Chemotherapeutics challenges in developing effective treatments for the endemic malarias

The endemic malarias threaten the several billion people residing where transmission occurs. Chemotherapeutic strategy pitted against these threats hinges upon species- and stage-specific treatments guided by diagnosis and screening against sometime dangerous contraindications. This approach suits malaria as it occurs among travelers in the developed, non-endemic world. However, limiting treatment to that which diagnosis affirms may not be rational in endemic zones. Most of the endemic malarias remain out of diagnostic reach, either by inaccessibility of the parasite stage, insensitivity of the technology, or unavailability of diagnostic services. The partial and fragmented chemotherapeutic attack of malaria guided by confirmed diagnostics leaves most of the endemic malarias unchallenged. Development of elimination therapy, a single course of treatment aimed at all species and stages, would significantly advance progress against the major killers known collectively as malaria

Malaria caused by \u3ci\u3ePlasmodium vivax\u3c/i\u3e: recurrent, difficult to treat, disabling, and threatening to life — averting the infectious bite preempts these hazards

The maxim ‘an ounce of prevention is worth a pound of cure’ finds few better demonstrations than with malaria caused by Plasmodium vivax. Thoroughly neglected over the past 60 years, the chemotherapy of this complex infection has been dangerous and ineffective until the present. Work is at last being done, but seeing that translate to real improvements at the periphery of care delivery will take years of deliberate effort. In the meantime, patients face substantial risk of debilitating, threatening, and fatal courses of illness associated with a diagnosis of vivax malaria. For some of the most vulnerable to such outcomes — pregnant women and infants — repeated attacks of acute vivax malaria from a single infectious anopheline bite is now not preventable. One of the few measures than can be immediately applied with rigor is vector control, thereby effectively preventing as many of these difficult and dangerous infections as possible. This commentary emphasizes the dire consequences of infection by P. vivax and the real difficulty of dealing with them. That, in turn, emphasizes the many benefits to be derived by preventing them in the first place

Letters to the Editor

Our colleague Dr. Meshnick has proposed that our Society change its name. He expresses the view that “Hygiene” may not represent the membership and the work we conduct. He suggests, “The American Society of Tropical Medicine and Global Health.” I don’t know what “Global Health” means, but I do understand “Hygiene” and argue its relevance to diseases of the tropics and our Society

Resurgent Malaria at the Millennium: Control Strategies in Crisis

Completion of the Panama Canal in 1914 marked the beginning of an era of vector control that achieved conspicuous success against malaria. In 1955 the World Health Organization (WHO) adopted the controversial Global Eradication Campaign emphasising DDT (dichlorodiphenyltrichloroethane) spraying in homes. The incidence of malaria fell sharply where the programme was implemented, but the strategy was not applied in holoendemic Africa. This, along with the failure to achieve eradication in larger tropical regions, contributed to disillusionment with the policy. The World Health Assembly abandoned the eradication strategy in 1969. Aresurgence of malaria began at about that time and today reaches into areas where eradication or control had been achieved. A global malaria crisis looms. In 1993 the WHO adopted a Global Malaria Control Strategy that placed priority in control of disease rather than infection. This formalises a policy that emphasises diagnosis and treatment in a primary healthcare setting, while de-emphasising spraying of residual insecticides. The newpolicy explicitly stresses malaria in Africa, but expresses the intent to bring control programmes around the world into line with the strategy. This review raises the argument that a global control strategy conceived to address the extraordinary malaria situation in Africa may not be suitable elsewhere. The basis of argument lies in the accomplishments of the Global Eradication Campaign viewed in an historical and geographical context. Resurgent malaria accompanying declining vector control activities in Asia and the Americas suggests that the abandonment of residual spraying may be premature given the tools now at hand. The inadequacy of vector control as the primary instrument of malaria control in holoendemic Africa does not preclude its utility in Asia and the Americas

Suppressive chemoprophylaxis invites avoidable risk of serious illness caused by \u3ci\u3ePlasmodium vivax\u3c/i\u3e malaria

Despite inadequacy in preventing vivax malaria after travel, suppressive chemoprophylaxis has dominated travel medicine strategy since the advent of chloroquine in 1946. The lethal threat of falciparum malaria versus the perceived benign consequence of vivax malaria underpins this strategic posture. Recent evidence demonstrating vivax malaria as often pernicious should prompt reconsideration of that posture. Causal prophylaxis kills early developing forms of plasmodia in the liver, thus preventing attacks of falciparum and vivax malaria during travel and delayed onset vivax malaria following travel. Primaquine is the only available drug for this application, and has good evidence of safety, tolerability and efficacy in nonpregnant, G6PD-normal travelers. The primaquine label, however, carries no such indication. Risk of pernicious vivax malaria from all across the endemic regions of the globe, including much of sub-Saharan Africa, should raise consideration of daily primaquine during travel as the preferred front-line option for chemoprophylaxis against malaria in travelers

Letters to the Editor

Our colleague Dr. Meshnick has proposed that our Society change its name. He expresses the view that “Hygiene” may not represent the membership and the work we conduct. He suggests, “The American Society of Tropical Medicine and Global Health.” I don’t know what “Global Health” means, but I do understand “Hygiene” and argue its relevance to diseases of the tropics and our Society

Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria

Malaria caused by \u3ci\u3ePlasmodium vivax\u3c/i\u3e: recurrent, difficult to treat, disabling, and threatening to life — averting the infectious bite preempts these hazards

The maxim ‘an ounce of prevention is worth a pound of cure’ finds few better demonstrations than with malaria caused by Plasmodium vivax. Thoroughly neglected over the past 60 years, the chemotherapy of this complex infection has been dangerous and ineffective until the present. Work is at last being done, but seeing that translate to real improvements at the periphery of care delivery will take years of deliberate effort. In the meantime, patients face substantial risk of debilitating, threatening, and fatal courses of illness associated with a diagnosis of vivax malaria. For some of the most vulnerable to such outcomes — pregnant women and infants — repeated attacks of acute vivax malaria from a single infectious anopheline bite is now not preventable. One of the few measures than can be immediately applied with rigor is vector control, thereby effectively preventing as many of these difficult and dangerous infections as possible. This commentary emphasizes the dire consequences of infection by P. vivax and the real difficulty of dealing with them. That, in turn, emphasizes the many benefits to be derived by preventing them in the first place

EDITORAL A RARE GLIMPSE AT THE EFFICACY OF PRIMAQUINE

Primaquine, the only tool in our drug toolbox for preventing relapse of Plasmodium vivax or P. ovale malaria, may be the most enigmatic of the most commonly prescribed drugs today. Despite more than 50 years of continuous use by millions of people each year, we do not understand how it works. Its complex metabolism generates a dozen known metabolites, and none of these has been definitively linked either to its potent activity against hypnozoites or to its hemolytic toxicity to people having an inborn deficiency of glucose-6- phosphate dehydrogenase

Resistance to Chloroquine Unhinges Vivax Malaria Therapeutics

After 6 decades during which it was almost completely neglected, malaria workers have begun to acknowledge that vivax malaria poses a serious threat to human health. Nearly 3 billion people live at risk of the infection, and 100 to 400 million suffer clinical attacks each year (21, 23). Recent studies challenge the notion of Plasmodium vivax as a benign infection. A spectrum of severe disease syndromes historically considered the reserve of Plasmodium falciparum have been demonstrated in vivax malaria (4, 20, 25, 28, 31). Realization of the threat posed by this parasite, along with acknowledgment of the need to eliminate all of the malarias (19), draws attention to several important problems in the chemotherapeutic management of vivax malaria