Drug resistance profiles of Mycobacterium tuberculosis clinical isolates by genotype MTBDRplus line probe assay in Zambia: findings and implications.

Background: The emergence of drug resistance is a threat to global tuberculosis (TB) elimination goals. This study investigated the drug resistance profiles of Mycobacterium tuberculosis (M. tuberculosis) using the Genotype MTBDRplus Line Probe Assay at the National Tuberculosis Reference Laboratory (NTRL) in Zambia. Methods: A cross-sectional study was conducted between January 2019 and December 2020. GenoType MTBDRplus line probe assay records for patients at the NTRL were reviewed to investigate drug susceptibility profiles of M. tuberculosis isolates to rifampicin and isoniazid. Data analysis was done using Stata version 16.1. Results: Of the 241 patient records reviewed, 77% were for females. Overall, 44% of patients were newly diagnosed with TB, 29% had TB relapse, 10% treatment after failure and 8.3% treatment after loss to follow-up. This study found that 65% of M. tuberculosis isolates were susceptible to rifampicin and isoniazid. Consequently, 35% of the isolates were resistant to rifampicin and/or isoniazid and 21.2% were multidrug-resistant (MDR). Treatment after failure [relative risk ratios (RRR) = 6.1, 95% CI: 1.691-22.011] and treatment after loss to follow-up (RRR = 7.115, 95% CI: 1.995-25.378) were significantly associated with MDR-TB. Unknown HIV status was significantly associated with isoniazid mono-resistance (RRR = 5.449, 95% CI: 1.054-28.184). Conclusions: This study found that 65% of M. tuberculosis isolates were susceptible to rifampicin and isoniazid while 35% were resistant. Consequently, a high prevalence of MDR-TB is of public health concern. There is a need to heighten laboratory surveillance and early detection of drug-resistant TB to prevent the associated morbidity and mortality.

Interrupted time-series analysis of active case-finding for tuberculosis during the COVID-19 pandemic, Zambia.

Objective: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent implementation of tuberculosis response measures on tuberculosis notifications in Zambia. Methods: We used an interrupted time-series design to compare monthly tuberculosis notifications in Zambia before the pandemic (January 2019 to February 2020), after implementation of national pandemic mitigation measures (April 2020 to June 2020) and after response measures to improve tuberculosis detection (August 2020 to September 2021). The tuberculosis response included enhanced data surveillance, facility-based active case-finding and activities to generate demand for services. We used nationally aggregated, facility-level tuberculosis notification data for the analysis. Findings: Pre-pandemic tuberculosis case notifications rose steadily from 2890 in January 2019 to 3337 in February 2020. After the start of the pandemic and mitigation measures, there was a -22% (95% confidence interval, CI: -24 to -19) immediate decline in notifications in April 2020. Larger immediate declines in notifications were seen among human immunodeficiency virus (HIV)-positive compared with HIV-negative individuals (-36%; 95% CI: -38 to -35; versus -12%; 95% CI: -17 to -6). Following roll-out of tuberculosis response measures in July 2020, notifications immediately increased by 45% (95% CI: 38 to 51) nationally and across all subgroups and provinces. The trend in notifications remained stable through September 2021, with similar numbers to the predicted number had the pandemic not occurred. Conclusion: Implementation of a coordinated public health response including active tuberculosis case-finding was associated with reversal of the adverse impact of the pandemic and mitigation measures. The gains were sustained throughout subsequent waves of the pandemic.

Field performance evaluation of dual rapid HIV and syphilis tests in three antenatal care clinics in Zambia.

