Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management.

PURPOSE OF REVIEW: This review addresses the escalating global challenge of multidrug-resistant tuberculosis (MDR-TB) in Sub-Saharan Africa, with a focus on its complex comorbidity with HIV/AIDS. Emphasizing the urgency of the issue, the review aims to shed light on the unique healthcare landscape shaped by the convergence of high prevalence rates and intersecting complexities with HIV/AIDS in the region. RECENT FINDINGS: A notable increase in MDR-TB cases across Sub-Saharan Africa is attributed to challenges in timely diagnoses, treatment initiation, and patient treatment defaulting. The literature underscores the critical need for proactive measures to address diagnostic and treatment gaps associated with MDR-TB, particularly concerning its comorbidity with HIV/AIDS. SUMMARY: To effectively manage MDR-TB and its co-morbidity with HIV/AIDS, proactive screening programs are imperative. The review highlights the necessity of active follow-up strategies to ensure treatment adherence and reduce default rates, offering evidence-based insights for improved disease management in the region.

Towards achieving transnational research partnership equity: lessons from implementing adaptive platform trials in low- and middle-income countries.

Background: Use of adaptive clinical trials, particularly adaptive platform trials, has grown exponentially in response to the coronavirus disease (COVID-19) pandemic. Implementation of these trials in low- and middle-income countries (LMICs) has been fostered through the formation or modification of transnational research partnerships, typically between research groups from LMICs and high-income countries (HICs). While these partnerships are important to promote collaboration and overcome the structural and economic disadvantages faced by LMIC health researchers, it is critical to focus attention on the multiple dimensions of partnership equity. Methods: Based on informal literature reviews and a meeting with leaders of one of the multinational COVID-19 adaptive platform trials, we describe some important considerations about research partnership equity in this context. Results: We organize these considerations into eight thematic categories: 1) epistemic structures, 2) funding, 3) ethics oversight, 4) regulatory oversight, 5) leadership, 6) post-trial access to interventions, data, and specimens, 7) knowledge translation and dissemination, and 8) research capacity strengthening and maintenance. Within each category we review normative claims that support its relevance to research partnership equity followed by discussion of how adaptive platform trials highlight new dimensions, considerations, or challenges. Conclusion: In aggregate, these observations provide insight into procedural and substantive equity-building measures within transnational global health research partnerships more broadly.

Changes in mobility patterns during the COVID-19 pandemic in Zambia: Implications for the effectiveness of NPIs in Sub-Saharan Africa.

The COVID-19 pandemic has impacted many facets of human behavior, including human mobility partially driven by the implementation of non-pharmaceutical interventions (NPIs) such as stay at home orders, travel restrictions, and workplace and school closures. Given the importance of human mobility in the transmission of SARS-CoV-2, there have been an increase in analyses of mobility data to understand the COVID-19 pandemic to date. However, despite an abundance of these analyses, few have focused on Sub-Saharan Africa (SSA). Here, we use mobile phone calling data to provide a spatially refined analysis of sub-national human mobility patterns during the COVID-19 pandemic from March 2020-July 2021 in Zambia using transmission and mobility models. Overall, among highly trafficked intra-province routes, mobility decreased up to 52% during the time of the strictest NPIs (March-May 2020) compared to baseline. However, despite dips in mobility during the first wave of COVID-19 cases, mobility returned to baseline levels and did not drop again suggesting COVID-19 cases did not influence mobility in subsequent waves.

Ethics of Adaptive Designs for Randomized Controlled Trials.

Over recent decades, adaptive trial designs have been used more and more often for clinical trials, including randomized controlled trials (RCTs). This rise in the use of adaptive RCTs has been accompanied by debates about whether such trials offer ethical and methodological advantages over traditional, fixed RCTs. This study examined how experts on clinical trial methods and ethics believe that adaptive RCTs, compared to fixed ones, affect the ethical character of clinical research. We conducted in-depth interviews with 17 researchers from bioethics, epidemiology, biostatistics, and/or medical backgrounds. While about half believed that adaptive trials are more complex and may thus threaten autonomy, these respondents also expressed that this challenge is not insurmountable. Most respondents expressed that efficiency and potential for participant benefit were the main justifications for adaptive trials. There was tension about whether adaptive randomization in response to increasing information disrupts clinical equipoise, with some respondents insisting that uncertainty still exists and therefore clinical equipoise is not disrupted. These findings suggest that further discussion is needed to increase the awareness and utility of these study designs.

