Transmission In Uganda Research Articles

Detection of antibodies against Ornithodoros moubata salivary antigens and their association with detection of African swine fever virus in pigs slaughtered in central Uganda.

African swine fever (ASF) is an important disease of pigs in sub-Saharan Africa and Uganda and is threatening the pig population and agricultural economy of other continents. ASF virus (ASFV) can be transmitted from wild suids to domestic pigs through soft ticks of the Ornithodoros species. The aim of this study was to understand the relationship between domestic pigs' O. moubata tick exposure and ASFV status. Pigs were sampled from six abattoirs in the Kampala metropolitan area of Uganda from May 2021 through June 2022. Blood, serum, and tissue samples were collected. Serum was tested for antibodies against the rtTSGP1 salivary antigens of O. moubata ticks using an indirect ELISA assay. Blood and tissue samples from pigs were tested to detect ASFV using qPCR. Probability of tick exposure was categorized based on sample-to-positive ratio cut-off points. Out of 1,328 serum samples tested, there were 828 (62.3%) samples with a negligible probability; 369 (27.8%) with a medium probability; 90 (6.8%) with a high probability, and 41 (3.1%) with a very high probability of exposure to the O. moubata salivary antigen. There was a statistically significant association between the pigs' O. moubata exposure and ASFV status with a higher proportion of pigs having a very high probability of infection if they were ASFV positive by blood, tonsil, and lymph nodes. These results suggested that tick exposure was associated with ASFV transmission in Uganda. There were ASFV qPCR positive pigs that had no O. moubata exposure as well, which highlights that pig-to-pig and indirect contact transmission still play a significant role. This work highlights the need for further work in Uganda to investigate these transmission factors related to the O. moubata tick and ASFV transmission.

Susceptibility of Anopheles gambiae to Natural Plasmodium falciparum Infection: A Comparison between the Well-Established Anopheles gambiae s.s Line and a Newly Established Ugandan Anopheles gambiae s.s. Line.

Much of our understanding of malaria transmission comes from mosquito feeding assays using Anopheles mosquitoes from colonies that are well adapted to membrane feeding. This raises the question whether results from colony mosquitoes lead to overestimates of outcomes in wild Anopheles mosquitoes. We successfully established an Anopheles colony using progeny of wild Anopheles gambiae s.s. mosquitoes (Busia mosquitoes) and directly compared their susceptibility to infection with Plasmodium falciparum with the widely used An. gambiae s.s. mosquitoes (Kisumu mosquitoes) using gametocyte-infected Ugandan donor blood. The proportion of infectious feeds did not differ between Busia (71.8%, 23/32) and Kisumu (68.8%, 22/32, P = 1.00) mosquitoes. When correcting for random effects of donor blood, we observed a 23% higher proportion of infected Busia mosquitoes than infected Kisumu mosquitoes (RR, 1.23; 95% CI, 1.10-1.38, P < 0.001). This study suggests that feeding assays with Kisumu mosquitoes do not overestimate outcomes in wild An. gambiae s.s. mosquitoes, the mosquito species most relevant to malaria transmission in Uganda.

Sexual pleasure and HIV-related worry in female sex workers on oral pre-exposure prophylaxis in south-western Uganda.

Female sex workers (FSWs) contribute disproportionately to HIV transmission in Uganda, and pre-exposure prophylaxis (PrEP) is effective in preventing HIV among cisgender women. Psychological factors are important for PrEP uptake, but few studies have examined psychosocial changes due to PrEP use in Uganda. In 2021, we recruited 524 FSWs in three Trans-African Highway towns and four fishing communities in south-western Uganda. We conducted structured interviews among women who were attending routine PrEP follow-up visits in six health units. Bivariable and multivariable modified regression using a robust covariance matrix estimator were used to identify factors associated with experiencing increased sexual pleasure and less worry about HIV because of PrEP. Overall, 80.9% participants reported that sex was more pleasurable because of taking PrEP. There were statistical trends for sex being more pleasurable when taking PrEP or when having condomless sex with casual paying partners (aPR=1.19, 95% CI=1.07-1.32, P=0.001). Almost three-quarters of the participants (76.3%) were less worried about getting HIV because of PrEP. Condomless sex with casual paying partners (aPR=1.17, 95% CI=1.05-1.31, P=0.032, P=0.003) and being On PrEP for the past 1-2years (aPR=1.18, 95% CI=1.00-1.38, P=0.032) was significantly associated with HIV-related worry (aPR=1.17, 95% CI=1.05-1.31, P=0.032, P=0.003)Conclusions:We found a positive impact of PrEP in Ugandan FSWs on two key psychosocial dimensions: (1) more pleasurable sex; and (2) less worry about acquiring HIV. Interventions aiming to increase PrEP uptake may find it useful to focus on psychosocial dimensions.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15–24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15–24 years) from older men declined by about one-third, transmission to women (aged 25–34 years) from men that were 0–6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.

