High post-exposure prophylaxis uptake but low completion rates and HIV testing follow-up in health workers, Harare, Zimbabwe.

INTRODUCTION: Health care workers (HCWs), especially from sub-Saharan Africa, are at risk of occupational exposure to HIV. Post exposure prophylaxis (PEP) can reduce this risk. There is no published information from Zimbabwe, a high HIV burden country, about how PEP works. We therefore assessed how the PEP programme performed at the Parirenyatwa Hospital, Harare, Zimbabwe, from 2017-2018. METHODOLOGY: This was a cohort study using secondary data from the staff clinic paper-based register. The chi square test and relative risks were used to assess associations. RESULTS: There were 154 HCWs who experienced occupational injuries. The commonest group was medical doctors (36%) and needle sticks were the most frequent type of occupational injury (74%). The exposure source was identified in 114 (74%) occupational injuries: 91% of source patients were HIV-tested and 77% were HIV-positive. All but two HCWs were HIV-tested, 148 were eligible for PEP and 142 (96%) started triple therapy, all within 48 hours of exposure. Of those starting PEP, 15 (11%) completed 28 days, 13 (9%) completed < 28 days and in the remainder PEP duration was not recorded. There were no HCW characteristics associated with not completing PEP. Of those starting PEP, 9 (6%) were HIV-tested at 6-weeks, 3 (2%) were HIV-tested at 3-months and 1 (< 1%) was HIV-tested at 6-months: all HIV-tests were negative. CONCLUSIONS: While uptake of PEP was timely and high, the majority of HCWs failed to complete the 28-day treatment course and even fewer attended for follow-up HIV-tests. Various changes are recommended to promote awareness of PEP and improve adherence to guidelines.

A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.

Rifapentine is a rifamycin used to treat tuberculosis. As is the case for rifampin, plasma exposures of rifapentine are associated with the treatment response. While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms. We evaluated the effects of functionally significant polymorphisms of the genes encoding OATP1B1, the pregnane X receptor (PXR), constitutive androstane (CAR), and arylacetamide deacetylase (AADAC) on rifapentine exposure. Two studies evaluating novel regimens among southern African patients with drug-susceptible pulmonary tuberculosis were included in this analysis. In the RIFAQUIN study, rifapentine was administered in the continuation phase of antituberculosis treatment in 1,200-mg-once-weekly or 900-mg-twice-weekly doses. In the Daily RPE study, 450 or 600 mg was given daily during the intensive phase of treatment. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics of rifapentine and to identify significant covariates. A total of 1,144 drug concentration measurements from 326 patients were included in the analysis. Pharmacogenetic information was available for 162 patients. A one-compartment model with first-order elimination and transit compartment absorption described the data well. In a typical patient (body weight, 56 kg; fat-free mass, 45 kg), the values of clearance and volume of distribution were 1.33 liters/h and 25 liters, respectively. Patients carrying the AA variant (65.4%) of AADAC rs1803155 were found to have a 10.4% lower clearance. HIV-infected patients had a 21.9% lower bioavailability. Once-weekly doses of 1,200 mg were associated with a reduced clearance (13.2%) compared to that achieved with more frequently administered doses. Bioavailability was 23.3% lower among patients participating in the Daily RPE study than in those participating in the RIFAQUIN study. This is the first study to report the effect of AADAC rs1803155AA on rifapentine clearance. The observed increase in exposure is modest and unlikely to be of clinical relevance. The difference in bioavailability between the two studies is probably related to the differences in food intake concomitant with the dose. HIV-coinfected patients had lower rifapentine exposures.

Validation of a screening tool to identify older children living with HIV in primary care facilities in high HIV prevalence settings.

