Evaluation of weight-based prescription of antiretroviral therapy in children.

OBJECTIVES: The aim of the study was to investigate the extent of and factors associated with incorrect dosing of antiretroviral therapy (ART) in HIV-infected children in Harare, Zimbabwe. METHODS: All children aged 0-10 years and children aged 11-17 years who weighed < 35 kg and taking ART were recruited from the paediatric HIV clinic at Harare Hospital. Their current doses of ART drugs were compared against doses recommended by the national guidelines. RESULTS: Among 309 children recruited [55% male; median age 7 years (interquartile range (IQR) 5-10 years)], the median CD4 count was 899 cells/µL and the median duration of their current ART regimen was 11.2 months (IQR 4.9-17.1 months). Overall, 110 (35.6%) children were prescribed incorrect doses of at least one drug component within their ART regimen; 64 (20.7%) under-dosed and 49 (15.9%) over-dosed on at least one drug. Children receiving a higher than recommended dose of at least one drug were younger compared with correctly dosed children (median 6 versus 7 years, respectively; P = 0.001), had been on their current ART regimen for a shorter time (median 7.2 versus 13 months, respectively; P = 0.003) and were less likely to be receiving a three-drug fixed-dose combination (FDC; 42.9 versus 63.3%, respectively; P = 0.009). Those who were under-dosed were also less likely to be on a three-drug FDC (25 versus 63.3%, respectively; P < 0.001). CONCLUSIONS: Over a third of children were prescribed incorrect doses of ART. Children taking triple-drug FDCs were likely to be correctly dosed. Our study highlights the importance of weight monitoring at each clinical contact, training of health care providers on paediatric drug dosing and the need for wider availability of FDCs for children.

Hearing impairment and deafness among HIV infected children and adolescents in Harare, Zimbabwe.

Background: Among HIV-infected children ear infections are recurrent and chronic, which may lead to hearing loss. Objective: To determine the prevalence, cause and severity of hearing impairment among HIV-infected children aged 5-17 years attending for HIV care in Harare. Design and Setting: An analytical cross-sectional survey conducted at Newlands Clinic, an opportunistic infections clinic in Harare. Materials and Methods: Participants underwent a standardised otoscopic examination of the ear and Pure Tone Audiometry (PTA). Factors associated with hearing impairment were investigated using multivariate logistic regression. Results: Three hundred and eighty (380) participants (55% female and mean age 11 years (SD: 3.3 years)) were consecutively recruited. The vast majority of participants (n=338; 89% were taking antiretroviral therapy (ART) for a median of 3 (IQR: 2-5) years at recruitment, and the most recent median CD4 Count (i.e. CD4 count measured within 6 months of the study recruitment) was 725 (IQR: 497-1000) cells/µL, with no difference by ART status. 61% (n= 231) of participants had an abnormal ear examination. Of the 359 participants who underwent audiometry, the prevalence of hearing impairment was 32.3% (95%CI: 27.5%-37.4%) based on a PTA threshold ≥26Db. Hearing impairment was associated with a recent CD4 count <350cell/µL (OR 2.1, P<0.037). Conclusion: There is a high prevalence of hearing impairment among HIV-infected children and adolescents. Low CD4 count remains a risk factor even among those who are on ART. We recommend that HIV infected children and adolescents, particularly those with low CD4 counts, should have routine evaluation of hearing as part of HIV care.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Chest radiography patterns in 75 adolescents with vertically-acquired human immunodeficiency virus (HIV) infection.

