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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022. World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.)

Objective: To examine the association between the duration of HIV infection and the stage of cervical cancer in Lusaka, Zambia., Methods: This retrospective case-case study included 1583 cervical cancer patients from the Cancer Diseases Hospital in Lusaka, Zambia. A sub-population of HIV-positive patients with additional clinical HIV information was identified following linkage of cancer and HIV databases. Logistic regression models examined the relationship between HIV status and early-onset cervical cancer diagnosis, and between HIV infection duration and initial diagnosis of metastatic cervical cancer., Results: The study population had an average age of 49 years and 40.9% had an initial diagnosis of metastatic cancer. HIV-positive women were more than twice as likely to be diagnosed at early-onset cervical cancer compared with HIV-negative women. Among the sub-population of HIV-positive patients, a longer duration of HIV infection was associated with 20% lowered odds of initial metastatic cancer diagnosis., Conclusion: The availability, accessibility, and impact of the cervical screening program in this population should be further examined to elucidate the relationship between cervical screening, age, and duration of HIV infection and the the stage of diagnosis of cervical cancer., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort., Methods: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level., Findings: Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 [77·8%]). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14-6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2-22·9) of screening positive., Interpretation: CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets., Funding: US President's Emergency Plan for AIDS Relief., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Zambia has one of the highest incidence and mortality rates of cervical cancer at 65.5 and 43.4 per 100 000 respectively. In line with efforts of the cervical cancer elimination strategy the Zambia national cervical cancer sub-committee undertook a resource mapping exercise of projected spending on the prevention and control program. The aim was to elicit the available resources over a prospective 4-year period and compare it to the projected costs., Materials and Methods: A 4-step approach was used for this activity. This included creation of tool adapted for the local program, orientation of stakeholders to the tool, population of the tool by stakeholders and collation, comparison and reporting of submitted data. Comparative analysis to the cervical cancer control costing report 2019-2023 was conducted., Results: Fifty-nine percent of resources in the stipulated period were allocated to prevention efforts. Isolated with diagnostic, treatment and palliation (14 %) the prevention allocation increased to 81 %. Community and stakeholder engagement was 5 % whilst technical assistance and health information were 12 % and 9 % respectively. The dispensation to research was the lowest at 0.7 %. For health system levels, secondary and primary levels were projected at 40 % and 12 % respectively following the central allotment of 45 %. Community and stakeholder engagement took up 3 %. The secondary prevention to tertiary intervention ratio was 4:1 in the projection compared to approximately 2:1 in the actual budgeted costs for the same period, showing a two-fold discordance., Conclusion: To achieve the accelerated elimination of cervical cancer as a public health problem policy cohesiveness is necessary. This can be facilitated with continuous stakeholder involvement in planning, implementation and review., Policy Summary: In order to accelerate the elimination of cervical cancer as a public health problem policy cohesiveness is vital and this can be achieved by continuous stakeholder involvement in planning, implementation and review., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Formal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa., Methods: An anonymous survey was distributed to members of the African Organization for Research and Treatment in Cancer Training Interest Group to assess current attitudes and practices toward radiation sciences education. A 2-week, on-site educational course in radiation biology and radiation physics was conducted at the Cancer Diseases Hospital in Lusaka, Zambia. Pre- and postcourse assessments in both disciplines were administered to gauge the effectiveness of an intensive high-yield course in the radiation sciences., Results: Significant deficiencies were identified in radiation sciences education, especially in radiation biology. Lack of expert instructors in radiation biology was reported by half of all respondents and was the major contributing factor to deficient education in the radiation sciences. The educational course resulted in marked improvements in radiation biology assessment scores (median pre- and posttest scores, 27% and 55%, respectively; P < .0001) and radiation physics assessment scores (median pre- and posttest scores, 30% and 57.5%, respectively; P < .0001)., Conclusion: Radiation sciences education in African oncology training programs is inadequate. International collaboration between expert radiation biology and radiation physics instructors can address this educational deficiency and improve trainee competence in the foundational radiation sciences that is critical for the safe and effective delivery of radiotherapy.