This cross-sectional study of 3212 pregnant women assessed the field performance, acceptability, and feasibility of two dual HIV/syphilis rapid diagnostic tests, the Chembio DPP HIV-syphilis Assay and the SD Bioline HIV/syphilis Duo in antenatal clinics. Sensitivity and specificity for HIV and syphilis were calculated compared to the rapid Determine HIV-1/2 with Uni-Gold to confirm positive results for HIV and the Treponema pallidum particle agglutination assay for syphilis. RPR titers ≥1:4 were used to define active syphilis detection. Acceptability and feasibility were assessed using self-reported questionnaires. For Chembio, the HIV sensitivity was 90.6% (95%CI = 87.4, 93.0) and specificity was 97.2% (95%CI = 96.2, 97.8); syphilis sensitivity was 68.6% (95%CI = 61.9, 74.6) and specificity was 98.5% (95%CI = 97.8, 98.9). For SD Bioline, HIV sensitivity was 89.4% (95%CI = 86.1, 92.0) and specificity was 96.3% (95%CI = 95.3, 97.1); syphilis sensitivity was 66.2% (95%CI = 59.4, 72.4) and specificity was 97.2% (95%CI = 96.4, 97.9). Using the reference for active syphilis, syphilis sensitivity was 84.7% (95%CI = 76.1, 90.6) for Chembio and 81.6% (95%CI = 72.7, 88.1) for SD Bioline. Both rapid diagnostic tests were assessed as highly acceptable and feasible. In a field setting, the performance of both rapid diagnostic tests was comparable to other published field evaluations and each was rated highly acceptable and feasible. These findings can be used to guide further research and proposed scale up in antenatal clinic settings.

A case study for a psychographic-behavioral segmentation approach for targeted demand generation in voluntary medical male circumcision.

Public health programs are starting to recognize the need to move beyond a one-size-fits-all approach in demand generation, and instead tailor interventions to the heterogeneity underlying human decision making. Currently, however, there is a lack of methods to enable such targeting. We describe a novel hybrid behavioral-psychographic segmentation approach to segment stakeholders on potential barriers to a target behavior. We then apply the method in a case study of demand generation for voluntary medical male circumcision (VMMC) among 15-29 year-old males in Zambia and Zimbabwe. Canonical correlations and hierarchical clustering techniques were applied on representative samples of men in each country who were differentiated by their underlying reasons for their propensity to get circumcised. We characterized six distinct segments of men in Zimbabwe, and seven segments in Zambia, according to their needs, perceptions, attitudes and behaviors towards VMMC, thus highlighting distinct reasons for a failure to engage in the desired behavior.

Attitudes and decision-making about early-infant versus early-adolescent male circumcision: Demand-side insights for sustainable HIV prevention strategies in Zambia and Zimbabwe.

As countries approach their scale-up targets for the voluntary medical male circumcision program for HIV prevention, they are strategizing and planning for the sustainability phase to follow. Global guidance recommends circumcising adolescent (below 14 years) and/or early infant boys (aged 0-60 days), and countries need to consider several factors before prioritizing a cohort for their sustainability phase. We provide community and healthcare provider-side insights on attitudes and decision-making process as a key input for this strategic decision in Zambia and Zimbabwe. We studied expectant parents, parents of infant boys (aged 0-60 days), family members and neo-natal and ante-natal healthcare providers in Zambia and Zimbabwe. Our integrated methodology consisted of in-depth qualitative and quantitative one-on-one interviews, and a simulated-decision-making game, to uncover attitudes towards, and the decision-making process for, early adolescent or early infant medical circumcision (EAMC or EIMC). In both countries, parents viewed early infancy and early adolescence as equally ideal ages for circumcision (38% EIMC vs. 37% EAMC in Zambia; 24% vs. 27% in Zimbabwe). If offered for free, about half of Zambian parents and almost 2 in 5 Zimbabwean parents indicated they would likely circumcise their infant boy; however, half of parents in each country perceived that the community would not accept EIMC. Nurses believed their facilities currently could not absorb EIMC services and that they would have limited ability to influence fathers, who were seen as having the primary decision-making authority. Our analysis suggests that EAMC is more accepted by the community than EIMC and is the path of least resistance for the sustainability phase of VMMC. However, parents or community members do not reject EIMC. Should countries choose to prioritize this cohort for their sustainability phase, a number of barriers around information, decision-making by parents, and supply side will need to be addressed.

Could Circumcision of HIV-Positive Males Benefit Voluntary Medical Male Circumcision Programs in Africa? Mathematical Modeling Analysis.