Malaria in Children with Sickle Cell Anaemia in Areas with Low, Moderate and High Transmission in Uganda

Background. Few large prospective studies have evaluated burden and outcomes of malaria in children with sickle cell anaemia (SCA) in malaria endemic countries. We evaluated the incidence, complications and outcome of malaria in three cohorts of Ugandan children with SCA in three areas with differing malaria transmission. Methods. Cohort 1 were SCA aged 3-9 years, enrolled in the hydroxyurea therapy for neurological and cognitive protection in Uganda (BRAINSAFE II) trial at Mulago Hospital, a low transmission area, while cohort 2 and 3 aged 6 months to 15 years, were enrolled in the dihydroartemisinin-piperaquine (DP) or sulphadoxine-pyrimethamine (SP) for the chemoprevention of malaria in SCA (CHEMCHA) trial at Jinja Hospital (moderate transmission) and Kitgum Hospital (high transmission). In cohort 1, all received SP for malaria chemoprophylaxis and hydroxyurea at 20-30mg/kg/day, while cohorts 2 and 3, received either DP or SP for malaria chemoprevention, and a proportion (10%) received hydroxyurea in the study. Results. A total of 706 participants were enrolled: 267, 249 and 190 at Mulago, Jinja and Kitgum respectively. The mean age was 6.5 (SD 3.4) years; 5.1 (1.7), 7.9 (4.3) and 6.8 (3.5) years for Mulago, Jinja, and Kitgum respectively. Incidence of malaria was 13 (95% CI 6, 20) per 100 child years in low, 38 (95% CI 26, 51) in moderate and 104 (95% CI 64, 144) in the high transmission area, p&amp;lt;0.001. Adjusting for hydroxyurea treatment, incidence of malaria was 33 (95%CI 14, 52) per 100 child year on hydroxyurea and 51 (95%CI 40, 62) per 100 child years without hydroxyurea, p=0.001. The most common SCA-related complications were anaemia (39.6%, 133/336), and pain (27.7%, 93/336) among children with malaria. Over a period of 1042.8 person years, there were 115 admissions for malaria, with an overall incidence of 11 per 100 child year (95% CI 9, 13), and this differed across sites, p&amp;lt;0.001. Overall, 1.5% (11/706) children died, and 18.2% (2/11) deaths were directly related to malaria infection. Conclusion. Malaria incidence remains high among Ugandan children with SCA, and differs by transmission patterns. Prevention strategies should be strengthened, especially in high transmission areas.

Knowledge, Practices, and Factors Affecting use of Condoms among the Youths in Lira District in HIV Prevention

As Uganda continues with the fight to end HIV epidemic by 2030, increasing condom use, especially in high-risk sexual encounters is one of the key strategies for reducing HIV transmission in Uganda. This study aimed to assess the knowledge, practices and factors affecting the utilization of condoms in the prevention of HIV among youths in Lira District. The study adopted a cross-sectional study design employing quantitative methods. A total of 189 respondents aged 15-35 years were recruited using a systematic random sampling technique. Data was obtained using an interviewer administered questionnaire and analysed using SPSS version 2.0. Descriptive analysis was used to generate frequencies and percentages. The measure and significance of association were determined using a Chisquare test and odds ratios with a P-value set at 0.05 corresponding to 95% confidence interval. Linear logistic regression analysis was used to generate Crude and Adjusted odds ratios to determine the factors associated with condom use among youths in HIV prevention. The results showed that 48% had ever used condoms. Majority had knowledge of condom use. Over 120(63.49%) were very knowledgeable, 28(14.82%) moderately knowledgeable while the rest 41(21.69%) were less knowledgeable. Likewise, over three quarters 71(78.02%) reported good condom use practices. Marital status (p=0.002), education (p=0.012), relationship status (p=0.019), number of sexual partners (p=0.011) and knowledge about condom use (p=0.018) were significant predictors of condom use in HIV prevention. Only marital status was independently associated with condom use after adjusting for possible cofounders. Although the study reveals relatively good knowledge and condom use practices, there is still some level of less knowledge and poor practices which may be driving the high prevalence of not using condoms among youths in HIV prevention. Reproductive health education programs targeting married, less educated, and youths in more than a single relationship should be tightened so as to increase condom use knowledge and eventually utilization in the fight against HIV. Keywords: Condom, HIV epidemic and sexually transmitted infections (STIs).

