Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Inferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data.

The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemiological data, typically collected in cluster-randomised control trials. The number of these trials that can be conducted is limited. Here we use a systematic review to highlight that efficacy estimates of the same intervention may vary substantially between trials. Analyses indicate that mosquito data collected in experimental hut trials can be used to parameterize mechanistic models for Plasmodium falciparum malaria and reliably predict the epidemiological efficacy of quick-acting, neuro-acting ITNs and IRS. Results suggest that for certain types of ITNs and IRS using this framework instead of clinical endpoints could support policy and expedite the widespread use of novel technologies.

Receptivity to malaria: meaning and measurement.

"Receptivity" to malaria is a construct developed during the Global Malaria Eradication Programme (GMEP) era. It has been defined in varied ways and no consistent, quantitative definition has emerged over the intervening decades. Despite the lack of consistency in defining this construct, the idea that some areas are more likely to sustain malaria transmission than others has remained important in decision-making in malaria control, planning for malaria elimination and guiding activities during the prevention of re-establishment (POR) period. This manuscript examines current advances in methods of measurement. In the context of a decades long decline in global malaria transmission and an increasing number of countries seeking to eliminate malaria, understanding and measuring malaria receptivity has acquired new relevance.

Comment on: Emergence of the invasive malaria vector Anopheles stephensi in Khartoum State, Central Sudan.

This letter comments on the article "Emergence of the invasive malaria vector Anopheles stephensi in Khartoum State, Central Sudan" published in Parasites and Vectors 2021, 14:511. Here we aim of provide a response to this paper in the broader context of the invasion and spread of An. stephensi in the Horn of Africa, and the required response to it. We agree with the authors that the arrival of this invasive vector in Khartoum State is of high public health concern. Equally concerning, however, we found that the detection of the vector by the authors in 2018 seemingly took 3 years to communicate to the Ministry of Health and World Health Organization (WHO), and was reliant on an academic journal. We consider that this short report sets a poor example of how public health threats should be reported. Suitable communication alternatives to alert public health authorities to such threats have been put in place by the WHO and its Member States, and are well known to at least some of the authors of the short report. We would like to encourage all readers not to follow the example of Ahmed et al. but instead act as responsible public health professionals by drawing on the established reporting mechanisms and escalate potential threats as soon as they are identified.

Costs and Cost-Effectiveness of Malaria Control Interventions: A Systematic Literature Review.

OBJECTIVES: To systematically review the literature on the unit cost and cost-effectiveness of malaria control. METHODS: Ten databases and gray literature sources were searched to identify evidence relevant to the period 2005 to 2018. Studies with primary financial or economic cost data from malaria endemic countries that took a provider, provider and household, or societal perspective were included. RESULTS: We identified 103 costing studies. The majority of studies focused on individual rather than combined interventions, notably insecticide-treated bed nets and treatment, and commonly took a provider perspective. A third of all studies took place in 3 countries. The median provider economic cost of protecting 1 person per year ranged from $1.18 to $5.70 with vector control and from $0.53 to $5.97 with chemoprevention. The median provider economic cost per case diagnosed with rapid diagnostic tests was $6.06 and per case treated $9.31 or $89.93 depending on clinical severity. Other interventions did not share enough similarities to be summarized. Cost drivers were rarely reported. Cost-effectiveness of malaria control was reiterated, but care in methodological and reporting standards is required to enhance data transferability. CONCLUSIONS: Important information that can support resource allocation was reviewed. Given the variability in methods and reporting, global efforts to follow existing standards are required for the evidence to be most useful outside their study context, supplemented by guidance on options for transferring existing data across settings.

Anopheles stephensi Mosquitoes as Vectors of Plasmodium vivax and falciparum, Horn of Africa, 2019.

Anopheles stephensi mosquitoes, efficient vectors in parts of Asia and Africa, were found in 75.3% of water sources surveyed and contributed to 80.9% of wild-caught Anopheles mosquitoes in Awash Sebat Kilo, Ethiopia. High susceptibility of these mosquitoes to Plasmodium falciparum and vivax infection presents a challenge for malaria control in the Horn of Africa.

