Evaluation of the Acute flaccid paralysis surveillance indicators in Zambia from 2015-2021: a retrospective analysis.

BACKGROUND: The resurgence of poliovirus infection in previously polio free regions and countries calls for renewed commitment to the global polio eradication efforts including strengthening of Acute Flaccid Paralysis (AFP) surveillance systems. Zambia is one of the countries substantially at risk for the importation of poliovirus infection from neighbouring countries including Malawi, Mozambique, and Democratic Republic of the Congo (DRC). This study describes a seven-year AFP surveillance, assesses the surveillance indicators, and highlights areas for improvement. METHODS: We conducted retrospective analysis of the routinely collected AFP surveillance data from January 2015 to December 2022. The AFP surveillance indicators performance was assessed using the World Health Organisation's recommended minimum AFP surveillance indicators performance. RESULTS: Cumulatively, a total of 1715 AFP cases were reported over the study period. More than half, 891 (52%) of reported cases were aged < 5 years with 917 (53.5%) of males. More than half, 1186 (69.2%) had fever at onset, 718 (41.9%) had asymmetric paralysis and 1164 (67.9%) had their paralysis progressed within 3 days of onset. The non-polio AFP rate ranges from 3.4 to 6.4 per 100,000 children < 15 years old and stool adequacy ranging from 70.9% to 90.2% indicating sensitive surveillance with late detection of cases. The percentage of cases with early stool collection, timely transportation was above the World Health Organisation (WHO) minimum of 80% but with declining proportion of stools arriving in the laboratory in optimal condition. Completeness of 60-days follow-up evaluation was suboptimal ranging from 0.9% to 28.2%. CONCLUSION: The AFP surveillance system in Zambia is doing well. However, additional efforts are needed to improve early detection of cases; stool sample collection, transportation and monitoring to ensure arrival in good condition in the laboratory; and improve 60-days follow-up evaluation for evidenced-based classification of inadequate AFP cases and proper care.

The Burden of Invasive Bacterial Disease and the Impact of 10-Valent Pneumococcal Conjugate Vaccine in Children <5 years hospitalized for Meningitis in Lusaka, Zambia, 2010-2019.

BACKGROUND: Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010-2012) and post- (2014-2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia. METHODS: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction. RESULTS: During the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W. CONCLUSIONS: There was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy.

Declines in Pneumonia and Meningitis Hospitalizations in Children Under 5 Years of Age After Introduction of 10-Valent Pneumococcal Conjugate Vaccine in Zambia, 2010-2016.

BACKGROUND: Pneumococcus is a leading cause of pneumonia and meningitis. Zambia introduced a 10-valent pneumococcal conjugate vaccine (PCV10) in July 2013 using a 3-dose primary series at ages 6, 10, and 14 weeks with no booster. We evaluated the impact of PCV10 on meningitis and pneumonia hospitalizations. METHODS: Using hospitalization data from first-level care hospitals, available at the Ministry of Health, and from the largest pediatric referral hospital in Lusaka, we identified children aged <5 years who were hospitalized with pneumonia or meningitis from January 2010-December 2016. We used time-series analyses to measure the effect of PCV10 on monthly case counts by outcome and age group (<1 year, 1-4 years), accounting for seasonality. We defined the pre- and post-PCV10 periods as January 2010-June 2013 and July 2014-December 2016, respectively. RESULTS: At first-level care hospitals, pneumonia and meningitis hospitalizations among children aged <5 years accounted for 108 884 and 1742 admissions in the 42 months pre-PCV10, respectively, and 44 715 and 646 admissions in the 30 months post-PCV10, respectively. Pneumonia hospitalizations declined by 37.8% (95% confidence interval [CI] 21.4-50.3%) and 28.8% (95% CI 17.7-38.7%) among children aged <1 year and 1-4 years, respectively, while meningitis hospitalizations declined by 72.1% (95% CI 63.2-79.0%) and 61.6% (95% CI 50.4-70.8%), respectively, in these age groups. In contrast, at the referral hospital, pneumonia hospitalizations remained stable and a smaller but significant decline in meningitis was observed among children aged 1-4 years (39.3%, 95% CI 16.2-57.5%). CONCLUSIONS: PCV10 introduction was associated with declines in meningitis and pneumonia hospitalizations in Zambia, especially in first-level care hospitals.

Multicountry Analysis of Spectrum of Clinical Manifestations of Children <5 Years of Age Hospitalized with Diarrhea.

