Investigation of Malaria, Leishmaniasis, and Scabies Risk after Earthquakes and Recommendations for Prevention.

Malaria control. generating evidence from local to global level

Economic evaluations of health intervention programs can provide decision makers with quantitative information on how to allocate the scare resources available for health investment. Malaria is the single most important parasitic infection in humans and accounts for a large proportion of the disease burden of sub-Saharan Africa. Currently many strategies are being employed for malaria prevention, and there is a need for evaluation of the various strategies being used. Additionally, routine malaria diagnosis in Africa often leads to mis-use of anti-malarial drugs and there is an urgent need to assess the cost implications of strategies for diagnostic improvement. Costs and cost-effectiveness of vector control Economic evaluations of ITNs (insecticide treated bednets) and IRS (indoor residual spraying) have been conducted in several settings but few of these evaluations relate to the scope and scale of interventions currently underway. Furthermore, few of these evaluations used comparable methodologies. We developed a standardized methodology for the economic evaluation of malaria vector control programs by reviewing and refining existing guidelines. Utilizing this methodology we collected new data from several settings (Eritrea, Malawi, Senegal, and Tanzania) and reanalyzed existing datasets from others (Togo, South Africa, and Mozambique). These sites were chosen to represent geographic variability as well as a diversity of implementation models for ITN delivery. The goals of this thesis were threefold: (1) to evaluate the relative cost and cost-effectiveness of ITNs and IRS for vector control in sub-Saharan Africa, (2) to evaluate the relative cost and cost-effectiveness of different implementation strategies for ITN delivery, and (3) to estimate the costs of introducing RDTs and their effect on the cost of case management of febrile patients. The ITN programs which we evaluated were chosen to represent five different delivery strategies: (1) free delivery through integrated vaccination campaigns (Togo), (2) free delivery through routine services and community mechanisms (Eritrea), (3) highly subsidized delivery through routine services (Malawi), (4) subsidized delivery through the commercial sector utilizing vouchers aimed at pregnant women and infants (Tanzania), and (5) pure commercial sector subsidization (Senegal). ITN/IRS Results The results of the studies generally showed that both interventions remained attractive uses of health resources in a low income country context under almost any scenario. More specifically, for conventional ITNs (targeted to children) the cost per treated net year of protection (TNY) and child death averted ranged from USD 1.21 to USD 6.05 and USD 438 to USD 2,199, respectively. Long-Lasting Insecticidal Net (LLIN) scenarios (also targeted to children) resulted generally in improved cost-effectiveness (USD 1.38 to USD 1.90 per TNY and USD 502 to USD 692 per death averted). IRS was more expensive in base scenarios, with a total cost per person year of protection of USD 3.27 in KwaZulu-Natal and USD 3.90 in Mozambique, this resulted in costs per death averted of USD 3,933 and USD 4,357. ITN programs appeared to be a more efficient strategy for the prevention of child mortality in highly endemic sub-Saharan African settings. However, this was dependant on both effective use of nets and a preferential usage of nets by children. Generally, the cost effectiveness of either strategy was heavily dependant on the cost of the commodities and their effective lifetime (nets for ITN programs and insecticide for IRS programs). ITN programs benefited clearly from a shift to LLINs. Under most scenarios free net delivery utilizing integrated campaigns appeared the most attractive method for short term “catch-up” in coverage levels for ITNs. The other strategies that were reviewed appeared to be better suited to the long term maintenance of coverage (“keep-up”). The data presented here provide a significant amount of new information collected and analyzed in a comparable manner to aid in decision making regarding vector control for malaria in sub-Saharan Africa. Costs of introducing rapid diagnostic tests in Tanzania We also conducted a study on the costs of implementation of Rapid Diagnostic Tests (RDTs) for malaria in Dar Es Salaam, Tanzania. Data were collected both at the level of individual patients and for entire health facilities. RDTs significantly lowered patient expenditure on drugs (by USD 0.37; p=0.001) and provider drug costs (by USD 0.44; p=0.014), but did not significantly reduce patients’ overall expenditures (USD 1.08 vs. USD 1.36) and have increased total provider costs (USD 3.62 vs. USD 2.31). Clinician’s compliance with tests was higher in clinics with RDTs than in those with routine microscopy. Use of the economic data in this thesis will hopefully help to provide a better evidence base for program managers to make more rational and efficient decisions about malaria control options and case management of febrile patients.