Systematic review and meta-analysis of the cost and cost-effectiveness of distributing insecticide-treated nets for the prevention of malaria.

Insecticide-treated nets are one of two core vector control interventions recommended by the World Health Organization for deployment in malaria-endemic regions around the world, especially sub-Saharan Africa. Although there are many factors that influence the type of distribution strategy chosen, among the most important considerations for the type of distribution strategy chosen is cost, both in terms of total expenditure required and in terms of relative cost-effectiveness. This research attempted to inform these decisions by conducting a systematic review and meta-analysis of the literature on the cost and cost-effectiveness of ITN distribution. The analysis compared the relative cost and cost-effectiveness of distribution strategies. Findings suggest that mass campaigns have lower average distribution costs per net compared with continuous/health facility distribution or sale/vouchers, although the relationship between distribution channel and cost were not statistically significant in the multivariate regression models. Continuous/health facility distribution channels were found to be more cost-effective than mass campaigns for averting DALYs, death, and cases of malaria. Those who design and budget for malaria programs should base decisions about distribution channels more on operational and epidemiological considerations than on cost per net, as the costs per net between distribution channels are not statistically different.

Country-Owned, Country-Driven: Perspectives from the World Health Organization on Malaria Elimination.

Malaria has infected and killed humans since long before history began recording evidence of the parasite's pernicious influence. The extraordinary discoveries of the Plasmodium parasite by Charles Louis Alphonse Laveran in 1880, and the role of the Anopheles mosquito in transmission of the parasite to humans by Sir Ronald Ross in 1897, led to an understanding of the parasite life cycle and ultimately to the development of interventions that would interrupt disease transmission. Almost as soon as the insecticidal properties of dichlorodiphenyltrichloroethane (DDT) were discovered in 1939, the public health profession began battling to achieve a world free of malaria. That vision persists as the aim of all malariologists and, increasingly, the goal of all nations that remain endemic for malaria. This chapter recounts the history of malaria eradication and elimination efforts throughout the world and focuses on the current status of country-led and country-driven malaria elimination programs, along with the technical strategies recommended by the World Health Organization (WHO) for achievement of malaria elimination.

Averting a malaria disaster: will insecticide resistance derail malaria control?

World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe.

Coverage and system efficiencies of insecticide-treated nets in Africa from 2000 to 2017.

Insecticide-treated nets (ITNs) for malaria control are widespread but coverage remains inadequate. We developed a Bayesian model using data from 102 national surveys, triangulated against delivery data and distribution reports, to generate year-by-year estimates of four ITN coverage indicators. We explored the impact of two potential 'inefficiencies': uneven net distribution among households and rapid rates of net loss from households. We estimated that, in 2013, 21% (17%-26%) of ITNs were over-allocated and this has worsened over time as overall net provision has increased. We estimated that rates of ITN loss from households are more rapid than previously thought, with 50% lost after 23 (20-28) months. We predict that the current estimate of 920 million additional ITNs required to achieve universal coverage would in reality yield a lower level of coverage (77% population access). By improving efficiency, however, the 920 million ITNs could yield population access as high as 95%.

Clinical epidemiology, diagnosis and treatment of visceral leishmaniasis in the Pokot endemic area of Uganda and Kenya.

Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.

Cystic echinococcosis in Mundari tribe-members of South Sudan.

Many neglected tropical diseases, including the zoonotic disease cystic echinococcosis (hydatidosis), are endemic to East Africa. However, their geographical distribution is heterogenous and incompletely characterized. The aim of this study was to determine if Mundari pastoralists harbor endemic human hydatidosis. The survey was conducted in cattle camps randomly selected from accessible sites provided by officials in Terekeka, South Sudan. Following informed consent, a questionnaire collected demographic data and hydatid exposure risk. A systematic sonographic abdominal exam was performed using General Electric's LOGIQ Book XP with a 3C-RS 2-5 MHz curvilinear transducer. Six hundred and ten individuals were screened from 13 camps. Four infections were identified, all in women. The prevalence of abdominal hydatid disease in the Mundari tribe-members in cattle camps was 0·7% and all individuals reporting at least one high-risk exposure to hydatid disease. Cystic echinococcosis is endemic among Mundari pastoralists; however, it would appear to be less endemic than in neighboring tribes.

