The acquisition and maintenance of antibodies to merozoite antigens of Plasmodium falciparum and their role in protective immunity to malaria

Measurement of antibodies at a single time point in malaria-endemic populations and associating them with protection and susceptibility has given insight into the development and maintenance of the immune response to malaria. Immunity to malaria is a dynamic process that takes place over a number of years in different stages, which implies that antibody measurement at a single time point may not adequately encompass acquisition of immunity. Antibody responses to merozoite antigens (AMA 1 and MSP2) were measured in 300 children aged 0-10 years twice a year for three years. Each child was followed up on a weekly basis for episodes of malaria. Factors affecting antibody responses at each time point and antibody contributions to protection from malaria were investigated, and the association between functional activity of anti-AMA 1 antibodies and protection was assessed. Anti-AMA 1 and anti-MSP2 antibody responses were dependent on the amount of prior and ongoing exposure and paralleled the decline in malaria transmission that occurred during the study period. High antibody responses were generated after 2-3 episodes of parasitemia and were likely to drop on further exposure. There was no evidence for polarisation of IgG responses to AMA 1. The association between antibody responses and protection/risk of malaria was dependent on both the sample time and analysis method used. Antibody responses to AMA 1(W2mef) were associated with an increased risk of malaria over the study period. Antibodies to MSP2(3D7) may be associated with protection from malaria. Antibodies to a functional invasion inhibitory epitope of AMA 1(3D7) were rare but associated with protection from malaria. Longitudinal assessment of antibody levels gives a more complete picture of acquisition and maintenance of malaria immunity. Antibodies can be both a measure of protection or susceptibility. These findings enrich knowledge on acquisition of immunity and will impact vaccination development and immunisation strategies

Viewpoint: Why do we need a point-of-care CD4 test for low-income countries?

In this paper, we discuss the reasons why we urgently need a point-of-care (POC) CD4 test, elaborate the problems we have experienced with the current technology which hampers CD4-count coverage and highlight the ideal characteristics of a universal CD4 POC test. It is high-time that CD4 technology is simplified and adapted for wider use in low-income countries to change the current paradigm of restricted access once and for all

Measuring the impact of gender equality innovations for transformative youth agricultural livelihoods project in Ntoroko and Kasese in western Uganda

This pilot sub-project of the Youth in Action (YiA) programme identifies and addresses discriminatory social and gender norms and practices in households, communities and market institutions that prevent young women from advancement and attaining their potential in the agricultural sector. The report reviews project milestones, curriculum development, implementation, learning and action phases, and includes the challenges from disruptive policies related to the COVID-19 pandemic. The YiA+ project builds on the successes of YiA

Sexual behaviour among persons living with HIV/AIDS in Kampala, Uganda

Objective:  Design: Setting: Results:  Conclusions:  This study demonstrates that abstinence and use of condoms on their own may not be enough for HIV prevention among PLWHAs who desire children. Additional methods such as use of ART to reduce HIV infectiousness and sperm washing are needed.In the past 12 months 227 (60%) of the PLWHAs were sexually active. Of the sexually active 42 (19%) never used a condom, and 92 (40%) used condoms inconsistently, thus 134 (35%) of PLWHAs engaged in high risk sex. Two hundred and sixty five (70%) said that PLWHAs can have healthy children and 115 (30%) desired more children with 21 (10%) of the women in the reproductive age group reporting a pregnancy and 22 (17%) of the men reporting having caused a pregnancy. Only three (7%) of the pregnancies were unplanned. Desire for more children was a strong independent predictor of engaging in high risk sex (Adjusted Odds Ratio 2.44, 95% CI 1.35-4.42).Joint Clinical Research Centre, Kampala Uganda. Participants: Three hundred and eighty PLWHAs, 50% of whom had initiated antiretro viral therapy (ART). Main outcome measures: PLWHAs answered questions regarding sexual behaviour, number and type of sexual partners, symptoms of sexually transmitted infections, having been pregnant or causing a pregnancy, social demographic characteristics, consumption of alcohol, having biological children, desire for more children and use of condoms.A cross sectional study.To identify sexual behaviour and reproductive health needs of people living with HIV/AIDS (PLWHAs)

Opportunities for improving the efficiency of paediatric HIV treatment programmes

Objectives: To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART. Design and methods: The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings. Results: Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4+ monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio =$769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to$12.0 per patient-year to ensure continued provision of cotrimoxazole. Conclusion: Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources

Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti.

BACKGROUND: Countries aiming for malaria elimination require a detailed understanding of the current intensity of malaria transmission within their national borders. National household sample surveys are now being used to define infection prevalence but these are less efficient in areas of exceptionally low endemicity. Here we present the results of a national malaria indicator survey in the Republic of Djibouti, the first in sub-Saharan Africa to combine parasitological and serological markers of malaria, to evaluate the extent of transmission in the country and explore the potential for elimination. METHODS: A national cross-sectional household survey was undertaken from December 2008 to January 2009. A finger prick blood sample was taken from randomly selected participants of all ages to examine for parasitaemia using rapid diagnostic tests (RDTs) and confirmed using Polymerase Chain Reaction (PCR). Blood spots were also collected on filter paper and subsequently used to evaluate the presence of serological markers (combined AMA-1 and MSP-119) of Plasmodium falciparum exposure. Multivariate regression analysis was used to determine the risk factors for P. falciparum infection and/or exposure. The Getis-Ord G-statistic was used to assess spatial heterogeneity of combined infections and serological markers. RESULTS: A total of 7151 individuals were tested using RDTs of which only 42 (0.5%) were positive for P. falciparum infections and confirmed by PCR. Filter paper blood spots were collected for 5605 individuals. Of these 4769 showed concordant optical density results and were retained in subsequent analysis. Overall P. falciparum sero-prevalence was 9.9% (517/4769) for all ages; 6.9% (46/649) in children under the age of five years; and 14.2% (76/510) in the oldest age group (≥50 years). The combined infection and/or antibody prevalence was 10.5% (550/4769) and varied from 8.1% to 14.1% but overall regional differences were not statistically significant (χ2=33.98, p=0.3144). Increasing age (p<0.001) and decreasing household wealth status (p<0.001) were significantly associated with increasing combined P. falciparum infection and/or antibody prevalence. Significant P. falciparum hot spots were observed in Dikhil region. CONCLUSION: Malaria transmission in the Republic of Djibouti is very low across all regions with evidence of micro-epidemiological heterogeneity and limited recent transmission. It would seem that the Republic of Djibouti has a biologically feasible set of pre-conditions for elimination, however, the operational feasibility and the potential risks to elimination posed by P. vivax and human population movement across the sub-region remain to be properly established

