Richard W. Steketee

How many child deaths can we prevent this year

This is the second of five papers in the child survival series. The first focused on continuing high rates of child mortality (over 10 million each year) from preventable causes: diarrhoea, pneumonia, measles, malaria, HIV/AIDS, the underlying cause of undernutrition, and a small group of causes leading to neonatal deaths. We review child survival interventions feasible for delivery at high coverage in low-income settings, and classify these as level 1 (sufficient evidence of effect), level 2 (limited evidence), or level 3 (inadequate evidence). Our results show that at least one level-1 intervention is available for preventing or treating each main cause of death among children younger than 5 years, apart from birth asphyxia, for which a level-2 intervention is available. There is also limited evidence for several other interventions. However, global coverage for most interventions is below 50%. If level 1 or 2 interventions were universally available, 63% of child deaths could be prevented. These findings show that the interventions needed to achieve the millennium development goal of reducing child mortality by two-thirds by 2015 are available, but that they are not being delivered to the mothers and children who need them.

HIV in the United States at the turn of the century: an epidemic in transition.

OBJECTIVES The current status of and changes in the HIV epidemic in the United States are described. METHODS Surveillance data were used to evaluate time trends in AIDS diagnoses and deaths. Estimates of HIV incidence were derived from studies done during the 1990s; time trends in recent HIV incidence were inferred from HIV diagnoses and seroprevalence rates among young persons. RESULTS Numbers of deaths and AIDS diagnoses decreased dramatically during 1996 and 1997 but stabilized or declined only slightly during 1998 and 1999. Proportional decreases were smallest among African American women, women in the South, and persons infected through heterosexual contact, HIV incidence has been roughly constant since 1992 in most populations with time trend data, remains highest among men who have sex with men and injection drug users, and typically is higher among African Americans than other racial/ethnic groups. CONCLUSIONS The epidemic increasingly affects women minorities, persons infected through heterosexual contact, and the poor. Renewed interest and investment in HIV and AIDS surveillance and surveillance of behaviors associated with HIV transmission are essential to direct resources for prevention to populations with greatest need and to evaluate intervention programs.

Malaria surveillance -- United States, 2009

Problem/Condition Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. Period Covered This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Description of System Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. Results CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000–2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). Interpretation The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. Public Health Actions The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC’s Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.

HIV-1/AIDS and the control of other infectious diseases in Africa.

The effect of HIV-1 on other infectious diseases in Africa is an increasing public health concern. In this review, we describe the role that three major infectious diseases--malaria, sexually transmitted diseases (STDs), and tuberculosis--have had in the HIV-1 epidemic. The high prevalence of untreated STD infections has been a major factor facilitating the spread of HIV-1 in Africa; with the synergistic interaction between HIV-1 transmission and genital herpes being of special concern for control of both diseases. Increased susceptibility to tuberculosis after infection with HIV-1 has led to a rising incidence and threat of increased transmission of tuberculosis. Clinical malaria occurs with an increased frequency and severity in HIV-1-infected individuals, especially during pregnancy. As with tuberculosis, STDs, and other communicable HIV-1-associated diseases, the net effect of HIV-1 might include increased rates of malaria transmission across communities. In addition to enhancing access to HIV-1 prevention and care, public health surveillance and control programmes should be greatly intensified to cope with the new realities of infectious disease control in Africa.

Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria

Summary Drug-resistant falciparum malaria is increasing in Africa and so methods to map resistance on a broad scale are needed. A molecular marker for chloroquine resistance, pfcrt T76, can be used for surveillance of clinical chloroquine resistance. The prevalence of pfcrt T76 and the prevalence of clinical chloroquine resistance and therapeutic failure were measured at sentinel sites and used to calculate age-adjusted genotype-resistance indices (GRIs) and genotype-failure indices (GFIs). We found stable GRIs and GFIs at different sites in Mali, West Africa. This model permits mapping of chloroquine resistance using molecular tools in rapid and simple cross-sectional surveys.

