Vector species composition and malaria infectivity rates in Mkuzi, Muheza District, north-eastern Tanzania.

Entomological surveys were conducted in Mkuzi village in Muheza District, north-east Tanzania from April to September 2003. The objectives were to determine the species composition and infectivity rates of mosquitoes in Mkuzi village. Mosquito collection was done using CDC light trap and pyrethrum spray catch (PSC) techniques. The light trap: spray catch ratio was 2.2:1. A total of 2157 mosquitoes were collected (light trap = 1483; PSC = 674). Anopheles gambiae s.s. accounted for 56.7% (N = 1224) of all mosquitoes collected. Other species were An. funestus complex (19.2%) and Culex quinquefasciatus (24.1%).The mosquito density per room was 74.15 and 33.7 for light trap and PSC techniques, respectively. A total of 1637 Anopheles mosquitoes were tested for circumsporozoite protein by Enzyme linked Immunosobent Assay (ELISA). The overall infectivity rate for circumsporozoite protein for P. falciparum in Anopheles mosquitoes was 21.14% (346/1637). Species-specific infectivity rates were 22.7% (278/1224) in An. gambiae s.s. and 24.0% (68/283) in An. funestus funestus, 0% (0/80) for An. rivulorum and 0% (0/50) for An. parensis. Blood meal analysis indicated that 92.3% of An. gambiae s.s, 88.9% of An. funestus s.s., 64.5% of An. rivulorum and 67.7% of An. parensis had taken blood meal from human hosts. In conclusion, malaria transmission in Mkuzi area of Muheza district is mainly by the highly anthropophagic An. gambiae s.s. and An. funestus s.s. More studies are needed to identify the seasonal variation of species composition and transmission dynamics in this village.

Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria.

CONTEXT: There are concerns that malaria control measures such as use of insecticide-treated bed nets, by delaying acquisition of immunity, might result in an increase in the more severe manifestations of malaria. An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely. OBJECTIVE: To describe the clinical manifestations and case fatality of severe P falciparum malaria at varying altitudes resulting in varying levels of transmission. DESIGN, SETTING, AND PATIENTS: A total of 1984 patients admitted for severe malaria to 10 hospitals serving populations living at levels of transmission varying from very low (altitude >1200 m) to very high (altitude <600 m) in a defined area of northeastern Tanzania, studied prospectively from February 2002 to February 2003. Data were analyzed in a logistic regression model and adjusted for potential clustering within hospitals. MAIN OUTCOME MEASURES: Specific syndromes of severe malaria; mortality. RESULTS: The median age of patients was 1 year in high transmission, 3 years in moderate transmission, and 5 years in low transmission areas. The odds of severe malarial anemia (hemoglobin <5 g/dL) peaked at 1 year of age at high transmission and at 2 years at moderate and low transmission intensities and then decreased with increasing age (P = .002). Odds were highest in infants (0-1 year: referent; 2-4 years: odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.96), 5 to <15 years: OR, 0.44; 95% CI, 0.27-0.72; > or =15 years: OR, 0.44; 95% CI, 0.27-0.73; P<.001) and high transmission intensity areas (altitude <600 m: referent; 600 m to 1200 m: OR, 0.55; 95% CI, 0.35-0.84; >1200 m: OR, 0.55; 95% CI, 0.26-1.15; P for trend = .03). The odds of cerebral malaria were significantly higher in low transmission intensity areas (altitude of residence <600 m: referent; 600 m to 1200 m: OR, 3.17; 95% CI, 1.32-7.60; >1200 m: OR, 3.76; 95% CI, 1.96-7.18; P for trend = .003) and with age 5 years and older (0-1 year: referent; 2-4 years: OR, 1.57; 95% CI, 0.82-2.99; 5 to <15 years: OR, 6.07; 95% CI, 2.98-12.38; > or =15 years: OR, 6.24; 95% CI, 3.47-11.21; P<.001). The overall case-fatality rate of 7% (139 deaths) was similar at high and moderate levels of transmission but increased to 13% in low transmission areas (P = .03), an increase explained by the increase in the proportion of cases with cerebral malaria. CONCLUSIONS: Age and level of exposure independently influence the clinical presentation of severe malaria. Our study suggests that an increase in the proportion of cases with more fatal manifestations of severe malaria is likely to occur only after transmission has been reduced to low levels where the overall incidence is likely to be low.

Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure.

The implementation and evaluation of malaria control programs would be greatly facilitated by new tools for the rapid assessment of malaria transmission intensity. Because acquisition and maintenance of antimalarial antibodies depend on exposure to malaria infection, such antibodies might be used as proxy measures of transmission intensity. We have compared the prevalence of IgG antibodies with three Plasmodium falciparum asexual stage antigens in individuals of all ages living at varying altitudes encompassing a range of transmission intensities from hyper- to hypoendemic in northeastern Tanzania, with alternative measures of transmission intensity. The prevalence of antibodies to merozoite surface protein-1(19) was significantly more closely correlated with altitude than either point-prevalence malaria parasitemia or single measures of hemoglobin concentration. Analysis of age-specific seroprevalence rates enabled differentiation of recent (seasonal) changes in transmission intensity from longer-term transmission trends and, using a mathematical model of the annual rate of seroconversion, estimation of the longevity of the antibody response. Thus, serological tools allow us to detect variations in malaria transmission over time. Such tools will be invaluable for monitoring trends in malaria endemicity and the effectiveness of malaria control programs.

The snout and palmomental reflexes in HIV disease in Tanzania.

Following earlier observations on the snout (SR) and palmomental(PMR) reflexes in AIDS in Tanzania, a series of 1127 adults, 649 HIV-positive and 478 HIV-negative, from 4 groups at different risk of HIV infection were examined neurologically between 1987 and 1992. The prevalence of SR and PMR was calculated according to HIV status, HIV stage, demographic factors and neurologic findings. In the total series of HIV positives the prevalence ranged from SR 39.3% and PMR 22.6% in asymptomatic HIV disease to SR 87% and PMR 69% in terminal AIDS. In HIV negatives the prevalence of SR was 19.2% and PMR 15.3%, and increased with age. There was no relationship with age in the HIV positives and no gender differences. SR and PMR were also associated with neuropathy, myelopathy and AIDS dementia complex independent of HIV stage. This study shows a strong association between SR and PMR and HIV disease in Africa. The prevalence increased with HIV stage and related neurological disorders.

Evaluation of a rapid membrane enzyme immunoassay (Testpack HIV-1/HIV-2) at zonal, regional and district hospital laboratories in Tanzania.

The performance of a rapid and simple membrane enzyme immunoassay for antibodies to HIV-1 and HIV-2 (Testpack HIV-1/HIV-2) was evaluated by testing 1000 sera from the Kilimanjaro region of Tanzania. A sensitivity of 100% (118/118 positives) and specificity of 95.1% were obtained following the manufacturer's procedure. The specificity was significantly enhanced to 97.2% (P = 0.026) by modifying the Testpack procedure by including an extra was after serum adsorption to the unit membrane. The testing of a single specimen could be completed in 8 min and up to 10 individual tests could be run simultaneously. There was complete agreement in interpretation when the results were read independently by two trained technicians. A built-in control insured against incorrect procedures or inactive reagents. In a subsequent field trial including 450 sera, one strongly reactive sample failed to be detected at a participating field hospital for unknown reasons. The Testpack reagents proved stable for up to one year at room temperature (25-30 degrees C). The data indicate that Testpack is suitable for the detection of serum antibodies to HIV and is especially applicable in laboratories with limited facilities. When used to test African sera which are known to produce a high degree of false positivity, an extra wash of the membrane after serum adsorption is recommended.

Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity.

Sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals from the United States and Tanzania were examined for antibody reactivity to four synthetic peptides which corresponded to the principal neutralizing determinant from the V3 region of HIV-1 gp120. We observed that the majority of sera from both countries contained antibodies reactive with a V3 peptide whose sequence is based on that of the HIV-1 MN isolate. We were unable to establish a relationship between the presence of V3-reactive antibodies, as measured by enzyme-linked immunosorbent assay and neutralization of homologous HIV-1 isolates, in sera from either the United States or Tanzania. We observed that some sera which contained high antibody titers to the V3 peptides failed to neutralize HIV-1, while others with no antibody reactivity to the panel of V3 peptides exhibited in vitro neutralizing activity. These results suggest that neutralizing epitopes exist outside the V3 loop and that the presence of V3-reactive antibodies in sera does not imply in vitro neutralization of the homologous HIV-1 isolate. In addition, it appears that the V3 loop may consist of both neutralizing and nonneutralizing epitopes. The identification of neutralizing as well as nonneutralizing epitopes will be important for the design of potential HIV-1 vaccines.

Fine specificity of the humoral immune response to HIV-1 GP160 in HIV-1 infected individuals from Tanzania.

A total of 160 sera from HIV-1 infected individuals from Tanzania were examined for their fine specificity characteristics relative to 9 synthetic peptides that define HIV-1 gp160 epitopes. Immunorecessive and immunodominant epitopes were identified in both gp120 and gp41 based on serologic reactivity of these HIV-1 infected sera. A significant difference in fine specificity among HIV-1 infected individuals from Tanzania and the United States was observed for an immunodominant gp41 epitope. No significant differences in reactivity among asymptomatic vs. symptomatic HIV-1 infected individuals were detected for the selected HIV-1 gp160 epitopes defined by these peptides. The majority of sera from HIV-1 infected Tanzanians contained antibodies that recognized a peptide corresponding to the V3 region of gp120 from the HIV-1 MN isolate. These data suggest that regional isolates of HIV-1 may exist in Tanzania that differ from HIV-1 isolated in the United States. However, based on serology, HIV-1 isolates exhibiting sequences with HIV-1 MN V3 similarity may also be prevalent in Tanzania. The results of this study may be useful for the design of more effective AIDS diagnostic and therapeutic products for use worldwide.

Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the United States.

In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.

Sexually transmitted diseases in prostitutes in Moshi and Arusha, Northern Tanzania.

Sexually transmitted diseases are thought to be important in facilitating transmission of HIV in sub-Saharan Africa. This study reports the prevalence of several sexually transmitted diseases in 106 prostitutes in Arusha and Moshi Northern Tanzania. The seroprevalence of HIV was 73% compared with 3% for local blood donors. Over half (51%) of the subjects had evidence of N. gonorrhoeae infection. Seventy-four per cent had a positive TPHA and 27% a positive RPR. Of 47 subjects tested 12 (25%) had Chlamydia trachomatis antigen detected in endocervical swabs. No significant statistical association was found between the presence of any of the STDs investigated and HIV seropositivity.

PIP: In the early 1990s, health workers spoke with, examined, and took blood samples from 106 low income 17-70 year old prostitutes mainly from the Haya tribe in their homes in the towns of Moshi in Kilimanjaro Region and Arusha in Arusha Region in Northern Tanzania (45 from Moshi and 61 from Arusha) to determine the prevalence of sexually transmitted diseases (STDs) and HIV. Number of sexual contacts/day ranged from 10-20. 40% did not use condoms at all even though they regularly received condoms as part of a health education campaign. 73% tested positive for HIV which is considerably higher than the seroprevalence in the general population in 1989 (.1-3%). Only 20% thought that they presently had an STD when actually 22-82% had at least 1 STD. About 50% tested positive for syphilis, 47% for gonorrhea, and 25% in Arusha for chlamydia. No significant association existed between HIV seropositivity and STD prevalence. Another study showed that HIV seroprevalence among the general population had only slightly increased since 1987 which suggests that these prostitutes experienced high HIV seroprevalence earlier in the epidemic. These prostitutes represented a reservoir for STDs including HIV. Unless condom use increases among these women, HIV will spread to the general population. Health education campaigns should expand beyond just provision of condoms and find other means to effectively target these women.

