analyses have reported sensitivity of 70% to 80% for cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) or more severe diagnoses.16,17 One large randomized clinical trial in India found a 35% reduction in cervical cancer-related mortality after a single screening by VIA,18 whereas a second trial did not find a statistically significant reduction8 in cervical cancer-related mortality compared with those randomized to the no-intervention arm of seeking standard services. Another approach that has recently become available is a lower-cost DNA test for detection of carcinogenic genotypes of HPV.19 Recent studies have shown that HPV testing used in a screen-and-treat approach was more effective than VIA in reducing the prevalence of CIN2+,20 and when used in a more traditional program (ie, colposcopy and excisional treatment of histologically confirmed CIN2+), it was more effective in reducing cervical cancer mortality than VIA and Papanicolaou test.8 In response to the need for more robust screening tools for low- and middle-income countries, a public-private collaboration led to the development of careHPV (QIAGEN, Gaithersburg, MD), a simplified, robust, and affordable HPV test that could be used in low-resource settings under a wider range of ambient conditions. The test can be run in any room because it does not need running water or air conditioning, and the process is simple and can be completed by people with limited laboratory training. Preliminary results for careHPV were promising and compared favorably to the US Food and Drug Administration–approved Hybrid Capture 2 (hc2; QIAGEN).21 Human papillomavirus DNA testing offers the possibility of using self-collected vaginal samples for primary screening. The advantages of self-collection are that it does not require pelvic evaluation; therefore, the sample collection process could be completed without the need for a speculum or even a health center facility because the sampling can be done at the community level. A recently pooled analysis of data from 5 studies in China found that HPV testing of self-collected specimens was at least as sensitive for CIN2+ and CIN grade 3 (CIN3+) as liquid-based cytology using clinician-collected specimens,22 and another review showed that population coverage can be increased by offering self-sampling.23 Further studies were needed to demonstrate whether careHPV truly had wide applicability under a variety of settings and how it compared with the 2 standards, VIA and Papanicolaou testing, in a more realistic setting. We therefore conducted a multisite study in routine public health settings in India, Nicaragua, and Uganda using existing staff and resources to assess the clinical performance of careHPV with both clinician-collected and self-collected specimens, VIA, and Papanicolaou testing for detection of cervical precancer and cancer.

A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study

Abstract: Please cite as follows: Payne, B. A. 2014. A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (pre-eclampsia integrated estimate of risk) multi-country prospective cohort study. PLoS Medicine, 11(1):e1001589, doi:10.1371/journal.pmed.1001589.

Malaria in school-age children in Africa: an increasingly important challenge.

Abstract: School-age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school-age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school-age children are presented and evidence that malaria adversely effects school performance is reviewed. Long-lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school-age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school-age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school-age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school-age children.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Abstract: Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Strengthening district-based health reporting through the district health management information software system: the Ugandan experience

Abstract: Background: Untimely, incomplete and inaccurate data are common challenges in planning, monitoring and evaluation of health sector performance, and health service delivery in many sub-Saharan African settings. We document Uganda’s experience in strengthening routine health data reporting through the roll-out of the District Health Management Information Software System version 2 (DHIS2).

Socio-economic hurdles to widespread adoption of small-scale biogas digesters in Sub-Saharan Africa: A review

Abstract: The unsustainable use of fossil fuels has led to increased awareness and widespread research on the accessibility of renewable energy resources such as biogas. Biogas is a methane rich gas that is produced by anaerobic fermentation of organic material. Despite its potential to replace biomass in Africa, where over 70% of the households use wood fuel and agricultural waste for cooking, biogas technology has not been adopted by Sub-Saharan African countries compared to their Asian counterparts. This paper examines the socioeconomic constraints to adoption of biogas in Sub-Saharan Africa and explores factors that could enhance adoption of the technology. These include standardization and quality control, as well as an approach of integrated farming using biogas and slurry. The article recommends mobilization of local and external funds to promote biogas, use of ready to use funds such as the Clean Development Mechanisms in overcoming the initial construction costs of biogas units, and formation of user and disseminator associations to reduce costs by joint procurement and linkage to finance. It further advocates the promotion of multiple uses of biogas for purposes other than cooking and lighting. It is expected that widespread adoption of the technology could lead to self-sufficiency in household energy provision for cooking. This would facilitate environmental management and economic development in Sub-Saharan Africa.

