The promise and potential challenges of intermittent preventive treatment for malaria in infants (IPTi)

Intermittent preventive treatment (IPT) administers a full therapeutic course of an anti-malarial drug at predetermined intervals, regardless of infection or disease status. It is recommended by the World Health Organization (WHO) for protecting pregnant women from the adverse effects of malaria (IPTp) and shows great potential as a strategy for reducing illness from malaria during infancy (IPTi). Administered concurrently with standard immunizations, IPTi is expected to reduce the frequency of clinical disease, but to allow blood-stage infections to occur between treatments, thus allowing parasite-specific immunity to develop. While wide deployment of IPTi is being considered, it is important to assess other potential effects. Transmission conditions, drug choice and administration schedule will likely affect the possibility of post-treatment rebound in child morbidity and mortality and the increased spread of parasite drug resistance and should be considered when implementing IPTi

COVID-19: Shining the Light on Africa.

COVID-19: Shining the Light on Africa

Artemisinin-Resistant Malaria: Research Challenges, Opportunities, and Public Health Implications

Artemisinin-based combination therapies are the most effective drugs to treat Plasmodium falciparum malaria. Reduced sensitivity to artemisinin monotherapy, coupled with the emergence of parasite resistance to all partner drugs, threaten to place millions of patients at risk of inadequate treatment of malaria. Recognizing the significance and immediacy of this possibility, the Fogarty International Center and the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health convened a conference in November 2010 to bring together the diverse array of stakeholders responding to the growing threat of artemisinin resistance, including scientists from malarious countries in peril. This conference encouraged and enabled experts to share their recent unpublished data from studies that may improve our understanding of artemisinin resistance. Conference sessions addressed research priorities to forestall artemisinin resistance and fostered collaborations between field- and laboratory-based researchers and international programs, with the aim of translating new scientific evidence into public health solutions. Inspired by this conference, this review summarizes novel findings and perspectives on artemisinin resistance, approaches for translating research data into relevant public health information, and opportunities for interdisciplinary collaboration to combat artemisinin resistance

Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

BACKGROUND: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. METHODS: In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines. RESULTS: For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. CONCLUSION: Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine

Keep Politics out of Funding Decisions for Medical Research and Public Health.

No abstract available

Discovery and Description of Ebola Zaire Virus in 1976 and Relevance to the West African Epidemic During 2013-2016.

BACKGROUND: In 1976, the first cases of Ebola virus disease in northern Democratic Republic of the Congo (then referred to as Zaire) were reported. This article addresses who was responsible for recognizing the disease; recovering, identifying, and naming the virus; and describing the epidemic. Key scientific approaches used in 1976 and their relevance to the 3-country (Guinea, Sierra Leone, and Liberia) West African epidemic during 2013-2016 are presented. METHODS: Field and laboratory investigations started soon after notification, in mid-September 1976, and included virus cell culture, electron microscopy (EM), immunofluorescence antibody (IFA) testing of sera, case tracing, containment, and epidemiological surveys. In 2013-2016, medical care and public health work were delayed for months until the Ebola virus disease epidemic was officially declared an emergency by World Health Organization, but research in pathogenesis, clinical presentation, including sequelae, treatment, and prevention, has increased more recently. RESULTS: Filoviruses were cultured and observed by EM in Antwerp, Belgium (Institute of Tropical Medicine); Porton Down, United Kingdom (Microbiological Research Establishment); and Atlanta, Georgia (Centers for Disease Control and Prevention). In Atlanta, serological testing identified a new virus. The 1976 outbreak (280 deaths among 318 cases) stopped in 2 years. Transmission indices (R0) are higher in all 3 countries than in 1976. CONCLUSIONS: An international commission working harmoniously in laboratories and with local communities was essential for rapid success in 1976. Control and understanding of the recent West African outbreak were delayed because of late recognition and because authorities were overwhelmed by many patients and poor community involvement. Despite obstacles, research was a priority in 1976 and recently

Responding to the Pandemic of Falsified Medicines

Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals

Using the entomological inoculation rate to assess the impact of vector control on malaria parasite transmission and elimination

Prior studies have shown that annual entomological inoculation rates (EIRs) must be reduced to less than one to substantially reduce the prevalence of malaria infection. In this study, EIR values were used to quantify the impact of insecticide-treated bed nets (ITNs), indoor residual spraying (IRS), and source reduction (SR) on malaria transmission. The analysis of EIR was extended through determining whether available vector control tools can ultimately eradicate malaria. The analysis is based primarily on a review of all controlled studies that used ITN, IRS, and/or SR and reported their effects on the EIR. To compare EIRs between studies, the percent difference in EIR between the intervention and control groups was calculated. Eight vector control intervention studies that measured EIR were found: four ITN studies, one IRS study, one SR study, and two studies with separate ITN and IRS intervention groups. In both the Tanzania study and the Solomon Islands study, one community received ITNs and one received IRS. In the second year of the Tanzania study, EIR was 90% lower in the ITN community and 93% lower in the IRS community, relative to the community without intervention; the ITN and IRS effects were not significantly different. In contrast, in the Solomon Islands study, EIR was 94% lower in the ITN community and 56% lower in the IRS community. The one SR study, in Dar es Salaam, reported a lower EIR reduction (47%) than the ITN and IRS studies. All of these vector control interventions reduced EIR, but none reduced it to zero. These studies indicate that current vector control methods alone cannot ultimately eradicate malaria because no intervention sustained an annual EIR less than one. While researchers develop new tools, integrated vector management may make the greatest impact on malaria transmission. There are many gaps in the entomological malaria literature and recommendations for future research are provided

The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

Using their experiences from, and analysis of, global campaigns to eradicate smallpox, poliomyelitis, and measles, Myron Levine and colleagues derive lessons for malaria eradication

Conquering the intolerable burden of malaria: what's new, what's needed: a summary.

Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria vaccine becomes deployed, consideration must be given to disease burden, cost-effectiveness, financing, delivery systems, and approval by regulatory agencies. Key to evaluation of vaccine effectiveness will be collection and prompt analysis of epidemiologic information. Training of persons in every aspect of malaria research and control is essential for programs to succeed. The Multilateral Initiative on Malaria (MIM) is actively promoting research capacity strengthening and has established networks of institutions and scientists throughout the African continent, most of whom are now linked by modern information-sharing networks. Evidence over the past century is that successful control malaria programs have been linked to strong research activities. To ensure effective coordination and cooperation between the growing number of research and control coalitions forming in support of malaria activities, an umbrella group is needed. With continued support for scientists and control workers globally, particularly in low-income malarious countries, the long-deferred dream of malaria elimination can become a reality