Spatial Epidemiologic Trends and Hotspots of Leishmaniasis, Sri Lanka, 2001-2018.

Leishmaniasis, a neglected tropical disease, is on the decline in South Asia. However, cases of cutaneous leishmaniasis have risen in Sri Lanka since 2001, and the lack of in-depth research on its epidemiologic characteristics hampers control efforts. We analyzed data collected from patients with cutaneous leishmaniasis in Sri Lanka during 2001-2018 to study temporal and geographic trends and identify and monitor disease hotspots. We noted a progression in case rates, including a sharp rise in 2018, showing temporal expansion of disease-prevalent areas and 2 persistent hotspots. The northern hotspot shifted and shrank over time, but the southern hotspot progressively expanded and remained spatially static. In addition, we noted regional incidence differences for age and sex. We provide evidence of temporally progressive and spatially expanding incidence of leishmaniasis in Sri Lanka with distinct geographic patterns and disease hotspots, signaling an urgent need for effective disease control interventions.

Poliovirus Type 2 Seroprevalence Following Full- or Fractional-Dose Inactivated Poliovirus Vaccine in the Period After Sabin Type 2 Withdrawal in Sri Lanka.

BACKGROUND: In July 2016, Sri Lanka replaced 1 intramuscular dose of inactivated poliovirus vaccine (IPV) with 2 doses of intradermal fractional-dose IPV (fIPV) in its routine immunization schedule. We carried out a survey of seroprevalence of antipolio antibodies in children who received 2 fIPV doses and compared it with those who received 1 full IPV dose. METHODS: Children born between March and December 2016 were randomly selected from 3 Sri Lankan districts (Colombo, Badulla, and Anuradhapura). Serum samples were collected and tested for presence of neutralizing antibodies to poliovirus types 1, 2, and 3. RESULTS: Seroprevalence of antipolio antibodies was 100% in all districts for poliovirus type 1 and poliovirus type 3; it ranged between 90% and 93% for poliovirus type 2 (PV2) in children who received 1 full IPV dose and between 78% and 100% in those receiving 2 fIPV doses (P = .22). The median reciprocal titers of anti-PV2 antibodies were similar in children who received full-dose IPV and those who received fIPV (1:64 vs 1:45, respectively; P = .11). CONCLUSIONS: Our study demonstrated not only that Sri Lanka succeeded in maintaining very high primary immunization coverage also but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application. The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV.

Prevalence and risk factors for impaired kidney function in the district of Anuradhapura, Sri Lanka: a cross-sectional population-representative survey in those at risk of chronic kidney disease of unknown aetiology.

BACKGROUND: Over the last 20 years there have been reports of a form of chronic kidney disease of unknown cause (CKDu) affecting rural communities in the North Central Province of Sri Lanka. Valid prevalence estimates, using a standardised methodology, are needed to assess the burden of disease, assess secular trends, and perform international comparisons. METHODS: We conducted a cross-sectional representative population survey in five study areas with different expected prevalences of CKDu. We used a proxy definition of CKDu involving a single measure of impaired kidney function (eGFR< 60 mL/min/1.7m2, using the CKD-Epi formula) in the absence of hypertension, diabetes or heavy proteinuria. RESULTS: A total of 4803 participants (88.7%) took part in the study and 202 (6.0%; 95% CI 5.2-6.8) had a low eGFR in the absence of hypertension, diabetes and heavy proteinuria and hence met the criteria for proxy CKDu. The proportion of males (11.2%; 95% CI 9.2-13.1) were triple than the females (3.7%; 95% CI 2.9-4.5). Advancing age and history of CKD among parents or siblings were risk factors for low GFR among both males and females while smoking was found to be a risk factor among males. CONCLUSIONS: These data, collected using a standardised methodology demonstrate a high prevalence of impaired kidney function, not due to known causes of kidney disease, in the selected study areas of the Anuradhapura district of Sri Lanka. The aetiology of CKDu in Sri Lanka remains unclear and there is a need for longitudinal studies to describe the natural history and to better characterise risk factors for the decline in kidney function.

Boosting of Mucosal Immunity After Fractional-Dose Inactivated Poliovirus Vaccine.

Background: Inactivated poliovirus vaccine (IPV) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine (OPV). We assessed whether fractional-dose IPV (fIPV, 1/5th of full dose) administered intradermally also boosts mucosal immunity. Methods: Children 10-12 years old were enrolled in Sri Lanka and randomized to receive one dose IPV, fIPV, or no IPV vaccine. One month later, they received OPV challenge. Blood was collected at enrolment and before challenge; stool was collected at 3, 7, and 14 days post-challenge. Sera were analysed for presence of poliovirus neutralizing antibodies; stool was analysed for poliovirus. Results: We analysed 304/309 (98%) enrolled subjects. There were 16/97 (16%), 9/99 (9%), and 72/95 (76%) subjects excreting poliovirus after challenge in the IPV, fIPV and "No IPV Vaccine" study arms, respectively (P < .001 for comparison of IPV [or fIPV] vs "No IPV Vaccine"; P = .1 for comparisons of fIPV vs IPV). Relative decrease in excretion prevalence was 80% and 88% to IPV and fIPV, respectively, compared with the "No IPV Vaccine" control arm. Conclusions: Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV. This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage. Clinical trials registration: Australia New Zealand Clinical Trial Registry ACTRN12616000124437p.

