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Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene.

BACKGROUND: The expansion of sleeping sickness caused by Trypanosoma brucei rhodesiense beyond its traditional focus in southeast Uganda has been linked with large-scale livestock restocking. To assess the risk presented to the human population by domestic livestock, human-infective T b rhodesiense must be distinguished from non-human-infective T brucei brucei, since both parasites can be present in cattle. We investigated the use of a simple genetic marker to characterise parasites collected from cattle in villages within the new sleeping sickness focus in Soroti District, Uganda. METHODS: 70 T brucei sl samples of known human infectivity status collected from human beings and cattle in Tororo District, Uganda, from 1989 to 1991 were screened for the presence of the human-serum-resistance-associated (SRA) gene by conventional PCR. In 2000-01, blood samples from 200 randomly selected cattle in six villages and two markets in Soroti District were screened for T brucei sl parasites by PCR; positive samples were screened for the presence of the SRA gene. FINDINGS: The SRA gene was present in all 29 samples from patients with sleeping sickness in Tororo District. Of the 41 samples collected from cattle at the same time, the SRA gene was present in the eight samples that tested resistant to human serum in vitro, whereas it was absent from all 33 isolates that were sensitive to human serum in vitro. Of the 200 cattle sampled in Soroti District, we estimated that up to 18% (95% CI 12-23) were infected with T b rhodesiense. INTERPRETATION: Detection of the SRA gene could provide the basis for a simple diagnostic test to enable targeted control of T b rhodesiense in the domestic livestock reservoir, thereby reducing the public-health burden of sleeping sickness in east Africa.

Animals↗

Towards improving hospital performance in Uganda and Zambia: reflections and opportunities for autonomy.

Hospitals have been relatively neglected although their high resource consumption implies that gains from improving the services they deliver may be substantial. Nevertheless, the challenges posed by hospital reforms are great. Hospital autonomy usually consists of both decentralisation, and a greater measure of exposure to market forces. In Uganda and Zambia, more traditional 'decentralisation' of authority to district level authorities includes district hospitals; and some measure of 'autonomy' (known as 'self-accounting status' in Uganda) has been applied to some or all second and third level referral hospitals. The hospital policies pursued in both countries present opportunities to tackle their hospital sectors. In Zambia, purchasing of services means that new incentives and policy mechanisms can come into play. Little advantage has been taken of these opportunities to date. In Uganda, there is no financial link between districts and higher levels of the system, but decentralisation of control over personnel is more advanced. These two components--the alignment of incentives (to promote access and quality for those intended to be covered by the public budget) and the effective decentralisation of control over key resources--seem to us the key tools to address the stubborn problems of hospitals.

Efficiency, Organizational↗

HIV vaccines: the Uganda experience.

By late 1980s Uganda was the epicenter of the AIDS epidemic in the world but strong preventive interventions and committed leadership has turned the epidemic round. HIV incidence and prevalence have declined but infection rates remain unacceptably high, making HIV vaccine research a priority. Uganda pioneered the first HIV vaccine trial in Africa but had to overcome ethical, scientific and logistical challenges. Preparation for HIV vaccine evaluation (PAVE) studies started in 1994 involving 3000 subjects followed up for 2 years. Results provided information on HIV vaccines acceptability, behavioral change, prevalence and incidence of HIV and gave indication for future successful HIV vaccine trial. In 1996, preparation for HIV vaccine trial of ALVAC (Clade B) HIV vCP205 to test for safety, immunogenicity and cross-clade reactivity started by building consensus in Uganda and addressing scientific, ethical, social, legal and political issues. The study recruited 40 healthy HIV negative volunteers (20 received the vaccine, 20 controls). The experience and skills gained forms a basis for more HIV vaccine trials and we will draw on this experience, and more trials using ALVAC (Clade A) HIV vaccine in both adults and children are being planned as a follow up.

AIDS Vaccines↗

Traditional herbal drugs of Southern Uganda, II: literature analysis and antimicrobial assays.

