Showing papers by "Makerere University published in 2008"

Transformation of the Nitrogen Cycle: Recent Trends, Questions, and Potential Solutions

Abstract: Humans continue to transform the global nitrogen cycle at a record pace, reflecting an increased combustion of fossil fuels, growing demand for nitrogen in agriculture and industry, and pervasive inefficiencies in its use. Much anthropogenic nitrogen is lost to air, water, and land to cause a cascade of environmental and human health problems. Simultaneously, food production in some parts of the world is nitrogen-deficient, highlighting inequities in the distribution of nitrogen-containing fertilizers. Optimizing the need for a key human resource while minimizing its negative consequences requires an integrated interdisciplinary approach and the development of strategies to decrease nitrogen-containing waste.

Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings.

Abstract: The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosis-associated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosis-associated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is envisaged that these definitions could be used by clinicians and researchers in a variety of settings to promote standardisation and comparability of data.

Part I: Cancer in Indigenous Africans—burden, distribution, and trends

Abstract: Cancer is an under-emphasised issue in Africa, partly because of the overwhelming burden of communicable diseases. However cancer is a common disease in Africa with 650 000 people, of a population of 965 million, diagnosed annually. Furthermore, the lifetime risk in females (between 0 and 64 years) of cancer is about 10%, which is only about 30% lower than the risk in developed countries. In females, the lifetime risk of dying from cancer in Africa is almost double the risk in developed countries. This Review is the first of two papers and focuses on the current knowledge of the distribution and trends of the most common cancers in Africa. The cancers with the highest incidence are cervical, breast, and now HIV-associated Kaposi's sarcoma. The top five cancers in males--Kaposi's sarcoma (constituting 12.9% of all cancers in males) and cancer of the liver (14.8%), prostate (9.5%), bladder (6.1%), and non-Hodgkin lymphoma (5.7%)--and in females--cancer of the cervix (constituting 23.3% of all cancers in females) and breast (19.2%), Kaposi's sarcoma (5.1%), cancer of the liver (5.0%), and non-Hodgkin lymphoma (3.7%)--are discussed in detail. The second paper will focus on the causes and control of cancer in Africa. The cancer burden in Africa is likely to increase as a result of increases in HIV-associated cancers, changes in lifestyles associated with economic development, and the increasing age of the population (despite AIDS). Although the knowledge of cancer in this region is improving, better surveillance of cancer incidence, mortality, and prevalence of risk factors is urgently needed to monitor the development of the cancer epidemic, formulate appropriate cancer-control strategies, and assess the outcomes of these strategies.

Cerebral malaria in children is associated with long-term cognitive impairment

Abstract: OBJECTIVE. Cerebral malaria affects >785000 African children every year. We previously documented an increased frequency of cognitive impairment in children with cerebral malaria 6 months after their initial malaria episode. This study was conducted to determine the long-term effects of cerebral malaria on the cognitive function of these children. METHODS. Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested. RESULTS. At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge. CONCLUSIONS. Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation.

Trichomonas vaginalis Infection and Human Immunodeficiency Virus Acquisition in African Women

Abstract: Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However its impact as a cofactor for HIV acquisition is poorly understood. Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls). All samples underwent polymerase chain reaction (PCR) analysis for Trichomonas vaginalis DNA. For cases analyzed samples were from the visit in which HIV seroconversion was detected and the visit preceding detection of seroconversion; for controls one analyzed sample was from the visit matched by follow-up duration to the cases seroconversion visit and the other sample was from the visit immediately preceding the matched visit. The prevalence of T. vaginalis infection before HIV infection was 11.3% in cases and 4.5% in controls (P = .002). In multivariable analysis controlling for hormonal contraception other STIs behavioral and demographic factors the adjusted odds ratio for HIV acquisition was 2.74 (95% confidence interval 1.25-6.00) for T. vaginalis-positive cases. The presence of behavioral risk factors for HIV infection study recruitment from a referral population at high-risk for HIV primary sex partner-associated risk for HIV infection and herpes simplex virus type 2 seropositivity were also predictive of incident HIV infection. T. vaginalis infection is strongly associated with an increased risk for HIV infection in this general population of African women. Given the high prevalence of T. vaginalis infection in HIV-endemic areas T. vaginalis control may have a substantial impact on preventing HIV acquisition among women. (authors)