Malaria-Related Deaths among U.S. Travelers, 1963–2001

Malaria is an enormous global public health problem, responsible for up to 500 million febrile illnesses and approximately 1 million deaths each year (1). The burden of disease is primarily in sub-Saharan Africa, where approximately 90% of all malaria-related deaths occur in children younger than 5 years of age (1). In contrast, nearly 1500 cases of malaria are reported each year in the United States (2). Almost all infections are acquired outside of the United States since indigenous transmission of malaria was interrupted in the United States in the late 1940s (3). Although some cases occur in refugees and immigrants, U.S. travelers overseas are now the largest group of persons given a diagnosis of malaria. In 2000 (the most recent year for which U.S. Department of Commerce data are available), approximately 27.7 million U.S. travelers visited countries affected by malaria (4), and 825 cases of imported malaria among U.S. civilians were reported to the National Malaria Surveillance System (NMSS) (2). Despite attempts at increasing awareness of malaria among travelers and health care workers, malaria-related deaths among travelers occur nearly every year. A previous review of mortality from Plasmodium falciparum malaria in travelers between 1959 and 1987 was published in 1990 (5); no systematic review has been conducted since. We therefore performed a systematic review of malaria deaths in the United States from 1963 (the first year for which complete case reports are still available) through 2001 (the last year for which data are complete) to describe trends, elucidate risk factors, and identify potential public health actions to prevent future malaria-related deaths among U.S. travelers. Methods Malaria is a notifiable disease in the United States. Malaria cases (including fatal cases) are reported to the NMSS, which is administered by the Centers for Disease Control and Prevention (CDC) Malaria Branch. The NMSS is a passive case detection system that relies on U.S. state and local health departments and health care providers to report laboratory-confirmed malaria cases. Cases diagnosed outside the United States or one of its territories are not included. The CDC publishes an annual summary of malaria surveillance in the United States as a supplement to Morbidity and Mortality Weekly Report, which includes case summaries of all fatal malaria cases. We reviewed and screened all fatal cases that occurred between 1963 and 2001, and we included only U.S travelers in our review. We defined a malaria-related death in a U.S. traveler as 1) a death reported to NMSS and subsequently published in the annual surveillance summary for which malaria was a direct or indirect cause of death, 2) a malaria diagnosis and death that occurred in the United States or one of its territories, 3) death from a malarial infection that was acquired outside of the United States or one of its territories, and 4) death of a U.S. resident who traveled abroad for any nonmilitary purpose for any length of time at any point before onset of malaria. We abstracted cases that met these inclusion criteria and entered them into a database (Epi-Info 6.01, CDC, Atlanta, Georgia). We used Stata software, version 7 (Stata Corp., College Station, Texas), for all statistical analyses. We also used several definitions. We defined time to seeking care as the number of days between symptom onset and first visit to a medical provider (coded as unknown if treatment-seeking details were not available in the case summary), time to diagnosis as the number of days between the first visit to a medical provider and the diagnosis of malaria (coded as unknown if these dates were not specified), time to treatment as the number of hours between a diagnosis of malaria and the initiation of antimalarial treatment, appropriateness of chemoprophylaxis regimen as the extent to which CDC recommendations published at the time of travel were followed, and appropriateness of treatment as the determination based on the most recent recommendation from The Medical Letter for that year. We coded adherence to chemoprophylaxis as adherent or nonadherent if this was specifically mentioned; if not, we coded this as unknown. We defined a preventable death as one in which the person 1) took no chemoprophylaxis, 2) took (or was prescribed) inappropriate chemoprophylaxis, 3) took the correct chemoprophylaxis but did not completely adhere to the prescribed regimen, 4) delayed seeking medical care for more than 2 days after the onset of symptoms, 5) sought medical care but did not receive a diagnosis on the day of initial presentation with malaria, 6) was given a diagnosis of malaria but treatment began more than 1 day after diagnosis, or 7) was treated with an antimalarial drug that was inappropriate for the infecting species and region of acquisition. Results From 1963 to 2001, 185 malaria-related deaths were reported to the CDC: 123 (66.5%) occurred among