Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.

Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) µg/mL, 7.39 (IQR 5.10-10.20) µg/mL, 7.00 (IQR 6.05-10.95) µg/mL and 3.86 (IQR 2.81-14.24) µg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P = 0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) µg/mL and those who did not 2.21 (1.45-3.11) µg/mL ( P = 0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

The effect of an intervention to promote isoniazid preventive therapy on leadership and management abilities.

BACKGROUND: Across sub-Saharan Africa, mid-level healthcare managers oversee implementation of national guidelines. It remains unclear whether leadership and management training can improve population health outcomes. METHODS: We sought to evaluate leadership/management skills among district-level health managers in Uganda participating in the SEARCH-IPT randomised trial to promote isoniazid preventive therapy (IPT) for persons with HIV (PWH). The intervention, which led to higher IPT rates, included annual leadership/management training of managers. We conducted a cross-sectional survey assessing leadership/management skills among managers at trial completion. The survey evaluated self-reported use of leadership/management tools and general leadership/management. We conducted a survey among a sample of providers to understand the intervention's impact. Targeted minimum loss-based estimation (TMLE) was used to compare responses between trial arms. RESULTS: Of 163 managers participating in the SEARCH-IPT trial, 119 (73%) completed the survey. Intervention managers reported more frequent use of leadership/management tools taught in the intervention curriculum than control managers (+3.64, 95% CI 1.98-5.30, P < 0.001). There were no significant differences in self-reported leadership skills in the intervention as compared to the control group. Among providers, the average reported quality of guidance and supervision was significantly higher in intervention vs control districts (+1.08, 95% CI 0.63-1.53, P = 0.001). CONCLUSIONS: A leadership and management training intervention increased the use of leadership/management tools among mid-level managers and resulted in higher perceived quality of supervision among providers in intervention vs control districts in Uganda. These findings suggest improved leadership/management among managers contributed to increased IPT use among PWH in the intervention districts of the SEARCH-IPT trial.

CONTEXTE: Dans toute l'Afrique subsaharienne, les gestionnaires de soins de santé de niveau intermédiaire supervisent la mise en œuvre des directives nationales. Il n'est toujours pas clair si la formation en leadership et en gestion peut améliorer les résultats en matière de santé de la population. MÉTHODES: Nous avons cherché à évaluer les compétences en leadership et en gestion des responsables de la santé au niveau des districts en Ouganda participant à l'essai randomisé SEARCH-IPT visant à promouvoir le traitement préventif à l'isoniazide (TPI) pour les personnes vivant avec le VIH (PWH, pour l'anglais « people living with HIV ¼). L'intervention, qui a permis d'augmenter les taux de TPI, comprenait une formation annuelle en leadership et en gestion des gestionnaires. Nous avons mené une enquête transversale pour évaluer les compétences en leadership et en gestion des gestionnaires à la fin de l'essai. L'enquête a évalué l'utilisation autodéclarée d'outils de leadership et de gestion et de leadership et de gestion en général. Nous avons mené une enquête auprès d'un échantillon de prestataires pour comprendre l'impact de l'intervention. L'estimation ciblée basée sur les pertes minimales (TMLE, « Targeted minimum loss-based estimation ¼) a été utilisée pour comparer les réponses entre les groupes de l'essai. RÉSULTATS: Sur les 163 gestionnaires qui ont participé à l'essai SEARCH-IPT, 119 (73%) ont répondu au sondage. Les gestionnaires d'intervention ont déclaré utiliser plus fréquemment les outils de leadership/gestion enseignés dans le programme d'intervention que les gestionnaires de contrôle (+3,64 ; IC à 95% 1,98­5,30 ; P < 0,001). Il n'y avait pas de différences significatives dans les compétences de leadership autodéclarées dans l'intervention par rapport au groupe témoin. Parmi les prestataires, la qualité moyenne déclarée de l'orientation et de la supervision était significativement plus élevée dans les districts d'intervention que dans les districts témoins (+1,08 ; IC à 95% 0,63­1,53 ; P = 0,001). CONCLUSIONS: Une intervention de formation au leadership et à la gestion a permis d'accroître l'utilisation d'outils de leadership et de gestion parmi les cadres intermédiaires et d'améliorer la perception de la qualité de la supervision parmi les prestataires dans les districts d'intervention par rapport aux districts de contrôle en Ouganda. Ces résultats suggèrent que l'amélioration du leadership et de la gestion chez les gestionnaires a contribué à l'augmentation de l'utilisation du TPI chez les personnes handicapées dans les districts d'intervention de l'essai SEARCH-IPT.

