Evolution of anti-malaria policies and measures in P.R. China for achieving and sustaining malaria-free.

Malaria is a major public health threat worldwide, and it was also widely prevalent in the history in China, seriously endangering people's health and affecting socioeconomic development. China was certified malaria elimination in 2021 with unremitting efforts since the founding of the People's Republic of China in 1949. This great achievement has been another milestone in the fight against major infectious diseases following the elimination of smallpox, poliomyelitis, leprosy, filariasis, neonatal tetanus and blinding trachoma in China. This paper briefly introduces the malaria burden dynamics and the corresponding malaria transmission risk stratificantions, as well as systematically reviews the evolution of anti-malaria policies and measures from severe epidemic to elimination in China. Meanwhile, five key lessons in malaria control and elimination in China are also briefly summarized. All of the above provide evidences for promoting global malaria eradication and preventing reestablishment of malaria transmission, finally benefit all individuals still suffering from the scourge of malaria.

Effectiveness of spatially targeted interventions for control of HIV, tuberculosis, leprosy and malaria: a systematic review.

BACKGROUND: As infectious diseases approach global elimination targets, spatial targeting is increasingly important to identify community hotspots of transmission and effectively target interventions. We aimed to synthesise relevant evidence to define best practice approaches and identify policy and research gaps. OBJECTIVE: To systematically appraise evidence for the effectiveness of spatially targeted community public health interventions for HIV, tuberculosis (TB), leprosy and malaria. DESIGN: Systematic review. DATA SOURCES: We searched Medline, Embase, Global Health, Web of Science and Cochrane Database of Systematic Reviews between 1 January 1993 and 22 March 2021. STUDY SELECTION: The studies had to include HIV or TB or leprosy or malaria and spatial hotspot definition, and community interventions. DATA EXTRACTION AND SYNTHESIS: A data extraction tool was used. For each study, we summarised approaches to identifying hotpots, intervention design and effectiveness of the intervention. RESULTS: Ten studies, including one cluster randomised trial and nine with alternative designs (before-after, comparator area), satisfied our inclusion criteria. Spatially targeted interventions for HIV (one USA study), TB (three USA) and leprosy (two Brazil, one Federated States of Micronesia) each used household location and disease density to define hotspots followed by community-based screening. Malaria studies (one each from India, Indonesia and Kenya) used household location and disease density for hotspot identification followed by complex interventions typically combining community screening, larviciding of stagnant water bodies, indoor residual spraying and mass drug administration. Evidence of effect was mixed. CONCLUSIONS: Studies investigating spatially targeted interventions were few in number, and mostly underpowered or otherwise limited methodologically, affecting interpretation of intervention impact. Applying advanced epidemiological methodologies supporting more robust hotspot identification and larger or more intensive interventions would strengthen the evidence-base for this increasingly important approach. PROSPERO REGISTRATION NUMBER: CRD42019130133.

Setting targets for HIV/AIDS-What lessons can be learned from other disease control programmes?

In a Collection Review, Richard Hayes and colleagues discuss metrics for assessing progress in control of the HIV/AIDS epidemic in the context of prior disease control programmes.

Correlates of GLA family adjuvants' activities.

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

BACKGROUND: We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. METHODS: Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. RESULTS: Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. CONCLUSION: It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation.

Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination.

Although the effectiveness of BCG vaccination in preventing adult pulmonary tuberculosis (TB) has been highly variable, epidemiologic studies have suggested that BCG provides other general health benefits to vaccinees including reducing the impact of asthma, leprosy, and possibly malaria. To further evaluate whether BCG immunization protects against malarial parasitemia and to define molecular correlates of this non-specific immunity, mice were vaccinated with BCG and then challenged 2 months later with asexual blood stage Plasmodium yoelii 17XNL (PyNL) parasites. Following challenge with PyNL, significant decreases in parasitemia were observed in BCG vaccinated mice relative to naïve controls. To identify immune molecules that may be associated with the BCG-induced protection, gene expression was evaluated by RT-PCR in i) naïve controls, ii) BCG-vaccinated mice, iii) PyNL infected mice and iv) BCG vaccinated/PyNL infected mice at 0, 1, 5, and 9 days after the P. yoelii infection. The expression results showed that i) BCG immunization induces the expression of at least 18 genes including the anti-microbial molecules lactoferrin, eosinophil peroxidase, eosinophil major basic protein and the cathelicidin-related antimicrobial peptide (CRAMP); ii) an active PyNL infection suppresses the expression of important immune response molecules; and iii) the extent of PyNL-induced suppression of specific genes is reduced in BCG-vaccinated/PyNL infected mice. To validate the gene expression data, we demonstrated that pre-treatment of malaria parasites with lactoferrin or the cathelicidin LL-37 peptide decreases the level of PyNL parasitemias in mice. Overall, our study suggests that BCG vaccination induces the expression of non-specific immune molecules including antimicrobial peptides which may provide an overall benefit to vaccinees by limiting infections of unrelated pathogens such as Plasmodium parasites.

Recent advances in tropical medicine.

There have been significant advances in both the classical and neglected tropical diseases, with Guinea worm looking set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration, together with the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual successful elimination. While the global incidence of new cases of leprosy continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not necessarily prevent disability. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism about the control of these diseases. However, ongoing education and access remain essential to increasing the uptake of HIV testing and decreasing transmission. Meanwhile, the rise of drug-resistant tuberculosis and malaria is concerning, and the emergence of the highly pathogenic avian influenza A and re-emergence of viruses such as chikungunya and West Nile virus, without significant recent progress in vaccine development, pose additional ongoing challenges to tropical medicine physicians worldwide.

Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers.

OBJECTIVES: To describe the prospects, achievements, challenges and opportunities for implementing intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania in light of national antenatal care (ANC) guidelines and ability of service providers to comply with them. METHODS: In-depth interviews were made with national level malaria control officers in 2006 and 2007. Data was analysed manually using a qualitative content analysis approach. RESULTS: IPTp has been under implementation countrywide since 2001 and the 2005 evaluation report showed increased coverage of women taking two doses of IPTp from 29% to 65% between 2001 and 2007. This achievement was acknowledged, however, several challenges were noted including (i) the national antenatal care (ANC) guidelines emphasizing two IPTp doses during a woman's pregnancy, while other agencies operating at district level were recommending three doses, this confuses frontline health workers (HWs); (ii) focused ANC guidelines have been revised, but printing and distribution to districts has often been delayed; (iii) reports from district management teams demonstrate constraints related to women's late booking, understaffing, inadequate skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision of peripheral health facilities has been inadequate and national guidelines on district budgeting for health services have been inflexible. IPTp coverage is generally low partly because IPTp is not systematically enforced like programmes on immunization, tuberculosis, leprosy and other infectious diseases. Necessary concerted efforts towards fostering uptake and coverage of two IPTp doses were emphasized by the national level officers, who called for further action including operational health systems research to understand challenges and suggest ways forward for effective implementation and high coverage of IPTp. CONCLUSION: The benefit of IPTp is appreciated by national level officers who are encouraged by trends in the coverage of IPTp doses. However, their appeal for concerted efforts towards IPTp scaling-up through rectifying the systemic constraints and operational research is important and supported by suggestions by other authors.

[The Amazon Sanitation Plan (1940-1942)]. / O Plano de Saneamento da Amazônia (1940-1942).

The article addresses the Amazon Sanitation Plan and the political context in which it was formulated between 1940 and 1941. It examines the role of Getúlio Vargas, the activities of the plan's main protagonists (such as Evandro Chagas, João de Barros Barreto, and Valério Konder), its key proposals, and its demise as of 1942 upon creation of the Special Public Health Service (Sesp), which grew out of cooperation agreements between Brazil and the US following both nations' involvement in World War II. A reproduction of the Plan as published in the Arquivos de Higiene in 1941 is included.

Current status of communicable and non-communicable diseases in India.

India is going through a period of transition, both epidemiological and demographic transition. Infectious diseases are still persisting as major health problems in spite of having national programmes for the control of most of these diseases for almost half a century now. This paper focuses on two national programmes: the success story of the National Leprosy Eradication Programme; and the National Anti-Malaria Programme that has failed to achieve its objectives. There are re-emerging infectious diseases which are adding to the burden of diseases. In addition, there is an increasing prevalence of non-communicable diseases as a result of lifestyle changes and urbanization. These are the challenges that are to be tackled in the new millennium.

Immunomodulatory potential of hydrophobic analogs of Rigin and their role in providing protection against Plasmodium berghei infection in mice.

Here, we report the immunomodulating potential of N-palmitoyl-amino-ethyl-rigin amide (PR) and N-cholestanyl-amino-ethyl-rigin amide (CR), the two new structural analogs of rigin (an IgG-derived tetrapeptide). Their activity profiles are compared with native tuftsin (NT) and/or N-palmitoyl-amino-ethyl-tuftsin amide (PT) taken as positive control. To explore the possibility of their use as targeting molecules, they are incorporated into the liposome bilayer and, subsequently, interacted with macrophages in an in vitro study. The new analogs of rigin with the hydrophobicity introduced at the C-terminus are found to considerably improve both the cell-mediated and the humoral immune responses in mice. However, unlike tuftsin and its analog, which mainly activate polymorphonuclear leukocytes and macrophages, the rigin analogs appear to manifest their response more through lymphocytes. When administered prophylactically to a group of mice, at the dose of 100 micrograms/0.5 ml/mouse/day for 2 days (i.v.), followed by a challenge presented with 1 x 10(6) rbcs parasitised with Plasmodium berghei on day 0, substantial reduction in parasitaemia and rate of mortality is observed. This led to increase the median survival time (MST) of the treated group in comparison to the control group. The response is found to be more prominent in CR-treated mice possibly because of the presence of steroid moiety, which is likely to have more productive interaction with cell membranes. Incorporation of these peptides into the bilayer of liposomes does not alter the permeability behavior of vesicles and, in fact, enhances their uptake by the macrophages in an in vitro study. The effect, however, is dependent on both, the concentration of peptide liposomes and the time of incubation. Present study, thus, establishes the possible use of these analogs not only as adjuvant in chemotherapy, but also as a prophylactic supplement to boost the natural immune status. The activity response of rigin analogs is manifested through lymphocytes, they can also find use in the chemotherapy of diseases, like leishmaniasis, tuberculosis and leprosy, where macrophage activity is either tamed or impaired by pathogens.

Reaching maturity - 25 years of the TDR.

In its first 25 years of existence, TDR has become a key player in the development of new tools for the control of tropical diseases and the training of researchers from disease-endemic countries. In order to maintain its leading position, cope with new health challenges and profit from new avenues opened by science and technology breakthroughs, a new strategic vision is now being implemented. It aims at a closer interaction with health systems and disease control programmes, capacity strengthening based on selected research initiatives and full exploitation of scientific and technological advances in the biomedical, social and information sciences, as discussed here by Carlos Morel.