OBJECTIVE: We previously proposed a simple tool consisting of five items to screen for risk of HIV infection in adolescents (10-19 years) in Zimbabwe. The objective of this study is to validate the performance of this screening tool in children aged 6-15 years attending primary healthcare facilities in Zimbabwe. METHODS: Children who had not been previously tested for HIV underwent testing with caregiver consent. The screening tool was modified to include four of the original five items to be appropriate for the younger age range, and was administered. A receiver operator characteristic analysis was conducted to determine a suitable cut-off score. The sensitivity, specificity and predictive value of the modified tool were assessed against the HIV test result. RESULTS: A total of 9568 children, median age 9 (interquartile, IQR: 7-11) years and 4971 (52%) men, underwent HIV testing. HIV prevalence was 4.7% (95% confidence interval, CI:4.2-5.1%) and increased from 1.4% among those scoring zero on the tool to 63.6% among those scoring four (P < 0.001). Using a score of not less than one as the cut-off for HIV testing, the tool had a sensitivity of 80.4% (95% CI:76.5-84.0%), specificity of 66.3% (95% CI:65.3-67.2%), positive predictive value of 10.4% and a negative predictive value of 98.6%. The number needed to screen to identify one child living with HIV would drop from 22 to 10 if this screening tool was used. CONCLUSION: The screening tool is a simple and sensitive method to identify children living with HIV in this setting. It can be used by lay healthcare workers and help prioritize limited resources.

Implementation and Operational Research: The Effectiveness of Routine Opt-Out HIV Testing for Children in Harare, Zimbabwe.

OBJECTIVE: HIV testing is the entry point to access HIV care. For HIV-infected children who survive infancy undiagnosed, diagnosis usually occurs on presentation to health care services. We investigated the effectiveness of routine opt-out HIV testing (ROOT) compared with conventional opt-in provider-initiated testing and counseling (PITC) for children attending primary care clinics. METHODS: After an evaluation of PITC services for children aged 6-15 years in 6 primary health care facilities in Harare, Zimbabwe, ROOT was introduced through a combination of interventions. The change in the proportion of eligible children offered and receiving HIV tests, reasons for not testing, and yield of HIV-positive diagnoses were compared between the 2 HIV testing strategies. Adjusted risk ratios for having an HIV test in the ROOT compared with the PITC period were calculated. RESULTS: There were 2831 and 7842 children eligible for HIV testing before and after the introduction of ROOT. The proportion of eligible children offered testing increased from 76% to 93% and test uptake improved from 71% to 95% in the ROOT compared with the PITC period. The yield of HIV diagnoses increased from 2.9% to 4.5%, and a child attending the clinics post intervention had a 1.99 increased adjusted risk (95% CI: 1.85 to 2.14) of receiving an HIV test in the ROOT period compared with the preintervention period. CONCLUSION: ROOT increased the proportion of children undergoing HIV testing, resulting in an overall increased yield of positive diagnoses, compared with PITC. ROOT provides an effective approach to reduce missed HIV diagnosis in this age group.

Typhoid outbreak investigation in Dzivaresekwa, suburb of Harare City, Zimbabwe, 2011.

INTRODUCTION: Typhoid fever is a systemic infection caused by a Gram negative bacterium, Salmonella typhi. Harare City reported 1078 cases of suspected typhoid fever cases from October 2011 to January 2012. We initiated an investigation to identify possible source of transmission so as to institute control measures. METHODS: An unmatched 1:1 case-control study was conducted. A questionnaire was administered to study participants to identify risk factors for contracting typhoid. A case was a resident of Dzivaresekwa who presented with signs and symptoms of typhoid between October and December 2011. Water samples were collected for microbiological analysis. RESULTS: 115 cases and 115 controls were enrolled. Drinking water from a well (OR=6.2 95% CI (2.01-18.7)), attending a gathering (OR=11.3 95% CI (4.3-29.95)), boiling drinking water (OR=0.21 95% CI (0.06-0.76)) and burst sewer pipe at home (OR=1.19 95% CI (0.67-2.14)) were factors associated with contracting typhoid. Independent risk factors for contracting typhoid were drinking water from a well (AOR=5.8; 95% CI (1.90-17.78)), and burst sewer pipe at home (AOR=1.20; 95% CI (1.10-2.19)). Faecal coli forms and E. coli were isolated from 8/8 well water samples. Stool, urine and blood specimens were cultured and serotyped for Salmonella typhi and 24 cases were confirmed positive. Shigella, Giardia and E coli were also isolated. Ciprofloxacin, X-pen and Rocephin were used for case management. No complications were reported. CONCLUSION: Contaminated water from unprotected water sources was the probable source of the outbreak. Harare City Engineer must invest in repairing water and sewage reticulation systems in the city.

