Improved microscopy diagnosis of pulmonary tuberculosis using sodium hypochlorite concentration technique in Tanga, Tanzania.

Pulmonary tuberculosis diagnosis commonly relies on the bacteriological examination of sputum. A cross-sectional hospital-based study was carried out to compare on "on the spot" sputum staining using sodium hypochlorite (bleach method) and routine Ziel-Neelsen (ZN) staining technique. Study candidates included individual patients presenting with cough <3 weeks (Group I) and > or =3 weeks (Group II). Sensitivity and specificity of the bleach method was calculated and compared at 100% using the ZN staining technique as the standard. A total of 171 patients (94 males, 77 females) with mean age 34.9 years (SD +/- 12.9) were recruited. Fifty-eight patients had coughed for <3 weeks while 113 had coughed for 23 weeks. Smear-positive TB in Group I was 13.8% (95% CI = 5-23) while in Group II was 25.7% (95% CI = 21-29). Using the bleach method, the prevalence of smear-positive TB in Group II was 28.3% (CI 95% = 20-36). This was an increase in smear-positivity rate of 15.6% as compared to the ZN technique. These results suggest that the use of bleach technique "on the spot" improve the sensitivity of tuberculosis diagnosis among patients with a history of coughing of over three weeks. However, further studies in different settings are recommended to validate the technique.

Community knowledge, attitudes and practices towards tuberculosis and its treatment in Mpwapwa district, central Tanzania.

Tuberculosis (TB) is one of the leading causes of adult mortality with 32% of the global population infected with Mycobacterium tuberculosis. The current control of TB depends mainly on case management using the Direct-Observed Treatment, Short-course (DOTs) regimen. Despite the measures taken, the disease burden is still on increase especially in the developing countries including Tanzania. Correct knowledge and positive perception of the community towards TB and its management is a prerequisite to early treatment seeking. This study was carried out in Mpwapwa district, central Tanzania, to assess the knowledge, attitudes and practice as regards to TB and its treatment. Focus group discussions involving men and women were conducted in six villages. Results show that TB was an important public health problem. However, community knowledge on its cause was poor. Symptoms of TB as mentioned by the community included persistent cough and weight loss. TB was reported to be transmitted mainly through air. Self medication was the first most preferred option, whereas health care facility consultation was the last one. Focus group discussants knew that TB cure requires a 8-month period of treatment. Friends and relatives were the main source of TB information in the community. In conclusion, rural communities of Mpwapwa District have a low knowledge on the causes and the transmission of tuberculosis which is a likely cause of the delay in seeking treatment. An intensive appropriate community health education is required for a positive behavioural change in tuberculosis control.

Implication of diethylcarbamazine induced morbidity and the role of cellular responses associated with bancroftian filariasis pathologies.

Pre and post-diethylcarbamazine treatment clinical expression, microfilaraemia prevalence and cellular responses were investigated in individuals in Tanga, Tanzania. Fifty-seven male individuals (aged = 15 years old) were identified for further studies on IL-4, IL-6, IL-8. IFN-gamma, IL-beta, TNF-alpha and nitric oxide in plasma and hydrocoele fluid. Microfilarial prevalence in the examined individuals was 12% with a geometric mean intensity (GMI) of 838 mff/ml in a community with a population of 1018 individuals. Microfilaraemic hydrocoele stage II and III were the most frequent pathologies observed with prevalence of 17.5% and 42. 1 %, respectively. All study individuals treated with diethylcarbamazine (DEC) standard dose of 6 mg/kg experienced post-treatment adverse events. There was no direct relationship between elevated IL-6 and the occurrence and severity of clinical adverse effects post-treatment. The findings from this study suggests that, blood elevated cytokine profile is not the main etiological factor in the inflammatory responses developing after treatment of bancroftian filariasis infections and pathology with DEC. Plasma levels of cellular (cytokines) responses during treatment revealed a proportion of symptomatic patients. Prior to treatment, patients with hydroecoele had high levels of IL-6 than those without the pathology. In conclusion these findings do not support the hypothesis that pro-inflammatory cytokines are directly responsible for adverse events to DEC chemotherapy in bancroftian filariasis infections and pathologies such as hydrocoele, lymphoedema and elephantiasis.

Hospital-based safety and tolerability study to assess efficacy of oral doxycycline in the treatment of Wuchereria bancrofti infection in north-eastern Tanzania.