BACKGROUND: The epidemiological and programmatic implications of inclusivity of HIV-positive males in voluntary medical male circumcision (VMMC) programs are uncertain. We modeled these implications using Zambia as an illustrative example. METHODS AND FINDINGS: We used the Age-Structured Mathematical (ASM) model to evaluate, over an intermediate horizon (2010-2025), the effectiveness (number of VMMCs needed to avert one HIV infection) of VMMC scale-up scenarios with varying proportions of HIV-positive males. The model was calibrated by fitting to HIV prevalence time trend data from 1990 to 2014. We assumed that inclusivity of HIV positive males may benefit VMMC programs by increasing VMMC uptake among higher risk males, or by circumcision reducing HIV male-to-female transmission risk. All analyses were generated assuming no further antiretroviral therapy (ART) scale-up. The number of VMMCs needed to avert one HIV infection was projected to increase from 12.2 VMMCs per HIV infection averted, in a program that circumcises only HIV-negative males, to 14.0, in a program that includes HIV-positive males. The proportion of HIV-positive males was based on their representation in the population (e.g. 12.6% of those circumcised in 2010 would be HIV-positive based on HIV prevalence among males of 12.6% in 2010). However, if a program that only reaches out to HIV-negative males is associated with 20% lower uptake among higher-risk males, the effectiveness would be 13.2 VMMCs per infection averted. If improved inclusivity of HIV-positive males is associated with 20% higher uptake among higher-risk males, the effectiveness would be 12.4. As the assumed VMMC efficacy against male-to-female HIV transmission was increased from 0% to 20% and 46%, the effectiveness of circumcising regardless of HIV status improved from 14.0 to 11.5 and 9.1, respectively. The reduction in the HIV incidence rate among females increased accordingly, from 24.7% to 34.8% and 50.4%, respectively. CONCLUSION: Improving inclusivity of males in VMMC programs regardless of HIV status increases VMMC effectiveness, if there is moderate increase in VMMC uptake among higher-risk males and/or if there is moderate efficacy for VMMC against male-to-female transmission. In these circumstances, VMMC programs can reduce the HIV incidence rate in males by nearly as much as expected by some ART programs, and additionally, females can benefit from the intervention nearly as much as males.

Employing Demand-Based Volumetric Forecasting to Identify Potential for and Roles of Devices in Scale-Up of Medical Male Circumcision in Zambia and Zimbabwe.

INTRODUCTION: Devices for male circumcision (MC) are becoming available in 14 priority countries where MC is being implemented for HIV prevention. Understanding potential impact on demand for services is one important programmatic consideration because countries determine whether to scale up devices within MC programs. METHODS: A population-based survey measuring willingness to undergo MC, assuming availability of surgical MC and 3 devices, was conducted among 1250 uncircumcised men, ages 10-49 years in Zambia and 1000 uncircumcised men, ages 13-49 years in Zimbabwe. Simulated Test Market methodology was used to estimate incremental MC demand and the extent to which devices might be preferred over surgery, assuming availability of: surgical MC in both countries; the devices PrePex, ShangRing, and Unicirc in Zambia; and PrePex in Zimbabwe. RESULTS: Modeled estimates indicate PrePex has the potential to provide an overall increase in MC demand ranging from an estimated 13%-50%, depending on country and WHO prequalification ages, replacing 11%-41% of surgical procedures. In Zambia, ShangRing could provide 8% overall increase, replacing 45% of surgical procedures, and Unicirc could provide 30% overall increase, replacing 85% of surgical procedures. CONCLUSIONS: In both countries, devices have potential to increase overall demand for MC, assuming wide scale awareness and availability of circumcision by the devices. With consideration for age and country, PrePex may provide the greatest potential increase in demand, followed by Unicirc (measured in Zambia only) and ShangRing (also Zambia only). These results inform one program dimension for decision making on potential device introduction strategies; however, they must be considered within the broader programmatic context.

Evaluating Opportunities for Achieving Cost Efficiencies Through the Introduction of PrePex Device Male Circumcision in Adult VMMC Programs in Zambia and Zimbabwe.