The COVID-19 pandemic has overwhelmed health systems around the globe even in countries with strong economies. This is of particular concern for nations with weaker health systems. This article reports the response of a comprehensive cancer centre in a lower-middle income country to prevent COVID-19 transmission and how the implementation of pragmatic strategies have served as a springboard to improve cancer services beyond the COVID-19 pandemic. The strategies included establishment of a local taskforce, increased education and facilitation of good hygiene practices, staff training, patient triaging, improved patient scheduling, remote review of patients and establishing a virtual platform for meetings., Competing Interests: The authors have no conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

Introduction: Sub-Saharan Africa has the highest global incidence of cervical cancer. Cervical cancer is the most common cause of cancer morbidity and mortality among women in Zambia. HIV increases the risk for cervical cancer and with a national Zambian adult HIV prevalence of 16%, it is important to investigate the impact of HIV on the progression of cervical cancer. We measured differences in cervical cancer progression between HIV-positive and HIV-negative patients in Zambia., Methods: This study included 577 stage I and II cervical cancer patients seen between January 2008 and December 2012 at the Cancer Diseases Hospital in Lusaka, Zambia. The inclusion criteria for records during the study period included known HIV status and FIGO stage I and II cervical cancer at initial date of registration in the Cancer Diseases Hospital. Medical records were abstracted for clinical and epidemiological data. Cancer databases were linked to the national HIV database to assess HIV status among cervical cancer patients. Logistic regression examined the association between HIV and progression, which was defined as metastatic or residual tumor after 3 months of initial treatment., Results: A total of 2451 cervical cancer cases were identified, and after exclusion criteria were performed the final analysis population totaled 537 patients with stage I and II cervical cancer with known HIV status (224 HIV-positive and 313 HIV-negative). HIV-positive women were, on average, 10 years younger than HIV-negative women who had a median age of 42, ranging between 25 and 72. A total of 416 (77.5%) patients received external beam radiation, and only 249 (46.4%) patients received the recommended treatment of chemotherapy, external beam radiation, and brachytherapy. Most patients were stage II (85.7%) and had squamous cell carcinoma (74.7%). HIV-positive patients were more likely to receive lower doses of external beam radiation than HIV-negative patients (47% vs 37%; P<0.05, respectively). The median total dose of external beam radiation for HIV-positive and HIV-negative patients was 46 Gy and 50 Gy, respectively. HIV positivity did not lead to tumor progression (25.4% in HIV-positive vs 23.9% in HIV-negative, OR 1.04, 95% CI [0.57, 1.92]). However, among a subset of HIV-positive patients, longer duration of infection was associated with lower odds of progression., Conclusion: There was no significant impact on non-metastatic cervical cancer progression by HIV status among patients in Lusaka, Zambia. The high prevalence of HIV among cervical cancer patients suggest that HIV-positive patients should be a primary target group for HPV vaccinations, screening, and early detection., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

In 2016, the Zambian government made cancer control a national priority and released a National Cancer Control Strategic Plan for 2016 to 2021, which focuses on malignancies of the breast, cervix, and prostate, and retinoblastoma. The plan calls for a collective reduction in the cancer burden by 50%. In support of this vision, Susan G. Komen sponsored a consultative meeting in Lusaka, Zambia, in September 2017 to bring together the country's main breast cancer stakeholders and identify opportunities to improve breast cancer control. The recommendations generated during the discussions are presented. There was general agreement that the first step toward breast cancer mortality reduction should consist of implementation of early detection service platforms focused on women who are symptomatic. Participants also agreed that the management of all components of the national breast cancer control program should be integrated and led by the Ministry of Health. As much as possible, early detection and treatment services presently offered by the Cervical Cancer Prevention Program of Zambia and Cancer Diseases Hospital should be leveraged. Efforts are under way through multiple stakeholders to implement the following recommendations: development of national guidelines for the early diagnosis of breast cancer, training of breast surgeons, implementation of early detection and surgical treatment service platforms at the district-hospital level, and epidemiologic research, including the improvement of electronic recording mechanisms.