Understanding patient-level costs of weekly isoniazid-rifapentine (3HP) among people living with HIV in Uganda.

BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention.

Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed the impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected nonpregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to nonpregnant women. DHA AUC0-8hr and piperaquine AUC0-21d were 27% and 38% lower, respectively, in pregnant women receiving efavirenz compared to HIV-uninfected pregnant women. Exposure to DHA and piperaquine were lower among pregnant women and particularly in women on efavirenz, suggesting a need for dose modifications. The study of modified dosing strategies for these populations is urgently needed.

Impact of mycobacterial culture among HIV-infected adults with presumed TB in Uganda: a prospective cohort study.

BACKGROUND: Implementation of new tuberculosis (TB) diagnostic strategies in resource-constrained settings is challenging. We measured the impact of solid and liquid mycobacterial cultures on treatment practices for patients undergoing TB evaluation in Kampala, Uganda. METHODS: We enrolled consecutive smear-negative, human immunodeficiency virus positive adults with cough of ⩾2 weeks from September 2009 to April 2010. Laboratory technicians performed mycobacterial cultures on solid and liquid media. We compared empiric treatment decisions with solid and liquid culture in terms of diagnostic yield and time to results, and assessed impact on patient management. RESULTS: Of 200 patients enrolled, 26 (13%) had culture-confirmed TB: 22 (85%) on solid culture alone, 2 (8%) on liquid culture alone, and 2 (8%) on both solid and liquid culture. Thirty-four patients received empiric anti-tuberculosis treatment, but only 10 (29%) were culture-positive. Median time to a positive result on solid culture was 92 days (interquartile range [IQR] 69-148) compared to 106 days (IQR 66-157) for liquid culture. No patients initiated treatment following a positive result on liquid culture. CONCLUSION: The introduction of mycobacterial culture did not influence care for patients undergoing evaluation for TB in Kampala, Uganda. Attention to contextual factors surrounding implementation is needed to ensure the effective introduction of new testing strategies in low-income countries.

Contexte : La mise en œuvre de nouvelles stratégies de diagnostic de la tuberculose (TB) dans les contextes de ressources limitées constitue un défi. Nous avons mesuré l'impact des cultures mycobactériennes en milieu solide et liquide sur les pratiques de traitement des patients ayant une évaluation de la TB à Kampala, Ouganda.Méthodes : Nous avons enrôlé des patients adultes consécutifs à frottis négatif, positifs pour le virus de l'immunodéficience humaine avec toux de ⩾2 semaines, de septembre 2009 à avril 2010. Les techniciens de laboratoire ont réalisé des cultures mycobactériennes en milieu solide et liquide. Nous avons comparé les décisions de traitement empirique aux cultures en milieu solide et liquide en termes de rendement diagnostique et de délai d'obtention des résultats et nous avons évalué l'impact sur la gestion des patients.Résultats : Des 200 patients enrôlés, 26 (13%) avaient une TB confirmée par culture, 22 (85%) par culture en milieu solide seule, 2 (8%) par culture en milieu liquide seul et 2 (8%) par culture à la fois en milieu solide et liquide. Trente-quatre patients ont reçu un traitement de TB empirique, mais seulement 10 (29%) ont eu une TB à culture positive. Le délai médian d'obtention d'un résultat de culture positive en milieu solide a été de 92 jours (IQR 69­148). Le délai médian d'obtention d'un résultat de culture positive en milieu liquide a été de 106 jours (IQR 66­157). Aucun patient n'a commencé un traitement à la suite d'un résultat de culture positive en milieu liquide.Conclusion : L'introduction de la culture mycobactérienne n'a pas influencé les soins aux patients bénéficiant d'une évaluation de TB à Kampala, Ouganda. Il est nécessaire d'être attentif aux facteurs contextuels entourant la mise en œuvre afin d'assurer une introduction effective de nouvelles stratégies de tests dans les pays à faible revenu.