Continuing field interviews brought the total species used for disease treatment by herbalists of the majority Baganda Tribe of southern Uganda to 168. Literature searches provided support for the ethnomedical claims for a number of these species, and provided criteria for the species classification into four categories of use validation. They also helped guide the selection of species for recollection, for chemical extraction and further testing in laboratories of the Uganda Ministry of Health and the University of Illinois at Chicago. Many species proved active against microorganisms in several susceptibility assays conducted in Uganda and the US.

Anti-Infective Agents↗

High prevalence of carriage of antibiotic-resistant Streptococcus pneumoniae in children in Kampala Uganda.

There are few data on antibiotic-resistant Streptococcus pneumoniae in Uganda. A total of 191 healthy children in Kampala, Uganda were screened for nasopharyngeal carriage of S. pneumoniae; 118 (62%) of the children were carriers. Antimicrobial susceptibility and serotype of 115 strains was determined. Ninety-six (83.5%) of the isolates were of intermediate resistance to penicillin and 19 (16.5%) were susceptible. All strains were susceptible to cefotaxime. The rates of resistance to other drugs were trimethoprim-sulphamethoxazole (83.5%), tetracycline (28.7%) and chloramphenicol (10.4%). All strains were susceptible to rifampicin, erythromycin and clindamycin. Serogroups 6, 9, 14, 19 and 23 accounted for 80% of the isolates. These data show that the rate of carriage of antibiotic-resistant pneumococci by children is high in Kampala, Uganda.

Anti-Bacterial Agents↗

Strain differentiation of Onchocerca volvulus from Uganda using DNA probes.

Polymerase chain reaction (PCR) combined with non-radioactive DNA hybridization was applied for the detection and characterization of a 150 bp tandem repeat of Onchocerca volvulus. DNA of worms from western Uganda was amplified and then probed with a digoxygenin-labelled oligonucleotide, specific for the forest form of O. volvulus and compared to samples from various African countries. Hybridization was only observed with PCR products from the forest in Liberia, south-eastern Ghana, Benin and southern Cameroon, but not with worms from Uganda or the savannah in Burkina Faso and northern Ghana. A nested PCR using primers derived form the forest form-specific DNA sequence confirmed these results. Morphometric studies revealed length differences between the microfilariae of Ugandan O. volvulus to those of West Africa, especially to those of the savannah in Burkina Faso. It is concluded that the forest/savannah classification of O. volvulus from West Africa is not suitable for Simulium neavei-transmitted O. volvulus from Uganda.

Africa, Western↗

Further studies of space-time clustering of Burkitt's lymphoma in Uganda.

All hospital-treated cases of Burkitt's lymphoma (BL), with onset of symptoms in the period 1963-68 and resident in the Lango and Acholi districts of Uganda, were identified. The average annual incidence of BL in the 6-year period was 1-87 X 10(-5), similar to that in the adjacent West Nile district. Contrary to findings in other areas of Uganda, there was no evidence of seasonal variation in the onset of cases, nor of space-time clustering, nor of a decline in the incidence of BL in the study period. An inverse relationship was noted between the median age at onset of BL and the incidence of the disease in different areas of Uganda, a finding consistent with intense malarial infection being a precipitating factor for BL. The variable observations with respect to space-time clustering of BL and seasonal variation in incidence in different areas remains unexplained, but it is suggested that a closer study of the patterns of malarial infection in these areas may help to account for the findings.

Age Factors↗

Cancer survival in Kampala, Uganda.

Epidemiological data on the occurrence of cancer in sub-Saharan Africa are sparse, and population-based cancer survival data are even more difficult to obtain due to various logistic difficulties. The population-based Cancer Registry of Kampala, Uganda, has followed up the vital status of all registered cancer patients with one of the 14 most common forms of cancer, who were diagnosed and registered between 1993 and 1997 in the study area. We report 5-year absolute and relative survival estimates of the Ugandan patients and compare them with those of black American patients diagnosed in the same years and included in the SEER Program of the United States. In general, the prognosis of cancer patients in Uganda was very poor. Differences in survival between the two patient populations were particularly dramatic for those cancer types for which early diagnosis and effective treatment is possible. For example, 5-year relative survival was as low as 8.3% for colorectal cancer and 17.7% for cervical cancer in Uganda, compared with 54.2 and 63.9%, respectively, for black American patients. The collection of good-quality follow-up data was possible in the African environment. The very poor prognosis of Ugandan patients is most likely explained by the lack of access to early diagnosis and treatment options in the country. On the policy level, the results underscore the importance of the consistent application of the national cancer control programme guidelines as outlined by the World Health Organization.