A hospital based open-label clinical trial of 19 apparently healthy adult males with microfilaraemia was conducted to assess safety, tolerability and efficacy of doxycycline on Wuchereria bancrofti. Study individuals were assigned 8 weeks treatment with doxycycline 200 mg daily. The results of different selected tests showed that, the haematological, hepatic, renal and clinical parameters pre-and post-drug administrations were within the normal range for all treated individuals. Clinical adverse events were mild, transient, tolerable and reported in 7/19 (36.8%) of the study cohort. The mf clearance rate was 100% at 12 months post treatment for the 13 individuals who completed the follow up. These findings indicate that, although the drug was administered for a long period, there was no evidence of toxicity to the myocardium, hepatocytes, renal, bone marrow and blood cells, suggesting that an 8-week course of 200 mg/day doxycycline is a safe and tolerable regime for the treatment of Wuchereria bancrofti infections.

Onchocerciasis: the clinical and epidemiological burden of skin disease in Africa.

An attempt was made to assess the true public-health importance of onchocercal skin disease throughout the African region and hence provide an objective basis for the rational planning of onchocerciasis control in the area. The seven collaborative centres that participated in the study (three in Nigeria and one each in Ghana, Cameroon, Tanzania and Uganda) were all in areas of rainforest or savannah-forest mosaic where onchocercal blindness is not common. A cross-sectional dermatological survey was undertaken at each site following a standard protocol. At each site, the aim was to examine at least 750 individuals aged 5 years and living in highly endemic communities and 220-250 individuals aged 5 years and living in a hypo-endemic (control) community. Overall, there were 5459 and 1451 subjects from hyper-and hypo-endemic communities, respectively. In the highly endemic communities, the prevalence of itching increased with age until 20 years and then plateaued, affecting 42% of the population aged 20 years. There was a strong correlation between the prevalence of itching and the level of endemicity (as measured by the prevalence of nodules; r=0.75; P<0.001). The results of a multivariate logistic regression analysis showed that, at the individual level, the presence of onchocercal reactive skin lesions (acute papular onchodermatitis, chronic papular onchodermatitis and/or lichenified onchodermatitis) was the most important risk factor for pruritus, with an odds ratio (OR) of 18.3 and 95% confidence interval (CI) of 15.19-22.04, followed by the presence of palpable onchocercal nodules (OR=4.63; CI=4.05-5.29). In contrast, non-onchocercal skin disease contributed very little to pruritus in the study communities (OR=1.29; CI=1.1-1.51). Onchocercal skin lesions affected 28% of the population in the endemic villages. The commonest type was chronic papular onchodermatitis (13%), followed by depigmentation (10%) and acute papular onchodermatitis (7%). The highest correlation with endemicity was seen for the prevalence of any onchocercal skin lesion and/or pruritus combined (r=0.8; P<0.001). Cutaneous onchocerciasis was found to be a common problem in many endemic areas in Africa which do not have high levels of onchocercal blindness. These findings, together with recent observations that onchocercal skin disease can have major, adverse, psycho-social and socio-economic effects, justify the inclusion of regions with onchocercal skin disease in control programmes based on ivermectin distribution. On the basis of these findings, the World Health Organization launched a control programme for onchocerciasis, the African Programme for Onchocerciasis Control (APOC), that covers 17 endemic countries in Africa.

Wolbachia bacteria in filarial immunity and disease.

Lymphatic filarial nematodes are infected with endosymbiotic Wolbachia bacteria. Lipopolysaccharide from these bacteria is the major activator of innate inflammatory responses induced directly by the parasite. Here, we propose a mechanism by which Wolbachia initiates acute inflammatory responses associated with death of parasites, leading to acute filarial lymphangitis and adverse reactions to antifilarial chemotherapy. We also speculate that repeated exposure to acute inflammatory responses and the chronic release of bacteria, results in damage to infected lymphatics and desensitization of the innate immune system. These events will result in an increased susceptibility to opportunistic infections, which cause acute dermatolymphangitis associated with lymphoedema and elephantiasis. The recognition of the contribution of endosymbiotic bacteria to filarial disease could be exploited for clinical intervention by the targeting of bacteria with antibiotics in an attempt to reduce the development of filarial pathology.

Clinical and parasitological aspects of itching caused by onchocerciasis in Morogoro, Tanzania.