High-dose rifapentine with moxifloxacin for pulmonary tuberculosis.

BACKGROUND: Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS: We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS: We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval [CI], -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS: The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).

Barriers to provider-initiated testing and counselling for children in a high HIV prevalence setting: a mixed methods study.

BACKGROUND: There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children. METHODS AND FINDINGS: Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive. CONCLUSIONS: The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.

Drug-resistant tuberculosis in high-risk groups, Zimbabwe.

To estimate prevalence of multidrug-resistant tuberculosis (MDR TB) in Harare, Zimbabwe, in 2012, we performed microbiologic testing on acid-fast bacilli smear-positive sputum samples from patients previously treated for TB. Twenty (24%) of 84 specimens were consistent with MDR TB. A national drug-resistance survey is needed to determine MDR TB prevalence in Zimbabwe.

Moxifloxacin population pharmacokinetics and model-based comparison of efficacy between moxifloxacin and ofloxacin in African patients.

Pharmacokinetic exposure and the MIC of fluoroquinolones are important determinants of their efficacy against Mycobacterium tuberculosis. Population modeling was used to describe the steady-state plasma pharmacokinetics of moxifloxacin in 241 tuberculosis (TB) patients in southern Africa. Monte Carlo simulations were applied to obtain the area under the unbound concentration-time curve from 0 to 24 h (fAUC0-24) after daily doses of 400 mg or 800 mg moxifloxacin and 800 mg ofloxacin. The MIC distributions of ofloxacin and moxifloxacin were determined for 197 drug-resistant clinical isolates of Mycobacterium tuberculosis. For a specific MIC, the probability of target attainment (PTA) was determined for target fAUC0-24/MIC ratios of ≥53 and ≥100. The PTAs were combined with the MIC distributions to calculate the cumulative fraction of response (CFR) for multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Even with the less stringent target ratio of ≥53, moxifloxacin at 400 mg and ofloxacin at 800 mg achieved CFRs of only 84% and 58% for multidrug-resistant isolates with resistance to an injectable drug, while the 800-mg moxifloxacin dose achieved a CFR of 98%. Using a target ratio of ≥100 for multidrug-resistant strains (without resistance to injectable agents or fluoroquinolones), the CFR was 88% for moxifloxacin and only 43% for ofloxacin, and the higher dose of 800 mg moxifloxacin was needed to achieve a CFR target of >90%. Our results indicate that moxifloxacin is more efficacious than ofloxacin in the treatment of MDR-TB. Further studies should determine the optimal pharmacodynamic target for moxifloxacin in a multidrug regimen and clarify safety issues when it is administered at higher doses.

Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.

BACKGROUND: The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. METHODS: In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. FINDINGS: Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). INTERPRETATION: Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients. FUNDING: European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation.

Etiology and antimicrobial susceptibility of pathogens responsible for urethral discharge among men in Harare, Zimbabwe.

BACKGROUND: Periodic etiological surveillance of sexually transmitted infection (STI) syndromes is required to validate treatment algorithms used to control STIs. However, such surveys have not been performed in Zimbabwe over the past decade. METHODS: A cross-sectional study design was used to determine the prevalence of the key STI etiological agents causing male urethral discharge (MUD). Urethral swab specimens were collected for molecular analysis and Neisseria gonorrhoeae isolation from consenting men 18 years and older who presented with MUD to the 12 clinics in Harare, Zimbabwe, between November 2010 and May 2011. A validated in-house multiplex polymerase chain reaction assay was used to detect the presence of N. gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. Gonococci were cultured on selective media, and antimicrobial susceptibilities were determined locally for ciprofloxacin, kanamycin, ceftriaxone, and cefixime using Etest strips, and minimum inhibitory concentrations were reported using defined breakpoints. RESULTS: Among 130 participants, N. gonorrhoeae was the most frequent pathogen detected (106; 82.8%), followed by C. trachomatis (15; 11.7%), M. genitalium (6; 4.7%), and T. vaginalis (2; 1.6%). Four (6.1%) of the 66 gonococci isolated were resistant to fluoroquinolones, whereas all viable isolates were susceptible to kanamycin, cefixime, and ceftriaxone. CONCLUSIONS: Gonorrhea is the most important cause of MUD in men in Harare, and our study highlights the emergence of fluoroquinolone-resistant N. gonorrhoeae. Further STI surveys are required in other regions of Zimbabwe to obtain a nationally representative picture of gonococcal burden and antimicrobial resistance among MUD patients.

