Passive case detection for canine visceral leishmaniasis control in urban Brazil: Determinants of population uptake

Background In Brazil, the transmission of Leishmania infantum in urban settings is closely related to infection among dogs, with occasional transmission to humans. Serological screening of dogs for Leishmania spp. infection on requests of their owners (passive case detection) represents a frequent, but little studied, practice within the scope of Brazilian public health. This study identified factors associated with canine visceral leishmaniasis (CVL) diagnosis-seeking behavior of dog owners in Rondonópolis (236,000 inhabitants), a municipality in Central-Western Brazil where VL is endemic. Also, we evaluated the profile of dog owners and their animals screened on free demand. Methodology/Principal findings Using mixed effects negative binomial regression, we modelled the number of dogs screened for Leishmania infection on free demand per neighborhood from 2011 to 2016 as a function of time-dependent predictors (current or recent canine seropositivity and human VL incidence), distance to the screening site, and demographic variables. We assessed potential delays in the effect of time-dependent predictors on the outcome. Among 12,536 dogs screened for Leishmania infection, 64.2% were tested during serosurveys and 35.8% were tested on free demand. Of these, 63.9% were positive. Uptake of screening under free demand was strongly associated with higher levels of canine seropositivity in the neighborhood (current or recent) and decreasing distance to the screening site. A subsample of dog owners (n = 93) who sought CVL screening between 2016 and 2017 were interviewed in more detail. Owners with better socioeconomic status and dogs with apparent CVL clinical manifestations prevailed among them. Conclusions/Significance To support timely CVL management, passive case detection along with awareness activities aimed at dog owners should be encouraged in endemic areas. Screening sites should be prioritized in accessible zones, as well as in socio-economically disadvantage areas. In parallel, CVL active case detection should be continued as a surveillance tool to guide control actions.

Sri Lanka’s early success in the containment of COVID-19 through its rapid response: Clinical & epidemiological evidence from the initial case series

Background Despite the rising global burden, Sri Lanka reported a relatively low caseload and mortality (13 deaths as of 20 October 2020) for COVID-19. This warrants exploration of the clinical and epidemiological characteristics of the case series during the initial passive case detection phase in Sri Lanka, in order to understand the success in containment of the disease for more than nine months in the country through its initial early and rapid pandemic response. Methods A retrospective study was conducted using secondary data (hospital records and investigation reports) extracted from all laboratory-confirmed patients admitted to the three main state-sector hospitals in Sri Lanka from 11 March to 7 April 2020. Clinical outcomes were categorized as mild, severe and critical, as per the international classification. Kruskal-Wallis H, Mann Whitney U and Fisher’s exact tests compared differences between the variables. Results The case series comprised 146 live discharges and six deaths. Majority were males (63.2%); mean age of 40.9 (SD = 17.9); and symptomatic (72.4%). Sixty-one (40.1%) had co-morbidities, the commonest being diabetes (20.4%) and hypertension (17.8%). Mild (93.4%), severe (2.6%) and critical (4.0%) disease outcomes were noted. Disease severity was significantly higher with older age (p = 0.037), co-morbidities (p = 0.026); and higher white-cell (p = 0.045) and lymphocyte (p = 0.043) counts; but not with being symptomatic (p = 0.683). The commonest symptoms were fever (62.5%), dry cough (48.0%) and sore throat (26.9%). The median duration (IQR) was 3.0 (1.0–5.0) and 18.0 (15.0–29.5) days, respectively before and during hospitalization. Conclusions In contrast to high-risk countries, the younger age, milder disease and low mortality observed in local patients during the initial phase of the pandemic, reflect the early success in containment of the pandemic in Sri Lanka. However, once the disease becomes severe, the factors determining disease fatality remain the same as in other countries. This highlights the value of establishing strong public health systems and disease surveillance in a country, which could provide long-term effects on disease control.

Persistence and baseline determinants of seropositivity and reinfection rates in health care workers up to 12.5 months after COVID-19

We assessed the duration and baseline determinants of antibody responses to SARS-CoV-2 spike antigens and the occurrence of reinfections in a prospective cohort of 173 Spanish primary health care worker patients followed initially for 9 months and subsequently up to 12.5 months after COVID-19 symptoms onset. Seropositivity to SARS-CoV-2 spike and receptor-binding domain antigens up to 149–270 days was 92.49% (90.17% IgG, 76.3% IgA, 60.69% IgM). In a subset of 64 health care workers who had not yet been vaccinated by April 2021, seropositivity was 96.88% (95.31% IgG, 82.81% IgA) up to 322–379 days post symptoms onset. Four suspected reinfections were detected by passive case detection, two among seronegative individuals (5 and 7 months after the first episode), and one low antibody responder. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking, and occupation. Stable sustainment of IgG responses raises hope for long-lasting COVID-19 vaccine immunity.