Outcomes of Cryptococcal Meningitis in Uganda Before and After the Availability of Highly Active Antiretroviral Therapy

Abstract: Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa. Two prospective observational cohorts enrolled human immunodeficiency virus (HIV)-infected antiretroviral-naive persons with CM in Kampala Uganda. The first cohort was enrolled in 2001-2002 (n = 92) prior to the availability of highly active antiretroviral therapy (HAART) and the second was enrolled in 2006-2007 (n = 44) when HAART was available. Ugandans presented with prolonged CM symptoms (median duration 14 days; interquartile range 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P less than .001). HAART was started 35_13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007 the survival rate continued to decrease after hospitalization with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients with 4 deaths. At 6 months after CM diagnosis 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H2O; 81% of patients had elevated pressure (greater than 200 mm H2O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures greater than 250 mm H2O (odds ratio [OR] 2.1; 95% confidence interval [CI] 0.9-5.2; P = .09). Initial CSF WBC counts of less than 5 cells/mL were associated with failure of CSF sterilization (OR 17.3; 95% CI 3.1-94.3; P less than .001) and protein levels less than 35 mg/dL were associated with higher mortality (OR 2.0; 95% CI 1.2-3.3; P = .007). Significant CM-associated mortality persists despite the administration of amphotericin B and HIV therapy because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed. (authors)

Effect of Human Immunodeficiency Virus Type 1 (HIV-1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV-1 Infection

Abstract: Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype viral load and CD4+ cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4+ cell count of less than or equal to 250 cells/mm3) and to AIDS-associated death. A total of 59.1% of study subjects had subtype D strains 15.1% had subtype A 21.1% had intersubtype recombinant subtypes 4.3% had multiple subtypes and 0.3% had subtype C. Of the 350 subjects 129 (37%) progressed to AIDS and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D(6.5 years) recombinant subtypes (5.6 years) or multiple subtypes (5.8 years) compared with persons with subtype A (8.0 years; P = .022). Relative tosubtype A adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI} 1.10-4.11] for subtype D 2.16 [95% CI 1.05-4.45] for recombinant subtypes and 4.40 [95% CI 1.71-11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR 5.65; 95% CI 1.37-23.4) recombinant subtypes (adjusted HR 6.70; 95% CI 1.56-28.8) and multiple subtypes (adjusted HR 7.67; 95% CI 1.27-46.3) compared with subtype A. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression. (authors)

Loop-Mediated Isothermal Amplification (LAMP) Method for Rapid Detection of Trypanosoma brucei rhodesiense

Abstract: Loop-mediated isothermal amplification (LAMP) of DNA is a novel technique that rapidly amplifies target DNA under isothermal conditions. In the present study, a LAMP test was designed from the serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense, the cause of the acute form of African sleeping sickness, and used to detect parasite DNA from processed and heat-treated infected blood samples. The SRA gene is specific to T. b. rhodesiense and has been shown to confer resistance to lysis by normal human serum. The assay was performed at 62°C for 1 h, using six primers that recognised eight targets. The template was varying concentrations of trypanosome DNA and supernatant from heat-treated infected blood samples. The resulting amplicons were detected using SYTO-9 fluorescence dye in a real-time thermocycler, visual observation after the addition of SYBR Green I, and gel electrophoresis. DNA amplification was detected within 35 min. The SRA LAMP test had an unequivocal detection limit of one pg of purified DNA (equivalent to 10 trypanosomes/ml) and 0.1 pg (1 trypanosome/ml) using heat-treated buffy coat, while the detection limit for conventional SRA PCR was ∼1,000 trypanosomes/ml. The expected LAMP amplicon was confirmed through restriction enzyme RsaI digestion, identical melt curves, and sequence analysis. The reproducibility of the SRA LAMP assay using water bath and heat-processed template, and the ease in results readout show great potential for the diagnosis of T. b. rhodesiense in endemic regions.