After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children <5 years of age. Our study in 33 hospitals in 7 countries found acute gastroenteritis accounted for most (84%) reported hospitalizations of children with diarrhea. Bloody and persistent diarrhea each accounted for <1%.

Impact of Rotavirus Vaccination on Diarrheal Hospitalizations in Children Aged <5 Years in Lusaka, Zambia.

BACKGROUND: Monovalent rotavirus vaccine was introduced in the routine public health immunization program in Lusaka, Zambia, in January 2012 and was rolled out countrywide in November 2013. We examined the effect of rotavirus vaccination on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE at a large referral hospital in Lusaka. METHODS: Data were derived from ongoing hospital-based AGE surveillance from January 2009 to December 2014. Pre-rotavirus vaccine introduction (2009-2011) and post-rotavirus vaccine introduction (2013-2014) periods were compared for annual changes in hospitalizations for AGE and rotavirus; 2012 was excluded as a transition year. Hospital administrative discharge data were used to compare trends in all-cause diarrhea discharges and in-hospital diarrhea deaths captured by HIMS pre- and post-rotavirus vaccine introduction. RESULTS: Between January 2009 and December 2014, 5937 children <5 years of age presenting with AGE had their stools collected and tested for rotavirus by enzyme immunoassay. The rotavirus positivity rate declined from 40.1% (449/1121) in prevaccine years to 30.2% (250/828;P< .001) in 2013 and 24.7% (157/635;P< .001) in 2014. The greatest reduction was noted in infants, with the rotavirus positivity rate in this age group declining from 40.9% in prevaccine years to 34.0% (P= .009) in 2013 and 26.2% (P< .001) in 2014. Following rotavirus vaccine introduction, seasonal peaks of rotavirus and all-cause AGE were dwarfed. From HIMS data, compared to the prevaccine era, reductions of 18%-29% in all-cause diarrhea hospitalizations and 27%-33% in-hospital diarrhea deaths among children <1 year of age were observed in 2013 and 2014. CONCLUSIONS: We observed a significant reduction in AGE-associated in-hospital morbidity and mortality following rotavirus vaccine introduction. The greatest reduction was seen in infants <1 year who accounted for 84.4% of rotavirus hospitalizations prior to vaccine introduction.

Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts.

Euvichol-plus vaccine campaign coverage during the 2017/2018 cholera outbreak in Lusaka district, Zambia: a cross-sectional descriptive study.

OBJECTIVE: To determine the coverage for the oral cholera vaccine (OCV) campaign conducted during the 2017/2018 cholera outbreak in Lusaka, Zambia. STUDY DESIGN: A descriptive cross-sectional study employing survey method conducted among 1691 respondents from 369 households following the second round of the 2018 OCV campaign. STUDY SETTING: Four primary healthcare facilities and their catchment areas in Lusaka city (Kanyama, Chawama, Chipata and Matero subdistricts). PARTICIPANTS: A total of 1691 respondents 12 months and older sampled from 369 households where the campaign was conducted. A satellite map-based sampling technique was used to randomly select households. DATA MANAGEMENT AND ANALYSIS: A pretested electronic questionnaire uploaded on an electronic tablet (ODK V.1.12.2) was used for data collection. Descriptive statistics were computed to summarise respondents' characteristics and OCV coverage per dose. Bivariate analysis (χ2 test) was conducted to stratify OCV coverage according to age and sex for each round (p<0.05). RESULTS: The overall coverage for the first, second and two doses were 81.3% (95% CI 79.24% to 83.36%), 72.1% (95% CI 69.58% to 74.62%) and 66% (95% CI 63.22% to 68.78%), respectively. The drop-out rate was 18.8% (95% CI 14.51% to 23.09%). Of the 81.3% who received the first dose, 58.8% were female. Among those who received the second dose, the majority (61.0%) were females aged between 5 and 14 years (42.6%) and 15 and 35 years (27.7%). Only 15.5% of the participants aged between 36 and 65 and 2.5% among those aged above 65 years received the second dose. CONCLUSION: These findings confirm the 2018 OCV campaign coverage and highlight the need for follow-up surveys to validate administrative coverage estimates using population-based methods. Reliance on health facility data alone may mask low coverage and prevent measures to improve programming. Future public health interventions should consider sociodemographic factors in order to achieve optimal vaccine coverage.

Effectiveness of two doses of Euvichol-plus oral cholera vaccine in response to the 2017/2018 outbreak: a matched case-control study in Lusaka, Zambia.