BACKGROUND: Results from recent costing studies have put into question potential Voluntary Medical Male Circumcision (VMMC) cost savings with the introduction of the PrePex device. METHODS: We evaluated the cost drivers and the overall unit cost of VMMC for a variety of service delivery models providing either surgical VMMC or both PrePex and surgery using current program data in Zimbabwe and Zambia. In Zimbabwe, 3 hypothetical PrePex only models were also included. For all models, clients aged 18 years and older were assumed to be medically eligible for PrePex and uptake was based on current program data from sites providing both methods. Direct costs included costs for consumables, including surgical VMMC kits for the forceps-guided method, device (US $12), human resources, demand creation, supply chain, waste management, training, and transport. RESULTS: Results for both countries suggest limited potential for PrePex to generate cost savings when adding the device to current surgical service delivery models. However, results for the hypothetical rural Integrated PrePex model in Zimbabwe suggest the potential for material unit cost savings (US $35 per VMMC vs. US $65-69 for existing surgical models). CONCLUSIONS: This analysis illustrates that models designed to leverage PrePex's advantages, namely the potential for integrating services in rural clinics and less stringent infrastructure requirements, may present opportunities for improved cost efficiency and service integration. Countries seeking to scale up VMMC in rural settings might consider integrating PrePex only MC services at the primary health care level to reduce costs while also increasing VMMC access and coverage.

Investigating Voluntary Medical Male Circumcision Program Efficiency Gains through Subpopulation Prioritization: Insights from Application to Zambia.

BACKGROUND: Countries in sub-Saharan Africa are scaling-up voluntary male medical circumcision (VMMC) as an HIV intervention. Emerging challenges in these programs call for increased focus on program efficiency (optimizing program impact while minimizing cost). A novel analytic approach was developed to determine how subpopulation prioritization can increase program efficiency using an illustrative application for Zambia. METHODS AND FINDINGS: A population-level mathematical model was constructed describing the heterosexual HIV epidemic and impact of VMMC programs (age-structured mathematical (ASM) model). The model stratified the population according to sex, circumcision status, age group, sexual-risk behavior, HIV status, and stage of infection. A three-level conceptual framework was also developed to determine maximum epidemic impact and program efficiency through subpopulation prioritization, based on age, geography, and risk profile. In the baseline scenario, achieving 80% VMMC coverage by 2017 among males 15-49 year old, 12 VMMCs were needed per HIV infection averted (effectiveness). The cost per infection averted (cost-effectiveness) was USD $1,089 and 306,000 infections were averted. Through age-group prioritization, effectiveness ranged from 11 (20-24 age-group) to 36 (45-49 age-group); cost-effectiveness ranged from $888 (20-24 age-group) to $3,300 (45-49 age-group). Circumcising 10-14, 15-19, or 20-24 year old achieved the largest incidence rate reduction; prioritizing 15-24, 15-29, or 15-34 year old achieved the greatest program efficiency. Through geographic prioritization, effectiveness ranged from 9-12. Prioritizing Lusaka achieved the highest effectiveness. Through risk-group prioritization, prioritizing the highest risk group achieved the highest effectiveness, with only one VMMC needed per infection averted; the lowest risk group required 80 times more VMMCs. CONCLUSION: Epidemic impact and efficiency of VMMC programs can be improved by prioritizing young males (sexually active or just before sexual debut), geographic areas with higher HIV prevalence than the national, and high sexual-risk groups.

Estimating disease burden of maternal syphilis and associated adverse pregnancy outcomes in India, Nigeria, and Zambia in 2012.

OBJECTIVE: To estimate maternal syphilis and its associated adverse pregnancy outcomes in India, Nigeria, and Zambia. METHODS: An online estimation tool was used to generate point estimates and uncertainty ranges of maternal syphilis and adverse pregnancy outcomes due to mother-to-child transmission (MTCT). The most recent data (2010-2012) on antenatal care coverage, syphilis seroprevalence, and syphilis screening and treatment coverage at the subnational level in India, Nigeria, and Zambia were used to estimate disease burden for 2012. Sensitivity analysis was conducted for three screening and treatment scenarios (current coverages, current coverages minus 20%, and ideal coverages consistent with WHO targets for eliminating MTCT of syphilis). RESULTS: A total of 103 960, 74 798, and 9072 pregnant women with probable active syphilis were estimated to occur in India, Nigeria, and Zambia, resulting in 53 187, 37 045, and 2973 adverse outcomes, respectively; approximately 1.6%, 4.8%, and 37.0% of these were averted under the current service coverages in India, Nigeria, and Zambia. The disease burden varied significantly in its subnational distribution within India and Nigeria, but was distributed evenly across Zambia. CONCLUSIONS: The obtained results suggest an ongoing, unaverted high burden of maternal syphilis and associated adverse outcomes in India, Nigeria, and Zambia. Screening and treatment for syphilis must be scaled-up significantly in these countries to achieve elimination of MTCT of syphilis.