Factors associated with intention to smoke cigarettes among never smoker school going adolescents in Zambia.

Background: Cigarette smoking intention is a strong predictor of cigarette smoking initiation. There is limited data on predictors of cigarette smoking intentions among adolescents in developing countries. Objective: To determine factors associated with cigarettes smoking intentions among never-smoked adolescents. Methods: The study utilized the Zambia 2011 Global Youth Tobacco Survey dataset on adolescents. Results: Being in grade nine compared to grade seven (AOR 0.43, 95%CI 0.23-0.82). Having a smoking father (AOR 2.38, 95%CI 1.25-453) mother (AOR 11.77, 95%CI 4.16-33.33), or both parents (AOR 7.05, 95%CI 2.91-17.10) showed significantly higher chance of having smoking intentions than having non-smoker parents. Also, having some (AOR 1.97, 95%CI 1.12-3.47), most (AOR 5.37, 95%CI 2.82-10.25), or all (AOR 3.75, 95%CI 1.64-8.56) smoker close friend was significantly associated with smoking intention compared to having none-smoker friends. Being around others who smoked in out-door places 1-2 days (AOR 2.16, 95%CI 1.19-3.93), 5-6 days (AOR 3.21, 95%CI 1.51-6.83) and 7 days/week (AOR 2.73, 95%CI 1.41-5.30) were also associated with one's intention to smoke cigarettes compared to not being around smokers in outdoor public places 7 days/week. Conclusion: Having smoking parents, smoking friends or around people who smoke in public places were associated with cigarette smoking intentions among adolescents.

Risk factors associated with zoonotic tuberculosis at the animal-human interface in a tuberculosis-endemic sub-Saharan country.

We aimed to assess the proportion of tuberculosis in humans and tuberculosis (TB)-associated abattoir condemnations from the animal sector, as well as determine risk factors of zoonotic tuberculosis at the animal-human interface in Zambia. The study involved 255 presumptive TB patients and 156 cattle carcasses and was conducted from April 2020 to December 2021. Univariable and multivariable logistic regressions were performed for risk factor analysis for zoonotic TB. The overall proportion of bovine tuberculosis in traditional cattle and the proportion of tuberculosis among presumptive TB patients were 39.7% and 10.2%, respectively. Consumption of raw milk (adjusted odds ratio (AOR)=2.72, 95% confidence interval (CI): 1.73-4.28) and history of previous contact with a TB patient (AOR=1.86, 95% CI: 1.17-2.95) were risk factors for zoonotic TB at the animal-human interface of Zambia. Therefore, community campaigns and sensitization on zoonotic TB transmission are recommended.

Preferences of Patients and Providers in High-Burden Malaria Settings for Long-Acting Malaria Chemoprevention.

Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia. Questions explored preferences and concerns around long-acting antimalarial formulations compared with oral formulations. We recruited 202 patient respondents (Kenya, n = 102; Zambia, n = 100) and 215 provider respondents (Kenya, n = 105; Zambia, n = 110). Long-acting injection was preferred to oral pills, whereas oral pills were preferred to implant or transdermal administration by patient respondents. Of 202 patient respondents, 80% indicated that they 'definitely would try' malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they 'definitely would' have their child age < 12 years and 90% of 88 'definitely would' have their child ≥12 years receive an injection for malaria prevention. Provider respondents indicated that they would be more likely to prescribe a long-acting injectable product compared with an oral product for malaria chemoprevention in adults (70%), adolescents ages 12 years and older (67%), and children <12 years (81%). Potential for prolonged adverse effects with long-acting products was the highest concern for patient respondents, while higher medication-related cost was cited as the most concerning barrier to implementation by providers. Overall, these findings indicate enthusiasm for the development of long-acting injectable antimalarials to provide individual delivery method options across age groups.

Measles immunity gaps among children and adolescents with HIV in Zambia despite high measles vaccination and antiretroviral therapy coverage.