Prevalence, Outcome and Associated Factors among Adolescents Delivering at Mbarara Regional Referral Hospital

Globally, almost one in five women aged 20 to 24 (19 %) had a live birth by their 18th birthday. Adolescent pregnancies and deliveries are universally recognized to be associated with many complications. Although many studies have been done on adolescent mothers globally, not much has been documented on the prevalence, outcomes and associated factors especially in Uganda. This study aimed at finding out the prevalence of adolescent deliveries, delivery outcomes and potential factors influencing these outcomes among adolescent mothers at Mbarara Regional Referral Hospital (MRRH), in Southwestern Uganda. We conducted a cross sectional study at MRRH between June and October 2015. We consecutively sampled 786 adolescent mothers within 24 hours postpartum and obtained their characteristics and delivery outcomes. The prevalence of adolescent deliveries at MRRH was 23.4% of all deliveries. Majority of the participants were aged 18-19 years (median 18.5years, standard deviation 0.87).  Majority had only attained primary education and almost all (90.5%) were married. Most had an average of 3 antenatal care visits, delivered by spontaneous vaginal delivery (59.4%). Caesarian section rate was 39.4% with the main indication of contracted pelvis (45.8%).  Majority had good fetal outcome (80.7%) while 50.2% of mothers had poor outcome. The main obstetric complication was perineal tears (32.6%) followed by prolonged labour (23%). Being referred and delivery by vacuum delivery remained significantly associated with poor outcomes while episiotomy and delivery by Caeserian section were protective. The prevalence of adolescent deliveries at MRRH is high with most of adolescent mothers having poor sociodemographic characteristics. Commonest poor maternal outcome was perineal tears followed by prolonged labour. Fetal outcomes were good. Being referred and delivery by vacuum delivery were associated with poor outcomes while episiotomy and delivery by Caeserian section were associated with good fetal outcome. Keywords: adolescent delivery, delivery outcome, maternal outcome, fetal outcome, associated factor

Frequency of HIV status disclosure, associated factors and outcomes among HIV positive pregnant women at Mbarara Regional Referral Hospital, southwestern Uganda

Introduction:&nbsp;positive HIV results disclosure plays a significant role in the successful prevention and care of HIV infected patients. It provides significant social and health benefits to the individual and the community. Non-disclosure is one of the contextual factors driving the HIV epidemic in Uganda. Study objectives: to determine the frequency of HIV disclosure, associated factors and disclosure outcomes among HIV positive pregnant women at Mbarara Hospital, southwestern Uganda. Methods:&nbsp;a cross-sectional study using quantitative and qualitative methods among a group of HIV positive pregnant women attending antenatal clinic was done and consecutive sampling conducted. Results:&nbsp;the total participant recruitment was 103, of which 88 (85.4%) had disclosed their serostatus with 57% disclosure to their partners. About 80% had disclosed within less than 2 months of testing HIV positive. Reasons for disclosure included their partners having disclosed to them (27.3%), caring partners (27.3%) and encouragement by health workers (25.0%). Following disclosure, 74%) were comforted and 6.8% were verbally abused. Reasons for non-disclosure were fear of abandonment (33.3%), being beaten (33.3%) and loss of financial and emotional support (13.3%). The factors associated with disclosure were age 26-35 years (OR 3.9, 95% CI 1.03-15.16), primary education (OR 3.53, 95%CI 1.10-11.307) and urban dwelling (OR 4.22, 95% CI 1.27-14.01). Conclusion:&nbsp;participants disclosed mainly to their partners and were comforted and many of them were encouraged by the health workers. There is need to optimize disclosure merits to enable increased participation in treatment and support programs

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 mu g, for prevention of PPH during active management of labor. Methods and Findings: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 mu g of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. Conclusions: Misoprostol 600 mu g is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol

CD4 T cell activation as a predictor for treatment failure in Ugandans with Plasmodium falciparum malaria.

Host immunity plays an important role in response to antimalarial therapy but is poorly understood. To test whether T cell activation is a risk factor for antimalarial treatment failure, we studied CD4(+) and CD8(+) T cell activation in 31 human immunodeficiency virus-negative Ugandan patients 5-37 years of age who were treated for uncomplicated Plasmodium falciparum malaria. Increased CD4(+) T cell activation, as indicated by co-expression of HLA-DR and CD38, was an independent risk factor for treatment failure (hazard ratio = 2.45, 95% confidence interval = 1.02-5.89, P = 0.05) in multivariate analysis controlling for age, baseline temperature, and pre-treatment parasite density. The results provide insight into the role of cellular immunity in response to antimalarial therapy and underscore the need to investigate the mechanisms behind immune activation