Trends in the incidence of cancer in Kampala, Uganda 1991–2010

Abstract: The Kampala cancer registry is the longest established in Africa. Trends in incidence rates for a 20-year period (1991-2010) for Kyadondo County (Kampala city and a rural hinterland) illustrate the effects of changing lifestyles in urban Africa, and the effects of the epidemic of HIV-AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with incidence rates of major cancers such as breast and prostate showing particularly marked increases (3.7% and 5.2% annually, respectively). In the 1960s cancer of the oesophagus was the most common cancer of men (and second in women), and incidence in the last 20 years has not declined. Cancer of the cervix, always the most frequent cancer of women, has shown an increase over the period (1.8% per year), although the rates appear to have declined in the last 4 years. HIV prevalence in adults in Uganda fell from a maximum in 1992 to a minimum (about 6%) in 2004, and has risen a little subsequently, while availability of antiretroviral drugs has risen sharply in recent years. Incidence of Kaposi sarcoma in men fell until about 2002, and has been relatively constant since then, while in women there has been a continuing decline since 2000. Other HIV related cancers-non-Hodgkin lymphoma of younger adults, and squamous cell carcinoma of conjunctiva-have shown major increases in incidence, although the former (NHL) has shown a small decline in incidence in the most recent 2 years.

The role of viral introductions in sustaining community-based HIV epidemics in rural Uganda: evidence from spatial clustering, phylogenetics, and egocentric transmission models.

Abstract: Background It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities—home to two-thirds of the African population—is driven by intra-community sexual networks versus viral introductions from outside of communities. Methods and Findings We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7–3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%–42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%–70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai. Conclusions Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities. Please see later in the article for the Editors' Summary

The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: a randomized placebo controlled clinical trial

Abstract: Oxidative stress plays a role in the pathogenesis of pre-eclampsia. Supplementing women with antioxidants during pregnancy may reduce oxidative stress and thereby prevent or delay the onset pre-eclampsia. The objective of this study was to evaluate the effect of supplementing vitamin C in pregnancy on the incidence of pre-eclampsia, at Mulago hospital, Kampala, Uganda. This was a (parallel, balanced randomization, 1:1) placebo randomized controlled trial conducted at Mulago hospital, Department of Obstetrics and Gynecology. Participants included in this study were pregnant women aged 15-42 years, who lived 15 km or less from the hospital with gestational ages between 12-22 weeks. The women were randomized to take 1000mg of vitamin C (as ascorbic acid) or a placebo daily until they delivered. The primary outcome was pre-eclamsia. Secondary outcomes were: severe pre-eclampsia, gestational hypertension, preterm delivery, low birth weight and still birth delivery. Participants were 932 pregnant women randomized into one of the two treatment arms in a ratio of 1:1. The participants, the care providers and those assessing the outcomes were blinded to the study allocation. Of the 932 women recruited; 466 were randomized to the vitamin and 466 to the placebo group. Recruitment of participants was from November 2011 to June 2012 and follow up was up to January 2013. Outcome data was available 415 women in the vitamin group and 418 women in the placebo group. There were no differences in vitamin and placebo groups in the incidence of pre-eclampsia (3.1% versus 4.1%; RR 0.77; 95% CI: 0.37-1.56), severe pre-eclampsia (1.2% versus 1.0%; RR 1.25; 95% CI: 0.34-4.65), gestational hypertension(7.7% versus 11.5%; RR 0.67; 95% CI: 0.43-1.03), preterm delivery (11.3% versus 12.2%; RR 0.92; 95% CI: 0.63-1.34), low birth weight (11.1% versus 10.3%; RR 1.07; 95% CI: 0.72-1.59) and still birth delivery (4.6% versus 4.5%; RR 1.01; 95% CI: 0.54-1.87). Supplementation with vitamin C did not reduce the incidence of pre-eclampsia nor did it reduce the adverse maternal or neonatal outcomes. We do not recommend the use of vitamin C in pregnancy to prevent pre-eclampsia. This study was registered at the Pan African Clinical Trial Registry, PACTR201210000418271 on 25th October 2012.

The Effect of Therapeutic Lumbar Punctures on Acute Mortality from Cryptococcal Meningitis

Abstract: Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown. Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7–11 days; thus, follow-up stopped at time of death, randomization, or 11 days. Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12–.82). The association was observed regardless of opening pressure at baseline. Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.

Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS.

Abstract: The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states.