Purpose: In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer., Methods: Our initiative sought to build capacity for breast cancer care through the (1) formation of a breast cancer advocacy alliance to raise awareness, (2) creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3) implementation of early detection and treatment capacity within two major health care facilities., Results: Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE) services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies)., Conclusion: This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer.

Introduction: Colon cancer is preventable. There is a plethora of data regarding epidemiology and screening guidelines, however this data is sparse from the African continent. Objective: we aim to evaluate the trends of colorectal cancer (CRC) in a native African population based on age at diagnosis, gender and stage at diagnosis., Methods: We conducted a retrospective analysis of the Cancer Disease Hospital (CDH) registry in Zambia, Southern Africa., Results: 377 charts were identified in the CDH registry between 2007 and 2015, of which 234 were included in the final analysis. The mean age at diagnosis was 48.6 years and 62% are males. Using descriptive analysis for patterns: mode of diagnosis was surgical in 195 subjects (84%), histology adenocarcinoma in 225 (96.5%), most common location is rectum 124 (53%) followed by sigmoid 31 (13.4%), and cecum 26 (11%). 122 subjects (54%) were stage 4 at diagnosis. Using the Spearman rank correlation, we see no association between year and stage at diagnosis (p = 0.30) or year and age at diagnosis (p = 0.92)., Conclusion: Colorectal cancer was diagnosed at a young age and late stage in the Zambian patients.

The hallmark of pediatric cerebral malaria (CM) is sequestration of parasitized red blood cells in the cerebral microvasculature. Malawi-based research using 0.35 Tesla (T) magnetic resonance imaging (MRI) established that severe brain swelling is associated with fatal CM, but swelling etiology remains unclear. Autopsy and clinical studies suggest several potential etiologies, but limitations of 0.35 T MRI precluded optimal investigations into swelling pathophysiology. A 1.5 T MRI in Zambia allowed for further investigations including susceptibility-weighted imaging (SWI). SWI is an ideal sequence for identifying regions of sequestration and microhemorrhages given the ferromagnetic properties of hemozoin and blood. Using 1.5 T MRI, Zambian children with retinopathy-confirmed CM underwent imaging with SWI, T2, T1 pre- and post-gadolinium, diffusion-weighted imaging (DWI) with apparent diffusion coefficients and T2/fluid attenuated inversion recovery sequences. Sixteen children including two with moderate/severe edema were imaged; all survived. Gadolinium extravasation was not seen. DWI abnormalities spared the gray matter suggesting vasogenic edema with viable tissue rather than cytotoxic edema. SWI findings consistent with microhemorrhages and parasite sequestration co-occurred in white matter regions where DWI changes consistent with vascular congestion were seen. Imaging findings consistent with posterior reversible encephalopathy syndrome were seen in children who subsequently had a rapid clinical recovery. High field MRI indicates that vascular congestion associated with parasite sequestration, local inflammation from microhemorrhages and autoregulatory dysfunction likely contribute to brain swelling in CM. No gross radiological blood brain barrier breakdown or focal cortical DWI abnormalities were evident in these children with nonfatal CM.

Importance: Surgical care is widely unavailable in developing countries; advocates recommend that countries evaluate and report on access to surgical care to improve availability and aid health planners in decision making., Objective: To analyze the infrastructure, capacity, and availability of surgical care in Zambia to inform health policy priorities., Design, Setting, and Participants: In this observational study, all hospitals providing surgical care were identified in cooperation with the Zambian Ministry of Health. On-site data collection was conducted from February 1 through August 30, 2011, with an adapted World Health Organization Global Initiative for Emergency and Essential Surgical Care survey. Data collection at each facility included interviews with hospital personnel and assessment of material resources. Data were geocoded and analyzed in a data visualization platform from March 1 to December 1, 2015. We analyzed time and distance to surgical services, as well as the proportion of the population living within 2 hours from a facility providing surgical care., Main Outcomes and Measures: Surgical capacity, supplies, human resources, and infrastructure at each surgical facility, as well as the population living within 2 hours from a hospital providing surgical care., Results: Data were collected from all 103 surgical facilities identified as providing surgical care. When including all surgical facilities (regardless of human resources and supplies), 14.9% of the population (2 166 460 of 14 500 000 people) lived more than 2 hours from surgical care. However, only 17 hospitals (16.5%) met the World Health Organization minimum standards of surgical safety; when limiting the analysis to these hospitals, 65.9% of the population (9 552 780 people) lived in an area that was more than 2 hours from a surgical facility. Geographic analysis of emergency and essential surgical care, defined as access to trauma care, obstetric care, and care of common abdominal emergencies, found that 80.7% of the population (11 704 700 people) lived in an area that was more than 2 hours from these surgical facilities., Conclusions and Relevance: A large proportion of the population in Zambia does not have access to safe and timely surgical care; this percentage would change substantially if all surgical hospitals were adequately resourced. Geospatial visualization tools assist in the evaluation of surgical infrastructure in Zambia and can identify key areas for improvement., Competing Interests: Disclosures: None reported.

