BACKGROUND: Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre-rainy season IRS may not reduce the post-rainy season peak abundance of the major vector, Anopheles funestus. METHODS: A controlled, pre-post, prospective cohort study assessed the impact of late-rainy season IRS on malaria prevalence, incidence, hazard, and vector abundance. Three hundred eighty-two individuals were enrolled across four household clusters, of which two were sprayed in April 2022 toward the end of the rainy season. Monthly household and individual surveys and indoor overnight vector collections were conducted through August 2022. Multivariate regression and time-to-event analyses estimated the impact of IRS on outcomes measured by rapid diagnostic tests, microscopy, and quantitative polymerase chain reaction. RESULTS: Seventy two percent of participants tested positive by rapid diagnostic test at least once and incidence by microscopy was 3.4 infections per person-year. Residing in a household in a sprayed area was associated with a 52% reduction in infection hazard (hazards ratio: 0.48, 95% confidence interval [0.29, 0.78]) but not with changes in incidence, prevalence, or vector abundance. The study-wide entomological inoculation rate was 34 infectious bites per person per year. CONCLUSION: Monthly tracking of incidence and prevalence did not demonstrate meaningful changes in holoendemic transmission intensity. However, hazard of infection, which provides greater power for detecting changes in transmission, demonstrated that late rainy season IRS reduced malaria risk.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% (P-value: 0.07) and VLS prevalence increased from 59.2% to 85.7% (P-value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes.

BACKGROUND: The US President's Emergency Plan for AIDS Relief (PEPFAR) aims to address the higher risk of cervical cancer among women living with HIV (WLHIV) by offering high quality screening services in the highest burden regions of the world. METHODS: We analyzed PEPFAR Monitoring, Evaluation, and Reporting data from CDC-supported sites in 13 countries in sub-Saharan Africa for WHLIV aged 15+ years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen, or routine rescreening). We fitted negative binomial random-coefficient models of log-linear trends in time to estimate the probabilities of testing positive, and any temporal trends in positivity. RESULTS: Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time, and among those women presenting to antiretroviral therapy (ART) clinics for routine rescreening. CONCLUSIONS: These positivity rates are lower than expectations set by the published literature. Further research is needed to determine if these lower rates are attributable to the high level of consistent ART use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure WLHIV have access to the highest possible quality prevention services.

Background COVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms.Methods In September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose PCR tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions.Results Of 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms.Conclusion A notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ‘post-acute COVID-19 clinics’ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the US Centres for Disease Control and PreventionAuthor DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The University of Zambia Biomedical Research Ethics Committee Ridgeway Campus, P.O. Box 50110 Lusaka, Zambia E-mail: unzarec{at}zamtel.zmAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data referred to in this manuscript is available for viewing and verification

IMPORTANCE: Few epidemiologic studies related to COVID-19 have emerged from countries in Africa, where demographic characteristics, epidemiology, and health system capacity differ from other parts of the world. OBJECTIVES: To describe the characteristics and outcomes of patients admitted to COVID-19 treatment centers, assess risk factors for in-hospital death, and explore how treatment center admissions were affected by COVID-19 waves in Zambia. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed patients admitted to COVID-19 treatment centers in 5 Zambian cities between March 1, 2020, and February 28, 2022. EXPOSURES: Risk factors for in-hospital mortality, including patient age and severity of COVID-19, at treatment center admission. MAIN OUTCOMES AND MEASURES: Patient information was collected, including inpatient disposition (discharged or died). Differences across and within COVID-19 waves were assessed. Mixed-effects logistic regression models were used to assess associations between risk factors and in-hospital mortality as well as between characteristics of admitted patients and timing of admission. RESULTS: A total of 3876 patients were admitted during 4 COVID-19 waves (mean [SD] age, 50.6 [19.5] years; 2103 male [54.3%]). Compared with the first 3 waves (pooled), the proportion of patients who were 60 years or older admitted during wave 4, when the Omicron variant was circulating, was significantly lower (250 of 1009 [24.8%] vs 1116 of 2837 [39.3%]; P<.001). Factors associated with in-hospital mortality included older age (60 vs <30 years; adjusted odds ratio [aOR], 3.55; 95% CI, 2.34-5.52) and HIV infection (aOR, 1.39; 95% CI, 1.07-1.79). Within waves, patients who were admitted during weeks 5 to 9 had significantly higher odds of being 60 years or older (aOR, 2.09; 95% CI, 1.79-2.45) or having severe COVID-19 at admission (aOR, 2.49; 95% CI, 2.14-2.90) than those admitted during the first 4 weeks. CONCLUSIONS AND RELEVANCE: The characteristics of admitted patients during the Omicron wave and risk factors for in-hospital mortality in Zambia reflect data reported elsewhere. Within-wave analyses revealed a pattern in which it appeared that admission of higher-risk patients was prioritized during periods when there were surges in demand for health services during COVID-19 waves. These findings support the need to expand health system capacity and improve health system resiliency in Zambia and other countries with resource-limited health systems.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data are limited from Sub-Saharan Africa. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. METHODS: We conducted a retrospective cohort study among admitted patients at 8 COVID-19 treatment centers across Zambia during April 2021 through March 2022, when the Delta and Omicron variants were circulating. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, hospitalization month, and COVID-19 treatment center. Vaccine effectiveness of 1 vaccine dose was calculated from the adjusted odds ratio. RESULTS: Among 1653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received 1 vaccine dose before hospital admission. Of the patients who had received 1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (P < .01). The median time since receipt of a first vaccine dose (interquartile range) was 52.5 (28-107) days. Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI, 42.3%-79.4%). CONCLUSIONS: Among patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating the benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.

