Robert Quick

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.

BACKGROUND Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. METHODS Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. FINDINGS Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

Babesiosis in Washington State: A New Species of Babesia?

Babesiosis is an intraerythrocytic protozoan infection, transmitted by ticks, and characterized by malaria-like symptoms and hemolytic anemia. The first reported zoonotic cases in Europe and the United States occurred in 1956 [1] and 1966 [2], respectively. In Europe, cases of this infection have generally been in splenectomized persons infected with the cattle parasites Babesia divergens and Babesia bovis [3, 4], which are thought to be maintained by Ixodes ricinus ticks. No national surveillance system for babesiosis exists in the United States, but hundreds of cases have been reported [4, 5]. Most have been attributed to infection with Babesia microti, a rodent parasite maintained by Ixodes dammini ticks, the primary vector of the agent of Lyme disease (Borrelia burgdorferi). Human babesiosis is endemic on various coastal islands in the northeastern United States, such as Nantucket Island and Marthas Vineyard, Block Island, Long Island, and Shelter Island, and in mainland Connecticut [6]. Cases acquired in Wisconsin have been reported as well [7, 8]. Asplenic, immunocompromised, and elderly persons infected with B. microti are at greatest risk for clinical illness [5, 7, 9-13], which may be severe, whereas other infected persons commonly are asymptomatic or only mildly symptomatic. Only three human cases of babesiosis acquired in the western United States have been reported previously, all of which occurred in splenectomized patients in California [2, 14, 15]; the infecting species was not definitively identified for any of these cases. In September 1991, the first recognized case of babesiosis acquired in Washington State was diagnosed. We present the clinical details of this case, which occurred in an apparently immunocompetent person, and provide evidence that it was not caused by B. microti. We also provide results of 1) serologic testing that was done in an attempt to identify the species of the patients Babesia isolate [referred to as WA1]; 2) experimental inoculations of various mammalian species to determine WA1s host specificity; 3) a comparison of the DNA hybridization patterns of WA1, B. microti, and B. gibsoni using a Babesia-specific, ribosomal-DNA (rDNA) probe [16]; 4) a serosurvey of the patients family members and neighbors for antibody to WA1; and 5) attempts to identify WA1s reservoir host and tick vector. Case Report A 41-year-old man from a rural forested area in south-central Washington State went to a local emergency room on 15 September 1991 because of a 1-week history of fever, rigors, anorexia, rhinorrhea, cough, and headache. He had previously been in good health, was not taking any medications, and had never had a blood transfusion. He had a dog, two cats, and two head of cattle and was exposed daily to tick habitats, but he did not recall any tick bites. He had not been outside the Washington-Oregon border region in many years and had never been in areas reported to be endemic for babesiosis or malaria. On evaluation, he had a few rales in his left-lung field and a platelet count of 48 109/L. He was treated for a presumed bronchopneumonia, with intravenous cefazolin to be followed with oral cefixime, and was sent home. He was hospitalized the next day (September 16) because of persistent fever, severe rigors, and dark-colored urine. He had a temperature of 39.5 C, tenderness in both upper quadrants of his abdomen without hepatosplenomegaly, a normal hematocrit (0.44) and leukocyte count, a platelet count of 46 109/L, 1+ occult blood on urine-dipstick analysis with no cells detected microscopically, a normal chest radiograph, and blood and urine culture results that were negative for bacteria. He was treated with cefazolin and gentamicin without improvement. On September 18, his temperature peaked at 40.4 C; his hematocrit was 0.36, his serum lactate dehydrogenase level was 21.34 kat/L (1280 U/L), and his total bilirubin level was 20.5 mol/L (1.2 mg/dL). Intraerythrocytic ring forms attributed to Plasmodium falciparum malaria were noted on his peripheral blood smear. He was treated with mefloquine and sent home at his request. He was rehospitalized the next day (September 19) with a temperature of 40 C, rigors, and vomiting. On re-examination of his blood smears from September 15 and 18, intraerythrocytic ring forms (in 1.2% and 3.0% of the erythrocytes) were noted as well as tetrad forms characteristic of Babesia (Figure 1). Therapy with oral quinine (650 mg, three times daily) and intravenous clindamycin (600 mg, four times daily) was begun on September 20, with symptomatic improvement by the next day. By September 23, he was afebrile, his hematocrit was 0.35, the parasitemia had decreased from 3.7% (September 20) to 0.4%, and his platelet count had increased to 143 109/L. On September 24, he was sent home on oral