Genomic signature of multidrug-resistant Salmonella enterica serovar typhi isolates related to a massive outbreak in Zambia between 2010 and 2012.

Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term "classical MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both.

Influenza surveillance in Zambia, 2008-2009.

BACKGROUND: Limited information exists about influenza viruses in Africa. We used data from a new sentinel surveillance system to investigate the seasonality and characteristics of influenza, including pandemic (pdm) influenza A H1N1, in Zambia. METHODS: In June 2008, we established sentinel surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 4 healthcare facilities in Zambia. Nasopharyngeal and oropharyngeal swabs and structured questionnaires were collected from eligible patients and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza virus types and subtypes. RESULTS: From June 2008 to December 2009, we collected 1234 specimens, of which 334 (27%) were ILI, and 900 (63%) were SARI. Overall, 4% (57) of specimens were positive for influenza. The influenza detection rate in ILI and SARI cases was 5% (17/334) and 4% (40/900), respectively. Among all influenza cases, 54 (95%) were influenza A and 3 (5%) were influenza B. Of the influenza A viruses, 16 (30%) were A(H1N1)pdm09, 29 (54%) were seasonal A(H1N1), 6 (11%) were A(H3N2), and 4 (7%) were unsubtyped. The detection rate for A(H1N1)pdm09 cases was highest in persons aged 5-24 years (5/98; 5%), 25-44 years (4/78; 5%), and 45-64 years (1/17; 6%). Conversely, for seasonal influenza the detection rate was highest in children aged 1-4 years (18/294; 6%). Influenza virus circulation peaked during June-August in both years and A(H1N1)pdm09 occurred at the end of the influenza season in 2009. CONCLUSIONS: Seasonal influenza virus infection was found to be associated with both mild and severe respiratory illness in Zambia. Future years of surveillance are necessary to better define the seasonality and epidemiology of influenza in the country.

Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: a retrospective cohort study.

BACKGROUND: Since 2003 pediatric antiretroviral treatment (ART) programs have scaled-up in sub-Saharan Africa and should be evaluated to assess progress and identify areas for improvement. We evaluated secular trends in the characteristics and treatment outcomes of children in three pediatric ART clinics in urban and rural areas in Zambia. METHODS: Routinely collected data were analyzed from three ART programs in rural (Macha and Mukinge) and urban (Lusaka) Zambia between program implementation and July 2008. Data were obtained from electronic medical record systems and medical record abstraction, and were categorized by year of program implementation. Characteristics of all HIV-infected and exposed children enrolled in the programs and all children initiating treatment were compared by year of implementation. RESULTS: Age decreased and immunologic characteristics improved in all groups over time in both urban and rural clinics, with greater improvement observed in the rural clinics. Among children both eligible and ineligible for ART at clinic enrollment, the majority started treatment within a year. A high proportion of children, particularly those ineligible for ART at clinic enrollment, were lost to follow-up prior to initiating ART. Among children initiating ART, clinical and immunologic outcomes after six months of treatment improved in both urban and rural clinics. In the urban clinics, mortality after six months of treatment declined with program duration, and in the rural clinics, the proportion of children defaulting by six months increased with program duration. CONCLUSIONS: Treatment programs are showing signs of progress in the care of HIV-infected children, particularly in the rural clinics where scale-up increased rapidly over the first three years of program implementation. However, continued efforts to optimize care are needed as many children continue to enroll in ART programs at a late stage of disease and thus are not receiving the full benefits of treatment.

The impact of an immunization programme administered through the Growth Monitoring Programme Plus as an alternative way of implementing Integrated Management of Childhood Illnesses in urban-slum areas of Lusaka, Zambia.