Purpose: To provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer., Methods: ASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines., Results: Five existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater., Recommendations: Clinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines., Competing Interests: Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article. The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Linus T. ChuangNo relationship to discloseSarah TeminNo relationship to discloseRolando CamachoNo relationship to discloseAlfonso Dueñas-GonzalezNo relationship to discloseSarah FeldmanNo relationship to discloseMurat GultekinNo relationship to discloseVandana GuptaNo relationship to discloseSusan HortonNo relationship to discloseGraciela JacobNo relationship to discloseElizabeth A. KiddResearch Funding: SiemensKennedy LishimpiNo relationship to discloseCarolyn NakisigeNo relationship to discloseJoo-Hyun NamResearch Funding: AstraZeneca, AbbVieHextan Yuen Sheung NganHonoraria: Merck Sharp & Dohme (Asia), Amgen (Asia), Ipsos Healthcare, Chindex Hong Kong, Pfizer Consulting or Advisory Role: Amgen (Asia) Speakers’ Bureau: Merck Sharp & Dohme (Asia), Chindex Hong Kong, Pfizer Research Funding: Amgen (Asia; Inst) Travel, Accommodations, Expenses: Roche Hong Kong, Chindex Hong Kong, Merck Sharp & Dohme (Asia), Pfizer, AstraZenecaWilliam SmallHonoraria: Carl Zeiss Meditec Speakers’ Bureau: Carl Zeiss Meditec Research Funding: Carl Zeiss Meditec Travel, Accommodations, Expenses: Carl Zeiss MeditecGillian ThomasNo relationship to discloseJonathan S. BerekConsulting or Advisory Role: Atara Biotherapeutics Research Funding: Tesaro (Inst), AstraZeneca (Inst)

Objectives: Cervical cancer is increasing but underestimated in developing countries. We calculated the observed and expected incidence of cervical cancer in Lusaka and Southern and Western provinces of Zambia., Methods/materials: Data for 2007 to 2012 were obtained for the 3 provinces. Data included age, residence, year of diagnosis, marital status, occupation, human immunodeficiency virus (HIV), stage, radiotherapy, and chemotherapy. Expected incidence in Southern and Western provinces was calculated based on observed incidence for Lusaka province, adjusting for HIV., Results: Crude and age-standardized incidence rates (ASRs) in Lusaka were 2 to 4 times higher than incidence in the other 2 provinces. Lusaka had a rate of 54.1 per 10(5) and ASR of 82.1 per 10(5) in the age group of 15 to 49 years. The Southern province had a rate of 17.1 per 10(5) and ASR of 25.5 per 10(5); the Western province had a rate of 12.3 per 10(5) and ASR rate of 17.2 per 10(5). The observed cervical cancer incidence rates in the Southern and Western provinces were lower than the rate in Lusaka, possibly because of the uncertainty of underreporting/underdiagnosis or actual lower risk for reasons yet unclear. The HIV seroprevalence rates in patients from the 3 provinces were 46% to 93% higher than seroprevalence in the respective general populations., Conclusions: Cervical cancer is significantly underestimated in Zambia, and HIV has a significant role in pathogenesis. Future studies should establish methods for case ascertainment and better utilization of hospital- and population-based registries in Zambia and other similar developing countries.

