Biomedical subjects
L Chitsulo
Publications and source records attributed to L Chitsulo.
The global epidemiological situation of schistosomiasis and new approaches to control and research.
While the distribution of schistosomiasis has changed over the last 50 years and there have been successful control programmes, the number of people estimated to be infected or at risk of infection has not been reduced. Today, 85% of the number of infected people are estimated to be on the African continent where few control efforts are made. In terms of disease burden, there is therefore a growing discrepancy between sub-Saharan Africa and the rest of the world. WHO has now developed a dual strategy for the control of schistosomiasis: a strategy for morbidity control adapted to the public health context in high burden areas, and a strategy to consolidate control in areas where a low endemic level has been reached and elimination may be feasible. Related to this new vision, some research needs are pointed out.
The global status of schistosomiasis and its control.
Schistosomiasis is being successfully controlled in many countries but remains a major public health problem, with an estimated 200 million people infected, mostly in Africa. Few countries in this region have undertaken successful and sustainable control programmes. The construction of water schemes to meet the power and agricultural requirements for development have lead to increasing transmission, especially of Schistosoma mansoni. Increasing population and movement have contributed to increased transmission and introduction of schistosomiasis to new areas. Most endemic countries are among the least developed whose health systems face difficulties to provide basic care at the primary health level. Constraints to control include, the lack of political commitment and infrastructure for public health interventions. Another constraint is that available anti-schistosomal drugs are expensive and the cost of individual treatment is a high proportion of the per capita drug budgets. There is need for increased support for schistosomiasis control in the most severely affected countries.
Therapeutic and operational profiles of metrifonate and praziquantel in Schistosoma haematobium infection.
A systematic analysis of the existing literature has been undertaken to compare the therapeutic and operational profiles of metrifonate (CAS 52-68-6), and praziquantel (CAS 55-268-74-1), two anti-schistosomal compounds. The criteria evaluated were therapeutic efficacy against Schistosoma haematobium and other helminths, impact on pathology commonly associated with S. haematobium infection, frequency, type and duration of adverse reactions, health risk associated with inadvertent overdosage, applicability and practicality of treatment in various medical settings, tolerance and resistance, pharmacological properties, toxicity and economic aspects. It is concluded that both medical and operational criteria indicate that praziquantel is superior to metrifonate for the treatment of schistosomiasis caused by S. haematobium. Since, compared to praziquantel, metrifonate has a number of disadvantages, future antischistosomal chemotherapy can do without this drug.
New opportunities for the control of fascioliasis.
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Schistosomiasis.
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Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi.
A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.
Female genital schistosomiasis (FGS): relationship between gynecological and histopathological findings.
Schistosomiasis of the lower female reproductive tract manifests itself in a broad spectrum of clinical features. However, clinical and histopathological findings have never been studied in a synoptic manner. Based on the assumption that any type of pathology present in the female reproductive tract is the expression of a complex pathophysiological reaction towards eggs sequestered in the genital tissues, we decided to analyze colposcopic and histopathological findings in a comprehensive manner. Thirty-three women in Malawi with urinary and genital schistosomiasis were examined parasitologically and gynecologically. A thorough colposcopic examination with photodocumentation was performed and biopsies were taken from the cervix, the vagina and/or the vulva for histological sectioning and immunohistochemistry. The predominant colposcopic findings were sandy patches on the cervical surface similar to those seen in the bladder and polypous/papillomatous tumors with irregular surface on the vaginal wall and in the vulvar area. The histopathological sections of sandy-patch-like lesions demonstrated only a small cellular reaction around S. haematobium eggs in various stages of disintegration. In contrast, in the case of polyps the histology revealed a more pronounced immunological reaction characterized by a heavy cellular infiltrate. One case of invasive squamous cell carcinoma of the cervix was diagnosed. We conclude that colposcopy is a useful tool in the detection of FGS related pathology in the lower female reproductive tract and that the synoptic assessment of surface and of corresponding histological sections helped to understand the pathophysiology of S. haematobium associated disease in genital tissue.
Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.
Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.
Urine reagent strips for diagnosis of schistosomiasis haematobium in women of fertile age.
Hematuria, proteinuria and leukocyturia were semiquantitatively assessed by reagent strips in single morning urine of women of fertile age visiting the outpatient department of the Mangochi district hospital, Malawi. This was part of a diagnostic approach to female genital schistosomiasis (FGS). In 51 women ova of Schistosoma haematobium were detected in urine by a filtration technique. In 33 of these women ova were also present in genital tissue as demonstrated by microscopic examination of biopsies. In 209 women no ova were found in the single urine filtered. There were significantly higher scores for hematuria, proteinuria and leukocyturia as well as of the combined reagent strip index (RSI) in egg-excreting than in egg-negative women. The sensitivity of a single hematuria, proteinuria and leukocyturia reading was 98, 84 and 73%, respectively. However, the respective specificity was only 24, 22 and 23%. The best prediction of urinary schistosomiasis was achieved by a +2 score for hematuria, of which the sensitivity was 94% and the specificity was 61%. The high false-positive rates can probably be explained by contamination of urine by vaginal secretion. Moreover, cases of schistosomiasis have probably been overlooked because only a single morning urine sample was examined. The total absence of hematuria, proteinuria and leukocyturia, however, may be used to rule out heavy infections in community surveys. There was no difference in reagent strip scores between women with genital and urinary schistosomiasis as compared with those with urinary tract lesions alone. Thus urine analysis reagent strip readings do not help to discriminate between S. haematobium infected women with and without FGS.