Access to and utilisation of health services for the poor in Uganda: a systematic review of available evidence

Abstract: Inequalities in the burden of disease and access to health care is a prominent concern in Uganda and other sub-Saharan African countries. This is a systematic review of socio-economic differences in morbidity and access to health care in Uganda. It includes published studies from electronic databases and official reports from surveys done by government, bilateral and multilateral agencies and universities. The outcome measures studied were: the distribution of HIV/AIDS; maternal and child morbidity; and access to and utilisation of health services for people belonging to different socio-economic and vulnerability groups. Forty-eight of 678 identified studies met our inclusion criteria. Results indicate that the poor and vulnerable experience a greater burden of disease but have lower access to health services than the less poor. Barriers to access arise from both the service providers and the consumers. Distance to service points, perceived quality of care and availability of drugs are key determinants of utilisation. Other barriers are perceived lack of skilled staff in public facilities, late referrals, health worker attitude, costs of care and lack of knowledge. Longitudinal and controlled studies are needed to see if strategies to improve access to services reach the poor.

Voluntary HIV counselling and testing among men in rural western Uganda: Implications for HIV prevention

Abstract: Voluntary HIV counselling and testing (VCT) is one of the key strategies in the prevention and control of HIV/AIDS in Uganda. However, the utilization of VCT services particularly among men is low in Kasese district. We therefore conducted a study to determine the prevalence and factors associated with VCT use among men in Bukonzo West health sub-district, Kasese district. A population-based cross-sectional study employing both quantitative and qualitative techniques of data collection was conducted between January and April 2005. Using cluster sampling, 780 men aged 18 years and above, residing in Bukonzo West health sub-district, were sampled from 38 randomly selected clusters. Data was collected on VCT use and independent variables. Focus group discussions (4) and key informant interviews (10) were also conducted. Binary logistic regression was performed to determine the predictors of VCT use among men. Overall VCT use among men was 23.3% (95% CI 17.2–29.4). Forty six percent (95% CI 40.8–51.2) had pre-test counselling and 25.9% (95%CI 19.9–31.9) had HIV testing. Of those who tested, 96% returned for post-test counselling and received HIV results. VCT use was higher among men aged 35 years and below (OR = 2.69, 95%CI 1.77–4.07), the non-subsistence farmers (OR = 2.37, 95%CI 2.37), the couple testing (OR = 2.37, 95%CI 1.02–8.83) and men with intention to disclose HIV test results to sexual partners (OR = 1.64, 95%CI 1.04–2.60). The major barriers to VCT use among men were poor utilization of VCT services due to poor access, stigma and confidentiality of services. VCT use among men in Bukonzo West, Kasese district was low. In order to increase VCT use among men, the VCT programme needs to address HIV stigma and improve access and confidentiality of VCT services. Among the more promising interventions are the use of routine counselling and testing for HIV of patients seeking health care in health units, home based VCT programmes, and mainstreaming of HIV counselling and testing services in community development programmes.

Gastrointestinal Bacterial Transmission among Humans, Mountain Gorillas, and Livestock in Bwindi Impenetrable National Park, Uganda

