The clinical utility of cystatin C based eGFR in assessing renal function among HIV/AIDs patients on ART at Mildmay Uganda.

BACKGROUND: In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. METHODS: A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. RESULTS: The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7-88.1) and 91.2% (95% CI 98.11-92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. CONCLUSION: Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.

A Quasi-experimental Study Evaluating the Effectiveness of Cryotherapy on Chemotherapy-induced Oral Mucositis Prevention at the Uganda Cancer Institute.

INTRODUCTION: Low-cost interventions such as cryotherapy are not routinely practiced in sub-Saharan Africa to prevent chemotherapeutic-induced oral mucositis. We investigated the feasibility and effect of cryotherapy on oral mucositis at the Uganda Cancer Institute. METHODS: This was a quasi-experimental nonequivalent research study design. We had two groups with each group meant to have 100 participants. We analyzed based on participants who underwent the protocol procedures. RESULTS: Only cancer types were significantly different between the control and intervention groups (χ2=31.09, df =18, p=.030). Twenty percent (n=19) out of the 95, while 8.2% (n=7) out of the 85 in the control and intervention groups respectively developed moderate to severe mucositis (Mantel-Cox and Generalized Wilcoxon p= .026 and p=.031, respectively). CONCLUSION: The use of cryotherapy in our local setting and many sub-Saharan African countries is feasible and affordable to prevent and control chemotherapy-induced oral mucositis.

Validity of smartphone-based retinal photography (PEEK-retina) compared to the standard ophthalmic fundus camera in diagnosing diabetic retinopathy in Uganda: A cross-sectional study.

INTRODUCTION: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus and is a significant cause of blindness worldwide. In Uganda, the prevalence of diabetes is approximately 2.7% of the urban population and 1% in rural areas. Many diabetics cannot access an eye exam due to the lack of less costly and user-friendly equipment that primary eye workers can use. Smartphone-based fundus photography allows for a cheap and mobile fundus examination. The study aimed to determine the sensitivity and specificity of the Portable Eye Examination Kit (PEEK) retina compared to a standard ophthalmic fundus camera (Zeiss Visucam 200) for the diagnosis of DR. METHODS: From January-March 2020, 286 people with diabetes (type 1 & 2) patients were seen at Kiruddu National referral hospital diabetes clinic. All participants had funduscopy with PEEK retina and the standard ophthalmic fundus camera following ophthalmic examination and pupillary dilation. The PEEK retina's sensitivity, specificity and reliability were determined using an ophthalmic fundus camera as the gold standard. RESULTS: The participants' mean age was 51 with a standard deviation of ±11years, 213 (74.5%) were females, and the majority (93.4%) had Type 2 diabetes. The overall Sensitivity of PEEK retina for DR was 84% (95% CI 70.9-83.5), while the specificity was 79.9% (95% CI 76-83.5) with a positive predictive value (PPV) of 30.9% (95% CI 23.2-39.4) and a negative predictive value (NPV) of 97.9% (95% CI 95.9-99.1). CONCLUSIONS: PEEK retina has high sensitivity and specificity, making it suitable for screening and diagnostic purposes. Therefore, we recommend the integration of the PEEK retina in the screening and diagnosis of DR in resource-limited settings.

Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Clinical presentation and outcomes in children with retinoblastoma managed at the Uganda Cancer Institute.

Background: The majority of patients with retinoblastoma, the most common intraocular cancer of childhood, are found in low-and middle-income countries (LMICs), with leukocoria being the most common initial presenting sign and indication for referral. Findings from the current study serve to augment earlier findings on the clinical presentation and outcomes of children with retinoblastoma in Uganda. Methods: This was a retrospective study in which we reviewed records of children admitted with a diagnosis of retinoblastoma at the Uganda Cancer Institute from January 2009 to February 2020. From the electronic database, using admission numbers, files were retrieved. Patient information was recorded in a data extraction tool. Results: A total of 90 retinoblastoma patients were studied, with a mean age at the first Uganda Cancer Institute (UCI) presentation of 36.7 months. There were more males (57.8%) than females, with a male to female ratio of 1.37 : 1. The majority (54.4%) had retinoblastoma treatment prior to UCI admission. The most common presenting symptoms were leukocoria (85.6%), eye reddening (64.4%), and eye swelling (63.3%). At 3 years of follow-up after index admission at UCI, 36.7% of the patients had died, 41.1% were alive, and 22.2% had been lost to follow-up. The median 3-year survival for children with retinoblastoma in our study was 2.18 years. Significant predictors of survival in the multivariate analysis were follow-up duration ( P ¯ < 0.001 ), features of metastatic spread (P = 0.001), history of eye swelling (P = 0.012), and bilateral enucleation (P = 0.011). Conclusions: The majority of children who presented to the Uganda Cancer Institute were referred with advanced retinoblastoma, and there was a high mortality rate. Retinoblastoma management requires a multidisciplinary team that should include paediatric ophthalmologists, paediatric oncologists, ocular oncologists, radiation oncologists, and nurses.