A clinical and parasitological assessment of onchodermatitis was conducted in a rural area of Morogoro district, Tanzania. The study population consisted of 1,005 individuals aged > or = 5 years: 749 from a hyper-endemic community and 256 from a hypo-endemic. The prevalence of troublesome itching was 67.0% in the hyper-endemic community but only 5% (13/256) in the hypo-endemic. The corresponding prevalences of nodules among the adult male subjects were 77.7% (171/220) and 2.3% (2/86). The most common onchocercal skin lesion in the hyper-endemic community was chronic papular onchodermatitis (CPOD) manifested by itching, which was often very severe. There was a strong association between skin itching and endemicity (r = 0.75; P < 0.001). The prevalence of CPOD in the hyper-endemic community was significantly higher in males than females (P< 0.001). CPOD was only observed in subjects aged > or = 7 years. Many of the subjects were checked for microfilaridermia, by skin-snipping. The prevalence of microfilaridermia [58.2% (393/675) v. 6.2% (3/48)] and its geometric mean intensity (8.9 v. 1.0 microfilariae/mg skin snip) were both higher in the hyper-endemic community than the hypo-endemic. Itching appears to be related to reactive onchodermatitis.

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Bancroftian filariasis: long-term effect of the DEC provocative day test on microfilaraemia.

The diethylcarbamazine (DEC) provocative day test has been widely used for daytime diagnosis of Wuchereria bancrofti infections in areas where microfilariae exhibit nocturnal periodicity. Since DEC is also the primary drug for treatment of bancroftian filariasis, we examined the long term effect of the test on microfilaraemia in 2 groups of individuals receiving either 100 mg of DEC (n = 51) or placebo (n = 20). The low dose of DEC had a significant therapeutic effect. One year after treatment, the geometric mean in-tensity of microfilaraemia was reduced by 86.1%, and 10.6% of the individuals were amicrofilaraemic. No significant reduction of microfilaraemia was observed in the placebo group. The results imply that the DEC provocative day test should not be used as a diagnostic tool in follow-up studies on microfilaraemias.

Mass DEC chemotherapy for control of bancroftian filariasis: comparative efficacy of four strategies two years after start of treatment.

The efficacy of 4 strategies for control of bancroftian filariasis using mass diethylcarbamazine (DEC) chemotherapy was evaluated and compared in 4 endemic communities in Tanzania 2 years after the start of treatment. The strategies used were the standard 12 d treatment (strategy I), a semi-annual single dose treatment (strategy II), a monthly low dose treatment (strategy III), and DEC medicated salt (strategy IV). Treatment took place during the first study year, and no treatment was given during the second year. Among individuals who were microfilaraemic before treatment, the microfilaria (mf) clearance rates were 41.5%, 75.0%, 84.0% and 89.1%, and the pre-treatment mf geometric mean intensities (GMIs) were reduced by 97.1%, 98.9%, 99.8% and 99.8%, for strategies I, II, III and IV, respectively, 2 years after starting treatment. Statistical analysis indicated that strategies III and IV were equally effective, and superior in clearing microfilaraemias and in reducing mf GMIs compared to strategies I and II; strategy II was significantly more effective than strategy I. The rate of occurrence of new cases of microfilaraemia among individuals who were amicrofilaraemic during the pre-treatment surveys was negligible over the study period in all communities. In all the communities combined, 66.6% of males presenting hydrocele before treatment, and 61.5% of individuals presenting elephantiasis before treatment, showed improvements in these conditions 2 years after the start of treatment, either as a reduction in size or complete disappearance.

Mass diethylcarbamazine chemotherapy for control of bancroftian filariasis: comparative efficacy of standard treatment and two semi-annual single-dose treatments.

The efficacy of 2 strategies for control of bancroftian filariasis using mass diethylcarbamazine (DEC) chemotherapy was evaluated and compared in 2 endemic communities in Tanzania with pre-treatment microfilarial (mf) prevalences of 28.5% and 17.7%, and mf geometric mean intensities (GMI) of 588 mf/mL and 251 mf/mL, respectively. All individuals in the first community were offered DEC treatment with 6 mg/kg body weight given daily for 12 d (standard treatment). The second community was offered DEC treatment with 2 single doses of 6 mg/kg body weight given with an interval of 6 months (semi-annual single-dose treatment). Among those who were microfilaraemic before treatment, the mf clearance rates were 51.2% and 36.0%, and the mf GMIs were reduced by 98.6% and 92.2% one year after the start of the standard and the semi-annual regimens, respectively. At community level, the standard strategy and the semi-annual strategy reduced the mf prevalences to 15.1% and 11.6% (reductions of 47.0% and 34.5%) and the mf GMIs to 112 mf/mL and 102 mf/mL (reductions of 81.0% and 59.4%, respectively) one year after start of treatment. Both regimens resulted in remarkable improvements in small hydroceles among males presenting this condition before treatment. The lower efficacy of the semi-annual single-dose treatment in relation to the standard treatment in reducing microfilaraemias might be compensated for by continuing semi-annual treatments for a slightly longer period of time. Considering that the semi-annual treatment is easy to administer and more acceptable to the treated individuals, it may in the long run be a more feasible strategy for mass DEC chemotherapy than the standard treatment.