U.S. travelers, 31 (16.8%) occurred among refugees and visitors, 17 (9.2%) occurred among military personnel, and 14 (7.6%) occurred among unknown or other groups (percentages add to 100.1% because of rounding) (Figure 1). The number of deaths among U.S. travelers has remained relatively constant over time, varying between 0 and 10 deaths (median, 3). Among the 123 U.S. travelers, 49 (39.8%) were women and the median age was 51 years (mean, 48.7 years [range, 12 to 91 years]). Most deaths (114 [92.7%]) were attributed to P. falciparum, 4 (3.3%) were attributed to P. vivax, 2 (1.6%) were attributed to P. malariae, and 1 (0.8%) was attributed to P. ovale. In 2 (1.6%) cases, the species was not determined or not reported. The percentage of erythrocytes infected with P. falciparum was reported for 46 cases (mean, 21.4% [range, 1% to 60%]). Figure 1. Number of malaria deaths among travelers, refugees or visitors, and military in the United States, 19632001. Estimated Case-Fatality Rate, Species of Infection, and Origin of Infection The estimated case-fatality rate for U.S. travelers with reported cases of imported malaria (all species) was 0.9% (range, 0% to 4.4% by year). For 1985 to 2001, the only years for which complete computerized data are available, the case-fatality rate was 1.3% for P. falciparum, 0.06% for P. vivax, 0.3% for P. malariae, and 0.3% for P. ovale. These case-fatality rates are probably an overestimate (particularly for nonP. falciparum malaria) because deaths are more likely to be reported than nonfatal cases. Most fatal cases (93 cases [75.6%]) were acquired in Africa: Kenya (25 cases), Nigeria (15 cases), and Liberia (10 cases) were the most probable frequent origins of infections, accounting for 40.6% of fatal cases. The duration of stay varied widely (<1 day to 23 years), with a median stay of 22 days. Tourism was the most frequently identified motive for travel (17.9%), with business (16.3%), missionary work (13.8%), and visiting friends or relatives (11.4%) as the next most common reasons. During the most recent years reviewed (1989 to 2001), the relative importance of these travel motives shifted: Visiting friends and relatives is now the most frequently reported motive for travel among fatal cases (21.3%), followed by business (19.2%), missionary work (10.6%), and tourism (8.5%). Use of Chemoprophylaxis Nearly half of persons (n= 57 [46.3%]) took no chemoprophylaxis, and information on the use of chemoprophylaxis was not available for an additional 32 persons (26%). Of the 34 persons who reported taking chemoprophylaxis, 12 (35.3%) took a drug or drug combination that was inappropriate for the region of travel, and 20 (58.8%) took an appropriate chemoprophylactic drug. Information was insufficient in 2 individuals to determine whether the drug regimen was appropriate. Of the 20 persons who took an appropriate drug, 6 (30%) did not adhere to the prescribed regimen. No information on adherence was available for an additional 7 persons (35%). Therefore, 7 of 123 individuals (5.7%) were known to take appropriate chemoprophylaxis and adhere to the regimen. The reasons these individuals became ill with malaria is not known, but the most likely reasons are unreported nonadherence to the recommended regimen and malabsorption of the antimalarial drug. Table 1 summarizes the chemoprophylaxis regimens currently recommended by the CDC (6). Table 1. Drugs Used in the Prophylaxis of Malaria Presenting Symptoms Fever was the most common presenting symptom, reported for 77.2% of fatal cases, followed by chills (45.9%) (Table 2). Although the classic symptoms of fever and chills or sweats were very common, 23 persons (18.7%) presented with no history of these symptoms. Symptom onset ranged from 18 days before return to 4 years after return (median, 5 days after return; P. ovale was the infecting species for the case 4 years after return). One woman, a 91-year-old who died after developing P. malariae infection, became symptomatic an unknown number of years after traveling to China. Table 2. Presenting Symptoms of 123 U.S. Travelers Who Died of Malaria, 19632001 Time to Seeking Care and Diagnosis Forty-six persons (37.4%) waited more than 1 day after symptom onset before seeking medical care (median, 4.5 days [range, 2 to 28 days]). We could not determine the timing of care-seeking for 58 persons (47.2%). Of the 90 individuals for whom the case report provides adequate information, 61 (67.8%) did not obtain a diagnosis of malaria on the same day as the medical visit. The time to diagnosis ranged from 1 day to 17 days (median, 4 days). In 4 persons, the species was initially misidentified. Diagnosis of P. malariae infection was later changed to P. falciparum infection in 2 cases, P. vivax infection was later changed to P. falciparum infection in 1 case, and P. falciparum infection was later corrected to P. vivax infection in 1 case. In 22 of the 123 U.S travelers (17.9%), malaria was diagnosed only at autopsy. Delay in Initiati