Human papillomavirus (HPV) vaccination program in Sri Lanka: Ongoing costs and operational context of a routinized program.

Existing evidence on the cost of human papillomavirus (HPV) vaccination programs has focused on pilot and demonstration projects or initial introductions, which resulted in a perceived high cost. We aimed to study the ongoing cost and operational context of an established HPV vaccination program in Sri Lanka. We conducted a retrospective operational research and microcosting study focusing on 2019. We collected data from 30 divisional health units, 10 districts, and the central level. We then evaluated financial and economic costs, reported by level of the health system, program activity, cost types, and per dose delivered. In 2019, Sri Lanka delivered a total of 314,815 doses of HPV vaccine. In our study sample, 95 % of the HPV vaccination sessions took place at schools, with peaks of delivery in February-March and September-October. The weighted mean financial cost per dose delivered was $0.27 (95 % confidence interval [CI]: $0.15-$0.39) and the economic cost per dose was $3.88 (95 % CI: $2.67-$5.10), excluding the cost of vaccines and supplies. Most of the cost was borne by the divisional health unit level. Service delivery and social mobilization were major contributors to overall costs at the divisional health unit level, and vaccine collection or distribution and storage were the most costly activities at the district and central levels. Cost drivers included the opportunity cost of health worker and non-health worker time at the divisional health unit level and capital costs for vehicles and equipment, along with fuel, maintenance, and energy, at the district and central levels. This study provides new evidence on the cost and cost drivers of a routinized HPV vaccination program. Results can be used for financial planning purposes in Sri Lanka and may inform other countries as they consider use of HPV vaccines.

Population-Level Risk Factors Related to Measles Case Fatality: A Conceptual Framework Based on Expert Consultation and Literature Review.

A better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators. Using expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We conducted a literature review by searching PubMed on 31 October 2021 to determine the scope of evidence for the expert-identified indicators. Studies were included if they contained evidence of an association between an indicator and CFR and were excluded if they were from non-human studies or reported non-original data. Included studies were assessed for study quality. Expert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators (average household size, educational attainment, first- and second-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, level of health care available, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, vitamin A treatment, and general malnutrition) and only non-significant associations for five indicators (antibiotic use for measles-related pneumonia, malaria prevalence, percent living in urban settings, pneumococcal conjugate vaccination coverage, vitamin A supplementation). Our study used expert consultation and a literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future measles CFR estimations.

Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries.

INTRODUCTION: There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. METHODS: Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). RESULTS: Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. CONCLUSION: HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

Use of existing systematic reviews for the development of evidence-based vaccination recommendations: Guidance from the SYSVAC expert panel.

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Incidence of hepatitis-C among HIV infected men who have sex with men (MSM) attending a sexual health service: a cohort study.

BACKGROUND: We aimed to determine the incidence of Hepatitis C (HCV) infection among HIV-infected men who have sex with men (MSM) attending a Sexual Health Centre. METHODS: A retrospective cohort study was carried out among HIV-infected MSM seen at least once between February 2002 and March 2010. The analysis was restricted to MSM who had had a negative HCV antibody test at least 6 months after their diagnosis for HIV. Duration of follow up was taken from the date of HIV diagnosis to the first positive or last negative HCV antibody test. RESULTS: During the time 1445 HIV-infected men attended the clinic of whom 1065 (74%) were MSM. Of these, 869 (82%) were tested for HCV at any time after HIV diagnosis. Of these 869, 69% (620) tested HCV negative at least 6 months after their HIV diagnosis. These 620 men had a mean age of 34 years (range 17-72) at HIV diagnosis and a total of 4,359 person years (PY) of follow up. There were 40 incident cases of HCV, of which 16 were in injecting drug users (IDU) and 24 in non-IDU. The overall incidence of HCV among HIV-infected MSM was 0.9/100 PY (95% CI 0.6-1.2). The incidence among HIV-infected IDU was 4.7/100 PY (95% CI 2.7-7.5) while the incidence among HIV-infected non-IDU was 0.6/100 PY (95% CI 0.4-0.8) (hazard ratio of 8.7 and 95% CI 4.6-16.6, P < 0.001).The majority (78%) were tested for HCV because they developed abnormal liver transaminases (n = 31) or hepatitis symptoms (n = 2), while others (n = 7) were identified through routine HCV testing. CONCLUSION: A considerable proportion of HIV-positive MSM who did not inject drugs contracted HCV, presumably via sexual transmission and the main trigger for investigation was abnormal liver transaminases.