Low ivermectin use among 5- to 6-year-old children: observations from door-to-door surveys in onchocerciasis-endemic regions in Africa.

During door-to-door surveys in onchocerciasis-endemic regions in Africa, the age-specific ivermectin coverage in 29 722 individuals was assessed. Children 5-6 y of age had significantly lower coverage compared with older participants. Insufficient ivermectin intake among young children could prolong onchocerciasis elimination prospects, as they may serve as human reservoirs of Onchocerca volvulus; moreover, it increases the risk of developing onchocerciasis-associated epilepsy (OAE). The causes of the low ivermectin coverage observed among children 5-6 y of age need to be explored. Integrating ivermectin distribution into chemoprophylaxis strategies for other neglected diseases could increase coverage in a cost-effective manner.

Reasons for first line ART modification over the years during the ART scale up in Uganda.

BACKGROUND: During the initial scale up of ART in sub-Saharan Africa, prescribed regimens included drugs with high potential for toxicity (particularly stavudine). More recently a growing number of patients requires second line treatment due to treatment failure, especially following the expansion of viral load testing. We aim to determine the reasons and risk factors for modification of first line ART across the years. METHODS: We included patients started on standard first line ART (2NRTI + 1 NNRTI) between 2005 and 2016 at the Infectious Diseases Institute, Kampala, Uganda. We described the reasons for treatment modification categorized in (1) toxicity (2) treatment failure (3) other reason (new TB treatment, new pregnancy). We used Cox proportional hazard to identify factors associated with treatment modification due to toxicity. RESULTS: We included 14,261 patients; 9114 (63.9%), were female, the median age was 34 years (IQR: 29-40), 60.8% were in WHO stage 3 and 4. The median BMI and CD4 count were 21.9 (IQR: 19.6-24.8) and 188 cell/µL (IQR: 65-353) respectively; 27.5% were started on stavudine, 46% on zidovudine, and 26.5% on a tenofovir containing regimens. We observed 6248 ART modifications in 4868/14,261 patients (34.1%); 1615 were due to toxicity, 1077 to treatment failure, 1330 to contraindications, and 1860 patients following WHO recommendation of phasing out stavudine and substituting with another NRTI. Modification for drug toxicity declined rapidly after the phase out of stavudine (2008), while switches to second line regimes increased after the implementation of viral load monitoring (2015). Patients with normal BMI compared to underweight, (HR: 0.79, CI 0.69-0.91), with CD4 counts 200-350 cells/µL compared to < 200 cells/µL (HR: 0.81- CI 0.71-0.93), and started on zidovudine (HR: 0.51 CI 0.44-0.59) and tenofovir (HR: 0.16, CI 0.14-0.22) compared to stavudine were less likely to have ART modification due to toxicity. Older patients (HR: 1.14 per 5-year increase CI 1.11-1.18), those in WHO stage 3 and 4 (HR: 1.19, CI 1.06-1.34) were more likely to have ART modification due to toxicity. CONCLUSIONS: Toxicity as reason for drugs substitution decreased over time mirroring the phase out of stavudine, while viral load expansion identified more patients in need of second line treatment.

Community-acquired pneumonia in Ugandan adults: short-term parenteral ampicillin therapy for bacterial pneumonia.

A hospital-based prospective study of 99 patients with community-acquired pneumonia (CAP) was carried out in Kampala, Uganda. We evaluated microbiological etiologies, clinical features and effectiveness of short-term parenteral ampicillin followed by oral amoxicillin for these patients in relation to HIV-status. We demonstrated a very high prevalence (75%) of HIV-1 infection. No significant difference was observed with respect to age, gender, prior antibiotic usage, symptoms, laboratory data or bacterial etiology between HIV-1-infected and HIV-uninfected CAP patients. Most strains of Streptococcus pneumoniae (n = 19) and Haemophilus influenzae (n = 8) isolated from HIV-1-infected patients were penicillin-resistant (95%) and beta-lactamase producing (75%) strains, respectively. A high percentage of good clinical response was found in both HIV-1-infected (81%) and HIV-uninfected (86%) among 39 patients with CAP due to a defined bacterial pathogen. These data support the use of short-term parenteral ampicillin for patients with bacterial CAP irrespective of HIV-status.

Activation of beta-chemokines and CCR5 in persons infected with human immunodeficiency virus type 1 and tuberculosis.