Synergies in integrated malaria control

To discuss epidemiological aspects of imported malaria and the potential impact of imported malaria cases reported in Sri Lanka 2008-2011 in terms of a possible resurgence of the disease. The national malaria database was used to assess details regarding country where the infection was possibly acquired, species of Plasmodium, number of days lapsed between disembarkation in Sri Lanka and diagnosis, compliance with national treatment guidelines including percentage of patients followed up as per the national guidelines. After the strengthening of malaria surveillance, during the 4-year period, 152 imported malaria cases were recorded: an increase of 176% in the number of cases. Most of the imported malaria infections were acquired by Sri Lankan Nationals mainly from South Asia, especially India. Plasmodium vivax accounted for 64% of the infections. Approximately 50% of the cases were diagnosed in the Western Province. The average period from disembarkation in Sri Lanka to malaria diagnosis was 3.6days. Patients were managed and treated according to the national guidelines. 82% of the patients were followed up for 28days to ensure parasite clearance. There is a possible increasing risk of re-introduction of malaria to the country from imported cases. Enhanced surveillance activities and the increase in international travel have contributed to an increase in recorded case numbers. There is a need to further strengthen surveillance, especially for monitoring and timely addressing of imported malaria, if the country is to prevent the re-establishment of transmission within. The importance of having an efficient response mechanism to deal with imported malaria is also highlighted.

BackgroundSince 2005, Cambodia’s national tuberculosis programme has been conducting active case finding (ACF) with mobile radiography units, targeting household contacts of TB patients in poor and vulnerable communities in addition to routine passive case finding (PCF). This paper examines the differences in the demographic characteristics, smear grades, and treatment outcomes of pulmonary TB cases detected through both active and passive case finding to determine if ACF could contribute to early case finding, considering associated project costs for ACF.MethodsDemographic characteristics, smear grades, and treatment outcomes were compared between actively (n = 405) and passively (n = 602) detected patients by reviewing the existing programme records (including TB registers) of 2009 and 2010. Additional analyses were performed for PCF cases detected after the ACF sessions (n = 91).ResultsThe overall cost per case detected through ACF was US$ 108. The ACF approach detected patients from older populations (median age of 55 years) compared to PCF (median age of 48 years; p < 0.001). The percentage of smear-negative TB cases detected through ACF was significantly higher (71.4%) than that of PCF (40.5%). Among smear-positive patients, lower smear grades were observed in the ACF group compared to the PCF group (p = 0.002). A fairly low initial defaulter rate (21 patients, 5.2%) was observed in the ACF group. Once treatment was initiated, high treatment success rates were achieved with 96.4% in ACF and with 95.2% in PCF. After the ACF session, the smear grade of TB patients detected through routine PCF continued to be low, suggesting increased awareness and early case detection.ConclusionsThe community-based ACF in Cambodia was found to be a cost-effective activity that is likely to have additional benefits such as contribution to early case finding and detection of patients from a vulnerable age group, possibly with an extended benefit for reducing secondary cases in the community. Further investigations are required to clarify the primary benefits of ACF in early and increased case detection and to assess its secondary impact on reducing on-going transmission.

BackgroundChildhood tuberculosis can be found via passive case finding (PCF), diagnosing a symptomatic child, and active case finding (ACF), discovering a child through contact tracing. Most high prevalence areas perform PCF, but as ACF is introduced, the clinical and radiologic findings may differ. We compare clinical, radiographic, microbiologic and epidemiological characteristics of children diagnosed through PCF and ACF.MethodsA retrospective cohort study of all patients diagnosed with TB from 01/01/2012-12/31/2019 at Texas Children’s Hospital. ACF is TB in a child who had not previously sought care before identified via contact tracing, immigration screening, or screening for incarceration. Severity of disease was based on location of illness, imaging and bacteriology/histopathology. Associations between PCF/ACF and demographics, disease severity, and microbiology were analyzed.ResultsOf 178 patients, 80 (45%) were diagnosed via ACF. ACF patients were more likely to be US-born (OR: 2.29, [95% Confidence interval (CI): 1.12-4.67]) and younger (mean 6.18 vs 8.84 years, p= 0.016). Only 2.5% of ACF patients had extrapulmonary disease, compared to 45% of the PCF group (p< 0.0001). All 14 severe extrathoracic cases were in the PCF group (10 central nervous system disease, 3 ocular disease, 1 spondylitis). Fewer patients in the ACF group had severe intrathoracic findings (11% vs 39%, p< 0.001): miliary disease (0% vs 10%, p=0.006), cavity (1% vs 9%, p=0.04), and multilobar involvement (7.5% vs 22.4%, p=0.006). ACF patients had more hilar/mediastinal adenopathy (OR: 2.51, [CI: 1.34-3.72], p=0.004). ACF patients were less often cultured (38% vs 89%, p< 0.0001) and had less microbiological confirmation by cultures or PCR (21% vs 52%, p=< 0.0001).ConclusionPatients in the ACF group were younger, had less severe clinical manifestations, and had almost no extrathoracic disease. Clinicians need to be aware that the common clinical and radiographic presentations in children differ between PCF and ACF.DisclosuresJeffrey R. Starke, MD, Otsuka Pharmaceuticals (Other Financial or Material Support, Member, Data Safety Monitoring Board)