INTRODUCTION: COVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms. METHODS: in September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose polymerase chain reaction (PCR) tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions. RESULTS: of 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms. CONCLUSION: a notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ´post-acute COVID-19 clinics´ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.

During the July 2020 first wave of severe acute respiratory syndrome coronavirus 2 in Zambia, PCR-measured prevalence was 13.4% among outpatients at health facilities, an absolute difference of 5.7% compared with prevalence among community members. This finding suggests that facility testing might be an effective strategy during high community transmission.

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

INTRODUCTION: Healthcare workers (HCWs) in Zambia have become infected with SARS-CoV-2, the virus that causes coronavirus disease (COVID-19). However, SARS-CoV-2 prevalence among HCWs is not known in Zambia. METHODS: We conducted a cross-sectional SARS-CoV-2 prevalence survey among Zambian HCWs in twenty health facilities in six districts in July 2020. Participants were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) and for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA). Prevalence estimates and 95% confidence intervals (CIs), adjusted for health facility clustering, were calculated for each test separately and a combined measure for those who had PCR and ELISA performed. RESULTS: In total, 660 HCWs participated in the study, with 450 (68.2%) providing nasopharyngeal swab for PCR and 575 (87.1%) providing a blood specimen for ELISA. Sixty-six percent of participants were females and the median age was 31.5 years (interquartile range 26.2-39.8 years). The overall prevalence of the combined measure was 9.3% (95% CI 3.8%-14.7%). PCR-positive prevalence of SARS-CoV-2 was 6.6% (95% CI 2.0%-11.1%) and ELISA-positive prevalence was 2.2% (95% CI 0.5%-3.9%). CONCLUSIONS: SARS-CoV-2 prevalence among HCWs was similar to a population-based estimate (10.6%) during a period of community transmission in Zambia. Public health measures such as establishing COVID-19 treatment centers before the first cases, screening for COVID-19 symptoms among patients accessing health facilities, infection prevention and control trainings, and targeted distribution of personal protective equipment based on exposure risk might have prevented increased SARS-CoV-2 transmission among Zambian HCWs.

BACKGROUND: Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. METHODS: Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. FINDINGS: Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7-31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3-13·9). The rtPCR-positive prevalence was 7·6% (4·7-10·6) and ELISA-positive prevalence was 2·1% (1·1-3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705-596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. INTERPRETATION: The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. FUNDING: US Centers for Disease Control and Prevention.

The increase in health research in sub-Saharan Africa (SSA) has led to a high demand for biostatisticians to develop study designs, contribute and apply statistical methods in data analyses. Initiatives exist to address the dearth in statistical capacity and lack of local biostatisticians in SSA health projects. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) led by African institutions was initiated to improve biostatistical capacity according to the needs identified by African institutions, through collaborative masters and doctoral training in biostatistics. SACCAB has created a critical mass of biostatisticians and a network of institutions over the last five years and has strengthened biostatistics resources and capacity for health research studies in SSA.  SSACAB comprises 11 universities and four research institutions which are supported by four European universities.  In 2015, only four universities had established Masters programmes in biostatistics and SSACAB supported the remaining seven to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics Masters programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of whom 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling of limited biostatistics resources in SSA combined with co-funding from external partners has shown to be an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates.