Mass diethylcarbamazine chemotherapy for control of bancroftian filariasis through community participation: comparative efficacy of a low monthly dose and medicated salt.

The efficacy of 2 strategies for the control of bancroftian filariasis using diethylcarbamazine (DEC) mass chemotherapy delivered through community participation was evaluated and compared in 2 endemic communities in Tanzania with pre-treatment microfilarial (mf) prevalences of 34.7% and 31.0%, and mf geometric mean intensities (GMI) of 1122 mf/mL and 933 mf/mL, respectively. In the first community, all individuals aged > or = 1 year were offered treatment for one year with a low monthly dose (50 mg DEC to children aged < 15 years and 100 mg DEC to adults aged > or = 15 years; given independently of body weight), and in the second community all households were offered 0.33% w/w DEC-medicated cooking salt for one year. Both treatment strategies resulted in dramatic reductions in the mf loads. Among those microfilaraemic before treatment, the low monthly dose and the DEC-medicated salt gave mf clearance rates of 55.3% and 92.1%, respectively, and the pre-treatment mf GMIs were reduced by 99.4% and 99.9%, respectively, one year after starting treatment. At community level, the mf prevalences were reduced to 15.8% and 2.4% (reductions of 54.5% and 92.3%) and the mf GMIs were reduced to 100 mf/mL and 32 mf/mL (reductions of 91.1% and 96.6%), one year after starting treatment with the low monthly dose and DEC-medicated salt respectively. Males with hydrocele before treatment improved remarkably one year after the start of treatment. Since both strategies were simple to administer and well accepted by the communities, they appear highly feasible for integration into large scale control programmes based on community participation.

Bancroftian filariasis: analysis of infection and disease in five endemic communities of north-eastern Tanzania.

Clinical and parasitological surveys for bancroftia filariasis were carried out in five endemic communities in north-eastern Tanzania, covering a population of 3086 individuals. High microfilarial (mf) prevalences (17.7%-34.7%) and mf geometric mean intensities (251-1122 microfilariae/ml) were observed in the communities. The mf prevalence generally increased with age, but often levelled out in the older age groups. Larger variability was observed in individual mf intensities and no clear association between mf geometric mean intensity and age or sex was seen. Hydrocele was the most common clinical manifestation (with a prevalence of 30.2%-40.0% in male subjects aged > or = 20 years) followed by leg elephantiasis (with a prevalence of 2.0%-6.8% in all subjects aged > or = 20 years). In four of the five communities, there was no significant difference in mf prevalence in males aged > or = 20 years between those with and without hydrocele. In all the communities, the mf geomtric mean intensities in microfilaraemic males with and without hydrocele were not significantly different. The present study therefore did not indicate any association between hydrocele in males (the most common type of chronic clinical manifestation seen) and presence or absence of microfilaraemia. In contrast, only two (4.4%) of the 45 subjects with leg elephantiasis were microfilaraemic. In children aged 1-15 years, mf prevalence was significantly higher among those with microfilaraemic mothers (18.0%) than among those with amicrofilaraemic mothers (7.9%). The children of microfilaraemic mothers were therefore at 2.3-fold higher risk of becoming microfilaraemic than the children of amicrofilaraemic mothers. No relationship between the mf prevalence of the children and the mf status of their fathers was observed.

A 16-year follow-up study on bancroftian filariasis in three communities of north-eastern Tanzania.

The results of a 16-year, parasitological and clinical, follow-up study on bancroftian filariasis in three villages in north-eastern Tanzania are reported and analysed with respect to the long-term development of microfilaraemia and disease. The study revealed an extraordinary static situation, both at the community level and at the individual level. No significant differences were observed in any of the three villages, with respect to total or age-specific prevalences of microfilaraemia, hydrocele in males aged > or = 20 years or leg elephantiasis in all subjects aged > or = 20 years, when the results from 1975 were compared with those from 1991. Overall, 542 of the subjects (37.2% of the total) examined in 1975 were re-identified and re-examined in 1991. Of those microfilaraeic in 1975, 81.9% were also microfilaraemic in 1991. Similarly, 81.3% of those amicrofilaraemic in 1975 were also amicrofilaraemic in 1991. Thus, most subjects had the same microfilarial (mf) status at both surveys. The low mf loss rate indicates that re-infection of microfilaraemic individuals commonly takes place, and results in repeated sequences of microfilaraemia in the same individuals. The rate of gain of microfilaraemia was independent of age, thus indicating no age-related change in the examined population's susceptibility to develop or sustain microfilaraemia. Individual differences in susceptibility to develop mirofilaraemia therefore appear to be innately determined, or to be acquired in pre-natal or early post-natal life. Neither the presence of hydrocele in 1991, nor the development of new cases of hydrocele over the 16-year period were related to the mf status in 1975 or 1991, and no association between microfilaraemia and this chronic clinical manifestation was observed. The association between leg elephantiasis and mf status could not be analysed because of the small sample size.