The impact of disease control can be either evaluated by a classical ecological study, or by multiplication of the effectiveness of control intervention and the disease burden. The latter approach has the advantage of circumventing ecological biases. To evaulate the effectiveness of the malaria control program implemented in Madagascar, we conducted a nationwide survey in 2012-2013 in 62 study sites. This survey included (1) a cross-sectional study to measure the effectiveness of each control intervention on reducing the transmission, and (2) a case-control study to measure the effectiveness on reducing the morbidity. We present here the results related to vector control interventions, i.e. Long Lasting Insecticidal Nets (LLIN) distribution and Indoor Residual Spraying (IRS) campaigns. The cross-sectional survey included 15,734 individuals of all age groups among which 3.7% had a positive Rapid Diagnostic Test (RDT). LLIN daily use was 52.3% in areas covered by universal distribution and IRS coverage was 64.8% in targeted areas. 818 uncomplicated clinical malaria cases were compared to 7,767 controls living in the same villages. Multilevel analysis of factors associated with a positive RDT or with the occurrence of an episode of non-complicated malaria revealed that LLIN daily use had a 45% protective effectiveness (PE) against infection (aOR 0.55 [95% CI 0.42, 0.72]) and a 48% PE against morbidity (aOR 0.52 [0.28, 0.96]). The PE of IRS was evaluated to be 23% against infection (aOR 0.77 [0.53, 1.13]) and 49% against morbidity (aOR 0.51 [0.39, 0.66]). In areas where both activities are implemented, coverage of LLIN was 21.3 percentage points lower than in areas where LLIN only were deployed. Combining IRS with LLIN provided almost no gain in preventing infection, but the PE of LLIN use against morbidity increased from 51% (aOR 0.49 [0.20, 1.20]) to 66% (aOR 0.34 [0.16, 0.74]) when IRS was added, although non significantly. Our results indicate that, taken separately, LLIN and IRS perform satisfactorily but that their concurrent use might have a limited benefit as compared with efforts to improve the coverage of a single intervention. Given that in Madagascar, approx. 220,000 clinical malaria cases and 770,000 malaria infections occur each year, we calculated that vector control interventions prevented approx. 96,000 malaria cases and 197,000 malaria infections annually. Distributions of LLIN were implicated in the major part of cases (73.7%) and infections (80.5%) prevented, while IRS campaigns were implicated in 37.3% of cases and 31.2% of infections prevented.

BackgroundNepal has a high burden of undetected tuberculosis (TB). In line with the World Health Organization’s End TB Strategy, the National TB Programme promotes active case-finding (ACF) as one strategy to find people with TB who are unreached by existing health services. The IMPACT TB (Implementing proven community-based active TB case-finding intervention) project was implemented in four districts in Nepal, generating a substantial yield of previously undetected TB. We aimed to identify the facilitators and barriers linked to the implementation of ACF within IMPACT TB, as well as how those facilitators and barriers have been or could be addressed.MethodsThis was an exploratory qualitative study based on 17 semi-structured key-informant interviews with people with TB who were identified through ACF, and community health workers who had implemented ACF. Thematic analysis was applied in NVivo 11, using an implementation science framework developed by Grol and Wensing to classify the data.ResultsWe generated five main themes from the data: (1) ACF addressed the social determinants of TB by providing timely access to free healthcare, (2) knowledge and awareness about TB among people with TB, communities and community health workers were the ‘oil’ in the ACF ‘machine’, (3) trust in community health workers was fundamental for implementing ACF, (4) community engagement and support had a powerful influence on ACF implementation and (5) improved working conditions and enhanced collaboration with key stakeholders could further facilitate ACF. These themes covered a variety of facilitators and barriers, which we divided into 22 categories cutting across five framework levels: innovation, individual professional, patient, social context and organizational context.ConclusionsThis study provides new insights into facilitators and barriers for the implementation of ACF in Nepal and emphasizes the importance of addressing the social determinants of TB. The main themes reflect key ingredients which are required for successful ACF implementation, while the absence of these factors may convert them from facilitators into barriers for ACF. As this study outlined “how-to” strategies for ACF implementation, the findings can furthermore inform the planning and implementation of ACF in Nepal and similar contexts in low- and middle-income countries.