OBJECTIVE: The study objective was to identify measles and rubella immunity gaps among people with HIV (PWH) in Zambia despite high measles vaccine coverage and widespread access to antiretroviral therapy. DESIGN: Nationally representative cross-sectional serosurvey using biorepository specimens. METHODS: Blood specimens collected in the Zambia Population HIV Impact Assessment survey (ZAMPHIA) of 2016 were tested for measles and rubella immunoglobulin G (IgG) antibodies by enzyme immunoassay. Hierarchical generalized additive models were fit to characterize age-specific measles and rubella seroprevalence profiles by HIV infection status. Log-binomial regression was performed to identify factors associated with seronegativity. RESULTS: Of the 25 383 specimens, a subsample of 11 500 were selected and 9852 (85%) were successfully tested. Measles seroprevalence was lower among PWH compared with HIV-uninfected individuals until approximately 30 years of age. Among children younger than the age of 10 years, measles seroprevalence was 47.2% [95% confidence interval (CI): 32.7, 61.7] in PWH and 76.4% (95% CI: 74.9, 78.0) in HIV-uninfected children in same age category. In contrast, rubella seroprevalence was higher among PWH than HIV-uninfected individuals, particularly for children younger than 10 years (68.6% vs. 44.3%, P  < 0.001). Having a detectable viral load was associated with being measles seronegative (adjusted prevalence ratio 0.15, 95% CI: 0.06, 0.38). CONCLUSIONS: These results from a nationally representative serosurvey demonstrate persistence of measles immunity gaps among PWH younger than 30 years of age. There is need to implement the World Health Organization's recommendation to revaccinate children living with HIV against measles following immune reconstitution with antiretroviral therapy to protect these children and prevent measles outbreaks.

COVID-19 positive cases among asymptomatic individuals during the second wave in Ndola, Zambia.

Background: Coronavirus disease 2019 (COVID-19) is a worldwide public health concern for healthcare workers. About 80% of cases appear to be asymptomatic, and about 3% may experience hospitalisation and later die. Less than 20% of studies have looked at the positivity rate of asymptomatic individuals. Objective: This study investigated the COVID-19 positivity rates among asymptomatic individuals during the second COVID-19 wave at one of Zambia's largest testing centre. Methods: This was a retrospective cross-sectional study conducted on routine surveillance and laboratory data at the Tropical Diseases Research Centre COVID-19 laboratory in Ndola, Zambia, from 01 December 2020 to 31 March 2021. The study population was made up of persons that had tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as a requirement for travel. Microsoft Excel was used to come up with an epidemiological curve of daily COVID-19 positive cases; proportions for gender were described using frequencies and percentages. Results: A total of 11 144 asymptomatic individuals tested for SARS-CoV-2 were sampled for the study and 1781 (16.0%) returned positive results. The median age among those tested was 36 years (interquartile range: 29-46). Testing for COVID-19 peaked in the month of January 2021 (37.4%) and declined in March 2021 (21.0%). The epidemiological curve showed a combination of continuous and propagated point-source transmission. Conclusion: The positivity rate of 16.0% among asymptomatic individuals was high and could imply continued community transmission, especially during January 2021 and February 2021. We recommend heightened testing for SARS-CoV-2 among asymptomatic individuals. What this study adds: This study adds critical knowledge to the transmission of COVID-19 among asymptomatic travellers who are usually a key population in driving community infection. This knowledge is critical in instituting evidence-based interventions in the screening and management of travellers, and its control.

Oesophageal cancer cases recorded in the Zambia National Cancer Registry: a cross-sectional study.

Introduction: the aim of this study was to determine what proportion of patients with confirmed esophageal cancer at the largest hospital in the country were recorded in the Zambia National Cancer Registry (ZNCR). Methods: we reviewed esophageal cancer records at the University Teaching Hospital (UTH) and ZNCR, between 2015 and 2017. Using Stata version 15, data were summarised and the Kruskal-Wallis was used to compute comparisons, Kaplan-Meier curves for survival estimates and Cox regression for associated factors. Results: included in the final analysis were records for 222 patients with confirmed esophageal cancer and of these 51/222 (41%) were appearing in the ZNCR. The mean age of the patients was 56.2 years (SD, 13.0) and only 2/222 (1%) were confirmed alive at the time of data analysis. The median time from endoscopic diagnosis to histological confirmation was 12.5 days (IQR 7.5 - 21.5) and arrival at the Cancer Diseases Hospital (CDH) for treatment was 20 days (IQR 10 - 34). The overall median survival time in the study was 259 days (CI 95%; 151 - 501). Age, sex, time to diagnosis, histological classification and grade of tumour did not show any evidence of predicting survival in both the univariate and multivariable cox regression model (p>0.05). Conclusion: a significant proportion of esophageal cancer cases seen at UTH were not included in the national registry suggesting that official figures for the prevalence of esophageal cancer in Zambia are underestimated. There is an urgent need to improve the collection of data on esophageal cancer in Zambia.