The effectiveness of contact investigation among contacts of tuberculosis patients: a systematic review and meta-analysis

BackgroundWe aimed to evaluate the effectiveness of contact investigation in comparison to passive case-detection alone and estimated the yield of co-prevalent and incident tuberculosis (TB), and latent tuberculosis infection (LTBI) among contacts of patients with TB.MethodsA systematic search was undertaken of studies published between January 1, 2011 and October 1, 2019 in the English language. The proportion of contacts diagnosed with co-prevalent TB, incident TB and/or LTBI was estimated. Evaluation of the effectiveness of contact investigation included randomised trials, while the yield of contact investigation (co-prevalent and incident TB and LTBI) was assessed in non-randomised studies.ResultsData were extracted from 244 studies, of which 187 studies measured the proportion of contacts diagnosed with TB disease and 135 studies measured LTBI prevalence. Individual randomised trials demonstrated that contact investigation increased TB case notification (RR 2.5 [95% CI: 2.0–3.2]), TB case detection (OR 1.34 [95% CI: 0.43–4.24]) and decreased mortality (RR 0.6 [95% CI: 0.4–0.8]) and population TB prevalence (risk ratio 0.82 [95% CI: 0.64–1.04]).The overall pooled prevalence of TB was 3.6% (95% CI: 3.3–4.0%; I2=98.9%, 181 studies). The pooled prevalence of microbiologically-confirmed TB was 3.2% (95% CI: 2.6–3.7%; I2=99.5%, 106 studies). The pooled incidence of TB was highest in the first year after exposure to index patients (2.0%, 95% CI: 1.1–3.3%; I2=96.2%, 14 studies) and substantially lower five years after exposure to index patient (0.5%, 95% CI: 0.3–0.9%; 1 study). The pooled prevalence of LTBI among contacts was 42.4% (95% CI: 38.5–46.4%; I2=99.8%, 135 studies).Conclusions and RelevanceThis systematic review and meta-analysis found that contact investigation was effective in high-burden settings. The higher pooled prevalence estimates of microbiologically-confirmed TB compared to previous reviews suggests newer rapid molecular diagnostics contribute to increased case detection.

Persistence and baseline determinants of seropositivity and reinfection rates in health care workers up to 12.5 months after COVID-19

We assessed the duration and baseline determinants of antibody responses to SARS-CoV-2 spike antigens and the occurrence of reinfections in a prospective cohort of 173 Spanish primary health care worker patients followed up initially for nine months and subsequently up to 12.5 months after COVID-19 symptoms onset. Seropositivity to SARS-CoV-2 spike and receptor binding domain antigens up to 149-270 days was 92.49% (90.17% IgG, 76.3% IgA, 60.69% IgM). In a subset of 64 health care workers who had not yet been vaccinated by April 2021, seropositivity was 96.88% (95.31% IgG, 82.81% IgA) up to 322-379 days post symptoms onset. There were four suspected reinfections detected by passive case detection, two among seronegative individuals (five and seven months after the first episode), and one low antibody responder. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking and occupation. Stable sustainment of IgG responses raises hope for long-lasting COVID-19 vaccine immunity.

Performance of passive case detection for malaria surveillance: results from nine countries in Mesoamerica and the Dominican Republic

Background In malaria elimination settings, available metrics for malaria surveillance have been insufficient to measure the performance of passive case detection adequately. An indicator for malaria suspected cases with malaria test (MSCT) is proposed to measure the rate of testing on persons presenting to health facilities who satisfy the definition of a suspected malaria case. This metric does not rely on prior knowledge of fever prevalence, seasonality, or external denominators, and can be used to compare detection rates in suspected cases within and between countries, including across settings with different levels of transmission. Methods To compute the MSCT, an operational definition for suspected malaria cases was established, including clinical and epidemiological criteria. In general, suspected cases included: (1) persons with fever detected in areas with active malaria transmission; (2) persons with fever identified in areas with no active transmission and travel history to, or residence in areas with active transmission (either national or international); and (3) persons presenting with fever, chills and sweating from any area. Data was collected from 9 countries: Belize, Colombia (in areas with active transmission), Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, and Panama (September–March 2020). A sample of eligible medical records for 2018 was selected from a sample of health facilities in each country. An algorithm was constructed to assess if a malaria test was ordered or performed for cases that met the suspected case definition. Results A sample of 5873 suspected malaria cases was obtained from 239 health facilities. Except for Nicaragua and Colombia, malaria tests were requested in less than 10% of all cases. More cases were tested in areas with active transmission than areas without cases. Travel history was not systematically recorded in any country. Conclusions A statistically comparable, replicable, and standardized metric was proposed to measure suspected malaria cases with a test (microscopy or rapid diagnostic test) that enables assessing the performance of passive case detection. Cross-country findings have important implications for malaria and infectious disease surveillance, which should be promptly addressed as countries progress towards malaria elimination. Local and easy-to-implement tools could be implemented to assess and improve passive case detection.