Marco de referencia: La ejecución de nuevas estrategias de diagnóstico de la tuberculosis (TB) en los entornos con limitación de recursos es problemática. En el presente estudio se midió la repercusión del uso del cultivo de micobacterias en medio sólido o liquido sobre las prácticas de tratamiento de los pacientes en curso de investigación diagnóstica de la TB en Kampala, Uganda.Métodos: Se incluyeron de manera consecutiva en el estudio los pacientes adultos, seronegativos frente al virus de la inmunodeficiencia humana, que consultaban por tos de ⩾2 semanas de duración y presentaban baciloscopia negativa, de septiembre del 2009 a abril del 2010. Los auxiliares de laboratorio practicaron el cultivo de micobacterias en medio sólido y medio líquido. Se compararon las decisiones empíricas de tratamiento y los tipos de cultivo, con respecto al rendimiento diagnóstico y al lapso hasta obtener los resultados y se evaluó su repercusión en el manejo de los pacientes.Resultados: De los 200 pacientes que participaron en el estudio, 26 obtuvieron confirmación del diagnóstico de TB mediante el cultivo (13%), 22 de ellos con el cultivo en medio sólido únicamente (85%), dos con el cultivo en medio líquido exclusivamente y dos con ambos tipos de cultivo (8%). Treinta y cuatro pacientes recibieron tratamiento antituberculoso empírico, pero solo 10 de ellos obtuvieron un cultivo positivo (29%). La mediana del lapso hasta obtener el resultado del cultivo en medio sólido fue 92 días (IQR 69­148). La mediana de este lapso con los cultivos en medio líquido fue 106 días (IQR 66­157). Ningún paciente inició el tratamiento antituberculoso después de haber obtenido el resultado positivo del cultivo en medio líquido.Conclusión: La introducción del cultivo para micobacterias no tiene ninguna influencia en la atención que reciben los pacientes en quienes se investiga la TB en Kampala, Uganda. Es importante prestar atención a los factores contextuales que rodean la ejecución, a fin de lograr una introducción eficaz de las nuevas estrategias diagnósticas en los países con recursos limitados.

Condom use with casual partners by men in Kampala, Uganda.

OBJECTIVE: To estimate the prevalence and correlates of condom use with casual sex partners by men in urban Uganda and to identify barriers to condom use that are amenable to intervention. DESIGN: Cross-sectional, door-to-door survey of men residing in a poor area of Kampala, Uganda. SUBJECTS AND METHODS: A multistage, probability sample was approximated by recruiting participants within randomly selected neighborhoods. A total of 301 men between the ages of 18 and 45 years answered questions about condom knowledge, attitudes, beliefs and practices. The respondents also provided demographic and HIV risk-related information. RESULTS: Condom use was higher than previously found in studies in Uganda: 46% of men reported using a condom at the last casual sexual encounter; 31% reported always using condoms with casual partners. In multivariate analysis, independent correlates of condom use included higher condom self-efficacy (4-item scale, odds ratio 1.3 per scale point), lower embarrassment around condoms (3-item scale, odds ratio 0.44 per scale point), knowing where to buy a condom (odds ratio 3.9), knowing how to use a condom (8-item scale, odds ratio 1.4 per scale point), and increasing number of casual sex partners (odds ratio 1.4 per partner). CONCLUSIONS: These data suggest that condom use may be further increased in this population by conducting demonstrations of condom use skills, preparing individuals to anticipate circumstances that make using condoms difficult and using a variety of outlets to dispense condoms.

Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda.

Chloroquine-resistant falciparum malaria is a serious problem in much of sub-Saharan Africa. However, it is desirable to continue to use chloroquine as first-line therapy for uncomplicated malaria where it remains clinically effective. To identify predictors of chloroquine treatment failure, a 14-day clinical study of chloroquine resistance in patients with uncomplicated falciparum malaria was performed in Kampala, Uganda. Among the 258 patients (88% follow-up), 47% were clinical failures (early or late treatment failure) and 70% had parasitological resistance (RI-RIII). Using multivariate analysis, an age less than five (odds ratio [OR] = 3.4, 95% CI = 1.8-6.3) and a presenting temperature over 38.0 degreesC (OR = 2.0, 95% CI = 1.1-3.7) were independent predictors of treatment failure. In addition, patients who last took chloroquine 3 to 14 days prior to study entry were significantly more likely to be treatment failures compared to patients with very recent (less than 3 days) or no recent chloroquine use. In areas with significant chloroquine resistance, easily identifiable predictors of chloroquine treatment failure might be used to stratify patients into those for whom chloroquine use is acceptable and those for whom alternative treatment should be used.

The comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in Kampala, Uganda.

Chloroquine (CQ) remains the first-line treatment for uncomplicated malaria in much of Africa despite the growing problem of resistance to this drug. Sulfadoxine-pyrimethamine (SP) is often used after CQ treatment failure and has replaced CQ as the first-line treatment in parts of Africa. To compare the efficacy of these 2 regimens, we evaluated, in March-August 1999, clinical and parasitological responses over 28 days in 214 children and adults from Kampala, Uganda, with uncomplicated falciparum malaria. Compared to SP, significantly more patients treated with CQ developed early or late clinical failure (54% vs 11%, P < 0.001) and parasitological failure (72% vs 30%, P < 0.001) during 14 days of follow-up. The risk of treatment failure occurring after day 14 was similar between the 2 treatment groups. Among those treated with CQ, children aged < 5 years were at higher risk of clinical failure than older individuals (76% vs 28%, P < 0.001), an association not seen with SP (11% vs 10%, P = 0.91). Although early parasite clearance was significantly better in the SP group (P = 0.001), fever clearance at day 3 was the same (CQ 85%, SP 86%). These and other recent findings suggest that consideration be given to replacing CQ as the first-line therapy for uncomplicated malaria in Uganda, particularly in young children.

Chest X-ray vs. Xpert® MTB/RIF assay for the diagnosis of sputum smear-negative tuberculosis in Uganda.

SETTING: An out-patient clinic in a country with high rates of tuberculosis-human immunodeficiency virus (TB-HIV) co-infection. DESIGN: Cross-sectional analytical study of 123 adults with chronic cough and no previous anti-tuberculosis treatment. Demographic, clinical, chest X-ray (CXR) and GeneXpert® MTB/RIF data were collected. Proportions of TB diagnoses using both tests were calculated and compared using an unpaired t-test. RESULTS: Sixty-six patients (53.7%) were female and 35 (28.5%) tested positive for HIV; 21 (17.1%) were Xpert-positive, while 51 (42.5%) had CXR suggestive of TB (P = 0.0018), of whom only 15 (29.4%) were Xpert-positive. CXR was suggestive of pulmonary TB in 15 (71.4%) of the 21 patients with a positive Xpert test. CONCLUSIONS: The majority of the sputum smear-negative patients did not have TB on single Xpert testing. CXR gave an overestimate of sputum smear-negative TB cases.

Causes and outcome of hospitalization among HIV-infected adults receiving antiretroviral therapy in Mulago hospital, Uganda.