quinine and clindamycin (600 mg, three times daily) to complete a 10-day course of therapy. Figure 1. Photographs of Giemsa-stained peripheral blood smears from a patient who acquired babesiosis in Washington State. Left. Right. On September 30, he was evaluated because of a diffuse urticarial rash. His blood smear was normal, and he was treated with a 12-day tapering course of prednisone for a presumed hypersensitivity reaction. On November 3, when he felt feverish and had a headache, his temperature was 37.5 C, his hematocrit 0.34, and he had a detectable parasitemia of <1%. Urticaria recurred after a dose of quinine (650 mg). Although he appeared to be improving without further therapy for babesiosis, he was treated with intravenous clindamycin (1.2 grams, twice daily for 10 days). His hematocrit decreased to 0.28 on November 7; his anemia had resolved by December 12. Because of slowly resolving fatigue, he did not return to work until 6 January 1992. No parasites were detected on his blood smear in December 1991 or on smears in January, March, July, and September 1992, during which time he remained asymptomatic. Evaluation of his immunologic status with a Western-blot test for human immunodeficiency virus; a liver-spleen scan; quantitative immunoglobulins (including immunoglobulin-G subtypes); and serologic testing for antibody to tetanus toxoid, rubella virus, and streptolysin O, indicated normal results. Methods Serologic Studies Serum specimens from the patient were tested at the Centers for Disease Control and Prevention (CDC) in serial fourfold dilutions by indirect immunofluorescent antibody (IFA) testing [17] for antibody to B. microti and the patients isolate (WA1), which was propagated in hamsters inoculated with his blood (see below). A titer of at least 64 to B. microti was considered positive. Stored serum specimens from patients in the northeastern United States with B. microti-antibody titers ranging from 64 to greater than 4096 and blood smears with intraerythrocytic ring forms were assayed for IFA reactivity with WA1. In another laboratory (University of California at Davis [UCD]) with a different IFA protocol [18], serum from the patient was assayed in serial twofold dilutions for reactivity with various Babesia isolates maintained by passage in animals (Table 1). A titer of at least 320 to B. microti was considered positive. Fluorescein-labeled, affinity-purified antibody to human IgG (Kirkegaard & Perry, Gaithersburg, Maryland) was used as the secondary antibody. Blood smears from the patient were examined for B. bovis, Babesia equi, and Babesia bigemina antigens by direct immunofluorescence testing with monoclonal antibodies specific for these species [24-26]. Table 1. Indirect Immunofluorescent Antibody Reactivity of Serum from November 1991 from a Patient Who Acquired Babesiosis (Isolate WA1) in Washington State* Animal Inoculations Whole blood specimens from the patient were inoculated intraperitoneally (1-mL inocula) into at least two hamsters (Mesocricetus auratus) or jirds (Mongolian gerbils; Meriones unguiculatus). Giemsa-stained thin smears of blood from the inoculated animals were examined (at least 25 oil-immersion fields per slide) weekly for 6 to 8 weeks. Erythrocytes from hamsters infected with WA1 were washed in Pucks Saline G and were inoculated into a splenectomized 1-year-old female golden Labrador retriever (5.6 109 parasitized erythrocytes were administered intravenously and an equal number, subcutaneously) and into a hamster (9 106 parasitized erythrocytes, intraperitoneally). During the 34-day monitoring period, the dogs clinical status and hematocrit were checked daily for 20 days and then 3 times weekly, and thin smears were examined (>5000 erythrocytes/slide) daily through day 20 and then twice weekly. Pre-and postinoculation serum samples from the dog were assayed for IFA reactivity (UCD) with WA1, B. microti (GI [20] and P20 isolates), and B. gibsoni. Southern-Blot Analysis Babesia-infected erythrocytes (P1 pellets) were obtained as previously described [16]; erythrocytes infected with WA1, a human isolate of B. microti (2Bm) [16], and a canine isolate of B. gibsoni (6Bg) were used. Control mammalian leukocytes were separated from uninfected blood of a hamster and a dog by differential centrifugation (400 x g, 4 C, 20 min) on Ficoll-paque (Pharmacia LDB Biotechnology, Piscataway, New Jersey) gradients. After Babesia and leukocyte DNA samples were prepared [27], approximately 1 g of each DNA sample was digested with restriction endonucleases (HindIII or HaeIII; Boehringer Mannheim, Indianapolis, Indiana), as previously described [16]. DNA fragments were separated by electrophoresis in horizontal 0.8% (weight/volume) agarose gels in 45 mM Tris-borate and 1 mM ethylenediaminetetraacetic acid at 40 V for 16 to 18 hours. A Babesia-specific rDNA probe was hybridized to Southern blots of the restriction-endonuclease- digested DNAs; the probe had been produced by polymerase chain reaction amplification of sequences from B. microti DNA, with universal primers directed against highly conserved portions of the nuclear sma

