Mark Kaddumukasa

A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

BACKGROUND GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda—A reflection of differences in policies regarding withdrawal of chloroquine?

BACKGROUND Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women. METHODS Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products. RESULTS The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates. CONCLUSIONS The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.

Rheumatic manifestations among HIV positive adults attending the Infectious disease clinic at Mulago hospital

BACKGROUND Intestinal parasitic infections play a vital role in the prognosis of HIV/AIDS in patients. OBJECTIVES The aim of this study was to determine the prevalence of intestinal parasitic infections (IPIs) in HIV-infected individuals in two health facilities in Abuja-Nigeria. METHODS A cross sectional study was conducted in two sites: the GEDE AIDS and Infectious Diseases Research Institute (GAIDRI), and the Human Virology Institute-General Hospital Asokoro-Abuja, Nigeria. A total of 119 subjects were recruited (85 HIV infected and 34 HIV negative). Stool specimens collected were analyzed macroscopically and microscopically for consistency and the presence of enteric parasites. RESULTS The overall prevalence rate of enteroparasites obtained in this study was 22.7% (27/119). The prevalence of intestinal parasitic infections in HIV infected patients was 24.7 %; while in HIV negative persons, it was 17.6%. However, the high rate obtained for HIV infected patients was not statistically significant (p> 0.05). CONCLUSION Although the prevalence rate of enteric parasites in HIV/AIDS patients was higher than in HIV negative individuals, this difference is not statistically significant. Even though there was no statistical difference in the two groups, parasitic infections in HIV/AIDS patients often result in debilitating illness.

Influence of sodium consumption and associated knowledge on poststroke hypertension in Uganda

Objective: We assessed 24-hour urine sodium levels as an index of dietary salt consumption and its association with dietary salt knowledge and hypertension among poststroke patients with and without a history of hypertension in Uganda. Methods: A case-control study in which poststroke patients with a history of hypertension (cases, n = 123) were compared to poststroke patients without known hypertension (controls, n = 112). Dietary salt intake was assessed by 24-hour urine sodium, a valid measure of dietary salt consumption. Dietary salt knowledge was determined by questionnaire. The independent relationships among salt knowledge, 24-hour urine sodium, and blood pressure control were assessed using multiple regression analysis. Results: High 24-hour urine sodium (≥8.5 g/d) was 2 times more prevalent among hypertensive poststroke patients than controls (p = 0.002). Patients with minimal poststroke disability who had a choice in determining their diets had higher urine sodium than their more disabled counterparts. Only 43% of the study population had basic dietary salt knowledge, 39% had adequate diet-disease–related knowledge, and 37% had procedural knowledge (report of specific steps being taken to reduce salt consumption). Dietary salt knowledge was similarly poor among cases and controls (p = 0.488) and was not related to education level (p = 0.205). Conclusions: High urine sodium and high salt-diet preferences were more frequent among poststroke hypertensive patients in Uganda than in their nonhypertensive counterparts. There was, however, no difference in dietary salt knowledge between these groups. The development of educational strategies that include salt-diet preferences may lead to better blood pressure control in this high-risk population.

Community knowledge of and attitudes toward epilepsy in rural and urban Mukono district, Uganda: A cross-sectional study

INTRODUCTION The lack of adequate knowledge poses a barrier in the provision of appropriate treatment and care of patients with epilepsy within the community. The purpose of this study was to determine the knowledge of and attitude towards epilepsy and its treatment by community dwellers in Uganda. METHODS A cross sectional population survey was conducted in urban and rural Mukono district, central Uganda. Adult respondents through multistage stratified sampling were interviewed about selected aspects of epilepsy knowledge, attitudes, and perception using a pretested structured questionnaire. RESULTS Ninety-one percent of the study respondents had heard or read about epilepsy or knew someone who had epilepsy and had seen someone having a seizure. Thirty-seven percent of the respondents did not know the cause of epilepsy, while 29% cited genetic causes. About seventeen percent of the subjects believed that epilepsy is contagious. Only 5.6% (21/377) of the respondents would take a patient with epilepsy to hospital for treatment. CONCLUSION Adults in Mukono are very acquainted with epilepsy but have many erroneous beliefs about the condition. Negative attitudes are pervasive within communities in Uganda. The national epilepsy awareness programs need to clarify the purported modes of transmission of epilepsy, available treatment options, and care offered during epileptic seizures during community sensitizations in our settings.