INTRODUCTION: Zambia experienced a major cholera outbreak in 2017-2018, with more than 5905 cases reported countrywide, predominantly from the peri-urban slums of Lusaka city. The WHO recommends the use of oral cholera vaccines (OCVs) together with traditional control measures, including health promotion, provision of safe water and improving sanitation, in cholera endemic areas and during cholera outbreaks. In response to this outbreak, the Zambian government implemented the OVC campaign and administered the Euvichol-plus vaccine in the high-risk subdistricts of Lusaka. Although OCVs have been shown to be effective in preventing cholera infection in cholera endemic and outbreak settings, the effectiveness of the Euvichol-plus vaccine has not yet been evaluated in Zambia. This study aimed to determine the effectiveness of two doses of OCV administered during the 2017/2018 vaccination campaign. METHODS: We conducted a matched case-control study involving 79 cases and 316 controls following the mass vaccination campaign in the four subdistricts of Lusaka (Chawama, Chipata, Kanyama and Matero). Matching of controls was based on the place of residence, age and sex. Conditional logistic regression was used for analysis. Adjusted OR (AOR), 95% CI and vaccine effectiveness (1-AOR) for two doses of Euvichol-plus vaccine and any dose were estimated (p<0.05). RESULTS: The AOR vaccine effectiveness for two doses of Euvichol-plus OCV was 81.0% (95% CI 66.0% to 78.0%; p<0.01). Secondary analysis showed that vaccine effectiveness for any dose was 74.0% (95% CI 50.0% to 86.0%; p<0.01). CONCLUSION: These findings show that two doses of Euvichol-plus OCV are effective in a cholera outbreak setting in Lusaka, Zambia. The findings also indicate that two doses are more effective than a single dose and thus support the use of two doses of the vaccine as part of an integrated intervention to cholera control during outbreaks.

Age distribution and mortality associated with intussusception in children under two years of age in nine sentinel surveillance hospitals in Zambia, 2007-2018.

INTRODUCTION: recipients of monovalent rotavirus vaccine have a low risk of developing intussusception (IS) in high- to medium-high-income countries. In sub-Saharan Africa, Zambia included, this risk of IS has not been assessed. Two-dose monovalent rotavirus vaccine, introduced in Zambia in 2012 in the capital of Lusaka, and rolled out countrywide in 2013, is administered at 6 and 10 weeks of age with no catch-up dose. Active IS surveillance monitoring in children < 2 years has been ongoing in Zambia since July 2009 and additional retrospective review was conducted from 2007- June 2009. METHODS: retrospective review (January 2007-June 2009) and prospective (July 2009-December 2018) IS surveillance was conducted at nine hospitals and four large paediatric hospital departments in Zambia, respectively. Demographic and clinical data were collected from medical folder abstraction and supplemented by parental interview during prospective surveillance. RESULTS: a total of 248 children < 2 years with IS were identified; 57.3% were male. Most cases with IS were infants (85.5%). IS admissions remained stable during the surveillance period with no seasonality pattern although an increase in cases occurred between August and October, hot dry season. The median time from symptom onset to presentation for treatment was 2 days and 63.6% (154/242) of IS diagnoses were made during surgery. The bowel resection rate was 46.6%. A high CFR of 23.3% was observed. CONCLUSION: the number of intussusception cases in Zambia was relatively small and remained stable over the 12-year study period. However, a high CFR was observed among cases.

Delayed second dose of oral cholera vaccine administered before high-risk period for cholera transmission: Cholera control strategy in Lusaka, 2016.

BACKGROUND: In April 2016, an emergency vaccination campaign using one dose of Oral Cholera Vaccine (OCV) was organized in response to a cholera outbreak that started in Lusaka in February 2016. In December 2016, a second round of vaccination was conducted, with the objective of increasing the duration of protection, before the high-risk period for cholera transmission. We assessed vaccination coverage for the first and second rounds of the OCV campaign. METHODS: Vaccination coverage was estimated after each round from a sample selected from targeted-areas for vaccination using a cross-sectional survey in to establish the vaccination status of the individuals recruited. The study population included all individuals older than 12 months residing in the areas targeted for vaccination. We interviewed 505 randomly selected individuals after the first round and 442 after the second round. Vaccination status was ascertained either by vaccination card or verbal reporting. Households were selected using spatial random sampling. RESULTS: The vaccination coverage with two doses was 58.1% (25/43; 95%CI: 42.1-72.9) in children 1-5 years old, 59.5% (69/116; 95%CI: 49.9-68.5) in children 5-15 years old and 19.9% (56/281; 95%CI: 15.4-25.1) in adults above 15 years old. The overall dropout rate was 10.9% (95%CI: 8.1-14.1). Overall, 69.9% (n = 309/442; 95%CI: 65.4-74.1) reported to have received at least one OCV dose. CONCLUSIONS: The areas at highest risk of suffering cholera outbreaks were targeted for vaccination obtaining relatively high vaccine coverage after each round. However, the long delay between doses in areas subject to considerable population movement resulted in many individuals receiving only one OCV dose. Additional vaccination campaigns may be required to sustain protection over time in case of persistence of risk. Further evidence is needed to establish a maximum optimal interval time of a delayed second dose and variations in different settings.