Abstract: Habitat overlap can increase the risks of anthroponotic and zoonotic pathogen transmission between humans, livestock, and wild apes. We collected Escherichia coli bacteria from humans, livestock, and mountain gorillas (Gorilla gorilla beringei) in Bwindi Impenetrable National Park, Uganda, from May to August 2005 to examine whether habitat overlap influences rates and patterns of pathogen transmission between humans and apes and whether livestock might facilitate transmission. We genotyped 496 E. coli isolates with repetitive extragenic palindromic polymerase chain reaction fingerprinting and measured susceptibility to 11 antibiotics with the disc-diffusion method. We conducted population genetic analyses to examine genetic differences among populations of bacteria from different hosts and locations. Gorilla populations that overlapped in their use of habitat at high rates with people and livestock harbored E. coli that were genetically similar to E. coli from those people and livestock, whereas E. coli from gorillas that did not overlap in their use of habitats with people and livestock were more distantly related to human or livestock bacteria. Thirty-five percent of isolates from humans, 27% of isolates from livestock, and 17% of isolates from gorillas were clinically resistant to at least one antibiotic used by local people, and the proportion of individual gorillas harboring resistant isolates declined across populations in proportion to decreasing degrees of habitat overlap with humans. These patterns of genetic similarity and antibiotic resistance among E. coli from populations of apes, humans, and livestock indicate that habitat overlap between species affects the dynamics of gastrointestinal bacterial transmission, perhaps through domestic animal intermediates and the physical environment. Limiting such transmission would benefit human and domestic animal health and ape conservation.

Delayed care seeking for fatal pneumonia in children aged under five years in Uganda: a case-series study

Abstract: Resumen Retraso en la busqueda de atencion para casos de neumonia mortal en menores de cinco anos en Uganda: estudio de serie de casos Objetivo Examinar las historias clinicas de ninos que habian muerto de neumonia en la Uganda rural e investigar las razones de que no sobrevivieran.Metodos Este estudio de serie de casos se llevo a cabo en el centro de vigilancia demografica de Iganga/Mayuge, Uganda, donde se visita una vez cada tres meses a unas 67 000 personas para registrar datos poblacionales y eventos vitales. El estudio abarco a una serie de ninos de 1 a 59 meses fallecidos entre noviembre de 2005 y agosto de 2007. Se llevaron a cabo autopsias verbales y sociales para determinar la causa probable de defuncion y las medidas de busqueda de atencion.Resultados Se determino la causa de defuncion de 164 ninos, el 27% de ellos con neumonia. De todas las muertes por esta enfermedad, la mitad se produjeron en el hospital y una tercera parte en el hogar. La duracion mediana de la neumonia fue de 7 dias, y el tiempo mediano transcurrido hasta buscar atencion fuera del hogar fue de 2 dias. Los primeros medicamentos recibidos en el hogar fueron en su mayoria antimalaricos, 52%, y antibioticos, 27%. La mayoria fueron trasladados a otros lugares para recibir atencion, y entre ellos el 36% fueron ingresados de entrada en hospitales publicos. Una tercera parte de los que llegaron al hospital de distrito fueron derivados al hospital regional, y un 19% mejoraron al parecer despues del tratamiento hospitalario. El costo mediano del tratamiento de un nino con neumonia mortal fue de US$ 5,8.Conclusion Los ninos con neumonia mortal fueron tratados incorrectamente con antimalaricos, sufrieron retrasos en la busqueda de atencion, y recibieron probablemente una atencion de mala calidad. A fin de mejorar el acceso a la atencion y la calidad de la misma, deberian analizarse la viabilidad y el efecto en la mortalidad de la formacion de los agentes de salud comunitarios y los vendedores de medicamentos en materia de tratamiento de la neumonia y la malaria.

Forest Fragmentation as Cause of Bacterial Transmission among Nonhuman Primates, Humans, and Livestock, Uganda

Abstract: We conducted a prospective study of bacterial transmission among humans, nonhuman primates (primates hereafter), and livestock in western Uganda. Humans living near forest fragments harbored Escherichia coli bacteria that were ≈75% more similar to bacteria from primates in those fragments than to bacteria from primates in nearby undisturbed forests. Genetic similarity between human/ livestock and primate bacteria increased ≈3-fold as anthropogenic disturbance within forest fragments increased from moderate to high. Bacteria harbored by humans and livestock were approximately twice as similar to those of redtailed guenons, which habitually enter human settlements to raid crops, than to bacteria of other primate species. Tending livestock, experiencing gastrointestinal symptoms, and residing near a disturbed forest fragment increased genetic similarity between a participant’s bacteria and those of nearby primates. Forest fragmentation, anthropogenic disturbance within fragments, primate ecology, and human behavior all infl uence bidirectional, interspecifi c bacterial transmission. Targeted interventions on any of these levels should reduce disease transmission and emergence.