A time-lag study design was used to examine the effects of an immunization programme implemented through an integrated community-based child health approach called the Growth Monitoring Programme Plus (GMP+) in peri-urban areas of Lusaka, Zambia. The immunization coverage and sociodemographic data of eligible children and households were obtained from three repeated surveys in two intervention areas. Logistic regression analysis was performed to explore the factors affecting immunization coverage. For assessing the timeliness of immunization, a Computerised Immunization Coverage Calculation System (CICCS) was used. Full immunization coverage significantly increased in both the primary intervention (P<0.001) and lagged intervention (P = 0.011) areas after the initiation of the GMP+. Frequent attendance to GMP+ sessions played a significant role in the improvement of immunization coverage (P<0.001 for the final survey in the primary intervention area), whereas other sociodemographic characteristics of the child and caretaker were not associated with immunization coverage. Analysis of the timeliness of three doses of diphtheria, pertussis and tetanus DPT3 immunization by CICCS showed that coverage in the primary intervention area had significantly improved compared to the lagged intervention area. Our study indicated that immunization coverage was improved effectively with the intervention of the GMP+ as a model of an integrated immunization programme for child health in line with the Integrated Management of Childhood Illnesses (IMCI) and the Global Immunization Vision and Strategy (GIVS).

Differences in presentation, treatment initiation, and response among children infected with human immunodeficiency virus in urban and rural Zambia.

BACKGROUND: Access to pediatric antiretroviral therapy (ART) in rural areas remains limited due to the unique challenges faced by providers and patients. Few rural ART programs have been evaluated to determine whether these challenges affect care and treatment response. METHODS: Routinely collected data from 3 pediatric ART programs in rural and urban Zambia were obtained from medical records. Participants included human immunodeficiency virus-infected children <15 years of age presenting for care between August 2004 and July 2008. Characteristics at presentation, time to ART initiation, and treatment response were compared between urban and rural children. RESULTS: A total of 863 children were enrolled (562 urban and 301 rural). At presentation, children in rural clinics were significantly younger (3.4 vs. 6.5 years), had higher CD4 T-cell percentages (18.0% vs. 12.8%), less advanced disease (47.5% vs. 62.3% in World Health Organization stage 3/4), lower weight-for-age Z-scores (-2.8 vs. -2.3), and traveled greater distances (29 vs. 2 km). Rural children eligible for ART at presentation took longer to initiate treatment (3.6 vs. 0.9 months); no differences were found in time to ART initiation among children ineligible at presentation (15.4 vs. 12.1 months). For the 607 children initiating ART, clinical and immunologic status improved in both urban and rural clinics. Mortality was highest in the first 90 days of treatment and was higher at all times in rural clinics. CONCLUSIONS: The findings support expansion of ART programs into rural areas to increase access to treatment services and reduce inequities.

Antiretroviral therapy in antenatal care to increase treatment initiation in HIV-infected pregnant women: a stepped-wedge evaluation.

BACKGROUND: The objective of the study was to evaluate whether providing antiretroviral therapy (ART) integrated in antenatal care (ANC) clinics resulted in a greater proportion of treatment-eligible women initiating ART during pregnancy compared with the existing approach of referral to ART. ANALYSIS DESIGN AND METHODS: The evaluation used a stepped-wedge design and included all HIV-infected, ART-eligible pregnant women in eight public sector clinics in Lusaka district, Zambia. Main outcome indicators were the proportion of treatment-eligible pregnant women enrolling into HIV care within 60 days of HIV diagnosis, and of these, the proportion initiating ART during pregnancy. Adjusted odds ratios (AORs) and confidence intervals (CIs) for enrollment and initiation proportions were estimated through a logistic regression model accounting for clinical site cluster and time effects. RESULTS: Between 16 July 2007 and 31 July 2008, 13,917 women started antenatal care more than 60 days before the intervention rollout and constituted the control cohort; 17 619 started antenatal care after ART integrated into ANC and constituted the intervention cohort. Of the 1566 patients found eligible for ART, a greater proportion enrolled while pregnant and within the 60 days of HIV diagnosis in the intervention cohort (376/846, 44.4%) compared with the control cohort (181/716, 25.3%), AOR 2.06, 95% CI (1.27-3.34); and initiated ART while pregnant in the intervention cohort (278/846, 32.9%) compared with the control cohort (103/716, 14.4%), AOR 2.01, 95% CI (1.37-2.95). CONCLUSION: An integrated ART in ANC strategy doubled the proportion of treatment-eligible women initiating ART while pregnant.

Predictors of rapid HIV testing acceptance and successful nevirapine administration in Zambian labor wards.