"You are wasting our drugs": health service barriers to HIV treatment for sex workers in Zimbabwe.

BACKGROUND: Although disproportionately affected by HIV, sex workers (SWs) remain neglected by efforts to expand access to antiretroviral treatment (ART). In Zimbabwe, despite the existence of well-attended services targeted to female SWs, fewer than half of women diagnosed with HIV took up referrals for assessment and ART initiation; just 14% attended more than one appointment. We conducted a qualitative study to explore the reasons for non-attendance and the high rate of attrition. METHODS: Three focus group discussions (FGD) were conducted in Harare with HIV-positive SWs referred from the 'Sisters with a Voice' programme to a public HIV clinic for ART eligibility screening and enrolment. Focus groups explored SWs' experiences and perceptions of seeking care, with a focus on how managing HIV interacted with challenges specific to being a sex worker. FGD transcripts were analyzed by identifying emerging and recurring themes that were specifically related to interactions with health services and how these affected decision-making around HIV treatment uptake and retention in care. RESULTS: SWs emphasised supply-side barriers, such as being demeaned and humiliated by health workers, reflecting broader social stigma surrounding their work. Sex workers were particularly sensitive to being identified and belittled within the health care environment. Demand-side barriers also featured, including competing time commitments and costs of transport and some treatment, reflecting SWs' marginalised socio-economic position. CONCLUSION: Improving treatment access for SWs is critical for their own health, programme equity, and public health benefit. Programmes working to reduce SW attrition from HIV care need to proactively address the quality and environment of public services. Sensitising health workers through specialised training, refining referral systems from sex-worker friendly clinics into the national system, and providing opportunities for SW to collectively organise for improved treatment and rights might help alleviate the barriers to treatment initiation and attention currently faced by SW.

Enhancing psychosocial support for HIV positive adolescents in Harare, Zimbabwe.

BACKGROUND: There is a recognized gap in the evidence base relating to the nature and components of interventions to address the psycho-social needs of HIV positive young people. We used mixed methods research to strengthen a community support group intervention for HIV positive young people based in Harare, Zimbabwe. METHODS: A quantitative questionnaire was administered to HIV positive Africaid support group attendees. Afterwards, qualitative data were collected from young people aged 15-18 through tape-recorded in-depth interviews (n=10), 3 focus group discussions (FGDs) and 16 life history narratives. Data were also collected from caregivers, health care workers, and community members through FGDs (n=6 groups) and in-depth interviews (n=12). Quantitative data were processed and analysed using STATA 10. Qualitative data were analysed using thematic analysis. RESULTS: 229/310 young people completed the quantitative questionnaire (74% participation). Median age was 14 (range 6-18 years); 59% were female. Self-reported adherence to antiretrovirals was sub-optimal. Psychological well being was poor (median score on Shona Symptom Questionnaire 9/14); 63% were at risk of depression. Qualitative findings suggested that challenges faced by positive children include verbal abuse, stigma, and discrimination. While data showed that support group attendance is helpful, young people stressed that life outside the confines of the group was more challenging. Caregivers felt ill-equipped to support the children in their care. These data, combined with a previously validated conceptual framework for family-centred interventions, were used to guide the development of the existing programme of adolescent support groups into a more comprehensive evidence-based psychosocial support programme encompassing caregiver and household members. CONCLUSIONS: This study allowed us to describe the lived experiences of HIV positive young people and their caregivers in Zimbabwe. The findings contributed to the enhancement of Africaid's existing programme of support to better promote psychological well being and ART adherence.

Burden of HIV among primary school children and feasibility of primary school-linked HIV testing in Harare, Zimbabwe: a mixed methods study.