Sustaining fragile gains: the need to maintain coverage with long-lasting insecticidal nets for malaria control and likely implications of not doing so.

Global commitment to malaria control has greatly increased over the last decade. Long-lasting insecticidal nets (LLINs) have become a core intervention of national malaria control strategies and over 450 million nets were distributed in sub-Saharan Africa between 2008 and 2012. Despite the impressive gains made as a result of increased investment in to malaria control, such gains remain fragile. Existing funding commitments for LLINs in the pipeline to 2016 were collated for 40 sub-Saharan African countries. The population-based model NetCALC was used to estimate the potential LLIN coverage achievable with these commitments and identify remaining gaps, and the Lives Saved Tool (LiST) was used to estimate likely consequences for mortality impact if these gaps remain unfilled. Overall, countries calculated a total need of 806 million LLINs for 2013-16. Current funding commitments meet just over half of this need, leaving approximately 374 million LLINs unfunded, most of which are needed to maintain coverage in 2015 and 2016. An estimated additional 938,500 child lives (uncertainty range: 559,400-1,364,200) could be saved from 2013 through 2016 with existing funding (relative to 2009 LLIN coverage taken as the 'baseline' for this analysis); if the funding gap were closed this would increase to 1,180,500 lives saved (uncertainty range: 707,000-1,718,900). Overall, the funding gap equates to approximately 242,000 avoidable malaria-attributable deaths amongst under-fives. Substantial additional resources will need to be mobilized to meet the full LLIN need of sub-Saharan countries to maintain universal coverage. Unless these resources are mobilized, the impressive gains made to date will not be sustained and tens of thousands of avoidable child deaths will occur.

Prevalence of trachoma in unity state, South Sudan: results from a large-scale population-based survey and potential implications for further surveys.

BACKGROUND: Large parts of South Sudan are thought to be trachoma-endemic but baseline data are limited. This study aimed to estimate prevalence for planning trachoma interventions in Unity State, to identify risk factors and to investigate the effect of different sampling approaches on study conclusions. METHODS AND FINDINGS: The survey area was defined as one domain of eight counties in Unity State. Across the area, 40 clusters (villages) were randomly selected proportional to the county population size in a population-based prevalence survey. The simplified grading scheme was used to classify clinical signs of trachoma. The unadjusted prevalence of trachoma inflammation-follicular (TF) in children aged 1-9 years was 70.5% (95% CI: 68.6-72.3). After adjusting for age, sex, county and clustering of cases at household and village level the prevalence was 71.0% (95% CI: 69.9-72.1). The prevalence of trachomatous trichiasis (TT) in adults was 15.1% (95% CI: 13.4-17.0) and 13.5% (95% CI: 12.0-15.1) before and after adjustment, respectively. We estimate that 700,000 people (the entire population of Unity State) require antibiotic treatment and approximately 54,178 people require TT surgery. Risk factor analyses confirmed child-level associations with TF and highlighted that older adults living in poverty are at higher risk of TT. Conditional simulations, testing the alternatives of sampling 20 or 60 villages over the same area, indicated that sampling of only 20 villages would have provided an acceptable level of precision for state-level prevalence estimation to inform intervention decisions in this hyperendemic setting. CONCLUSION: Trachoma poses an enormous burden on the population of Unity State. Comprehensive control is urgently required to avoid preventable blindness and should be initiated across the state now. In other parts of South Sudan suspected to be highly trachoma endemic, counties should be combined into larger survey areas to generate the baseline data required to initiate interventions.

Plasmodium-helminth coinfection and its sources of heterogeneity across East Africa.