Regional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial.

Abstract: Background Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. Methodology/Principal Findings The Partners in Prevention HSV-2/HIV-1 Transmission Trial (“Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8–31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). Conclusions/Significance HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.

Exploring the e-Learning State of Art

Abstract: e‑Learning implementation is an area in progress that continues to evolve with time and further research. Researchers in the field argue that e‑Learning is still in its infancy, resulting into nume ...

Factors Determining the Heterogeneity of Malaria Incidence in Children in Kampala, Uganda

Abstract: Background. Malaria risk may be heterogeneous in urban areas of Africa. Identifying those at highest risk for malaria may lead to more targeted approaches to malaria control. Methods. A representative sample of 558 children aged 1-10 years were recruited from a census population in a single parish of Kampala and followed up for 2 years. Malaria was diagnosed when a child presented with a new episode of fever and a thick blood smear positive for parasites. Multivariate analysis was used to identify independent predictors of malaria incidence. Results. A total of 695 episodes of uncomplicated malaria were diagnosed after 901 person years of follow-up. Sickle cell trait (relative risk [RR], 0.68 [95% confidence interval {CI}, 0.52-0.90]), glucose-6-phosphate dehydrogenase deficiency in female children (RR, 0.48 [95% CI, 0.31-0.75]), and use of an insecticide-treated bed net (RR, 0.52 [95% CI, 0.32-0.83]) were associated with a lower risk of malaria. The distance of the subject's residence from a swamp bordering the parish showed a strong "dose-response" relationship; living in the swamp was the strongest predictor of malaria risk (RR, 3.94 [95% CI, 2.61-5.97]). Conclusion. Malaria incidence was highly heterogeneous in this urban cohort of children. Malaria control interventions in urban areas should target populations living in pockets of high malaria risk.

Feasibility and acceptability of artemisinin-based combination therapy for the home management of malaria in four African sites

Abstract: The Home Management of Malaria (HMM) strategy was developed using chloroquine, a now obsolete drug, which has been replaced by artemisinin-based combination therapy (ACT) in health facility settings. Incorporation of ACT in HMM would greatly expand access to effective antimalarial therapy by the populations living in underserved areas in malaria endemic countries. The feasibility and acceptability of incorporating ACT in HMM needs to be evaluated. A multi-country study was performed in four district-size sites in Ghana (two sites), Nigeria and Uganda, with populations ranging between 38,000 and 60,000. Community medicine distributors (CMDs) were trained in each village to dispense pre-packaged ACT to febrile children aged 6–59 months, after exclusion of danger signs. A community mobilization campaign accompanied the programme. Artesunate-amodiaquine (AA) was used in Ghana and artemether-lumefantrine (AL) in Nigeria and Uganda. Harmonized qualitative and quantitative data collection methods were used to evaluate CMD performance, caregiver adherence and treatment coverage of febrile children with ACTs obtained from CMDs. Some 20,000 fever episodes in young children were treated with ACT by CMDs across the four study sites. Cross-sectional surveys identified 2,190 children with fever in the two preceding weeks, of whom 1,289 (59%) were reported to have received ACT from a CMD. Coverage varied from 52% in Nigeria to 75% in Ho District, Ghana. Coverage rates did not appear to vary greatly with the age of the child or with the educational level of the caregiver. A very high proportion of children were reported to have received the first dose on the day of onset or the next day in all four sites (range 86–97%, average 90%). The proportion of children correctly treated in terms of dose and duration was also high (range 74–97%, average 85%). Overall, the proportion of febrile children who received prompt treatment and the correct dose for the assigned duration of treatment ranged from 71% to 87% (average 77%). Almost all caregivers perceived ACT to be effective, and no severe adverse events were reported. ACTs can be successfully integrated into the HMM strategy.

Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda.

Abstract: Author(s): Yeka, Adoke; Dorsey, Grant; Kamya, Moses R; Talisuna, Ambrose; Lugemwa, Myers; Rwakimari, John Bosco; Staedke, Sarah G; Rosenthal, Philip J; Wabwire-Mangen, Fred; Bukirwa, Hasifa | Abstract: BackgroundUganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Methodology/principal findingsPatients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.Conclusions/significanceDP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.Trial registrationControlled-Trials.com ISRCTN75606663.

Acceptability of evidence-based neonatal care practices in rural Uganda - implications for programming.

Abstract: Although evidence-based interventions to reach the Millennium Development Goals for Maternal and Neonatal mortality reduction exist, they have not yet been operationalised and scaled up in Sub-Saharan African cultural and health systems. A key concern is whether these internationally recommended practices are acceptable and will be demanded by the target community. We explored the acceptability of these interventions in two rural districts of Uganda. We conducted 10 focus group discussions consisting of mothers, fathers, grand parents and child minders (older children who take care of other children). We also did 10 key informant interviews with health workers and traditional birth attendants. Most maternal and newborn recommended practices are acceptable to both the community and to health service providers. However, health system and community barriers were prevalent and will need to be overcome for better neonatal outcomes. Pregnant women did not comprehend the importance of attending antenatal care early or more than once unless they felt ill. Women prefer to deliver in health facilities but most do not do so because they cannot afford the cost of drugs and supplies which are demanded in a situation of poverty and limited male support. Postnatal care is non-existent. For the newborn, delayed bathing and putting nothing on the umbilical cord were neither acceptable to parents nor to health providers, requiring negotiation of alternative practices. The recommended maternal-newborn practices are generally acceptable to the community and health service providers, but often are not practiced due to health systems and community barriers. Communities associate the need for antenatal care attendance with feeling ill, and postnatal care is non-existent in this region. Health promotion programs to improve newborn care must prioritize postnatal care, and take into account the local socio-cultural situation and health systems barriers including the financial burden. Male involvement and promotion of waiting shelters at selected health units should be considered in order to increase access to supervised deliveries. Scale-up of the evidence based practices for maternal-neonatal health in Sub-Saharan Africa should follow rapid appraisal and adaptation of intervention packages to address the local health system and socio-cultural situation.

The neglect of the global surgical workforce: experience and evidence from Uganda.

Abstract: Africa’s health workforce crisis has recently been emphasized by major international organizations. As a part of this discussion, it has become apparent that the workforce required to deliver surgical services has been significantly neglected. This paper reviews some of the reasons for this relative neglect and emphasizes its importance to health systems and public health. We report the first comprehensive analysis of the surgical workforce in Uganda, identify challenges to workforce development, and evaluate current programs addressing these challenges. This was performed through a literature review, analysis of existing policies to improve surgical access, and pilot retrospective studies of surgical output and workforce in nine rural hospitals. Uganda has a shortage of surgical personnel in comparison to higher income countries, but the precise gap is unknown. The most significant challenges to workforce development include recruitment, training, retention, and infrastructure for service delivery. Curricular innovations, international collaborations, and development of research capacity are some of the initiatives underway to overcome these challenges. Several programs and policies are addressing the maldistribution of the surgical workforce in urban areas. These programs include surgical camps, specialist outreach, and decentralization of surgical services. Each has the advantage of improving access to care, but sustainability has been an issue for all of these programs. Initial results from nine hospitals show that surgical output is similar to previous studies and lags far behind estimates in higher-income countries. Task-shifting to non-physician surgical personnel is one possible future alternative. The experience of Uganda is representative of other low-income countries and may provide valuable lessons. Greater attention must be paid to this critical aspect of the global crisis in human resources for health.

Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria

Abstract: Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-alpha levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-alpha production is associated with subsequent neurologic and cognitive morbidity.