Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission. METHODS: We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438). FINDINGS: Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30·6 years (IQR 26·0-34·7), 1480 (98·4%) of 1504 were receiving ART, and 169 (11·5%) of 1466 had a viral load ≥1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0·19 per 100 person-years (95% CI 0·005-1·04) in the intervention group and 1·16 per 100 person-years (0·43-2·53) in the control group, which did not reach statistical significance (p=0·066). HIV-free survival and serious adverse events were similar in both groups. INTERPRETATION: Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination. FUNDING: The EDCTP2 programme with the support of the UK Department of Health & Social Care.

Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.

BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.

Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. METHODS AND FINDINGS: HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. CONCLUSIONS: In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01900977.

Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia.

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.

Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia.

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

The effect of COVID-19 on malaria cases in Zambia: a mixed effect multilevel analysis.

BACKGROUND: The burden of Malaria in Zambia remains a challenge, with the entire population at risk of contracting this infectious disease. Despite concerted efforts by African countries, including Zambia, to implement malaria policies and strategies aimed at reducing case incidence, the region faces significant hurdles, especially with emerging pandemics such as COVID-19. The efforts to control malaria were impacted by the constraints imposed to curb its transmission during the COVID-19 pandemic. The aim of the study was to assess the effect of the COVID-19 pandemic on malaria cases in Zambia and the factors associated by comparing the COVID-19 period and the pre-COVID-19 era. METHODS: This was a cross-sectional panel study in which routinely collected programmatic data on malaria was used. The data were extracted from the Health Management Information System (HMIS) for the period January 2018 to January 2022. The period 2018 to 2022 was selected purely due to the availability of data and to avoid the problem of extrapolating too far away from the period of interest of the study. A summary of descriptive statistics was performed in which the number of cases were stratified by province, age group, and malaria cases. The association of these variables with the COVID-19 era was checked using the Wilcoxon rank-sum test and Kruskal‒Wallis test as applicable. In establishing the factors associated with the number of malaria cases, a mixed-effect multilevel model using the Poisson random intercept and random slope of the COVID-19 panel. The model was employed to deal with the possible correlation of the number of cases in the non-COVID-19 panel and the expected correlation of the number of cases in the COVID-19 panel. RESULTS: A total of 18,216 records were extracted from HMIS from January 2018 to January 2022. Stratifying this by the COVID-19 period/era, it was established that 8,852 malaria cases were recorded in the non-COVID-19 period, whereas 9,364 cases were recorded in the COVID-19 era. Most of the people with malaria were above the age of 15 years. Furthermore, the study found a significant increase in the relative incidence of the COVID-19 panel period compared to the non-COVID-19 panel period of 1.32, 95% CI (1.18, 1.48, p < 0.0001). The observed numbers, as well as the incident rate ratio, align with the hypothesis of this study, indicating an elevated incidence rate ratio of malaria during the COVID-19 period. CONCLUSION: This study found that there was an increase in confirmed malaria cases during the COVID-19 period compared to the non-COVID-19 period. The study also found Age, Province, and COVID-19 period to be significantly associated with malaria cases.

HIV estimation using population-based surveys with non-response: A partial identification approach.

HIV estimation using data from the demographic and health surveys (DHS) is limited by the presence of non-response and test refusals. Conventional adjustments such as imputation require the data to be missing at random. Methods that use instrumental variables allow the possibility that prevalence is different between the respondents and non-respondents, but their performance depends critically on the validity of the instrument. Using Manski's partial identification approach, we form instrumental variable bounds for HIV prevalence from a pool of candidate instruments. Our method does not require all candidate instruments to be valid. We use a simulation study to evaluate and compare our method against its competitors. We illustrate the proposed method using DHS data from Zambia, Malawi and Kenya. Our simulations show that imputation leads to seriously biased results even under mild violations of non-random missingness. Using worst case identification bounds that do not make assumptions about the non-response mechanism is robust but not informative. By taking the union of instrumental variable bounds balances informativeness of the bounds and robustness to inclusion of some invalid instruments. Non-response and refusals are ubiquitous in population based HIV data such as those collected under the DHS. Partial identification bounds provide a robust solution to HIV prevalence estimation without strong assumptions. Union bounds are significantly more informative than the worst case bounds without sacrificing credibility.

Nationwide survey of Helicobacter pylori seropositivity and gastric atrophy in Zambia.

BACKGROUND: Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology. MATERIALS AND METHODS: This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy. RESULTS: The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5-2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5-0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years. CONCLUSIONS: We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years.

Effectiveness of trauma-focused cognitive behavioral therapy compared to psychosocial counseling in reducing HIV risk behaviors, substance use, and mental health problems among orphans and vulnerable children in Zambia: a community-based randomized controlled trial.