Diversity of rotavirus strains circulating in children under five years of age who presented with acute gastroenteritis before and after rotavirus vaccine introduction, University Teaching Hospital, Lusaka, Zambia, 2008-2015.

BACKGROUND: Following the introduction of rotavirus vaccine into the routine immunization schedule, the burden of rotavirus disease has significantly reduced in Zambia. Although rotavirus vaccines appear to confer good cross-protection against both vaccine and non-vaccine strains, concerns about strain replacement following vaccine implementation remain. We describe the diversity of the circulating rotavirus strains before and after the Rotarix® vaccine was introduced in Lusaka from January 2012. METHODS: Under five children were enrolled through active surveillance at University Teaching Hospital using a standardized WHO case investigation form. Stool samples were collected from children who presented with ≥3 loose stool in 24 h and were admitted to the hospital for acute gastroenteritis as a primary illness. Samples were tested for group A rotavirus antigen enzyme-linked immunosorbent assay. Randomly selected rotavirus positive samples were analysed by reverse transcription polymerase chain reaction for G and P genotyping and and Nucleotide sequencing was used to confirm some mixed infections. RESULTS: A total of 4150 cases were enrolled and stool samples were collected from 4066 (98%) children between 2008 and 2011, before the vaccine was introduced. Rotavirus antigen was detected in 1561/4066 (38%). After vaccine introduction (2012 to 2015), 3168 cases were enrolled, 3092 (98%) samples were collected, and 977/3092 (32%) were positive for rotavirus. The most common G and P genotype combinations before vaccine introduction were G1P[8] (49%) in 2008; G12P[6] (24%) and G9P[8] (22%) in 2009; mixed rotavirus infections (32%) and G9P[8] (20%) in 2010, and G1P[6] (46%), G9P[6] (16%) and mixed infections (20%) in 2011. The predominant strains after vaccine introduction were G1P[8] (25%), G2P[4] (28%) and G2P[6] (23%) in 2012; G2P[4] (36%) and G2P[6] (44%) in 2013; G1P[8] (43%), G2P[4] (9%), and G2P[6] (24%) in 2014, while G2P[4] (54%) and G2P[6] (20%) continued to circulate in 2015. CONCLUSION: These continual changes in the predominant strains suggest natural secular variation in circulating rotavirus strains post-vaccine introduction. These findings highlight the need for ongoing surveillance to continue monitoring how vaccine use affects strain evolution over a longer period of time and assess any normal seasonal fluctuations of the rotavirus strains.

Intussusception incidence rates in 9 Zambian hospitals, 2007-2011: prerotavirus vaccine introduction.

BACKGROUND: Intussusception, a rare adverse event associated with rotavirus vaccines in some settings, is a common cause of intestinal obstruction in infants and toddlers globally with a peak age of 4-6 months. This age group may overlap with the extended age of administering rotavirus vaccine. METHODS: A retrospective (January 2007 to June 2009) and prospective (July 2009 to June 2012) survey was conducted in 9 Zambian hospitals. Children between 0 and 24 months who were operated on for intestinal obstruction/intussusception were identified in theatre log books. In the latter part of the survey, patients were recruited prospectively. Demographic, clinical and surgical data from hospital files were collected for each patient. RESULTS: One-hundred and five children were identified to have undergone surgery for intussusceptions. Many were boys 57.6% (57/99). Of those with complete data, intussusception was common in infants 86.9% (86/99) and many children (68.0%) were between 3 and 8 months of age with a peak age of 5-6 months. Lusaka had the highest number of children with intussusception with an estimated annual incidence rate of 12/100,000 in children <2 years of age. The overall case fatality rate was very high 33.7% (31/92). CONCLUSION: Intussusception was common in infants with a peak age of 5-6 months, and of particular concern is the group of 2-4 months the age of rotavirus vaccination. The estimated incidence rate of 12/100,000 is an underestimate as many cases may not present for care. The high case fatality rate of 33.7% is due to both delayed presentation and diagnosis in hospital.