Widespread exposure to Crimean-Congo haemorrhagic fever in Uganda might be driven by transmission from Rhipicephalus ticks: Evidence from cross-sectional and modelling studies

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral infection, present across Africa and Eurasia, which might pose a cryptic public health problem in Uganda. We aimed to understand the magnitude and distribution of CCHF risk in humans, livestock and ticks across Uganda by synthesising epidemiological (cross-sectional) and ecological (modelling) studies. We conducted a cross-sectional study at three urban abattoirs receiving cattle from across Uganda. We sampled humans (n=478), livestock (n=419) and ticks (n=1065) and used commercially-available kits to detect human and livestock CCHF virus (CCHFV) antibodies and antigen in tick pools. We developed boosted regression tree models to evaluate the correlates and geographical distribution of expected tick and wildlife hosts, and of human CCHF exposures, drawing on continent-wide data. The cross-sectional study found CCHFV IgG/IgM seroprevalence in humans of 10·3% (7·8-13·3), with antibody detection positively associated with reported history of tick bite (age-adjusted odds ratio=2·09 (1·09-3·98)). Cattle had a seroprevalence of 69·7% (65·1-73·4). Only one Hyalomma tick (CCHFV-negative) was found. However, CCHFV antigen was detected in Rhipicephalus (5·9% of 304 pools) and Amblyomma (2·9% of 34 pools) species. Modelling predicted high human CCHF risk across much of Uganda, low environmental suitability for Hyalomma, and high suitability for Rhipicephalus and Amblyomma. Our epidemiological and ecological studies provide complementary evidence that CCHF exposure risk is widespread across Uganda. We challenge the idea that Hyalomma ticks are consistently the principal reservoir and vector for CCHFV, and postulate that Rhipicephalus might be important for CCHFV transmission in Uganda, due to high frequency of infected ticks and predicted environmental suitability. UCL Global Challenges Research Fund (GCRF) and Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under the EU Horizon 2020 Framework Programme for Research and Innovation.

Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children

T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.

Preparedness and community led response stops cross border Ebola transmission in Uganda, 2019

Preparedness and community led response stops cross border Ebola transmission in Uganda, 2019

Age-dependent carriage of alleles and haplotypes of Plasmodium falciparum sera5, eba-175, and csp in a region of intense malaria transmission in Uganda

BackgroundThe development of malaria vaccines is constrained by genetic polymorphisms exhibited by Plasmodium falciparum antigens. The project the age-dependent distribution of alleles or haplotypes of three P. falciparum malaria vaccine candidates, Circumsporozoite Protein (csp), Erythrocyte Binding Antigen 175 (eba-175) and Serine Repeat Antigen 5 (sera5) in a region of intense malaria transmission in Uganda.MethodsA cross-sectional study was carried out between August and November 2009 in which 250 study participants were selected from a population of 600. Finger prick blood samples were collected after informed consent from participants below 5 years, 5–10 years, and above 10 years of age. Blood was used for microscopy, RDT and dried blood spots. Plasmodium falciparum DNA was extracted by chelex method. Alleles of sera5 and eba-175 were determined by polymerase chain reaction (PCR) amplification followed by resolution of products by agarose gel electrophoresis. Allele calling was done using gel photographs from ethiduim bromide stained gels. Haplotypes of csp were identified by sequencing 63 PCR products using the P. falciparum 7G8 laboratory strain sequence as a reference. The data were analysed using SPSS 16, EQX for windows and Chi-square test was used to calculate associations (P-values), Excel was used to generate graphs. The BioEdit and NCBI blast software programs were used to analyse the sequences from which csp haplotypes map was constructed.ResultsEba-175 FCR3 (48/178) and CAMP (16/178) alleles were observed, the FCR3 (24/67) allele being predominant among children aged below 5 years old while the CAMP (12/67) allele was predominant among older participants. Sera5 alleles ORI (6/204) and ORII (103/204) were observed in the population, ORII was more prevalent and was significantly associated with age (P values < 0.0001), parasite density (P-value < 0.0001) and clinical outcomes (P value = 0.018). There was marked csp diversity in the Th2/Th3 region. Out of 63 sequences, 16 conformed to the reference strain and one (1/16) was similar to a West African haplotype and the majority (14/16) of the haplotypes were unique to this study region. There was an age-dependent distribution of csp haplotypes with more haplotypes being harbored by children < 5-year of age, (10/16) compared to adults (2/16). Interestingly, the csp haplotype corresponding to 3D7 whose prototypical sequence is identical to the sequence of the leading malaria vaccine candidate RTS, S was not observed.ConclusionThis data suggest that the eba-175 FCR3 allele, sera5 ORII allele, and csp haplotypes are targets of host immunity and under immune selection pressure in Apac District. These molecules could provide alternative malaria vaccine candidates as sub-unit vaccines.