Adolescent↗

Increasing antimalarial drug resistance in Uganda and revision of the national drug policy.

Chloroquine (CQ) resistance was first documented in Uganda in 1988. Subsequent surveillance of antimalarial drug resistance, conducted by the Ugandan Ministry of Health and several research organizations, suggests that resistance to CQ is now widespread, reaching critical levels in many areas of the country. In June 2000, the Ministry of Health held a National Consensus Meeting to evaluate the available drug efficacy data and review the national antimalarial drug policy. After extensive debate, the combination of CQ + sulfadoxine-pyrimethamine (SP) was chosen to replace CQ as the first-line treatment of uncomplicated malaria as an interim policy. This review evaluates the in vivo drug efficacy studies conducted in Uganda since 1988 and issues confronted in revision of the drug policy. The Ugandan experience illustrates the challenges faced by sub-Saharan African countries confronted with rising CQ resistance but limited data on potential alternative options. The choice of CQ + SP as a provisional policy in the absence of prerequisite efficacy, safety and cost-effectiveness data reflects the urgency of the malaria treatment problem, and growing pressure to adopt combination therapies. Surveillance of CQ + SP treatment efficacy, collection of additional data on alternative regimens and active consensus building among key partners in the malaria community will be necessary to develop a rational long-term antimalarial treatment policy in Uganda.

Animals↗

Epidemiology and geography of Schistosoma mansoni in Uganda: implications for planning control.

Intestinal schistosomiasis caused by infection with Schistosoma mansoni is a widespread public health problem in Uganda. Although long known to be endemic, its current distribution within the country requires updating of parasitological data to help guide planned control. We report such data collected between 1998 and 2002 from 201 schools and 68 communities across Uganda. In accordance with epidemiological expectation, prevalence and intensity increased with age, peaking at 10-20 years and thereafter declined moderately with age, whereas intensity declined more rapidly with age, and the prevalence of infection in a school was non-linearly related to the mean intensity of infection. We used geographical information systems to map the distribution of infection and to overlay parasitological data with interpolated environmental surfaces. The derived maps indicate both a widespread occurrence of infection and a marked variability in infection prevalence, with prevalence typically highest near the lakeshore and along large rivers. No transmission occurred at altitudes >1400 m or where total annual rainfall was <900 mm; limits which can help estimate the population at risk of schistosomiasis. The results are discussed in reference to the ecology of infection and provide an epidemiological framework for the design and implementation of control efforts underway in Uganda.

Adolescent↗

FCGR3 variants and expression of human neutrophil antigen-1a, -1b, and -1c in the populations of northern Germany and Uganda.