Population-based surveys in Southern Africa suggest a substantial burden of undiagnosed HIV-infected long-term survivors of mother-to-child transmission. We conducted an HIV prevalence survey of primary school pupils in Harare, Zimbabwe, and evaluated school-linked HIV counselling and testing (HCT) for pupils, their families and schoolteachers. Population-weighted cluster sampling was used to select six primary schools. Randomly selected class-grade pupils underwent anonymous HIV testing, with concurrent school-linked family HCT offered during the survey. Focus group discussions and interviews were conducted with pupils, parents/guardians, counsellors, and schoolteachers. About 4386 (73%) pupils provided specimens for anonymous HIV testing. Median age was 9 years (IQR 8-11), and 54% were female. HIV prevalence was 2.7% (95% CI: 2.2-3.1) with no difference by gender. HIV infection was significantly associated with orphanhood, stunting, wasting, and being one or more class grades behind in school due to illness (p<0.001). After adjusting for covariates, orphanhood and stunting remained significantly associated with being HIV positive (p<0.001). Uptake of diagnostic HIV testing by pupils was low with only 47/4386 (1%) pupils undergoing HCT. The HIV prevalence among children under 15 years who underwent HIV testing was 6.8%. The main barrier to HIV testing was parents' fear of their children experiencing stigma and of unmasking their own HIV status should the child test HIV positive. Most guardians believed that a child's HIV-positive result should not be disclosed and the child could take HIV treatment without knowing the reason. Increased recognition of the high burden of undiagnosed HIV infection in children is needed. Despite awareness of the benefits of HIV testing, HIV-related stigma still dominates parents/guardians' psychological landscape. There is need for comprehensive information and support for families to engage with HIV testing services.

Detection of Mycobacterium tuberculosis in sputum by gas chromatography-mass spectrometry of methyl mycocerosates released by thermochemolysis.

Tuberculosis requires rapid diagnosis to prevent further transmission and allow prompt administration of treatment. Current methods for diagnosing pulmonary tuberculosis lack sensitivity are expensive or are extremely slow. The identification of lipids using gas chromatography- electron impact mass spectrometry (GC-EI/MS) could provide an alternative solution. We have studied mycocerosic acid components of the phthiocerol dimycocerosate (PDIM) family of lipids using thermochemolysis GC-EI/MS. To facilitate use of the technology in a routine diagnostic laboratory a simple extraction procedure was employed where PDIMs were extracted from sputum using petroleum ether, a solvent of low polarity. We also investigated a method using methanolic tetramethylammonium hydroxide, which facilitates direct transesterification of acidic components to methyl esters in the inlet of the GC-MS system. This eliminates conventional chemical manipulations allowing rapid and convenient analysis of samples. When applied to an initial set of 40 sputum samples, interpretable results were obtained for 35 samples with a sensitivity relative to culture of 94% (95%CI: 69.2,100) and a specificity of 100% (95%CI: 78.1,100). However, blinded testing of a larger set of 395 sputum samples found the assay to have a sensitivity of 61.3% (95%CI: 54.9,67.3) and a specificity of 70.6% (95%CI: 62.3,77.8) when compared to culture. Using the results obtained we developed an improved set of classification criteria, which when applied in a blinded re-analysis increased the sensitivity and specificity of the assay to 64.9% (95%CI: 58.6,70.8) and 76.2% (95%CI: 68.2,82.8) respectively. Highly variable levels of background signal were observed from individual sputum samples that inhibited interpretation of the data. The diagnostic potential of using thermochemolytic GC-EI/MS of PDIM biomarkers for diagnosis of tuberculosis in sputum has been established; however, further refinements in sample processing are required to enhance the sensitivity and robustness of the test.

Adult mortality in the cities of Bulawayo and Harare, Zimbabwe: 1979-2008.