INTRODUCTION: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. METHODS: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. RESULTS: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16-24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. CONCLUSIONS: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely.

BACKGROUND: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. METHODS: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). RESULTS: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074). CONCLUSION: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors.

In May 2018, an unscheduled analysis from the Botswana-Harvard AIDS Institute Partnership Tsepamo birth-outcomes surveillance study showed a higher prevalence of neural-tube defects among infants born to women who were using dolutegravir-based antiretroviral treatment (ART) regimens at the time of conception relative to infants born to women taking other types of ART.1 In response to this safety signal, the Botswana Ministry of Health and Wellness expanded surveillance for neural-tube defects in selected non-Tsepamo health facilities.

BACKGROUND: In 2015, the World Health Organization (WHO) updated the global methodology for assessing and reducing missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. This paper presents the results of two pilot assessments conducted in Chad and Malawi. METHODS: Using the ten-step global WHO MOV strategy, we purposively selected districts and health facilities, with non-probabilistic sampling of <24 month old children for exit interviews of caregivers and self-administered knowledge, attitudes, and practices (KAP) surveys of health workers. MOV were calculated based on a child's documented vaccination history (i.e., from a home-based record (HBR) or a health facility vaccination register), including selected vaccines in the national schedule. RESULTS: Respondents included caregivers of 353 children in Chad and of 580 children in Malawi. Among those with documented vaccination history, 82% (195/238) were eligible for vaccination in Chad and 47% (225/483) in Malawi. Among eligible children, 51% (99/195) in Chad, and 66% (149/225) in Malawi had one or more MOV on the survey date. During non-vaccination visits, 77% (24/31) of children eligible for vaccination in Chad and 92% (119/129) in Malawi had a MOV compared to 46% (75/164) and 31% (30/96) during vaccination visits, respectively. Among health workers, 92% in Chad and 88% in Malawi were unable to correctly identify valid contraindications for vaccination. CONCLUSION: The new MOV tool was able to characterize the type and potential causes of MOV. In both countries, the findings of the assessments point to two major barriers to full vaccination of eligible children-a lack of coordination between vaccination and curative health services and incomplete vaccination during vaccination visits. National immunization programs should explore tailored efforts to improve health worker practices and to increase vaccine delivery by making better use of existing health service contacts.

BACKGROUND: Rotavirus vaccination reduces childhood hospitalization in Africa, but cost-effectiveness has not been determined using real-world effectiveness and costing data. We sought to determine monovalent rotavirus vaccine cost-effectiveness in Malawi, one of Africa's poorest countries and the first Gavi-eligible country to report disease reduction following introduction in 2012. METHODS: This was a prospective cohort study of children with acute gastroenteritis at a rural primary health center, a rural first referral-level hospital and an urban regional referral hospital in Malawi. For each participant we itemized household costs of illness and direct medical expenditures incurred. We also collected Ministry of Health vaccine implementation costs. Using a standard tool (TRIVAC), we derived cost-effectiveness. RESULTS: Between 1 January 2013 and 21 November 2014, we recruited 530 children aged <5 years with gastroenteritis. Costs did not differ by rotavirus test result, but were significantly higher for admitted children and those with increased severity on Vesikari scale. Adding rotavirus vaccine to the national schedule costs Malawi $0.42 per dose in system costs. Vaccine copayment is an additional $0.20. Over 20 years, the vaccine program will avert 1 026 000 cases of rotavirus gastroenteritis, 78 000 inpatient admissions, 4300 deaths, and 136 000 disability-adjusted-life-years (DALYs). For this year's birth cohort, it will avert 54 000 cases of rotavirus and 281 deaths in children aged <5 years. The program will cost $10.5 million and save $8.0 million in averted healthcare costs. Societal cost per DALY averted was $10, and the cost per rotavirus case averted was $1. CONCLUSIONS: Gastroenteritis causes substantial economic burden to Malawi. The rotavirus vaccine program is highly cost-effective. Together with the demonstrated impact of rotavirus vaccine in reducing population hospitalization burden, its cost-effectiveness makes a strong argument for widespread utilization in other low-income, high-burden settings.