Background: Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear., Methods: CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups., Results: Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)]., Conclusions: Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.

Background: There are few data on predictors of HIV progression in untreated children in resource-limited settings., Methods: Children with HIV Antibiotic Prophylaxis (CHAP) was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected Zambian children. The prognostic value of baseline characteristics was investigated using Cox models., Results: Five hundred fourteen children aged 1 to 14 (median 5.5) years contributed 607 years follow-up (maximum 2.6 years). Half were boys, and in 67%, the mother was the primary carer; at baseline, median CD4 percentage was 11% and weight was less than third percentile in 67%. One hundred sixty-five children died (27.2 per 100 years at risk; 95% confidence interval 23.3-31.6). Low weight-for-age, CD4 percentage, hemoglobin, mother as primary carer, current malnutrition, and previous hospital admissions for respiratory tract infections or recurrent severe bacterial infections were independent predictors of poorer survival, whereas oral candidiasis predicted poorer survival only when baseline CD4 percentage was not considered. Mortality rates per 100 child years of 44.5 (37.2-53.2), 14.7 (10.9-19.8), and 2.3 (0.3-16.7) were associated with new World Health Organization stages 4, 3, and 1/2, respectively, applied retrospectively; very low weight-for-age was the only staging feature for 42% of stage 4 children., Conclusions: Malnutrition and hospitalizations for respiratory/bacterial infections predict mortality independent of immunosuppression, suggesting that they capture HIV- and non-HIV-related mortality, whereas oral candidiasis is a proxy for immunosuppression.

Polymerase chain reaction (PCR) using Pneumocystis carinii-specific primers pAZ 102-H(5'-GTGTACGTTGCAAAGTACTC-3') and pAZ 102-E(5'-GATGGCTGTTTCCAAGCCCA-3') was performed on oropharyngeal washes obtained at autopsy from 22 AIDS children with histologically confirmed P. carinii pneumonia (PCP), and 48 control AIDS children who died from other infections. Fifteen of 22 (68%) PCP samples and none of 48 (0%) control samples had detectable P. carinii DNA (sensitivity 68%; specificity 100%; positive predictive value 100%; negative predictive value 87%). This method requires further validation in clinical practice.

Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy lung samples from children by means of P carinii -specific primers.P carinii DNA was identified in 22 of 22 (100%) samples with histologically proven P carinii pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of polymerase chain reaction as an alternative to histopathologic diagnosis.

Background: Among adults with advanced HIV infection in developing countries, bacteremia due to Mycobacterium tuberculosis (MTB) is common and bacteremia due to M. bovis (bacille Calmette-Guérin; BCG) is rare. Comparable data are not available for children with HIV., Objective: To compare the prevalence of bacteremia due to M. tuberculosis or M. bovis BCG in hospitalized children and adults with HIV infection in a developing country with a high prevalence of tuberculosis and HIV and > 95% BCG immunization coverage., Design: Descriptive cross-sectional study., Methods: Prospectively hospitalized patients in Lusaka, Zambia who were suspected to have HIV infection underwent phlebotomy for HIV ELISA, HIV viral load, and lysis-centrifugation blood culture for mycobacteria. Histories were obtained and patients were examined for BCG scars. Mycobacterial isolates were identified using DNA probes for MTB complex (MTBC), multiplex PCR and IS6110 typing., Results: The median age of 387 HIV-positive children was 15 months; 98% were BCG immunized. The median age of 344 HIV-positive adults was 32 years; 44% were BCG immunized. Blood cultures were positive for mycobacteria in six children (2%) and 38 adults(11%) (P < 0.001). The six pediatric isolates included five MTBC (40% clustered) and one BCG. The 38 adult isolates included 36 MTBC (16% clustered) and two M. avium complex., Conclusion: Bacteremia due to MTB is less common among children than adults with advanced HIV infection in Zambia. Bacteremia due to M. bovis BCG is rare even among children with recent BCG immunization and symptomatic HIV infection.