BACKGROUND: Cohorts describing cause specific mortality in HIV-infected patients initiating antiretroviral therapy (ART) operate on an outpatient basis. Hospitalized patients represent the spectrum and burden of severe morbidity and mortality in patients on ART. OBJECTIVE: To determine the causes and outcomes of hospitalization among adults receiving ART. METHODS: A prospective cohort study. We enrolled 201 participants (50% female) with median (IQR) age and CD4 count of 34 (28-40) years and 91(29-211) cells/uL respectively. RESULTS: The most frequent causes of hospitalization were tuberculosis (TB) (37, 18%), cryptococcal meningitis (22, 11%), zidovudine (AZT) - associated anemia (19, 10%), sepsis (10, 5%) and Kaposi's sarcoma (10, 5%). Forty two patients (21%) died: 10 (24%) had TB, 8 (19%) had cryptococcal meningitis and 5 (12%) had sepsis, 9 (21%) had undiagnosed neurological syndromes while 10 (24%) had other illnesses. Predictors of death included low Karnofsky performance score of < 40 (OR, 21.1; CI 1.43- 31.6) and age >34 years (OR, 7.65; CI 1.09- 53.8). CONCLUSIONS: Opportunistic infections, malignancy and AZT-associated anemia contributed to most hospitalizations and mortality. It is important to intensify prevention, screening, and treatment for these opportunistic diseases and early ART initiation in HIV-infected patients. Tenofovir-based regimens, unless contraindicated should be scaled up to replace AZT-based regimens as first line ART drugs.

Diagnostic accuracy of ultrasensitive heat-denatured HIV-1 p24 antigen in non-B subtypes in Kampala, Uganda.

We evaluated the accuracy of heat-denatured, amplification-boosted ultrasensitive p24 assay (Up24) compared with reverse transcriptase polymerase chain reaction (RT-PCR). We tested 394 samples from Ugandans infected with HIV-1 non-B subtypes. We compared Up24 levels (HIV-1 p24 Core Profile enzyme-linked immunosorbent assay (ELISA), NEN Life Science Products) to RNA viral loads (Amplicor HIV-1 Monitor 1.5, Roche) by linear regression, and calculated sensitivity, specificity, positive and negative predictive values. Median viral load was 4.9 log10 copies/mL (interquartile range [IQR], 2.6-5.5); 114 samples (29%) were undetectable (<400 copies/mL). Sensitivity of the Up24 assay to detect viral load ≥400 copies/mL was 69%, specificity was 67%, and positive and negative predictive values were 84% and 47%, respectively. Sensitivity of Up24 was 90%, 80%, 68%, 62% and 45% to detect viral loads of >500,000, 250,000-500,000, 100,000-250,000, 50,000-100,000 and 400-50,000 copies/mL, respectively. In conclusion, when compared with RT-PCR for patients infected with non-B subtypes, the Up24 demonstrated limited sensitivity especially at low viral loads. Moreover, the Up24 was positive in 33% of samples deemed undetectable by RT-PCR, which may limit the use of the Up24 to detect viral suppression.

Low frequency of liver enzyme elevation in HIV-infected patients attending a large urban treatment centre in Uganda.

Liver enzyme elevations among patients on antiretroviral therapy (ART) were determined by prospectively evaluating aspartate aminotransferase (AST) data in a cohort of patients in Kampala over 36 months. A proportion of patients had hepatitis B virus (HBV) status determined. Hepatotoxicity was graded I to IV according to the AIDS Clinical Trial Group criteria. Of 546 patients, 377 (69%) were women; overall median baseline CD4+ T-cell was 97/µL (interquartile range [IQR] 20-164). Hepatitis B surface antigen (HBsAg) was detected in 42 (9%) of 470 persons. ART included lamivudine, with either nevirapine and d4T (74%) or efavirenz and AZT (26%). Median (IQR) AST level at baseline was 35 (27, 53 IU/L). Over 36 months, only eight patients had grade III AST elevation. Neither HBsAg nor ART regimen influenced AST levels. Male gender and CD4+ change from baseline were correlated with AST elevation. Patients with HIV/HBV co-infection were not at an increased risk of AST elevation, which occurred uncommonly in this setting.

Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda.

SETTING: Mulago Hospital, Uganda. OBJECTIVE: To evaluate the burden of TB-HIV (tuberculosis-human immunodeficiency virus) co-infections and their predictors in an urban hospital-based HIV programme. DESIGN: Prospective observational study. METHODS: Clinicians screened all patients with HIV/AIDS (acquired immune-deficiency syndrome) for previous and current TB treatment at enrolment and throughout follow-up. RESULTS: Of 10,924 patients enrolled between August 2005 and February 2009, co-prevalent TB was 157/10,924 (1.4%), which included 88/157 (56%) with TB confirmed at enrolment and 65/157 (41%) with TB diagnoses established during follow-up in whom symptoms were present at enrolment. Male sex (adjusted odds ratio [aOR] 2.3, 95%CI 1.6-3.2) and body mass index (BMI) ≤ 20 kg/m(2) (aOR 3.8, 95%CI 2.5-5.4) were associated with co-prevalent TB. Overall, 749/10,767 (7%) were diagnosed with incident TB at a higher rate among antiretroviral treatment (ART) patients (8/100 patient years of observation [PYO]) than non-ART patients (5/100 PYO, log rank P < 0.001). Female sex (adjusted hazard ratio [aHR] 1.4, 95%CI 1.2-1.7) and baseline BMI ≤ 20 (aHR 1.9, 95%CI 1.6-2.2) predicted incident TB. CONCLUSION: Routine TB screening in the HIV/AIDS care programme identified a significant number of TB-HIV co-infections among patients with and without ART, and is therefore a potential strategy to improve HIV treatment outcomes in resource-limited settings.

Health care related factors associated with severe malaria in children in Kampala, Uganda.

BACKGROUND: Severe malaria is responsible for the high load of malaria mortality. It is not clearly understood why some malaria episodes progress to severe malaria. OBJECTIVE: To determine factors associated with severe malaria in children aged 6 months to 5 years living in Kampala. METHODS: Over a 6-month period, 100 children with severe malaria were matched by age and place of residence with 100 children with non-severe malaria. We collected health care information from care takers. RESULTS: Mean duration of illness before getting antimalarial treatment was shorter for controls than cases (8 hours vs. 20 hours, p 0.015). Children with severe malaria were less likely to have been treated with sulphadoxine-pyrimethamine in the preceding 2 weeks (OR 0.2, 95% CI 0.04-0.85, p 0.016). Odds of severe malaria were higher in those who reported lack of protective measures (mosquito coils (OR = 20.63, 95% CI 1.5-283.3, p=0.02 and insecticide sprays OR 10.93, 95% CI 1.13-105.64, p=0.03), although few reported their use. CONCLUSIONS: Early anti-malarial treatment and use of barriers against mosquitoes prevent severe malaria in children. There is need to increase the use of barriers against mosquito bites and to scale up prompt treatment and community-based interventions to reduce the incidence of severe malaria in children.

Malaria in Uganda: challenges to control on the long road to elimination. II. The path forward.

In the recent past there have been several reports of successes in malaria control, leading some public health experts to conclude that Africa is witnessing an epidemiological transition, from an era of failed malaria control to progression from successful control to elimination. Successes in control have been attributed to increased international donor support leading to increased intervention coverage. However, these changes are not uniform across Africa. In Uganda, where baseline transmission is very high and intervention coverage not yet to scale, the malaria burden is not declining and has even likely increased in the last decade. In this article we present perspectives for the future for Uganda and other malaria endemic countries with high baseline transmission intensity and significant health system challenges. For these high burden areas, malaria elimination is currently not feasible, and early elimination programs are inappropriate, as they would further fragment already fragmented and inefficient malaria control systems. Rather, health impacts will be maximized by aiming to achieve universal coverage of proven interventions in the context of a strengthened health system.(AU)