Orphans and vulnerable children (OVC) in sub-Saharan Africa are at high risk for HIV infection and transmission. HIV prevention and treatment efforts with OVC are hindered by mental health and substance use problems. This randomized controlled trial compared a mental health intervention, Trauma Focused Cognitive Behavioral Therapy (TF-CBT), to an enhanced version of an existing HIV Psychosocial Counseling (PC+) program among 610 adolescents who met PEPFAR criteria for OVC and had HIV risk behaviors in Lusaka, Zambia. Outcomes included HIV risk behaviors (e.g., risky sexual behaviors), mental health (internalizing symptoms, externalizing behaviors, PTSD) and substance use. At 12-month follow-up, there were significant within group reductions in both groups for all outcomes, with the only significant between group difference being for substance use, in which OVC who received TF-CBT had significantly greater reductions than OVC who received PC+. In a subgroup analysis of OVC with high levels of PTSD symptoms, TF-CBT was superior to PC + in reducing internalizing symptoms, functional impairment, and substance use. Findings support TF-CBT for reducing substance use among OVC. Subgroup analysis results suggest that a robust intervention such as TF-CBT is warranted for OVC with significant mental and behavioral health comorbidities. The similar performance of TF-CBT and PC + in the overall sample for risky sexual behavior and mild mental health problems indicates that enhancing existing psychosocial programs, such as PC, with standard implementation factors like having a defined training and supervision schedule (as was done to create PC+) may improve the efficacy of HIV risk reduction efforts.Clinical Trials Number: NCT02054780.

Stigmatizing clinical setting erodes physician-patient interaction quality for sexual minority men through perceived HIV stigma and HIV infection concerns in Zambia.

This study investigated whether perceived HIV stigma and HIV infection concerns among healthcare providers (HCPs) mediate the association between stigmatizing clinical setting and their interaction quality with sexual minority men (SMM) patients in Zambia. In 2021, a cross-sectional survey was conducted with 91 HCPs offering HIV-related services to SMM in Zambia. Path analysis was conducted to examine the potential mediation effect of "perceived HIV stigma" and "HIV infection concern" among HCPs in the association between "stigmatizing clinical setting" and their "interaction quality with SMM". Mediators i.e., "perceived HIV stigma" and "HIV infection concern" among HCPs, were associated positively with the stigmatizing clinical setting (ß = 0.329, p < .01, ß = 0.917, p < 0.01), and negatively with physician-patient interaction quality (ß = -0.167, p = 0.051; ß = -0.126, p < 0.05). Stigmatizing clinical setting had a significant and negative indirect effect on HCPs interaction quality with SMM through increased perceived HIV stigma (z = -1.966, p < 0.05) and increased HIV infection concern (z = -1.958, p = 0.050). To improve physician-patient interaction quality, stigma reduction interventions among HCPs, who serve SMM in Zambia, should target development of development of inclusive policies and the cultivation of cultural norms that are supportive and respectful to SMM, and protection of HCPs from enacted stigma due to offering care to SMM.

Endoscopic diagnosis of gastric and oesophageal cancer in Lusaka, Zambia: a retrospective analysis.

INTRODUCTION: There are uncertainties surrounding the spectrum of upper gastrointestinal (UGI) diseases in sub-Saharan Africa. This is mainly due to the limitations of data collection and recording. We previously reported an audit of UGI endoscopic diagnoses in Zambia spanning from 1977 to 2014. We now have extended this analysis to include subsequent years, in order to provide a more comprehensive picture of how the diagnoses have evolved over 4 decades. METHODS: We combined data collected from the endoscopy unit at the University Teaching Hospital (UTH) in Lusaka during a previous review with that collected from the beginning of 2015 to the end of 2021. Since 2015, an electronic data base of endoscopy reports at the UTH was kept. The electronic data base was composed of drop-down menus that allowed for standardised reporting of findings. Collected data were coded by two experienced endoscopists and analysed. RESULTS: In total, the analysis included 25,849 endoscopic records covering 43 years. The number of endoscopic procedures performed per year increased drastically in 2010. With the exception of the last 2 years, the proportion of normal endoscopies also increased during the time under review. In total, the number of gastric cancer (GC) cases was 658 (3%) while that of oesophageal cancer (OC) was 1168 (5%). The number of GC and OC diagnoses increased significantly over the period under review, (p < 0.001 for both). For OC the increase remained significant when analysed as a percentage of all procedures performed (p < 0.001). Gastric ulcers (GU) were diagnosed in 2095 (8%) cases, duodenal ulcers (DU) in 2276 (9%) cases and 239 (1%) had both ulcer types. DU diagnosis showed a significantly decreasing trend over each decade (p < 0.001) while GU followed an increasing trend (p < 0.001). CONCLUSIONS: UGI endoscopic findings in Lusaka, Zambia, have evolved over the past four decades with a significant increase of OC and GU diagnoses. Reasons for these observations are yet to be established.

Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains in Zambia: A Sub-Saharan African Country.

INTRODUCTION: Helicobacter pylori (H. pylori) is one of the most important infections globally, affecting more than 50% of the human population. Clarithromycin (CLA)-containing regimens are recommended for empirical eradication of H. pylori in populations with less than 15% resistance. The aim of this study was to estimate the prevalence of CLA resistance in samples collected from Zambian patients to determine if CLA is suitable for first-line H. pylori empirical treatment. METHODOLOGY: We used archival biopsy samples collected from dyspeptic patients undergoing endoscopy. The samples had been snap-frozen immediately after collection and stored at -80°C. We performed multiplex real-time PCR using Bosphore Helicobacter pylori Genotyping Kits v1, Istanbul, Turkey, to determine the presence of wild-type H. pylori and three mutations, A2142G, A2142C, and A2143G, of domain V in 23s rRNA gene. RESULTS: We tested 259 gastric biopsy samples from patients with dyspepsia, of which 136 (53%) were from females. The median age was 48 years (IQR 40-61 years). Endoscopically, most of the patients, 164 (63%), had a normal gastric mucosa. CLA resistance was found in 48 (28%) samples, with A2142G mutation in 23 (13%), A2143G mutation in 32 (18%), and double mutations A2142C and A2143G in 6 (3%). CONCLUSIONS: The presence of significant levels of CLA resistance in Zambia suggests that it should not be used as first-line empirical treatment for H. pylori infection. However, with a limitation of suitable alternatives, there is an urgent need to formulate new treatment approaches.

The clinical profile and outcomes of drug resistant tuberculosis in Central Province of Zambia.

BACKGROUND: The emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia. METHODS: This was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital's Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed. RESULTS: The study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36-45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70-0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107-0.638] p = 0.003). CONCLUSION: The research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.

Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia.

BACKGROUND: Southern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening. METHODS: A clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays. RESULTS: Three thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7-73.4) with SD Bioline and 67.9% (95%CI 58.2-76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6-85.7) and 81.0% (95%CI 71.9-88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4-94.2) with SD Bioline; and 91.5% (95%CI 88.2-93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8-98.5) with SD Bioline and 96.7% (95%CI 95.1-97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level. CONCLUSIONS: Based on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS: This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION: The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

Trends in prevalence and factors associated with unintended pregnancies in Zambia (2001-2018).

BACKGROUND: Unintended pregnancies can pose significant public health concerns for both maternal and child health because of their associated risks and implications. Experience of unintended pregnancies may lead to delay in seeking antenatal care, thus leading to increased risk of complications during pregnancy and childbirth. Globally, the prevalence of unintended pregnancies has declined. However, the problem remains acute in sub-Saharan Africa. This study was conducted to examine the factors associated with an experience of unintended pregnancy among women of reproductive ages in Zambia. METHODS: This study used secondary data from the Zambia Demographic and Health Surveys (ZDHSs) which were conducted between 2001 and 2018. A pooled weighted sample of 4,090 pregnant women of reproductive age 15-49 years at the time of the survey was included in the analysis. Multivariable binary logistic regression model was employed to examine the association between independent correlates and experience of unintended pregnancy. All statistical analyses were conducted using Stata software. RESULTS: Findings show that the proportion of women of reproductive age who experienced unintended pregnancy in Zambia declined from 50.4% (95% CI: 47.1, 53.8) in 2001 to 45.2% (95% CI: 40.5, 49.9) in 2018. The decline in the prevalence of unintended pregnancy is more pronounced among women age groups 25-29 years and 30-34 years. Increasing age was associated with an increased risk of experiencing unintended pregnancies. On the other hand, women who were living in rural areas (aOR = 0.76; 95% CI: 0.58, 1.00) and those with tertiary education (aOR = 0.46; 95% CI: 0.26, 0.80) were less likely to experience an unintended pregnancy. Women who desired a large family (aOR = 0.45; 95% CI: 0.24, 0.85) and those who watched television (aOR = 0.75; 95% CI: 0.59, 0.94) had lower odds of experiencing unintended pregnancies. CONCLUSIONS: The study has established that the prevalence of unintended pregnancy is still high in Zambia. Women's age, place of residence, level of education, desired family size and exposure to media were associated with the risk of experiencing an unintended pregnancy. Enhancing access to family planning services and commodities targeting women with low education levels will be key to further reduce unintended pregnancies.