BACKGROUND: Plasmodium-helminth coinfection can have a number of consequences for infected hosts, yet our knowledge of the epidemiology of coinfection across multiple settings is limited. This study investigates the distribution and heterogeneity of coinfection with Plasmodium falciparum and 3 major helminth species across East Africa. METHODS: Cross-sectional parasite surveys were conducted among 28 050 children in 299 schools across a range of environmental settings in Kenya, Uganda, and Ethiopia. Data on individual, household, and environmental risk factors were collected and a spatially explicit Bayesian modeling framework was used to investigate heterogeneities of species infection and coinfection and their risk factors as well as school- and individual-level associations between species. RESULTS: Broad-scale geographical patterns of Plasmodium-helminth coinfection are strongly influenced by the least common infection and by species-specific environmental factors. At the individual level, there is an enduring positive association between P. falciparum and hookworm but no association between P. falciparum and Schistosoma species. However, the relative importance of such within-individual associations is less than the role of spatial factors in influencing coinfection risks. CONCLUSIONS: Patterns of coinfection seem to be influenced more by the distribution of the least common species and its environmental risk factors, rather than any enduring within-individual associations.

Integrated rapid mapping of neglected tropical diseases in three States of South Sudan: survey findings and treatment needs.

BACKGROUND: Integrated rapid mapping to target interventions for schistosomiasis, soil-transmitted helminthiasis (STH) and lymphatic filariasis (LF) is ongoing in South Sudan. From May to September 2010, three states--Unity, Eastern Equatoria and Central Equatoria--were surveyed with the aim of identifying which administrative areas are eligible for mass drug administration (MDA) of preventive chemotherapy (PCT). METHODS AND PRINCIPAL FINDINGS: Payams (third administrative tier) were surveyed for Schistosoma mansoni, S. haematobium and STH infections while counties (second administrative tier) were surveyed for LF. Overall, 12,742 children from 193 sites were tested for schistosome and STH infection and, at a subset of 50 sites, 3,980 adults were tested for LF. Either S. mansoni or S. haematobium or both species were endemic throughout Unity State and occurred in foci in Central and Eastern Equatoria. STH infection was endemic throughout Central Equatoria and the western counties of Eastern Equatoria, while LF was endemic over most of Central- and Eastern Equatoria, but only in selected foci in Unity. All areas identified as STH endemic were co-endemic for schistosomiasis and/or LF. CONCLUSIONS: The distribution and prevalence of major NTDs, particularly schistosomiasis, varies considerably throughout South Sudan. Rapid mapping is therefore important in identifying (co)-endemic areas. The present survey established that across the three surveyed states between 1.2 and 1.4 million individuals are estimated to be eligible for regular MDA with PCT to treat STH and schistosomiasis, respectively, while approximately 1.3 million individuals residing in Central- and Eastern Equatoria are estimated to require MDA for LF.

The cost of antibiotic mass drug administration for trachoma control in a remote area of South Sudan.

BACKGROUND: Mass drug administration (MDA) of antibiotics is a key component of the so-called "SAFE" strategy for trachoma control, while MDA of anthelminthics provides the cornerstone for control of a number of other neglected tropical diseases (NTDs). Simultaneous delivery of two or more of these drugs, renowned as "integrated NTD control," is being promoted to reduce costs and expand intervention coverage. A cost analysis was conducted alongside an MDA campaign in a remote trachoma endemic area, to inform budgeting for NTD control in South Sudan. METHODS AND FINDINGS: A first round of antibiotic MDA was conducted in the highly trachoma endemic county of Mayom, Unity state, from June to August 2010. A core team of seven staff delivered the intervention, including recruitment and training of 44 supervisors and 542 community drug distributors. Using an ingredients approach, financial and economic costs were captured from the provider perspective in a detailed costing database. Overall, 123,760 individuals were treated for trachoma, resulting in an estimated treatment coverage of 94%. The economic cost per person treated was USD 1.53, excluding the cost of the antibiotic azithromycin. Ninety four per cent of the delivery costs were recurrent costs, with personnel and travel/transport costs taking up the largest share. CONCLUSIONS: In a remote setting and for the initial round, MDA of antibiotics was considerably more expensive than USD 0.5 per person treated, an estimate frequently quoted to advocate for integrated NTD control. Drug delivery costs in South Sudan are unlikely to decrease substantially during subsequent MDA rounds, as the major cost drivers were recurrent costs. MDA campaigns for delivery of one or more drugs in South Sudan should thus be budgeted at around USD 1.5 per person treated, at least until further costing data for delivery of other NTD drugs, singly or in combination, are available.