Long-distance truck drivers and the increasing risk of COVID-19 spread in Uganda

ObjectiveTo examine the patterns of COVID-19 transmission in Uganda. MethodsWe reviewed ten weeks of press releases from the Uganda Ministry of Health from the day when the first case was announced, March 22, through May 29, 2020. We obtained the press releases from the MoH website and the Twitter handle (@MinofHealthUG). Data include the number of persons tested and the categories were classified as international arrivals, community members, and long-distance truck drivers. ResultsThe first cases were international arrivals from Asia and Europe, and after that, community cases emerged. However, in the middle of April 2020, COVID-19 cases were detected among long-distance truck drivers. By May 29, 2020, 89, 224 persons had been tested; overall, 442 tested positive. Of those that tested positive, the majority, or 317 (71.8%) were truck drivers, 75 (16.9%) were community cases, and 50 (11.3%) were international arrivals. The majority of community cases have been linked to contact with truck drivers. ConclusionsTruck drivers were the most frequently diagnosed category, and have become a core group for COVID-19 in Uganda. They have generated significant local transmission, which now threatens a full-blown epidemic unless strict controls are put in place.

Identification and characterization of immature Anopheles and culicines (Diptera: Culicidae) at three sites of varying malaria transmission intensities in Uganda

BackgroundOver the last two decades, there has been remarkable progress in malaria control in sub-Saharan Africa, due mainly to the massive deployment of long-lasting insecticidal nets and indoor residual spraying. Despite these gains, it is clear that in many situations, additional interventions are needed to further reduce malaria transmission. The World Health Organization (WHO) has promoted the Integrated Vector Management (IVM) approach through its Global Vector Control Response 2017–2030. However, prior roll-out of larval source management (LSM) as part of IVM, knowledge on ecology of larval aquatic habitats is required.MethodsAquatic habitats colonized by immature Anopheles and culicines vectors were characterized at three sites of low, medium and high malaria transmission in Uganda from October 2011 to June 2015. Larval surveys were conducted along transects in each site and aquatic habitats described according to type and size. Immature Anopheles, culicines and pupae from the described habitats were sampled using standard dipping methods to determine larval and pupae densities. Larvae were identified as anopheline or culicine, and counted. Pupae were not identified further. Binary logistic regression analysis was used to identify factors associated with the presence of immature Anopheles and culicines in each site.ResultsA total of 1205 larval aquatic habitats were surveyed and yielded a total of 17,028 anopheline larvae, 26,958 culicine larvae and 1189 pupae. Peaks in larval abundance occurred in all sites in March–May and August-October coinciding with the rainy seasons. Anopheles larvae were found in 52.4% (n = 251) of aquatic habitats in Tororo, a site of high transmission, 41.9% (n = 536) of habitats in Kanungu, a site with moderate malaria transmission, and 15.8% (n = 418) in Jinja, a site with low malaria transmission. The odds of finding larvae was highest in rice fields compared to pools in both Tororo (odds ratio, OR = 4.21, 95% CI 1.22–14.56, p = 0.02) and Kanungu (OR = 2.14, 95% CI 1.12–4.07, p = 0.02), while in Jinja the odd were highest in containers (OR = 4.55, 95% CI = 1.09–19.14, p = 0.03). In Kanungu, larvae were less likely to be found in containers compared to pools (OR = 0.26, 95% CI 0.09–0.66, p = 0.008) and river fringe (OR = 0.19, 95% CI 0.07–0.52, p = 0.001). Medium sized habitats were associated with high odds of finding larvae compared to small habitats (OR = 3.59, 95% CI 1.18–14.19, p = 0.039).ConclusionsThese findings show that immature Anopheles and culicines were common in areas of high and moderate transmission but were rare in areas of low transmission. Although immature Anopheles and culicines were found in all types of water bodies, they were most common in rice fields and less common in open drains and in river fringes. Methods are needed to reduce the aquatic stages of anopheline mosquitoes in human-made habitats, particularly rice fields.

Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate

Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine candidate for next-generation vaccines against P. falciparum.

Factors associated with married women's support of male circumcision for HIV prevention in Uganda: a population based cross-sectional study.

BackgroundDespite the protective effect of male circumcision (MC) against HIV in men, the acceptance of voluntary MC in priority countries for MC scale–up such as Uganda remains limited. This study examined the role of women’s sociodemographic characteristics, knowledge of HIV and sexual bargaining power as determinants of women’s support of male circumcision (MC).MethodsData from the Uganda AIDS Indicator Survey, 2011 were analyzed (n = 4,874). Bivariate and multivariate logistic regression analyses with random intercept were conducted to identify factors that influence women’s support of MC.ResultsOverall, 67.0 % (n = 3,276) of the women in our sample were in support of MC but only 28.0 % had circumcised partners. Women who had the knowledge that circumcision reduces HIV risk were about 6 times as likely to support MC than women who lacked that knowledge [AOR (adjusted odds ratio) = 5.85, 95 % CI (confidence interval) = 4.83–7.10]. The two indicators of women’s sexual bargaining power (i.e., ability to negotiate condom use and ability to refuse sex) were also positively associated with support of MC. Several sociodemographic factors particularly wealth index were also positively associated with women’s support of MC.ConclusionsThe findings in this study will potentially inform intervention strategies to enhance uptake of male circumcision as a strategy to reduce HIV transmission in Uganda.

Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children.

BackgroundAsymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda.MethodsInfants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim–sulfamethoxazole, monthly sulfadoxine–pyrimethamine, or monthly dihydroartemisinin–piperaquine (DP), to be given between enrollment (4–6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU).ResultsDP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01).ConclusionsMalaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings.

Age-dependent carriage of alleles and haplotypes of Plasmodium falciparum sera5, eba-175, and csp in a region of intense malaria transmission in Uganda

Background: The development of malaria vaccines is constrained by genetic polymorphisms exhibited by Plasmodium falciparum antigens. We investigated the age-dependent distribution of alleles or haplotypes of three P. falciparum malaria vaccine candidates, circumsporozoite protein (csp), erythrocyte binding antigen 175 (eba-175) and serine repeat antigen 5 (sera5) in a region of intense malaria transmission in Uganda. Methods & Materials: A cross sectional study was carried out between August and November 2009. Blood samples were collected after informed consent from 250 individuals below 5 years, 5-10 years and above 10 years olds. P. falciparum DNA was extracted from all samples. Alleles of sera5 and eba-175 were determined by polymerase chain reaction (PCR) amplification followed by resolution of PCR products by agarose gel electrophoresis and allele calling using photographs of ethidium bromide-stained gels. Haplotypes of CSP were identified by sequencing 63 PCR products and using P.falciparum 7G8 strain sequence as a reference. Results: Both eba-175 FCR3 (48/178) and CAMP (16/178) alleles were observed with the FCR3 (24/67) allele being predominant among children aged below 5 years old while the CAMP (12/67) allele was predominant among older individuals. Both sera5 alleles ORI (6/204) and ORII (103/204) were observed in the population but ORII was more prevalent. SERA5 ORII allele was significantly associated with age (P values < 0.0001), parasite density (P value < 0.0001) and clinical outcomes (P value = 0.018). There was marked CSP diversity in the Th2/Th3 region. Out of 63 sequences, 16 conformed to the reference strain and one (1/16) was similar with a West African haplotype and the majority (14/16) of the haplotypes were unique to this study region. Conclusion: There was an age-dependent distribution of CSP haplotypes with more haplotypes being harbored by < 5-year olds, (10/16) compared to adults (2/16). Interestingly, the CSP haplotype corresponding to 3D7 whose prototypical sequence is identical to the sequence of the leading malaria vaccine candidate RTS, S was not observed. Our data suggest that eba-175 FCR3 allele, sera5 ORII allele, and CSP haplotypes are targets of host immunity and under immune selection pressure in Apac District.