Malaria remains a significant global health challenge, with an estimated 247 million cases and 619,000 deaths reported in 2021 (WHO, 2022). Despite substantial progress in reducing the burden of malaria through vector control, improved diagnostics, and the introduction of vaccines, complete eradication remains elusive. The emergence of drug-resistant Plasmodium strains, insecticide resistance in mosquito vectors, and the limited efficacy of current vaccines present significant barriers to achieving malaria elimination. While new technologies such as genomics and gene editing offer promising avenues for research, their implementation in endemic regions remains challenging. This article provides a critical assessment of the current state of malaria research, discussing major obstacles and potential solutions. It also presents an opinion on the strategies that should be prioritized to accelerate malaria elimination efforts. The frontline artemisinin-based combination therapies (ACTs) have played a pivotal role in malaria control. However, Plasmodium falciparum has developed resistance to artemisinin and its partner drugs in Southeast Asia, with signs of emerging resistance in Africa (1)(2). New drug candidates such as KAF156 and MMV048 are in clinical trials, but delays in drug development and regulatory approvals limit their immediate impact (3). A shift towards host-targeted therapies and multi-drug regimens should be explored to mitigate resistance. Additionally, repurposing existing drugs with antimalarial potential could accelerate the availability of new treatment options. The RTS,S/AS01 (Mosquirix) vaccine, despite being the first WHO-recommended malaria vaccine, offers only 30–40% efficacy, requiring multiple booster doses (4). The newer R21/Matrix-M vaccine has demonstrated higher efficacy in early trials but requires further validation in large-scale studies (5). A multi-target vaccine approach, incorporating transmission-blocking and blood-stage antigens, may provide more durable protection. Increased investment in mRNA-based malaria vaccines, inspired by COVID-19 vaccine success, could accelerate malaria vaccine development. Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) have been effective in reducing malaria transmission. However, widespread insecticide resistance among Anopheles mosquitoes threatens these strategies (6). Novel interventions, including genetically modified mosquitoes and Wolbachia-based vector control, offer alternative solutions (7). While genetically modified mosquitoes show promise, ethical concerns and ecological implications must be addressed through transparent regulatory frameworks and community engagement. Rapid diagnostic tests (RDTs) and microscopy remain the primary malaria diagnostic tools. However, their sensitivity is often compromised in cases of low parasite density and asymptomatic infections (8). AI-powered diagnostic tools and portable sequencing technologies have shown potential in improving malaria detection and surveillance (9). Scaling up point-of-care molecular diagnostics and digital surveillance tools is essential for early detection and targeted interventions. Malaria funding has stagnated in recent years, with significant shortfalls in meeting global malaria control targets (IHME, 2020)(10). Policy challenges, including delays in approving new interventions and the lack of local capacity in endemic regions, further hinder progress. Greater investment in research and development (R&amp;D), particularly through public-private partnerships, is crucial to sustaining malaria control efforts. Decentralizing malaria research by strengthening scientific infrastructure in endemic countries can also accelerate innovation. Future malaria research must integrate multi-disciplinary approaches, leveraging advances in genomics, AI, and precision medicine. AI-driven drug discovery and big data analytics can accelerate biomarker identification and treatment optimization (11). Additionally, multi-omics approaches integrating genomics, proteomics, and metabolomics can provide deeper insights into parasite biology and host responses (12). Public health strategies should also prioritize integrating malaria interventions into primary healthcare systems, ensuring accessibility and sustainability. Strengthening collaborations between governments, research institutions, and pharmaceutical companies can drive innovation and implementation of novel malaria control strategies. While scientific advancements offer hope, global collaboration, sustained funding, and political will remain the ultimate determinants of malaria eradication success. In conclusion, malaria research has made remarkable progress, but persistent challenges—such as drug resistance, limited vaccine efficacy, and vector adaptation—threaten elimination efforts. Addressing these challenges requires a multi-pronged approach, combining novel therapeutics, innovative vector control strategies, improved diagnostics, and robust public health policies. Increased investment in malaria research, particularly in endemic regions, is necessary to develop sustainable solutions. Governments, funding agencies, and the global scientific community must work together to accelerate malaria control and eradication. Malaria elimination is within reach, but achieving this goal will require continued commitment, innovation, and global cooperation.