AIM: To evaluate lung disease on chest radiography (CR), the relative frequency of CR abnormalities, and their clinical correlates in adolescents with vertically-acquired human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: CRs of 75 patients [59 inpatients (33 males; mean age 13.7±2.3 years) and 16 outpatients (eight males; mean age 14.1±2.1 years)] were retrospectively reviewed by three independent observers. The overall extent of disease (to the nearest 5%), its distribution, and the proportional extents (totalling 100%) of different radiographic patterns (including ring/tramline opacities and consolidation) were quantified. CR features and clinical data were compared. RESULTS: CRs were abnormal in 51/75 (68%) with "extensive" disease in 38/51 (74%). Ring/tramline opacities and consolidation predominated (i.e., proportional extent >50%) in 26 and 21 patients, respectively. Consolidation was significantly more common in patients hospitalized primarily for a respiratory illness than patients hospitalized for a non-respiratory illness or in outpatients (p<0.005, χ(2) for trend); by contrast, ring/tramline opacities did not differ in prevalence across the groups. On stepwise logistic regression, predominant consolidation was associated with progressive dyspnoea [odds ratio (OR) 5.60; 95% confidence intervals (CI): 1.60, 20.1; p<0.01] and was associated with a primary respiratory cause for hospital admission (OR: 22.0; CI: 2.7, 181.1; p<0.005). Ring/tramline opacities were equally prevalent in patients with and without chronic symptoms and in those admitted to hospital with respiratory and non-respiratory illness. CONCLUSION: In HIV-infected adolescents, evaluated in secondary practice, CR abnormalities are prevalent. The presence of ring/tramline opacities, believed to reflect chronic airway disease, is not linked chronic respiratory symptoms.

A comparison of HIV outpatient care in primary and secondary healthcare-level settings in Zimbabwe.

SETTING: Decentralisation of HIV care to nurse-led primary care services is being implemented across low- and middle-income countries in sub-Saharan Africa. OBJECTIVE: To compare services offered to clients attending for HIV care at a physician-led and a nurse-led service in Harare, Zimbabwe. DESIGN: A cross-sectional study was performed at Harare Central Hospital (HCH) and Budiriro Primary Care Clinic (PCC) from June to August 2018. An interviewer-administered questionnaire was used to collect sociodemographics, HIV treatment and clinical history from clients attending for routine HIV care. The Mann-Whitney U-test was used to evaluate for differences between groups for continuous variables. For categorical variables, the χ2 test was used. RESULTS: The median age of the 404 participants recruited was 38 years (IQR 28-47); 69% were female. Viral suppression was comparable between sites (HCH, 70% vs. PCC, 80%; P = 0.07); however, screening for comorbidities such as cervical cancer screening (HCH, 61% vs. PCC, 41%; P = 0.001) and provision of referral services (HCH, 23% vs. PCC, 13%; P = 0.01) differed between sites. CONCLUSION: Efforts to improve service provision in primary care settings are needed to ensure equity for users of health services.

Auditing use of antibiotics in Zimbabwean neonates.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in low-income settings. As signs of sepsis are non-specific and deterioration precipitous, antibiotics are often used profusely in these settings where diagnostics may not be readily available. Harare Central Hospital, Zimbabwe, delivers 12000 babies per annum admitting ∼4800 to the neonatal unit. Overcrowding, understaffing and rapid staff turnover are consistent problems. Suspected sepsis is highly prevalent, and antibiotics widely used. We audited the impact of training and benchmarking intervention on rationalizing antibiotic prescription using local, World Health Organization-derived, guidelines as the standard. METHODS: An initial audit of admission diagnosis and antibiotic use was performed between 8th May - 6th June 2018 as per the audit cycle. An intern training programme, focusing on antimicrobial stewardship and differentiating between babies 'at risk of' versus 'with' clinically-suspected sepsis was instituted post-primary audit. Re-audit was conducted after 5 months. RESULTS: Sepsis was the most common admitting diagnosis by interns at both time points but reduced at repeat audit (81% versus 59%, P<0.0001). Re-audit after 5 months demonstrated a decrease in antibiotic prescribing at admission and discharge. Babies prescribed antibiotics at admission decreased from 449 (98%) to 96 (51%), P<0.0001. Inpatient days of therapy (DOT) reduced from 1243 to 1110/1000 patient-days. Oral amoxicillin prescription at discharge reduced from 349/354 (99%) to 1% 1/161 (P<0.0001). CONCLUSION: A substantial decrease in antibiotic use was achieved by performance feedback, training and leadership, although ongoing performance review will be key to ensuring safety and sustainability.

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance.

OBJECTIVE: The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged > or =13 years. METHODS: A retrospective review of HIV diagnoses reported to well-established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted. RESULTS: Forty-two young people with vertically acquired HIV diagnosed aged > or =13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub-Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13-20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/microL (range, 0-689 cells/microL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis. CONCLUSION: A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age > or =13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV-infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.

Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution.

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.

Chronic knee stiffness and swelling in a Zimbabwean adolescent.

A 12-year-old Zimbabwean girl presented with tuberculous monoarthritis. She was moderately wasted, stunted and sexually immature. These clinical findings lead to the diagnosis of underlying HIV infection, which was thought to have been acquired from mother-to-child transmission.

Tackling STI epidemics through the HIV clinic: is sex high enough on the agenda?

Sexually transmitted infection (STI) rates among men having sex with men continue to increase. HIV services may operate independently to genitourinary medicine clinics and the sexual health of HIV-positive patients may be of low priority in the context of medical problems related to HIV. A prospective study of HIV-positive gay men was conducted in a London outpatient clinic over a three-month period. Data were available for 90 men. Forty-five percent had STI screens in the preceding six months. These revealed a high rate of infections; 26 infections diagnosed in 14 men in the study period. Fifty-seven percent of the 90 men in the study had more than one partner in the past three months and approximately one-third had unprotected sexual activity. A significant proportion of men were unaware of recent outbreaks of hepatitis C and lymphogranuloma venereum and of HIV postexposure prophylaxis. We therefore recommend that sexual history-taking, STI screens and health promotion should become a routine feature of HIV outpatient consultations in this group.

Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV infection.

An adolescent with long-standing HIV infection who was severely immunosuppressed during HIV diagnosis developed cholangiocarcinoma 1.5 years after starting antiretroviral therapy.

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood.

Impact of scaling up Xpert® MTB/RIF testing for the detection of rifampicin-resistant TB cases in Karachi, Pakistan.

SETTING: Pakistan ranks fourth among the countries with a high burden of multidrug-resistant tuberculosis (MDR-TB), with only 19.2% of the 15 000 estimated incident cases being notified. Increasing treatment coverage for MDR-TB is a key priority for Pakistan's National Tuberculosis Programme. The World Health Organization recommends the use of the Xpert® MTB/RIF assay as the first-line diagnostic test for individuals with presumed TB. OBJECTIVE: To describe a multifaceted case-finding intervention targeting public and private sector health care facilities that used the Xpert assay as a frontline diagnostic test for individuals with presumptive TB, in Karachi, Pakistan, and its impact on case notifications of MDR-TB. DESIGN: Cross-sectional study. RESULTS: A total of 51 168 individuals were tested using Xpert, of whom respectively 7581 and 1534 people were diagnosed with TB in the public sector (reverse public-private mix) and private sector (social business model) arms; 574 (6.3% of all TB cases) were identified as having rifampicin (RMP) resistance. A total of 517 (90.1%) people with RMP-resistant TB (RR-TB) identified through the project were initiated on second-line treatment. The intervention resulted in 194 additional cases of RR-TB, an increase of 43% over the baseline. CONCLUSION: This project, one of the largest Xpert testing programmes conducted at city level, resulted in significantly increased detection and treatment of MDR-TB.

Management of HIV infection in adolescents attending inner London HIV services.

Increasing numbers of HIV-infected children are now reaching adulthood and young people account for 10% of new HIV diagnosis in the UK each year. This audit of young people attending specialist and generic HIV services in Inner London in 2006 (n=39) highlights the complex medical and psychosocial needs of this patient group: 63% were diagnosed with HIV because of poor health, 39% had received more than three antiretroviral regimens, 21% had resistance to two antiretroviral classes and 32% had significant mental health problems. In addition, 45% reported to be sexually active with poor uptake of contraception other than condoms and frequent non-disclosure of their HIV status to a sexual partner.

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection.

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.

Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe.