Challenges in Implementing a Point-of-Use Water Quality Intervention in Rural Kenya

To prevent diarrheal diseases in western Kenya, CARE Kenya initiated the Water, Sanitation, and Education for Health (WASEH) Project in 1998. The project targets 72 farming and fishing communities with a total population of 43 000. Although the WASEH Project facilitated construction of shallow wells and pit latrines, the water quality still needed improvement. Consequently, in 2001, CARE implemented the Safe Water System (which consists of point-of-use water treatment with sodium hypochlorite, safe storage, and behavior change techniques) within the already established WASEH infrastructure, using existing community organizations in combination with a social marketing approach that introduced affordable products. The project has resulted in adoption rates of 33.5% for chemical water treatment and 18.5% for clay pots modified for safe water storage.

Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members.

Background:The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown. Objective:To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members. Design:Prospective cohort in rural Uganda. Methods:A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months. Findings:During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14–0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53–0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45–0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36–0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1–8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41). Interpretation:Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.

Seroincidence of Helicobacter pylori Infection in a Cohort of Rural Bolivian Children: Acquisition and Analysis of Possible Risk Factors

High seroprevalence rates for Helicobacter pylori are reported in developing countries, yet few seroincidence studies exist that determine age of initial acquisition and risk factors for H. pylori seroconversion. Two H. pylori serosurveys were conducted in August 1996 and November 1997. Of 188 children aged 21 months to 6 years who were seronegative in the first survey, 44 (23%) had seroconverted at follow-up, yielding an 18% annual seroincidence. The largest increase in seroincidence occurred between children aged 2 years (10%) and children aged 3 years (32%). Use of a lidded, narrow-mouthed water vessel was protective against seroconversion (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), and the presence of another H. pylori-seropositive sibling in the household was a risk factor for seroconversion (OR, 3.1; 95% CI, 1.3-8.7). Although not a randomized intervention trial, this study suggests that the use of a narrow-mouthed water vessel may prevent the transmission of H. pylori in households in developing countries.

Diarrhoea prevention in a high-risk rural Kenyan population through point-of-use chlorination, safe water storage, sanitation, and rainwater harvesting

Lack of access to safe water and sanitation contributes to diarrhoea moribidity and mortality in developing countries. We evaluated the impact of household water treatment, latrines, shallow wells, and rainwater harvesting on diarrhoea incidence in rural Kenyan children. We compared diarrhoea rates in 960 children aged <5 years in 556 households in 12 randomly selected intervention villages and six randomly selected comparison villages during weekly home visits over an 8-week period. On multivariate analysis, chlorinating stored water [relative risk (RR) 0.44, 95% confidence interval (CI) 0.28-0.69], latrine presence (RR 0.71, 95% CI 0.54-0.92), rainwater use (RR 0.70, 95% CI 0.52-0.95), and living in an intervention village (RR 0.31, 95% CI 0.23-0.41), were independently associated with lower diarrhoea risk. Diarrhoea risk was higher among shallow well users (RR 1.78, 95% CI 1.12-2.83). Chlorinating stored water, latrines, and rainwater use all decreased diarrhoea risk; combined interventions may have increased health impact.

Selling Sprinkles micronutrient powder reduces anemia, iron deficiency, and vitamin A deficiency in young children in Western Kenya: a cluster-randomized controlled trial