The impact of mass drug administration and long-lasting insecticidal net distribution on Wuchereria bancrofti infection in humans and mosquitoes: an observational study in northern Uganda.

BACKGROUND: Lymphatic filariasis (LF) in Uganda is caused by Wuchereria bancrofti and transmitted by anopheline mosquitoes. The mainstay of elimination has been annual mass drug administration (MDA) with ivermectin and albendazole, targeted to endemic districts, but has been sporadic and incomplete in coverage. Vector control could potentially contribute to reducing W. bancrofti transmission, speeding up progress towards elimination. To establish whether the use of long-lasting insecticidal nets (LLINs) can contribute towards reducing transmission of W. bancrofti in a setting with ongoing MDA, a study was conducted in an area of Uganda highly endemic for both LF and malaria. Baseline parasitological and entomological assessments were conducted in 2007, followed by high-coverage LLIN distribution. Net use and entomological surveys were carried out after one year, and final parasitological and entomological evaluations were conducted in 2010. Three rounds of MDA had taken place before the study commenced, with a further three rounds completed during the course of the study. RESULTS: In 2007, rapid mapping indicated 22.3% of schoolchildren were W. bancrofti antigen positive, and a baseline survey during the same year found age-adjusted microfilaraemia prevalence was 3.7% (95% confidence interval (CI): 2.6-5.3%). In 2010, age-adjusted microfilaraemia prevalence had fallen to 0.4%, while antigenaemia rates were 0.2% in children < 5 years and 6.0% in ≥ 5 years. In 2010, universal coverage of mosquito nets in a household was found to be protective against W. bancrofti antigen (odds ratio = 0.44, 95% CI: 0.22-0.89). Prevalence of W. bancrofti larvae in anopheline mosquitoes had decreased significantly between the 2007 and 2010 surveys, but there was an apparent increase in vector densities. CONCLUSION: A marked reduction in W. bancrofti infection and infectivity in humans was observed in the study area, where both MDA and LLINs were used to reduce transmission. The extent to which LLINs contributed to this decline is equivocal, however. Further work investigating the impact of vector control on anopheline-transmitted LF in an endemic area not benefitting from MDA would be valuable to determine the effect of such interventions on their own.

Accuracy of circulating cathodic antigen tests for rapid mapping of Schistosoma mansoni and S. haematobium infections in Southern Sudan.

OBJECTIVE: To evaluate the diagnostic accuracy of a circulating cathodic antigen (CCA) urine dipstick test for detecting Schistosoma mansoni and S. haematobium alongside an integrated rapid mapping survey in Southern Sudan. METHODS AND RESULTS: A total of 373 children aged 5-16 years were included in the study. Of these 26.0% were infected with S. haematobium and 24.5% were infected with S. mansoni, as identified by urine filtration or single Kato-Katz thick smear, respectively. The CCA performed moderately in detecting S. mansoni, with sensitivity of 89.1% and specificity of 74.2%, and poorly in detecting S. haematobium infections, with a sensitivity of 36.8% and specificity of 78.9%. This may be a slight underestimate of true CCA accuracy, since only single stool and urine samples were examined by microscopy. The true 'gold standard' for comparison would have been the collection of multiple stool samples over consecutive days. CONCLUSION: The poor CCA accuracy for diagnosis of urinary schistosomiasis means that this test is currently not suitable for rapid mapping of schistosomiasis in areas where both S. mansoni and S. haematobium may be endemic.