Africa counts greater successes against malaria

Marburg virus disease: lesson learned from the first outbreak encounter in Tanzania

BackgroundAfrican countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed.MethodsCross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1–15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed.ResultsOverall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%–57.1%) in children 1–15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%–27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%–77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR) = 0.6; 95%CI: 0.4–0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3–0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5–0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0–1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1–4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3–2.4) versus other roofing materials and bigger household size (8–15 people: OR = 1.6; 95%CI: 1.3–2.1) versus small households (1–4 persons).ConclusionMalaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs.

Community views on active case finding for tuberculosis in low-and middle-income countries: a qualitative evidence synthesis (Protocol).

To assess the impact of intensified malaria control interventions in an ethnic minority community in Betul using existing tools. Two rounds of indoor residual spraying with synthetic pyrethroid insecticide were applied and larvivorous fish introduced, followed by intensive surveillance for early detection of Plasmodium falciparum with rapid diagnostic tests and prompt treatment with sulphadoxine pyrimethamine. Pre-intervention surveys revealed a very high fever rate in the community in all age groups with a slide positivity rate of >50% with >90%P. falciparum. The post-intervention phase showed a sharp steady decline in number of malaria cases (beta 0.972; P < 0.0001, 95% CI 0.35-0.47). Monitoring of entomological results revealed a significant decline in both Anopheles species and An. culicifacies (P < 0.0001). A combination of indoor residual spraying and early detection and prompt treatment complemented by rapid diagnostic tests and larvivorous fishes successfully brought malaria under control. These approaches could be applied in other regions of different endemicity to control malaria in India.

BackgroundThe National Malaria Control Programme (NMCP) of Mali has had recent success decreasing malaria transmission using 3rd generation indoor residual spraying (IRS) products in areas with pyrethroid resistance, primarily in Ségou and Koulikoro Regions. In 2015, national survey data showed that Mopti Region had the highest under 5-year-old (u5) malaria prevalence at 54%—nearly twice the national average—despite having high access to long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC). Accordingly, in 2016 the NMCP and other stakeholders shifted IRS activities from Ségou to Mopti. Here, the results of a series of observational analyses utilizing routine malaria indicators to evaluate the impact of this switch are presented.MethodsA set of retrospective, eco-observational time-series analyses were performed using monthly incidence rates of rapid diagnostic test (RDT)-confirmed malaria cases reported in the District Health Information System 2 (DHIS2) from January 2016 until February 2018. Comparisons of case incidence rates were made between health facility catchments from the same region that differed in IRS status (IRS vs. no-IRS) to describe the general impact of the 2016 and 2017 IRS campaigns, and a difference-in-differences approach comparing changes in incidence from year-to-year was used to describe the effect of suspending IRS operations in Ségou and introducing IRS operations in Mopti in 2017.ResultsCompared to communities with no IRS, cumulative case incidence rates in IRS communities were reduced 16% in Ségou Region during the 6 months following the 2016 campaign and 31% in Mopti Region during the 6 months following the 2017 campaign, likely averting a total of more than 22,000 cases of malaria that otherwise would have been expected during peak transmission months. Across all comparator health facilities (HFs) where there was no IRS in either year, peak malaria case incidence rates fell by an average of 22% (CI95 18–30%) from 2016 to 2017. At HFs in communities of Mopti where IRS was introduced in 2017, peak incidence fell by an average of 42% (CI95 31–63%) between these years, a significantly greater decrease (p = 0.040) almost double what was seen in the comparator HFCAs. The opposite effect was observed in Ségou Region, where peak incidence at those HFs where IRS was withdrawn after the 2016 campaign increased by an average of 106% (CI95 63–150%) from year to year, also a significant difference-in-differences compared to the comparator no-IRS HFs (p < 0.0001).ConclusionAnnual IRS campaigns continue to make dramatic contributions to the seasonal reduction of malaria transmission in communities across central Mali, where IRS campaigns were timed in advance of peak seasonal transmission and utilized a micro-encapsulated product with an active ingredient that was of a different class than the one found on the LLINs used throughout the region and to which local malaria vectors were shown to be susceptible. Strategies to help mitigate the resurgence of malaria cases that can be expected should be prioritized whenever the suspension of IRS activities in a particular region is considered.