BACKGROUND: Human neutrophil antigen-1c (HNA-1c) (SH) has been described as the third alloantigen of the Fc receptor type IIIb (FcgammaRIIIb) for IgG beside the known alloantigens HNA-1a (NA1) and HNA-1b (NA2). Controversy exists on the assignment of the HNA-1c coding gene to the FCGR3B locus and on a possible linkage between the HNA-1c and HNA-1a coding genes. STUDY DESIGN AND METHODS: Two hundred sixty northern German blood donors and 43 individuals from Uganda were typed for FCGR3B*1 (NA1), FCGR3B*2 (NA2), and FCGR3B*3 (SH) by allele-specific PCR. In a subset of FCGR3B*3-positive probands, PCR-amplified FCGR3 fragments were subcloned and sequenced. Transmission of FCGR3B*3 was analyzed in family studies. A possible correlation with the FcgammaRIIIb alloantigen expression was investigated by flow cytometry. RESULTS: In the northern German population, FCGR3B*3 was found exclusively in individuals carrying FCGR3B*1 independent of the existence of FCGR3B*2 at a frequency of 5 percent. In the individuals from Uganda, each possible combination of FCGR3B*1, FCGR3B*2, and FCGR3B*3 was detected. FCGR3B*3 frequency was 34.9 percent. Within both populations, some individuals carried each of the three genotypes. DNA sequencing revealed new FCGR3 variants caused by single nucleotide exchanges at the typical polymorphic positions. In one individual, six different FCGR3 variants were detected. CONCLUSION: The coincidence of the three known FCGR3B alleles varies within the population of Germany and Uganda. Three simultaneous FCGR3B forms may be explained by two gene loci, but the basis of the high number of different variants in some individuals still remains unclear. Possible explanations may be a hypermutation mechanism or a number of FCGR3 higher than expected hitherto.

Alleles↗

Evidence for the occurrence of Trypanosoma brucei rhodesiense sleeping sickness outside the traditional focus in south-eastern Uganda.

The occurrence of Trypanosoma brucei rhodesiense west of the River Nile, in Masindi district in the mid-western part of Uganda, is confirmed. Masindi borders the traditional belt of T. b. gambiense infection in the north-west, Gulu in the north and the Democratic Republic of Congo in the west. Of the 702 persons tested for sleeping sickness in Masindi, 113 (16%) were positive by the card agglutination test for trypanosomiasis (CATT). Trypanosomes were observed in samples of cerebrospinal fluid (CSF) from two (0.3%) of the subjects: a 7-year-old girl, who had been ill for 2 weeks and yet was in good general condition, with three white blood cells (WBC)/microliter CSF; and a 47-year-old woman who had been ill for 8 months, looked sickly, had seven WBC/microliter CSF, but was still able to dig in her gardens. Rats and mice inoculated with blood from the two parasitologically confirmed cases became parasitaemic on day 3 post-inoculation, indicating that the parasites were T. b. rhodesiense. Isoenzyme analysis revealed that the parasites isolated from one of these confirmed cases belonged to a zymodeme (449) which has not been previously observed among isolates from south-eastern or north-western Uganda. Although the isolate shared PGM2 and ICD3 patterns with T. b. gambiense and T. b. rhodesiense, respectively, it did not have the SOD3:5 pattern characteristic of T. b. gambiense. The spread of T. b. rhodesiense beyond its traditional focus and the development of areas where this subspecies and T. b. gambiense are co-endemic will complicate the control of sleeping sickness in Uganda; although the CATT is very useful for the mass screening of populations for T. b. gambiense area, it is not applicable in the detection of T. b. rhodesiense.

Agglutination Tests↗

Evaluating herbal medicine for the management of Herpes zoster in human immunodeficiency virus-infected patients in Kampala, Uganda.

OBJECTIVE: This study was carried out to evaluate the potential effectiveness of herbal treatments used for herpes zoster (HZ) by a great number of people living with acquired immunodeficiency syndrome (PLWAs) in Uganda. SETTING: Kampala, Uganda. Clinics of indigenous traditional healers, at the Department of Medicine of Mulago Hospital, Makerere University, and at The AIDS Support Organization (TASO) Clinic, providing primary care to people living with HIV and AIDS. DESIGN, PATIENTS, AND PARTICIPANTS: Nonrandomized, nonplacebo controlled, observational study in two phases. Inclusion criteria included HIV seropositivity and a recent HZ attack. In phase 1, 52 patients were enrolled, treated, and followed for up to 3 months at three healers' clinics, and compared to 52 TASO Clinic controls receiving ambulatory care. Phase 2 was similar in design to phase 1, but lasted longer (6-month follow-up) and involved 154 hospital outpatients treated with herbal medicine and 55 TASO controls. In both phases, healer patients were given herbal treatment according to healers' prescriptions, while controls received either symptomatic treatment or acyclovir. RESULTS: Healer patients and controls experienced similar rates of resolution of their HZ attacks. Fewer healer patients than controls experienced superinfection in phase 1 (18% versus 42%, p < 0.02) and fewer healer patients showed keloid formation in either phase. This difference was not statistically significant. In both phases, zoster-associated pain resolved substantially faster among healer patients with a higher degree of significance in phase 2 where the progression of pain over time could be seen because of the longer follow-up (phase 1: maximum p value (pmax) < pmax < 0.02 at 1 month, pmax < 0.005 at 2 months, pmax < 0.0001 at 3 months). CONCLUSION: Herbal treatment is an important local and affordable primary care alternative for the management of HZ in HIV-infected patients in Uganda and similar settings.