Prevalence and factors associated with hypertension among adults with and without HIV in Western Kenya.

INTRODUCTION: The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. METHODS: In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. RESULTS: Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p<0.002). In multivariate analyses, persons with HIV were 37% less likely to have hypertension compared to HIV-negative individuals (adjusted prevalence ratio 0.63; 95% confidence interval: 0.46-0.86). Other factors that were associated with hypertension in all participants included older age >40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. CONCLUSION: Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

Experiences of patients who developed oral mucositis during solid neoplasms treatment: a Ugandan qualitative study.

BACKGROUND: Research on the management of complications of chemotherapy is important in facilitating the growing approaches to individualized patient management. Hence the need to document patient's perspectives about chemotherapy-induced mucositis and the support they need from cancer care teams. METHODS: We carried out a qualitative study using in-depth interviews (IDI) and focus group discussions (FGD). We collected patient's experiences on chemotherapy-induced mucositis by conducting 5 FGD and 13 IDIs. RESULTS: One glaring improvement that we need to make is the provision of information and counseling before, during, and after chemotherapy. Additionally, we need to explore inexpensive mucositis preventive strategies to aid our patients as they undergo treatment. CONCLUSION: As a country, we must move away from taking cancer patients' needs as those of common tropical diseases. This will allow us to provide that extra help needed outside the usual diagnosis and administration of medication.

Chest X-ray interpretation does not complement Xpert MTB/RIF in diagnosis of smear-negative pulmonary tuberculosis among TB-HIV co-infected adults in a resource-limited setting.

BACKGROUND: Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients. METHODS: HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard. RESULTS: Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28-39) years and CD4 count 112 (23-308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6-77.8) and 53.7% (95%CI 47.7-59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0-75.7) and 95.8% (95%CI 92.8-97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5-93.9) and 51.6% (95%CI 45.6-57.5) respectively; 86.2% (95%CI 75.3-93.5) and 48.1% (95%CI 40.7-55.6) among inpatients and 93.8% (95%CI 69.8-99.8) and 58.0% (95%CI 47.7-67.8) among outpatients respectively. CONCLUSION: In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.

Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression.

BACKGROUND: Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. METHODS: We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1ß, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. RESULTS: We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4-10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1ß (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). CONCLUSIONS: We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.

Factors associated with delayed uptake of cataract surgery among adult patients at Mulago National Referral Hospital, Uganda.

BACKGROUND: Cataract is the leading cause of blindness globally. Many patients with cataract in developing countries delay to come for cataract surgery. OBJECTIVES: This study aimed to determine the factors associated with delayed uptake of cataract surgery among adult patients seen at Mulago National Referral Hospital eye clinic in Uganda. METHODS: Employing a hospital based cross-sectional study, adult patients with cataract and having moderate visual impairment or blindness were recruited. Patient-related factors for delayed surgery were assessed using a predetermined questionnaire. Data was analyzed using stata version 14.2. Logistic regressions were used to determine the factors associated with delayed uptake of cataract surgery among these patients. RESULTS: Eighty two participants with operable cataract were evaluated. Females were 44 (54%) and the mean age of participants was 67 years. Fifty three (65%) had delayed uptake of cataract surgery. The factors associated with delayed uptake of cataract surgery among patients with cataract were financial constraint, felt no need for surgery and good unilateral vision. CONCLUSIONS: Financial constraints, no felt need for cataract surgery and having good unilateral vision are the factors associated with delayed uptake of cataract surgery among cataract patients. We recommend cataract surgical outreach to remote areas and health education.