BACKGROUND: Zimbabwe has been severely affected by the HIV/AIDS and tuberculosis epidemics, with an estimated 80% of tuberculosis patients being HIV infected. We set out to use annual population-mortality records from the cities of Harare and Bulawayo to describe trends and possible causes of mortality from 1979 to 2008. The specific objectives were to document overall, sex and age-specific mortality, proportion of deaths attributed to AIDS and tuberculosis, and changes in death rates since the start of antiretroviral therapy in 2004. METHODS: This retrospective descriptive study used existing mortality records of the Health Services departments in Harare and Bulawayo. Data points included: estimated yearly total population; groupings by sex and age; deaths (total and by sex and age groups for each year of the study period); and most frequently reported causes of death (for age groups <15 years, 15-44 years and ≥ 45 years). Data on deaths were aggregated by year, and crude, sex- and age-specific death rates were calculated per 1000 population. Tuberculosis and HIV-related disease-specific death rates and proportion of deaths attributed to these conditions were computed. RESULTS: In both cities, crude death rates were lowest in the late 1980s, increased three- to five-fold by the early 2000s, and began a slow and, in the case of Bulawayo, intermittent decline from 2004. Sex-specific death rates followed a similar trend, being higher in males than in females. The death rates in the age groups <5 years, 15-44 years and ≥ 45 years showed significant increases, with a gradual levelling off and decline from 2002 onwards; death rates in those aged 5-14 years were relatively unaffected. Tuberculosis and HIV caused 70% of deaths in the age group of 15-44 years from the early 1990 s. CONCLUSIONS: This study used routinely collected population-mortality data that are rare in resource-limited settings, and it described, for the first time in Zimbabwe, the effects of the HIV/AIDS epidemic and the introduction of antiretroviral therapy on death rates in two large cities. After a substantial rise in crude mortality rates, there has been a decline associated with the introduction of ART. Such routine population data must continue to be collected, collated and analyzed.

Perception of risk of vertically acquired HIV infection and acceptability of provider-initiated testing and counseling among adolescents in Zimbabwe.

OBJECTIVES: We investigated attitudes toward provider-initiated HIV testing and counseling (PITC) in the suburbs of Harare, Zimbabwe, where late presentation after mother-to-child HIV transmission (MTCT) is a major cause of adolescent mortality. METHODS: Adolescents (10-18 years) attending 2 primary clinics were offered PITC. Participants completed a questionnaire investigating acceptability of PITC, and in-depth interviews with 41 adolescents and 30 guardians explored understanding of long-term survival after MTCT. RESULTS: Of 506 participants, 16 were known to be HIV-positive; of the remaining 490, only 5 (1%) declined HIV testing. Infected adolescents and their guardians often anticipated a positive result and reported being advised by relatives (but not health workers) to be tested because of chronic illness, especially if parents or siblings had died or were HIV-infected. However, HIV-negative participants were not aware that long-term survival following MTCT could occur. All adolescents felt that HIV diagnosed at their age would be assumed to have been sexually acquired regardless of the true mode of transmission. CONCLUSIONS: Including late diagnosis of MTCT in pretest counseling and health educational messages may facilitate PITC for older children and adolescents, especially for those who have not had their sexual debut.

A primary care level algorithm for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission.

OBJECTIVE: To present an algorithm for primary-care health workers for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission. METHODS: Five hundred and six adolescent (10-18 years) attendees to two primary care clinics in Harare, Zimbabwe, were recruited. A randomly extracted 'training' data set (n = 251) was used to generate an algorithm using variables identified as associated with HIV through multivariable logistic regression. Performance characteristics of the algorithm were evaluated in the remaining ('test') records (n = 255) at different HIV prevalence rates. RESULTS: HIV prevalence was 17%, and infection was independently associated with client-reported orphanhood, past hospitalization, skin problems, presenting with sexually transmitted infection and poor functional ability. Classifying adolescents as requiring HIV testing if they reported >1 of these five criteria had 74% sensitivity and 80% specificity for HIV, with the algorithm correctly predicting the HIV status of 79% of participants. In low-HIV-prevalence settings (<2%), the algorithm would have a high negative predictive value (≥ 99.5%) and result in an estimated 60% decrease in the number of people needing to test to identify one HIV-infected individual, compared with universal testing. CONCLUSIONS: Our simple algorithm can identify which individuals are likely to be HIV infected with sufficient accuracy to provide a screening tool for use in settings not already implementing universal testing policies among this age-group, for example immigrants to low-HIV-prevalence countries.