While HIV prevention research conducted among adolescent populations may encounter parental resistance, the active engagement of parents from inception to trial completion may alleviate opposition. In preparation for implementing a large randomised controlled trial (RCT) examining the efficacy of a behavioural intervention targeting adolescent sexual risk behaviours, a formative evaluation was undertaken to assess parental reactions to the proposed trial. Six focus groups were conducted with parents of adolescents (aged 13-17) from rural, peri-urban and urban junior secondary schools in Botswana. Focus groups explored comprehension and acceptability among parents of the forthcoming trial including HSV-2 testing, the return of results to the adolescent (not the parent), trial information materials and the parental consent process. Parents welcomed the study and understood and accepted its moral and ethical considerations. Their reactions regarding return of HSV-2 results only to adolescents (not the parent) were mixed. Parents understood the consent process and most agreed to consent, while indicating their desire to remain informed and involved throughout the RCT. The focus group discussions (FGDs) provided valuable information and insights that helped strengthen the study. As a result of parents' feedback, counselling procedures were strengthened and direct linkages to local services and care were made. Informational materials were revised to increase clarity, and materials and procedures were developed to encourage and support parental involvement and parent-child dialogue. Ultimately, parental feedback led to a decision by the Government of Botswana to allow parents to access their child's HSV-2 test results.

BACKGROUND: Repeat national household surveys suggest highly variable malaria transmission and increasing coverage of high-impact malaria interventions throughout Zambia. Many areas of very low malaria transmission, especially across southern and central regions, are driving efforts towards sub-national elimination. CASE DESCRIPTION: Reactive case detection (RCD) is conducted in Southern Province and urban areas of Lusaka in connection with confirmed incident malaria cases presenting to a community health worker (CHW) or clinic and suspected of being the result of local transmission. CHWs travel to the household of the incident malaria case and screen individuals living in adjacent houses in urban Lusaka and within 140 m in Southern Province for malaria infection using a rapid diagnostic test, treating those testing positive with artemether-lumefantrine. DISCUSSION: Reactive case detection improves access to health care and increases the capacity for the health system to identify malaria infections. The system is useful for targeting malaria interventions, and was instrumental for guiding focal indoor residual spraying in Lusaka during the 2014/2015 spray season. Variations to maximize impact of the current RCD protocol are being considered, including the use of anti-malarials with a longer lasting, post-treatment prophylaxis. CONCLUSION: The RCD system in Zambia is one example of a malaria elimination surveillance system which has increased access to health care within rural communities while leveraging community members to build malaria surveillance capacity.

BACKGROUND: Accurate and timely malaria data are crucial to monitor the progress towards and attainment of elimination. Lusaka, the capital city of Zambia, has reported very low malaria prevalence in Malaria Indicator Surveys. Issues of low malaria testing rates, high numbers of unconfirmed malaria cases and over consumption of anti-malarials were common at clinics within Lusaka, however. The Government of Zambia (GRZ) and its partners sought to address these issues through an enhanced surveillance and feedback programme at clinic level. METHODS: The enhanced malaria surveillance programme began in 2011 to verify trends in reported malaria, as well as to implement a data feedback loop to improve data uptake, use, and quality. A process of monthly data collection and provision of feedback was implemented within all GRZ health clinics in Lusaka District. During clinic visits, clinic registers were accessed to record the number of reported malaria cases, malaria test positivity rate, malaria testing rate, and proportion of total suspected malaria that was confirmed with a diagnostic test. RESULTS AND DISCUSSION: Following the enhanced surveillance programme, the odds of receiving a diagnostic test for a suspected malaria case increased (OR = 1.54, 95 % CI = 0.96-2.49) followed by an upward monthly trend (OR = 1.05, 95 % CI = 1.01-1.09). The odds of a reported malaria case being diagnostically confirmed also increased monthly (1.09, 95 % CI 1.04-1.15). After an initial 140 % increase (95 % CI = 91-183 %), costs fell by 11 % each month (95 % CI = 5.7-10.9 %). Although the mean testing rate increased from 18.9 to 64.4 % over the time period, the proportion of reported malaria unconfirmed by diagnostic remained high at 76 %. CONCLUSIONS: Enhanced surveillance and implementation of a data feedback loop have substantially increased malaria testing rates and decreased the number of unconfirmed malaria cases and courses of ACT consumed in Lusaka District within just two years. Continued support of enhanced surveillance in Lusaka as well as national scale-up of the system is recommended to reinforce good case management and to ensure timely, reliable data are available to guide targeting of limited malaria prevention and control resources in Zambia.