OBJECTIVE: To evaluate the diagnostic performance of Xpert® MTB/RIF on stool samples from children with clinical suspicion of pulmonary tuberculosis (PTB) at primary care clinics. DESIGN: A cross-sectional diagnostic evaluation enrolling 5-16 year olds from whom one induced sputum (IS) sample was tested for microbiological TB confirmation. Results of a single stool sample tested using Xpert were compared against microbiologically confirmed TB, defined as a positive result on sputum microscopy and/or culture and/or IS Xpert. RESULTS: Of 222 children enrolled, 218 had complete microbiological results. The median age was 10.6 years (interquartile range 8-13). TB was microbiologically confirmed in 19/218 (8.7%) children. Of these, respectively 5 (26%), 9 (47%) and 15 (79%) were smear-, culture- and IS Xpert-positive. Stool Xpert was positive in 13/19 (68%) microbiologically confirmed cases and 4/199 (2%) microbiologically negative cases. Stool Xpert detected 76.9% (10/13) of human immunodeficiency virus (HIV) infected and 50% (3/6) of non-HIV-infected children with microbiologically confirmed TB (P = 0.241). CONCLUSION: Stool Xpert is a potential alternative screening test for children with suspected TB if sputum is unavailable. Strategies to optimise the diagnostic yield of stool Xpert assay need further study.

Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe.

BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS: Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available.

Hypercalcaemia complicating immune reconstitution in an HIV-infected patient with disseminated tuberculosis.

An HIV positive man being treated for disseminated tuberculosis developed hypercalcaemia 17 days after starting highly active antiretroviral therapy (HAART). Hypercalcaemia resolved with stopping HAART and was thought to be due to immune reconstitution inflammatory syndrome.

Interferon-gamma responses to ESAT-6 in tuberculosis patients early into and after anti-tuberculosis treatment.

OBJECTIVE: To investigate T-cell responses to ESAT-6 by an interferon-gamma (IFN-gamma) ex vivo enzyme-linked immunospot (ELISpot) assay in tuberculosis (TB) patients early during treatment and in patients who have completed a course of anti-tuberculosis chemotherapy. DESIGN: T-cell responses following overnight stimulation with 6-kD early secretory antigenic target (ESAT-6) antigen were compared to responses obtained using cells cultured with ESAT-6 for 6 days, using an ELISpot assay. RESULTS: In the ex vivo ELISpot assay, the median IFN-gamma responses in TB patients, irrespective of treatment status, were significantly higher than in healthy BCG-vaccinated controls. In the 6-day ELISpot assay, median IFN-gamma responses were significantly higher in TB patients who had completed treatment than in patients early during therapy. There was considerable individual variability in the degree of expansion of ESAT-6 specific T-cells from day 1 to day 6 in both treatment groups. CONCLUSION: Further studies are required to assess which type of assay provides the best indicator of a memory T-cell response and how ESAT-6 specific T-cells relate to protective immunity in TB infection.

Enhancing patient safety with an electronic results checking system in a large HIV outpatient service.

OBJECTIVE: To establish whether an automated electronic tracker system for reporting blood results would expedite clinician review of abnormal results in HIV-positive outpatients and to pilot the use of this system in routine clinical practice. SETTING: An outpatient service in central London providing specialist HIV-related care to 3900 HIV positive patients. DESIGN: A comparison of the time taken from sampling to identification and clinician review of abnormal blood results for biochemical tests between the original paper-based checking system and an automated electronic system during a 3-week pilot. RESULTS: Of 513 patients undergoing one or more blood tests, 296 (57%) had one or more biochemical abnormalities identified by electronic checking system. Out of 371 biochemical abnormalities, 307 (82.7%) were identified simultaneously by the paper-based system. Of the 307, 33 (10.7%) were classified as urgent, 130 (42.3%) as non-urgent and 144 (46.9%) as not clinically significant. The median interval between sampling and receipt of results was 1 (interquartile range 1-2) vs 4 days ( interquartile range 3-5), P <0.0001; clinician review 3 (interquartile range 1-4) vs 3 days (interquartile range 3-6), P<0.037; and review of non-urgent abnormalities by the regular clinician 2 (interquartile range 1-4) vs 10 days ( interquartile range 9-12), P=0.136, for electronic and paper-based systems respectively. Seven (11%) of the missing paper-based system results were classified as urgent. The electronic system missed three abnormalities as a result of a software processing error which was subsequently corrected. CONCLUSIONS: The electronic tracker system allows faster identification of biochemical abnormalities and allowed faster review of these results by clinicians. The pilot study allowed for a software error to be identified and corrected before full implementation. The system has since integrated successfully into routine clinical practice.