Mathematical models in the evaluation of health programmes

Modelling is valuable in the planning and evaluation of interventions, especially when a controlled trial is ethically or logistically impossible. Models are often used to calculate the expected course of events in the absence of more formal assessments. They are also used to derive estimates of rare or future events from recorded intermediate points. When developing models, decisions are needed about the appropriate level of complexity to be represented and about model structure and assumptions. The degree of rigor in model development and assessment can vary greatly, and there is a danger that existing beliefs inappropriately influence judgments about model assumptions and results.

Pregnancy, Nutrition and Parasitic Diseases

In the developing world, young women, pregnant women, and their infants and children frequently experience a cycle where undernutrition (macronutrient and micronutrient) and repeated infection, including parasitic infections, lead to adverse consequences that can continue from one generation to the next. Among parasitic infections, malaria and intestinal helminths coexist widely with micronutrient deficiencies and contribute importantly to anemia and this cycle of retarded growth and development. In somewhat more limited or focal geographic settings, other parasitic diseases (e.g., schistosomiasis, filariasis) contribute similarly to this cycle. It is undoubtedly much better to enter a pregnancy free of infection and nutritionally replete than the various alternatives. Existing intervention strategies for micronutrient support and for the control of common parasitic infections before or during pregnancy, particularly malaria and intestinal helminths, should be followed. However, further research to identify barriers and priority approaches to achieving this goal remain very important in resource-poor settings where targeted public health efforts are required.

Can the world afford to save the lives of 6 million children each year

BACKGROUND In July, 2003, the Bellagio Study Group on Child Survival estimated that the lives of 6 million children could be saved each year if 23 proven interventions were universally available in the 42 countries responsible for 90% of child deaths in 2000. Here we assess the cost of delivering these interventions, and discuss whether the achievement of the Millennium Development Goal (MDG) for child survival falls within the financial capacities of donors and developing countries. METHODS All child survival interventions shown to reduce mortality from the major causes of death in children younger than 5 years were incorporated into a delivery timetable comprised of 18 contacts between a child or mother and a health-care provider in the period from before birth until the child reaches 5 years. The running costs of delivering the interventions at universal coverage levels were calculated as the sum of unit costs for drugs and materials, delivery costs, and programme management and support costs, including supervision. We estimated the cost of providing interventions at coverage levels reported for 2000 and the additional costs of providing services at universal coverage levels. FINDINGS USD 5.1 billion in new resources is needed annually to save 6 million child lives in the 42 countries responsible for 90% of child deaths in 2000. This cost represents 1.23 dollars per head in these countries, or an average cost per child life saved of 887 dollars. Sensitivity analyses for salary levels for community delivery agents, drug costs, and coverage rates for 2000 were used to develop uncertainty estimates around the USD 5.1 billion annual price tag that range from about 3.1 billion dollars to 8.0 billion dollars. INTERPRETATION Achieving the MDG for child survival is affordable for donors and developing countries. Scaling up health delivery is the challenge, and, along with the lack of funds, will be the limiting factor in reducing child mortality by two-thirds by 2015.

Scaling-up coverage with insecticide-treated nets against malaria in Africa: who should pay?

Insecticide-treated nets (ITNs) have been shown to reduce the burden of malaria in African villages by providing personal protection and, if coverage of a community is comprehensive, by reducing the infective mosquito population. We do not accept the view that scaling-up this method should be by making villagers pay for nets and insecticide, with subsidies limited so as not to discourage the private sector. We consider that ITNs should be viewed as a public good, like vaccines, and should be provided via the public sector with generous assistance from donors. Our experience is that teams distributing free ITNs, replacing them after about 4 years when they are torn and retreating them annually, have high productivity and provide more comprehensive and equitable coverage than has been reported for marketing systems. Very few of the free nets are misused or sold. The estimated cost would be an annual expenditure of about US