Patterns and Predictors of Self-Medication in Northern Uganda

Abstract: Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only one adult individual. Data was analyzed using STATA at 95% level of significance. The study found that a high proportion (75.7%) of the respondents practiced antimicrobial self-medication. Fever, headache, lack of appetite and body weakness were the disease symptoms most treated through self-medication (30.3%). The commonly self-medicated antimicrobials were coartem (27.3%), amoxicillin (21.7%), metronidazole (12.3%), and cotrimoxazole (11.6%). Drug use among respondents was mainly initiated by self-prescription (46.5%) and drug shop attendants (57.6%). On average, participants obtained 13.9±8.8 (95%CI: 12.6-13.8) tablets/capsules of antimicrobial drugs from drug shops and drugs were used for an average of 3.7±2.8 days (95%CI: 3.3-3.5). Over half (68.2%) of the respondents would recommend self-medication to another sick person. A high proportion (76%) of respondents reported that antimicrobial self-medication had associated risks such as wastage of money (42.1%), drug resistance (33.2%), and masking symptoms of underlying disease (15.5%). Predictors of self-medication with antimicrobial agents included gender, drug knowledge, drug leaflets, advice from friends, previous experience, long waiting time, and distance to the health facility. Despite knowledge of associated risks, use of self-medication with antimicrobial drugs in management of disease symptoms is a common practice in post-conflict northern Uganda.

Gender Stereotypes of Personality Universal and Accurate

Abstract: Numerous studies have documented subtle but consistent sex differences in self-reports and observer-ratings of five-factor personality traits, and such effects were found to show well-defined developmental trajectories and remarkable similarity across nations. In contrast, very little is known about perceived gender differences in five-factor traits in spite of their potential implications for gender biases at the interpersonal and societal level. In particular, it is not clear how perceived gender differences in five-factor personality vary across age groups and national contexts and to what extent they accurately reflect assessed sex differences in personality. To address these questions, we analyzed responses from 3,323 individuals across 26 nations (mean age = 22.3 years, 31% male) who were asked to rate the five-factor personality traits of typical men or women in three age groups (adolescent, adult, and older adult) in their respective nations. Raters perceived women as slightly higher in openness, agreeableness, and conscientiousness as well as some aspects of extraversion and neuroticism. Perceived gender differences were fairly consistent across nations and target age groups and mapped closely onto assessed sex differences in self- and observer-rated personality. Associations between the average size of perceived gender differences and national variations in sociodemographic characteristics, value systems, or gender equality did not reach statistical significance. Findings contribute to our understanding of the underlying mechanisms of gender stereotypes of personality and suggest that perceptions of actual sex differences may play a more important role than culturally based gender roles and socialization processes.

IFNγ/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children.

Abstract: Although evidence suggests that T cells are critical for immunity to malaria, reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking. We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific T cells in 78 four-year-old children enrolled in a longitudinal cohort study in Tororo, Uganda, a highly malaria-endemic region. More than 1800 episodes of malaria were observed in this cohort, with no cases of severe malaria. We quantified production of IFNγ, TNFα, and IL-10 (alone or in combination) by malaria-specific T cells, and analyzed the relationship of this response to past and future malaria incidence. CD4(+) T cell responses were measurable in nearly all children, with the majority of children having CD4(+) T cells producing both IFNγ and IL-10 in response to malaria-infected red blood cells. Frequencies of IFNγ/IL10 co-producing CD4(+) T cells, which express the Th1 transcription factor T-bet, were significantly higher in children with ≥2 prior episodes/year compared to children with <2 episodes/year (P<0.001) and inversely correlated with duration since malaria (Rho = -0.39, P<0.001). Notably, frequencies of IFNγ/IL10 co-producing cells were not associated with protection from future malaria after controlling for prior malaria incidence. In contrast, children with <2 prior episodes/year were significantly more likely to exhibit antigen-specific production of TNFα without IL-10 (P = 0.003). While TNFα-producing CD4(+) T cells were not independently associated with future protection, the absence of cells producing this inflammatory cytokine was associated with the phenotype of asymptomatic infection. Together these data indicate that the functional phenotype of the malaria-specific T cell response is heavily influenced by malaria exposure intensity, with IFNγ/IL10 co-producing CD4(+) T cells dominating this response among highly exposed children. These CD4(+) T cells may play important modulatory roles in the development of antimalarial immunity.