The HIV prevalence rate among pregnant women is 37% in Botswana. According to UNICEF (2011), maternal and under-5 mortality rates in Botswana were 160 per 100000 live births and 26 per 1000 live births, respectively. Therefore, this study sought to identify the effects of ongoing clinic audits of the prevention of mother-to-child transmission of HIV (PMTCT) in Francistown, Botswana for the period 2008–2012. | Methods: | Existing data for all women attending antenatal and postnatal clinics were collected and collated manually from monthly from clinic PMTCT registers. | Results: | There were 19 720 new antenatal clinic visits between 2008 and 2012 with an HIV prevalence of 35% among the women. Mother-to-child transmission of HIV decreased from 3% in 2008 to 1% in 2012. The decrease was due, in part, to the introduction of triple antiretroviral prophylaxis/antiretroviral therapy (TAP/ARV) (PMTCT Option B) in 2011. | Conclusions: | Audit results over a 5-year period showed a steady improvement in the cascade of PMTCT interventions. Clinic audits should be implemented nationally to reduce maternal and under-5 mortality.

BACKGROUND: In Botswana, the prevention of mother-to-child transmission (PMTCT) programme has succeeded in reducing rates of transmission of HIV from mother to child since the start of the national antiretroviral (ARV) programme in 2002. METHODS: Data on PMTCT interventions for women who delivered at Nyangabgwe Referral Hospital (NRH), the second largest hospital in Botswana, from 2003 to 2012 were collected from maternity registers. RESULTS: Of 46,354 women, 33% were HIV-positive, 58% were HIV-negative, and 9% were not tested. The percentage of women with a known HIV status increased from 50% in 2003 to 97% in 2012. PMTCT uptake for women on any ARV increased from 61% in 2003 to 86% in 2012. Infants given azidothymidine (AZT) and nevirapine prophylaxis increased from 61% to 85%. CONCLUSIONS: Review of maternity registers demonstrated improvement of multiple PMTCT interventions at NRH. This is a useful approach for monitoring programme quality and guiding strategic planning.

The 2011 prevalence of human immunodeficiency virus (HIV) among pregnant women in Botswana was 30.4%. High coverage rates of HIV testing and antiretroviral prophylaxis have reduced the rate of mother-to-child transmission of HIV in Botswana from as high as 40% with no prophylaxis to <4% in 2011. In June 2005, the national Early Infant Diagnosis (EID) Program began testing HIV-exposed infants (i.e., those born to HIV-infected mothers) for HIV using polymerase chain reaction (PCR) at 6 weeks postpartum. During 2005-2012, follow-up of all HIV-infected infants diagnosed in all 13 postnatal care facilities in Francistown, Botswana, was conducted to ascertain patient outcomes. A total of 202 infants were diagnosed with HIV. As of September 2013, 82 (41%) children were alive and on antiretroviral therapy (ART), 79 (39%) had died, and 41 (20%) were either lost to follow-up, had transferred, or their mothers declined ART. Despite success in preventing mother-to-child transmission in Botswana, results of the EID program highlight the need for early diagnosis of HIV-infected infants, prompt initiation of ART, and retention in care.

We examined CD4 cell count and plasma viral load patterns among Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2 study) participants who seroconverted, comparing participants assigned to receive tenofovir/emtricitabine with participants assigned to receive placebo. We also evaluated for antiretroviral drug resistance among the breakthrough HIV infections. Among nine seroconverters assigned to tenofovir/emtricitabine and 24 to placebo, there were no significant differences in their CD4 cell count or viral load profiles over time. Of the four participants who seroconverted on-study while receiving tenofovir/emtricitabine, none became infected as a result of drug-resistant HIV; moreover, no resistance mutations emerged following seroconversion.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669 .).

BACKGROUND: To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. METHODS: Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. RESULTS: Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). CONCLUSIONS: Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.