Knowledge and Attitudes of Parkinson's Disease in Rural and Urban Mukono District, Uganda: A Cross-Sectional, Community-Based Study.

Background. Parkinsons disease (PD) negatively affects the quality of life. There is limited information on PD published from Africa. Lack of adequate knowledge poses a barrier in the provision of appropriate treatment and care for individuals with PD. Methods. A cross-sectional survey was conducted in urban and rural Mukono district, central Uganda. Through the systematic sampling method, data were gathered from 377 adult participants, interviewed on selected aspects of PD knowledge and attitudes. Results. Of the 377 participants, 47% were from urban settings and 68% (260/377) were women with a median age (IQR) of 34 (26–48) years. Half of the study respondents did not know the body part involved in or apparent cause of PD. Nearly 1/3 of individuals believed that PD is a form of insanity and 17% believed that PD is contagious. Rural dwellers were more likely to have incorrect knowledge regarding selected aspects of PD. Conclusions. Understanding the cause of PD is very limited in our setting. Some beliefs about PD aetiology may potentially worsen stigma and social isolation. This study highlights the need for increasing PD awareness in our settings. Public health approaches that improve knowledge are urgently needed to promote care access and community response to Parkinsons disease.

Post-stroke depression among stroke survivors attending two hospitals in Kampala Uganda.

BACKGROUND The burden of stroke worldwide is increasing rapidly. There is paucity of data on post-stroke depression (PSD) among stroke survivors in Uganda, despite the high prevalence of PSD reported elsewhere. METHODS In a cross-sectional study, we assessed adult participants with confirmed first stroke with a standardized questionnaire. The Patient Health Questionnaire-9 was used to assess for depression among non-aphasic patients while the Aphasic Depression Rating Scale was administered to aphasic patients. Univariable and multivariable analyses performed to describe associations with PSD. RESULTS Forty three females (58.9%) and 30 males (41.1%) who had a stroke participated. Fifty eight (79.5%) had ischemic strokes and 12 participants (16.4%) were aphasic. The prevalence of PSD among the study participants was 31.5%. PSD was higher among patients assessed within 6 months after the onset of stroke. PSD was strongly associated with the total Barthel index of activities of daily living (BIADL) score; p=0.001. There was no significant association between demographic characteristics and PSD. CONCLUSION There is a high prevalence of unrecognized post-stroke depression. Post-stroke depression was strongly associated with the patients inability to undertake activities of daily life. There is urgent need for integration of screening for and management of post-stroke depression among stroke survivors.

Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with Plasmodium falciparum infection among children in Iganga distric in Uganda.

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) is a metabolic enzyme involved in the pentose phosphate pathway, its especially important in red blood cell metabolism. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of G6PD. About 400 million people worldwide have a deficiency of this enzyme. The remarkable geographic correlation of G6PD deficiency distribution with historical endemicity patterns of malaria has led to suggestions that the two could be linked. Some studies have concluded that G6PD deficiency confers resistance to malaria.ObjectiveTo determine the prevalence of G6PD deficiency, and determine its relationship with prevalence and incidence of P. falciparum infection among children in Uganda.MethodsThis was longitudinal study involving 245 children, 135 were actively followed up for 12 months. G6PD status was assessed for using PCR-RFLP method. A thick smear was done to determine presence of plasmodium trophozoites and parasite densities.ResultsA total of 245 children between 6 months and 9 years were recruited. Of these 46.5% were males. Overall prevalence for the X-linked G6PD A- mutation was; 79.59% wild type, 12.65% heterozygous and 7.76% homozygous or hemizygous. Among the males 14% were hemizygous. At baseline, 40.8% had asymptomatic P falciparum infection. There was no statistically significant difference in prevalence and incidence rates of malaria infection among the different G6PD genotypes with prevalence among heterozygous, homozygous, and wild type being 29%, 42.6% and 43% respectively (p = 0.11) and incidence among heterozygous and wild type being 0.56 and 0.52 episodes/year (p = 0.5). The heterozygous G6PD A- females had a lower parasite density compared to the wild type (2505 vs 941 parasites/μL; P = 0.024).ConclusionsThis study showed that 20.41% of the population in this part of Uganda carry the G6PD A-mutation, within the range of 15-32% seen in other parts of Africa. P. falciparum infection incidence and prevalence rates are similar among the G6PD genotypes though, once infected, P. falciparum parasite densities are lowest among G6PD A- heterozygous females. This suggests differences in P. falciparum infection rates and severity of disease could be mediated by differences in parasite densities among the different G6PD genotypes.