Adolescent↗

Rates of public investment for road safety in developing countries: case studies of Uganda and Pakistan.

OBJECTIVE: This paper assesses the magnitude of public investment in road safety in Uganda and Pakistan. METHODS: The study reviewed government budgetary records on expenditure for road safety for each country, as well as World Bank estimates of bilateral and NGO assistance directed to road safety. The authors interviewed key informants in each government who would know about public or NGO activity on road safety. RESULTS: Budgetary expenditure on road safety at all levels of government in Uganda and Pakistan is $0.09 and $0.07 per capita respectively. DISCUSSION: The scale of public activity in road safety in Uganda and Pakistan is extremely limited. If there are diminishing returns to scale for road safety investments, this would suggest that the potential effectiveness of properly chosen safety measures could never be higher. CONCLUSION: Large reductions in morbidity and mortality are likely if investment in road safety is expanded.

Accidents, Traffic↗

Abolition of cost-sharing is pro-poor: evidence from Uganda.

OBJECTIVE: To document the effects of the abolition of user fees on utilization of health services in Uganda with emphasis on poor and vulnerable groups. METHODS: A longitudinal study using quantitative and qualitative methods was carried out in 106 health facilities across the country. Health records were reviewed to determine trends in overall utilization patterns and use among vulnerable groups. A modification of wealth ranking as defined by the Uganda Poverty Participatory Assessment Project was used to categorize households by socio-economic status in order to compare utilization by the poor against that of other socio-economic groups. FINDINGS: There was a marked increase in utilization in all population groups that was fluctuating in nature. The increase in utilization varied from 26% in public referral facilities in 2001, rising to 55% in 2002 compared with 2000. The corresponding figures for the lower level facilities were 44% and 77%, respectively. Increase in utilization among the poor was more than for other socio-economic categories. Women utilized health services more than men both before and after cost-sharing. Higher increases in utilization were noted among the over-five age group compared with the under-fives. There were no increases in utilization for preventive and inpatient services. With respect to quality of care, there were fewer drug stock-outs in 2002 compared with 2000 and 2001. There was no deterioration of other indicators such as cleanliness, compound maintenance and staff availability reported. CONCLUSION: The study suggests that there is a financial barrier created by cost-sharing that decreases access to services, especially among the poor in Uganda. However, further studies are needed to clarify issues of utilization by age and gender.

Age Factors↗

Integrating refugee and host health services in West Nile districts, Uganda.

Refugees are a common feature in Africa and Uganda is no exception. However, Uganda does not have the resources to provide health care to all its own citizens, let alone to refugees. Refugee health services are therefore usually set up and provided separately by international organizations such as the United Nations High Commissioner for Refugees (UNHCR). However, such services often end up being the only available or reliable services in a particular location for both host and refugee populations. Yet the host populations are often denied access to these services because, in theory, other services are being provided by their government. The case study in the West Nile region of Uganda describes how host and refugee services were integrated in an attempt to address the concerns of inequity of access to care for host populations, when reasonably good health services were available to nearby refugee populations. The paper identifies and discusses the challenges encountered and those remaining.

Delivery of Health Care, Integrated↗

Trends in antenatal human immunodeficiency virus prevalence in Western Kenya and Eastern Uganda: evidence of differences in health policies?