Prevalence, severity and factors associated with dental caries among school adolescents in Uganda: a cross-sectional study

Abstract Dental caries is one of the most prevalent diseases in developing countries. However, there is limited data on the prevalence and factors associated with dental caries in Ugandan adolescents. The purpose of the present study was to describe the prevalence, severity of dental caries and to determine the factors associated with the disease among school adolescents in Uganda. A cross sectional study was conducted at two secondary schools from Kampala (n=197) and Mukono (n=209) districts, Uganda. At both schools, random sampling was used to select the participating classes and the 406 adolescents (11-19 years) eligible to participate in the research. Dental caries was examined using the Decayed, Missing and Filled Teeth (DMFT) index, and a questionnaire was used to collect other relevant data in form of an oral interview. The data were analyzed using STATA version 12. The data was declared as survey data and all analyses were done with svy command. The prevalence of caries was determined as a percentage of individuals with DMFT score ≥1. Modified Poisson regression models were utilized to assess the association between prevalence, severity of dental caries and independent variables. The overall prevalence of dental caries was 66.0% and mean DMFT score of 2.18±2.67. Dental caries prevalence and severity were significantly (p<0.05) associated with tooth cleaning device, age and history of previous dental visit. There was a high prevalence and severity of dental caries among adolescents, which emphasizes the urgent need to develop and design appropriate interventions to reduce the disease burden.

Resumo A cárie dentária é uma das doenças mais prevalentes nos países em desenvolvimento. No entanto, existem dados limitados sobre a prevalência e os fatores associados à cárie dentária em adolescentes de Uganda. O objetivo do presente estudo foi descrever a prevalência e severidade da cárie dentária e determinar os fatores associados à doença em adolescentes escolares de Uganda. Um estudo transversal foi realizado em duas escolas secundárias dos distritos de Kampala (n = 197) e Mukono (n = 209), Uganda. Nas duas escolas, foi utilizada amostragem aleatória para selecionar as turmas participantes e os 406 adolescentes (11 a 19 anos) elegíveis para participar da pesquisa. A cárie dentária foi examinada usando o índice de dentes cariados, perdidos e obturados (CPOD), e um questionário foi usado para coletar outros dados relevantes na forma de uma entrevista oral. Os dados foram analisados no STATA versão 12. Os dados foram declarados como dados da pesquisa e todas as análises foram realizadas com o comando svy. A prevalência de cárie foi determinada como porcentagem de indivíduos com escore de CPOD ≥1. Modelos de regressão de Poisson modificados foram utilizados para avaliar a associação entre prevalência, gravidade da cárie dentária e variáveis independentes. A prevalência geral de cárie dentária foi de 66,0% e o escore médio do CPOD de 2,18 ± 2,67. A prevalência e severidade de cárie dentária foram significativamente (p<0,05) associadas ao dispositivo de limpeza dentária, idade e histórico de visita odontológica prévia. Houve alta prevalência e gravidade de cárie dentária entre os adolescentes, o que enfatiza a necessidade urgente de desenvolver e projetar intervenções apropriadas para reduzir a carga da doença.

Prevalence and factors associated with dental caries in patients attending an HIV care clinic in Uganda: a cross sectional study.

BACKGROUND: Chronic Human Immunodeficiency Virus (HIV) infection is associated with reduced saliva flow rate due to infiltration of HIV and proliferation of CD8 lymphocytes in salivary glands. It is unclear whether HIV infection and antiretroviral therapy (ART) increase caries risk. This study aimed to determine the prevalence and factors associated with dental caries in HIV infected adults attending the Mulago Immune Suppression Syndrome (ISS) clinic in Uganda. METHODS: A cross-sectional study was conducted among HIV infected persons. Dental examinations were performed by two calibrated dentists using the WHO Radke's caries classification criteria and reported using the decayed (D), missing (M), filled (F), teeth (DMFT) index. The prevalence and factors associated with dental caries was examined through linear regression analyses. RESULTS: Overall, 748 participants (females = 491, 65.6%) with a mean age of 39 ± 9.4 years were included in the final analysis; of whom 83.7% had caries (DMFT> 0), with a significantly (p < 0.05) higher prevalence among females 86.6% than males 78.2%. The mean DMFT was 5.9 ± 5.5, with statistically significant differences based on gender (males 4.9 ± 4.8 and females 6.3 ± 5.9, p < 0.05) and duration on ART (< 2 years 4.8 ± 4.4, > 2 years but < 5 years 5.7 ± 5.5, > 5 years 6.6 ± 6.0 p < 0.05). The majority (67.2%) of participants reported brushing their teeth twice or more a day, and sugar intake was not associated with dental caries. CONCLUSION: Caries prevalence is high among HIV infected adults under care. Duration of ART was associated with increased risk and severity of caries. Therefore, we recommend integration of dental care in HIV treatment programs.