Tuberculosis (TB) in human immunodeficiency virus type 1 (HIV-1)-infected persons is associated with progression of HIV-1 disease. The expression of macrophage inflammatory protein (MIP)-1alpha and CCR5 was assessed in HIV-1-infected patients with pulmonary TB (HIV-1/PTB) and without PTB (HIV-1/C), PTB patients not infected with HIV-1 (PTB), and control subjects. Mycobacterium tuberculosis (MTB)-induced MIP-1alpha production was lower in peripheral blood mononuclear cells (PBMC) of HIV-1/PTB patients than in those of PTB patients (P< .05) and was lower in PBMC of HIV-1/C patients than in those of control subjects (P< .005). However, MIP-1alpha production was higher in PBMC of HIV/PTB patients than in those of HIV-1/C patients (P< .01). The pattern of MTB-induced RANTES production was similar to that of MIP-1alpha. However, MTB induced greater expression of mRNA for CCR5 in PBMC of HIV-1/PTB patients than in those of HIV-1/C patients (P< .04). Furthermore, the MTB-induced HIV p24 antigen level in PBMC of HIV-1/PTB patients with a CD4 cell count <500 cells/microL was higher (P< .05) than that in HIV-1/C patients. Thus, perturbations in chemokine pathways in HIV-1/PTB patients may accelerate HIV-1 disease.

Macrophage-activating cytokines in human immununodeficiency virus type 1-infected and -uninfected patients with pulmonary tuberculosis.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected patients globally and occurs throughout the course of HIV-1 disease. Here the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMC) of HIV-1-infected versus -uninfected patients with newly diagnosed pulmonary TB (PTB) was compared. Findings were correlated with cytokine profiles, clinical presentation, and expression of inducible nitric oxide (iNOS). Most HIV-1/PTB patients with a CD4 cell count of 200-500 cells/microL had high IFN-gamma production and radiographic evidence of atypical PTB. Low IFN-gamma production and radiographic evidence of reactivated PTB characterized both HIV-1/PTB patients with a CD4 cell count >or=500 cells/microL and HIV-1-uninfected patients. TNF-alpha levels were similar in all HIV-1/PTB patients, regardless of CD4 cell count. Induction of iNOS in PBMC was low and was associated with low IFN-gamma production. These data underscore the potential pathogenic role of macrophage-activating cytokines in TB in HIV-1-infected patients.

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

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

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.

Comparative humoral responses to HIV-1 p24gag and gp120env in subjects from East Africa and the UK.

We compared 1616 sera from HIV-1-infected subjects and matched HIV-negative local controls in Uganda, Kenya and the UK. Sera were screened for specific antibody to HIV-1 p24 Gag and gp120 Env proteins and for p24 antigenaemia. In contrast to the UK, the majority of African HIV-1-infected subjects maintained detectable anti-p24 antibodies. However, lower reactivity of anti-p24 was observed in African AIDS patients, compared with those with asymptomatic HIV-1 infection. This reduction in anti-p24 reactivity with more advanced clinical stage was less marked in African HIV-1 infection than in the UK. Correspondingly, p24 antigenaemia was more common in patients with AIDS from the UK than in African patients (65 versus 4%). Reductions in anti-gp120 reactivity were observed in African AIDS patients, compared with the asymptomatic group. However, median reactivity of anti-gp120 in UK patients remained unchanged in both asymptomatic and AIDS subjects. The differences in humoral response to p24 and gp120 between Africa and the UK are semi-quantitative rather than qualitative and could be explained by initial higher antibody response to HIV-1 in African subjects.

Development and Evaluation of Guidelines for the Clinical Management of HIV Infection in Adults and Children in Uganda

Objective: To assist health workers in diagnosis and treatment and rational use of drugs in symptomatic HIV infection. Methods: The different stages of the development and evaluation: 1. Development of draft guidelines through national consensus of policy makers; programme managers and AIDS Care workers. 2. Training of personnel in selected health units in the use of the guidelines. 3. Field testing of the guidelines for a period of 5 months. 4. Evaluation workshop. 5. Second National Consensus Seminar. Results and Conclusions: 1. The guidelines were applicable in the field and were mostly used by nurses and medical assistants. 2. Restriction of the number of drugs was difficult because of the multiple complaints of the patients: 24; of the patients received more than 3 different drugs. 3. Most conditions were easily managed but for chronic diarrhoea only 40of the health workers adhered to the treatment guidelines. 4. Further training with regular evaluation is required in the use of the guidelines