OBJECTIVE: To observe recent trends in human immunodeficiency virus (HIV) prevalence in antenatal clinic attendees to determine if previously noted falls in HIV prevalence are occurring on both sides of the Kenyan-Ugandan border. Design An ecologic study was conducted at the district level comparing HIV prevalence rates over time using data available through reports published by the Kenyan and Ugandan Ministries of Health and UNAIDS. METHODS: Sentinel sites were compared with respect to population, ethnicity, language group, and the prevalence of circumcision practice. The prevalence of HIV found at each sentinel site was recorded for the years 1990-2000 and analysed visually and by conducting bivariate correlations. RESULTS: Ethnographic analysis revealed a wide mix of ethnic and language groups and circumcision rates on both sides of the border. All sentinel surveillance sites in Uganda showed trends towards decreasing HIV prevalence, with three of five sites showing statistically significant declines (r = -0.87, -0.85, -0.86, P < 0.05). In contrast, all of the surveillance sites in Kenya showed trends toward increasing HIV prevalence, with two of the five sites showing statistically significant increases (r = 0.62, 0.84, P < 0.05). CONCLUSIONS: The declines in HIV prevalence occurring in Uganda are not being seen in geographically proximal districts of Kenya. No obvious differences in ethnic groupings or their associated prevalence of circumcision appeared to explain these differences. This suggests that decreasing HIV prevalence in Uganda is not due to the natural course of the epidemic but reflects real success in terms of HIV control policies.

Circumcision, Male↗

Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda.

BACKGROUND: Kaposi's sarcoma (KS) is associated epidemiologically with HIV infection and with human herpesvirus 8 (HHV-8 or KSHV). Both KS and HIV infection are common in Uganda. We conducted a case-control study of 458 HIV-seropositive. Ugandan adults with KS and 568 HIV-seropositive subjects without KS to examine risk factors for HIV-associated KS. METHODS: We recruited newly diagnosed adult KS cases from five hospitals in Kampala, Uganda and controls from a large referral clinic for HIV infection at Mulago Hospital. All cases and controls were counselled and tested for HIV and answered an interviewer-administered questionnaire about their home, socio-economic conditions, lifestyle and sexual behaviour before they became ill. Only HIV-seropositive subjects were included in the analysis. RESULTS: There were 295 males and 163 females with KS and 227 male and 341 female controls. Age distribution was similar but there was a higher proportion of cases (45%) than controls (29%) residing in rural regions of Uganda. KS cases were more likely than controls to have a higher level of education (X2 for trend, 4.8; P = 0.03), to have occupations associated with affluence [chi 2 for heterogeneity, 17.3 on 5 degrees of freedom (df); P = 0.004] and to come from larger settlements [adjusted odds ratio (OR) for settlements of > 1000 versus 10-99 houses, 1.8; 95% confidence interval (CI), 1.1-3.0]. Cases were more likely than controls to have high household income (chi 2 for trend, 32.6; P < 0.001) and other markers of urban or rural wealth such as owning several cows (chi 2 for trend, 9.5; P = 0.002). Cases were more likely to travel away from home (adjusted OR, 1.6; 95% CI, 1.1-2.3) and more likely to have spent increasing time in contact with water (chi 2 for trend, 12.3; P < 0.001). Few indices of sexual behaviour were related to risk of KS, including reported number of sexual partners. Cases were more likely than controls to be married to one rather than several spouses (adjusted OR, 1.6; 95% CI, 1.2-2.2) and to have reported a history of sexually transmitted diseases (STD) (adjusted OR, 1.6; 95% CI, 1.2-2.3). CONCLUSIONS: Among HIV-infected subjects, KS cases are characterized by better education and greater affluence, compared with controls. Urban address, travel away from home, exposure to water, monogamous marriage and self-reported STD were also more frequent among KS cases than controls. The higher socio-economic status of persons with HIV and KS may be a marker for enhanced exposure to a possibly sexually transmitted agent, or for a delayed exposure to a childhood infection. The risk posed by exposure to water among KS cases requires further study.

AIDS-Related Opportunistic Infections↗