A cross-sectional population survey on stroke knowledge and attitudes in Greater Kampala, Uganda

Abstract Background: Stroke is a neurological condition with rapidly increasing burden in many low- and middle income countries. Africa is particularly hard-hit due to rapid population growth, patterns of industrialization, adoption of harmful western diets, and increased prevalence of risk factors such as hypertension and obesity. Reducing stroke risk factors and teaching people to respond to stroke warning signs can prevent stroke and reduce burden. However, being able to address gaps in knowledge and improving both preventative and early-response care requires a clear understanding of practical and potentially modifiable topics. In this cross sectional study, we assessed the knowledge and attitudes among an urban population residing within the greater Kampala, Uganda. Methods: A population cross sectional survey was conducted in urban Mukono, district, central Uganda. Through the systematic sampling method, data were gathered from 440 adult participants who were interviewed about selected aspects of stroke knowledge, attitudes and perception using a pretested structured questionnaire. Results: A total of 440 study participants were enrolled. The leading risk factors for stroke identified by the participants were stress (75.7%) and hypertension (45.2%) respectively. Only two (0.5%) of the study participants identified cigarette smoking as a stroke risk factor. Individuals with hypertension have poor knowledge regarding stroke in spite their high risk for stroke. Conclusion: Stroke knowledge is poor while, stress and hypertension are the leading perceived risk factors in our settings. While stress is contributing factor, hypertension is likely a more amenable and practical intervention target. Targeting individuals with stroke risk factors to increase stroke knowledge and education is crucial for engagement in healthcare. Implementing a self-management program to support and motivate this high-risk group as well as adopting healthy life-styles may be a way to reduce stroke burden in Uganda.

Feasibility study of a targeted self-management intervention for reducing stroke risk factors in a high-risk population in Uganda

INTRODUCTION Stroke remains a global concern due to increasing lifespan, patterns of industrialization, adoption of harmful western diets, and an increasing prevalence of risk factors such as hypertension, obesity, and diabetes. We investigated an adopted novel self-management intervention, TargetEd mAnageMent Intervention (TEAM) to reduce modifiable stroke risk factors in Uganda. METHODS A six-month, uncontrolled, prospective pilot study to establish feasibility, acceptability and preliminary efficacy of TEAM in Ugandans at high risk for stroke was conducted. The primary outcome was change in systolic BP from baseline to 24-week follow-up. Secondary outcomes included change in diastolic BP, serum cholesterol, high and low density lipoprotein (HDL, LDL) and triglycerides. RESULTS Mean (SD) baseline systolic BP was 162.9 (±25.6) mmHg while mean (SD) baseline diastolic BP was 99.1 (±13.8) mmHg. There was a significant reduction in mean baseline blood pressure of 163/98.8mmHg to blood pressure of 147.8/88.0mmHg at 24weeks, P=0.023. There were also significant reductions in the serum total cholesterol levels at 24weeks with P=0.001. CONCLUSION Targeted training in self-management (TEAM) adapted to the Ugandan setting is feasible, highly acceptable to participants and appears to be associated with reduced blood pressure, improved lipid profiles and improved glucose control in diabetics.