BACKGROUND Although the efficacy of micronutrient powders [MNPs; eg, Sprinkles MNP (Sprinkles Global Health Initiative)] in the reduction of anemia has been established, the effectiveness of these powders in real-world programs has seldom been assessed. OBJECTIVE In this study, we evaluated the effect of community-based marketing and distribution of Sprinkles MNP on childhood rates of anemia and iron and vitamin A deficiency. DESIGN In a cluster-randomized trial in children aged 6-35 mo in Western Kenya, 60 villages were randomly assigned to either intervention or control groups. Community vendors marketed and sold sachets of Sprinkles MNP in intervention villages. Biweekly household visits monitored the use of Sprinkles MNP. Hemoglobin, ferritin, retinol binding protein, malaria, and anthropometric measures were assessed at baseline (n = 1063) and 12 mo of follow-up (n = 862). Data were analyzed by using an intention-to-treat analysis and generalized linear mixed models. RESULTS On average, 33% of households in intervention villages purchased Sprinkles MNP; the average weekly intake per child was 0.9 sachets (∼11.3 mg Fe and ∼328 μg vitamin A). Compared with control subjects, intervention children had greater improvements in hemoglobin concentrations (increase of 0.9 compared with 0.6 g/dL, respectively; P = 0.02), iron deficiency (decrease of 19.3% compared with 5.3%, respectively; P = 0.001), and vitamin A deficiency (decrease of 7.5% compared with an increase of 2.5%, respectively; P = 0.01). Results adjusted for age, sex, socioeconomic status, and maternal education showed a significant association between the hemoglobin, iron, and vitamin A concentrations of children and the number of Sprinkles MNP sachets the children consumed. The prevalence of malaria, wasting, and stunting did not change significantly in either group. CONCLUSION Even with relatively low and infrequent use, Sprinkles MNP sales through community vendors were associated with decreased rates of anemia and iron and vitamin A deficiency in children in a resource-poor setting. This trial was registered at clinicaltrials.gov as NCT01088958.

Monitoring the marketing, distribution, and use of Sprinkles micronutrient powders in rural western Kenya.

Background In 2007, the US Centers for Disease Control and Prevention partnered with local Kenyan institutions to implement the Nyando Integrated Child Health and Education Project, an effectiveness study that used social marketing and a community-based distribution program to promote the sale of Sprinkles and other health products. Objective To describe monitoring of wholesale sales, household demand, promotional strategies, and perceived factors influencing Sprinkles sales among vendors. Methods Ongoing quantitative and qualitative monitoring of Sprinkles sales began in May 2007 in 30 intervention villages. Data sources included baseline and follow-up cross-sectional surveys; office records of Sprinkles sales to vendors; biweekly household monitoring of Sprinkles use; and qualitative data collection, including vendor focus groups and key informant interviews. Results A total of 550 children aged 6 to 35 months were enrolled at baseline, and 451 were available at 12-month follow-up. During this period, nearly 160,000 sachets were sold wholesale to vendors, with variability in sales influenced by the social, political, and economic context. Vendors living closer to the wholesale office purchased more Sprinkles, so a second office was opened closer to remote vendors. On average, 33% of house-holds purchased Sprinkles during household monitoring visits. Training sessions and community launches were important for community support and raising awareness about Sprinkles. Vendor incentives motivated vendors to sell Sprinkles, and consumer incentives promoted purchases. Conclusions Sprinkles program monitoring in Kenya was critically important for understanding sales and distribution trends and vendor perceptions. Understanding these trends led to strategic changes to the intervention over time.

Collaboration, cholera, and cyclones: a project to improve point-of-use water quality in Madagascar.

In November 1999, CARE Madagascar, Population Services International (PSI), and the Centers for Disease Control and Prevention (CDC) selected 30 poor communities in urban Antananarivo as the target population for launch of the Safe Water System. The system consists of behavior change techniques along with point-of-use treatment and safe storage of water. The project was launched in March 2000, ahead of schedule, because a cholera epidemic struck Madagascar in January. Because of the enormous demand created by the cholera epidemic and by 3 cyclones that followed in the next 3 months, the project grew to national scale in less than a year. The combination of community mobilization and social marketing resulted in increased demand for and use of the Safe Water System.

High Mortality in a Cholera Outbreak in Western Kenya after Post-Election Violence in 2008

In 2008, a cholera outbreak with unusually high mortality occurred in western Kenya during civil unrest after disputed presidential elections. Through active case finding, we found a 200% increase in fatal cases and a 37% increase in surviving cases over passively reported cases; the case-fatality ratio increased from 5.5% to 11.4%. In conditional logistic regression of a matched case-control study of fatal versus non-fatal cholera infection, home antibiotic treatment (odds ratio [OR] 0.049; 95% CI: < 0.001-0.43), hospitalization (OR, 0.066; 95% CI, 0.001-0.54), treatment in government-operated health facilities (OR, 0.15; 95% CI, 0.015-0.73), and receiving education about cholera by health workers (OR, 0.19; 95% CI, 0.018-0.96) were protective against death. Among 13 hospitalized fatal cases, chart review showed inadequate intravenous and oral hydration and substantial staff and supply shortages at the time of admission. Cholera mortality was under-reported and very high, in part because of factors exacerbated by widespread post-election violence.