"Tuberculosis in advanced HIV infection is associated with increased expression of IFNγ and its downstream targets".

BACKGROUND: Tuberculosis (TB) is the major cause of death in Human Immunodeficiency Virus (HIV)-infected individuals. However, diagnosis of TB in HIV remains challenging particularly when HIV infection is advanced. Several gene signatures and serum protein biomarkers have been identified that distinguish active TB from latent infection. Our study was designed to assess if gene expression signatures and cytokine levels would distinguish active TB in advanced HIV. METHODS: We conducted a case-control study of whole blood RNA-Seq and plasma cytokine/chemokine analysis in HIV-infected with CD4+ T cell count of ≤ 100 cells/µl, with and without active TB. Next, the overlap of the differentially expressed genes (DEG) with the published signatures was performed and then receiver operator characteristic (ROC) analysis was done on small gene discriminators to determine their performance in distinguishing TB in advanced HIV. ELISA was performed on plasma to evaluate cytokine and chemokine levels. RESULTS: Hierarchical clustering of the transcriptional profiles showed that, in general, HIV-infected individuals with TB (TB-HIV) clustered separately from those without TB. IPA indicated that the TB-HIV signature was characterized by an increase in inflammatory signaling pathways. Analysis of overlaps between DEG in our data set with published TB signatures revealed that significant overlap was seen with one TB signature and one TB-IRIS signature. ROC analysis revealed that transcript levels of FcGR1A (AUC = 0.85) and BATF2 (AUC = 0.82), previously reported as consistent single gene classifiers of active TB irrespective of HIV status, performed successfully even in advanced HIV. Plasma protein levels of IFNγ, a stimulator of FcGR1A and BATF2, and CXCL10, also up-regulated by IFNγ, accurately classified active TB (AUC = 0.98 and 0.91, respectively) in advanced HIV. Neither of these genes nor proteins distinguished between TB and TB-IRIS. CONCLUSIONS: Gene expression of FcGR1A and BATF2, and plasma protein levels of IFNγ and CXCL10 have the potential to independently detect TB in advanced HIV. However, since other lung diseases were not included in this study, these final candidates need to be validated as specific to TB in the advanced HIV population with TB.

Reaching the First 90 in Uganda: Predictors of Success in Contacting and Testing the Named Sexual Partners of HIV+ Index Clients in Kiboga District.

Assisted partner notification programs represent one strategy for targeted HIV testing and treatment of exposed individuals in high-risk populations. This study of a pilot Partner Services program in rural Uganda describes predictors of successful contact tracings and testing of partners of HIV+ individuals and possible barriers to contact. Partner contact tracing data was extracted from registers at seven Ministry of Health facilities between May and October 2016, to inform program implementation and scale up. A total of 464 HIV+ index clients named 660 sexual partners; 334/660 (51%) were contacted, 193/334 (58%) tested for HIV, and 61/193 (32%) tested HIV+. Current relationship status predicted contact [AOR = 0.23; (95% CI 0.15, 0.37), p < 0.0001] and testing [AOR = 0.19; (95% CI 0.09, 0.36), p < 0.0001]. Partner contact information type was associated with contact (p < 0.0001), and assisted disclosure with testing (p < 0.0001). Partner contact tracing is an effective means of identifying undiagnosed HIV infections.

Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda.

BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients.

CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda.

BACKGROUND: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. METHODS: In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+(Bright) and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. RESULTS: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p=0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p=0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<0.0001. CONCLUSION: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.

Low prevalence of Plasmodium falciparum antigenaemia among asymptomatic HAART-treated adults in an urban cohort in Uganda.

BACKGROUND: Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV). METHODS: Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect Plasmodium falciparum antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months. RESULTS: Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic P. falciparum antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months. CONCLUSIONS: In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. falciparum antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.

Effect of home-based water chlorination and safe storage on diarrhea among persons with human immunodeficiency virus in Uganda.

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.