Leveraging health infrastructure to optimize HPV vaccination for adolescents in Zambia: Protocol for an implementation study.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14-15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents-those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination schedule for ALHIV (3 versus 2 doses). Integrating HPV vaccination into routine care in adolescent HIV clinics may ensure that ALHIV have access to vaccine at the WHO-recommended schedule. Such integration requires a multilevel approach, stakeholder engagement, and diversified implementation strategies, given known challenges of providing the HPV vaccine in LMICs, including Zambia. METHODS: Our study aims to integrate HPV vaccination into routine care in adolescent HIV clinics. To achieve success, we will co-design a package of implementation strategies using a previously successful implementation research approach developed for cervical cancer prevention in LMICs: the Integrative Systems Praxis for Implementation Research (INSPIRE). INSPIRE is a novel, comprehensive approach to develop, implement, and evaluate implementation science efforts. Following key elements of INSPIRE, our specific aims are to: 1) Identify the unique multilevel contextual factors (barriers and facilitators) across HIV settings (rural, urban, peri-urban) that influence HPV vaccine uptake; 2) Use Implementation Mapping to translate stakeholder feedback and findings from Aim 1 into a package of implementation strategies to integrate HPV vaccine into HIV clinics; 3) Conduct a Hybrid Type 3 effectiveness-implementation trial to evaluate the package of multilevel implementation strategies for integrating HPV vaccine into HIV clinics. DISCUSSION: Our research team has strong support, technical expertise, and resources (e.g., vaccines) from the Zambian Ministry of Health; and political will for scale-up. This stakeholder-based implementation model has the potential to be transported to HIV clinics across Zambia and serve as a model to address cancer prevention priorities for those with HIV in other LMICs. TRIAL REGISTRATION: To be registered prior to Aim 3, when implementation strategies finalized.

Losses along the tuberculosis sputum sample referral cascade for Mpongwe District, Zambia.

BACKGROUND: In resource limited-settings, timely tuberculosis (TB) diagnosis depends upon referral of sputum samples from non-diagnostic to diagnostic facilities for examination. The TB programme data for 2018 suggested losses in Mpongwe District's sputum referral cascade. AIM: This study aimed to identify the referral cascade stage where loss of sputum specimen occurred. SETTING: Primary health care facilities in Mpongwe District, Copperbelt Province, Zambia. METHODS: Data were retrospectively collected from one central laboratory and six referring health facilities between January and June 2019, using a paper-based tracking sheet. Descriptive statistics were generated in SPSS version 22. RESULTS: Of the 328 presumptive pulmonary TB patients found in presumptive TB registers at referring facilities, 311 (94.8%) submitted sputum samples and were referred to the diagnostic facilities. Of these, 290 (93.2%) were received at the laboratory, and 275 (94.8%) were examined. The remaining 15 (5.2%) were rejected for reasons such as 'insufficient sample'. Results for all examined samples were sent back and received at referring facilities. Referral cascade completion rate was 88.4%. Median turnaround time was six days (IQR = 1.8). CONCLUSION: Losses in the sputum referral cascade for Mpongwe District mainly occurred between dispatch of sputum samples and receipt at diagnostic facility. Mpongwe District Health Office needs to establish a system to monitor and evaluate the movement of sputum samples along the referral cascade to minimize losses and ensure timely TB diagnosis.Contribution: This study has highlighted, at primary health care level for resource limited settings, the stage in the sputum sample referral cascade where losses mainly occur.

Mortality among persons receiving tuberculosis treatment in Itezhi-Tezhi District of Zambia: A retrospective cohort study.