Prevalence and risk of burnout among HIV service providers in South Africa and Zambia: findings from the HPTN 071 (PopART) trial.

BACKGROUND: In the high disease burden and resource-constrained contexts of sub-Saharan Africa (SSA), health workers experience a range of psychosocial stressors that leave them vulnerable to developing burnout, which can reduce service quality and negatively impact their own health and wellbeing. As universal testing and treatment (UTT) for HIV scales up across SSA, we sought to understand the implications of this human resource-intensive approach to HIV prevention to inform decision-making about health workforce staffing and support needs. METHODS: Using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), we assessed the prevalence of three domains of burnout-emotional exhaustion, depersonalization, and personal accomplishment-among three cadres of health workers delivering health services in areas receiving a UTT intervention in Zambia and South Africa. These cadres included health facility workers (n = 478), community health workers (n = 159), and a study-specific cadre of community HIV care providers (n = 529). We used linear regression to assess risk factors associated with emotional exhaustion, the only domain with sufficient variation in our sample. RESULTS: The MBI-HSS was completed by 1499/2153 eligible participants (69.6% response rate). Less than 1% of health workers met Maslach's definition for burnout. All groups of health workers reported lower levels of emotional exhaustion than found in previous studies of this type (mean score scores ranged from 10.7 to 15.4 out of 54 across health cadres). Higher emotional exhaustion was associated with higher educational attainment (ßadj = 2.24, 95% CI 0.76 to 3.72), greater years providing HIV services (ßadj = 0.20, 95% CI 0.03 to 0.36), and testing negative for HIV at last HIV test (ßadj = - 3.88 - 95% CI 5.69 to - 2.07). Working as a CHW was significantly associated with lower emotional exhaustion (ßadj = - 2.52, 95% CI - 4.69 to - 0.35). Among all health workers, irrespective of HIV status, witnessing stigmatizing behaviors towards people living with HIV among their co-workers was associated with significantly increased emotional exhaustion (ßadj = 3.38, 95% CI 1.99 to 4.76). CONCLUSIONS: The low level of burnout detected among health workers is reassuring. However, it remains important to assess how UTT may affect levels of emotional exhaustion among health workers over time, particularly in the context of emerging global pandemics, as burnout may impact the quality of HIV services they provide and their own mental health and wellbeing. Interventions to reduce HIV stigma in health facilities may protect against emotional exhaustion among health workers, as well as interventions to increase mindfulness and resilience among health workers at risk of burnout. Trial registration ClinicalTrials.gov number: NCT01900977.

Gaps in treatment of epileptic seizures in a Zambian rural area.

BACKGROUND: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area. METHODS: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap. RESULTS: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine. CONCLUSION: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap.

Mortality from non-communicable diseases and associated risk factors in Zambia; analysis of the sample vital registration with verbal autopsy 2015/2016.

BACKGROUND: Non-communicable diseases (NCDs) are the world's growing cause of preventable illness, disability, morbidity, and mortality which account for 71% of deaths. The aim of this study was to determine the factors associated with mortality from NCDs among persons aged 15 years and above in Zambia. METHODOLOGY: The study used data from Sample Vital Registration with Verbal Autopsy (SAVVY) 2015/16 (Zambia). A total of 3529 Verbal Autopsy were completed in the study, with only 2599 of death where among people aged 15 years and above. Three-level data analysis was applied; univariate analysis, bivariate analysis, and multivariate analysis (binary logistic regression). FINDINGS: The overall number of deaths from NCDs was 28.81%. Stratified analysis by gender showed that deaths from NCDs were higher among women (32.60%) as compared to men (26.25%). Among all persons, dying from NCDs was associated with tobacco use, age, and education. Tobacco use was negatively associated with mortality from NCDs (adjusted odds ratio [aOR] = 0.68; 95% confidence interval [CI]: 0.48-0.98). Age was positively associated with the odds of dying from NCDs among persons aged 45-59 years (aOR = 3.87, 95% CI: 2.13-7.01), 60-74 years (aOR = 12.05, 95% CI: 6.44-22.55), and 75 + years (aOR = 15.16, 95% CI: 7.93-28.97). The likelihood of dying from NCDs was higher among persons with secondary education as compared to those with no education (aOR = 1.93, 95% CI: 1.11-3.33). CONCLUSION: The findings from this study suggest that public health interventions targeting NCDs need to consider behavioural factors, especially tobacco use which exposes people to second-hand smoke. We also recommend large-scale national-level studies to further examine the contribution of each factor leading to mortality from NCDs.