Evaluation of rapid tests for HIV antibody screening of blood donors

The enzyme-linked immunosorbent assay (ELISA) is currently the most accepted method used to screen for antibodies to HIV Conventional ELISA assays require from 1.5 to 3.5 hours to complete and an optical density (OD) reader to record results. We have therefore considered the applicability of using rapid tests for the screening of blood donors. The Testpack method is quick to perform; easy to interpret and sensitive. Results indicate that the Testpack method is suitable for the screening of blood donors and in emergency situations

Evaluation of rapid tests for HIV antibody screening of blood donors

The enzyme-linked immunosorbent assay (ELISA) is currently the most accepted method used to screen for antibodies to HIV. Conventional ELISA assays require from 1.5 to 3.5 hours to complete and an optical density (OD) reader to record results. We have therefore considered the applicability of using rapid tests for the screening of blood donors. The Testpack method is quick to perform; easy to interpret and sensitive. Results indicate that the Testpack method is suitable for the screening of blood donors and in emergency situations

Neurological disorders in AIDS and HIV disease in the northern zone of Tanzania.

This study presents the main clinical findings on 200 AIDS patients at Kilimanjaro Christian Medical Centre in the northern zone of Tanzania, with detailed neurological findings on 135 out of 200 cases and 53 controls. Results show that 21 out of 200 (10.5%) had an obvious focal neurological disorder, including cranial nerve palsies, hemiparesis and paraparesis. Ninety-seven out of 135 (72%) had less obviously detectable neurological disorders, versus 36% of controls (P less than 0.005). Most frequent were AIDS dementia complex (54%), retinopathy (23%), areflexia (21%), pyramidal tract signs (19%) and tremor and incoordination (19%). Frontal lobe release signs (FLRS) were found in 103 out of 135 (76%) patients, versus 36% of controls (P less than 0.005). Advanced and terminal AIDS cases were more likely to have neurological disorders than early AIDS patients. A further study on 87 non-AIDS patients with acute unexplained neurological disorders showed 10 out of 87 to be HIV seropositive. Three case studies are presented. This study suggests that neurological disorders are among the main clinical features of AIDS and HIV disease in Africa.

Schistosoma haematobium: effect of non-schistosomicidal drugs (tetracycline and sulphadimidine) on schoolchildren.

Pupils attending four secondary boarding schools in Mwanza Municipality, Tanzania, were examined parasitologically for Schistosoma haematobium. Prevalence of infection was highest in the age group 17 to 18 years in both sexes whereas the intensity was highest in the age group 15 to 16 years in girls and 17 to 18 in boys. Absence on grounds of sickness among the pupils studied was not related to the infection and the over-all academic performance was not clearly related to S. haematobium infection in either. Two drugs (tetracycline-HCL and sulphadimidine) commonly used for treatment of many bacterial infections in Tanzania were used. Administration of these drugs to schistosomiasis patients showed that both significantly lowered egg excretion and the degree depended on the dosage. Neither drugs affected the hatching of miracidia. It is speculated that the administration of both drugs might contribute to a higher accumulation of the eggs in the tissues. This effect could lead to more pathogenic effects as well as introducing an element of error in the studies on drug trials and chemotherapy. Treatment using metrifonate (Bilarcil) resulted in cure rates of 76% for girls and 93% for boys.

Infection intensity and specific antibody response in schistosomiasis.

The antibody titres in hamsters that were experimentally infected and in humans that were naturally infected with S. mansoni or S. haematobium were determined with the IFAT. The infection intensity was measured directly in the hamsters by counting the worms collected after perfusion and indirectly in humans by counting the eggs in faeces or in urine. In general antibody titre reflected infection intensity.