Itezhi-Tezhi District in southern Zambia has been reporting tuberculosis (TB) mortality rates that are fourfold higher than the national average of six percent. We conducted a retrospective cohort study to establish the demographic and clinical characteristics associated with mortality among persons under treatment for TB in Itezhi-Tezhi District, as well as the likely causes and time to death. We reviewed medical records for persons with TB registered in 19 public health facilities in Itezhi-Tezhi District between January 2015 and December 2018. Of the 506 persons with TB registered in the study period, 426 were included in the analysis. Of these, 71 (16.7%) died before completing treatment. The overall mortality rate was 31.8 per 1,000 person-months of observation. Most of the deaths (53 [74.7%]) occurred in the first month of treatment (median: 16 days; interquartile range: 5-52 days). In a multivariate Cox regression model, type of TB was found to be an independent predictor of mortality while on TB treatment. The risk of dying was more than twice higher for persons with clinically diagnosed PTB compared to those with bacteriologically confirmed PTB (adjusted hazard ratio = 2.2, 95% CI: 1.4-3.6). In a sub-analysis of persons with clinically diagnosed PTB, persons with TB who were on a community-based DOT plan were more than twice more likely to die compared to those on facility-based DOT plan (adjusted hazard ratio = 2.21, 95% CI: 1.1-4.8). Common likely causes of death were pulmonary TB disease (66.0%), anemia (12.8%), cardiac failure (4.3%), pneumocystis jiroveci pneumonia (4.3%), and gastroenteritis (4.2%). These findings show that most deaths occurred during the first month of treatment. Clinical evaluation at initiation of anti-TB treatment and during follow-up care, especially in persons with clinically diagnosed PTB, should include screening and treatment of other conditions.

First and Second-Line Anti-Tuberculosis Drug-Resistance Patterns in Pulmonary Tuberculosis Patients in Zambia.

BACKGROUND: Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study. METHODS: A total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants' social-demographic characteristics were obtained using a pre-test checklist. RESULTS: Overall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5-31.6%). A total of 9.8% (13/132, 95% CI: 5.3-16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3-16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1-146.5%) to have drug-resistant TB than those who had no history of being treated for TB. CONCLUSION: This study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring.

Malaria in Refugee Children Resettled to a Holoendemic Area of Sub-Saharan Africa.

BACKGROUND: Malaria is a leading cause of morbidity and mortality in refugee children in high-transmission parts of Africa. Characterizing the clinical features of malaria in refugees can inform approaches to reduce its burden. METHODS: The study was conducted in a high-transmission region of northern Zambia hosting Congolese refugees. We analyzed surveillance data and hospital records of children with severe malaria from refugee and local sites using multivariable regression models and geospatial visualization. RESULTS: Malaria prevalence in the refugee settlement was similar to the highest burden areas in the district, consistent with the local ecology and leading to frequent rapid diagnostic test stockouts. We identified 2197 children hospitalized for severe malaria during the refugee crisis in 2017 and 2018. Refugee children referred from a refugee transit center (n = 63) experienced similar in-hospital mortality to local children and presented with less advanced infection. However, refugee children from a permanent refugee settlement (n = 110) had more than double the mortality of local children (P < .001), had lower referral rates, and presented more frequently with advanced infection and malnutrition. Distance from the hospital was an important mediator of the association between refugee status and mortality but did not account for all of the increased risk. CONCLUSIONS: Malaria outcomes were more favorable in refugee children referred from a highly outfitted refugee transit center than those referred later from a permanent refugee settlement. Refugee children experienced higher in-hospital malaria mortality due in part to delayed presentation and higher rates of malnutrition. Interventions tailored to the refugee context are required to ensure capacity for rapid diagnosis and referral to reduce malaria mortality.

RETRACTED: Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa.

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

Leveraging a national biorepository in Zambia to assess measles and rubella immunity gaps across age and space.

High-quality, representative serological surveys allow direct estimates of immunity profiles to inform vaccination strategies but can be costly and logistically challenging. Leveraging residual serum samples is one way to increase their feasibility. We subsampled 9854 residual sera from a 2016 national HIV survey in Zambia and tested these specimens for anti-measles and anti-rubella virus IgG antibodies using indirect enzyme immunoassays. We demonstrate innovative methods for sampling residual sera and analyzing seroprevalence data, as well as the value of seroprevalence estimates to understand and control measles and rubella. National measles and rubella seroprevalence for individuals younger than 50 years was 82.8% (95% CI 81.6, 83.9%) and 74.9% (95% CI 73.7, 76.0%), respectively. Despite a successful childhood vaccination program, measles immunity gaps persisted across age groups and districts, indicating the need for additional activities to complement routine immunization. Prior to vaccine introduction, we estimated a rubella burden of 96 congenital rubella syndrome cases per 100,000 live births. Residual samples from large-scale surveys can reduce the cost and challenges of conducting serosurveys, and multiple pathogens can be tested. Procedures to access quality specimens, ensure ethical approvals, and link sociodemographic data can improve the timeliness and value of results.