Bancroftian filariasis: the pattern of microfilaraemia and clinical manifestations in three endemic communities of Northeastern Tanzania.

Individuals from three villages in northeastern Tanzania, located 40 km inland from the Indian Ocean coast, were surveyed for parasitological and clinical evidence of bancroftian filariasis. Microfilarial (mf) prevalences ranged from 22.2 to 37.6%, and mf geometric mean intensities (GMI) ranged from 546 to 735 mf/ml blood, in the three villages. Microfilaraemia was rare in children below five years. The mf prevalences increased with age, reaching from 35.9 to 49.2% in individuals aged 45 years and above. No association between mf GMI and age was observed in any of the villages. Hydrocele was the most common chronic clinical manifestation, with prevalences ranging from 14.5 to 21.3% for all males, and from 52.9 to 62.1% for males aged 45 years and above. From 0.6 to 3.3% of the inhabitants in the three villages had elephantiasis, which most often affected the legs. Microfilaraemia was common in males with hydrocele, and in males of 45 years and above there was no significant difference in mf prevalence between males with (42.5%) and without (55.2%) hydrocele. In contrast, microfilariae were only detected in the blood from one of 18 individuals with elephantiasis. With respect to hydrocele, the present results do not support recently forwarded hypotheses assuming a general negative relationship between microfilaraemia and chronic clinical manifestations in bancroftian filariasis.

Selective diethylcarbamazine chemotherapy for control of Bancroftian filariasis in two communities of Tanzania: compared efficacy of a standard dose treatment and two semi-annual single dose treatments.

The efficacy of two strategies for control of Bancroftian filariasis using selective rather than community-wide diethylcarbamazine (DEC) chemotherapy was evaluated and compared in two endemic communities of north-eastern Tanzania, with pretreatment microfilariae (mf) prevalences of 22% and 38%, and geometric mean intensities (GMIs) of 668 mf/ml and 735 mf/ml of blood. All mf-positive cases in the first community were offered treatment with 6 mg of DEC/kg of body weight a day for 12 days (group 1), and those in the second community were offered treatment with two doses of 6 mg of DEC/kg of body weight at an interval of six months (group 2). The effect of treatment was followed both among those treated and at the community level. In treated individuals, there was a rapid decrease in the mf load that was significantly greater among those receiving the 12-day standard dose. One year after the start of treatment, the mf clearance rates were 59% and 39% and the GMIs were reduced by 99% and 97% among treated individuals in groups 1 and 2, respectively. However, at the community level, the mf prevalences were 16.3% and 27.9% (reduced by 27% and 26%) and the GMIs were 129 mf/ml and 224 mf/ml (reduced by 81% and 70%) one year after the start of treatment with the two regimens, respectively, suggesting that transmission continued at a significant level in the villages after treatment. The limitations of selective chemotherapy are discussed, and it is argued that strategies based on mass DEC chemotherapy would be more effective in reducing the microfilarial load in the community and thereby in reducing transmission.

Chronic pulmonary disorders, including tropical pulmonary eosinophilia, in villages with endemic lymphatic filariasis in Tanga region and in Tanga town, Tanzania.

To investigate the occurrence of tropical pulmonary eosinophilia (TPE), studies were undertaken in 3 villages with endemic lymphatic filariasis in the coastal area of Tanga Region, Tanzania, and in the outpatient clinic of Bombo Regional Hospital in Tanga town; 73 persons from the villages and 104 from the outpatient clinic with a history of lung disease suggestive of TPE were included in the study. Following clinical examination, lung function tests and chest X-rays were performed. Total leucocyte and eosinophil counts were recorded. Parasitological examinations included blood for microfilariae and stools and urine for eggs of intestinal helminths and Schistosoma haematobium respectively. Total immunoglobulin (Ig) E and specific antifilarial IgE and IgG4 were measured. Suspected TPE cases were treated with diethylcarbamazine, 6 mg/kg for 12 d, and were followed up 14, 90 and 360 d after treatment. Three persons fulfilled the criteria for TPE. Their response to treatment was marked, with clinical improvement, reduction in eosinophil count and reduced titres of specific antifilarial IgE and IgG4. Although TPE is present in Wuchereria bancrofti endemic areas of East Africa, it appears to be rare, as in other endemic areas.