Reversibility of lower reproductive tract abnormalities in women with Schistosoma haematobium infection after treatment with praziquantel--an interim report.
Little is known whether and to what extent antiparasitic treatment cures female genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women with FGS nine were re-examined at two to nine weeks after they had been treated with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of the urinary tract and to a lesser extent of genital pathology subsided in most patients. Schistosoma haematobium ova were no longer detectable in urine of any of the patients post-treatment. Efficiency of chemotherapy against adult worms was confirmed by the disappearance of circulating anodic antigen (CAA) in serum. Sandy patches showed resolution in two of four cases after chemotherapy. Papillomata due to schistosomiasis alone improved, but persisted in mixed infection with human papilloma virus (HPV) or when HPV was the only underlying cause. In one patient ulcera could not be related with certainty to schistosomiasis at admission, but resolved after treatment with parziquantel. Leukoplakia (two cases) was not influenced by chemotherapy, or even increased during follow-up, regardless of whether ova had been detected or not. Although the follow-up period was rather short, time intervals were not standardized, and a relatively small number of patients was investigated, it could be shown that genital pathology due to sequestered S. haematobium ova is, at least partially, reversible already two to nine weeks after killing the adult worms by praziquantel. This is paralleled by a normalization of inflammatory immune responses detectable in histological sections and vaginal lavage.
Schistosomiasis in Lake Malawi.
BACKGROUND: In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS: A volunteer cohort of expatriates and visitors representing a cross-section of Malawi's foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawi's southwestern shore. FINDINGS: The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION: S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.
Clinical algorithm for treatment of Plasmodium falciparum malaria in children.
BACKGROUND: Identification of children who need antimalarial treatment is difficult in settings where confirmatory laboratory testing is not available, as in much of sub-Saharan Africa. The current national policy in Malawi is to treat all children with fever, usually defined as the mother's report of fever in the child, for presumed malaria. To assess this policy and to find out whether a better clinical case definition could be devised, we studied acutely ill children presenting to two hospital outpatient departments in Malawi. METHODS: The parent or guardian of each enrolled child (n = 1124) was asked a standard series of questions about the symptoms and duration of the child's illness. Each child was examined, axillary and rectal temperatures and blood haemoglobin concentrations were measured, and a giemsastained thick smear was examined for malaria parasites. Logistic regression procedures were used to identify clinical predictors of parasitaemia. FINDINGS: High temperature (37.7 degrees C or above), nailbed pallor, enlarged spleen, and being seen at one of the clinics rather than the other were associated with an increased risk of malaria parasitaemia in univariate analyses. A revised malaria case definition of rectal temperature of 37.7 degrees C or higher, splenomegaly, or nailbed pallor was 85% sensitive in identifying parasitaemic children and 41% specific; the corresponding sensitivity and specificity for the nationally recommended definition that equates mother's history of fever with malaria were 93% and 21%. The revised case definition had 89% sensitivity in identifying parasitaemic children with haemoglobin concentration below 80 g/L and 89% sensitivity in identifying children with parasite density greater than 10,000/microL, characteristics that indicate a clear need for antimalarial treatment. INTERPRETATION: These results suggest that better clinical definitions are feasible, that splenomegaly and pallor are helpful in identifying children with malaria, and that much overtreatment of children without parasitaemia could be avoided.
Efficacy of sulphadoxine/pyrimethamine for Plasmodium falciparum malaria in Malawian children under five years of age.
In March 1993, sulphadoxine/pyrimethamine (SP) replaced chloroquine as the first line drug for malaria treatment in Malawi. Since then, the Ministry of Health has been receiving anecdotal and written reports of SP treatment failures in children. To determine whether treatment failure with SP was a widespread problem, children < 5 years of age with axillary temperature > 38.0 degrees C and parasite density > 2000/mm3 attending the outpatient clinics of the Mangochi and Karonga District Hospitals were enrolled in the study with parental consent. These were then followed for 28 days or until they failed clinically. Of 159 patients enrolled, 145 (91.2%) were followed for 28 days or until clinical failure. Of these, none had RII resistance and 3 (1.9%) had RIII resistance: 2/69 (2.9%) in Mangochi and 1/76 (1.3%) in Karonga; 142/145 (97.9%) exhibited RI/sensitive patterns. Of those followed to day 28 or to clinical failure, 77.1% had parasite clearance by day 3 and 98.6% had parasite clearance by day 7. Of those with temperature readings (n = 140), 129 (92.1%) clinically improved on day 3 and 98.6% improved by day 7. Other indicators of clinical improvement (from day 0 to day 3) included, reported increased level of activity in 136 (97.1%) of the children, and mother's impression of child's improvement in 113 (80.7%). Of the 14 patients not followed to day 28 or to clinical failure, 11 were lost to follow-up by day 7. No allergic skin reactions were noted, and no deaths were observed. These data show that after one year of widespread use of SP in Malawi, Plasmodium falciparum parasite resistance remains very low, and therefore contradicts reports of widespread parasite resistance to SP.
Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1.
In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival.
Evaluation of maternal practices, efficacy, and cost-effectiveness of alternative antimalarial regimens for use in pregnancy: chloroquine and sulfadoxine-pyrimethamine.
With the knowledge that an efficacious antimalarial administered to pregnant women would markedly reduce placental malaria and its associated risk of low birth weight (LBW), investigations were conducted to identify an antimalarial regimen practical for nationwide implementation through the antenatal clinic (ANC) system. Maternal practices, including ANC utilization and malaria treatment and prevention during pregnancy were evaluated as part of a national malaria knowledge, attitudes, and practices survey. A second study was conducted to evaluate the efficacy and cost of selected alternative antimalarial regimens. Women in their first or second pregnancy were placed on chloroquine (CQ) treatment (25 mg/kg) followed by weekly CQ (300 mg) (CQ/CQ); sulfadoxine-pyrimethamine (SP) treatment followed by CQ (300 mg weekly) (SP/CQ); or SP treatment during the second trimester and repeated at the beginning of the third trimester (SP/SP). With 87% of women attending ANC two or more times during pregnancy, most pregnant women in Malawi could be reached with an antimalarial intervention. Among 159 women in their first or second pregnancy receiving CQ/CQ, SP/CQ, and SP/SP, placental malaria parasitemia rates were 32%, 26%, and 9%, respectively (P = 0.006, by chi-square test). The SP/SP regimen was also markedly more cost-effective in preventing infant deaths, costing $75 per infant death prevented, compared with $481 for SP/CQ and $542 for CQ/CQ. These investigations suggest that a regimen consisting of two treatment doses of SP during pregnancy is an efficacious and cost-effective intervention to prevent placental malaria, and LBW-associated mortality, that can be delivered to pregnant women through ANCs in settings similar to those found in rural Malawi.
Using clinical signs to diagnose anaemia in African children.
Anaemia is a serious and common problem among young children in sub-Saharan Africa. As a first step towards developing guidelines for its recognition and treatment, we conducted a study to evaluate the ability of health workers to use clinical findings to identify children with anaemia. Health care workers examined a total of 1104 children under 5 years of age at two hospital-based outpatient clinics in rural Malawi. Blood samples were taken to determine haemoglobin concentrations. Pallor of the conjunctiva, tongue, palm or nail beds was 66% sensitive and 68% specific in distinguishing children with moderate a anaemia (haemoglobin concentration, 5-8 g/dl) and 93% sensitive and 57% specific in distinguishing those with severe anaemia (haemoglobin concentration, < 5 g/dl). Even without laboratory support, which is often unavailable in rural Africa, clinical findings can identify the majority of children with anaemia.
Antimalarials during pregnancy: a cost-effectiveness analysis.
Antenatal clinics (ANC) provide an avenue for interventions that promote maternal and infant health. In areas hyperendemic for Plasmodium falciparum, malaria infection during pregnancy contributes to low birth weight (LBW), which is the greatest risk factor for neonatal mortality. Using current data and costs from studies in Malawi, a decision-analysis model was constructed to predict the number of LBW cases prevented by three antimalarial regimens, in an area with a high prevalence of chloroquine (CQ)-resistant malaria. Factors considered included local costs of antimalarials, number of ANC visits, compliance with dispensed antimalarials, prevalence of placental malaria, and LBW incidence. For a hypothetical cohort of 10,000 women in their first or second pregnancy, a regimen consisting of one dose of sulfadoxine-pyrimethamine (SP) in the second trimester followed by a second dose at the beginning of the third trimester would prevent 205 cases of LBW at a cost of US$ 9.66 per case of LBW prevented. A regimen using a treatment dose of SP followed by CQ 300 mg (base) weekly would prevent 59 cases of LBW at a cost of $62 per case prevented, compared with only 30 cases of LBW prevented at a cost of $113 per case when the regimen involves initial treatment with CQ (25 mg/kg) followed by CQ 300 mg (base) weekly. In areas hyperendemic for CQ-resistant P. falciparum, a two-dose SP regimen is a cost-effective intervention to reduce LBW incidence and it should be included as part of the antenatal care package.