A comparative analysis of the outcome of malaria case surveillance strategies in Sri Lanka in the prevention of re-establishment phase

Background Sri Lanka sustained its malaria-free status by implementing, among other interventions, three core case detection strategies namely Passive Case Detection (PCD), Reactive Case Detection (RACD) and Proactive Case Detection (PACD). The outcomes of these strategies were analysed in terms of their effectiveness in detecting malaria infections for the period from 2017-2019. Methods Comparisons were made between the surveillance methods and between years, based on data obtained from the national malaria database and individual case reports of malaria patients. The number of blood smears examined microscopically was used as the measure of the volume of tests conducted. The yield from each case detection method was calculated as the proportion of blood smears which were positive for malaria. Within RACD and PACD, the yield of sub categories of travel cohorts and spatial cohorts was ascertained for 2019. Results A total of 158 malaria cases were reported in 2017-2019. During this period between 666,325-725,149 blood smears were examined annually. PCD detected 95.6%, with a yield of 16.1 cases per 100,000 blood smears examined. RACD and PACD produced a yield of 11.2 and 0.3, respectively. The yield of screening the sub category of travel cohorts was very high for RACD and PACD being 806.5 and 44.9 malaria cases per 100,000 smears, respectively. Despite over half of the blood smears examined being obtained by screening spatial cohorts within RACD and PACD, the yield of both was zero over all three years. Conclusions The PCD arm of case surveillance is the most effective and, therefore, has to continue and be further strengthened as the mainstay of malaria surveillance. Focus on travel cohorts within RACD and PACD should be even greater. Screening of spatial cohorts, on a routine basis and solely because people are resident in previously malarious areas, may be wasteful, except in situations where the risk of local transmission is very high, or is imminent. These findings may apply more broadly to most countries in the post-elimination phase.

Eliminating Plasmodium falciparum malaria: results from tailoring active case detection approaches to remote populations in forested border areas in north-eastern Cambodia

Background Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From January 2018 to December 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of P. falciparum malaria.Methods Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Testing for malaria was conducted independent of fever symptoms. Routine monitoring of programmatic data informed tactical adaptations, while supervision exercises ensured service quality. Results Despite operational challenges, service delivery sites were able to maintain consistently high testing rates throughout the implementation period, with each of 45 (standard deviation, SD 1) sites testing a monthly average of 64 (SD 6) people in 2020. In 2020, MMWs detected only 32 P. falciparum cases. Over the project period, the P. falciparum/P. vivax ratio steadily inversed. Including data from neighbouring health centres and village malaria workers, 45% (80,988/180,732) of all people tested and 39% (1,280/3,243) of P. falciparum cases detected in the area can be attributed to project MMWs.Remaining challenges: maintaining intensified elimination efforts, addressing the issue of detecting low parasitaemia cases and shifting focus to P. vivax malaria challenge the last phase of malaria elimination.Conclusions Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. This case study presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.

A comparative analysis of the outcome of malaria case surveillance strategies in Sri Lanka in the prevention of re‐establishment phase

Background Sri Lanka sustained its malaria-free status by implementing, among other interventions, three core case detection strategies namely Passive Case Detection (PCD), Reactive Case Detection (RACD) and Proactive Case Detection (PACD). The outcomes of these strategies were analysed in terms of their effectiveness in detecting malaria infections for the period from 2017 to 2019. Methods Comparisons were made between the surveillance methods and between years, based on data obtained from the national malaria database and individual case reports of malaria patients. The number of blood smears examined microscopically was used as the measure of the volume of tests conducted. The yield from each case detection method was calculated as the proportion of blood smears which were positive for malaria. Within RACD and PACD, the yield of sub categories of travel cohorts and spatial cohorts was ascertained for 2019. Results A total of 158 malaria cases were reported in 2017–2019. During this period between 666,325 and 725,149 blood smears were examined annually. PCD detected 95.6 %, with a yield of 16.1 cases per 100,000 blood smears examined. RACD and PACD produced a yield of 11.2 and 0.3, respectively. The yield of screening the sub category of travel cohorts was very high for RACD and PACD being 806.5 and 44.9 malaria cases per 100,000 smears, respectively. Despite over half of the blood smears examined being obtained by screening spatial cohorts within RACD and PACD, the yield of both was zero over all three years. Conclusions The PCD arm of case surveillance is the most effective and, therefore, has to continue and be further strengthened as the mainstay of malaria surveillance. Focus on travel cohorts within RACD and PACD should be even greater. Screening of spatial cohorts, on a routine basis and solely because people are resident in previously malarious areas, may be wasteful, except in situations where the risk of local transmission is very high, or is imminent. These findings may apply more broadly to most countries in the post-elimination phase.

Costs and outcomes of active and passive case detection for visceral leishmaniasis (Kala-Azar) to inform elimination strategies in Bihar, India

Background Effective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India’s most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence. Methods Expenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider’s perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD. Results During 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81, $4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from $1.6–4 million, depending on the extent to which blanket and camp ACD was relied upon. Conclusion Cost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India.