Assessing the Potential Role of Pigs in the Epidemiology of Ebola Virus in Uganda.

Uganda has experienced 4 Ebola outbreaks since the discovery of the virus. Recent epidemiological work has shown pigs are hosts for Ebola viruses. Due to their high reproduction rates, rapid weight gain, potential to provide quick financial returns and rising demand for pork, pig production in Uganda has undergone massive expansion. The combination of pork sector growth supported by development programmes and Ebola virus risk prompted a foresight exercise using desk, interview and spatial methods. The study found that the lack of serological evidence for specific reservoir species, the number of human index cases unable to account for their source of infection, domestic pig habitat overlap with potential Ebola virus zoonotic host environments, reported interactions at the human-pig-wildlife interface that could support transmission, fever in pigs as a commonly reported problem by pig farmers and temporal correlation of outbreaks with peak pork consumption periods warrants further research into potential zoonotic transmission in Uganda from pigs.

The past, present and future use of epidemiological intelligence to plan malaria vector control and parasite prevention in Uganda.

BackgroundAn important prelude to developing strategies to control infectious diseases is a detailed epidemiological evidence platform to target cost-effective interventions and define resource needs.MethodsA review of published and un-published reports of malaria vector control and parasite prevention in Uganda was conducted for the period 1900–2013. The objective was to provide a perspective as to how epidemiological intelligence was used to design malaria control before and during the global malaria eradication programme (GMEP) and to contrast this with the evidence generated in support of the Roll Back Malaria (RBM) initiative from 1998 to date.ResultsDuring the GMEP era, comprehensive investigations were undertaken on the effectiveness of vector and parasite control such as indoor residual house-spraying (IRS) and mass drug administration (MDA) at different sites in Uganda. Nationwide malariometric surveys were undertaken between 1964 and 1967 to provide a profile of risk, epidemiology and seasonality leading to an evidence-based national cartography of risk to characterize the diversity of malaria transmission in Uganda. At the launch of the RBM initiative in the late 1990s, an equivalent level of evidence was lacking. There was no contemporary national evidence-base for the likely impact of insecticide-treated nets (ITN), no new malariometric data, no new national cartography of malaria risk or any evidence of tailored intervention delivery based on variations in the ecology of malaria risk in Uganda.DiscussionDespite millions of dollars of overseas development assistance over the last ten years in ITN, and more recently the resurrection of the use of IRS, the epidemiological impact of vector control remains uncertain due to an absence of nationwide basic parasite and vector-based field studies.ConclusionReadily available epidemiological data should become the future business model to maximize malaria funding from 2015. Over the next five to ten years, accountability, impact analysis, financial business cases supported by a culture of data use should become the new paradigm by which malaria programmes, governments and their development partners operate.

Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda.

ObjectiveUnlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV.MethodsAntibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children.ResultsKaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies.ConclusionThe association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.

Effector Phenotype ofPlasmodium falciparum–Specific CD4+T Cells Is Influenced by Both Age and Transmission Intensity in Naturally Exposed Populations

Mechanisms mediating immunity to malaria remain unclear, but animal data and experimental human vaccination models suggest a critical role for CD4(+) T cells. Advances in multiparametric flow cytometry have revealed that the functional quality of pathogen-specific CD4(+) T cells determines immune protection in many infectious models. Little is known about the functional characteristics of Plasmodium-specific CD4(+) T-cell responses in immune and nonimmune individuals. We compared T-cell responses to Plasmodium falciparum among household-matched children and adults residing in settings of high or low malaria transmission in Uganda. Peripheral blood mononuclear cells were stimulated with P. falciparum antigen, and interferon γ (IFN-γ), interleukin 2, interleukin 10, and tumor necrosis factor α (TNF-α) production was analyzed via multiparametric flow cytometry. We found that the magnitude of the CD4(+) T-cell responses was greater in areas of high transmission but similar between children and adults in each setting type. In the high-transmission setting, most P. falciparum-specific CD4(+) T-cells in children produced interleukin 10, while responses in adults were dominated by IFN-γ and TNF-α. In contrast, in the low-transmission setting, responses in both children and adults were dominated by IFN-γ and TNF-α. These findings highlight major differences in the CD4(+) T-cell response of immune adults and nonimmune children that may be relevant for immune protection from malaria.