BACKGROUND: Provision of HIV testing in labor provides an opportunity to reach susceptible women and infants. METHODS: As part of a cluster randomized trial of labor ward-based prevention of mother-to-child transmission services in Lusaka, Zambia, we determined predictors of testing acceptance and nevirapine (NVP) administration in labor. HIV counseling and testing were offered to women unaware of their HIV status. NVP was administered to women who tested positive, and an inert (calcium) tablet was provided to women who tested negative, to avoid stigmatization. RESULTS: Among the 2435 women who presented in labor, 393 (16%) were unaware of their HIV status, of whom 278 (71%) met eligibility criteria. We offered counseling to 217 (78%) of eligible women: 146 (67%) agreed, 82 (56%) of those counseled were tested for HIV, and 23 (28%) were seropositive. Testing rates were higher among primigravida women [adjusted odds ratio (AOR) 1.5; 95% confidence interval (CI): 1.1 to 2.1] and among those not offered HIV testing during their pregnancy (AOR 3.7; 95% CI: 2.8 to 5.1). Cervical dilation 1 hour (AOR 11.5; 95% CI: 4.5 to 29.2) and >2 hours (AOR 11.4; 95% CI: 4.7 to 27.5) before delivery. CONCLUSION: Labor ward HIV testing is feasible in this resource-limited setting.

Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia.

BACKGROUND: High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence. METHODS: We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (> or =95%), suboptimal (80-94%) and poor (<80%). RESULTS: Overall, 27 115 treatment-naïve adults initiated and continued ART for > or =12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9-1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4-2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/microl vs 217 cells/microl; P < 0.001), 24 months (213 cells/microl vs 246 cells/microl; P < 0.001), 30 months (226 cells/microl vs 261 cells/microl; P < 0.001) and 36 months (245 cells/microl vs 275 cells/microl; P < 0.01) when compared with those above this threshold. CONCLUSIONS: MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.

Improvement in mothers' immediate care-seeking behaviors for children's danger signs through a community-based intervention in Lusaka, Zambia.

The large number of child deaths in developing countries is associated with delays in care-seeking by families, but the community-based efforts of the Integrated Management of Childhood Illnesses developed by WHO/UNICEF has remained ineffectual. To improve caregivers' ability to recognise potentially life-threatening symptoms of major childhood illnesses, we provided education about the importance of danger signs and immediate care-seeking practices through a community-based intervention of 'the Growth Monitoring Programme Plus (GMP+)' in low-income areas of Lusaka, Zambia. Using repeated cross-sectional data from interviews, we compared attendance and non-attendance groups to assess the impacts of intervention on mothers' care-seeking. Of 1717 and 1546 attendance mothers in the baseline and the final survey, 1097 and 1035, respectively, sought care from a health centre after perceiving the danger signs. The proportion of mothers with immediate response increased from 35.7% (392/1097) to 51.5% (533/1035) (p < 0.01). In the final survey, the attendance mothers became more likely to respond immediately to the danger signs than the non-attendance mothers (adjusted odds ratio: 2.140, 95% confidence interval: [1.408-3.252]), and the higher educational level the attendance mothers had, the more likely they were to respond immediately to the danger signs (primary level: 2.067 [1.050-4.068], secondary level and above: 2.174 [1.098-4.306]). In conclusion, GMP+ with danger sign education can improve mothers' care-seeking for severely sick children. Therefore, GMP+ has the potential to reduce child death in developing countries, i.e., contribute to the Millennium Development Goal 4 aiming at reducing child mortality by two-thirds by 2015.

Spatial analysis of risk factor of cholera outbreak for 2003-2004 in a peri-urban area of Lusaka, Zambia.

A cholera outbreak occurred in Lusaka city between November 28, 2003 and June 8, 2004, and 6,542 cases with 187 deaths (case fatality rata: 2.86) were reported. We analyzed the distribution of cholera cases, the mode of cholera transmission, and the risk factors affecting cholera infection in a peri-urban area of Lusaka by using a Geographic Information System (GIS) and a matched case-control method. Chloropleth mapping of the incidences of cholera showed variation of the incidences in the study area. Our analysis indicated a significant association between the lack of latrine and drainage systems surrounding houses and high incidence of cholera. The matched case-control study showed the protective role of chlorination of drinking water and of hand washing with soap for cholera prevention. We concluded that cholera occurred because of personal behavior and the environment conditions of daily life.